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Nevin Manimala Statistics

Reliability of the pre-operative imaging to assess neck nodal involvement in oral cancer patients, a single-center study

Med Oral Patol Oral Cir Bucal. 2022 Mar 1;27(2):e191-e197. doi: 10.4317/medoral.25228.

ABSTRACT

BACKGROUND: Primary sites for the metastasis of oral cancer are the cervical lymph nodes. Although there has been considerable technical advancement in the radiological imaging, capability to recognize all metastatic lymph nodes pre-operatively has remained as a challenge. Thus elective neck dissection (END) has remained as reliable practice to treat cervical lymph nodes. This study evaluated the accuracy of pre-operative imaging in pre-operative diagnostics of cervical lymph node status using computed tomography or magnetic resonance imaging in patients with oral squamous cell carcinoma (OSCC). We have also considered the reasons for the difficulties to recognise metastatic nodes in cervical area.

MATERIAL AND METHODS: Patient charts of patients who had had elective neck dissection as a treatment for primary OSCC in the Department of Oral and Maxillofacial Surgery, Helsinki University Hospital between 2016 and 2017 were assessed retrospectively. The outcome variable was post-operatively histologically confirmed lymph node metastasis in the neck area. The primary predictor variable was radiologically confirmed metastasis in the neck area. The explanatory variables were age, sex, pT-class, imaging modality, delay and location of the tumour. Descriptive statistics, sensitivity, specificity and Youden-J index were computed.

RESULTS: Eighty-three patients were included in the study. The sensitivity to detect pathological lymph nodes was 44.8%, and the specificity for the examination was 87.0%. 19.3% of cN0 patients had metastasis in the cervical nodes, whereas of the cN+ patients 8.4% were actually pN0. Patients having cN0, the largest neck metastasis was over 10 mm in 12.5%, whereas cN1-3 patients the corresponding rate was 45.5%. The computational threshold to diagnose a metastatic node was 7 mm.

CONCLUSIONS: Especially small metastases are difficult to diagnose. Limitations of radiological diagnostics must be considered when treating OSCC.

PMID:35218648 | DOI:10.4317/medoral.25228

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Nevin Manimala Statistics

Can cystic lesions of the jaws be considered as the cause of mandibular asymmetry?

Med Oral Patol Oral Cir Bucal. 2022 Mar 1;27(2):e159-e163. doi: 10.4317/medoral.25134.

ABSTRACT

BACKGROUND: The aim of this study is to investigate the presence of condylar and ramal asymmetry in patients with a cyst larger than 10 mm in the maxilla or mandible.

MATERIAL AND METHODS: Condylar and ramal asymmetry index measurements of 47 patients (mean age: 28.85 ± 15.348) in the study group and 40 patients in the control group (mean age: 33.73 ± 13.095) were performed using panoramic radiographs. The study group consists of patients with cysts larger than 10 mm in diameter in the maxilla or mandible. The control group consisted of patients with no radiolucent lesions and no history of trauma. The possible statistical difference between the groups was evaluated by the Mann-Whitney U test.

RESULTS: No statistically significant difference was observed in asymmetry indices according to gender and the jaw (maxilla or mandible) in which the cyst was located. However, it was determined that CAI and RAI values were statistically significantly different between the study and control groups (p = 0.047 and p = 0.016, respectively).

CONCLUSIONS: The presence of intraosseous cysts larger than 10 mm in the jaws was found to be associated with condylar and ramal asymmetry.

PMID:35218644 | DOI:10.4317/medoral.25134

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Nevin Manimala Statistics

Analysis of clinical indications of acupoint Yinbai (SP1) and its compatible regularities based on data mining technology

Zhen Ci Yan Jiu. 2022 Feb 25;47(2):177-84. doi: 10.13702/j.1000-0607.20210096.

ABSTRACT

OBJECTIVE: To explore the dominant indications and laws of acupoint compatibility of Yinbai (SP1) by using modern statistics and data mining techniques.

