bluuebunny/crossref_metadata_2025 huggingface dataset:
The effective multiplicity of infection for HCMV depends on the activity of the cellular 20S proteasome
Authors: Cataldo Katie M. , Roche Kathryn L. , Monti Christopher E. , Dash Ranjan K. , Murphy Eain A. , Terhune Scott S.
Published: December 2024

Human cytomegalovirus (HCMV) is a betaherpesvirus capable of infecting numerous cell types and persisting throughout an infected individual’s life. Disease usually occurs in individuals with compromised or underdeveloped immune systems. Several antivirals exist but have limitations relating to toxicity and resistance. HCMV replication involves upregulation of host proteasomal activities, which play important roles in the temporal stages of replication. Here, we defined the impact on replication kinetics of the proteasome inhibitor, bortezomib. We demonstrate that bortezomib significantly reduces levels of viral genomes and infectious virions produced from a population of cells. Inhibition reduced expression of viral proteins that are influenced by genome synthesis. When added prior to 24 hpi, we observe decreases in PCNA and Cdk1 while increases in p21 whose regulations contribute to efficient replication. This response synergized with an antiviral, maribavir. Since some replication occurred, we tested the hypothesis that a subset of infected cells might break through inhibition. Initially, we simulated bortezomib activities using a mechanistic computational model of late-lytic replication. Upon reducing multiplicity of infection (MOI)
in silico
, we observed near-identical simulated results compared to experimental data. Next, we analyzed replication using live-cell imaging. This revealed treated cultures do contain a population of cells with fully developed late-stage cytoplasmic assembly compartments but at significantly lower numbers. We refer to this as the effective MOI. Overall, our studies support a hypothesis in which 20S proteasome inhibition disrupts HCMV replication by reducing the MOI to an effective MOI, defined by a fraction of infected cells capable of progressing to fulminant infection.

IMPORTANCE

Human cytomegalovirus (HCMV) infection and reactivation continues to contribute to morbidity and mortality around the world. Antiviral compounds are available but have limitations. Here, we have defined the impact of the proteasome inhibitor bortezomib on HCMV replication. Proteasomal activities play a critical role in temporal changes required for replication. We demonstrate that disrupting these activities inhibits viral replication while likely supporting increased antiviral activity of the anti-HCMV agent, maribavir. Using a combination of live-cell imaging and computational tools, we discover that a subset of infected cells progresses to fulminant infection, which we define as the effective multiplicity of infection, and this subset would otherwise be missed when analyzing the average of the population.
Enteroviral 3C protease cleaves N4BP1 to impair the host inflammatory response
Authors: Zhang Dongjie , Xie Yifan , Cao Jie , Huang Lisu , Fan Wenchun
Published: December 2024

Enteroviral 3C protease (3Cpro) is an essential enzyme for viral replication and is responsible for combating the host anti-viral immune response by targeting cellular proteins for cleavage. The identification and characterization of 3Cpro substrates will contribute to our understanding of viral pathogenesis. In this study, we performed a motif search for 3Cpro substrates in the human protein database using FIMO, which refers to a common cleavage sequence of 3Cpro. We identified and characterized NEDD4-binding protein 1 (N4BP1), a key negative regulator of the NF-κB pathway, as a novel 3Cpro substrate. N4BP1 is cleaved at residue Q816 by 3Cpro from several human enteroviruses, resulting in the loss of its ability to regulate tumor necrosis factor alpha-activated NF-κB signaling. In addition, we found that mouse N4BP1, which has a threonine at the P1′ site, is resistant to human enteroviral 3Cpro cleavage. However, rodent enteroviral 3Cpro derived from encephalomyocarditis virus (EMCV) can cleave both human and mouse N4BP1 at a species-specific site. By combining bioinformatic, biochemical, and cell biological approaches, we identified and characterized N4BP1 as a novel substrate of enteroviral 3Cpro. These findings provide valuable insights into the interplay between 3Cpro, its substrates, and viral pathogenesis.

IMPORTANCE

Targeting cellular proteins for cleavage by enteroviral 3Cpro is a conserved strategy used by enteroviruses to promote viral replication. While the cleavage of certain host proteins by 3Cpro may not affect viral replication, it is strongly associated with the pathogenesis of viral infection. In this study, we identified and characterized N4BP1, which plays such a role, using a combination of bioinformatic, biochemical, and cell biological approaches. Our data show that multiple 3Cpros cleave N4BP1 at residue Q816 and that cleavage of endogenous N4BP1 can occur during viral infection. N4BP1 has no effect on coxsackievirus B3 replication, but 3Cpro-induced N4BP1 cleavage abolishes its regulatory function in NF-κB signaling. We also show that mouse N4bp1 resists human enteroviral 3Cpro cleavage. In contrast, rodent enteroviral EMCV 3Cpro can target human and mouse N4BP1 for cleavage at different residues, which indicates that future investigations are needed to elucidate the potential mechanisms involved.
Draft genome sequence of the plant growth-promoting rhizobacteria
Streptomyces
sp. CLV115
Authors: Ruschel Soares Natasha , Fernández Campos Juan Felipe , Zardin Missau Luiza , Rosa Pianetti Thiago , Budelon Gonçalves Júlia , Romanato Santarém Eliane , Vieira Astarita Leandro
Published: December 2024

