bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analysis of ROS1+ non-small cell lung cancer reveals an upregulation of nucleotide synthesis and cell adhesion pathways
Authors: Terrones Marc , Op de Beeck Ken , Van Camp Guy , Vandeweyer Geert , Mateiu Ligia 
Published: December 2024

IntroductionThe transcriptomic characteristics of ROS1+ non-small cell lung cancer (NSCLC) represent a crucial aspect of its tumor biology. These features provide valuable insights into key dysregulated pathways, potentially leading to the discovery of novel targetable alterations or biomarkers.MethodsFrom The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, all available ROS1+ (n = 10), ALK+ (n = 5) and RET+ (n = 5) NSCLC tumor and ROS1+ cell line (n = 7) RNA-sequencing files were collected. In addition, 10 healthy lung RNA-seq samples were included. Differential gene expression with DESeq2 (R package) and gene co-expression (WGCNA, R package) analyses were performed. Functional annotation was performed through Gene Set Enrichment Analysis (GSEA) using Webgestalt and RNAseqChef, Over-Representation Analysis (ORA) through Enrichr. iRegulon was used to identify enriched transcription factors that regulate a gene co-expression module.ResultsROS1+ NSCLC samples were significantly enriched for the nucleotide synthesis and cell adhesion KEGG pathways compared to ALK+ and RET+ samples. Moreover, NOTCH1 was significantly downregulated in ROS1+ NSCLC and PD-L1 was weakly expressed. When comparing ROS1+ tumor versus cell line transcriptomes, an upregulation of MYC and MET was found in cell lines together with a significantly decreased expression of HER3, HER4 and BRAF. Within ROS1-tumors, GJB2 was overexpressed in the CD74- and CLTC-ROS1+ subgroups. The differential expression of IL20RB and GJB2 in cell lines was confirmed through RT-qPCR. Finally, the gene co-expression analysis unveils a gene cluster involving cell cycle-related genes which significantly correlates with the disease stage of patients. In addition, we propose TFDP1 and ISL1 as key ROS1-specific transcription factors.ConclusionThis study highlights cell adhesion and nucleotide synthesis as crucial signatures in ROS1+ NSCLC. The upregulation of GJB2 may serve as a prognostic biomarker, along with IL20RB, a known mediator of bone metastases. Furthermore, TDFP1 and ISL1 were identified as relevant transcription factors that could potentially regulate the biological processes in ROS1-rearranged NSCLC.
Optimal exercise dose-response improves health-related quality of life in cancer survivors: a systematic review and Bayesian network meta-analysis of RCTs
Authors: Xiong Zhiyu , Yuan Yuan , Yang Yong , Qiu Bopeng , Bai Ying , Wang Tao , Wang Junyu , Zhang Lin , Li Yawen 
Published: December 2024

ObjectiveCancer survivors often face significant health-related quality of life (HRQoL) challenges. Although exercise has been proven to improve HRQoL in cancer survivors, the optimal dose and intensity of exercise for this population has not been fully determined. Adherence to exercise may vary based on exercise intensity, affecting results. This study explored the dose-response relationship of different exercise types and intensities to better understand their impact on HRQoL in cancer survivors.MethodsWe searched five databases—PubMed, Embase, the Cochrane Library, Web of Science, and Scopus—from their inception until 1 December 2023. Data analysis was performed using R software with the MBNMA and RJAGS packages. Due to combining data from different scales, effect sizes were reported as standardized mean differences (SMD) with 95% credible intervals (95% CrI). The risk of bias was assessed independently by three reviewers using the RoB2 tool.ResultsA total of 48 studies involving 3050 cancer survivors. Across all exercise types, the most beneficial exercise dose was identified to be 850 metabolic equivalents of task (METs)-min/week (SMD: 0.753, 95%Crl: 0.463 to 1.096), with diminishing returns observed beyond 1,100 METs-min/week. Among the various types of exercises, mixed training (MT) emerged as the optimal choice, demonstrating its efficacy at 970 METs-min/week (SMD: 0.883, 95% Crl: 0.455 to 1.345). Aerobic exercise (AE) at a dose of 430 METs-min/week (SMD: 0.681, 95% Crl: 0.206 to 1.099) and resistance training (RT) at 450 METs-min/week (SMD: 0.695, 95% Crl: 0.227 to 1.203) also showed significant benefits. Additionally, mind-body exercises, such as tai chi, qigong, or yoga, exhibited optimal effects at a dose of 390 METs-min/week (SMD: 0.672, 95% Crl: 0.259 to 1.087).ConclusionOur study sheds light on the intricate relationship between exercise interventions and health-related quality of life in cancer survivors, as elucidated through a systematic review and Bayesian network meta-analysis. The identified optimal exercise dose of 850 METs-min/week resulted in a significant improvement in health-related quality of life, underscoring the importance of regular exercise in cancer survivorship. MT emerged as the most effective modality, closely followed by RT, AE, and MBE.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=493328, identifier CRD42024493328.
Serum PD-1 regulation and PD-1 expression of CD4+Foxp3+ regulatory T cells in patients in thyroid eye disease associated with immunosuppression treatment
Authors: Sakai Atsushi , Tagami Mizuki , Misawa Norihiko , Haruna Yusuke , Tomita Mami , Honda Shigeru 
Published: December 2024