METHODS: Literature about indications and acupoint prescriptions of SP1 published before October of 1949 were retrieved from books Chinese Medical Dictionary (5th edition) and Collection of Modern Medical Journals of Traditional Chinese Medicine, and those published from October 1st of 1949 to January of 2021 retrieved from databa-ses of CNKI, Wanfang, VIP, CBM, Web of Science and Pubmed by using key words of Yinbai (SP1),”Guilei”(),”Guiyan”() and Jing (Well)-point of Spleen Meridian, followed by screening the data and establishing a SQL Server database after standardized processing. Then, the descriptive analysis, clustering analysis and association rule analysis were conducted by using Gephi visualization software, SPSS Statistics 25.0 and SPSS Modeler, separately.

RESULTS: Before October of 1949, the single SP1 acupoint was usually used to treat 12 types of diseases (mainly the internal diseases as asthma, abdominal distension, vomiting, etc.), and the compound prescriptions of SP1 were usually used to treat 20 types of diseases (mainly the internal diseases as insomnia and dreamful sleep, blood syndrome, etc.), and its adjunct acupoints belong to the first three meridians: the Foot Yangming Stomach Meridian, Foot Taiyang Bladder Meridian and Foot Taiyin Spleen Meridian. After October of 1949, the single SP1 was used to dominantly treat 2 types of diseases (mainly the gynecological diseases as metrorrhagia and metrostaxis, and hypermenorrhea, etc.), and the compound prescriptions of SP1 were frequently used to treat 10 diseases (metrorrhagia and metrostaxis, sequela of apoplexy, mental disorders, insomnia and dreamful sleep, etc.), and the adjunct acupoints of compound prescriptions belong to the first three meridians, namely the Foot Taiyin Spleen Meridian, Concept Vessel and Foot Yangming Stomach Meridian. Before and after October of 1949, the adjunct acupoints with the highest degree of correlation were Lidui (ST45), Shaoshang(LU11), Zusanli(ST36), Sanyinjiao (SP9), and Guanyuan (CV4). Cluster analysis showed that 9 effective clusters obtained may be used as potential prescriptions of SP1, and association rule analysis displayed that the first three strongly connected acupoint matching groups were: SP1-ST45, SP1-LU11, and SP1-ST36 frequently used before October of 1949, and SP1-SP9, SP1-ST36 and SP1-CV4 employed after October of 1949.

CONCLUSION: Data mining technology reveals that acupoint SP1 alone is mainly used to treat internal diseases before 1949, and gynecological diseases after 1949; and compound acupoint recipes of SP1 are mainly to treat the internal diseases before 1949, and the gynecological diseases and mental disorders after 1949 in China. The frequently employed adjunct acupoints of SP1 are ST45, LU11, ST36, SP9 and CV4 both before and after 1949.

PMID:35218630 | DOI:10.13702/j.1000-0607.20210096

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Nevin Manimala Statistics

Association of Osteopontin gene single nucleotide polymorphism with lupus nephritis

Int J Rheum Dis. 2022 Feb 26. doi: 10.1111/1756-185X.14308. Online ahead of print.

ABSTRACT

AIM: To determine the association of single nucleotide polymorphism at 9250 C/T in exon 7 of the Osteopontin (OPN) gene among Egyptian patients with lupus nephritis (LN) and healthy controls and assess its relation with clinical and laboratory features in addition to both activity and chronicity indices in these patients.

MATERIALS AND METHOD: The study population includes 100 patients with LN and 100 age- and gender-matched controls. OPN gene 9250 C/T polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism.

RESULTS: We observed a significant difference in the frequencies of the OPN gene 9250 T allele between the patients with LN and the controls (74.5% vs 57.5%, P < .001); also, TT and CT + TT genotypes showed significant differences in frequencies between LN patients versus controls (59% vs 35% P = .005 and 90% vs. 80% P = .048, respectively). We also observed a non-significant association between OPN gene 9250 genotypes and each of the laboratory data and clinical features in addition to activity and chronicity indices in all studied LN patients. There were no statistically significant increased TT and CT + TT genotypes and T allele frequencies in LN patients with renal failure compared to those without renal failure. Logistic regression analysis revealed that only OPN (CT + TT) genotype could predict LN development in Egyptian patients.

