Tag: statistics

Blood Adv. 2023 Oct 24:bloodadvances.2023011389. doi: 10.1182/bloodadvances.2023011389. Online ahead of print.

ABSTRACT

Deleterious germline variants in DDX41 are a common cause of genetic predisposition to hematological malignancies, particularly myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Targeted next generation sequencing (NGS) was performed on large cohort of sequential patients with myeloid malignancy covering DDX41 as well as 30 other genes frequently mutated in myeloid malignancy. Whole genome transcriptome sequencing data was analyzed on a separate cohort of patients with a range of hematological malignancies to investigate the spectrum of cancer predisposition. 5737 patients with myeloid malignancies were studied with 152 different DDX41 variants detected. Multiple novel variants were detected, including synonymous variants affecting splicing as demonstrated by RNA-sequencing. The presence of a somatic DDX41 variant was highly associated with DDX41 germline variants in MDS and AML patients and we developed a statistical approach to incorporate the co-occurrence of a somatic DDX41 variant into germline variant classification at a “very strong” level (ACMG). Using this approach, the MDS cohort contained 3.8% (108/2865) patients with germline likely pathogenic/pathogenic (LP/P) variants and the AML cohort 4.9% (106/2157). DDX41 LP/P variants were markedly enriched in patients with AML and MDS compared to patients with myeloproliferative neoplasms (MPN), B-cell neoplasm and T- or B-cell acute lymphoblastic leukemia. In summary we have developed a framework to enhance DDX41 variant curation as well as highlighted the importance of assessment of all types of genomic variants (including synonymous and multi-exon deletions) in order to fully detect the landscape of possible clinically relevant DDX41 variants.

PMID:37874914 | DOI:10.1182/bloodadvances.2023011389

Chaos. 2023 Oct 1;33(10):103135. doi: 10.1063/5.0166846.

ABSTRACT

A variety of nonlinear models of biological systems generate complex chaotic behaviors that contrast with biological homeostasis, the observation that many biological systems prove remarkably robust in the face of changing external or internal conditions. Motivated by the subtle dynamics of cell activity in a crustacean central pattern generator (CPG), this paper proposes a refinement of the notion of chaos that reconciles homeostasis and chaos in systems with multiple timescales. We show that systems displaying relaxation cycles while going through chaotic attractors generate chaotic dynamics that are regular at macroscopic timescales and are, thus, consistent with physiological function. We further show that this relative regularity may break down through global bifurcations of chaotic attractors such as crises, beyond which the system may also generate erratic activity at slow timescales. We analyze these phenomena in detail in the chaotic Rulkov map, a classical neuron model known to exhibit a variety of chaotic spike patterns. This leads us to propose that the passage of slow relaxation cycles through a chaotic attractor crisis is a robust, general mechanism for the transition between such dynamics. We validate this numerically in three other models: a simple model of the crustacean CPG neural network, a discrete cubic map, and a continuous flow.

PMID:37874881 | DOI:10.1063/5.0166846

PLoS One. 2023 Oct 24;18(10):e0275374. doi: 10.1371/journal.pone.0275374. eCollection 2023.

ABSTRACT

The durability of dental restorations is highly determined by an accurate marginal fit, which is in turn affected by the high temperature of porcelain firing. Information is inadequate about the marginal adaptation of metal-ceramic restorations fabricated by soft metal milling technologies after repeated firings. This study aimed to compare the effect of repeated ceramic firings on the marginal fit of copings fabricated from cobalt-chromium through soft metal milling and a conventional nickel-chromium casting alloy. A single standard brass die was designed, machined, and scanned, based on which, 20 frameworks were designed and fabricated through either soft metal milling or conventional casting (n = 10 per group) and porcelain veneered. The vertical marginal fit of the metal copings was measured after 3, 5, and 7 firing cycles by using a digital microscope on 16 points around the finish line of the metal die at ×80 magnification. The data were analyzed through repeated measures ANOVA and independent t-test (α = 0.05). The marginal fit of neither metal group was significantly affected by the number of firing cycles (P = 0.747). However, the marginal discrepancy was statistically lower in the soft metal milling group than that in the casting group (P<0.001). Repeated porcelain firings did not significantly affect the marginal fit of either alloy and remained within the clinically acceptable range after firings. However, the milled alloy had superior marginal fit regardless of the number of firing cycles.

PMID:37874843 | DOI:10.1371/journal.pone.0275374

PLoS One. 2023 Oct 24;18(10):e0293251. doi: 10.1371/journal.pone.0293251. eCollection 2023.

