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Pathology, Research and Practice Aug 2023Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing's...
Non-functioning pituitary adenomas (NFPAs) are a group of pituitary tumors lacking manifestations linked to high hormone production, such as acromegaly and Cushing's syndrome. NFPA carcinogenesis depends on several molecular players. Long non-coding RNAs (lncRNAs) are a class of molecular players whose role in tumorigenesis has just recently been recognized. In the current study, we appraised expressions of 5 lncRNAs, namely FGD5-AS1, ATP6V0E2-AS1, ARHGAP5-AS1, WWC2-AS2 and EPB41L4A-AS1 in NFPAs versus their corresponding non-tumoral samples. Expressions of ATP6V0E2-AS1, EPB41L4A-AS1, FGD5-AS1 and WWC2-AS2 were significantly increased in NFPA samples compared with adjacent non-tumoral samples (P values = 0.037, 0.007, 0.008 and 0.03, respectively). However, expression of ARHGAP5-AS1 was not different between NFPA samples and controls (P value = 0.62). EPB41L4A-AS1 and FGD5-AS1 could discriminate between NFPA samples and adjacent non-tumoral samples (P values = 0.03 and 0.04, respectively). However, the AUC values were not appropriate. There was a significant positive association between age of NFPA patients and invasiveness of NFPA (χ = 4.24, P value = 0.039). Moreover, there was a significant positive association between diseases duration and CSF leak (χ = 11.4, p value = 0.023). Finally, there was a significant positive association between tumor size and Knosp classification (χ = 11.5, p value = 0.02) and invasiveness of NFPA (χ = 6.12, p value = 0.04). The current study provides information about dysregulation of lncRNAs in NFPAs and warrants additional studies in this field.
Topics: Humans; Pituitary Neoplasms; RNA, Long Noncoding; Adenoma
PubMed: 37418994
DOI: 10.1016/j.prp.2023.154668 -
Statistical Applications in Genetics... Jan 2023Permutation tests are widely used for statistical hypothesis testing when the sampling distribution of the test statistic under the null hypothesis is analytically...
Permutation tests are widely used for statistical hypothesis testing when the sampling distribution of the test statistic under the null hypothesis is analytically intractable or unreliable due to finite sample sizes. One critical challenge in the application of permutation tests in genomic studies is that an enormous number of permutations are often needed to obtain reliable estimates of very small -values, leading to intensive computational effort. To address this issue, we develop algorithms for the accurate and efficient estimation of small -values in permutation tests for paired and independent two-group genomic data, and our approaches leverage a novel framework for parameterizing the permutation sample spaces of those two types of data respectively using the Bernoulli and conditional Bernoulli distributions, combined with the cross-entropy method. The performance of our proposed algorithms is demonstrated through the application to two simulated datasets and two real-world gene expression datasets generated by microarray and RNA-Seq technologies and comparisons to existing methods such as crude permutations and SAMC, and the results show that our approaches can achieve orders of magnitude of computational efficiency gains in estimating small -values. Our approaches offer promising solutions for the improvement of computational efficiencies of existing permutation test procedures and the development of new testing methods using permutations in genomic data analysis.
Topics: Entropy; Genomics; Research Design; Algorithms; Data Analysis
PubMed: 37622330
DOI: 10.1515/sagmb-2021-0067 -
Journal of Thoracic Oncology : Official... Feb 2024Traditionally, relapsed SCLC has been classified as "sensitive" or "refractory" on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy...
INTRODUCTION
Traditionally, relapsed SCLC has been classified as "sensitive" or "refractory" on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy and disease progression. Nevertheless, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain.
METHODS
We conducted a retrospective multicenter study on patients with extensive-stage SCLC who underwent second-line therapy after platinum-doublet chemotherapy with or without immune checkpoint inhibitor (ICI) resistance before (pre-ICI cohort) and after (post-ICI cohort) approval of combination immunotherapy. We selected the optimal platinum-free interval cutoff value with the lowest two-sided p value in the multivariable Cox regression model for second-line overall survival. The internal validity of the chosen cutoff value was assessed using twofold cross-validation.
