bluuebunny/crossref_metadata_2025 huggingface dataset:
Women's perceptions and preferences for cervical cancer screening in light of updated guidelines
Authors: Bustamante Gabriela , Liebermann Erica , McNair Katelyn , Fontenot Holly B.
Published: July 2023

Background:

Updated risk-based guidelines for cervical cancer screening (CCS) allow for individualized screening that minimizes unnecessary testing. However, these guidelines are complex and may not be easily understandable to patients.

Purpose:

To describe women's perceptions and preferences about CCS in light of recent guideline changes.

Methodology:

This qualitative study conducted in February 2020 used online, text-based focus groups with a sample of US women (n = 49) ages 27–45. After participants completed a short demographic survey, an experienced moderator used a semistructured guide to solicit participants' perceptions of routine gynecologic care and CCS. We summarized survey data using descriptive statistics. Two authors analyzed transcripts using conventional content analysis and met with other team members to resolve discrepancies and determine final themes.

Results:

Most participants were non-Hispanic White (65%), had health insurance (90%), and reported having a routine gynecologic examination in the past year (70%). We identified four common themes: (1) low perceived risk of human papillomavirus (HPV) coupled with low knowledge about HPV as a causative factor for cervical cancer, (2) confusion about—and mistrust of—recent individual risk-based guidelines that determine the indicated timing and type of CCS test (Pap or HPV testing), (3) mixed opinions about performing a self-swab for HPV testing, and (4) conflicting perceptions of trust toward providers and the health care industry.

Conclusions:

Findings highlight women's uncertainty and hesitancy about updated CCS guidelines.

Implications:

Provider–patient communication strategies should consider women's gaps in knowledge about HPV, include the rationale for guidelines and types of tests, and build trust between patients and providers.
Treatment of hyperhidrosis with Botox (onabotulinumtoxinA): Development, insights, and impact
Authors: Lowe Nicholas , Naumann Markus , Eadie Nina
Published: July 2023

Hyperhidrosis (chronic excessive sweating) may substantially affect an individual’s emotional and social well-being. Therapies available before onabotulinumtoxinA were generally topical, with limited effectiveness, application-site skin reactions, and frequent, time-consuming treatments. Intradermal injection of onabotulinumtoxinA to treat sweat glands arose as a novel therapeutic approach. To develop this treatment, appropriate dosing needed to be established, and training on administration was required. Further, no previous scale existed to measure the effects of hyperhidrosis on patients’ lives, leading Allergan to develop and validate the 4-point Hyperhidrosis Disease Severity Scale (HDSS), which measures the disease’s impact on daily activities.

The onabotulinumtoxinA clinical development program for hyperhidrosis included 2 double-blind, placebo-controlled pivotal trials, immunogenicity studies, long-term studies of safety and efficacy, and quality of life assessments. In Europe and North America, the primary efficacy measures were, respectively, axillary sweat production measured gravimetrically and HDSS improvement. Compared with placebo, onabotulinumtoxinA treatment significantly reduced axillary sweat production and axillary hyperhidrosis severity, as measured by a 2-point or greater reduction on the HDSS. The effects of onabotulinumtoxinA occurred rapidly, within 1 week after injection, and lasted ≥6 months. Treatment with onabotulinumtoxinA was associated with significant quality of life improvements based on Short Form-12 physical and mental component scores. The Hyperhidrosis Impact Questionnaire also indicated greater treatment satisfaction, reduced negative impact on aspects of daily life, and improved emotional well-being with onabotulinumtoxinA versus placebo. The clinical development program and subsequent clinical experience showed that onabotulinumtoxinA treatment for hyperhidrosis was well tolerated with no new safety signals, and led to greater disease awareness.
Fatigue and Physical Activity Patterns in Children With Inflammatory Bowel Disease
Authors: Bevers Nanja , Van de Vijver Els , Hanssen Adrienne , Aliu Arta , Vande Velde Saskia , Roelant Ella , Rezazadeh Ardabili Ashkan , Rosias Philippe , Stapelbroek Janneke , Maartens Imke Bertrams , van de Feen Cathelijne , Escher Johanna , Oudshoorn Annemarie , Teklenburg-Roord Sarah , Vreugdenhil Anita , Pierik Marie , van Rheenen Patrick
Published: July 2023

Objectives:

Fatigue is a common symptom in children with inflammatory bowel disease (IBD). Diagnostic tests to evaluate biological causes of fatigue commonly include markers of inflammation and hemoglobin (Hb), yet functional parameters have been inadequately studied in pediatric IBD. In this study, we compared fatigued and non-fatigued children with IBD from both a biological and functional point of view.

Methods:

A cross-sectional study of 104 pediatric IBD patients with mild to moderately active IBD was conducted. Fatigued children were defined as those with a Pediatric Quality of Life Inventory Multidimensional Fatigue Scale z score <−2.0. Non-fatigued children had a z score ≥−2.0. Disease-specific quality of life (measured with IMPACT-III score), C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin z score (Hb z score), and physical activity tests including 6-minute walking distance z score (6MWD z score) and triaxial accelerometry (TA) were evaluated.