CONCLUSION: TT and CT + TT genotypes and T alleles of OPN 9250 are considered risk factors for LN development in Egyptian systemic lupus erythematosus patients. However, these genotypes showed no association with each laboratory data and clinical feature or activity and chronicity indices in these patients. OPN 9250 (CT + TT) genotype could be used to predict LN development in SLE.

PMID:35218609 | DOI:10.1111/1756-185X.14308

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Nevin Manimala Statistics

Neural tube defect prevalence does not increase after modification of the folic acid fortification program in Chile

Birth Defects Res. 2022 Feb 26. doi: 10.1002/bdr2.1994. Online ahead of print.

ABSTRACT

BACKGROUND: In 2000, Chile’s Ministry of Health mandated fortification of wheat flour with folic acid at a concentration of 2.2 mg/kg to prevent neural tube defects (NTDs), resulting in a 50% reduction in NTD prevalence. Concerns about possible collateral effects of high folic acid intake led, in 2009, to decrease the folic acid fortification to 1.8 mg/kg of flour. Our study evaluated the impact of this modification on the prevalence of NTDs in Santiago.

METHODS: This study measured the prevalence of NTDs in live births and stillbirths born in Santiago. We calculated prevalence ratios (PR) and 95% confidence intervals (CI) between pre-folic acid fortification (1999-2000), post-folic acid fortification (2001-2009), and post-modified folic acid fortification (2010-2015) periods for all NTDs and their specific types. We used chi-square tests to analyze proportions, and a Joinpoint regression to visualize prevalence time trends.

RESULTS: The NTD prevalence for the period 2001-2015 was 8.9 per 10,000 births, which represents a 48% reduction (PR = 0.52; 95% CI = 0.45-0.61; p < .001) from the pre-folic acid fortification period. During 2010-2015, the NTD prevalence was 9.5/10,000 births, which was higher, but not statistically significantly different from 2001 to 2009 prevalence of 8.6/10,000 (PR = 1.11; 95% CI = 0.96-1.30, p = .17).

CONCLUSIONS: Decreasing the concentration of folic acid fortification was not associated with a statistically significant change in the prevalence of NTDs. Mandatory folic acid fortification continues to be a safe and highly effective policy to prevent NTDs. Future studies should evaluate the prevalence of NTDs across Chile and adherence to folic acid fortification mandates.

PMID:35218603 | DOI:10.1002/bdr2.1994

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Nevin Manimala Statistics

Genetically predicted fasting blood glucose level plays a causal role in intraocular pressure: A Mendelian randomization study

Clin Exp Ophthalmol. 2022 Feb 26. doi: 10.1111/ceo.14067. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to examine possible causal associations between various components of metabolic syndrome and glaucoma-related phenotypes.

METHODS: A two-sample Mendelian randomization study was conducted with the models of IVW, maximum likelihood, weighted median, and MR-Egger regression. We accessed data from publicly available genome-wide association studies for individual parameters of metabolic syndrome as the exposures and the data for glaucoma and its endophenotypes as the outcomes.

RESULTS: Among eleven exposures and six outcomes examined in this Mendelian randomization study, only fasting blood glucose level showed evidence of a causal influence on intraocular pressure. Results analyzed by the inverse-variance weighted model suggested that each one-SD increase in genetically predicted fasting blood glucose level was significantly associated with 0.80 SD elevation in intraocular pressure (β: 0.80, 95%CI: 0.38-1.22, P: 2.12e-4). The maximum likelihood model (β: 0.82, 95%CI: 0.39-1.25, P:1.616e-4) also supported a significant causal effect. The weighted median model (β: 0.78,95%CI: 0.17-1.39, P: 0.012) showed a nominally significant effect whereas the MR-Egger model (β: 0.63, 95%CI: -0.32-1.59, P: 0.212) showed a consistent direction of effect but was not statistically significant. Several sensitivity analyses indicated no evidence of directional horizontal pleiotropy that would bias the result.