RESULTS
There were 235 and 98 patients in the pre-ICI and post-ICI cohorts, respectively. In the pre-ICI cohort, the optimal cutoff was 59 days (p = 0.0001); the hazard ratio calculated using twofold cross-validation was 1.31 (95% confidence interval: 0.95-1.82]). In the post-ICI cohort, although the 60- and 90-day cutoff values could predict prognosis (60 d; p = 0.002, 90 d; p = 0.005), the optimal cutoff value was 75 days (p = 0.0002), which resulted in a median second-line overall survival of 15.9 and 5.0 months for patients with sensitive and refractory relapse, respectively (hazard ratio = 2.77, 95% confidence interval: 1.56-4.93).
CONCLUSIONS
We clarified the previously ambiguous cutoff values for classifying relapsed SCLC and revealed that the 75-day cutoff most accurately predicts subsequent prognosis than the traditional cutoffs in the post-ICI era.
Topics: Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Small Cell Lung Carcinoma; Prognosis; Immunotherapy; Retrospective Studies
PubMed: 37748690
DOI: 10.1016/j.jtho.2023.09.1446 -
Frontiers in Endocrinology 2024Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention...
INTRODUCTION
Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM.
METHODS
The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome.
RESULTS
The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method.
CONCLUSION
We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.
Topics: Child; Pregnancy; Humans; Female; Diabetes, Gestational; Sex Hormone-Binding Globulin; Genome-Wide Association Study; Mendelian Randomization Analysis; Polycystic Ovary Syndrome; Lipoproteins, HDL; Testosterone
PubMed: 38375192
DOI: 10.3389/fendo.2024.1337562 -
Nutrition Journal Oct 2023A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about...
BACKGROUND
A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children.
METHODS
Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight.
RESULTS
Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity.
CONCLUSIONS
This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.
Topics: Adult; Humans; Child; Overweight; Chronotype; Cross-Sectional Studies; Jet Lag Syndrome; Feeding Behavior; Sleep; Exercise; Surveys and Questionnaires; Schools
PubMed: 37798740
DOI: 10.1186/s12937-023-00875-4 -
Medicine Nov 2023To examine the effect of low-frequency acupoint electrical stimulation (LFES) on the surface electromyographic (sEMG) signals of the thumb-to-finger movement muscles in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To examine the effect of low-frequency acupoint electrical stimulation (LFES) on the surface electromyographic (sEMG) signals of the thumb-to-finger movement muscles in stroke patients, and to evaluate the clinical efficacy of LFES on hand function recovery after stroke.
METHODS
Sixty patients who met the inclusion criteria were randomly assigned to a LFES group or an electroacupuncture (EA) group, with 30 patients in each group. Both groups received conventional treatment, and the EA group was treated with acupoints from the book of Acupuncture and Moxibustion, while the LFES group was treated with acupoints from a previous study. The sEMG characteristic values (maximum value and RMS), Chinese Stroke Clinical Neurological Deficit Scale (CSS), Brunnstrom Motor Function Evaluation, Modified Ashworth Scale (MAS), Lindmark Hand Function Score and Lovett Muscle Strength Classification were measured before and after treatment.
RESULTS
After treatment, both groups showed improvement in sEMG characteristic values, Brunnstrom motor function score, Lindmark hand function score, and Lovett muscle strength classification compared with before treatment, and the improvement in the LFES group was significantly better than that in the EA group (P < .05). The CSS score and MAS classification of both groups decreased compared with before treatment, and the decrease in the LFES group was significantly better than that in the EA group (P < .05). The total effective rate of the LFES group was 92.86%, and that of the EA group was 79.31%. The difference between the 2 groups was statistically significant (P < .05).
