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Evaluating the expression pattern of ATXN1 and CDC42EP1 genes and related long noncoding RNAs in oral squamous cell carcinoma

Mol Biol Rep. 2024 Jul 13;51(1):796. doi: 10.1007/s11033-024-09719-8.

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a significant health issue worldwide, and the expression of long non-coding RNAs (lncRNAs) are altered in these malignancies. The present study evaluated the expression level of ATXN1 CDC42EP1 genes and the lncRNAs related to these genes (lnc-ATXN1L, lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1) in paraffin blocks of oral and pharyngeal squamous cell carcinoma (SCC) samples from patients referred to Amir Alam Hospital in Tehran, Iran.

METHODS AND RESULTS: This cross-sectional study was conducted on 76 paraffin blocks of oral and pharyngeal squamous cell carcinoma (SCC) samples from patients referred to Amir Alam Hospital in Tehran. The expression levels of ATXN1, CDC42EP1, lnc-ATXN1L, lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 were measured in all samples using a qPCR Master Mix kit. Real-time PCR was used to perform the reactions, and GAPDH was considered the housekeeping gene. Statistical analyses were conducted utilizing the Statistical Package for the Social Sciences (SPSS) version 22.0. The expression of lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 significantly differed between the two groups. All of them were downregulated (p < 0.05), and no significant difference was observed between the SCC samples and the adjacent tissue in other genes (p > 0.05). The expression of genes was not related to age, sex, size, and tumor location (p > 0.05).

CONCLUSIONS: Dysexpression of lnc-ATXN1, lnc-ATXN10, and lnc-CDC42EP1 can be used for diagnosing OSCC.

PMID:39002033 | DOI:10.1007/s11033-024-09719-8

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Genome-wide association study on meningioma risk in Japan: a multicenter prospective study

J Neurooncol. 2024 Jul 13. doi: 10.1007/s11060-024-04727-x. Online ahead of print.

ABSTRACT

PURPOSE: Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility.

METHODS: In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan.

RESULTS: The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 – 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population.

CONCLUSION: This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

PMID:39002029 | DOI:10.1007/s11060-024-04727-x

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Stereotactic radiosurgery versus combined stereotactic radiosurgery and bevacizumab for recurrent glioblastoma; a systematic review and meta-analysis of survival

Neurosurg Rev. 2024 Jul 13;47(1):323. doi: 10.1007/s10143-024-02585-9.

ABSTRACT

Recurrent glioblastoma (rGBM) is a brain tumor that is resistant to standard treatments. Although stereotactic radiosurgery (SRS) is a non-invasive radiation technique, it cannot fully prevent tumor recurrence and progression. Bevacizumab blocks tumor blood supply and has been approved for rGBM. However, the best way to combine SRS and bevacizumab is still unclear. We did a systematic review and meta-analysis of studies comparing SRS alone and SRS plus bevacizumab for rGBM. We searched three databases for articles published until June 2023. All statistical analysis was performed by STATA v.17. Our meta-analysis included 20 studies with 926 patients. We found that the combination therapy had a significantly lower rate of overall survival (OS) than SRS alone at 6-month 0.77[95%CI:0.74-0.85] for SRS alone and (100%) for SRS plus bevacizumab. At 1-year OS, 0.39 [95%CI: 0.32-0.47] for SRS alone and 0.61 [95%CI:0.44-0.77] for SRS plus bevacizumab (P-value:0.02). However, this advantage was not seen in the long term (18 months and two years). Additionally, the combination therapy had lower chances of progression-free survival (PFS) than SRS alone at the 6-month and 1-year time points, but the differences were insignificant. Our study indicates that incorporating bevacizumab with SRS may lead to a short-term increase in OS for rGBM patients but not long-term. Additionally, the PFS rate did not show significant improvement in the group receiving combination therapy. Further clinical trials are necessary to validate the enhanced overall survival with combination therapy for rGBM.

