bluuebunny/crossref_metadata_2025 huggingface dataset:
A Panoramic View of Cell Population Dynamics in Mammalian Aging
Authors: Zhang Zehao , Schaefer Chloe , Jiang Weirong , Lu Ziyu , Lee Jasper , Sziraki Andras , Abdulraouf Abdulraouf , Wick Brittney , Haeussler Maximilian , Li Zhuoyan , Molla Gesmira , Satija Rahul , Zhou Wei , Cao Junyue
Published: March 2024

To elucidate the aging-associated cellular population dynamics throughout the body, here we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissue samples, encompassing a range of organs across different life stages, sexes, and genotypes. This comprehensive dataset allowed us to identify more than 3,000 unique cellular states and catalog over 200 distinct aging-associated cell populations experiencing significant depletion or expansion. Our panoramic analysis uncovered temporally structured, organ- and lineage-specific shifts of cellular dynamics during lifespan progression. Moreover, we investigated aging-associated alterations in immune cell populations, revealing both widespread shifts and organ-specific changes. We further explored the regulatory roles of the immune system on aging and pinpointed specific age-related cell population expansions that are lymphocyte-dependent. The breadth and depth of our ‘cell-omics’ methodology not only enhance our comprehension of cellular aging but also lay the groundwork for exploring the complex regulatory networks among varied cell types in the context of aging and aging-associated diseases.

One Sentence Summary

PanSci, a single-cell transcriptome atlas of over 20 million cells throughout the mouse lifespan, unveils the temporal architecture of aging-associated cellular population dynamics, organ-specific immune cell shifts, and the lymphocyte’s role in organismal aging.
Effects of electroconvulsive shock on the function, circuitry, and transcriptome of dentate gyrus granule neurons
Authors: Santiago Adrienne N. , Nguyen Phi , Castello-Saval Julia , Chung Hannah M. , Luna Victor M. , Hen Rene , Chang Wei-li
Published: March 2024

Therapeutic use of electroconvulsive shock (ECS) is particularly effective for treatment-resistant depression. Like other more common forms of antidepressant treatment such as SSRIs, ECS has been shown to increase neurogenesis in the hippocampal dentate gyrus of rodent models. Yet the question of how ECS-induced neurogenesis supports improvement of depressive symptoms remains unknown. Here, we show that ECS-induced neurogenesis is necessary to improve depressive-like behavior of mice exposed to chronic corticosterone (Cort). We then use slice electrophysiology to show that optogenetic stimulation of adult-born neurons produces a greater hyperpolarization in mature granule neurons after ECS vs Sham treatment. We identify that this hyperpolarization requires the activation of group II metabotropic glutamate receptors. Consistent with this finding, we observe reduced expression of the immediate early gene cFos in the granule cell layer of ECS vs Sham subjects. Using single nucleus RNA sequencing, we reveal major transcriptomic shifts in granule neurons after treatment with ECS+Cort or fluoxetine+Cort vs Cort alone. We identify a population of immature cells which has greater representation in both ECS+Cort and fluoxetine+Cort treated samples vs Cort alone. We also find global differences in ECS-vs fluoxetine-induced transcriptomic shifts. Together, these findings highlight a critical role for immature granule cells in the antidepressant action of ECS.
Bacteria in honeybee crops are decoupled from those in floral nectar and bee mouths
Authors: Warren Magdalena L. , Tsuji Kaoru , Decker Leslie E. , Kishi Manabu , Yang Jihoon , Howe Adina C. , Fukami Tadashi
Published: March 2024

Bacteria in the honeybee gut are a well-recognized factor affecting bee health. However, the primary focus of this research has been the hindgut, while the crop, or honey stomach, is assumed to be dominated by environmentally acquired transient taxa that matter little to the bees. To evaluate this assumption, we examined bacterial taxa in the crop and mouth ofApis melliferaandA. cerana japonicaforagers and in the nectar ofPrunus mumeflowers visited by the bees in the Minabe-Tanabe region of Japan. We found that in bacterial composition, the crop was distinct from both the mouth and the nectar, whereas mouth and nectar samples were indistinguishable. Furthermore, the crop remained similar in bacterial composition and diversity, while the mouth showed a sharp drop in alpha diversity and a large increase in beta diversity, from summer to winter. These results refute the conventional assumption, suggesting instead that the crop contains a conserved bacterial community largely distinct from environmental taxa. We also found that strains of a crop-associated species,Apilactobacillus kunkeei, could be season- and host species-specific. Together, these findings suggest that crop-associated bacterial communities should be studied further to better understand the relationship between honeybees and their gut bacteria.
A comprehensive investigation of intracortical and corticothalamic models of the alpha rhythm
Authors: Bastiaens Sorenza P. , Momi Davide , Griffiths John D.
Published: March 2024

