bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism
Authors: Castells-Nobau Anna , Moreno-Navarrete José Maria , de la Vega-Correa Lisset , Puig Irene , Federici Massimo , Sun Jiuwen , Burcelin Remy , Guzylack-Piriou Laurence , Gourdy Pierre , Cazals Laurent , Arnoriaga-Rodríguez María , Frühbeck Gema , Seoane Luisa Maria , López-Miranda José , Tinahones Francisco J , Dieguez Carlos , Dumas Marc-Emmanuel , Pérez-Brocal Vicente , Moya Andrés , Perakakis Nikolaos , Mingrone Geltrude , Bornstein Stefan , Rodriguez Hermosa Jose Ignacio , Castro Ernesto , Fernández-Real Jose Manuel , Mayneris-Perxachs Jordi 
Published: October 2024

Background
The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.

Objective
To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.

Design
Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).

Results

Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in
Drosophila melanogaster
validated these human insulin sensitivity-associated changes.

Conclusion

These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.
Cite Now
Bullying victimisation and perpetration of foster and kinship youth in the USA
Authors: Helton Jesse J , Hong Jun Sung , Kong Vibol 
Published: October 2024

BackgroundChildhood bullying can result in serious injury. Our objective was to compare bullying victimisation and perpetration of school-aged youth from 2018 to 2022 in different households: foster care, kinship care and birth families. A second objective examined correlations between bullying and adverse childhood experiences, child gender, age and race while stratifying by household type.MethodsThe 2018–2022 samples of the National Surveys of Children’s Health were used. Bullying victimisation and perpetration were reported by caregivers and ranged from none, yearly, monthly to weekly or daily. Adversities include parental separation, death or incarceration; witnessing or experiencing violence; living with an adult with a substance problem or severe mental illness; or racial discrimination. Pearson χ2and ordinal logistic regression models were used.ResultsPre-COVID-19, 69% of foster youth were victimised compared with 44% of kinship and 48% of birth-family youth, and 57% of foster youth perpetrated compared with 21% of kinship and 20% of birth-family youth. During COVID-19, the relative risk of both victimisation and perpetration flipped between groups: 25% of fosters were victimised compared with 34% of both kinship and birth youth, and 24% of fosters perpetrated compared with 35% of kinship and 33% of birth youth. In 2022, younger foster youth were at a higher risk of victimisation and perpetration, while males were at risk of perpetration.Discussion and conclusionsFoster youth are at high risk for victimisation and perpetration compared with youth living with kinship or birth families. Results indicate that prevention efforts in school settings may be the most effective.
Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses
Authors: Dong Yijun , Zhang Zongliang , Luan Siyuan , Zheng Meijun , Wang Zeng , Chen Yongdong , Chen Xiaoting , Tong Aiping , Yang Hui 
Published: October 2024

BackgroundAntibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.MethodsThis study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E.ResultsOur findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress.ConclusionIn conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.
Gal-3 blocks the binding between PD-1 and pembrolizumab
Authors: Greisen Stinne Ravn , Bendix Mia , Nielsen Morten Aagaard , Pedersen Kathrine , Jensen Nina Haunstrup , Hvid Malene , Mikkelsen Jakob Hauge , Drace Taner , Boesen Thomas , Steiniche Torben , Schmidt Henrik , Deleuran Bent 
Published: October 2024