PurposeThyroid eye disease (TED) primarily occurs in hyperthyroid patients, sometimes resulting in poor visual prognosis. Although other autoimmune diseases have been reported to be associated with serum programmed cell death 1 (PD-1), the relationship with TED remains unknown. This study investigated the relationship between TED and immune checkpoint molecules.MethodsSerum immune checkpoint molecules were measured in TED and control patient blood samples. In TED patients, blood samples were compared before and 6 months after steroid pulse treatment. Cytometry analysis was additionally performed in TED and control patients to compare the expression of (PD-1) of T cells.ResultsSerum concentrations of PD-1 in TED and control patients were 163.49 ± 79.01 (pg/mL) and 123.58 ± 46.61 (pg/mL) (P = 0.03). Serum PD-L1 concentration in TED was 157.89 ± 55.34 (pg/mL), while 152.58 ± 22.70 (pg/mL) in control patients (P = 0.92). For flow cytometry analysis, the mean fluorescence intensity (MFI) ratio of PD-1 in Foxp3high CD45RA- of the CD4+ T cells and CD127-CD25high of the CD4+ T cells were higher in TED versus control patients (P = 0.04, P = 0.02). There was also a higher percentage of PD-1 expressions on CD4+ T cells and Foxp3high CD45- T cells in TED patients versus that for control patients (P &lt; 0.001, P = 0.003).ConclusionsPD-1 expression of CD4+Foxp3+ regulatory T cells appear to be associated with TED pathogenesis before and after treatment. Regulatory T cells expressed PD-1 have possibilities of clinical activity and autoimmune pathology of TED.
In vitro elimination of antimicrobials during ADVanced Organ Support hemodialysis
Authors: König Christina , Frey Otto , Himmelein Susanne , Mulack Lisa , Brinkmann Alexander , Perez Ruiz de Garibay Aritz , Bingold Tobias 
Published: December 2024

BackgroundAcute kidney injury (AKI) requiring continuous renal replacement therapy is common in critically ill patients. The ADVanced Organ Support (ADVOS) system is a novel hemodialysis machine that uses albumin enriched dialysate which allows the removal of protein-bound toxins and drugs. To date, data on antimicrobial removal under ADVOS has not yet been reported.MethodsAn in vitro study was conducted using whole porcine blood and continuous infusions of different antimicrobial agents to investigate the effect of ADVOS on drug exposure. Drugs with varying protein binding, molecular weights and renal clearances, anidulafungin, cefotaxime, daptomycin, fluconazole, ganciclovir, linezolid, meropenem and piperacillin were studied.ResultsAll studied drugs were removed during the in vitro ADVOS experiment. Clearance under ADVOS (CLADVOS) for low protein-bound drugs, such as cefotaxime, fluconazole, ganciclovir, linezolid, meropenem and piperacillin ranged from 2.74 to 3.4 L/h at a blood flow of 100 mL/min. With a doubling of flow rate CL for these drugs increased. Although efficiently removed, this effect was not seen for CLADVOS in high protein-bound substances such as daptomycin (1.36 L/h) and anidulafungin (0.84 L/h).ConclusionThe ADVOS system effectively removed protein-bound and unbound antimicrobials to a significant extent indicating that dose adjustments are required. Further, clinical studies are necessary to comprehensively assess the impact of ADVOS on antimicrobial drug removal. Until clinical data are available, therapeutic drug monitoring should guide antimicrobial dosing under ADVOS.
Comparative genetic mapping and a consensus interspecific genetic map reveal strong synteny and collinearity within the Citrus genus
Authors: Ollitrault Patrick , Hufnagel Barbara , Curk Franck , Perdereau Aude , Mournet Pierre , Miranda Maëva , Costantino Gilles , Froelicher Yann , Alves Mônica , Forner Giner Maria Angeles , Smith Malcolm W. , Aleza Pablo , Luro François , Wulff Nelson A. , Peña Leandro , Morillon Raphaël , Lemainque Arnaud 
Published: December 2024