ABSTRACT

BACKGROUND: To inform preparedness and population health action, we need to understand the effects of COVID-19 on health inequities. In this study, we assess the impact of COVID-19 on opioid toxicity deaths among people who experience incarceration compared to others in the general population in Ontario, Canada.

METHODS: We conducted a retrospective cohort study for the period of January 1, 2015 to December 31, 2020. We accessed and linked coronial data on all opioid toxicity deaths in Ontario with correctional data for people aged 18 years and older who were incarcerated in a provincial correctional facility. We used data from the Statistics Canada Census to calculate whole population rates. We used an interrupted time series design and segmented regression to assess for change in the level or rate of increase in deaths due to opioid toxicity coinciding with the COVID-19 pandemic. We compared the impact of COVID-19 on the opioid toxicity death rates for people exposed and not exposed to incarceration.

RESULTS: Rates of opioid toxicity death increased with a linear positive slope in both persons exposed to incarceration and those not exposed over the study period. The start of COVID-19 measures coincided with a marked upward shift in the trend lines with modification of the effect of COVID-19 by both sex and exposure to incarceration. For persons exposed to incarceration, the risk ratio (RR) was 1.50 (95%CI 1.35-1.69) for males and 1.21 (95%CI 1.06-1.42) for females, and for persons not exposed to incarceration, the RR was 1.25 (95%CI 1.13-1.38) for males and not significant for females.

CONCLUSIONS: COVID-19 substantially exacerbated the risk of opioid toxicity death, impacting males and females who experienced incarceration more than those who had not, with an immediate stepwise increase in risk but no change in the rate of increase of risk over time. Public health work, including pandemic preparedness, should consider the specific needs and circumstances of people who experience incarceration.

PMID:37874825 | DOI:10.1371/journal.pone.0293251

PLoS One. 2023 Oct 24;18(10):e0288543. doi: 10.1371/journal.pone.0288543. eCollection 2023.

ABSTRACT

BACKGROUND: Early maladaptive schemas (EMSs) have been theorised to contribute to reoccurring interpersonal problems. This study developed a novel experimental paradigm that aimed to assess if EMSs moderate the impact of interpersonal situations on interpersonal responses by manipulating the degree of rejection in a series of interpersonal vignettes depicting acceptance, ambiguous rejection and rejection.

METHOD: In a sample of 158 first-year psychology students (27.2% male; 72.2% female; 0.6% other) participant responses to interpersonal scenarios were measured including degree of perceived rejection, emotional distress, conviction in varying cognitive appraisals consistent with attribution theory and behavioural responses to scenarios. Qualitative data was analysed using inductive content analysis and statistical analyses were conducted using multi-level mixed effect linear and logistic regression models using the software Jamovi.

RESULTS: People reporting higher EMSs reported increased emotional distress (F(1, 156) = 24.85, p < .001), perceptions of rejection (F(1, 156) = 34.33, p < .001), self-blame (F(1, 156) = 53.25, p < .001), other-blame (F(1, 156) = 13.16, p < .001) and more intentional (F(1, 156) = 9.24, p = .003), stable (F(1, 156) = 25.22, p < .001) and global (F(1, 156) = 19.55, p < .001) attributions but no differences in reported behavioural responses. The results also supported that EMSs moderate the relationship between interpersonal rejection and perceptions of rejection (F(2, 1252) = 18.43, p < .001), emotional distress (F(2, 1252) = 12.64, p < .001) and self-blame (F(2, 1252) = 14.00, p < .001).

CONCLUSION: Together these findings suggest that people with EMSs experience increased distress and select negative cognitions in situations where there are higher levels of rejection but that distress and negative cognitions are generally higher in people with EMSs irrespective of the situation.

PMID:37874818 | DOI:10.1371/journal.pone.0288543

PLoS One. 2023 Oct 24;18(10):e0288630. doi: 10.1371/journal.pone.0288630. eCollection 2023.

ABSTRACT

This study examines the relationship between globalization, ecological footprint, innovation, and subjective wellbeing in the form of happiness, using a comprehensive assessment of OECD countries from 2008 to 2020. The study employs FGLS, Quantile, and Bootstrap Quantile regression estimation to investigate the quadratic effects of globalization, ecological footprint, and the moderating effect of innovation while controlling for renewable energy and population density. Happiness is a multidisciplinary subject, and this study focuses on the economic dimensions of happiness. The findings reveal a nonlinear relationship between ecological footprint and globalization, with negative effects on subjective wellbeing at high levels of ecological footprint and globalization. However, the moderating effect of innovation mitigates these adverse effects, indicating that innovation can help to offset the detrimental impacts of ecological footprint and globalization on subjective wellbeing. The study’s implications are significant for policymakers promoting sustainable economic growth while enhancing subjective wellbeing. The findings highlight the importance of investing in innovation and sustainable development to promote subjective wellbeing in the face of increasing ecological footprint and globalization. Additionally, this research contributes to the multidisciplinary understanding of happiness and provides valuable insights for future research in this area.