Streptomyces
sp. CLV115 isolated from Solanaceae rhizosphere in southern Brazil shows promising plant growth-promoting traits; thus, whole-genome sequencing aids the unraveling of its genomic potential, offering insights into developing natural crop solutions and advancing
Streptomyces
genomics.
Draft genome sequencing of
Enterococcus faecium
MBBL3, a probiotic strain isolated from healthy cow milk
Authors: Siddique Naim , Rahman Md. Morshedur , Rahaman Monira , Rahman A. N. M. Aminoor , Talukder Anup Kumar , Das Ziban Chandra , Hoque M. Nazmul
Published: December 2024

We sequenced the whole genome of
Enterococcus faecium
MBBL3, isolated from healthy cow milk. The draft genome of MBBL3 is 2,971,195 bp with 95.61× coverage, spanned over 106 contigs.
Draft genome sequence of
Mycobacterium intracellulare
strain HYG9370 isolated from Japanese Black Cattle in Japan
Authors: Kawaguchi Reiko , Ueno Yuichi , Kurita Kanako , Wako Toshiyuki , Mori Yasuyuki , Ogawa Yohsuke
Published: December 2024

Here, we report the draft genome sequence of
Mycobacterium intracellulare
strain HYG9370 (ID: JD563) isolated from a clinically healthy Japanese Black steer. The genome information of this strain provides valuable insights into the genetic diversity of
M. intracellulare
, which has been isolated from multiple hosts and environments.
Complete genome sequence of a marine
Pseudoalteromonas
bacterial strain
Authors: Manirakiza Eric , Chaumier Timothée , Tirichine Leïla
Published: December 2024

Pseudoalteromonas
is an abundant bacterial genera, found ubiquitously, including in extreme environments. Its broad metabolic capacity enables unique associations with various organisms. Using PacBio sequencing, we generated the complete genome sequence of a marine
Pseudoalteromonas
, revealing two circular chromosomes and one putative plasmid. The genome data are accessible at
https://BacBrowse.univ-nantes.fr
.
Complete genome sequence of a human influenza a virus (H1N1) detected in Kazakhstan in the fall of 2022
Authors: Sarsenov Radmir , Babenko Dmitriy , Kamalova Dinara , Amirgazin Asylulan , Begaidarova Rosaliya , Atshabarova Saule , Shevtsov Alexandr , Sidelyova Yekaterina , Yegorov Sergey , Kadyrova Irina
Published: December 2024

An
Orthomyxoviridae Alphainfluenza virus Influenza A
virus strain,
A/Kazakhstan/Flu-H11-6/2022(H1N1
), was isolated in Karaganda, Central Kazakhstan during a study of acute respiratory infections among hospital inpatients in 2022. Here, we present the complete genome sequence of this strain.
Genome sequences of three electrochemically active bacteria isolated from an anaerobic digester
Authors: Yoshizu Daichi , Tomita Keisuke , Tsuchiya Miyu , Kouzuma Atsushi , Watanabe Kazuya
Published: December 2024

Three electrochemically active bacteria (EAB), strains ADMFC1, ADMFC2, and ADMFC3, were isolated from an anaerobic digester. Here, we report on genome sequences of the three EAB, which help deepen our understanding of the diversity and niches of EAB inhabiting anaerobic digesters.
A metabologenomics approach reveals the unexplored biosynthetic potential of bacteria isolated from an Amazon Conservation Unit
Authors: de Oliveira Ana Carolina Favacho Miranda , Vieira Bruna Domingues , de Felício Rafael , Silva Lucas da Silva e , Veras Adonney Allan de Oliveira , Graças Diego Assis das , Silva Artur , Azevedo Baraúna Rafael , Barretto Barbosa Trivella Daniela , Schneider Maria Paula Cruz
Published: December 2024

The Amazon, an important biodiversity hotspot, remains poorly explored in terms of its microbial diversity and biotechnological potential. The present study characterized the metabolic potential of Gram-positive strains of the Actinomycetes and Bacilli classes isolated from soil samples of an Amazon Conservation Unit. The sequencing of the 16S rRNA gene classified the strains ACT015, ACT016, and FIR094 within the genera
Streptomyces
,
Rhodococcus
, and
Brevibacillus
, respectively. Genome mining identified 33, 17, and 14 biosynthetic gene clusters (BGCs) in these strains, including pathways for the biosynthesis of antibiotic and antitumor agents. Additionally, 40 BGCs (62,5% of the total BGCs) were related to unknown metabolites. The OSMAC approach and untargeted metabolomics analysis revealed a plethora of metabolites under laboratory conditions, underscoring the untapped chemical diversity and biotechnological potential of these isolates. Our findings illustrated the efficacy of the metabologenomics approach in elucidating secondary metabolism and selecting BGCs with chemical novelty.