CONCLUSIONS: This Mendelian randomization study provides evidence for a causal role for genetically determined higher fasting blood glucose level in the development of increased intraocular pressure. This finding could be considered in the monitoring and control of intraocular pressure and may be instrumental in prevention strategies for ocular hypertension.

PMID:35218584 | DOI:10.1111/ceo.14067

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Nevin Manimala Statistics

Abnormal placental cord insertion, hypertensive disorders of pregnancy and birth length may be involved in development of hypospadias in male fetuses

Birth Defects Res. 2022 Feb 26. doi: 10.1002/bdr2.1995. Online ahead of print.

ABSTRACT

OBJECTIVES: Hypospadias is a congenital disease characterized by morphological abnormalities of the penis, including abnormal urethral opening and penile flexion, which cause urination disorders and/or sexual intercourse difficulty. Various factors have been suggested to cause this anomaly, but evidence concerning risk factors causing this anomaly is insufficient. We evaluated the etiology of hypospadias in Japan using the Common Database of the National Hospitals’ Neonatal study group.

STUDY DESIGN: We retrospectively evaluated 7,865 male neonates registered in the NICU Common Database of the National Hospitals’ Neonatal study group. The subjects were divided into two groups by the presence (n = 43) or absence (n = 7,822) of hypospadias. Statistical analyses were performed to compare nominal variables between the groups by Fisher’s direct establishment calculation method and logistic regression analyses.

RESULTS: A univariate analysis showed significant between-group differences in hypertensive disorders in pregnancy (odds ratio [OR]: 4.02, 95% confidence interval [CI]: 1.95-7.90), placental weight <-1.28 standard deviation (SD; OR: 5.06, 95% CI: 2.45-10.32), abnormal placental cord insertion (OR: 4.7, 95% CI: 2.62-9.76), birth length <-2SD (OR: 10.56, 95% CI: 5.00-21.1) and birth weight <-2SD (OR: 8.17, 95% CI: 4.17-15.68). A multivariate analysis showed a significant between-group difference in hypertensive disorders of pregnancy (adjusted OR [AOR]: 2.30, 95% CI: 1.09-4.85), abnormal placental cord insertion (AOR: 3.69, 95% CI: 1.83-7.44) and birth length <-2SD (AOR: 3.44, 95% CI: 1.26-9.42).

CONCLUSION: Abnormal placental cord insertion, hypertensive disorders of pregnancy and birth length may be involved in hypospadias development in male neonates in conjunction with placental dysfunction in early pregnancy.

PMID:35218598 | DOI:10.1002/bdr2.1995

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Nevin Manimala Statistics

Leveraging a surrogate outcome to improve inference on a partially missing target outcome

Biometrics. 2022 Feb 26. doi: 10.1111/biom.13629. Online ahead of print.

ABSTRACT

Sample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray) for leveraging information from a correlated surrogate outcome (e.g. expression in blood) to improve inference on a partially missing target outcome (e.g. expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Spray jointly models the target and surrogate outcomes within a bivariate regression framework. Unobserved values of either outcome are treated as missing data. We describe and implement an expectation conditional maximization algorithm for performing estimation in the presence of bilateral outcome missingness. Spray estimates the same association parameter estimated by standard eQTL mapping and controls the type I error even when the target and surrogate outcomes are truly uncorrelated. We demonstrate analytically and empirically, using simulations and GTEx data, that in comparison with marginally modeling the target outcome, jointly modeling the target and surrogate outcomes increases estimation precision and improves power. This article is protected by copyright. All rights reserved.

PMID:35218565 | DOI:10.1111/biom.13629

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Nevin Manimala Statistics

Searching for a mechanistic description of pairwise epistasis in protein systems

Proteins. 2022 Feb 26. doi: 10.1002/prot.26328. Online ahead of print.