Results:

Fatigued children (n = 24) had a significant lower IMPACT-III score than non-fatigued children (n = 80). Hb z scores, CRP, FC, and 6MWD z scores were not significantly different between groups. TA was performed in 71 patients. Wear time validation requirements were met in only 31 patients. Fatigued patients spent significant shorter median time in moderate-to-vigorous activity than non-fatigued patients (18.3 vs 37.3 minutes per day, P = 0.008).

Conclusion:

Biological parameters did not discriminate fatigued from non-fatigued patients. TA possibly distinguishes fatigued from non-fatigued patients; the potential association may provide a target for interventions to combat fatigue and improve quality of life.
The Predictive Power of Pain Characteristics and Sleep Quality on Fatigue in Adolescents With Cancer
Authors: Akdeniz Kudubes Asli , Bektas Murat , Gerceker Gülçin Özalp
Published: July 2023

This study was conducted as descriptive, methodological, and cross-sectional research to determine the predictive power of pain characteristics and sleep quality on fatigue in adolescents with cancer. The study was conducted between November 2020 and April 2021 with 139 adolescents with cancer who reported pain. The study data were collected via an AdolescentInformation Form, the Adolescent Pediatric Pain Tool, the Scale For The Assessment Of Fatigue in Pediatric Oncology Patients Aged 13-18, and the Sleep Assessment Scale for Children with Cancer—Adolescent Form. Mean values, percentage calculations, Pearson correlation analysis, and linear regression analysis were used in the analysis of the data. There was a high level and negative correlation between pain characteristics (pain location, severity, and quality) of the adolescents participating in the study and their mean scores from the overall fatigue scale and its subdimensions and a high level and positive correlation with their mean scores from the overall sleep quality scale. Pain characteristics and sleep quality of adolescents with cancer explained 74% of fatigue. Pain, sleep quality, and fatigue are symptoms that should be closely addressed in adolescents with cancer.
Predictors of Outcomes in 900 Alveolar Bone Grafts
Authors: Padwa Bonnie L. , Tio Pauline , Garkhail Prakriti , Nuzzi Laura C.
Published: July 2023

Background:

Significant discrepancies exist in the reported variables influencing alveolar bone graft outcomes. The purpose of this study was to evaluate graft success and identify outcome predictors in a large patient cohort using an objective cone beam computed tomography assessment tool.

Methods:

Consecutive patients with cleft lip/palate who underwent alveolar bone grafting by 1 surgeon were included. Predictor variables were age at graft, oronasal fistula, canine position, concurrent premaxillary osteotomy, size of cleft, presence of bony palatal bridge, history of failed graft, location of primary repair, and surgeon experience. The outcome variable was graft success, determined using a cone beam computed tomography assessment tool and defined as a score of 3 or 4 (out of 4) in the following domains: vertical bone level, labiopalatal thickness, and nasal piriform symmetry.

Results:

The sample included 900 alveolar cleft sites (median graft age, 9.9 years). The success rate was 94.6%. Presence of an erupted canine, large cleft defect, or premaxillary osteotomy were independent predictors of graft failure; presence of a bony palatal bridge was associated with graft success (P < 0.05).

Conclusions:

Presence of an erupted canine, large bony defect, or premaxillary osteotomy increase the risk of failure, and a bony palatal bridge portends success. Age 12 years or older, visible oronasal fistula, history of failed graft, primary cleft repaired at outside institution, and surgeon experience were associated with higher graft failure, but were not independent predictors when controlling for covariates. Surgeons should be aware that these factors in combination increase the odds of graft failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Convergent Validity of 2 Widely Used Methodologies for Calculating the Hospital Standardized Mortality Ratio in Flanders, Belgium
Authors: Cox Bianca , Van Wilder Astrid , De Ridder Dirk , Tambeur Wim , Maertens Pieter , Stijnen Pieter , Voorspoels Wouter , Vanden Boer Guy , Bruyneel Luk , Vanhaecht Kris
Published: July 2023

Objectives

To assess their construct validity, we compared results from 2 models used for estimating hospital standardized mortality ratios (HSMRs) in Belgium. The method of the Flemish Hospital Network (FHN) is based on a logistic regression for each of the 64 All Patient Refined Diagnosis-Related Groups that explain 80% of mortality and uses the Elixhauser score to correct for comorbidities. (H)SMRs published on the 3M-Benchmark-Portal are calculated by a simpler indirect standardization for All Patient Refined Diagnosis-Related Groups and risk of mortality (ROM) at discharge.

Methods

We used administrative data from all eligible hospital admissions in 22 Flemish hospitals between 2016 and 2019 (FHN, n = 682,935; 3M, n = 2,122,305). We evaluated model discrimination and accuracy and assessed agreement in estimated HSMRs between methods.