IntroductionUseful germplasm for citrus breeding includes all sexually compatible species of the former genera Citrus, Clymenia, Eremocitrus, Fortunella, Microcitrus, Oxanthera, and Poncirus, now merged in the single Citrus genus. An improved knowledge on the synteny/collinearity between the genome of these different species, and on their recombination landscapes, is essential to optimize interspecific breeding schemes.MethodWe have performed a large comparative genetic mapping study including several main clades of the Citrus genus. It concerns five species (C. maxima, C. medica, C. reticulata, C. trifoliata and C. glauca), two horticultural groups resulting from interspecific admixture (clementine and lemon) and two recent interspecific hybrids (C. australis x C. australasica and C. maxima x C. reticulata). The nine individual genetic maps were established from GBS data of 1,216 hybrids.Results and discussionThe number of SNPs mapped for each parent varies from 760 for C. medica to 4,436 for the C. maxima x C. reticulata hybrid, with an average of 2,162.3 markers by map. Their comparison with C. clementina v1.0 assembly and inter-map comparisons revealed a high synteny and collinearity between the nine genetic maps. Non-Mendelian segregation was frequent and specific for each parental combination. The recombination landscape was similar for the nine mapped parents, and large genomic regions with very low recombination were identified. A consensus genetic map was successfully established. It encompasses 10,756 loci, including 7,915 gene-based markers and 2,841 non-genic SNPs. The anchoring of the consensus map on 15 published citrus chromosome-scale genome assemblies revealed a high synteny and collinearity for the most recent assemblies, whereas discrepancies were observed for some older ones. Large structural variations do not seem to have played a major role in the differentiation of the main species of the Citrus genus. The consensus genetic map is a useful tool to check the accuracy of genome assemblies, identify large structural variation and focus on analyzing potential relationships with phenotypic variations. It should also be a reference framework to integrate the positions of QTLs and useful genes identified in different analyses.
The mediating role of rumination in the relationship between insomnia and non-suicidal self-injury of college students
Authors: Wang Hanqing , Sun Hongli 
Published: December 2024

IntroductionNon-suicidal self-injury (NSSI) is a high-risk factor for suicide, which is widespread among college students and is closely associated with psychological issues. Insomnia tends to cause mental instability, and chronic insomnia can trigger severe mood swings, including anxiety, depression, and irritability. It can also lead to memory loss and metabolic disorders. College students are in a critical period of self-development, with significant vulnerability to insomnia and NSSI. This study investigated the influence of insomnia on NSSI among college students and examined the significance of rumination as a mediating factor.MethodsUsing random cluster sampling, we selected 667 college students from Jiangsu, China, and evaluated them using the Athens Insomnia Scale (AIS), Adolescent Self-Injury Scale (ASIS), and Ruminative Responses Scale (RRS). The significance of the mediating effect of rumination on the relationship between insomnia and NSSI among college students was tested using Bootstrap methods.ResultsThe fact that the students were only children was statistically significant for rumination scores (p &lt; 0.05). The results showed a significant positive correlation among insomnia, NSSI, and rumination (r = 0.198, 0.737, 0.243, respectively; p &lt; 0.001). Insomnia of college students affects NSSI directly and indirectly through rumination.ConclusionRumination fully mediated the relationship between insomnia and NSSI among college students, indicating an indirect influence of insomnia on NSSI. Total effect value is 0.192. Rumination plays a complete mediating role in the relationship between insomnia and NSSI among college students, with a mediating effect of 84.21%.
I-CONECT intervention effects on weekly time spent outside of home and social contacts among socially isolated older adults
Authors: Yu Kexin , Wu Chao-Yi , Silbert Lisa C. , Kaye Jeffrey A. , Dodge Hiroko H. 
Published: December 2024