PMID:37874811 | DOI:10.1371/journal.pone.0288630

Bratisl Lek Listy. 2023;124(11):842-847. doi: 10.4149/BLL_2023_129.

ABSTRACT

OBJECTIVES: The aim of the study is to investigate the effects of Protocatechuic Acid (PCA), which is an antioxidant, anti-inflammatory and anti-apoptotic agent, on ovarian tissue and ovarian reserve against ischemia-reperfusion (IR) injury in a rat ovarian torsion model.

BACKGROUND: Reactive oxygen radicals cause histopathological changes in the ovarian tissue during the reperfusion phase. PCA may have protective effects on ovarian tissue and reserve due to its antioxidant and antiapoptotic properties.

METHODS: A total of 24 Wistar adult female rats were divided into 3 groups as the control (sham operation, n = 8), IR (Ischemia-Reperfusion, n = 8), and IR+PCA (Ischemia-Reperfusion + 80 mg/kg protocatechuic acid, n = 8). The IR and IR + PCA groups underwent 3 hours of ischemia followed by 3 hours of ovarian reperfusion. Protocatechuic acid (80 mg/kg) was administered to the IR+PCA group 30 minutes before reperfusion. After reperfusion, the ovaries were removed for histopathological and biochemical examination.

RESULTS: Histopathological score and TUNEL+ cell count were significantly lower and AMH expression level was significantly higher in the IR+PCA group when compared to the IR group (p <0.05). However, in the comparison of the follicle counts, there was no statistically significant difference between all groups. Due to the increase in antioxidant activity, the MDA levels were found to be significantly lower in the IR+PCA group compared to the IR group (p < 0.05).

CONCLUSION: Protocatechuic acid may be an effective antioxidant in protecting ovarian tissue and follicle reserve against IR injury of the ovary (Tab. 1, Fig. 4, Ref. 36).

PMID:37874807 | DOI:10.4149/BLL_2023_129

Bratisl Lek Listy. 2023;124(11):827-832. doi: 10.4149/BLL_2023_127.

ABSTRACT

OBJECTIVES: The aim of our study is to determine whether mapping the lymphatic drainage and diagnostic excision of lymph nodes from lateral neck compartment is able to detect ultrasound unknown metastases in this compartment early and thus favorably affect the prognosis of patients with papillary thyroid cancer (PTC).

BACKGROUND: Lymph node involvement in the lateral neck compartment is seen in 30-60 % of patients with PTC at the time of diagnosis and affects the prognosis of patients in terms of disease recurrence.

METHODS: From June 2012 to December 2016, 154 patients with no evidence of lateral nodal involvement on imaging studies were treated with total thyroidectomy and central comparment neck dissection. A volume of 0.2 ml of Patent Blue dye was applied in the upper half of the thyroid gland with subsequent exposure of lymphatic drainage in the lateral compartment and 2-3 sentinel lymph nodes (SLN) were removed for frozen section (Group 1). In case of metastatic involvement, a lateral comparment neck dissection was performed. The reference groups were composed of a set of patients without detected lymphatic drainage (Group 2) and a set of patients who underwent lateral compartment neck dissection for preoperatively detected metastases in the lymph nodes (Group 3). The biochemical, structural and overall persistence of the disease at the time of administration of adjuvant radioiodine ablation was evaluated.

RESULTS: The SLN identification rate was 95.45 %. In Group 1, a total of 32 patients had a positive SLN. Out of these, 24 patients had positive SLNs based on the analysis of frozen section, while in 8 patients, the positive diagnosis was confirmed through definitive histology. The comparison of data from the entire follow-up period in all three groups of patients revealed statistically significant differences in persistence of disease, namely in favor of Group 1. The percentage of reoperations for persistence and recurrence of disease was significantly lowest in Group 1 (2.04 %) compared to Groups 2 and 3 (6.94 % and 45.45 % respectively).

CONCLUSION: The method is safe and sensitive for detecting unknown lymph node metastases in the lateral neck compartment, and may facilitate a decision to perform accurate surgical treatment of patients with PTC (Tab. 4, Fig. 2, Ref. 38).