IntroductionImmune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic malignant melanoma (MM) and improved long-term survival. Despite the impressive results, some patients still have progressive disease, and the search for biomarkers predicting response to ICI treatment is ongoing. In this search, galectin-3 (Gal-3) has been suggested as a molecule of interest, both as a marker of treatment response and as a treatment target to potentiate ICI therapy. We have previously demonstrated the binding between programmed cell death 1 (PD-1) and Gal-3, and here, we investigated the interaction between PD-1, pembrolizumab, and Gal-3 in metastatic MM patients.MethodsThe binding between PD-1, pembrolizumab and Gal-3 was investigated by surface plasmon resonance (SPR) and cryogenic electron microscopy (cryo-EM). The function was studied in in vitro cultures and soluble levels of both PD-1 and Gal-3 were measured in metastatic MM patients, treated with pembrolizumab.ResultsBy SPR, we demonstrated that Gal-3 can block the binding between PD-1 and pembrolizumab, and further visualized a steric inhibition using cryo-EM. T cells cultured with Gal-3 had reduced pro-inflammatory cytokine production, which could not be rescued by pembrolizumab. In patients with metastatic MM, high levels of Gal-3 in plasma were found in patients with a longer progression-free survival in the study period, whereas high Gal-3 expression in the tumor was seen in patients with disease progression. Soluble PD-1 levels in plasma increased after treatment with pembrolizumab and correlated with disease progression.ConclusionWe demonstrate that the interaction between PD-1 and Gal-3 interferes with the binding of pembrolizumab, supporting that an immune suppression induced by Gal-3 in the tumor microenvironment cannot be rescued by pembrolizumab.
Classification ofPTENgermline non-truncating variants: a new approach to interpretation
Authors: Margot Henri , Jones Natalie , Matis Thibaut , Bonneau Dominique , Busa Tiffany , Bonnet Françoise , Conrad Solene , Crivelli Louise , Monin Pauline , Fert-Ferrer Sandra , Mortemousque Isabelle , Raad Sabine , Lacombe Didier , Caux Frédéric , Sevenet Nicolas , Bubien Virginie , Longy Michel 
Published: October 2024

BackgroundPTEN hamartoma tumour syndrome (PHTS) encompasses distinct syndromes, including Cowden syndrome resulting fromPTENpathogenic variants. Missense variants account for 30% of PHTS cases, but their classification remains challenging. To address these difficulties, guidelines were published by the Clinical Genome Resource PTEN Variant Curation Expert Panel.MethodsBetween 2010 and 2020, the Bergonie Institute reference laboratory identified 76 different non-truncatingPTENvariants in 166 patients, 17 of which have not previously been reported. Variants were initially classified following the current guidelines. Subsequently, a new classification method was developed based on four main criteria: functional exploration, phenotypic features and familial segregation, in silico modelling, and allelic frequency.ResultsThis new method of classification is more discriminative and reclassifies 25 variants, including 8 variants of unknown significance.ConclusionThis report proposes a revision of the currentPTENvariant classification criteria which at present rely on functional tests evaluating only the phosphatase activity of PTEN and apply a particularly stringent clinical PHTS score.The classification of non-truncating variants ofPTENis facilitated by taking into consideration protein stability for variants with intact phosphatase activity, clinical and segregation criteria adapted to the phenotypic variability of PHTS and by specifying the allelic frequency of variants in the general population. This novel method of classification remains to be validated in a prospective cohort.
Novel therapies in CIDP
Authors: Mair Devan , Madi Heba , Eftimov Filip , Lunn Michael P , Keddie Stephen 
Published: October 2024

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous but clinically well-described disease within circumscribed parameters. It is immunologically mediated through several poorly understood mechanisms. First-line therapies with steroids, intravenous immunoglobulin (IVIG) or plasma exchange are each effective in about two-thirds of patients. These treatments are seldom associated with complete resolution or cure, and often pose considerable practical, financial and medical implications.Our understanding of many of the key pathological processes in autoimmune diseases is expanding, and novel targeted therapeutics are being developed with promise in several autoimmune neurological disorders.This narrative review looks first at detailing key pathogenic mechanisms of disease in CIDP, followed by an in-depth description of potential novel therapies and the current evidence of their application in clinical practice.
Post COVID-19 syndrome among 5248 healthcare workers in England: longitudinal findings from NHS CHECK
Authors: Dempsey Brendan , Blake Helen A , Madan Ira , Stevelink Sharon A M , Greenberg Neil , Raine Rosalind , Rafferty Anne-Marie , Bhundia Rupa , Wessely Simon , Lamb Danielle 
Published: October 2024

