bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Field 7T MRI in a drug-resistant paediatric epilepsy cohort: image comparison and radiological outcomes
Authors: Vecchiato Katy , Casella Chiara , Dokumaci Ayse Sila , Carney Olivia , Cleary Jon O. , Ciò Pierluigi Di , Cleri Michela , Colford Kathleen , Piper Rory J. , Arichi Tomoki , Eyre Michael , Aitken Fraser , Tomi-Tricot Raphael , Wilkinson Tom , McGinnity Colm J , Yaakub Siti N , Giles Sharon L. , Malik Shaihan , Hammers Alexander , Bridgen Philippa , Carmichael David W. , O’Muircheartaigh Jonathan 
Published: August 2024

AbstractBackground and ObjectivesEpileptogenic lesions in focal epilepsy can be subtle or undetected on conventional brain MRI. Ultra-high field (7T) MRI offers higher spatial resolution, contrast and signal-to-noise ratio compared to conventional imaging systems and has shown promise in the presurgical evaluation of adult focal epilepsy. However, the utility of ultra-high field MRI in paediatric focal epilepsy, where malformations of cortical development are more common, is unclear. This study compared 7T to conventional 3T MRI in children with epilepsy by comparing: (i) scan tolerability; (ii) radiological image quality; (iii) lesion yield.Materials and MethodsChildren with drug-resistant focal epilepsy and healthy controls were recruited prospectively and imaged at both 3T and 7T. Safety and tolerability during scanning was assessed via a questionnaire. Image quality was evaluated by an expert paediatric neuroradiologist and estimated quantitatively by comparing cortical thickness between field strengths. To assess lesion detection yield of 7T MRI, a multi-disciplinary team jointly reviewed patients’ images.Results41 patients (8-17 years, mean=12.6 years, 22 male) and 22 healthy controls (8-17 years, mean=11.7 years, 15 male) were recruited. All children completed the scan, with no significant adverse events. Higher discomfort due to dizziness was reported at 7T (p=0.02), with side-effects more frequently noted in younger children (p=0.02). However, both field strengths were generally well-tolerated and side-effects were transient. 7T images had increased inhomogeneity and artefacts compared to those obtained at 3T. Cortical thickness measurements were significantly thinner at 7T (p<0.001). 8/26 (31%) patients had new lesions identified at 7T which were not identified at 3T, influencing the surgical management in 4/26 (15%).Discussion7T MRI in children with epilepsy is feasible, well-tolerated and is associated with a 31% improvement in lesion detection rates.
The Impact of In Utero Tobacco Exposure on Cardiovascular Disease Risk and All-cause Mortality in Adulthood: a UK Biobank Study
Authors: Zheng Yanxu , Xiong Xinyu , Bao Jing , Liu Jingyu , Wang Jin , Chen Zixi , Zou Fang , Guo Yang , Wang Qingyao , Qiu Yixuan , Zhu Zhaowei 
Published: August 2024

AbstractAimThe negative impacts of in utero tobacco exposure (IUTE) on cardiovascular disease (CVD) have been insufficiently described. This study aims to assess the association between IUTE and the risks of CVD incidence and all-cause mortality, discuss the inter-group difference based on genetic susceptibility and smoking behaviors after birth, and explore the potential mediating factors.MethodsUtilizing a total of 375,024 participants from the UK Biobank, the outcomes include myocardial infarction, stroke, chronic ischemic heart disease, nonrheumatic aortic valve disorders, cardiomyopathy, heart failure, atherosclerosis, aortic aneurysm and dissection, and all-cause mortality.ResultsDuring a median follow-up period of 14.6 years, 50,434 cases of CVD were recorded. IUTE was significantly associated with increased CVD incidence (HR 1.10, 95% CI 1.08-1.12) and all-cause mortality (HR 1.11, 95% CI 1.09-1.14). Interaction effects between IUTE, smoking behaviors after birth, and genetic risk scores for CVD were observed significant (P for interaction < 0.005). The results of the cross-sectional study revealed a significant positive association between IUTE and smoking behaviors after birth (OR 1.08, 95% CI 1.06-1.09). Mediation analysis indicated that smoking behaviors (Proportion = 12.40%, P < 0.001) and HDL-c levels (Proportion = 14.20%, P < 0.001) partially mediated the IUTE-CVD relationship.ConclusionsThis study demonstrated that individuals with IUTE have a higher risk of developing CVD, and smoking behaviors after birth have multifaceted influence on this correlation. These findings underscore the importance of mothers avoiding smoking during pregnancy to mitigate adverse effects on their offspring.
Health-Seeking Behavior and Anxiety of Cancer Patients in Bangladesh during the COVID-19 Pandemic: A Cross-Sectional Study
Authors: Rahman Nur-A-Safrina , Mustafa Munmun , Tabassum Tahsin Tasneem , Simu Sumona Haque , Gupta Mridul , Afrin Sumaiya , Samiha Maisha , Moulee Shahra Tanjim , Abdullah Faisal , Sharmin Sifat , Loken Bilkis Akhter , Trisha Sadia Mahmud , Saimon Md. , Podder Vivek , Singhania Priya , Islam ANM Shamsul 
Published: August 2024