PMID:39002028 | DOI:10.1007/s10143-024-02585-9

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Death anxiety among caregivers of patients with advanced cancer: a cross-sectional survey

Support Care Cancer. 2024 Jul 13;32(8):510. doi: 10.1007/s00520-024-08707-9.

ABSTRACT

PURPOSE: This study aimed to investigate death anxiety (DA) in caregivers of patients with advanced cancer and identify associated factors in the context of Chinese culture.

METHODS: Caregivers (N = 588) of advanced cancer patients in a tertiary cancer hospital completed anonymous questionnaire surveys. Measures included the Chinese version of the Templer Death Anxiety Scale (C-T-DAS), the Quality-of-Life Scale, the State-Trait Anxiety Scale, and the Social Support Rating Scale. Data were analyzed in SPSS (IBM Corp, Armonk, NY, USA) using descriptive statistics, Pearson’s correlation test, and linear regression.

RESULTS: Respondents returned 588 (93.03%) of the 632 questionnaires. The total C-T-DAS score was 7.92 ± 2.68 points. The top-scoring dimension was “Stress and pain” (3.19 ± 1.29 points), followed by “Emotion” (2.28 ± 1.31 points) and “Cognition” (1.40 ± 0.94 points). In contrast, the lowest-scoring dimension was “Time” (1.06 ± 0.77 points). Factors associated with DA (R2 = 0.274, F = 13.348, p < 0.001) included quality of life (QoL), trait anxious personality, social support, caregiver length of care, caregiver gender, and patients’ level of activities of daily living (ADL).

CONCLUSIONS: Our results demonstrated high levels of DA in caregivers of patients with advanced cancer. Generally, female caregivers and those with low social support had high DA. Caregivers caring for patients with low ADL levels or with a low QoL and trait anxious personality reported high DA. Certain associated factors help to reduce caregivers DA. Social interventions are recommended to improve the end-of-life transition and trait anxious personality as well as quality of life for caregivers.

PMID:39002026 | DOI:10.1007/s00520-024-08707-9

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Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis

Eur J Clin Pharmacol. 2024 Jul 13. doi: 10.1007/s00228-024-03730-5. Online ahead of print.

ABSTRACT

OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism.

METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes.

RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, – 3.72 to – 0.15) and etelcalcetide (- 7.80, – 11.80 to – 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, – 9.73 to – 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, – 6.72 to – 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, – 8.91 to – 2.37), calcitriol (- 9.36, – 14.81 to – 3.92), and paricalcitol (- 9.30, – 13.78 to – 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions.

CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.

PMID:39002024 | DOI:10.1007/s00228-024-03730-5

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Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis

Dokl Biochem Biophys. 2024 Jul 13. doi: 10.1134/S1607672924700996. Online ahead of print.

ABSTRACT

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

MATERIALS AND METHODS: : The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices).

RESULTS AND DISCUSSION: : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(-) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(-) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(-) patients.

CONCLUSIONS: . In patients with ACPA(-) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less “bright” course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

PMID:39002008 | DOI:10.1134/S1607672924700996

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Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis

Dokl Biochem Biophys. 2024 Jul 13. doi: 10.1134/S1607672924700960. Online ahead of print.

ABSTRACT

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.

MATERIALS AND METHODS: . The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL).

RESULTS AND DISCUSSION: . Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(-) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691-0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(-) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(-) RA group.

CONCLUSIONS: . We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(-) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more “erosive” subtype of the disease than ACPA(+) anti-CarP(-) patients. In ACPA(-) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(-) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

PMID:39002007 | DOI:10.1134/S1607672924700960

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Oral bacterial genic expression detection in aneurysm wall of a French population sample – preliminary monocentric study

Neurosurg Rev. 2024 Jul 13;47(1):325. doi: 10.1007/s10143-024-02548-0.

ABSTRACT

INTRODUCTION: The etiology of brain aneurysms remains poorly understood. Finnish research suggests that oral bacteria might contribute to the development and rupture of brain aneurysms. Previous studies by our team have not confirmed these findings, likely due to methodological differences. We aimed to replicate the Finnish study with a French population, using the same primers and comparing the results to internal controls.