IMPORTANCE

The largest rainforest in the world is globally recognized for its biodiversity. However, until now, few studies have been conducted to prospect natural products from the Amazon microbiome. In this work, we isolated three free-living bacterial species from the microbiome of pristine soils and used two high-throughput technologies to reveal the vast unexplored repertoire of secondary metabolites produced by these microorganisms.
Evaluation of the double-zone hemolysis (DZH) test for the detection of livestock-associated methicillin-resistant
Staphylococcus aureus
Authors: Latorre-Fernández Javier , Aspiroz Carmen , Abdullahi Idris Nasir , Campaña-Burguet Allelen , Eguizábal Paula , González-Azcona Carmen , Tenorio Carmen , Zarazaga Myriam , Shittu Adebayo O. , Lozano Carmen , Torres Carmen
Published: December 2024

Livestock-associated methicillin-resistant
Staphylococcus aureus
(LA-MRSA), such as clonal-complex (CC)398, are of clinical relevance due to their multi-drug resistance profiles, adding to the overall burden of MRSA in humans. The objective was to evaluate the double-zone hemolysis (DZH) test as a simple and reliable method for detecting LA-MRSA in the clinical microbiology laboratory.
S. aureus
isolates assigned to CC398 (
n
= 183; 152 MRSA/31 methicillin-susceptible
S. aureus
[MSSA]), CC1 (
n
= 44; MRSA), and other CCs (
n
= 144; 94 MRSA/50 MSSA) were investigated. These isolates were screened for DZH on sheep blood agar plates after incubation at 37°C for 24 h. Identification of the
scn
(human adaptation marker) and
hlb
genes (encoding hemolysin, intact or truncated) was performed by PCR. The positive and negative predictive values (PPV and NPV), sensitivity (SS), and specificity (SP) of the DZH test were determined. The DZH-positive phenotype was observed in 94.7%, 25%, and 6.4% of MRSA-CC398, MRSA-CC1, and MRSA of other lineages, respectively. Moreover, the DZH-positive phenotype was identified in 9.7% of MSSA-CC398 isolates but not in other MSSA lineages. All 164 DZH-positive isolates carried
hlb
intact, and 99.4% was
scn
negative, suggesting an animal origin. Of the 207 DZH-negative isolates, 99.5% was
scn
positive (indicating human adaptation), and 95.2% possessed a truncated
hlb
gene. The PPV/NPV/SS/SP values (in %) of the DZH test were as follows: detection of (i) LA-MRSA-CC398: (87.8/96.1/94.7/90.9); (ii) LA-MRSA-CC398/CC1
scn
negative: (94.5/100/100/95.8); and (iii)
S. aureus scn
negative: (99.4/99.5/99.4/99.5). The DZH is a reliable strategy to detect and distinguish LA-MRSA in the clinical microbiology laboratory and is recommended as an adjunct diagnostic test.

IMPORTANCE

This study evaluated a simple and reliable phenotypic test that can be very useful in the clinical microbiology laboratory to detect livestock-associated (LA) methicillin-resistant
Staphylococcus aureus
(MRSA) isolates and
S. aureus
of potential animal origin. The proposed double-zone hemolysis test has shown high positive and negative predictive values, sensitivity, and specificity to detect these LA-MRSA clones and
S. aureus
of potential animal origin. Most LA-MRSA clones exhibit resistance to different classes of antibiotics, with unique epidemiological characteristics, and their early detection has public health relevance and patient management.
The increasing burden of group B
Streptococcus
from 2013 to 2023: a retrospective cohort study in Beijing, China
Authors: Li Yingxing , Yang Wenhang , Li Yi , Hua Kexin , Zhao Ying , Wang Taie , Liu Lingli , Liu Yali , Wang Yao , Liu Wenjing , Zhang Li , Zhu Renyuan , Yu Shuying , Sun Hongli , Dou Hongtao , Yang Qiwen , Xu Yingchun , Guo Lina
Published: December 2024

Group B
Streptococcus
(GBS) is a leading pathogen responsible for fatal infections in newborns primarily due to vertical transmission from colonized mothers. Cases of invasive GBS infections in adults have also increased and attracted attention recently. To comprehensively understand the evolving burden of vaginal GBS carriage in pregnant and non-pregnant women, as well as the trends in invasive GBS diseases and antibiotic resistance in China, we conducted a retrospective study using data from a large tertiary hospital in Beijing from 2013 to 2023. Over the past decade, improvements in GBS screening methods for pregnant women have significantly increased the GBS recovery rate. The detection rate of GBS and its proportion among vaginal pathogens have shown a gradual increase in GBS colonization in both pregnant and non-pregnant women. An analysis of vaginal pathogen composition revealed variations in GBS prevalence across different age groups, as well as a potential competitive relationship between GBS and
Enterococcus faecalis
in the vaginal environment. Additionally, we analyzed 165 invasive GBS cases, including three in newborns. The incidence of invasive GBS cases has risen since 2016, particularly among individuals over the age of 40. The 5,858 GBS isolates exhibited notably high resistance rates to erythromycin (72.2%), clindamycin (60%), and levofloxacin (50.1%), with 30.8% classified as multidrug-resistant. Importantly, invasive GBS strains exhibited a higher resistance rate to levofloxacin (61.2%) compared to colonizing strains (49.8%). This study highlights the importance of continuous screening and monitoring for GBS, especially given the concerning antibiotic resistance rates of GBS.

