Tag: statistics

BMC Cancer. 2022 Sep 17;22(1):990. doi: 10.1186/s12885-022-10014-7.

ABSTRACT

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC).

METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis.

RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa.

CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

PMID:36115941 | DOI:10.1186/s12885-022-10014-7

Mod Pathol. 2022 Sep 17. doi: 10.1038/s41379-022-01145-0. Online ahead of print.

ABSTRACT

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semi-quantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OS/PFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naïve and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OS/PFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis non-epithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p < 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies.

PMID:36115922 | DOI:10.1038/s41379-022-01145-0

Health Econ Rev. 2022 Sep 17;12(1):47. doi: 10.1186/s13561-022-00395-7.

ABSTRACT

BACKGROUND: Maternal and neonatal mortality is high in South Asia. Recent studies have identified factors such as adolescent female fertility, healthcare spending is reducing maternal and neonatal mortality. The objective of this study is to examine the effect of adolescent female fertility and healthcare spending on maternal and neonatal mortality in South Asian countries.

METHODS: A retrospective panel study design was used, a total of 8 South Asian countries (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) data from World development indicator 1990-2020 considered for analysis. Descriptive statistical method was used for summary. The effect of adolescent female fertility and healthcare spending on maternal and neonatal mortality were analysed using fixed and random effect regression with multiple imputation.

FINDINGS: Adolescent female fertility, maternal, and neonatal mortality is very high in the aforementioned countries, and considerably varies among countries. A significant relationship between the maternal mortality and healthcare spending, neonatal mortality and adolescent female fertility was observed. We found neonatal and maternal mortality are more likely to decrease depends on healthcare spending. Healthcare spending has a significantly negative effect on neonatal mortality (- 0.182, 95% CI: [- 0.295 to -.069]; P-value < 0.01) and maternal mortality (- 0.169, 95% CI: [- 0.243 to – 0.028]; P-value < 0.05). A change in 1 % increases in healthcare spending should decrease by 0.182 neonatal mortality per 1000 live births and maternal mortality by 0.169 per 100,000 live births.

CONCLUSIONS: In south Asian countries, increasing healthcare spending and decreasing adolescent female fertility may contribute to reduce maternal and neonatal mortality. In addition, number of service providers such as physicians supplied contributed to the decline of neonatal mortality. These findings have important implications for future improvement of healthcare spending in maternal and neonatal health programs.

PMID:36115901 | DOI:10.1186/s13561-022-00395-7

Neuropsychol Rev. 2022 Sep 17. doi: 10.1007/s11065-022-09562-3. Online ahead of print.

ABSTRACT

Migraine is a poorly understood neurological disorder and a leading cause of disability in young adults, particularly women. Migraines are characterized by recurring episodes of severe pulsating unilateral headache and usually visual symptoms. Currently there is some disagreement in the electrophysiological literature regarding the universality of all migraineurs exhibiting physiological visual impairments also during interictal periods (i.e., the symptom free period between migraines). Thus, this meta-analysis investigated the evidence for altered visual function as measured electrophysiologically via pattern-reversal visual evoked potential (VEP) amplitudes and habituation in adult migraineurs with or without visual aura and controls in the interictal period. Twenty-three studies were selected for random effects meta-analysis which demonstrated slightly diminished VEP amplitudes in the early fast conducting P100 component but not in N135, and substantially reduced habituation in the P100 and the N135 in migraineurs with and without visual aura symptoms compared to controls. No statistical differences were found between migraineurs with and without aura, possibly due to inadequate studies. Overall, insufficient published data and substantial heterogeneity between studies was observed for all latency components of pattern-reversal VEP, highlighting the need for further electrophysiological experimentation and more targeted temporal analysis of visual function, in episodic migraineurs.

PMID:36115887 | DOI:10.1007/s11065-022-09562-3

Sci Rep. 2022 Sep 17;12(1):15625. doi: 10.1038/s41598-022-19996-7.