CONCLUSION
Both LFES and EA were effective in restoring thumb-to-finger movement function after stroke, as evidenced by the increased maximum value and root mean square values of the first dorsal interosseous muscle and the extensor pollicis brevis muscle, the decreased CSS score, the increased Brunnstrom motor function score, the decreased MAS classification, the increased Lindmark hand function score, and the increased Lovett muscle strength classification. However, LFES showed more obvious improvement and better efficacy than EA, which is worthy of clinical promotion.
Topics: Humans; Acupuncture Points; Thumb; Electroacupuncture; Stroke; Electric Stimulation; Treatment Outcome
PubMed: 38013325
DOI: 10.1097/MD.0000000000035755 -
Urologia Aug 2023To investigate the predictive value of systemic immune-inflammation index (SII) in recurrence of urethral stricture in patients undergoing internal urethrotomy.
PURPOSE
To investigate the predictive value of systemic immune-inflammation index (SII) in recurrence of urethral stricture in patients undergoing internal urethrotomy.
METHODS
In this two-center, retrospective study, 703 patients who had internal urethrotomy for urethral stricture were included. Demographic, clinical, and laboratory characteristics and operative data were obtained. Two groups were formed from the patients as non-recurrent urethral stricture ( = 490) and recurrent urethral stricture ( = 213).
RESULTS
There was no significant difference in the mean age between the patients with and without recurrence. There was a significant difference in the mean SII values and albumin levels between the recurrence and non-recurrence groups ( = 0.001 and = 0.006, respectively). Using a cut-off value of 252 for the SII; the sensitivity was 59.62%, the specificity was 70.41%, the positive predictive value was 46.69%, the negative predictive value was 80.05% and the accuracy was 67.14%, respectively. Statistically significant correlation was found between the presence of recurrence and the established cut-off value of the SII ( = 0.001 and < 0.01, respectively). The risk of recurrence was stated that 3.514 times higher in patients with a SII value of ⩾252.
CONCLUSION
Using the SII the inflammatory state of the urethral tissue can be evaluated. Thus the risk of recurrence after internal urethrotomy operation can be predicted. Open urethroplasty technique instead of DVIU in patients with high SII values may increase the surgical success rates.
Topics: Humans; Male; Urethral Stricture; Retrospective Studies; Treatment Outcome; Urethra; Urologic Surgical Procedures, Male
PubMed: 36321780
DOI: 10.1177/03915603221132033 -
Korean Journal of Anesthesiology Jun 2024The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance... (Review)
Review
The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance testing. However, statistical significance does not always align with meaningful clinical effects; thus, assigning clinical relevance to statistical significance is unreasonable. A statistical result incorporating a clinically meaningful difference is a better approach to present statistical significance. Thus, the minimal clinically important difference (MCID), which requires integrating minimum clinically relevant changes from the early stages of research design, has been introduced. As a follow-up to the previous statistical round article on P values, confidence intervals, and effect sizes, in this article, we present hands-on examples of MCID and various effect sizes and discuss the terms statistical significance and clinical relevance, including cautions regarding their use.
Topics: Humans; Minimal Clinically Important Difference; Probability; Research Design; Clinical Trials as Topic; Data Interpretation, Statistical; Confidence Intervals
PubMed: 38835136
DOI: 10.4097/kja.23630 -
Acta Neurologica Belgica Oct 2023NF-κB partakes in the pathophysiology of neurologic conditions. We quantified levels of NF-κB-associated genes in 119 patients with migraine versus healthy controls.
PURPOSE
NF-κB partakes in the pathophysiology of neurologic conditions. We quantified levels of NF-κB-associated genes in 119 patients with migraine versus healthy controls.
METHODS
We measured levels of NF-κB-associated genes in 42 patients with migraine compared with age- and sex-matched controls.