IMPORTANCE

Group B
Streptococcus
(GBS) is an important pathogen that commonly causes infections in newborns and the elderly. This retrospective study provides a comprehensive analysis of GBS strains isolated from a large tertiary hospital in Beijing between 2013 and 2023, revealing an increasing colonization rate of GBS in both pregnant and non-pregnant women. Analysis of vaginal pathogens indicates a growing proportion of GBS among vaginal pathogens. Additionally, the high resistance rates of GBS to erythromycin, clindamycin, and levofloxacin, as well as the prevalence of multidrug resistance, are issues that merit attention. We also examined the differences in resistance rates of GBS strains from various sample types, finding that the levofloxacin resistance rate in GBS strains causing invasive infections was significantly higher than in colonizing strains. This study provides new data and insights for clinical research on GBS.
Emission reduction strategies and health: a systematic review on the tools and methods to assess co-benefits
Authors: Abdala Sammila Andrade , Khomsi Kenza , Houdou Anass , El Marouani Ihssane , El Badisy Imad , Najmi Houda , Obtel Majdouline , Belyamani Lahcen , Ibrahimi Azeddine , Khalis Mohamed
Published: December 2024

Objective

The objective of this study is to review the current literature on the health co-benefits of emission reduction strategies and the methods and tools available to assess them.

Design

Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

PubMed, Scopus, Web of Science, ScienceDirect and GreenFILE were searched from January of 2017 to March of 2023.

Eligibility criteria

We included original, peer-reviewed journal articles that described emission (ambient air pollutant and greenhouse gases) reduction strategies and assessed their health co-benefits.

Data extraction and synthesis

Two independent reviewers employed standardised methods to search, screen and code the included studies, documenting their findings in an Excel spreadsheet.

Results

From 6687 articles, 82 were included. Most studies show that emissions reduction strategies improve air quality, reducing mortality and morbidity. Health risk assessment and health impact assessment are common, though procedures may cause confusion. About 33% used established models like the integrated exposure-response and global exposure mortality model. Out of all studies, 16% of them used Environmental Benefits Mapping and Analysis Program—Community Edition. Only 17.8% carried out cost–benefit analyses, but these show economic worth in investing in emission reduction strategies.

Conclusions

Emission reduction strategies significantly enhance human health, with potential co-benefits offsetting intervention costs, which can be an incentive for action in low and middle-income countries. This review emphasises investing in cost–benefit analyses and research, particularly in regions with limited studies on emission reduction and health co-benefits. It provides decision-makers insights into selecting assessment methods and underscores the ongoing need for model and tool evaluation.

PROSPERO registration number

CRD42022332480.
Determinants of traditional birth attendant utilisation among reproductive age women in Ethiopia: a multilevel analysis of the 2019 Ethiopian Demographic and Health Survey
Authors: Tilahun Befkad Derese , Ayele Mulat , Alamaw Addis Wondmagegn , Lake Eyob Shitie , Abate Biruk Beletew , Yilak Gizachew , Bizuayehu Molla Azmeraw , Zemariam Alemu Birara , Kitaw Tegene Atamenta
Published: December 2024

Objectives

To identify the determinants of traditional birth attendants’ utilisation among reproductive-age women in Ethiopia.

Design

Cross-sectional study design.

Setting

Ethiopia.

Participants

A total of 3979 weighted samples of reproductive-age women were included.

Outcome measure

Traditional birth attendant utilisation.

Results

This study found a high prevalence (29.76%) of Ethiopian mothers using traditional birth attendants for delivery, based on data from the 2019 Ethiopian Demographic and Health Survey. Mothers with higher education (adjusted OR (AOR)=0.11, 95% CI: 0.01 to 0.62), who had four or more antenatal care visits (AOR=0.34, 95% CI: 0.21 to 0.54), communities with lower levels of education (AOR=2.21, 95% CI: 1.30 to 3.73), communities with higher poverty levels (AOR=1.71, 95% CI: 1.99 to 2.96) and those from peripheral regions (AOR=3.41, 95% CI: 1.77 to 6.56) were found to be predictors of traditional birth attendants.

Conclusion

This study indicates a high prevalence (29.76%) of Ethiopian mothers using traditional birth attendants, highlighting the need for targeted interventions to promote skilled birth attendance. Policymakers should focus on implementing educational programmes targeting reproductive-age women and improving access to quality antenatal care. Specific initiatives could include community-based educational workshops and subsidies for transportation to healthcare facilities. Furthermore, mothers in remote and border districts should receive specialised attention in terms of resource allocation, including skilled personnel and enhanced healthcare access.
KindMap: an e-mental health tool to promote the well-being and mental health of people facing infertility—study protocol for a feasibility randomised control trial
Authors: Carolino Naír , Cunha Marina , Pinto-Gouveia José , Gameiro Sofia , Galhardo Ana
Published: December 2024

Introduction

Fertility patients increasingly use web-based and mobile-based apps to access psychosocial care. These digital tools may be a helpful alternative to traditional psychological interventions. Developing and evaluating patient-centred e-mental health tools rooted in evidence-based interventions is a priority. The KindMap is a stand-alone, cost-free e-mental health intervention derived from adapting the Mindfulness Based Programme for Infertility (MBPI) contents to a digital format. The KindMap integrates mindfulness and self-compassion skills training and Acceptance and Commitment Therapy components. This protocol is intended to evaluate the KindMap’s feasibility and explore the extent to which the web-app mode of delivery limited efficacy results are similar to the MBPI in-person format results. Furthermore, it will test the causal theory underlying KindMap.