PMID:37874805 | DOI:10.4149/BLL_2023_127

Bratisl Lek Listy. 2023;124(11):821-826. doi: 10.4149/BLL_2023_126.

ABSTRACT

BACKGROUND: Some symptoms such as fatigue and dyspnea decrease the quality of life in patients with heart failure. The effectiveness of self-management programs on management of chronic conditions was discussed. So, this study aimed to investigate the effectiveness of self-management program based on 5A model on fatigue and dyspnea in patients with heart failure.

METHODS: In this clinical trial study, 60 patients with heart failure were included. The intervention group underwent self-management program based on 5A model and the control group received routine care. All the enrolled patients were evaluated once at baseline and once after 3 months using fatigue severity and Borg dyspnea scales. The obtained data were analyzed using SPSS software version 16 by descriptive statistics and independent t-test, covariance test, and paired sample t- test. The significance level was set at 0.05.

RESULTS: There was no significant difference in the mean scores of fatigue and dyspnea at the beginning of the study between control and intervention groups (p > 0.05), but 3 months after intervention a significant difference was found in mean scores of fatigue and dyspnea between two groups, (p < 0.05). The difference between pre- and post-intervention scores in terms of the dyspnea and fatigue variables was significant based on the result of paired sample t-test (p < 0.05).

CONCLUSION: According to the results of this study, self-management program based on 5A Model can be used to reduce the severity of fatigue and dyspnea as well as improve the quality of life in patients with heart failure (Tab. 4, Fig. 1, Ref. 33).

PMID:37874804 | DOI:10.4149/BLL_2023_126

Bratisl Lek Listy. 2023;124(11):802-809. doi: 10.4149/BLL_2023_123.

ABSTRACT

RATIONALE: Acute pancreatitis (AP) is a serious acute abdominal disease. AP is often referred to as an unpredictable illness, which can take a mild to severe (fatal) course.

AIMS OF THE STUDY: 1) To identify clinical parameters that are significantly related to the clinical course of acute pancreatitis. 2) To compile a scoring system enabling the severity of AP to be predicted when the patient is first admitted to hospital.

METHODS: Analysis of available publications and clinical guidance, and retrospective analysis of data on patients hospitalised with AP at our clinic enable us to identify clinical details and laboratory results recorded at the time of patients’ admission to hospital that are related to the subsequent severity of the disease. For the purposes of statistical analysis, the sample of patients was divided into two groups: group A (mild AP, without local or organ complications), group B (moderately severe and severe AP with local and/or organ complications).

PATIENT GROUPS AND RESULTS: In total, between 01.01.2013 and 30.06.2022, 312 patients with acute pancreatitis were allocated to the retrospective-prospective study sample. 74 % (231/312) of these patients were allocated to group A and 26 % (81/312) were allocated to group B. Univariate analysis of the data collected on the patient sample identified 5 parameters that are statistically significantly associated with the severity of the clinical course of the disease. Presence of SIRS on admission (A vs B, Odds ratio 10.787, 95% CI 5.09-22.85, p < 0.0001), diabetes mellitus type 2 in case history (A vs B, Odds ratio 7.703, 95% CI 3.04-19.51, p 2 mmol/l (A vs B, Odds ratio 3.293, 95% CI 1.59-6.82, p = 0.0013).In order to develop a scoring system, each of these parameters was allocated a points value based on its Odds ratio (OR): presence of SIRS 3 points, hypocalcaemia 3 points, diabetes mellitus type 2 in case history 2 points, urea concentration > 8 mmol/l 1 point and lactate concentration > 2 mmol/l 1 point. The authors refer to their scoring system as The Acute Pancreatitis Admission Score (APAS). The accuracy of APAS was modelled for various cut off values. Across the whole sample, we ascertained that an APAS ≥ 4 points predicts moderately severe or severe AP with a sensitivity of 81 % (95% CI: 71 – 89 %) and specificity of 87 % (95 CI: 81 – 91 %). The positive predictive value (PPV) of APAS ≥ 4 is 0.68, while its negative predictive value (NPV) is 0.93 and accuracy 0.85 (95% CI 0.81 – 0.89).

CONCLUSION: In this study we identify significant simple clinical and laboratory parameters that are commonly tested as part of an initial examination when admitting a patient with AP to hospital. Having identified these parameters we are able to establish a simple scoring system that is able to predict the severity of the course of AP at the moment of hospitalisation (Tab. 5, Fig. 2, Ref. 27).

PMID:37874801 | DOI:10.4149/BLL_2023_123