The electroencephalographic alpha rhythm is one of the most robustly observed and widely studied empirical phenomena in all of neuroscience. However, despite its extensive implication in a wide range of cognitive processes and clinical pathologies, the mechanisms underlying alpha generation in neural circuits remain poorly understood. In this paper we offer a renewed foundation for research on this question, by undertaking a systematic comparison and synthesis of the most prominent theoretical models of alpha rhythmogenesis in the published literature. We focus on four models, each studied intensively by multiple authors over the past three decades: i) Jansen-Rit, ii) Moran-David-Friston, iii) Robinson-Rennie-Wright, and iv) Liley-Wright. Several common elements are identified, such as the use of second-order differential equations and sigmoidal potential-to-rate operators to represent population-level neural activity. Major differences are seen in other features such as wiring topologies and conduction delays. Through a series of mathematical analyses and numerical simulations, we nevertheless demonstrate that the selected models can be meaningfully compared, by associating parameters and circuit motifs of analogous biological significance. With this established, we conduct explorations of rate constant and synaptic connectivity parameter spaces, with the aim of identifying common patterns in key behaviours, such as the role of excitatory-inhibitory interactions in the generation of oscillations. Finally, using linear stability analysis we identify two qualitatively different alpha-generating dynamical regimes across the models: i) noise-driven fluctuations, and ii) self-sustained limit-cycle oscillations, emerging due to an Andronov-Hopf bifurcation. The comprehensive survey and synthesis developed here can, we suggest, be used to help guide future theoretical and experimental work aimed at disambiguating these and other candidate theories of alpha rhythmogenesis.
High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations
Authors: Heriyanto Didik Setyo , Yoshuantari Naomi , Akbariani Gilang , Lau Vincent , Hanini Hanifa , Hidayati Zulfa , Arief Muhammad Zulfikar , Gunawan Andrew Nobiantoro , Ridwanuloh Asep Muhamad , Kusharyoto Wien , Handaya Adeodatus Yuda , Ilyas Mohammad , Kurnianda Johan , Hutajulu Susanna Hilda , Susanti Susanti
Published: March 2024

Background

In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients <50 years old compared to western populations, possibly due to a higher frequency of Lynch Syndrome (LS) in CRC patients. We aim to examine the association of KRAS and PIK3CA mutation with LS.

Methods

In this cross-sectional study, the PCR-HRM-based test was used for screening of MSI mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF(V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples.

Results

All the samples (n=244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples respectively. PIK3CA mutation was significantly associated with female sex and lower levels of TILs in 62/107 (57.94%) and 26/107 (30.23%) samples respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients.

Conclusions

High probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.
Oncology Researchers’ and Clinicians’ Perceptions of Complementary, Alternative, and Integrative Medicine: An International, Cross-Sectional Survey
Authors: Ng Jeremy Y. , Kochhar Jassimar , Cramer Holger
Published: March 2024

Background

Complementary, alternative, and integrative medicine (CAIM) has become an increasingly popular supportive therapy option for patients with cancer. The objective of this study was to investigate how researchers and clinicians in the oncology field perceive CAIM.

Methods

We conducted an online, anonymous, cross-sectional survey for researchers and clinicians who have published their work in oncology journals that are indexed in MEDLINE. The link to the survey was sent to 47, 991 researchers and clinicians whose contact information was extracted from their publications. The survey included various multiple-choice questions, and one open-ended question at the end to allow for any additional comments.

Results

751 respondents completed the survey, and they mostly identified themselves as researchers (n=329, 45.13%), or as both researchers and clinicians (n=332, 45.45%) in the field of oncology. Over half of the respondents perceive mind-body therapies (n=354, 54.97%) to be the most promising CAIM category with regards to the prevention, treatment, and/or management of diseases related to oncology, and many respondents agreed that most CAIM therapies are safe (n=218, 37.39%), and that clinicians should receive training on CAIM therapies via formal (n=225, 38.59%) and supplemental education (n=290, 49.83%). However, many respondents were unsure when asked if most CAIM therapies are effective (n=202, 34.77%).