Methods and analysis

A two-arm 2:1 non-blinded feasibility randomised controlled trial (RCT) will be conducted. Participants are people dealing with infertility, who are able to access the Internet and understand Portuguese or English. Consent participants will complete an online survey at 3-time assessment moments. After baseline assessment, participants will be randomised into the KindMap experimental group (KindMap-EG; with immediate access to the web app) or the waiting-list control group. The primary outcome is well-being (WHO Index-5); secondary outcomes are infertility-related stress (Fertility Problem Inventory—Short Form), anxiety and depression (Patient Health Questionnaire for Depression and Anxiety-4); mindfulness (Five Facet Mindfulness Questionnaire—Short Form), self-compassion (Self-Compassion Scale—Short Form), psychological flexibility (Psy-Flex) and infertility-related self-efficacy are the potential mechanisms of change. KindMap-EG will also complete a feasibility survey.

Ethics and dissemination

The study was approved by the Ethics Committee of the Faculty of Psychology and Educational Sciences of the University of Coimbra (Identifier: CEDI/FPCEUC:78/R_10). The KindMap study may contribute to the existing research on e-health technologies applied to mental health. The study outcomes will be disseminated through publications in peer-reviewed journals and national and international conference presentations.

Trial registration number

NCT05899374.
Acceptance and the influencing factors towards intermittent self-catheterisation among patients with neurogenic lower urinary tract dysfunction in China: a multicentre cross-sectional study
Authors: Hao Fengming , Hu Yingjie , Luo Senying , Chen Ling , Wang Laifu , Wu Dan , Cai Wenzhi
Published: December 2024

Objectives

The psychological acceptance of intermittent self-catheterisation (ISC) significantly impacts its initial adoption and long-term compliance among patients. However, our understanding of this acceptance remains limited. This study aims to investigate ISC’s psychological acceptance and identify influencing factors among neurogenic lower urinary tract dysfunction (NLUTD) patients in China.

Design

A cross-sectional study design.

Participants

A total of 394 patients with NLUTD were recruited from 15 tertiary general hospitals in China.

Outcome measure

The patients completed a comprehensive questionnaire that included demographic and clinical characteristics, along with study instruments such as the Intermittent Catheterization Acceptance Test (I-CAT), the Intermittent Catheterization Satisfaction Questionnaire (InCaSaQ), the Intermittent Catheterization Difficulty Questionnaire and the Intermittent Self-Catheterization Questionnaire (ISC-Q). Pearson’s correlation analysis explored interrelationships among questionnaire scores, while Spearman’s correlation assessed relationships between categorical independent variables and I-CAT scores. Additionally, multiple linear regression analysis identified key factors influencing psychological acceptance of ISC.

Results

Nearly half of the participants (46.2%) reported psychological challenges in accepting ISC, and more than 50% of the participants exhibited fear and low self-esteem in their I-CAT questionnaire scores. The I-CAT scores were strongly correlated with ISC training (r=0.861), ISC follow-up (r=0.766) and psychological well-being (r=−0.774). Regression analysis identified significant factors influencing ISC acceptance, including urinary tract infections, types of catheters, ISC training, ISC follow-up, province, and scores on the ISC-Q and InCaSaQ questionnaires, which collectively explained 85.5% of the variance in acceptance rates (F=161.409).

Conclusions

Psychological difficulties in accepting ISC are prevalent among NLUTD patients. Key factors that facilitate ISC acceptance include receiving ISC training, follow-up support and favourable ISC-Q scores. In contrast, barriers like the use of non-hydrophilic catheters present significant challenges. Notably, ISC acceptance varies significantly across different regions. Therefore, targeted strategies are recommended to enhance positive factors, reduce negative ones and consider regional disparities, thereby improving overall ISC acceptance.
What do parents, professionals and policy colleagues want from a universal assessment of child development in the early years? A qualitative study in England
Authors: Lysons Joanna L , Mendez Pineda Rocio , Aquino Maria Raisa Jessica , Cann Hannah , Fearon Pasco , Kendall Sally , Kirman Jennifer , Woodman Jenny
Published: December 2024

Objective

Every child in England should be offered a health and development review at age 2–2½ years by the health visiting service, part of which includes an assessment of child development. The Department of Health and Social Care mandates the use of the Ages and Stages Questionnaire (ASQ-3) at this review as a tool to collect population-level data on children’s early development for monitoring of trends and disparities. This tool also forms part of the practitioner’s assessment of the child’s early development. To inform policy and practice, the present study gathered the views and experiences of parents and health visiting professionals on key priorities for, and barriers to, a universal assessment of early child development at age 2–2½ years.

Design, setting, participants

We held 15 focus groups with 29 parents, 24 health visitors and nursery nurses, five service managers and five policy colleagues in England. Participants were asked to reflect on their experiences of, and priorities for, measuring child development at the 2–2½ year universal review.

Analysis

We analysed data using Reflexive Thematic Analysis.

Results

We identified two overarching themes in the data. The first theme,‘just a part of the puzzle’: a useful tool in a holistic review,reflected a consistent priority—across all focus groups—for a measure of child development that was well embedded in the wider review, that facilitated conversations about the child and family system and allowed negotiation of parent and professional judgement of the child’s development and had a clear stated purpose. The second theme,‘they need to know why they’re doing it: a need for clarification’reflected the need for a clear purpose for, and less variable delivery of, the tool, including a need for clarification on its intended purpose to provide population-level data.

