bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders
Authors: Kundura Lucy , Cezar Renaud , Pastore Manuela , Reynes Christelle , Deverdun Jérémy , Le Bars Emmanuelle , Sotto Albert , Reynes Jacques , Makinson Alain , Corbeau Pierre 
Published: October 2023

BackgroundHIV infection induces a 75% increase in the risk of developing neurocognitive impairment (NCI), which has been linked to immune activation. We therefore looked for immune activation markers correlating with NCI.MethodSixty-five people aged 55-70 years living with controlled HIV-1 infection were enrolled in the study and their neurocognitive ability was assessed according to the Frascati criteria. Fifty-nine markers of T4 cell, T8 cell, NK cell, and monocyte activation, inflammation and endothelial activation were measured in their peripheral blood. White matter hyperintensities (WMH) were identified by magnetic resonance imaging. Double hierarchical clustering was performed for the activation markers and 240 patients including the 65 whose neurocognitive performance had been evaluated.ResultsThirty-eight percent of volunteers presented NCI. Twenty-four percent of them were asymptomatic and fourteen percent had a mild disorder. Strikingly, activated (HLA-DR+) as well as senescent (CD57+CD28-CD27±) T4 cells and T8 cells were less prevalent in the peripheral blood of participants with NCI than in participants without the disorder. Accordingly, the percentage of HLA-DR+ T4 cells was lower in volunteers with periventricular and deep WMH. The double hierarchical clustering unveiled six different immune activation profiles. The neurocognitive performances of participants with two of these six profiles were poor. Here again, these two profiles were characterized by a low level of T4 and T8 cell activation and senescence.ConclusionOur observation of low circulating levels of activated and senescent T cells in HIV-1 patients with NCI raises the interesting hypothesis that these lymphocytes may be recruited into the central nervous system.
Unveiling the intricate causal nexus between pancreatic cancer and peripheral metabolites through a comprehensive bidirectional two-sample Mendelian randomization analysis
Authors: Sun Rong , Xu Haoyu , Liu Feng , Zhou Bin , Li Minli , Sun Xiangdong 
Published: October 2023

Aim: Pancreatic cancer (PC) is a devastating malignancy characterized by its aggressive nature and poor prognosis. However, the relationship of PC with peripheral metabolites remains not fully investigated. The study aimed to explore the causal linkage between PC and peripheral metabolite profiles.Methods: Employing publicly accessible genome-wide association studies (GWAS) data, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. The primary analysis employed the inverse-variance weighted (IVW) method. To address potential concerns about horizontal pleiotropy, we also employed supplementary methods such as maximum likelihood, weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO).Results: We ascertained 20 genetically determined peripheral metabolites with causal linkages to PC while high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles accounted for the vast majority. Specifically, HDL particles exhibited an elevated PC risk while VLDL particles displayed an opposing pattern. The converse MR analysis underscored a notable alteration in 17 peripheral metabolites due to PC, including branch chain amino acids and derivatives of glycerophospholipid. Cross-referencing the bidirectional MR results revealed a reciprocal causation of PC and X-02269 which might form a self-perpetuating loop in PC development. Additionally, 1-arachidonoylglycerophosphocholine indicated a reduced PC risk and an increase under PC influence, possibly serving as a negative feedback regulator.Conclusion: Our findings suggest a complex interplay between pancreatic cancer and peripheral metabolites, with potential implications for understanding the etiology of pancreatic cancer and identifying novel early diagnosis and therapeutic targets. Moreover, X-02269 may hold a pivotal role in PC onset and progression.
Original research: initial development of a pragmatic tool to estimate cognitive decline risk focusing on potentially modifiable factors in Parkinson’s disease
Authors: Carlisle Tara C. , Medina Luis D. , Holden Samantha K. 
Published: October 2023