Conclusions

The findings from this study demonstrated great current interest in the use of CAIM in oncology. This information can serve as a foundation for conducting additional research and creating customized educational materials for researchers and clinicians in oncology.
Prospective Clinical Surveillance for Severe Acute Respiratory Illness in Kenyan Hospitals during the COVID-19 pandemic
Authors: Lucinde Ruth Khadembu , Gathuri Henry , Isaaka Lynda , Ogero Morris , Mumelo Livingstone , Kimego Dennis , Mbevi George , Wanyama Conrad W , Otieno Edwin Onyango , Mwakio Stella , Saisi Metrine , Isinde ELizabeth , Oginga Irene Njeri , Wachira Alvin , Manuthu Evans , Kariuki Hazel , Nyikuli Jared , Wekesa Cyprian , Otedo Amos , Bosire Hannah , Okoth Steve Biko , Ongalo Winston , Mukabi David , Lusamba Wilber , Muthui Beatrice , Adembesa Isaac , Mithi Caroline W , Sood Mohammed , Aliyan Nadia , Gituma Bernard , Giabe Matiko , Omondi Charles , Aman Rashid , Amoth Patrick , Kasera Kadondi , Were Fred , Nganga Wangari , Berkley James A , Tsofa Benjamin A , Mwangangi Joseph , Bejon Phillip , Barasa Edwine , English Mike , Scott J Anthony G , Akech Samuel , Kagucia E Wangeci , Agweyu Ambrose , Etyang Anthony O
Published: March 2024

There are limited data from sub–Saharan Africa describing the pattern of admissions to public hospitals with severe acute respiratory infections during the COVID–19 pandemic. We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. Demographic and clinical characteristics, COVID–19 infection and vaccination status and outcome data were collected. Of the 52,714 patients included in the study, 18,001 (35%) were admitted with severe acute respiratory illness (SARI). The mean age was 51 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, HIV and diabetes mellitus were the most common comorbidities. COVID–19 test results were positive in 2,370 (28%) of the 8,517 (47%) patients that underwent testing. Overall inpatient case fatality for SARI was 21% (n=3,828). After adjusting for age, sex and presence of a comorbidity, SARI patients had higher inpatient mortality compared to non-SARI patients regardless of their COVID–19 status (aHR 1.31, 95% CI 1.19 – 1.46). COVID–19 positive SARI patients had a higher inpatient mortality rate compared to their negative counterparts (aHR 1.31, 95% CI 1.12 – 1.54, p value < 0.0001). COVID-19 vaccine effectiveness against mortality due to SARI after adjusting for age, sex and presence of a comorbidity was 34% (95% CI 11% – 51%). We have provided a comprehensive description of the pattern of admissions with respiratory illnesses in Kenyan hospitals during the COVID–19 pandemic period. We have demonstrated the utility of routine surveillance activities within public hospitals in low-income settings which if strengthened can enhance the response to emerging health threats.
Multichannel tDCS with Advanced Targeting for Major Depressive Disorder: A Tele-Supervised At-Home Pilot Study
Authors: Ruffini Giulio , Salvador Ricardo , Castaldo Francesca , Baleeiro Thais , Camprodon Joan A. , Chopra Mohit , Cappon Davide , Pascual-Leone Alvaro
Published: March 2024

Introduction

Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS).

Methods

Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits.

Results

34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge’sg= −3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements.

Conclusions

These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.
Meditation Experience is Associated with Increased Structural Integrity of the Pineal Gland and greater total Grey Matter maintenance
Authors: Plini Emanuele RG , Melnychuk Michael C , Dockree Paul M
Published: March 2024

Growing evidence demonstrates that meditation practice supports cognitive functions including attention and interoceptive processing, and is associated with structural changes across cortical networks including prefrontal regions, and the insula. However, the extent of subcortical morphometric changes linked to meditation practice is less appreciated. A noteworthy candidate is the Pineal Gland, a key producer of melatonin, which regulates circadian rhythms that augment sleep-wake patterns, and may also provide neuroprotective benefits to offset cognitive decline. Increased melatonin levels as well as increased fMRI BOLD signal in the Pineal Gland has been observed in mediators vs. controls. However, it is not known if long-term meditators exhibit structural change in the Pineal Gland linked to lifetime duration of practice. In the current study we performed Voxel-based morphometry (VBM) analysis to investigate: 1) whether long-term meditators (LTMs) (n=14) exhibited greater Pineal Gland integrity compared to a control group (n=969), 2) a potential association between the estimated lifetime hours of meditation (ELHOM) and Pineal Gland integrity, and 3) whether LTMs show greater Grey Matter (GM) maintenance (BrainPAD) that is associated with Pineal Gland integrity. The results revealed greater Pineal Gland integrity and lower BrainPAD scores (younger brain age) in LTMs compared to controls. Exploratory analysis revealed a positive association between ELHOM and greater signal intensity in the Pineal Gland but not with GM maintenance as measured by BrainPAD score. However, greater Pineal integrity and lower BrainPAD scores were correlated in LTMs. The potential mechanisms by which meditation influences Pineal Gland function, hormonal metabolism, and GM maintenance are discussed – in particular melatonin’s roles in sleep, immune response, inflammation modulation, and stem cell and neural regeneration.
Multi-omics Integration Identifies Genes Influencing Traits Associated with Cardiovascular Risks: The Long Life Family Study
Authors: Acharya Sandeep , Liao Shu , Jung Wooseok J. , Kang Yu S. , Moghaddam Vaha A. , Feitosa Mary , Wojczynski Mary , Lin Shiow , Anema Jason A. , Schwander Karen , Connell Jeff O , Province Mike , Brent Michael R.
Published: March 2024