BackgroundSocially isolated individuals tend to have less access to cognitively stimulating activities, which could adversely impact their cognitive health. The Internet-Based Conversational Engagement Clinical Trial (I-CONECT) intervention was designed to deliver online conversation sessions to socially isolated older old adults to prevent cognitive decline. The current study examined the intervention efficacy on participants’ weekly time spent out-of-home and their social interaction with family and friends.MethodsThe intervention group engaged in frequent conversations with trained interviewers via the Internet. Both intervention and control group participants received 10-min weekly phone check-in calls over 48 weeks, during which they were asked to self-report their time (in hours) spent out of home and whether they had contacted family or friends during this week (yes/no). Linear mixed-effect models for repeated measures were run for time spent out-of-home, and mixed-effect models with a logistic link for contact with family and friends. The intervention effect was modeled by including an interaction term of time (measured in weeks) and group assignments (intervention vs. control). We ran subgroup analyses for participants with normal cognition (NC) and mild cognitive impairment (MCI). All models controlled for age, sex, race, education, and the historical event of COVID-19.Results5,495 weekly records were included in the analysis. The main effect of time was statistically significant (p &lt; 0.001), suggesting participants spent more time out of home over time. Among the participants with NC, the intervention group had a steeper increase in their time spent out-of-home (p = 0.016) compared with the control group. Among the participants with MCI, the intervention group had an increased likelihood of contacting friends over time (p = 0.001) than the control group. The intervention effect on contact with family was not significant for either the NC or MCI group.DiscussionThe I-CONECT intervention enhanced social activities among socially isolated older old participants, which could provide additional cognitive stimulation and prevent cognitive decline.
A study on anxiety and depression symptoms among menopausal women: a web based cross sectional survey
Authors: Kandasamy Geetha , Almaghaslah Dalia , Almanasef Mona 
Published: December 2024

BackgroundAn essential part of aging is menopause, which indicates the final phase of the female reproductive cycle. The objective of this research was to assess anxiety and depressive symptoms among menopausal women in Asir region, Saudi Arabia.MethodsThe cross-sectional survey was carried out in February to June 2024, using a random sampling procedure, study participants were selected. All menopausal women including &lt;50 and ≥60 years old, were included, and symptoms of depression and anxiety were collected using Patient Health Questionnaire-9 (PHQ-9) Generalized Anxiety Disorder-7 (GAD-7) respectively.ResultsOf the 396 menopausal women, the majority 170 (42.9%) were &lt;50 years old and 92 (23.2%) were between 50 and 54 years old. Two hundred eighty-one were married (71%) and 273 (68.9%) were literate. Most of them, 229 (57.8%) got married at &lt;18 years and 196 (49.5%) have a parity of 3–5 and 189 (47.7%) women attained menopause at &lt;50 years old. In terms of menopausal symptoms, 268 (67.7%) women experienced hot flushes; 252 (63.6%) had night sweats and were more irritable 256 (64.6%) followed by 244 (61.6%) had decreased sexual desire. In general, 258 (65.2%) and 206 (52.02%) menopausal women reported having depression and anxiety symptoms, respectively. Married (OR = 0.317; 95% CI = 0.182–0.551, p = 0.000) and literate (OR = 0.518; 95% CI = 0.309–0.868, p = 0.013) are less likely to be in depression compared to widowed/separated individuals. Literates (OR = 0.271; 95% CI = 0.165–0.443, p = 0.000), are less likely to have anxiety compared to illiterates.ConclusionThe study found that a significant percentage of menopausal women had depression and anxiety symptoms. These results emphasize the significance of screening and assessing women experiencing anxiety and depression symptoms throughout the menopausal transition. To alleviate menopausal symptoms, it is also suggested to conduct activities to educate menopausal women, such as a health awareness program in shopping centers and other public places, etc.
Lung cancer risk and its potential association with PM2.5 in Bagmati province, Nepal—A spatiotemporal study from 2012 to 2021
Authors: Neupane Basanta Kumar , Acharya Bipin Kumar , Cao Chunxiang , Xu Min , Taylor Pornpimol Kodsup , Wang Shaohua , Yang Yujie 
Published: December 2024