Conclusions

Parents and practitioners wanted a tool that facilitated a holistic conversation about development, well-being and health across the family system, with direct observation of the child by the professional. Used skilfully, the tool can constitute an intervention in itself, as it helps scaffold a conversation about how parents can support their child’s optimal growth and development. Consideration should be given to the experience of and support available to the practitioner using the tool within the health and developmental review.
Healthcare professionals’ perception of the World Health Organization Surgical Safety Checklist and psychological safety: a cross-sectional survey
Authors: Møller Kjestine Emilie , McLeskey Olivia Wisborg , Rosthøj Susanne , Trbovich Patricia , Grantcharov Teodor , Sorensen Jette Led , Strandbygaard Jeanett
Published: December 2024

Background

The Surgical Safety Checklist (SSC) is a cornerstone of ensuring the safety and accuracy of communication among interdisciplinary teams in the operating room. Central to the successful implementation of such a checklist is the concept of psychological safety. Despite the extensive body of research on the checklists’ efficacy, the association between healthcare professionals’ (HCPs) perceptions of the checklist and their level of psychological safety remains uninvestigated. This study attempts to address this gap by examining how their perceptions of the checklist intersect with their sense of psychological safety.

Methods

A cross-sectional survey comprising 25 items was conducted from November 2022 to January 2023 on; Demographics (6 items), the SSC (12 items), and the Psychological Safety Scale (7 items). We invited 125 HCPs from five different professional groups in the operation ward to complete the survey.

Results

Of the 125 asked to participate, 107 responded, and 100 of whom completed the entire survey. The level of psychological safety increased by 1.25 (95 % CI 0.36 to 2.14, p=0.006) per one-point increase of the perception that colleagues listen when checklist items are being reviewed, and increased by 1.1 (95% CI 0.4 to 1.7, p=0.002) per one-point increase in the perception that the checklist enhances interdisciplinary teamwork, and increased by 0.86 (95% CI 0.15 to 1.57, p=0.02) per one-point increase in the perception that the checklist provides structure in the operating room. Conversely, the level of psychological safety decreased by 1.4 (95 % CI 0.5 to 2.3, p=0.004) per one-point increase in the perception that the checklist is time-consuming.

Conclusion

Our findings reveal a significant association between psychological safety levels and perceptions of the SSC. Increased psychological safety was linked to more positive views on the checklist’s role in enhancing interdisciplinary teamwork, creating structure and attentiveness among colleagues. While seeing the checklist as time-consuming was associated with a lower psychological safety rating. These results suggest that psychological safety influences how individuals view and engage with patient safety measures like the checklist, highlighting the importance of fostering a supportive environment to optimise safety practice.
Development and evaluation of an ovarian hormone profile classification tool for female athletes: step one of a two-step process to determine ovarian hormone profiles
Authors: Elliott-Sale Kirsty J , Birdsey Laurence P , Burden Richard J , Cable Nigel T , Clausen Emma , D'Souza Alysha C , Dos’Santos Thomas , Field Adam , Flood Tessa R , Harris Rachel , McCall Alan , McNulty Kelly L , Ní Chéilleachair Niamh , O'Catháin Ciaran , Phillips Stuart M , Sherwin Glenn , Stebbings Georgina K , Taim Bernadette C , Van Every Derrick W , Więckowska Joanna , Minahan Clare
Published: December 2024

Objective

This study aimed to develop a reliable, comprehensive and fit-for-purpose tool for classifying ovarian hormone profiles (OHPs) (step one of a two-step process) in postmenarcheal to perimenopausal female athletes.

Methods

The OHP classification tool was designed by a team of sport scientists, practitioners and medics and is intended for use by sport practitioners. It incorporates self-reported data and guides subsequent verification methods. Written feedback was received from practitioners currently working with elite female athletes (n=5), ensuring its applicability in an applied sport setting. In addition, inter-user (n=2) and intra-user (n=30) repeatability was assessed.

Results

All practitioners agreed that the online tool was user-friendly. Four (out of five) practitioners stated they would include the tool in their practice, with the fifth stating that they did not have the capacity to incorporate it in their practice at present. The OHP classification tool showed excellent test–retest reliability with Cronbach’s alpha values exceeding 0.9.

Conclusion

This tool facilitates the classification of OHPs and promotes discussions between athletes and practitioners, enhancing understanding and management of ovarian hormone health in sportswomen.
Age-stratified comparison of heart age and predicted cardiovascular risk in 370 000 primary care patients
Authors: Stjernholm Kathrine , Kerr Andrew , Poppe Katrina K , Jensen Anders Elkær , Mehta Suneela , Nielsen Jesper Bo , Jackson Rod , Wells Susan
Published: December 2024

Background

Cardiovascular disease (CVD) preventive medications are recommended for patients at high short-term CVD risk. As most younger people with multiple raised CVD risk factors levels have low short-term risk, they could be falsely reassured to take no action. Heart age—the chronological age of a hypothetical person with the same short-term absolute CVD risk as the patient being assessed, but with an ‘ideal’ risk profile—is a complementary relative CVD risk metric developed to encourage these younger patients to make long-term lifestyle changes. However, clinicians sometimes use heart age to inform medication decisions. We assessed the appropriateness of this practice by comparing heart age and short-term CVD risk.