Results

The Spearman correlation between HSMRs generated by the FHN model and the standard 3M model was 0.79. Although 2 of 22 hospitals showed opposite classification results, that is, an HSMR significantly <1 according to the FHN method but significantly >1 according to the 3M model, classification agreement between methods was significant (agreement for 59.1% of hospitals, κ = 0.45). The 3M model (c statistic = 0.96, adjusted Brier score = 26%) outperformed the FHN model (0.87, 17%). However, using ROM at admission instead of at discharge in the 3M model significantly reduced model performance (c statistic = 0.94, adjusted Brier score = 21%), but yielded similar HSMR estimates and eliminated part of the discrepancy with FHN results.

Conclusions

Results of both models agreed relatively well, supporting convergent validity. Whereas the FHN method only adjusts for disease severity at admission, the ROM indicator of the 3M model includes diagnoses not present on admission. Although diagnosis codes generated by complications during hospitalization have the tendency to increase the predictive performance of a model, these should not be included in risk adjustment procedures.
Safety, Tolerability, and Pharmacokinetics of a Novel Macrocyclic Gadolinium-Based Contrast Agent, HNP-2006, in Healthy Subjects
Authors: Huh Ki Young , Chung Woo Kyung , Lee Heejeong , Choi Seung Hong , Yu Kyung-Sang , Lee SeungHwan
Published: July 2023

Objectives

Gadolinium-based contrast agents (GBCAs) are indispensable in contrast-enhanced magnetic resonance imaging. A higher risk of gadolinium deposition in linear GBCAs required the introduction of macrocyclic GBCAs with a stable molecular structure. We conducted the first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (PKs) of HNP-2006, a novel macrocyclic GBCA, in healthy male subjects.

Materials and Methods

A randomized, placebo-controlled, double-blind, single-ascending dose study was conducted. Subjects received either a single intravenous bolus injection of HNP-2006 or its matching placebo with a treatment-to-placebo ratio of 6:2 at the dose level of 0.02, 0.05, 0.1, 0.2, and 0.3 mmol/kg. Safety was assessed through routine clinical assessments. Blood sampling and urine collection were performed up to 72 hours postdose for PK assessments. Noncompartmental methods were used to calculate PK parameters, and a population PK model was constructed.

Results

Overall, 40 subjects completed the study. Fourteen subjects reported 22 treatment-emergent adverse events (TEAEs). The severity of all TEAEs was mild, and the HNP-2006 dose was associated with the incidence of TEAEs. The most common TEAEs included nausea and dizziness, which occurred within an hour of administration. HNP-2006 was rapidly eliminated by urinary excretion with a half-life of 1.8–2.0 hours and showed a dose-proportional PK. A 2-compartment model had the best fit with the population PK analysis.

Conclusions

A single intravenous dose of HNP-2006 was well-tolerated and safe up to 0.30 mmol/kg. HNP-2006 was rapidly excreted in urine and exhibited dose-independent PK profiles.
Retrospective Study of an Epidemic Vibrio Cholerae in the Central Region of Ghana; An Evidence from Surveillance Data
Authors: Acheampong Gideon K. , Owusu Isaac , Zumah Fidelis , Akyereko Ernest , Mpangah Rebecca Ann
Published: July 2023

Background: In the Central region of Ghana, cases of cholera were detected in October 2016, in the Cape Coast Metropolis. The number of cases detected in the peri-urban communities rose exponentially indicating a high transmission potential of infections. We conducted a descriptive analysis of surveillance data of the 2016 cholera outbreak in the Central Region with the aim of describing the epidemiological features of the outbreak. Methods: A retrospective analysis of cholera cases between October and December 2016 was conducted using variables including date of onset of symptoms, age, sex, rapid diagnostic test (RDT) results and district of residence of cases. Cases were descriptively characterized in terms of time, place, and person, attack rates were computed, and an epidemic curve was constructed using the date of onset of symptoms of cases.Pearson chi-square/Fisher exact tests were used to determine associations among selected variables of cases. Results: A total of 731 cases of cholera were reported with an overall attack rate of 67 cases per 100,000 population; no fatalities were recorded. The epi-curve showed multiple progressive peaks denoting a propagated type of outbreak driven by person-to-person transmission of infections. The mean age was 23 years, with 40% of cases occurring in the age group 15-24 years. The difference between the number of cases for males and females was not significant (p-value = 0.619). Close to 90% of all cases were reported from the Cape Coast Metropolis. Abura-Asebu-Kwamankese (AAK) and Komenda-Edina-Eguafo Abirem (KEEA) had a combined number of 64 cases (10%). There was a significant association between RDT results and the bacterial culture test (p<0.001), as well as that between sex and final case classification (p=0.004). Conclusion: The cholera outbreak affected a total of 731 people, with the highest number of cases reported in the 15-24 year age group. The outbreak was driven by person-to-person transmission and contaminated food and water sources. Rampant open defecation, open roadside food and water vending, and poor personal hygiene practices including hand washing were identified as major risk factors. The Cape Coast Metropolis and the KEEA were the most affected with the highest number of cases and the highest attack rate. The outbreak was predominantly confirmed through rapid diagnostic tests and culture confirmation. Current and future development projects must be geared towards effective town planning and decongestion, provision of designated dumping sites, toilet facilities and more water treatment plants. It is also imperative that district health officials also explore the issues of poor health-seeking behavior and access to care as possible factors contributing to high morbidities. Keywords; Cholera, Cape Coast Metropolis, Attack rate, Retrospective analysis
Sequential colonization events with restricted gene flow in a widespread European carnation species
Authors: Kaczmarek T. , Chen X. , Fior S. , Venon A. , Roman A. , Ursu T. , Giraud T. , Mezhenskyj V. , Koupilova K. , Hood M.E. , Widmer A. , Cornille A.
Published: July 2023