RESULTS
Comparison between patients without aura and controls revealed down-regulation of PACER [expression ratio (95% CI) 0.15 (0.06-0.36), P value < 0.0001]. Similar results were detected when comparing expression of PACER in patients with aura and controls [expression ratio (95% CI) 0.05 (0.02-0.12), P value < 0.0001]. Both DILC and CEBPA were over-expressed in patients with aura [expression ratio (95% CI) 4.9 (2.96-7.83), P value < 0.0001 and expression ratio (95% CI) 3.65 (2.39-5.24), P value < 0.0001, respectively] and in patients without aura compared with controls [expression ratio (95% CI) 3.6 (2.21-5.69), P value < 0.0001 and expression ratio (95% CI) 4.5 (2.53-7.11), P value < 0.0001, respectively]. ADINR was over-expressed in patients with aura [expression ratio (95% CI) 4.98 (3.09-8.33), P value < 0.0001] as well as patients without aura compared with controls [expression ratio (95% CI) 13.15 (7.41-23.58), P value < 0.0001]. Notably, ADINR levels were lower in patients with aura compared with patients without aura. When comparing ATG5 levels in patients with aura and controls, significant up-regulation was detected [expression ratio (95% CI) 4.4 (3.01-6.32), P value < 0.0001]. This pattern was also detected in patients without aura compared with controls [expression ratio (95% CI) 3.5 (2.28-5.35), P < 0.0001]. Finally, expression of DICER1-AS1 was elevated in patients with aura compared with patients without aura [expression ratio (95% CI) 2.47 (1.14-5.85), P = 0.03]. This lncRNA was under-expressed in patients without aura compared with controls [expression ratio (95% CI) 0.4 (0.21-1.31), P = 0.03]. CEBPA, ATG5 and ADINR had the best AUC values for distinguishing patients with aura from controls (AUC values = 0.91, 0.85 and 0.83, respectively). The AUC values for separation between patients without aura and controls were 0.90, 0.86 and 0.75 for CEBPA, ATG5 and ADINR, respectively.
CONCLUSION
Taken together, several genes in the NF-κB pathway has been revealed to be dysregulated in migraineurs and expression of these genes can be used as markers for this neurological condition.
Topics: Humans; NF-kappa B; RNA, Long Noncoding; Migraine Disorders; Epilepsy; Migraine with Aura; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 36066813
DOI: 10.1007/s13760-022-02071-3 -
Iranian Journal of Otorhinolaryngology Sep 2023Considering the inconsistent results regarding the association between the severity and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease...
INTRODUCTION
Considering the inconsistent results regarding the association between the severity and duration of olfactory dysfunction (OD), and the viral load in coronavirus disease 2019 (COVID-19) patients, we aimed to conduct this study.
MATERIALS AND METHODS
This is a prospective cohort study in which COVID-19 patients were evaluated for the initial cycle threshold value (Ct values) measured by the nasopharyngeal samples along with olfactory function measured by the University of Pennsylvania Smell Identification Test (UPSIT) within 2 months of COVID-19 onset.
RESULTS
Among 309 COVID-19 patients who were included in this study, 108 (34.9%), 112 (36.2%) and 89 (28.8%) were normosmic, hyposmic, and anosmic, respectively based on the UPSIT. The severity of COVID-19 and the rate of hospitalization were higher in anosmic patients (p<0.0001, and p<0.0001, respectively). Moreover, significant associations between the initial Ct value and the severity of OD at admission and follow-ups were detected (p<0.0001 and p<0.0001, respectively). Anosmic patients had higher Ct values in comparison with hyposmic (approx. 3-fold) and normosmic (approx. 12-fold) patients. The recovery rate after one- and two-month follow-ups was 47% and 84%, respectively. At the follow-ups, OD-recovered patients significantly had lower Ct values (mean Ct value: 27.79 ± 2 and 28.21 ± 2.08) in comparison with those who have not recovered yet (mean Ct value: 30.19 ± 3.36, and 33.6 ± 3.37) (p<0.0001, and p<0.0001, respectively).
CONCLUSIONS
Ct value seems to be a significant factor not only in predicting OD severity in COVID-19 patients but also in the OD recovery duration. This finding may be helpful to investigate the underlying mechanisms of OD in COVID-19 patients.
PubMed: 38090619
DOI: 10.22038/IJORL.2023.71462.3429