Methods

New Zealand primary care patients are recruited to the PREDICT cohort when their CVD risk is assessed. PREDICT is an ongoing prospective study in one-third of New Zealand general practices, designed to derive CVD risk prediction algorithms. Five-year CVD risk was calculated for 35–74-year-old PREDICT participants using published equations. Heart age was calculated using non-smoking, systolic blood pressure of 120 mm Hg and total cholesterol/high-density lipoprotein ratio of 3.5, as the ‘ideal’ risk profile. CVD risk and heart age gaps (difference between chronological age and heart age) were compared.

Results

Among 371 676 PREDICT participants, 5-year CVD risk increased with age, approximately doubling every 10 years, whereas heart age gaps decreased with increasing age, approximately halving between 35 and 44-year olds and 65–74-year olds. There were 5–40-year heart age gap differences between groups with similar 5-year CVD risks, but different ages.

Conclusion

Short-term CVD risk and heart age are not interchangeable risk metrics. Short-term risk increases with increasing age whereas heart age gaps generally decline, with major differences between younger and older people with similar short-term risk. If heart age is used to inform medication decisions rather than encourage long-term lifestyle changes, older people at high short-term risk could be undertreated and younger people at low short-term risk could be unnecessarily medicated.
Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve
Authors: DiGregorio Helene , Mansoorshahi Sara , Carlisle Steven G , Tovar Pensa Catherina , Watts Abi , McNeely Courtney , Sabate-Rotes Anna , Yetman Anji , Michelena Hector I , De Backer Julie F A , Mosquera Laura Muiño , Bissell Malenka M , Andreassi Maria Grazia , Foffa Ilenia , Hui Dawn S , Caffarelli Anthony , Kim Yuli Y , Citro Rodolfo , De Marco Margot , Tretter Justin T , McBride Kim L , Body Simon C , Milewicz Dianna M , Prakash Siddharth K
Published: December 2024

Background

Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications.

Methods

Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset valve or aortic disease (EBAV) and 272 biological relatives. CNVs were detected using three independent algorithms, focusing on the 22q11.2 region (18–24 Mb). CNV burden in the EBAV cohort was compared with unselected European ancestry controls.

Results

Rare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of EBAV probands. These CNVs were significantly enriched compared with the general population and segregated with BAV in families. Individuals carrying rare 22q11.2 CNVs had a higher prevalence of psychiatric diagnoses and learning difficulties, although they did not exhibit the typical features of 22q11.2DS. Importantly, these CNVs were associated with early onset or complex BAV cases, underscoring their potential clinical relevance.

Conclusions

Rare 22q11.2 CNVs play a role in non-syndromic BAV, particularly in cases with early onset or complex presentations. CNV screening could be considered as part of risk stratification for patients with BAV, helping to predict complications and guide management.

Trial registration number

NCT01823432.
CAR T cells secreting NGF-neutralizing scFv enhance efficacy in clear cell renal cell carcinoma by relieving immunosuppression through immunosympathectomy
Authors: Yang Peiwei , Chen Xi , Yu Fan , Wang Lan , Li Meng , Bai Zongke , Xu Hanmei
Published: December 2024

Background

Chimeric antigen receptor (CAR) T cells have demonstrated remarkable breakthroughs in treating hematologic malignancies, yet their efficacy in solid tumors is limited by the immunosuppressive microenvironment. Sympathetic nerves significantly contribute to this immunosuppressive milieu in solid tumors. However, the impact of tumor sympathetic denervation on enhancing CAR T-cell antitumor efficacy remains unclear.

Methods

We screened for sympathetic gene sets in various types of cancers and investigated the association of sympathetic nerves with immunosuppression in renal clear cell carcinoma. Using antibodies to block the nerve growth factor (NGF) pathway, we explored sympathetic nerve distribution in tumor tissues and tumor progression. Additionally, we engineered CAR T cells to secrete NGF single chain fragment variable (scFv) to achieve tumor immunosympathectomy and assessed their antitumor efficacy. Bulk RNA sequencing and single-cell RNA sequencing analyses were conducted to evaluate changes in immune cell phenotypes within the tumor microenvironment.

Results

Blocking the NGF pathway with antibodies effectively reduced sympathetic nerve distribution in tumor tissues and delayed tumor progression. CAR T cells engineered to secrete NGF scFv achieved a similar tumor immunosympathectomy and exhibited enhanced tumor suppression. RNA sequencing analyses revealed that this augmented effect was primarily due to the inhibition of the terminal exhaustion phenotype in tumor-infiltrating CD8 T cells and the prevention of macrophage polarization from M1 to M2. This approach maintained a stronger antitumor immune state at the tumor site. Additionally, splenic T cells also exhibited a more potent immune effector phenotype following the infusion of NGF scFv-secreting CAR T cells.