The key questions relating to the evolutionary processes underlying plant colonization success pertain to the geographic origin of the source population(s), the location of the migration routes, the extent to which genetic diversity is reduced via founder effects, and the extent of gene flow among populations during expansion. However, these questions must still be addressed for perennial herbaceous plants with large geographic distributions. We investigated the colonization history ofDianthus carthusianorum(the Carthusian Pink), one of the most widespread European carnation species. We called genome-wide 236,964 SNPs from a large sample across theD. carthusianorumdistribution range, and used up-to-date population genomics approaches (approximate Bayesian computation Random-Forest method, ABC-RF) to infer population demographic history. Spatial genetic structure and diversity analyses and demographic inferences indicated successive East-West colonization events by the Carthusian Pink. ABC-RF also revealed gene flow during colonization, but only among geographically close populations. This study provides important insights into the colonization processes of herbaceous perennial species belonging to one of Europe’s most diverse plant genera.
MLOsMetaDB, a meta-database to centralize the information on Liquid-liquid phase separation proteins and Membraneless organelles
Authors: Orti Fernando , Fernández María Laura , Marino-Buslje Cristina
Published: July 2023

Over the past few years, there has been a focus on proteins that create separate liquid phases in the intracellular liquid environment, known as membraneless organelles (MLO). These organelles allow for the spatiotemporal associations of macromolecules that dynamically exchange within the cellular milieu. They provide a form of compartmentalization crucial for organizing key functions in many cells. Metabolic processes and signaling pathways in both the cytoplasm and nucleus are among the functions performed by MLOs, which are facilitated by diverse combinations of proteins and nucleic acids. However, disruptions in these liquid-liquid phase separation processes (LLPS) may lead to several diseases, such as neurodegenerative disorders and cancer, among others.

To foster the study of this process and MLOs function, we presentMLOsMetaDB(http://mlos.leloir.org.ar), a comprehensive resource of information on MLO and LLPS related proteins. Our database integrates and centralizes available information for every protein involved in MLOs, which is otherwise disseminated across a plethora of different databases.

Our manuscript outlines the development and features of MLOsMetaDB which provides an interactive and user-friendly environment with modern biological visualizations and easy and quick access to proteins based on LLPS role, MLO location, and organisms. Additionally, it offers an advanced search for making complex queries to generate customized information.

Furthermore, MLOsMetaDB provides evolutionary information by collecting the orthologs of every protein in the same database.

This is a crucial resource for transferring knowledge to other species because the LLPS protein databases are highly biased towards human proteins and, to a lesser extent, a few other well-studied or model organisms. Overall, MLOsMetaDB is a valuable resource as a starting point for researchers studying the many processes driven by LLPS proteins and membraneless organelles.
Cell Surface β-Lactamase Recruitment: A Facile Selection to Identify Protein-Protein Interactions
Authors: Hinmon Jordan A. , King Jade M. , Mayo Latrina J. , Faries Cierra R. , Street Ya’hnis T. , Crawford David W. , Beardslee Patrick C. , Hendricks Alexander , McNaughton Brian R.
Published: July 2023

Protein-protein interactions are central to many cellular processes, and the identification of novel protein-protein interactions is a critical step in the discovery of protein therapeutics. Simple methods to identify naturally existing or laboratory evolved protein-protein interactions are therefore valuable research tools. We have developed a facile selection that links protein-protein interaction-dependent β-lactamase recruitment on the surface of E. coli with resistance to ampicillin. Bacteria displaying a protein which form a complex with a specific protein-β-lactamase fusion are protected from ampicillin-dependent cell death. In contrast, bacteria that do not recruit β-lactamase to the cell surface are killed by ampicillin. Given its simplicity and tunability, we anticipate this selection will be a valuable addition to the palette of methods for illuminating and interrogating protein-protein interactions.
Shrew evolution in hybrid zones: a meiotic undecavalent as an exclusive chromosomal supermultivalent and its weak effect on fertility
Authors: Matveevsky Sergey , Kolomiets Oxana , Shchipanov Nikolay A. , Pavlova Svetlana V.
Published: July 2023