AbstractBackgroundThe COVID-19 pandemic has posed unique challenges for cancer patients, who not only require ongoing medical care but also face an elevated risk of infection. Investigating the health-seeking behavior and barriers among adult cancer patients during this global crisis is crucial for ensuring their access to essential care amidst the pandemic’s complexities.ObjectiveThis cross-sectional study aimed to assess the health-seeking behavior, perceived barriers, and anxiety among adult cancer patients during the COVID-19 pandemic.Materials and MethodsThe study, conducted from August 2020 to December 2020, involved 210 participants purposively selected from the National Institute of Cancer Research and Hospital and Ahsania Mission Cancer and General Hospital in Dhaka. Data was collected through face-to-face interviews using a pre-tested semi-structured questionnaire and analyzed using SPSS (Version 26).ResultsAmong the 210 participants, 56.2% were male, 28.6% aged 46-55, and 36.7% had no formal education. Approximately 52.3% preferred public healthcare facilities, while 6.2% sought homeopathy or pharmacy advice for symptoms. Significant differences emerged in post-pandemic healthcare provider contact (p-0.0). Notably, 88.1% missed appointments, with 78.3% taking no action. Barriers included transport issues (77.1%), reduced income (59%), and lacking financial (53.4%) and mental support (56.6%). Conversely, respondents downplayed public awareness (80%), infection risk from others (84.7%), healthcare provider infection risk (82.4%), and hospital overcrowding (64.8%). Fear of hospitals correlated with public awareness (p-0.0). On the GAD-7 scale, most had minimal anxiety (53.8%), with a weak provider contact-anxiety correlation (p-0.03). Healthcare providers excelled in precautions (99.5%) and health status communication (85.3%).ConclusionDespite the barriers and risks posed by the pandemic, cancer patients prioritized their care. Given the need for continued cancer care and the elevated risk of COVID-19 among cancer patients, adapting measures to align with the population’s real needs could prove highly beneficial.
Structural brain correlates of depression and anxiety in middle-aged and older adults: A systematic review
Authors: Johns Sasha , Maharani Asri , Lea-Carnall Caroline , Shryane Nick 
Published: August 2024

ABSTRACTDepression and anxiety are associated with structural brain changes, however, research in middle-aged and older adults is inconclusive regarding the regions implicated and the magnitude or direction of changes. We hypothesised that the impact on brain structure may be greater in this age group. We conducted a systematic review on the associations between brain structure with depression and anxiety separately to determine: i) if there are brain regions consistently implicated in depression and/or anxiety, ii) if these are the same for depression and anxiety or distinct, and iii) the extent to which research has dealt with both disorders together. Brain regions consistently associated with depression include the hippocampus, orbitofrontal cortex, prefrontal cortex, insula and temporal lobe. Relationships were mostly negative, with diminished brain structure being associated with increased depression. We were unable to identify regions consistently implicated in anxiety due to a lack of studies investigating its links with brain structure. This review has highlighted the urgent need for research into brain structure and anxiety in middle-aged and older adults.
Association between sleep-disordered breathing and moderate to severe depression in systemic lupus erythematosus: the TRUMP2-SLE study
Authors: Ishikawa Yuichi , Oguro Nao , Ichikawa Takanori , Kishida Dai , Sakurai Natsuki , Hidekawa Chiharu , Shidahara Kenta , Hayashi Keigo , Miyawaki Yoshia , Shimojima Yasuhiro , Yoshimi Ryusuke , Sada Ken-ei , Yajima Nobuyuki , Kurita Noriaki 
Published: August 2024