ABSTRACT

When two or more amino acid mutations occur in protein systems, they can interact in a non-additive fashion termed epistasis. One way to quantify epistasis between mutation pairs in protein systems is by using free energy differences: ϵ = 𝚫𝚫G1,2 – (𝚫𝚫G1 + 𝚫𝚫G2 ) where 𝚫𝚫G refers to the change in the Gibbs free energy, subscripts 1 and 2 refer to single mutations in arbitrary order and 1,2 refers to the double mutant. In this study, we explore possible biophysical mechanisms that drive pairwise epistasis in both protein-protein binding affinity and protein folding stability. Using the largest available datasets containing experimental protein structures and free energy data, we derived statistical models for both binding and folding epistasis (ϵ) with similar explanatory power (R2 ) of 0.299 and 0.258, respectively. These models contain terms and interactions that are consistent with intuition. For example, increasing the Cartesian separation between mutation sites leads to a decrease in observed epistasis for both folding and binding. Our results provide insight into factors that contribute to pairwise epistasis in protein systems and their importance in explaining epistasis. However, the low explanatory power indicates that more study is needed to fully understand this phenomenon.

PMID:35218569 | DOI:10.1002/prot.26328

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Nevin Manimala Statistics

The Paradoxical Effect of Creatine Monohydrate on Muscle Damage Markers: A Systematic Review and Meta-Analysis

Sports Med. 2022 Feb 26. doi: 10.1007/s40279-022-01640-z. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several studies indicate that the benefits of CrM on recovery dynamics are limited.

OBJECTIVE: This systematic review and meta-analysis determined whether the ergogenic effects of CrM ameliorated markers of muscle damage and performance following muscle-damaging exercises.

METHODS: In total, 23 studies were included, consisting of 240 participants in the CrM group (age 23.9 ± 10.4 years, height 178 ± 5 cm, body mass 76.9 ± 7.6 kg, females 10.4%) and 229 participants in the placebo group (age 23.7 ± 8.5 years, height 177 ± 5 cm, body mass 77.0 ± 6.6 kg, females 10.0%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the CrM and placebo groups at 24-36 h and 48-90 h following muscle-damaging exercises, using standardised mean differences (SMDs) and associated p-values via forest plots. Furthermore, sub-group analyses were conducted by separating studies into those that examined the effects of CrM as an acute training response (i.e., after one muscle-damaging exercise bout) and those that examined the chronic training response (i.e., examining the acute response after the last training session following several weeks of training).

RESULTS: According to the meta-analysis, the CrM group exhibited significantly lower indirect muscle damage markers (i.e., creatine kinase, lactate dehydrogenase, and/or myoglobin) at 48-90 h post-exercise for the acute training response (SMD – 1.09; p = 0.03). However, indirect muscle damage markers were significantly greater in the CrM group at 24 h post-exercise (SMD 0.95; p = 0.04) for the chronic training response. Although not significant, a large difference in indirect muscle damage markers was also found at 48 h post-exercise (SMD 1.24) for the chronic training response. The CrM group also showed lower inflammation for the acute training response at 24-36 h post-exercise and 48-90 h post-exercise with a large effect size (SMD – 1.38 ≤ d ≤ – 1.79). Similarly, the oxidative stress markers were lower for the acute training response in the CrM group at 24-36 h post-exercise and 90 h post-exercise, with a large effect size (SMD – 1.37 and – 1.36, respectively). For delayed-onset muscle soreness (DOMS), the measures were lower for the CrM group at 24 h post-exercise with a moderate effect size (SMD – 0.66) as an acute training response. However, the inter-group differences for inflammation, oxidative stress, and DOMS were not statistically significant (p > 0.05).

CONCLUSION: Overall, our meta-analysis demonstrated a paradoxical effect of CrM supplementation post-exercise, where CrM appears to minimise exercise-induced muscle damage as an acute training response, although this trend is reversed as a chronic training response. Thus, CrM may be effective in reducing the level of exercise-induced muscle damage following a single bout of strenuous exercises, although training-induced stress could be exacerbated following long-term supplementation of CrM. Although long-term usage of CrM is known to enhance training adaptations, whether the increased level of exercise-induced muscle damage as a chronic training response may provide potential mechanisms to enhance chronic training adaptations with CrM supplementation remains to be confirmed.

PMID:35218552 | DOI:10.1007/s40279-022-01640-z