IntroductionCognitive decline is common in Parkinson’s disease (PD). Calculating personalized risk of cognitive decline in PD would allow for appropriate counseling, early intervention with available treatments, and inclusion in disease-modifying trials.MethodsData were from the Parkinson’s Progression Markers Initiative de novo cohort. Baseline scores were calculated for Lifestyle for Brain Health (LIBRA) and the Montreal Parkinson Risk of Dementia Scale (MoPaRDS) per prior literature and preliminary Parkinson’s disease Risk Estimator for Decline In Cognition Tool (pPREDICT) by attributing a point for fourteen posited risk factors. Baseline and 5-year follow-up composite cognitive scores (CCSs) were calculated from a neuropsychological battery and used to define cognitive decliners (PD-decline) versus maintainers (PD-maintain).ResultsThe PD-decline group (n = 44) had higher LIBRA (6.76 ± 0.57, p &lt; 0.05), MoPaRDS (2.45 ± 1.41, p &lt; 0.05) and pPREDICT (4.52 ± 1.66, p &lt; 0.05) scores compared to the PD-maintain group (n = 263; LIBRA 4.98 ± 0.20, MoPaRDS 1.68 ± 1.16, pPREDICT 3.38 ± 1.69). Area-under-the-curve (AUC) for LIBRA was 0.64 (95% confidence interval [CI], 0.55–0.73), MoPaRDS was 0.66 (95% CI, 0.58–0.75) and for pPREDICT was 0.68 (95% CI, 0.61–0.76). In linear regression analyses, LIBRA (p &lt; 0.05), MoPaRDS (p &lt; 0.05) and pPREDICT (p &lt; 0.05) predicted change in CCS. Only age stratified by sex (p &lt; 0.05) contributed significantly to the model for LIBRA. Age and presence of hallucinations (p &lt; 0.05) contributed significantly to the model for MoPaRDS. Male sex, older age, excessive daytime sleepiness, and moderate–severe motor symptoms (all p &lt; 0.05) contributed significantly to the model for pPREDICT.ConclusionAlthough MoPaRDS is a PD-specific tool for predicting cognitive decline relying on only clinical features, it does not focus on potentially modifiable risk factors. LIBRA does focus on potentially modifiable risk factors and is associated with prediction of all-cause dementia in some populations, but pPREDICT potentially demonstrates improved performance in cognitive decline risk calculation in individuals with PD and may identify actionable risk factors. As pPREDICT incorporates multiple potentially modifiable risk factors that can be obtained easily in the clinical setting, it is a first step in developing an easily assessable tool for a personalized approach to reduce dementia risk in people with PD.
Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies
Authors: Decruyenaere Philippe , Giuili Edoardo , Verniers Kimberly , Anckaert Jasper , De Grove Katrien , Van der Linden Malaïka , Deeren Dries , Van Dorpe Jo , Offner Fritz , Vandesompele Jo 
Published: October 2023

IntroductionDiffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin’s lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients.Materials and methodsBlood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit.ResultsHigher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score.ConclusionTotal RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.
Identification of prognosis-related lncRNAs and cell validation in lung squamous cell carcinoma based on TCGA data
Authors: Cui Yishuang , Wu Yanan , Zhang Mengshi , Zhu Yingze , Su Xin , Kong Wenyue , Zheng Xuan , Sun Guogui 
Published: October 2023

ObjectiveTo discern long non-coding RNAs (lncRNAs) with prognostic relevance in the context of lung squamous cell carcinoma (LUSC), we intend to predict target genes by leveraging The Cancer Genome Atlas (TCGA) repository. Subsequently, we aim to investigate the proliferative potential of critical lncRNAs within the LUSC milieu.MethodsDESeq2 was employed to identify differentially expressed genes within the TCGA database. Following this, we utilized both univariate and multivariate Cox regression analyses to identify lncRNAs with prognostic relevance. Noteworthy lncRNAs were selected for validation in cell lines. The intracellular localization of these lncRNAs was ascertained through nucleocytoplasmic isolation experiments. Additionally, the impact of these lncRNAs on cellular proliferation, invasion, and migration capabilities was investigated using an Antisense oligonucleotides (ASO) knockdown system.ResultsMultivariate Cox regression identified a total of 12 candidate genes, consisting of seven downregulated lncRNAs (BRE-AS1, CCL15-CCL14, DNMBP-AS1, LINC00482, LOC100129034, MIR22HG, PRR26) and five upregulated lncRNAs (FAM83A-AS1, LINC00628, LINC00923, LINC01341, LOC100130691). The target genes associated with these lncRNAs exhibit significant enrichment within diverse biological pathways, including metabolic processes, cancer pathways, MAPK signaling, PI3K-Akt signaling, protein binding, cellular components, cellular transformation, and other functional categories. Furthermore, nucleocytoplasmic fractionation experiments demonstrated that LINC00923 and LINC01341 are predominantly localized within the cellular nucleus. Subsequent investigations utilizing CCK-8 assays and colony formation assays revealed that the knockdown of LINC00923 and LINC01341 effectively suppressed the proliferation of H226 and H1703 cells. Additionally, transwell assays showed that knockdown of LINC00923 and LINC01341 significantly attenuated the invasive and migratory capacities of H226 and H1703 cells.ConclusionThis study has identified 12 candidate lncRNA associated with prognostic implications, among which LINC00923 and LINC01341 exhibit potential as markers for the prediction of LUSC outcomes.
Dietary fatty acids improve perceived sleep quality, stress, and health in migraine: a secondary analysis of a randomized controlled trial
Authors: Faurot Keturah R. , Park Jinyoung , Miller Vanessa , Honvoh Gilson , Domeniciello Anthony , Mann J. Douglas , Gaylord Susan A. , Lynch Chanee E. , Palsson Olafur , Ramsden Christopher E. , MacIntosh Beth A. , Horowitz Mark , Zamora Daisy 
Published: October 2023