The Long Life Family Study (LLFS) enrolled 4,953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8×10−7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein-Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genesFCER1A, MS4A2, GATA2, HDC, andHRH4in atherosclerosis risks. Our findings also suggest that lower expression ofATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest thatENPP3may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform (https://nf-co.re/omicsgenetraitassociation).
Leveraging molecular-QTL co-association to predict novel disease-associated genetic loci using a graph convolutional neural network
Authors: Ng-Kee-Kwong Julian , Bretherick Andrew D.
Published: March 2024

Genome-wide association studies (GWAS) have successfully uncovered numerous associations between genetic variants and disease traits to date. Yet, identifying significantly associated loci remains a considerable challenge due to the concomitant multiple-testing burden of performing such analyses genome-wide. Here, we leverage the genetic associations of molecular traits – DNA CpG-site methylation status and RNA expression – to mitigate this problem. We encode their co-association across the genome using PinSage, a graph convolutional neural network-based recommender system previously deployed at Pinterest. We demonstrate, using this framework, that a model trained only on methylation quantitative trait locus (QTL) data could recapitulate over half (554,209/1,021,052) of possible SNP-RNA associations identified in a large expression QTL meta-analysis. Taking advantage of a recent ‘saturated’ map of height associations, we then show that height-associated loci predicted by a model trained on molecular-QTL data replicated comparably, following Bonferroni correction, to those that were genome-wide significant in UK Biobank (88% compared to 91%). On a set of 64 disease outcomes in UK Biobank, the same model identified 143 independent novel disease associations, with at least one additional association for 64% (41/64) of the disease outcomes examined. Excluding associations involving the MHC region, we achieve a total uplift of over 8% (128/1,548). We successfully replicated 38% (39/103) of the novel disease associations in an independent sample, with suggestive evidence for six additional associations from GWAS Catalog. Replicated associations included for instance that between rs10774625 (nearest gene: SH2B3/ATXN2) and coeliac disease, and that between rs12350420 (nearest gene: MVB12B) and glaucoma. For many GWAS, attaining such an enhancement by simply increasing sample size may be prohibitively expensive, or impossible depending on disease prevalence.
Cognitive Effects ofToxoplasmaand CMV Infections: A Cross-Sectional Study of 557 Young Adults Considering Modulation by Sex and Rh Factor
Authors: Flegr Jaroslav , Chvátalová Veronika , Příplatová Lenka , Tureček Petr , Kodym Petr , Šebánková Blanka , Kaňková Šárka
Published: March 2024

One-third of humanity harbors a lifelong infection withToxoplasma gondii. This parasite undergoes sexual reproduction in cats and asexual reproduction in any warm-blooded intermediate hosts. The cycle progresses as cats ingest these hosts, containing the parasite’s tissue cysts. Such infections can alter behaviors in both animals and humans, potentially increasing predation risk by felines—usually seen as parasite-induced manipulations. This study aims to delineate toxoplasmosis’s effects on cognitive abilities and compare these to the effects of human cytomegalovirus (CMV), which also infects the brain but is not spread through predation. We evaluated the cognitive performance of 557 students, who had been examined forToxoplasmaand CMV infections, using intelligence, memory, and psychomotor tests. Results indicated cognitive impairments in seropositive individuals for both pathogens, with variations in cognitive impact related to sex and Rh factor. Specifically,Toxoplasmawas associated with lower IQ in men, whereas CMV predominantly with worse women’s memory and reaction speeds. Analysis of antibody concentrations hinted that certainToxoplasma-associated cognitive detriments may wane (impaired intelligence) or worsen (impaired reaction times) over time following infection. The findings imply that cognitive impairments from both neurotropic pathogens are likely due to pathological changes in the brain rather than direct manipulative actions by the parasites.
DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers
Authors: Øgaard Nadia , Iden Cecilie R. , Jensen Sarah Østrup , Mustafa Salah Mohammad , Aagaard Emilie , Bramsen Jesper Bertram , Ahlborn Lise Barlebo , Hasselby Jane Preuss , Rohrberg Kristoffer Staal , Achiam Michael Patrick , Andersen Claus Lindbjerg , Mau-Sørensen Morten
Published: March 2024

Background

Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ AC) face poor outcomes. Thus, sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ AC.