ABSTRACTObjectiveDepression is the most frequent mood disorder that impairs quality of life and medication adherence in patients with systemic lupus erythematosus (SLE). Although sleep-disordered breathing (SDB) is a contributor to depression in the general population, its prevalence in SLE patients and its impact on depression are not clear. We employed a clinical epidemiologic approach to examine them in a multicenter cohort of SLE patients.MethodsThis was a cross-sectional study of 414 Japanese adults with SLE at five university hospitals. The main exposure was high-risk SDB, assessed with the Berlin Questionnaire. The main outcome was moderate to severe depression assessed using the Patient Health Questionnaire-9. Poisson regression models were fitted with a robust error variance to estimate adjusted prevalence ratios (aPRs).ResultsThe mean age was 47.5 years and the mean body mass index (BMI) was 22.1 kg/m2. The prevalence of high-risk SDB was 15.2% (95% confidence interval [95% CI] 11.9%–19.0%). The prevalence of moderate or severe depression was 19.1% (95% CI 15.4%–23.2%). High-risk SDB was associated with a greater likelihood of moderate to severe depression (aPR 2.62, 95% CI 1.62–4.24). All the 1-, 2-, and 3-positive risk categories for SDB were associated with moderate to severe depression, in a dose-dependent manner.ConclusionAmong patients with SLE, SDB is common, and high-risk SDB is strongly associated with moderate to severe depression. The signs and symptoms of SDB should prompt a simultaneous evaluation for concomitant depression.KEY MESSAGESSDB and depression are common among SLE patients with relatively low disease activity.High-risk SDB was associated with a greater prevalence of moderate to severe depression.SDB should be evaluated in SLE patients with concomitant depression.
Disentangling the relationship between biological age and frailty in community-dwelling older Mexican adults
Authors: Fermín-Martínez Carlos A. , Ramírez-García Daniel , Antonio-Villa Neftali Eduardo , López-Teros Miriam Teresa , Seiglie Jacqueline A. , Castrejón Pérez Roberto Carlos , García Peña Carmen , Gutiérrez-Robledo Luis Miguel , Bello-Chavolla Omar Yaxmehen 
Published: August 2024

ABSTRACTOBJECTIVEOlder adults have heterogeneous aging rates. Here, we explored the impact of biological age (BA) and accelerated aging on frailty in community-dwelling older adults.METHODSWe assessed 735 community-dwelling older adults from the Coyocan Cohort. BA was measured using AnthropoAge, accelerated aging with AnthropoAgeAccel, and frailty using both Fried’s phenotype and the frailty index. We explored the association of BA and accelerated aging (AnthropoAgeAccel ≥0) with frailty at baseline and characterized the impact of both on body composition and physical function. We also explored accelerated aging as a risk factor for frailty progression after 3-years of follow-up.RESULTSOlder adults with accelerated aging have higher frailty prevalence and indices, lower handgrip strength and gait speed. AnthropoAgeAccel was associated with higher frailty indices (β=0.0053, 95%CI 0.0027-0.0079), and increased odds of frailty at baseline (OR 1.16, 95%CI 1.09-1.25). We observed a sexual dimorphism in body composition and physical function linked to accelerated aging in non-frail participants; however, this dimorphism was absent in pre-frail/frail participants. Accelerated aging at baseline was associated with higher risk of frailty progression over time (OR 1.74, 95%CI 1.11-2.75).CONCLUSIONSDespite being intertwined, biological accelerated aging is largely independent of frailty in community-dwelling older adults.
Impaired DNA damage response and inflammatory signalling underpins hematopoietic stem cell defects inGata2haploinsufficiency
Authors: Abdelfattah Ali , Habib Ahmad , Thomas Leigh-anne , Menendez-Gonzalez Juan Bautista , Almotiri Alhomidi , Alqahtani Hind , Lawson Hannah , Taha Sarab , Steadman Millie , Athalye Radhika , Gibbs Alex , Alzahrani Hamed , Cato Alice , Giles Peter , Tonks Alex , Boyd Ashleigh S. , Kranc Kamil R. , Rodrigues Neil P. 
Published: August 2024