ABSTRACT

Seasonal influenza epidemics circulate globally every year with varying levels of severity. One of the major drivers of this seasonal variation is thought to be the antigenic drift of influenza viruses, resulting from the accumulation of mutations in viral surface proteins. In this study, we aimed to investigate the association between the genetic drift of seasonal influenza viruses (A/H1N1, A/H3N2 and B) and the epidemiological severity of seasonal epidemics within a Canadian context. We obtained hemagglutinin protein sequences collected in Canada between the 2006/2007 and 2019/2020 flu seasons from GISAID and calculated Hamming distances in a sequence-based approach to estimating inter-seasonal antigenic differences. We also gathered epidemiological data on cases, hospitalizations and deaths from national surveillance systems and other official sources, as well as vaccine effectiveness estimates to address potential effect modification. These aggregate measures of disease severity were integrated into a single seasonal severity index. We performed linear regressions of our severity index with respect to the inter-seasonal antigenic distances, controlling for vaccine effectiveness. We did not find any evidence of a statistical relationship between antigenic distance and seasonal influenza severity in Canada. Future studies may need to account for additional factors, such as co-circulation of other respiratory pathogens, population imprinting, cohort effects and environmental parameters, which may drive seasonal influenza severity.

PMID:36115880 | DOI:10.1038/s41598-022-19996-7

Sleep Breath. 2022 Sep 17. doi: 10.1007/s11325-022-02707-x. Online ahead of print.

ABSTRACT

PURPOSE: Chronic intermittent hypoxia associated with obstructive sleep apnea (OSA) can affect neurons and glial cells, leading to cell stress and damage, and changes in brain-derived neurotrophic factor (BDNF) levels. This study investigated the relation between BDNF, OSA, and continuous positive airway pressure (CPAP) – the standard of care in patients with OSA.

METHODS: Five databases were searched for studies that evaluated BDNF serum and/or plasma levels in patients with OSA and controls or publications assessing the effect of CPAP treatment on BDNF levels. We used standardized mean difference (SMD) with its 95% confidence interval (CI) comparison between patients with OSA and controls.

RESULTS: Ten studies were included in our study assessing the relation between BDNF levels, OSA, and CPAP treatment. Five studies of BDNF levels in OSA compared to controls showed no significant difference (SMD = – 0.52, 95% CI [- 1.93; 0.89], p-value = 0.47). No statistically significant difference was found between CPAP treatment in patients with OSA and BDNF levels (SMD = – 0.78, 95% CI [- 1.77; 0.21], p-value = 0.12).

CONCLUSION: BDNF peripheral levels are not significantly altered in OSA or by its related treatment, preventing its use as a biomarker.

PMID:36115874 | DOI:10.1007/s11325-022-02707-x

Transl Psychiatry. 2022 Sep 17;12(1):392. doi: 10.1038/s41398-022-02153-z.

ABSTRACT

Structural differences in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus, and amygdala were reported in adults who experienced childhood trauma; however, it is unknown whether metabolic differences accompany these structural differences. This multimodal imaging study examined structural and metabolic correlates of childhood trauma in adults with major depressive disorder (MDD). Participants with MDD completed the Childhood Trauma Questionnaire (CTQ, n = 83, n = 54 female (65.1%), age: 30.4 ± 14.1) and simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI). Structure (volume, n = 80, and cortical thickness, n = 81) was quantified from MRI using Freesurfer. Metabolism (metabolic rate of glucose uptake) was quantified from dynamic ¹⁸F-fluorodeoxyglucose (FDG)-PET images (n = 70) using Patlak graphical analysis. A linear mixed model was utilized to examine the association between structural/metabolic variables and continuous childhood trauma measures while controlling for confounding factors. Bonferroni correction was applied. Amygdala volumes were significantly inversely correlated with continuous CTQ scores. Specifically, volumes were lower by 7.44 mm³ (95% confidence interval [CI]: -12.19, -2.68) per point increase in CTQ. No significant relationship was found between thickness/metabolism and CTQ score. While longitudinal studies are required to establish causation, this study provides insight into potential consequences of, and therefore potential therapeutic targets for, childhood trauma in the prevention of MDD. This work aims to reduce heterogeneity in MDD studies by quantifying neurobiological correlates of trauma within MDD. It further provides biological targets for future interventions aimed at preventing MDD following trauma. To our knowledge, this is the first simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) study to assess both structure and metabolism associated with childhood trauma in adults with MDD.

PMID:36115855 | DOI:10.1038/s41398-022-02153-z

Pulmonology. 2022 Sep 15:S2531-0437(21)00152-5. doi: 10.1016/j.pulmoe.2021.07.004. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by limited airflow and is influenced by genetic and environmental factors. The purpose of this study was to investigate the effects of gene polymorphisms in MIR5708 and MIR1208 on COPD risk.