Conclusions

Our results suggest that immunosympathectomy is a novel approach to weaken tumor microenvironment immunosuppression and synergistically enhance CAR T-cell efficacy against solid tumors.
Modelling the thermo-mechanical behavior of saturated fine-grained soils
Authors: Zhao Naifeng , Wang Lili , Lu Yu , Ye Weimin , Jiang Gang , Zhang Rihong
Published: December 2024

This paper presents a simple thermo-elasto-plastic constitutive model for saturated fine-grained soils, addressing thermal volume change, excess pore pressure, and shear strength. The model incorporates a novel temperature-dependent plastic modulus formulation that attributes the thermoplastic strain to an internal state variable representing the thermal stabilization of soils due to cyclic thermal loading. It can capture the accumulative volume expansion of highly overconsolidated (OC) soils, and the accumulative contraction of normally consolidated (NC) and slight OC soils after several heating–cooling cycles. A thermally induced pore pressure formula is derived with consideration of thermo-elastic expansion of pore water and soil particles, thermo-plasticity of soil skeleton as well as the elastic unloading due to the decrease of effective stress under undrained heating. The effect of temperature on the shear strength was emphasized. An insight into the evolution of shear strength with temperature is provided. The consolidated stress history and stress path play a vital role in the thermal effect on the shear strength. The proposed model comprises nine parameters, which can be easily calibrated by element tests (triaxial tests and oedometer tests). The adequacy of the proposed model has been verified with experimental results from fine-grained soils documented in the literature.
Optimization of inputs for the application of ANN to rail track granular materials
Authors: Indraratna Buddhima , Hunt Haydn , Malisetty Rakesh Sai , Alagesan Srinivas , Qi Yujie , Rujikiatkamjorn Cholachat
Published: December 2024

Machine learning (ML) models such as artificial neural networks (ANNs) have gained increasing popularity in geotechnical engineering applications as an alternative to conventional empirical and computational models. At present, very few ML models exist for predicting the mechanical responses of track granular materials such as ballast and subballast which may even comprise of composite mixtures of blended granular materials. Moreover, the performance of any ML model depends not only on the quality and quantity of available data but also on the selection process for input parameters, which often lacks adequate justification in the past literature. In this context, the current study introduces ANN models for track granular materials based on published laboratory data with special emphasis on the selection of an optimal set of input parameters. Two applications of ANN are considered to (i) predict the peak friction angle ([Formula: see text]) of a variety of granular mixtures under static loading and (ii) predict ballast breakage under cyclic loading. The selection process involves prudent analysis of key influential parameters in a geotechnical perspective, while also ensuring that they are conveniently measurable. Performance evaluation of these models with various input combinations is carried out, while proposing optimal input parameters for both applications.
Anomaly induced inflation in the minimal quartic extension of Einstein’s gravity
Authors: Demirel Kerim , Tekin Bayram
Published: December 2024

A particular extension of Einstein’s General Relativity up to and including quartic terms in the curvature tensor is minimal in the sense that it has a unique maximally symmetric vacuum and only a massless spin-2 excitation in its spectrum around the vacuum. We study the inflation phase of the universe in this minimal quartic extension of Einstein’s gravity in the presence of trace anomaly terms coming from the Standard Model fields and the fields of the Minimal Supersymmetric Standard Model. We show that the theory allows a quasi-de Sitter phase with sufficient e-foldings.
Mesozoic to Cenozoic deformation of the western Central Andes: an update from structural and U–Pb data of the Calama Basin and surrounding areas
Authors: Martínez F. , López C. , Patiño A. , Parra M. , González R. , Torres C.
Published: December 2024

The Mesozoic to Cenozoic deformation of the Andean forearc of northern Chile is interpreted as a mix of crustal extension, contraction and strike-slip faulting. The effects of these diverse processes on the evolution of the western slope of the Central Andes have been widely debated. However, some factors (e.g. the initial distribution of the Pre-Andean structural and stratigraphic elements, the location and nature of the main sediment sources active during the deformation, the timing of Andean uplift and the location of synorogenic depocenters) are still unknown. In response to these questions and to update our previous knowledge of the tectonic evolution of the Andean forearc, we developed a regional study of the Calama Basin and surrounding areas considering the occurrence of good exposures and the availability of subsurface data. We integrated previous and new field data, 2D seismic profiles and zircon U–Pb ages from Mesozoic to Cenozoic units. Our results indicate a Triassic–Jurassic deformation dominated by rifting that progressed from an intracontinental domain, with the development of isolated half-graben in the Triassic, to the opening of broad marine rift-related basins during Jurassic times, thus confirming many of the interpretations made previously for the Pre-Andean evolution of northern Chile. The new ages of the continental post-rift units suggest that the rift system remained active at 95 Ma. After the post-rift units, the Late Cretaceous orogenic history started with the inversion of pre-existing Triassic and Jurassic rift-related structures, thus allowing the extrusion of synrift and post-rift strata. The latter is well outlined by the Chintoraste Fault exposed in the Loa and San Salvador rivers. During this period, the Andean deformation front was positioned in this region, as recorded by nearly 2 km of Upper Cretaceous to Paleocene synorogenic strata deposited on the inversion anticlines. From the Eocene, an important basement-involved tectonism took place as a result of the eastward migration of the Andean deformation front. The latter allowed the unroofing of the Paleozoic pre-rift basement blocks, creating a topographic relief dominated by contractional intermontane basins (e.g. the Calama Basin). These were filled by sediments eroded from the basement blocks (e.g. the Sierra Limón Verde and Tuina sectors) elevated by reverse faults and by the Mio-Pliocene volcanic products of the magmatic arc.