AbstractClinicalGATA2deficiency syndromes arise from germline haploinsufficiency inducing mutations inGATA2, resulting in immunodeficiency that evolves to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). HowGATA2haploinsufficiency disrupts the function and transcriptional network of hematopoietic stem/progenitors (HSCs/HSPCs) to facilitate the shift from immunodeficiency to pre-leukemia is poorly characterised. Using a conditional mouse model harboring a single allele deletion ofGata2from the start of HSC developmentin utero, we identified pervasive defects in HSPC differentiation from young adultGata2haploinsufficient mice during B-cell development, early erythroid specification, megakaryocyte maturation to platelets and inflammatory cell generation.Gata2haploinsufficiency abolished HSC self-renewal and multi-lineage differentiation capacity. These functional alterations closely associated with deregulated DNA damage responses and inflammatory signalling conveyed fromGata2haploinsufficient HSCs. We identified genetic interplay betweenGata2andAsxl1, a driver of DNA damage and inflammation and, notably, a recurrent secondary mutation found inGATA2haploinsufficiency disease progression to MDS/AML. shRNA mediated knockdown ofAsxl1inGata2haploinsufficient HSPCs led to an enhanced differentiation blockin vitro. By analysis of HSCs from young adult compoundGata2/Asxl1haploinsufficient mice, we discovered hyperproliferation of double haploinsufficient HSCs, which were also functionally compromised in transplantation compared to their singleGata2 or Asxl1haploinsufficient counterparts. Through bothGata2/Asxl1dependent and unique transcriptional programs, HSCs from compoundGata2/Asxl1haploinsufficient fortified deregulated DNA damage responses and inflammatory signalling initiated inGata2haploinsufficient HSCs and established a broad pre-leukemic program. Our data reveal howGata2haploinsufficiency initially drives deregulation of HSC genome integrity and suggest the mechanisms of how secondary mutations likeASXL1take advantage of HSC genomic instability to nurture a pre-leukemic state inGATA2haploinsufficiency syndromes.
Dev-Atlas: A reference atlas of functional brain networks for typically developing adolescents
Authors: Doucet Gaelle E. , Goldsmith Callum , Myers Katrina , Rice Danielle L. , Ende Grace , Pavilka Derek J. , Joliot Marc , Calhoun Vince , Wilson Tony W. , Uddin Lucina Q. 
Published: August 2024

AbstractAdolescence is a critical period for neural changes, including maturation of the brain’s cognitive networks, but also a period of increased vulnerability to psychopathology. It is well accepted that the brain is functionally organized into multiple interacting networks and extensive literature has demonstrated that the spatial and functional organization of these networks shows major age-related changes across the lifespan, but particularly during adolescence. Yet, there is limited option for a reference functional brain atlas derived from typically developing adolescents, which is especially problematic as the reliable and reproducible identification of functional brain networks crucially depends on the use of such reference functional atlases. In this context, we utilized resting-state functional MRI data from a total of 1,391 typically developing youth between the ages of 8 and 17 years to create a new adolescent-specific reference atlas of functional brain networks. We further investigated the impact of age and sex on these networks. Using a multiscale individual component clustering algorithm (MICCA), we identified 24 reliable functional brain networks, classified within six domains: Default-Mode (5 networks), Control (4 networks), Salience (3 networks), Attention (4 networks), Somatomotor (5 networks), and Visual (3 networks). We identified reliable and large effects of age on the spatial topography of these majority of networks, as well as on the functional network connectivity (FNC) between networks. The DMN showed reduced FNC with the other networks with older age. Sex effects were not as widespread. No significant sex-by-age interactions were detected. Overall, we created a novel brain atlas, named Dev-Atlas, focused on a typically developing sample, with the hope that this atlas can be used in future independent developmental network neuroscience studies. Dev-Atlas is freely available to the research community.
Endoplasmic reticulum patterns insect cuticle nanostructure
Authors: Inagaki Sachi , Wada Housei , Itabashi Takeshi , Itakura Yuki , Nakagawa Reiko , Chen Lin , Murata Kazuyoshi , Iwane Atsuko H. , Hayashi Shigeo 
Published: August 2024