Methods

Tumor DNA from 29 patients, and plasma cell-free DNA from 17 patients with advanced- and 17 patients with resectable G-GEJ AC, and from 50 healthy controls was analyzed. A tumor-agnostic, digital PCR test – TriMeth - targeting the gastrointestinal cancer-specific methylated genesC9orf50, KCNQ5, andCLIP4, was performed.

Results

TriMeth detected tumor DNA in 29/29 (100%) of the tumor tissue samples. Furthermore, TriMeth detected ctDNA in plasma from 13/17 (76%) of patients with advanced disease, 7/17 (41%) of patients with resectable disease, and in 0/50 (0%) of healthy controls.

Conclusions

This study demonstrates that TriMeth may hold potential as a biomarker for identification of ctDNA in patients with G-GEJ AC. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.
Modelling long COVID using Bayesian networks
Authors: Pérez Chacón Gladymar , Mascaro Steven , Estcourt Marie J. , Phetsouphanh Chan , Nicholson Ann E. , Snelling Tom , Wu Yue
Published: March 2024

Motivated by the ambiguity of operational case definitions for long COVID and the impact of the lack of a common causal language on long COVID research, in early 2023 we began developing a research framework on this post-acute infection syndrome. We used directed acyclic graphs (DAGs) and Bayesian networks (BNs) to depict the hypothesised mechanisms of long COVID in an agnostic fashion. The DAGs were informed by the evolving literature and subsequently refined following elicitation workshops with domain experts. The workshops were structured online sessions guided by an experienced facilitator. The causal DAGs aim to summarise the hypothesised pathobiological pathways from mild or severe COVID-19 disease to the development of pulmonary symptoms and fatigue over four different time points. The DAG was converted into a BN using qualitative parametrisation. These causal models aim to assist the identification of disease endotypes, as well as the design of randomised controlled trials and observational studies. The framework can also be extended to a range of other post-acute infection syndromes.
The Emerging Applications of Synthetic Data in Neurosurgery Research and Practice: A Systematic Review
Authors: Bouras Andrew
Published: March 2024

Background

The integration of data-driven technologies into neurosurgery, particularly through the advent of synthetic data, marks a significant evolution in the field. This qualitative systematic review explores the impact of synthetic data on neurosurgical practices, including preoperative planning, intraoperative navigation, postoperative care, training, and research. The goal is to provide a comprehensive assessment of the current applications, benefits, challenges, and future directions of synthetic data in neurosurgery.

Methods

A thorough literature review was conducted, focusing on peer-reviewed articles and conference proceedings that detail the use of synthetic data in neurosurgery. The review prioritized studies offering qualitative evaluations, case studies, technological developments, and expert perspectives on synthetic data’s integration into neurosurgical practices. Inclusion criteria were established to select studies that explicitly discuss the generation, utilization, and impact of synthetic data in the discipline.

Results

The analysis reveals that synthetic data contributes significantly to neurosurgery, enhancing surgical planning precision, training simulation accuracy, and enabling personalized care. Identified benefits include addressing the scarcity of clinical data, maintaining patient privacy, and facilitating machine learning model development. Challenges such as ensuring data realism and variability, along with the integration of synthetic data into clinical workflows, were also identified. The review further highlights synthetic data’s role in supporting collaborative research, navigating data sharing obstacles, and fostering innovation in neurosurgical methods and patient outcomes.

Conclusions

Synthetic data presents a transformative opportunity for neurosurgery, addressing historical challenges and fostering advancements. Despite existing hurdles, its application across neurosurgical domains indicates a shift towards more personalized, precise, and effective patient care. Overcoming these challenges requires ongoing interdisciplinary cooperation and technological progress. The review emphasizes the necessity for standardized methodologies, ethical considerations, and a proactive stance to leverage synthetic data’s potential fully in neurosurgical advancements.
Visualization ofBacillus subtilisSpore Structure and Germination using Quick-Freeze Deep-Etch Electron Microscopy
Authors: Jalil Kiran , Tahara Yuhei O. , Miyata Makoto
Published: March 2024

Bacterial spores, known for their complex and resilient structures, have been the focus of visualization using various methodologies. In this study, we applied quick-freeze and replica electron microscopy techniques, allowing observation ofBacillus subtilisspores in high-contrast and three-dimensional detail. This method facilitated visualization of the spore structure with enhanced resolution and provided new insights into the spores and their germination processes. We identified and described five distinct structures: (i) hair-like structures on the spore surface, (ii) spike formation on the surface of lysozyme-treated spores, (iii) the fractured appearance of the outer spore cortex during germination, (iv) potential connections between small vesicles and the core membrane, and (v) the evolving surface structure of nascent vegetative cells during germination.
Gretl - Variation GRaph Evaluation TooLkit
Authors: Vorbrugg Sebastian , Bezrukov Ilja , Bao Zhigui , Weigel Detlef
Published: March 2024