METHODS: We used RT-qPCR to retrospectively analyze the expression of oral bacterial genes in eight patients. During surgical procedures, four tissue types were consistently sampled from each patient: the aneurysmal wall, the superficial temporal artery (STA), the middle meningeal artery (MMA), and the dura mater (DM). Results were expressed as fold differences employing the 2-∆∆Ct method, and statistical analyses were performed accordingly.

RESULTS: Our cohort included eight patients, evenly split into ruptured and unruptured groups. The sex distribution was balanced (4 females, 4 males). We observed DNA expression from oral bacteria in all sampled tissues; however, there were no significant differences between the ruptured and unruptured groups.

CONCLUSION: We detected oral bacterial gene expression in the aneurysmal wall, STA, MMA, and DM in a sample of French patients. Although limited by the small sample size, our results suggest a potential role for bacterial involvement in vascular invasiveness related to bacteremia. These findings do not definitively link oral bacteria to the pathogenesis of aneurysm development and rupture.

PMID:39001998 | DOI:10.1007/s10143-024-02548-0

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Entering the Classroom: Do Newcomers Experience More Peer Victimization than Their Established Peers?

Res Child Adolesc Psychopathol. 2024 Jul 13. doi: 10.1007/s10802-024-01225-6. Online ahead of print.

ABSTRACT

Students changing classrooms or schools may face challenges from entering a new peer context without friends and standing out from the crowd as newcomers. Two studies examined whether newcomer status predicts peer victimization at school, exploring several potential moderating factors (e.g., social anxiety, immigrant background and having good friends in the classroom) (Study 1: n = 6,199; Mage=12.53) and whether being victimized as a newcomer varied based on the different reasons for mobility (e.g., parental dissolution, residential move, previous victimization, changing into a more suitable school) (Study 2: n = 58,738). In both studies, newcomers reported higher peer victimization compared to established students. Having good friends in the classroom was found as a protective factor in Study 1, being the only statistically significant moderator. All reasons for mobility, except changing into a more suitable school, predicted slightly higher peer victimization in Study 2, with the highest risk for those changing schools due to previous peer victimization experiences.

PMID:39001989 | DOI:10.1007/s10802-024-01225-6

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Association of histidine-rich glycoprotein C633T single nucleotide polymorphism and recurrent miscarriage in Iranian women

Mol Biol Rep. 2024 Jul 13;51(1):793. doi: 10.1007/s11033-024-09758-1.

ABSTRACT

BACKGROUND: Recurrent miscarriage (RM) is defined as the occurrence of at least two or three subsequent miscarriages within the 20th -24th weeks of pregnancy. The primary objective of this study was to investigate whether histidine-rich glycoprotein C633T single nucleotide polymorphism (HRG C633T SNP) statistically correlates with the occurrence of RM among Iranian women.

METHODS AND RESULTS: Blood samples from 200 women were taken at the outset of the study. Then, the blood samples of 100 women who had a record of RM (case group) were compared with the other 100 women’s blood samples who had no record of RM (control group). Following DNA extraction, the polymorphism of histidine-rich glycoprotein C633T (HRG C633T) for every case was specified and all women were genotyped by the amplification-refractory mutation system (ARMS) method. The results of the study revealed that there was a statistically significant difference between T/T genotype (OR = 3.5, CI (1.39-8.77), p = 0.007), and C/T genotype (OR = 1.83, CI (0.99-3.37), p = 0.05) in the case and control groups. Also, a statistically significant association was observed in T allelic frequency in the RM participants compared to the control group (OR = 2.01, CI (1.31-3.09), p = 0.01).

CONCLUSIONS: The present study determined that there was a statistically significant relationship between HRG C633T SNP and increased RM regarding allelic and genotypical aspects. Moreover, it became apparent that women with homozygous T/T genotype were more susceptible to the risk of RM.

PMID:39001985 | DOI:10.1007/s11033-024-09758-1