BackgroundMigraine is a prevalent disabling condition often associated with comorbid physical and psychological symptoms that contribute to impaired quality of life and disability. Studies suggest that increasing dietary omega-3 fatty acid is associated with headache reduction, but less is known about the effects on quality of life in migraine.MethodsAfter a 4-week run-in, 182 adults with 5–20 migraine days per month were randomized to one of the 3 arms for sixteen weeks. Dietary arms included: H3L6 (a high omega-3, low omega-6 diet), H3 (a high omega-3, an average omega-6 diet), or a control diet (average intakes of omega-3 and omega-6 fatty acids). Prespecified secondary endpoints included daily diary measures (stress perception, sleep quality, and perceived health), Patient-Reported Outcome Measurement Information System Version 1.0 ([PROMIS©) measures and the Migraine Disability Assessment (MIDAS). Analyses used linear mixed effects models to control for repeated measures.ResultsThe H3L6 diet was associated with significant improvements in stress perception [adjusted mean difference (aMD): −1.5 (95% confidence interval: −1.7 to −1.2)], sleep quality [aMD: 0.2 (95% CI:0.1–0.2)], and perceived health [aMD: 0.2 (0.2–0.3)] compared to the control. Similarly, the H3 diet was associated with significant improvements in stress perception [aMD: −0.8 (−1.1 to −0.5)], sleep quality [aMD: 0.2 (0.1, 0.3)], and perceived health [aMD: 0.3 (0.2, 0.3)] compared to the control. MIDAS scores improved substantially in the intervention groups compared with the control (H3L6 aMD: −11.8 [−25.1, 1.5] and H3 aMD: −10.7 [−24.0, 2.7]). Among the PROMIS-29 assessments, the biggest impact was on pain interference [H3L6 MD: −1.8 (−4.4, 0.7) and H3 aMD: −3.2 (−5.9, −0.5)] and pain intensity [H3L6 MD: −0.6 (−1.3, 0.1) and H3 aMD: −0.6 (−1.4, 0.1)].DiscussionThe diary measures, with their increased power, supported our hypothesis that symptoms associated with migraine attacks could be responsive to specific dietary fatty acid manipulations. Changes in the PROMIS© measures reflected improvements in non-headache pain as well as physical and psychological function, largely in the expected directions. These findings suggest that increasing omega-3 with or without decreasing omega-6 in the diet may represent a reasonable adjunctive approach to reducing symptoms associated with migraine attacks.
Trial Registration: ClinicalTrials.gov NCT02012790.
Family characteristics in adolescents with overweight or obesity: a network analysis
Authors: Huang Lidong , Zhao Kang , Zhu Hanfei , Li Xiaonan , Yang Yiqing , Hou Caiyun , Zhu Shuqin , Xu Qin 
Published: October 2023

BackgroundRates of overweight and obesity continue to grow in adolescents. Overweight and obesity in adolescence are associated with numerous immediate and long-term adverse health conditions. Throughout adolescence, parents and the family have an important and central influence on adolescents' health and lifestyle. The home environment may be a major factor in shaping children's weight. However, our current understanding of the interplay between family-related variables in adolescents with overweight or obesity is limited and fragmented. This study aimed to assess the relationship between family-related variables in adolescents who are overweight or obese using network analysis and inform future health promotion for family-based intervention.MethodsParticipants (n = 488) were recruited from middle schools in Nanjing from October 2022 to March 2023. Participants, together with their parents, completed a questionnaire at school about the family food environment, family size, family APGAR index, family physical activity facilities, parental mental health, rearing behavior, parental weight status, drinking history, marital satisfaction, and sociodemographic characteristics.ResultsThe network split into three distinct communities of items. Network analysis showed that parental mental health and paternal rearing styles-rejection were the most central nodes in the network. In contrast, maternal weight status was the most peripheral and least connected nodes.ConclusionFamily-related variables constituted a connected network in adolescents with overweight or obesity. The pattern of network node connections supports that interventions could prioritize targeting changing parental mental health and paternal rearing styles in adolescents with overweight or obesity.
Comparison of biologics and small-molecule drugs in axial spondyloarthritis: a systematic review and network meta-analysis
Authors: Zhou Erye , Wu Jian , Zeng Keqin , Wang Mingjun , Yin Yufeng 
Published: October 2023