BackgroundDespite examining the role of an association between particulate matter and lung cancer in low-income countries, studies on the association between long-term exposure to particulate matter and lung cancer risk are still contradictory. This study investigates the spatiotemporal distribution patterns of lung cancer incidence and potential association with particulate matter (PM2.5) in Bagmati province, Nepal.MethodsWe performed a spatiotemporal study to analyze the LC – PM2.5 association, using LC and annual mean PM2.5 concentration data from 2012 to 2021. The study assessed the global spatial autocorrelation test using global Moran's I, applied hotspot analysis. A bivariate statistical analysis was performed to evaluate the association, we also applied the geographically weighted regression model (GWR) to look for possible relationships.ResultsThe annual mean crude incidence rate (CIR) and standardized incidence rate (SIR) were 5.16, and 6.09 respectively. The study reveals an increasing trend with notable municipal-level spatial variations. Bhaktapur municipality exhibits the highest CIR (243.88), followed by Panchkhal and Sunapati. Males consistently exhibit higher rates, particularly in middle-aged and older adult populations. Bhaktapur displayed the highest CIR in males (171.9) but very low in females (72). The spatial analysis identified concentration trends and hotspots developed in the Bhaktapur, Panchkhal, and Sunapati municipalities. The SIR showed fluctuating patterns of continuous rise until 2019, decrease in 2020, and rise again thereafter. Similar fluctuation association patterns were observed with PM2.5, the r-squared value consistently fluctuated during the study period.ConclusionIn this study, we found an association between PM2.5 exposure and lung cancer incidence. The findings underscore the need for targeted public health interventions, highlighting the role of PM2.5. Future research is suggested to explore the relationship between lung cancer distribution and various environmental risk factors for effective control and prevention. Addressing air pollution could potentially reduce future lung cancer risk.
High consciousness—low application: sustainable development and sustainable healthcare in undergraduate physiotherapy education in Sweden
Authors: Swärdh Emma , Brodin Nina , Palstam Annie , Pettersson Anna 
Published: December 2024

BackgroundSwedish undergraduate physiotherapy education lacks comprehensive integration of sustainable development in curricula. Factors related to educators’ perspectives in preparing future physiotherapists for sustainable development and sustainable healthcare may shed light on this shortcoming.AimThis study aims to describe Swedish physiotherapy educators’ (i) consciousness of sustainable development and its inclusion in teaching and learning activities, (ii) ecological worldviews, (iii) attitudes toward sustainability and climate change in physiotherapy, (iv) perceptions of education for sustainable development and sustainable healthcare and (v) examine the relationship between ecological worldview and attitudes toward sustainability and climate change in physiotherapy.MethodA cross-sectional, descriptive study was performed using a digital survey to collect data from educators within undergraduate physiotherapy education at five higher education institutions in Sweden. Data was collected using the Sustainability Consciousness Questionnaire, the New Ecological Paradigm Scale, the Sustainability Attitudes in Nursing Survey 2, and questions related to knowledge, attitudes, and self-efficacy for education for sustainable development and sustainable healthcare.ResultMost, but not all, of the 72 educators, (76%) were aware of Agenda 2030 and the sustainable development goals, and 17% included perspectives related to sustainable development in teaching and learning activities. The educators endorsed an eco-centered ecological worldview and had largely positive overall attitudes toward sustainability and climate change within physiotherapy. However, almost one-third (28%) disagreed that issues about climate change should be included in the physiotherapy curriculum. Most agreed about having content knowledge on climate and health (81%), while a smaller part agreed on having pedagogical content knowledge regarding how to inspire or educate for sustainable development (17–28%). There was also a wide variation in perceived self-efficacy in education for sustainable development and sustainable healthcare.ConclusionDespite the endorsement of eco-centered ecological worldviews and a rather high consciousness of sustainable development as an overall concept, there remains a disconnect to educational attitudes and actions among Swedish physiotherapy educators. This points to the need to explore the narrative of sustainable development within physiotherapy in Sweden rooted in broader concept understanding, ethics, and reflective practice for sustainable development. A key priority should be to offer new perspectives on professional identity and continuing professional development within sustainable development.