ObjectivesThe objectives of this study were to examine post COVID-19 syndrome (PCS) among healthcare workers (HCWs) in England and explore risk factors for the condition.MethodsData were collected by National Health Service (NHS) CHECK, a longitudinal study exploring HCWs’ mental and physical well-being during and after the COVID-19 pandemic. NHS CHECK collected data at four timepoints: the baseline survey between April 2020 and January 2021, and then three follow-up surveys at approximately 6, 12 and 32 months post baseline. PCS data were collected at 12 and 32 months, while risk factor data were from baseline. HCWs were asked what COVID-19 symptoms they experienced and for how long and were classified as having PCS if they had any symptom for ≥12 weeks. Multilevel regressions were used to examine risk factors for PCS.ResultsThis study included 5248 HCWs. While 33.6% (n=1730) reported prolonged COVID-19 symptoms consistent with PCS, only 7.4% (n=385) reported a formal diagnosis of PCS. Fatigue, difficult concentrating, insomnia and anxiety or depression were the most common PCS symptoms. Baseline risk factors for reporting PCS included screening for common mental disorders, direct contact with COVID-19 patients, pre-existing respiratory illnesses, female sex and older age.ConclusionsWhile a third of HCWs reported prolonged COVID-19 symptoms consistent with PCS, a smaller percentage reported a formal diagnosis of the condition. We replicate findings that direct contact with COVID-19 patients, older age, female sex, pre-existing respiratory illness and symptoms of common mental disorders are associated with increased risk of PCS.
Development of a web-based ecological momentary assessment tool to measure day-to-day variability of the symptoms in patients with Sjögren’s disease
Authors: Georgel Laurie , Benyoussef Anas-Alexis , Berrouiguet Sofian , Guellec Dewi , Carvajal Alegria Guillermo , Marhadour Thierry , Jousse-Joulin Sandrine , Cochener-Lamard Béatrice , Labetoulle Marc , Gottenberg Jacques-Eric , Bourcier Tristan , Nocturne Gaétane , Saraux Alain , Mariette Xavier , Consigny Maëlys , Gravey Michel , Devauchelle-Pensec Valérie , Seror Raphaele , Cornec Divi 
Published: October 2024

ObjectivesTo develop and validate a web-based ecological momentary assessment (EMA) tool to enhance symptoms monitoring among patients with Sjögren’s disease (SjD).MethodsConsecutive adults with SjD were enrolled in this pilot observational study. Participants used the WebApp over a 3-month period, for the daily collection of individual EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scales and separate assessment of eyes and mouth dryness, using 0–10 numerical scales. Primary outcome was the measure of the interdaily variability of symptoms. Data collected through the WebApp were compared with those obtained with paper-based questionnaires administered during a final visit, using distinct approaches (predicted error, maximum negative error and maximum positive error). User experience was assessed using the System Usability Scale (SUS) score.ResultsAmong the 45 participants, 41 (91.1%) were women. Median age was 57 years (IQR: 49–66). Daily variability of symptoms ranged between 0.5 and 0.8 points across the scales. Over the 3-month period, the predicted error ranged between −1.2 and −0.3 points of the numerical scales. The greatest differences were found for fatigue (−1.2 points (IQR: −2.3 to −0.2)) and ESSPRI score (−1.2 points (IQR: −1.7 to −0.3)). Over the last 2 weeks, the predicted error ranged between – 1.2 and 0.0 points. Maximum negative error ranged between −2.0 and −1.0 points, and maximum positive error between −0.3 and 0.0 points. Median SUS score was 90 (IQR: 85–95).ConclusionOur results demonstrate the usability and the relevance of our web-based EMA tool for capturing data that closely reflects daily experiences of patients with SjD.
An evaluation of an online STI service across London: reviewing uptake, utility and outcomes over a 4-year period
Authors: Tittle Victoria , Day Sara Louise , Tostevin Anna , Kelly Adrian M , Spate Jonathan , Burns Fiona , Gibbs Jo , Howarth Alison , Sullivan Ann 
Published: October 2024