Hybrid zones are “natural laboratories” for studying speciation. In the common shrewSorex araneus, the hybrid zone between extremely divergent in karyotypes the Moscow and Seliger chromosomal races is unique, because complex heterozygotes (interracial hybrids) form the longest meiotic configuration consisting of 11 chromosomes with monobrachial homology (undecavalent or chain-of-eleven – CXI). Different studies suggested that such a multivalent would negatively affect meiotic progression and, in general, would significantly reduce fertility. In this work, using immunocytochemical and electron microscopy methods, we investigated chromosome synapsis, recombination, and meiotic silencing in pachytene spermatocytes carrying undecavalent. Despite some abnormalities detected in spermatocytes, such as single associations of chromosomes, stretched centromeres in the multivalent, shifted recombinational peak towards distal parts of chromosomal arms of superchain, heterozygous shrews were able to form a large number of morphologically normal and active spermatozoa. Possible low stringency of pachytene checkpoints, proper segregation of homologous chromosomes, and the ability of hybrids to form mature germ cells imply rapid evolutionary fixation and circulation of Rb chromosomes within shrew populations, leading to a variety of chromosomal races.
Multi-modal representation of the size of space in the human brain
Authors: Lee Jaeeun , Park Soojin
Published: July 2023

To estimate the size of an indoor space, we must analyze the visual boundaries that limit the spatial extent and acoustic cues from reflected interior surfaces. We used fMRI to examine how the brain processes geometric size of indoor scenes when various types of sensory cues are presented individually or together. Specifically, we asked whether the size of space is represented in a modality-specific way or in an integrative way that combines multimodal cues. In a block-design study, images or sounds that depict small and large sized indoor spaces were presented. Visual stimuli were real-world pictures of empty spaces that were small or large. Auditory stimuli were sounds convolved with different reverberation. By using a multi-voxel pattern classifier, we asked whether the two sizes of space can be classified in visual, auditory, and visual-auditory combined conditions. We identified both sensory specific and multimodal representations of the size of space. To further investigate the nature of the multimodal region, we specifically examined whether it contained multimodal information in a coexistent or integrated form. We found that AG and the right IFG pars opercularis had modality-integrated representation, displaying sensitivity to the match in the spatial size information conveyed through image and sound. Background functional connectivity analysis further demonstrated that the connection between sensory specific regions and modality-integrated regions increase in the multimodal condition compared to single modality conditions. Our results suggest that the spatial size perception relies on both sensory specific and multimodal representations, as well as their interplay during multimodal perception.
Discovering genetic biomarkers for targeted cancer therapeutics with eXplainable AI
Authors: Chakraborty Debaditya , Gutierrez-Chakraborty Elizabeth , Rodriguez-Aguayo Cristian , Başağaoğlu Hakan , Lopez-Berestein Gabriel , Amero Paola
Published: July 2023

Explainable Artificial Intelligence (XAI) enables a holistic understanding of the complex and nonlinear relationships between genes and prognostic outcomes of cancer patients. In this study, we focus on a distinct aspect of XAI – to generate accurate and biologically relevant hypotheses and provide a shorter and more creative path to advance medical research. We present an XAI-driven approach to discover otherwise unknown genetic biomarkers as potential therapeutic targets in high-grade serous ovarian cancer, evidenced by the discovery of IL27RA, which leads to reduced peritoneal metastases when knocked down in tumor-carrying mice given IL27-siRNA-DOPC nanoparticles.

Explainable Artificial Intelligence is amenable to generating biologically relevant testable hypotheses despite their limitations due to explanations originating from post hoc realizations.
tidysdm: leveraging the flexibility oftidymodelsfor Species Distribution Modelling in R
Authors: Leonardi Michela , Colucci Margherita , Pozzi Andrea Vittorio , Scerri Eleanor M. L. , Manica Andrea
Published: July 2023

In species distribution modelling (SDM), it is common practice to explore multiple machine-learning algorithms and combine their results into ensembles. This is no easy task in R: different algorithms were developed independently, with inconsistent syntax and data structures. Specialised SDM packages integrate multiple algorithms by creating a complex interface between the user (providing a unified input and receiving a unified output), and the back-end code (that tackles the specific needs depending on the algorithm). This requires a lot of work to create and maintain the right interface, and it prevents an easy integration of other methods that may become available.

Here we presenttidysdm, an R package that solves this problem by taking advantage of thetidymodelsuniverse. Being part of thetidyverse, (i) it has standardised grammar and data structures providing a coherent interface for modelling, (ii) includes packages designed for fitting, tuning, and validating various models, and (iii) allows easy integration of new algorithms and methods.

tidysdmallows easy, flexible and quick species distribution modelling by supporting standard algorithms, including additional SDM-oriented functions, and giving the opportunity of using any algorithm or procedure to fit, tune and validate a large number of different models. Additionally, it provides further functions to easily fit models based on paleo/time-scattered data.