Motivation: As genome graphs are powerful data structures for representing the genetic diversity within populations, they can help identify genomic variations that traditional linear references miss, but their complexity and size makes the analysis of genome graphs challenging. We sought to develop a genome graph analysis tool that helps these analyses to become more accessible by addressing the limitations of existing tools. Specifically, we improve scalability and user-friendliness, and we provide many new statistics for graph evaluation.

Results: We developed an efficient, comprehensive, and integrated tool,gretl, to analyse genome graphs and gain insights into their structure and composition by providing a wide range of statistics.gretlcan be utilised to evaluate different graphs, compare the output of graph construction pipelines with different parameters, as well as perform an in-depth analysis of individual graphs, including sample-specific analysis. With the assistance ofgretl, novel patterns of genetic variation and potential regions of interest can be identified, for later, more detailed inspection. We demonstrate thatgretloutperforms other tools in terms of speed, particularly for larger genome graphs.

Availability and implementation:gretlis implemented in Rust. Commented source code is available under MIT licence athttps://github.com/MoinSebi/gretl. Examples of how to rungretlare provided in the documentation. Several Jupyter notebooks are part of the repository and can help visualisegretlresults.
A synthesis on alien mammals threatened in their native range
Authors: Tedeschi Lisa , Lenzner Bernd , Schertler Anna , Biancolini Dino , Rondinini Carlo , Essl Franz
Published: March 2024

Many alien species are safe in their native ranges; however, some are threatened, posing a challenging conundrum for conservation and invasion science. We focused on alien threatened mammals, examining their distribution, pathways, threats, and conservation strategies. We also reassessed their IUCN Red List category to evaluate the effect of including alien populations in extinction risk assessments. Of 242 alien mammals, we identified 41 aliens that are threatened, classified as critically endangered (19%), endangered (27%), or vulnerable (54%). They were primarily introduced for hunting and exchanged within Asia, with introduced ranges concentrated in eastern Australia. They were subject to multiple threats, most notably biological resource use. Including alien populations in the categorization assessments reduces extinction risk of 22% of the species. We highlighted the conservation value of alien populations for threatened mammals. However, conservation managers and extinction risk assessors shall carefully consider their use, to avoid negative impacts on native biodiversity.
The Role of the Co-Chaperone DNAJB11 in Polycystic Kidney Disease: Molecular Mechanisms and Cellular Origin of Cyst Formation
Authors: Busch Tilman , Neubauer Björn , Schmitt Lars , Cascante Isabel , Knoblich Luise , Wegehaupt Oliver , Schöler Felix , Tholen Stefan , Hofherr Alexis , Schell Christoph , Schilling Oliver , Westermann Lukas , Köttgen Anna , Köttgen Michael
Published: March 2024

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations inPKD1andPKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regulation of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident proteins through mechanisms that are not well understood. Here, we investigate the function of DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with constitutive and conditionalDnajb11inactivation andDnajb11-deficient renal epithelial cells to investigate the mechanism underlying autosomal dominant inheritance, the specific cell types driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic kidney disease. We show that biallelic loss ofDnajb11causes cystic kidney disease and fibrosis, mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly originate from proximal tubules. Cyst formation beginsin uteroand the timing ofDnajb11inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis ofDnajb11- andPkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.
The Interplay Between Nutrition and the Dynamics of the Midgut Microbiome of the MosquitoAedes aegyptiReveals Putative Symbionts
Authors: Salgado João Felipe M. , Premkrishnan Balakrishnan N. V. , Oliveira Elaine L. , Vettath Vineeth Kodengil , Goh Feng Guang , Hou Xinjun , Drautz-Moses Daniela I. , Cai Yu , Schuster Stephan C. , Junqueira Ana Carolina M.
Published: March 2024