ObjectivesSince 2018, Sexual Health London (SHL) has provided remote sexually transmitted infection (STI) testing services to London residents over 16 years of age. SHL was an asymptomatic screening service. In 2020, SHL widened access to non-urgent symptomatic testing. We undertook a 4-year evaluation on the uptake of SHL’s online testing pathway and outcomes, including the association of positive chlamydia and gonorrhoea nucleic acid amplification test (NAAT) outcomes with user demographics and user utility.MethodsThis is a retrospective data analysis of routine SHL clinical data from 8 January 2018 to 31 March 2022 of all STI test kit orders, focusing on HIV, chlamydia and gonorrhoea outcomes. Descriptive analysis on uptake of each stage of SHL’s clinical care pathway is provided, including HIV testing outcomes. Binary logistic regression was used to examine the association between SHL user-completed online consultation information, SHL uptake and chlamydia and gonorrhoea NAAT results (negative or positive).ResultsDuring the evaluation period, there were 1 476 187 orders made by 670 293 unique users. The return rate for chlamydia and gonorrhoea NAATs was 79.5% and 67.6% for HIV blood samples. The positivity rate from sufficient samples was 4.5% for chlamydia, 1.6% for gonorrhoea and 0.3% reactivity for HIV. There were increased odds of a positive chlamydia and gonorrhoea NAAT result in non-cisgender women, those with a high number of STI orders, non-UK born and those who collected an STI test kit from a clinic-based service.ConclusionsTo date, this is the largest number of orders in an evaluation of online postal sexual health infection testing in the UK, and highest return rate of samples, suggesting acceptability of SHL for STI testing. Positivity rates for chlamydia and gonorrhoea NAAT tests are lower than national figures, which may reflect asymptomatic screening prior to 2020 and testing of non-urgent symptoms since 2020.
Advance Consent for participation in Acute Stroke Trials (ACTION): protocol for a feasibility study
Authors: Udoh Ubong , Seeger Rena , Dewar Brian , Cummings Emma , Gocan Sophia , Nicholls Stuart , Fedyk Mark , Shepherd Victoria , Perry Jeff , Fahed Robert , Ramsay Tim , Brehaut Jamie , Hill Michael D , Poppe Alexandre Y , Menon Bijoy K , Swartz Richard H , Dowlatshahi Dar , Shamy Michel 
Published: October 2024

IntroductionObtaining informed consent for research from patients in medical emergencies remains a challenge, particularly in acute stroke care as treatment must be administered quickly and patients often arrive in the hospital in a state of incapacitation. Adaptations to standard consenting approaches—such as the use of surrogate consent or deferral of consent—have significant limitations. This feasibility study aims to test a new consenting approach in acute stroke care that we call advance consent. Advance consent has the potential to render emergency trial enrolment faster, fairer and more transparent, leading to more generalisable results.Methods and designWe will conduct a five-part study at The Ottawa Hospital, a quaternary care stroke centre: (1) administering questionnaires in the Ottawa Hospital Stroke Prevention Clinic that will examine patients’ perspectives on research participation and advance consent; (2) inviting participants to consent in advance to any or both currently enrolling acute stroke trials; (3) tracking patient enrolment into these trials over 1 year; (4) administering a follow up questionnaire to participants at 1 year and (5) administering a questionnaire to participating hospital staff in order to interrogate their experiences with advance consent. Outcomes include but are not limited to eligibility rate, recruitment rate, withdrawal rate and the proportion of patients whose advance consent results in trial enrolment.ConclusionThis study will test the feasibility of enrolling patients at risk of stroke into acute stroke trials using advance consent.
Definitions of white matter hyperintensity change: impact on estimates of progression and regression
Authors: Jochems Angela C C , Muñoz Maniega Susana , Clancy Una , Arteaga Reyes Carmen , Jaime Garcia Daniela , Valdés Hernández Maria del C. , Chappell Francesca M , Barclay Gayle , Jardine Charlotte , McIntyre Donna , Gerrish Iona , Wiseman Stewart , Stringer Michael S , Thrippleton Michael J , Doubal Fergus , Wardlaw Joanna M 
Published: October 2024