The package includes two vignettes detailing standard procedures for present-day and time-scattered data. These vignettes also showcase the integration withpastclim(Leonardiet al. 2023) to allow easier access to palaeoclimatic data series, if needed, but users can bring in their own climatic data in standard formats.
Origin of eukaryotic-like Vps23 shapes an ancient functional interplay between ESCRT and ubiquitin system in Asgard archaea
Authors: Lu Zhongyi , Zhang Siyu , Liu Yang , Xia Runyue , Li Meng
Published: July 2023

Functional interplay between the endosomal sorting complexes required for transport (ESCRT) and ubiquitin system underlies the ubiquitin-dependent sorting pathway, a specific trait of eukaryotic endomembrane system. Yet, its evolutionary origin remains unclear. Here, we show that a novel UEV-Vps23 family protein, that contains UEV and Vps23 domains, mediates an ancient ESCRT and ubiquitin system interplay in Asgard archaea. The UEV binds ubiquitin with high-affinity, making the UEV-Vps23 a sensor for sorting ubiquitinated cargo. A steadiness box in the Vps23 domain undergoes ubiquitination through a eukaryotic-like Asgard E1, E2, and RING E3 cascade. The UEV-Vps23 can switch between autoinhibited and active forms, by which likely regulates the ESCRT and ubiquitin system interplay. Furthermore, the shared sequence and structural homology among the UEV-Vps23, eukaryotic Vps23 and archaeal CdvA, implying that these proteins share a common evolutionary origin. Together, this work presents evidence that the ESCRT and ubiquitin system interplay had arisen early in Asgard evolution, antedating emergence of endomembrane system in eukaryogenesis.

Teaser

The ESCRT and ubiquitin system interplay, a specific trait of eukaryotic endomembrane system, likely inherited from an Asgard archaeal ancestor.
Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex
Authors: Dubiez Etienne , Pellegrini Erika , Brask Maja Finderup , Garland William , Foucher Anne-Emmanuelle , Huard Karine , Jensen Torben Heick , Cusack Stephen , Kadlec Jan
Published: July 2023

The nuclear cap-binding complex (CBC) co-ordinates co-transcriptional maturation, transport, or degradation of nascent Pol II transcripts. CBC with its partner ARS2 form mutually exclusive complexes with diverse ‘effectors’ that promote either productive or destructive outcomes. Combining Alphafold predictions with structural and biochemical validation, we show how effectors NCBP3, NELF-E, ARS2, PHAX and ZC3H18 form competing binary complexes with CBC and how PHAX, NCBP3, ZC3H18 and other effectors compete for binding to ARS2. In ternary CBCA complexes with either PHAX, NCBP3 or ZC3H18, ARS2 is responsible for the initial effector recruitment but inhibits their direct binding to the CBC. We show thatin vivoZC3H18 binding to both CBC and ARS2 is required for nuclear RNA degradation. We propose that recruitment of PHAX to CBC-ARS2 can lead, with appropriate cues, to competitive displacement of ARS2 and ZC3H18 from the CBC, thus promoting a productive rather than a degradative RNA fate.
Systematic assessment of ISWI subunits reveals that NURF creates local accessibility for proper CTCF function
Authors: Iurlaro Mario , Masoni Francesca , Wirbelauer Christiane , Iskar Murat , Burger Lukas , Schübeler Dirk
Published: July 2023

Catalytic activity of the ISWI family of remodelers is critical for nucleosomal organization and DNA binding of transcription factors, including the insulator protein CTCF. To define which subcomplex mediates these diverse functions, we derived a panel of isogenic mouse stem cell lines each lacking one of six ISWI accessory subunits. Individual deletions of subunits of either CERF, RSF, ACF, WICH or NoRC subcomplexes only moderately affect the chromatin landscape, while removal of the NURF-specific subunit BPTF leads to drastic reduction in chromatin accessibility and SNF2H ATPase localization around CTCF sites. While this affects adjacent nucleosome occupancy, it only modestly impacts CTCF binding itself. In the absence of accessibility, the structural function of CTCF is nevertheless impaired resulting in lower occupancy of cohesin and cohesin release factor, and reduced physical insulation at these sites, highlighting the need of NURF-mediated remodeling for open chromatin and proper CTCF function.

These results separate local CTCF binding from insulator function in nuclear organization and reveal a specific role for NURF in mediating SNF2H localization and chromatin opening at bound CTCF sites. They designate local accessibility as critical for cohesin positioning and establishment of physical insulation.
A geminivirus AC5 protein interacts with plant hormonal signalling and impacts plant defence
Authors: Kumar Rohit , Dasgupta Indranil
Published: July 2023

Geminiviruses are a large group of plant viruses responsible for yield loss in various crops, mainly in the tropical and sub-tropical regions. Geminiviruses encode six to nine multifunctional proteins, which interact with plant components to cause pathogenesis. One of the least studied geminiviral proteins is AC5. This study presents the first evidence of an AC5 protein interacting with a component of the abscisic acid signalling pathway, resulting in a depressed state. We show that the AC5 protein, encoded by Sri Lankan cassava mosaic virus is important for symptom development and virus accumulation in the experimental hostNicotiana benthamiana. The above interaction perturbs the abscisic acid signalling pathways, leading to compromised expression of defense-related genes and insensitivity to abscisic acid in transgenic Arabidopsis plants. This suggests a novel role of AC5 to facilitate virus propagation. Furthermore, we show that transiently suppressing the expression inN. benthamiana PP2Cwith which AC5 interacts, results in a reduction in viral titers possibly due to augmented ABA signaling and its defense-related roles. This research provides valuable insights into how geminiviral proteins manipulate ABA-mediated defence pathways, paving the way for further investigation into the underlying mechanisms and potential applications in plant protection against viral infections.
Novel centriolar defects underlie a primary ciliary dyskinesia phenotype in an adenylate kinase 7 deficient ciliated epithelium
Authors: Sheridan Jennifer , Grata Aline , Suva Eve E. , Bresteau Enzo , Mitchell Linus R. , Hassan Osama , Mitchell Brian
Published: July 2023

