Tag: nevin manimala

J Clin Oncol. 2022 Jan 6:JCO2101422. doi: 10.1200/JCO.21.01422. Online ahead of print.

ABSTRACT

PURPOSE: To establish a patient-specific polygenic score derived from cytarabine (ara-C) pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment.

MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in the ara-C-pathway genes were analyzed with outcome in patients from the multicenter-AML02 trial (N = 166). Multi-SNP predictor modeling was used to develop 10-SNP Ara-C_SNP score (ACS10) using top SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02-cohort and four SNPs previously associated with ara-C triphosphate levels in the AML97 trial. ACS10 was evaluated for association with outcomes in each clinical trial arms: the standard low-dose ara-C (LDAC, n = 91) and augmented high-dose ara-C (HDAC, n = 75) arms of AML02 and the standard Ara-C, daunorubicin and etoposide (ADE) (n = 465) and the augmented ADE + gemtuzumab ozogamicin (GO; n = 466) arms of AAML0531 trial.

RESULTS: In the standard LDAC-arm of AML02 cohort, the low-ACS10 score group (≤ 0) had significantly worse EFS (ACS10 low v high hazard ratio [HR] = 2.81; 95% CI, 1.45 to 5.43; P = .002) and overall survival (OS; HR = 2.98; 95% CI, 1.32 to 6.75; P = .009) compared with the high-ACS10 group (score > 0). These results were validated in the standard-ADE arm of AAML0531, with poor outcome in the low-ASC10 group compared with the high-ACS10 group (EFS: HR = 1.35, 95% CI, 1.04 to 1.75, P = .026; OS: HR = 1.64, 95% CI, 1.2 to 2.22, P = .002). Within the augmented arms (AML02-HDAC and AAML0531-ADE + GO), EFS and OS did not differ between low- and high-ACS10 score groups. In both cohorts, patients with low-ACS10 consistently showed a 10-percentage point improvement in 5-year EFS with augmented therapy (AML02-HDAC or AAML0531-ADE + GO arms) than with standard therapy (AML02-LDAC or AAML0531-ADE arms).

CONCLUSION: Patients with low-ACS10 score experienced significantly poor outcome when treated on standard regimen. Augmentation with either high-dose ara-C or GO addition improved outcome in low-ACS10 group. A polygenic ACS10 score can identify patients with unfavorable pharmacogenetic characteristics and offers a potential for an elective augmented therapy option.

PMID:34990262 | DOI:10.1200/JCO.21.01422

Br J Radiol. 2022 Jan 6:20210832. doi: 10.1259/bjr.20210832. Online ahead of print.

ABSTRACT

OBJECTIVE: Our single-centre retrospective study aimed to evaluate the relationship between magnetic resonance (MR)-directed ultrasound (MDUS) detectability and magnetic resonance imaging (MRI) findings of non-mass enhancement (NME) lesions, regarding the morphologic and enhancement features, the distance from the skin and nipple, and the presence of concomitant landmarks.

METHODS: A total of 350 MRI-detected NME lesions that were determined between January 2015 and May 2019 and subsequently underwent MDUS were analyzed. The MRI findings, biopsy results, and follow-up outcomes of lesions were recorded. The correlation between the MRI findings of the lesions and MDUS detectability was analyzed.

RESULTS: One hundred fourteen (32.6%) of the 350 lesions had a counterpart in the MDUS. Respectively, 66 (37.9%), 38 (43.2%) and 59 (38.3%) of the lesions detected in MDUS were larger than 20 mm in size, with a distance of less than 20 mm to the nipple and 15 mm to the skin. The lesion size and lesion distance to the nipple and skin were significantly associated with a US correlate (p < 0.05). The MDUS detection rate was significantly higher in NME lesions with MR findings including diffuse distribution (p < 0.001), clustered-ring enhancement pattern (p < 0.001), washout kinetic curve (p = 0.006), and MR-BIRADS category 5 (p < 0.001). Multivariate logistic regression showed that only the clustered-ring enhancement pattern was significantly associated with an MDUS correlation (p < 0.001).