METHODS: Four single nucleotide polymorphisms (SNPs) in MIR5708 (rs6473227 and rs16907751) and MIR1208 (rs2608029 and rs13280095) were selected and genotyped among 315 COPD patients and 314 healthy controls using the Agena MassARRAY platform. SPSS 18.0 was used for statistical analysis and data processing. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between genetic variants of MIR1208 and MIR5708 and COPD risk.

RESULTS: The results suggested that rs16907751 variants in MIR5708 contributed to an increased susceptibility to COPD in the allelic (P = 0.001), co-dominant (homozygous) (P = 0.001), dominant (P = 0.017), recessive (P = 0.002), and additive (P = 0.002) models. The effects of MIR5708 and MIR1208 gene polymorphisms on the risk of COPD were age-, sex-, smoking status-, and BMI-related. Furthermore, the C-A and G-A haplotypes of rs2608029 and rs13280095 in MIR1208 were identified as risk factors for COPD in the population over 70 years (P = 0.029) and in women (P = 0.049), respectively. Finally, significant associations between rs16907751genotypes with pulse rate and forced expiratory volume in 1 s were found among COPD patients.

CONCLUSION: Genetic polymorphisms in MIR5708 and MIR1208 are associated with increased risk of COPD in China.

PMID:36115827 | DOI:10.1016/j.pulmoe.2021.07.004

Eur Urol Oncol. 2022 Sep 14:S2588-9311(22)00142-0. doi: 10.1016/j.euo.2022.08.003. Online ahead of print.

ABSTRACT

BACKGROUND: Most patients diagnosed with renal cancer today present with small renal masses (SRMs). Although these patients have a low risk of dying from their disease and many are followed with active surveillance protocols, a small subset of renal cell carcinomas (RCCs) behave aggressively. Knowledge regarding features of aggressive behavior would enable better adoption of active surveillance strategies among these patients.

OBJECTIVE: We sought to improve prognostic models to predict metastasis-free survival after nephrectomy through focused analyses of clinicopathologic characteristics of SRMs associated with adverse outcomes.

DESIGN, SETTING, AND PARTICIPANTS: We identified consecutive patients with surgically resected SRMs (≤4 cm) at the University of Texas Southwestern Kidney Cancer Program between 1998 and 2020. In addition, we evaluated the ability of SRMs to form tumors when implanted in mice, an indicator of tumor aggressiveness.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the clinicopathologic factors associated with metastasis including prospectively performed BAP1 immunohistochemistry at our Clinical Laboratory Improvement Amendments laboratory. Multivariable Cox proportional hazard regression was used to predict metastasis-free survival.

RESULTS AND LIMITATIONS: A total of 3900 evaluable nephrectomies (from 3674 ethnically diverse patients) were identified, of which 1984 (51%) were SRMs including 1720 RCC. Of these patients with RCC (SRM^RCC), 1576 did not have synchronous or metachronous larger RCCs and among these, 37 (2%) developed metastases. SRM^RCC that metastasized were significantly enriched for aggressive morphologic phenotypes and engrafted in mice at comparable rates as larger metastatic tumors. BAP1 loss remained significantly associated with metastasis-free survival after accounting for TNM (tumor-node-metastasis) stage and SSIGN (stage, size, grade, and necrosis) score in multivariable analysis.

CONCLUSIONS: We identified clinicopathologic features that influence metastasis-free survival for patients with SRM^RCC. If validated independently, these data should assist with patient prognosis and help with active surveillance strategies.

PATIENT SUMMARY: We report the identification of features of aggressiveness in small renal tumors that influence the likelihood of metastases after surgery.

PMID:36115820 | DOI:10.1016/j.euo.2022.08.003

Cardiovasc Revasc Med. 2022 Sep 12:S1553-8389(22)00773-4. doi: 10.1016/j.carrev.2022.09.005. Online ahead of print.

ABSTRACT

INTRODUCTION: In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of therapeutic hypothermia (TH). However, results from previous studies are contradictory.

METHOD: We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcomes were the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door-to-balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95 % confidence intervals (CIs) were calculated using the random-effects model.

RESULTS: A total of 10 RCTs, including 706 patients were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door-to-balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation.

CONCLUSIONS: According to our meta-analysis of published RCTs, TH is not beneficial in awake patients with STEMI and has a marginal safety profile with potential for care delays. Larger-scale RCTs are needed to further clarify our results.

PMID:36115819 | DOI:10.1016/j.carrev.2022.09.005