Blood meals are crucial for the reproductive cycle ofAedes aegyptiand represent the means by which arboviruses are transmitted to its hematophagy hosts. It also has been postulated that feeding on blood may modulate the mosquito microbiome, but the compositional shifts in microbial diversity and function remain elusive. In this paper, we analyzed the modulation of the midgut microbiome in 60 females ofAedes aegyptithroughout the digestive period, 12, 24, and 48 hours after blood or sugar meals using whole-genome shotgun sequencing. Microbial transstadial transmission between larvae and adults was also assessed. This approach provided a high coverage of the midgut metagenome, allowing microbial taxonomic assignments at the species level and gene-based functional profiling. Females at later hours post-feeding and larvae display low microbiome diversities and little evidence of transstadial transmission. However, a striking proliferation of Enterobacterales was observed during early hours of digestion in blood-fed mosquitoes. The compositional shift was concomitant with a predicted functional change in genes associated with carbohydrate and protein metabolism. The observed shifts in blood-fed females’ midguts are restored to a sugar-fed-like microbial profile after 48h, when blood digestion is completed. Conversely, as in all blood-fed females, a high abundance of the opportunistic human pathogenElizabethkingia anophelis(Flavobacteriales) takes place in this post-digestion stage. This bacterial species has also been described as a symbiont of mosquitoes of the genusAnopheles(Culicidae). This work is the first report of the adaptation of the midgut microbiomeof A. aegyptito a digestive role after a blood meal, at the expense of the proliferation of potential symbionts.

Significance statement

The findings in this paper can contribute to a better understanding of the dynamics of the mosquito microbiome during digestion and its potential implications for host physiology and metabolism, also informing the future development of sustainable methods for insect-borne diseases control based on microbial components that might influence vectorial capacity and pathogen transmission byA. aegypti.
Characterization of early and late events of adherens junction assembly
Authors: Troyanovsky Regina B. , Indra Indrajyoti , Troyanovsky Sergey M.
Published: March 2024

Cadherins are transmembrane adhesion receptors. Cadherin ectodomains form adhesive 2D clusters through cooperativetransandcisinteractions, whereas its intracellular region interacts with specific cytosolic proteins, termed catenins, to anchor the cadherin-catenin complex (CCC) to the actin cytoskeleton. How these two types of interactions are coordinated in the formation of specialized cell-cell adhesions, adherens junctions (AJ), remains unclear. We focus here on the role of the actin-binding domain of α-catenin (αABD) by showing that the interaction of αABD with actin generates actin-bound CCC oligomers (CCC/actin strands) incorporating up to six CCCs. The strands are primarily formed on the actin-rich cell protrusions. Once in cell-cell interface, the strands become involved in cadherin ectodomain clustering. Such combination of the extracellular and intracellular oligomerizations gives rise to the composite oligomers,transCCC/actin clusters. To mature, these clusters then rearrange their actin filaments using several redundant pathways, two of which are characterized here: one depends on the α-catenin-associated protein, vinculin and the second one depends on the unstructured C-terminus of αABD. Thus, AJ assembly proceeds through spontaneous formation oftransCCC/actin clusters and their successive reorganization.
Many-Species Ecological Fluctuations as a Jump Process from the Brink of Extinction
Authors: Arnoulx de Pirey Thibaut , Bunin Guy
Published: March 2024

Highly diverse ecosystems exhibit a broad distribution of population sizes and species turnover, where species at high and low abundances are exchanged over time. We show that these two features generically emerge in the fluctuating phase of many-variable model ecosystems with disordered species interactions, when species are supported by migration from outside the system at a small rate. We show that these and other phenomena can be understood through the existence of a scaling regime in the limit of small migration, in which large fluctuations and long timescales emerge. We construct an exact analytical theory for this asymptotic regime that provides scaling predictions on timescales and abundance distributions that are verified exactly in simulations. In this regime, a clear separation emerges between rare and abundant species at any given time, despite species moving back and forth between the rare and abundant subsets. The number of abundant species is found to lie strictly below a well-known stability bound, maintaining the system away from marginality. At the same time, other measures of diversity, which also include some of the rare species, go above this bound. In the asymptotic limit where the migration rate goes to zero, trajectories of individual species abundances are described by non-Markovian jump-diffusion processes, which proceeds as follows: A rare species remains so for some time, then experiences a jump in population sizes after which it becomes abundant (a species turnover event) and later sees its population size gradually decreasing again until rare, due to the competition with other species. The asymmetry of abundance trajectories under time reversal is maintained at a small but finite migration rate. These features may serve as fingerprints of endogenous fluctuations in highly diverse ecosystems.