CONCLUSION: Statistically significant correlations were found between the size, distance to the nipple and skin, distribution pattern, enhancement pattern and kinetic curve of the NME lesions on MRI and ultrasound detectability.

ADVANCES IN KNOWLEDGE: We found that clustered-ring enhancement patterns were significantly more frequent in MR-directed US detectable lesions.

PMID:34990263 | DOI:10.1259/bjr.20210832

Personal Disord. 2022 Jan 6. doi: 10.1037/per0000528. Online ahead of print.

ABSTRACT

Several psychiatric conditions (e.g., substance use, mood, and personality disorders) are characterized, in part, by greater delay discounting (DD)-a decision-making bias in the direction of preferring smaller, more immediate over larger, delayed rewards. Narcissistic personality disorder (NPD) is highly comorbid with substance use, mood, and other personality disorders, suggesting that DD may be a process underpinning risk for NPD as well. This meta-analysis examined associations between DD and theoretically distinct, clinically relevant dimensions of narcissism (i.e., grandiosity, entitlement, and vulnerability). Literature searches were conducted and articles were included if they were written in English, published in a peer-reviewed journal, contained measures of DD and narcissism and reported their association, and used an adult sample. Narcissism measures had to be systematically categorized according to clinically relevant dimensions (Grijalva et al., 2015; Wright & Edershile, 2018). Seven studies met inclusion criteria (N = 2,705). DD was positively associated with narcissism (r = .21; 95% confidence interval [.10, .32]), with this association being largely attributable to measures of trait grandiosity that were used in each study (r = .24; 95% confidence interval [.11, .37]). No studies included diagnostic NPD assessments. These findings provide empirical evidence that DD is related to trait narcissism and perhaps risk for NPD (e.g., grandiosity listed in Criterion B of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, alternative model of personality disorders). Considering the positive evidence from this review, and the dearth of research examining DD in individuals with NPD, investigators studying NPD may consider incorporating DD measures in future studies to potentially inform clinical theory and novel adjunctive treatment options. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:34990195 | DOI:10.1037/per0000528

Plant Biol (Stuttg). 2022 Jan 6. doi: 10.1111/plb.13382. Online ahead of print.

ABSTRACT

Increases in environmental temperature are directly linked to the issue of climate change and are known to significantly disrupt plant growth and development. Studies of gene expression in plants commonly include RT-qPCR but the reliability of the method depends on the use of suitable reference genes for data normalization. Despite this, no reference genes have been validated specifically for experiments in Arabidopsis thaliana employing treatments with elevated temperature. Here, ten genes were selected for expression stability analysis based on the screening of available literature and microarray data from temperature-treated A. thaliana. Expression levels of candidate reference genes were measured in 12-day-old seedlings, rosette leaves and flower buds of 5-week-old A. thaliana plants exposed to five different temperatures (22°C, 27°C, 32°C, 37°C and 42°C) and their expression stabilities were assessed using four statistical algorithms (BestKeeper, geNorm, NormFinder and comparative ΔC_q method). This study provides reliable reference genes for use in A. thaliana RT-qPCR expression analyses employing elevated temperature treatments, namely OGIO and PUX7 in seedlings, UBC21 and PUX7 in leaves, TIP41 and UBC21 in buds, and TIP41 and UBC21 in all three tissues combined. Orthologues of these genes can be of potential use in less studied plants, especially agricultural species heavily affected by climate change.

PMID:34990067 | DOI:10.1111/plb.13382

J Exp Psychol Gen. 2022 Jan 6. doi: 10.1037/xge0001166. Online ahead of print.