Background: Biologics and small-molecule drugs have become increasingly accepted worldwide in the treatment of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). However, a quantitative multiple comparison of their efficacy and safety is lacking. This study aims to provide an integrated assessment of the relative benefits and safety profiles of these drugs in axSpA treatment.Methods: We included randomized clinical trials that compared biologics and small-molecule drugs in the treatment of axSpA patients. The primary outcomes assessed were efficacy, including the Assessment of SpondyloArthritis International Society (ASAS) improvement of 20% (ASAS20) and 40% (ASAS40). Safety outcomes included treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). We used the surface under the cumulative ranking (SUCRA) curve value and ranking plot to evaluate and rank clinical outcomes and safety profiles of different treatments. The two-dimensional graphs were illustrated to visually assess both the efficacy (horizontal axis) and safety (vertical axis) of each intervention.Results: Our analysis included 57 randomized clinical trials involving a total of 11,787 axSpA patients. We found that seven drugs (TNFRFc, TNFmAb, IL17Ai, IL17A/Fi, IL17RAi, JAK1/3i, and JAK1i) were significantly more effective in achieving ASAS20 response compared to the placebo (PLA). Except for IL17RAi, these drugs were also associated with higher ASAS40 responses. TNFmAb demonstrated the highest clinical response efficacy among all the drugs. Subgroup analyses for AS and nr-axSpA patients yielded similar results. IL17A/Fi emerged as a promising choice, effectively balancing efficacy and safety, as indicated by its position in the upper right corner of the two-dimensional graphs.Conclusion: Our findings highlight TNFmAb as the most effective biologic across all evaluated efficacy outcomes in this network meta-analysis. Meanwhile, IL17A/Fi stands out for its lower risk and superior performance in achieving a balance between efficacy and safety in the treatment of axSpA patients.
Constrained model assumptions using recent data of α-particle reactions on 144Sm
Authors: Avrigeanu Vlad , Avrigeanu Marilena 
Published: October 2023

Analysis of the latest high–precision cross sections of (α,γ) and (α,n) reactions on 144Sm below the Coulomb barrier is carried out using a consistent parameter set of the statistical model. This prevents the need to use empirical rescaling factors of either γ or neutron widths. Particular attention is paid to uncertainties of the calculated cross sections which are related to the accuracy of the primary data that were used to set up the consistent input parameters. The calculated cross sections are found in good agreement with the new experimental data for the 144Sm(α,n)147Gd reaction; however, the same is not true for the excitation function of 144Sm(α,γ)148Gd which decreases faster at incident energies below ∼12 MeV. An increase of the α-particle direct collective inelastic scattering at lower energies is found responsible for this decrease of the (α,γ) reaction cross sections. The consequent lower nuclear effects may correspond to the Coulomb excitation effect assumed, although in a different manner, within the so-called “α-potential mystery” for the same optical–potential account of α-particle absorption and emission as well.
“A place without walls, only opportunities”: personal accounts of attending Recovery Colleges in Norway
Authors: Selbekk Anne Schanche , Kvelland Linda Teie , Nordås Rebecca , Kvia Aasa , Robertson Inger Eide 
Published: October 2023

IntroductionRecovery colleges (RCs) are learning environments, first established in the UK, based on principles that support positive life changes and reduce stigma related to challenges with mental health and substance use problems. RCs offer courses based on co-production processes and are designed and delivered jointly by individuals with lived experience and professional experts. The courses are open to anyone, attracting people with a variety of life experiences. RCs are non-clinical environments that provide individuals with the identities of students and/or trainers as autonomous and independent agents. In this paper, we investigate experiences of being a part of a RC in Norway, either as a student and/or as a course trainer with lived experiences of mental health or substance use challenges. We ask the following research question: What kinds of personal and social processes are enabled by being part of a recovery college from the perspective of persons with experience-based competence?Materials and methodsThe study is qualitative and explorative based on 11 individual (N= 11) and two focus group interviews (N= 8). Participants were recruited from two of the first RCs in Norway between August 2021 and January 2022.ResultsStudy participants describe how their involvement in a RC provided them with opportunities to assume new positions in their recovery process, both related to former institutional identities given in the course of treatment and related to the way they see themselves as people struggling with mental health and substances use challenges. Attending a RC represented significant transitions (1) from an institutional position as “sick” or as “what’s on the paper” into a position as “a whole person”; (2) from being in in a position as a recipient of care to the position as actively responsible for life changes; (3) from seeing themselves as worthless to seeing themselves as persons with resources; (4) from being alone to being part of a fellowship. Participants describe being part of a RC as an invaluable addition to other kind of support or help.DiscussionIt is important to provide alternative arenas like RC for facilitating work with life changes, as an invaluable addition to regular services.