Published by the American Physical Society
2024
Droplet microfluidics for time-resolved serial crystallography
Authors: Stubbs Jack , Hornsey Theo , Hanrahan Niall , Esteban Luis Blay , Bolton Rachel , Malý Martin , Basu Shibom , Orlans Julien , de Sanctis Daniele , Shim Jung-uk , Shaw Stewart Patrick D. , Orville Allen M. , Tews Ivo , West Jonathan
Published: March 2024

Serial crystallography requires large numbers of microcrystals and robust strategies to rapidly apply substrates to initiate reactions in time-resolved studies. Here, we report the use of droplet miniaturization for the controlled production of uniform crystals, providing an avenue for controlled substrate addition and synchronous reaction initiation. The approach was evaluated using two enzymatic systems, yielding 3 µm crystals of lysozyme and 2 µm crystals of Pdx1, anArabidopsisenzyme involved in vitamin B6 biosynthesis. A seeding strategy was used to overcome the improbability of Pdx1 nucleation occurring with diminishing droplet volumes. Convection within droplets was exploited for rapid crystal mixing with ligands. Mixing times of <2 ms were achieved. Droplet microfluidics for crystal size engineering and rapid micromixing can be utilized to advance time-resolved serial crystallography.
Structural changes in Rochelle salt on phase transitions revisited in a multi-temperature single-crystal X-ray diffraction study
Authors: Sharaya Svetlana S. , Zakharov Boris A. , Boldyreva Elena V.
Published: March 2024

Phase transitions in Rochelle salt [sodium potassium L(+)-tartrate tetrahydrate] are revisited in a single-crystal X-ray diffraction multi-temperature study on cooling from 308 to 100 K across the high-temperature paraelectric (PE) ↔ ferroelectric ↔ low-temperature PE phase transition points. The results of structure refinement using three different models (a harmonic with and without disorder, and an anharmonic) were compared. The temperature dependencies of anisotropic displacement parameters (ADPs) and U
eq, which can be calculated directly from ADPs, for the low-temperature PE phase indicate clearly the dynamic nature of disorder of the K1 atoms. The structures of the low-temperature and the high-temperature PE phases are compared for the first time at multiple temperatures for each phase based on diffraction data collected from the same single crystal. The data indicate that the high-temperature and the low-temperature paraelectric phases are probably not two different phases, as was assumed in earlier works, but are structurally the same phase at different temperatures.
Deterministic and stochastic finite element modeling of reinforced concrete beams without stirrups containing plastic wastes
Authors: Ghannoum Maria , Assaad Joseph , Daaboul Michel , El-Mir Abdulkader
Published: March 2024

Purpose

The use of waste polyethylene terephthalate (PET) plastics derived from shredded bottles in concrete is not formalized yet, especially in reinforced members such as beams and columns. The disposal of plastic wastes in concrete is a viable alternative to manage those wastes while minimizing the environmental impacts associated to recycling, carbon dioxide emissions and energy consumption.

Design/methodology/approach

This paper evaluates the suitability of 2D deterministic and stochastic finite element (FE) modeling to predict the shear strength behavior of reinforced concrete (RC) beams without stirrups. Different concrete mixtures prepared with 1.5%–4.5% PET additions, by volume, are investigated.

Findings

Test results showed that the deterministic and stochastic FE approaches are accurate to assess the maximum load of RC beams at failure and corresponding midspan deflection. However, the crack patterns observed experimentally during the different stages of loading can only be reproduced using the stochastic FE approach. This later method accounts for the concrete heterogeneity due to PET additions, allowing a statistical simulation of the effect of mechanical properties (i.e. compressive strength, tensile strength and Young’s modulus) on the output FE parameters.

Originality/value

Data presented in this paper can be of interest to civil and structural engineers, aiming to predict the failure mechanisms of RC beams containing plastic wastes, while minimizing the experimental time and resources needed to estimate the variability effect of concrete properties on the performance of such structures.
Global talent management – talents, mobility and global experiences – a systematic literature review
Authors: Sousa Bianca , Ferreira João J.M. , Jayantilal Shital , Dabic Marina
Published: March 2024

Purpose

The purpose of this paper is to provide a comprehensive framework that identifies thematic clusters and their interconnections within Global Talent Management (GTM), global careers and talent management (TM).

Design/methodology/approach

In this paper, this study conducted a co-citation analysis using bibliographic data to unveil the intellectual connections and relationships among thematic articles related to GTM sourced from the Web of Science.

Findings

This review highlights three key research themes: experiences working abroad, TM approaches and the complex nature of GTM as a living system.

Research limitations/implications

The main limitation of this research is the sample itself. Content analysis based on the co-citation method resulted in some more recent releases being omitted.

Practical implications

The practical implications of the paper include providing a structured framework for understanding the complexities of GTM.

Social implications

Research into the academic literature in this area is divided into various clusters, empirically demonstrating how GTM and global mobility are intertwined, revealing the need for us to more thoroughly comprehend the social ramifications of GTM practices and activities and the need to further analyse the influencing social aspects in a GTM strategy, like diversity, increased mobility and virtual reality.

Originality/value

The analysis revealed the emergence of three distinct thematic groups: (1) global work experiences, (2) TM approaches and (3) GTM.