ABSTRACT

The statistical relation between two events influences the perception of how one event relates to the presence or absence of another. Interestingly, the simultaneous absence of both events, just like their mutual occurrence, is relevant for describing their contingency. In three experiments, we explored the relevance of coabsent events by varying the duration and frequency of trials without stimuli. We used a rapid trial streaming procedure and found that the perceived association between events is enhanced with increasing frequency of coabsent events, unlike the duration of coabsent events, which had little effect. These findings suggest ways in which the benefits of trial spacing, during which both events are absent, could be obtained without increasing total training time. Centrally, this can be done by frequent repeating of shortened coabsent events, each marked by a trial contextual cue. We discuss four potential accounts of how coabsent experience might be processed contributing to this effect: (a) contingency sensitivity, (b) testing effect, (c) reduced associative interference by the context, and (d) reduced encoding interference. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:34990159 | DOI:10.1037/xge0001166

Support Care Cancer. 2022 Jan 6. doi: 10.1007/s00520-021-06735-3. Online ahead of print.

ABSTRACT

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India.

METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading “Additional concerns.” The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve.

RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients’ physical, functional, emotional, and social well-being.

CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

PMID:34988703 | DOI:10.1007/s00520-021-06735-3

Eur J Pediatr. 2022 Jan 6. doi: 10.1007/s00431-021-04322-6. Online ahead of print.

ABSTRACT

Increasing concerns have been raised on the health-related risks connected with energy drink (ED) consumption in children and adolescents, with high acute or chronic consumers exceeding 10% in either age group in Europe in 2011. Preliminary evidence has suggested a common pattern of ED and substance use, especially alcohol. Additional evidence has been accumulating very fast; in addition, other lifestyle and risky behaviors may contribute to shed light on the complex interplay of factors involved in ED consumption. We have undertaken a comprehensive systematic review of the evidence on psychosocial correlates of ED consumption in 0-18 years subjects, as published up to April 1, 2021, in MEDLINE/PubMed, PsycINFO, and Cochrane Reviews and Central Register of Controlled Trials, which allowed to select 104 original articles. Only ~ 10% of the papers provided results based on longitudinal analyses. A common pattern of ED consumption and polysubstance use, including alcohol, tobacco, and soft and hard drugs, was still confirmed in adolescents; violent and risky behaviors were also related to a higher ED consumption. In addition, frequent ED consumers are more likely to have bad dietary habits, including consumption of sugar-sweetened beverages and junk foods. A generally inconclusive evidence was found for sport/physical activities, although sedentary behaviors were generally related to ED consumption.Conclusions: Frequent ED consumption might be a screening indicator to identify students at risk of substance use or other risky/problem behaviors; enquiring about an adolescent’s recent ED consumption could create opportunities for early intervention/prevention by informed pediatricians. What is Known: • Substances, especially alcohol, are associated with energy drinks in most cross-sectional studies. What is New: • Violent behaviors are associated with energy drink consumption, in the absence of longitudinal studies; problematic use of internet/videogames deserves further investigation; unhealthy dietary patterns are related to energy drinks; evidence on physical activity is inconclusive, but sedentary behaviors are related to energy drinks.

PMID:34988663 | DOI:10.1007/s00431-021-04322-6

Acta Diabetol. 2022 Jan 6. doi: 10.1007/s00592-021-01830-7. Online ahead of print.

ABSTRACT

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disorders worldwide. Some hypoglycemic drugs can improve NAFLD. However, it is unclear which of these types of hypoglycemic drugs are more effective for NAFLD. Therefore, we conducted a network meta-analysis to determine the effect of thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on NAFLD patients.

METHODS: A literature search of PubMed, EMBASE, the Cochrane Library, and Medline was conducted, and the literature from database inception up to April 30, 2021 was obtained. Liver function tests, lipid profiles, body mass index (BMI) and glycemic parameters were obtained from randomized controlled trials. Weighted mean differences (WMDs), relative risks and 95% confidence intervals (CIs) were calculated for continuous outcomes, and the I² statistic was used to evaluate the heterogeneity of the studies.