BackgroundWhite matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression.MethodsWe recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1–3 months after stroke and 1 year later. We assessed WMH volume (in absolute mL and % intracranial volume) and applied four different definitions, including two thresholds (based on SD or mL), percentile and quintile approaches.ResultsIn 198 participants, mean age 65.5 (SD=11.13), baseline WMH volume was 15.46 mL (SD=19.2), the mean net WMH volume change was 0.98 mL (SD=2.84), range −7.98 to +12.84 mL. Proportion regressing/stable/progressing WMH were threshold 1 (SD), 29.8%/55.6%/14.6%; threshold 2(mL), 29.8%/16.7%/53.5%; percentile approach, 28.3%/21.2%/50.5%. The quintile approach includes five groups with quintile 3 reflecting no change (N=40), quintiles 1 and 2 any WMH decrease (N=80) and quintiles 4 and 5 any WMH increase (N=78).ConclusionsDifferent WMH change definitions cause big differences in how participants are categorised; additionally, non-normal WMH distribution precludes use of some definitions. Consistent use of an appropriate definition would facilitate data comparisons, particularly in clinical trials of potential WMH treatments.
Exosomes-mediated delivery of miR-486-3p alleviates neuroinflammation via SIRT2-mediated inhibition of mitophagy after subarachnoid hemorrhage
Authors: Sheng Bin , Gao Sen , Chen XiangXin , Liu Yang , Lai Niansheng , Dong Jin , Sun Jiaqing , Zhou Yan , Wu Lingyun , Hang Chun-Hua , Li Wei 
Published: October 2024

BackgroundNeuroinflammation participates in the pathogenesis of subarachnoid haemorrhage (SAH); however, no effective treatments exist. MicroRNAs regulate several aspects of neuronal dysfunction. In a previous study, we found that exosomal miR-486-3p is involved in the pathophysiology of SAH. Targeted delivery of miR-486-3p without blood-brain barrier (BBB) restriction to alleviate SAH is a promising neuroinflammation approach.MethodsIn this study, we modified exosomes (Exo) to form an RVG-miR-486-3p-Exo (Exo/miR) to achieve targeted delivery of miR-486-3p to the brain. Neurological scores, brain water content, BBB damage, flow cytometry and FJC staining were used to determine the effect of miR-486-3p on SAH. Western blot analysis, ELISA and RT-qPCR were used to measure relevant protein and mRNA levels. Immunofluorescence staining and laser confocal detection were used to measure the expression of mitochondria, lysosomes and autophagosomes, and transmission electron microscopy was used to observe the level of mitophagy in the brain tissue of mice after SAH.ResultsTail vein injection of Exo/miR improved targeting of miR-486-3p to the brains of SAH mice. The injection reduced levels of neuroinflammation-related factors by changing the phenotype switching of microglia, inhibiting the expression of sirtuin 2 (SIRT2) and enhancing mitophagy. miR-486-3p treatment alleviated neurobehavioral disorders, brain oedema, BBB damage and neurodegeneration. Further research found that the mechanism was achieved by regulating the acetylation level of peroxisome proliferator-activated receptor γ coactivator l alpha (PGC-1α) after SIRT2 enters the nucleus.ConclusionExo/miR treatment attenuates neuroinflammation after SAH by inhibiting SIRT2 expression and stimulating mitophagy, suggesting potential clinical applications.