AbstractInsect cuticles with nano-level structures exhibit functional surface properties such as structural color and superhydrophobicity. Despite the enormous influence the cuticle has had on biomimetic industrial applications, molecular and cellular mechanisms of cuticular extracellular matrix (ECM) assembly into nanoscale structures remain poorly understood in insects and other taxa. Ghiradella (1989) described how a crystallin-like lattice of endoplasmic reticulum (ER) prefigures the patterning of the porous cuticle of the butterfly wing scale with structural color1. Building on that insight, we show that the nanopore structure of the olfactory (olf) organs, which serve as molecular filters inDrosophila,is built through a novel process in which ER material is trafficked to the plasma membrane mediated by the autophagy pathway. The process is controlled by the insect-specific protein Gore-tex/Osiris23 (Gox)2, which is localized to the tubular ER of olf hair cells. Gox recruits Ref(2)P, the fly counterpart of mammalian p62/SQSTM13, to initiate ER scission. The excised ER fragments are processed by autophagy to gain access to the plasma membrane and trigger membrane invagination, which plays a role in remodeling the cuticular envelope layer to the nanopore formation. This repurposing of the ER phagy for machinery to support the fabrication of nanoscale ECM by the Gox protein sheds light on the nanopatterning of insect cuticles and their genetic control.
Evidencing the role of a conserved polar signaling channel in the activation mechanism of the μ-opioid receptor
Authors: Sarkar Arijit , Dvorácskó Szabolcs , Lipinszki Zoltán , Mitra Argha , Harmati Mária , Buzás Krisztina , Borics Attila 
Published: August 2024

AbstractThe activity of G protein-coupled receptors has been generally linked to dynamically interconverting structural and functional states and the process of activation was proposed to be controlled by an interconnecting network of conformational switches in the transmembrane domain. However, it is yet to be uncovered how ligands with different extent of functional effect exert their actions. According to our recent hypothesis, the transmission of the external stimulus is accompanied by the shift of macroscopic polarization in the transmembrane domain, furnished by concerted movements of conserved polar amino acids and the rearrangement of polar species. Previously, we have examined the μ-opioid, β2-adrenergic and type 1 cannabinoid receptors by performing molecular dynamics simulations. Results revealed correlated dynamics of a polar signaling channel connecting the orthosteric binding pocket and the intracellular G protein-binding surface in all three class A receptors. In the present study, the interplay of this polar signaling channel in the activation mechanism was evidenced by systematic mutation of the channel residues of the μ-opioid receptor. Mutant receptors were analyzed utilizing molecular dynamics simulations and characterizedin vitroby means of radioligand receptor binding and G protein stimulation assays. Apart from one exception, all mutants failed to bind the endogenous agonist endomorphin-2 and to stimulate the Giprotein complex. Furthermore, mutation results confirmed strong allosteric coupling between the binding pocket and the intracellular surface. The strong association and optimal bioactive orientation of the bound agonist was found to be crucial for the initiation of correlated motions and consequent signaling.
Herpes Simplex Virus 1 Envelope Glycoprotein C Shields Glycoprotein D to Protect Virions from Entry-Blocking Antibodies
Authors: Hull McKenna A. , Pritchard Suzanne M. , Nicola Anthony V. 
Published: August 2024

AbstractHerpes simplex virus 1 (HSV-1) gD interaction with the host cell receptor nectin-1 triggers the membrane fusion cascade during viral entry. Potent neutralizing antibodies to gD prevent receptor-binding or prevent gD interaction with gH/gL critical for fusion. HSV has many strategies to evade host immune responses. We investigated the ability of virion envelope gC to protect envelope gD from antibody neutralization. HSV-1 lacking gC was more sensitive to neutralization by anti-gD monoclonal antibodies than a wild type rescuant virus. gD in the HSV-1 gC-null viral envelope had enhanced reactivity to anti-gD antibodies compared to wild type. HSV-1 ΔgC binding to the nectin-1 receptor was more readily inhibited by a neutralizing anti-gD monoclonal antibody. HSV-1 ΔgC was also more sensitive to inhibition by soluble nectin-1 receptor. The viral membrane protein composition of HSV-1 ΔgC was equivalent to that of wild type, suggesting that the lack of gC is responsible for the increased reactivity of gD-specific antibodies and the consequent increased susceptibility to neutralization by those antibodies. Together, the results suggest that gC in the HSV-1 envelope shields both receptor-binding domains and gH/gL-interacting domains of gD from neutralizing antibodies, facilitating HSV cell entry.ImportanceHSV-1 causes lifelong infections. There is no vaccine and no cure. Understanding HSV immune evasion strategies is an important goal. HSV-1 gC is a multi-functional envelope glycoprotein. This study suggests that virion gC physically shields neighboring gD from antibodies, including neutralizing monoclonal antibodies. This mechanism may allow HSV to escape immune detection, promoting HSV infection in the host.