RESULTS: In total, 22 trials, including 1361 patients, were selected. In direct meta-analysis, GLP-1 receptor agonists were superior to TZDs in decreasing alanine aminotransferase (WMD, -0.40, 95% CI: -0.60 to -0.20), γ-glutamyl transferase (WMD, -5.00, 95% CI: -6.47 to -3.53), BMI (WMD, -4.10, 95%CI: -6.55 to -1.65) and triglycerides (WMD, – 0.50, 95% CI: -0.68 to -0.32). Based on Bayesian network meta-analysis, the effect of SGLT-2 inhibitors on weight loss was superior to that of TZDs (WMD, -1.80, 95%CI: -3.30 to -0.41).

CONCLUSIONS: GLP-1 receptor agonists and SGLT-2 inhibitors improved liver enzymes, BMI, blood lipid, blood glucose and insulin resistance in NAFLD patients.

PMID:34988690 | DOI:10.1007/s00592-021-01830-7

Arch Gynecol Obstet. 2022 Jan 6. doi: 10.1007/s00404-021-06369-0. Online ahead of print.

ABSTRACT

PURPOSE: Voiding difficulties in the context of pelvic organ prolapse are often neglected or underestimated. To date, there are heterogeneous data available on the outcome of a surgical correction of pelvic organ prolapse and the impact on concomitant voiding dysfunction. The primary aim of this study was to evaluate whether laparoscopic sacrocolpopexy would resolve preoperative voiding dysfunction and the impact on objective uroflowmetry parameters.

METHODS: Data from 103 women undergoing sacrocolpopexy for prolapse stage ≥ II with concurrent objective and/or subjective voiding dysfunction were prospectively evaluated. All women underwent full urogynecological examination, and completed a validated questionnaire pre- and postoperatively. Objective uroflowmetry parameters and subjective outcome data regarding voiding functions were compared pre- and postoperatively.

RESULTS: All points of the POP-Q system improved significantly pre- to postoperatively (p < 0.001). Preoperatively, 42 of 103 women showed a postvoid residual ≥ 100 ml, whereas only six women had a relevant postvoid residual postoperatively. In total, the postoperative postvoid residual in all women decreased significantly (p < 0.001). Voiding time decreased significantly postoperatively (p < 0.001) with no significant change in the voided volume (p = 0.352). The maximum flow rate increased postoperatively, reaching no statistically significant change (p = 0.132). Subjective outcome measurements (weak or prolonged stream, incomplete bladder emptying, and straining to void) improved significantly (p < 0.001 for all the questions).

CONCLUSION: Our prospective study demonstrates that sacrocolpopexy to correct pelvic organ prolapse can successfully resolve voiding dysfunction, as both objective and subjective parameters improved significantly after surgery.

PMID:34988660 | DOI:10.1007/s00404-021-06369-0

Hum Genet. 2022 Jan 6. doi: 10.1007/s00439-021-02417-6. Online ahead of print.

ABSTRACT

Deep generative models can learn the underlying structure, such as pathways or gene programs, from omics data. We provide an introduction as well as an overview of such techniques, specifically illustrating their use with single-cell gene expression data. For example, the low dimensional latent representations offered by various approaches, such as variational auto-encoders, are useful to get a better understanding of the relations between observed gene expressions and experimental factors or phenotypes. Furthermore, by providing a generative model for the latent and observed variables, deep generative models can generate synthetic observations, which allow us to assess the uncertainty in the learned representations. While deep generative models are useful to learn the structure of high-dimensional omics data by efficiently capturing non-linear dependencies between genes, they are sometimes difficult to interpret due to their neural network building blocks. More precisely, to understand the relationship between learned latent variables and observed variables, e.g., gene transcript abundances and external phenotypes, is difficult. Therefore, we also illustrate current approaches that allow us to infer the relationship between learned latent variables and observed variables as well as external phenotypes. Thereby, we render deep learning approaches more interpretable. In an application with single-cell gene expression data, we demonstrate the utility of the discussed methods.

PMID:34988661 | DOI:10.1007/s00439-021-02417-6