The skin ofXenopusembryos contains numerous multiciliated cells (MCCs), which collectively generate a directed fluid flow across the epithelial surface essential for distributing the overlaying mucous. MCCs develop into highly specialized cells to generate this flow, containing approximately 150 evenly spaced centrioles that give rise to motile cilia. MCC-driven fluid flow can be impaired when ciliary dysfunction occurs, resulting in primary ciliary dyskinesia (PCD) in humans. Mutations in a large number of genes (∼50) have been found to be causative to PCD. Recently, studies have linked low levels of Adenylate Kinase 7 (AK7) gene expression to patients with PCD; however, the mechanism for this link remains unclear. Additionally, AK7 mutations have been linked to multiple PCD patients. Adenylate kinases modulate ATP production and consumption, with AK7 explicitly associated with motile cilia. Here we reproduce an AK7 PCD-like phenotype inXenopusand describe the cellular consequences that occur with manipulation of AK7 levels. We show that AK7 localizes throughout the cilia in a DPY30 domain-dependent manner, suggesting a ciliary function. Additionally, we find that AK7 overexpression increases centriole number, suggesting a role in regulating centriole biogenesis. We find that in AK7-depleted embryos, cilia number, length, and beat frequency are all reduced, which in turn, significantly decreases the tissue-wide mucociliary flow. Additionally, we find a decrease in centriole number and an increase in sub-apical centrioles, implying that AK7 influences both centriole biogenesis and docking, which we propose underlie its defect in ciliogenesis. We propose that AK7 plays a role in PCD by impacting centriole biogenesis and apical docking, ultimately leading to ciliogenesis defects that impair mucociliary clearance.
UropathogenicEscherichia coliwield enterobactin-derived catabolites as siderophores
Authors: Zou Zongsen , Robinson John I. , Steinberg Lindsey K. , Henderson Jeffrey P.
Published: July 2023

UropathogenicE. coli(UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here we find the siderophore enterobactin and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined enterobactin biosynthesis and import mutants, we identify lower molecular weight, dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. InE. coli,iron acquisition from iron(III)-enterobactin complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed enterobactin, we find that enterobactin and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis.
Stress-induced vascular remodeling: novel insight into the role of omega-3 fatty acid metabolite, 4-oxoDHA
Authors: Nishimori Makoto , Hayasaka Naomi , Otsui Kazunori , Inoue Nobutaka , Nagao Manabu , Toh Ryuji , Ishida Tatsuro , Hirata Ken-ichi , Furuyashiki Tomoyuki , Shinohara Masakazu
Published: July 2023

Background

Stress has garnered significant attention as a prominent risk factor for inflammation-related diseases, particularly cardiovascular diseases (CVDs). However, the precise mechanisms underlying stress-driven CVDs remain elusive, thereby impeding the development of effective preventive and therapeutic strategies.

Methods

To explore the correlation between plasma lipid metabolites and depressive states, we conducted a study involving healthy volunteers (n=408). Liquid chromatography (LC)/mass spectrometry (MS)/MS-based lipidomics and the self-rating depression (SDS) scale questionnaire were employed for data collection. In addition, we utilized a mouse model by subjecting mice to restraint stress and investigating the impact of stress on plasma lipid metabolites and vascular remodeling following carotid ligation. In vitro functional and mechanistic studies were performed using macrophages, endothelial cells, and neutrophil cells.

Results

Our findings revealed a significant association between depressive state and reduced plasma levels of 4-oxoDHA, a specific omega-3 fatty acid metabolite regulated by 5-lipoxygenase (LO) in neutrophils in healthy volunteers. In mice, restraint stress led to decreased plasma 4-oxoDHA levels and exacerbated vascular remodeling. Moreover, 4-oxoDHA demonstrated the ability to enhance Nrf2-HO-1 pathways, exerting anti-inflammatory effects on endothelial cells and macrophages. Mechanistically, stress-induced noradrenaline triggered the degradation of 5-LO in neutrophils through the proteasome system, facilitated by dopamine D2-like receptor activation. The reduction in circulating 4-oxoDHA resulted in the downregulation of the Nrf2-HO-1 anti-inflammatory axis and an increase in ICAM-1 expression, vascular permeability, and remodeling.

Conclusions

Our study unveiled a novel stress-induced pathway of vascular inflammation, mediated through the regulation of omega-3 fatty acid metabolites. Reduced levels of circulating 4-oxoDHA under stress conditions may serve as a promising biomarker for stress. This understanding of the interplay between neurobiology and lipid metabolism provides a potential avenue for the development of treatments aimed at preventing stress-induced systemic neuroinflammation.

Highlights

– Our study reveals that stress-induced reduction in circulating levels of a specific omega-3 fatty acid metabolite, 4-oxoDHA, contributes to vascular inflammation.

– We have identified a novel pathway that explains how stress promotes systemic vascular inflammation by regulating omega-3 fatty acid metabolites in the circulation.

– Our findings provide new evidence for the role of 4-oxoDHA in maintaining Nrf2-ARE-related anti-inflammatory functions in endothelial cells and macrophages.
Russulasubgen.Cremeoochraceaesubgen. nov.: a very small and ancient lineage sharing withMultifurca(Russulaceae) an identical, largely circum-Pacific distribution pattern
Authors: Buyck B , Horak E. , Cooper J.A. , Wang X.H
Published: July 2023

The application of DNA data on a worldwide sampling has revolutionized the infrageneric classification of the highly diverse ectomycorrhizal genusRussula. Based on collections made in New Zealand, East Asia and North America, this study describes the new subgenusCremeoochraceae, the ninth subgenus inRussula. Even though BLASTn of the ITS sequences suggested affinities with species of subgeneraRussulaandHeterophyllidiae, the phylogenetic analysis based on a five-locus DNA dataset placed the target samples in an independent major clade that is systematically equivalent to subgenus. The new subgenus shares with subgen.Brevipedumsubsect.Pallidosporinaethe general field habit, the unequal lamellae and the relatively small spores with inamyloid suprahilar spot and similar spore ornamentation. It differs from the latter subsection principally in the poor contents of all types of cystidioid cells and the often areolate-scurfy pileus surface composed of slender, undulating hyphal terminations with frequent subcapitate apices. Biogeographically, subgen.Cremeoochraceaeshares withMultifurca, the sister genus ofLactarius, a circum-Pacific distribution pattern with the exception of South America. Both lineages lack representatives in Europe and Africa. The hypothesis proposing an African origin for the genus is considered unlikely.
Histone variant H2A.Z is required for plant salt response by regulating gene transcription
Authors: Miao Rongqing , Zhang Yue , Liu Xinxin , Yuan Yue , Zang Wei , Li Zhiqi , Yan Xiufeng , Pang Qiuying , Zhang Aiqin
Published: July 2023

As a well-conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analyzing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large-scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome-wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, TSS and TES (−1 kb to +1kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.
The effect of perceived social support on postpartum depression in immigrant and Turkish women
Authors: Karadeniz Benli Cansu , Kulakaç Özen
Published: July 2023

Purpose

The purpose of this study was to examine the effect of perceived social support on postpartum depression (PPD) in Arab immigrant mothers and Turkish mothers.

Design/methodology/approach

This descriptive study was conducted with 140 mothers between September 2017 and January 2018. The data was collected via the Turkish and Arabic versions of the sociodemographic questionnaire, the Edinburgh Postnatal Depression Scale (EPDS) and the Multidimensional Scale of Perceived Social Support. Percentage and arithmetic mean calculations, independent samples t-test, Mann–Whitney U test, paired logistic regression analysis backward elimination method and Pearson and Spearman correlation analyses were conducted to analyze the data.

Findings

The data revealed that the risk of PPD was twice as high in Arab immigrant mothers (56.3%) compared to Turkish mothers (29%). The EPDS mean score was 12.37 ± 6.28 for Arab immigrant mothers and 8.81 ± 5.48 for Turkish mothers. The social support mean score was found to be 50.70 ± 19.27 for Arab immigrant mothers and 61.41 ± 16.51 for Turkish mothers. The independent risk factors for Turkish mothers included mother’s age, monthly income level and infant’s age, while the independent risk factors for Arab immigrant mothers included number of children, husband’s status of employment and access to regular medical care during pregnancy. The negative correlation between EPDS and social support overall scores and subscale scores was found to be significant for both groups.

Originality/value

To the best of the authors’ knowledge, this is the first study on the impact of social support on PPD in Arab immigrant and Turkish women in the national and international literature. The study helped reveal the correlation between perceived social support and PPD, the PPD risk rates and risk factors according to citizenship status for the first time.
Can crowdfunding creators learn from previous experiences to have a better future financing performance?
Authors: Fang Xing
Published: July 2023

Purpose

This paper aims to explore whether crowdfunding creators can learn from previous experiences to have a better financing performance of future crowdfunding projects.

Design/methodology/approach

This paper uses Python to capture the data of 6,267 crowdfunding projects from one of the largest crowdfunding platforms in China (JingDong Crowdfunding) and the author use the negative binomial regression model and the OLS model in this empirical study.

Findings

The empirical results show that both the early-stage experience of creating a crowdfunding project and the early-stage experience of supporting projects of other crowdfunding creators can improve the financing performance of their newly launched projects. The social network of the previous projects and the “Blockbuster” projects initiated before can also make the newly initiated projects obtain better financing performance.

Originality/value

Current research on entrepreneurial experience shows that serial entrepreneurs have significantly different success rates than novice or inexperienced entrepreneurs but there is limited literature on the learning effect of crowdfunding creators. This study adds to the literature on entrepreneurial learning and provides suggestions to crowdfunding creators.