Nevin Manimala

PLoS Comput Biol. 2021 Jun 11;17(6):e1008944. doi: 10.1371/journal.pcbi.1008944. Online ahead of print.

ABSTRACT

Cancer cells display massive dysregulation of key regulatory pathways due to now well-catalogued mutations and other DNA-related aberrations. Moreover, enormous heterogeneity has been commonly observed in the identity, frequency and location of these aberrations across individuals with the same cancer type or subtype, and this variation naturally propagates to the transcriptome, resulting in myriad types of dysregulated gene expression programs. Many have argued that a more integrative and quantitative analysis of heterogeneity of DNA and RNA molecular profiles may be necessary for designing more systematic explorations of alternative therapies and improving predictive accuracy. We introduce a representation of multi-omics profiles which is sufficiently rich to account for observed heterogeneity and support the construction of quantitative, integrated, metrics of variation. Starting from the network of interactions existing in Reactome, we build a library of “paired DNA-RNA aberrations” that represent prototypical and recurrent patterns of dysregulation in cancer; each two-gene “Source-Target Pair” (STP) consists of a “source” regulatory gene and a “target” gene whose expression is plausibly “controlled” by the source gene. The STP is then “aberrant” in a joint DNA-RNA profile if the source gene is DNA-aberrant (e.g., mutated, deleted, or duplicated), and the downstream target gene is “RNA-aberrant”, meaning its expression level is outside the normal, baseline range. With M STPs, each sample profile has exactly one of the 2M possible configurations. We concentrate on subsets of STPs, and the corresponding reduced configurations, by selecting tissue-dependent minimal coverings, defined as the smallest family of STPs with the property that every sample in the considered population displays at least one aberrant STP within that family. These minimal coverings can be computed with integer programming. Given such a covering, a natural measure of cross-sample diversity is the extent to which the particular aberrant STPs composing a covering vary from sample to sample; this variability is captured by the entropy of the distribution over configurations. We apply this program to data from TCGA for six distinct tumor types (breast, prostate, lung, colon, liver, and kidney cancer). This enables an efficient simplification of the complex landscape observed in cancer populations, resulting in the identification of novel signatures of molecular alterations which are not detected with frequency-based criteria. Estimates of cancer heterogeneity across tumor phenotypes reveals a stable pattern: entropy increases with disease severity. This framework is then well-suited to accommodate the expanding complexity of cancer genomes and epigenomes emerging from large consortia projects.

PMID:34115745 | DOI:10.1371/journal.pcbi.1008944

PLoS Comput Biol. 2021 Jun 11;17(6):e1008979. doi: 10.1371/journal.pcbi.1008979. Online ahead of print.

ABSTRACT

Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods’ capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.

PMID:34115744 | DOI:10.1371/journal.pcbi.1008979

Holist Nurs Pract. 2021 Jul-Aug 01;35(4):182-190. doi: 10.1097/HNP.0000000000000457.

ABSTRACT

Chronic low back pain (CLBP) is a major problem throughout the world and getting worse because of population increase and aging. The cost of treatment increases as the population of people with CLBP increases. This study aimed to examine the effect of auricular acupressure (AA) on pain and disability in elders with chronic low back pain. The randomized, single-blinded, and placebo-controlled study was conducted on 51 elders with CLBP in South Korea from June 2019 to August 2019. The experimental group (n = 26) received AA on low back pain-related points, whereas the placebo control group (n = 25) received AA on points unrelated to low back pain. Participants received 6 weeks of AA in weekly cycles. Collected data were analyzed using IBM SPSS Statistics, version 25. Statistically significant differences between the 2 groups emerged in the visual analog scale (P < .001), pain threshold (P < .001), and Oswestry Disability Index (P < .001). This study showed that 6 weeks of AA improved CLBP and pain-related disability. Therefore, AA can be used as a noninvasive and self-managed alternative intervention for CLBP in older adults.

PMID:34115736 | DOI:10.1097/HNP.0000000000000457

Med Sci Sports Exerc. 2021 Jun 11. doi: 10.1249/MSS.0000000000002726. Online ahead of print.

ABSTRACT

PURPOSE: To present age- and sex- specific percentiles for daily wrist-worn movement metrics in U.S. youth and adults. This metric represents a summary of all recorded movement, regardless of the purpose, context, or intensity.

METHODS: Wrist-worn accelerometer data from the combined 2011-2014 National Health and Nutrition Examination Survey (NHANES) cycles and the 2012 NHANES National Youth Fitness Survey (NNYFS) were used for this analysis. Monitor-Independent Movement Summary units (MIMS-units) from raw triaxial accelerometer data were used. We removed the partial first and last assessment days and days with ≥5% non-wear time. Participants with ≥1 valid day were included. Mean MIMS-units were calculated across all valid days. Percentile tables and smoothed curves of daily MIMS-units were calculated for each age and sex using Generalized Additive Models for Location Shape and Scale (GAMLSS).

RESULTS: The analytical sample included 14,705 participants ages ≥3 years. The MIMS-unit activity among youth was similar for both sexes while adult females generally had higher MIMS-unit activity than males. Median daily MIMS-units peaked at age 6 for both sexes (males: 20,613; females: 20,706). Lowest activity was observed for males and females 80+ years of age; 8,799 and 9,503, respectively.

CONCLUSION: Population referenced MIMS-unit percentiles for U.S. youth and adults are a novel means of characterizing total activity volume. By using MIMS-units, we provide a standardized reference that can be applied across various wrist-worn accelerometer devices. Further work is needed to link these metrics to activity intensity categories and health outcomes.

PMID:34115727 | DOI:10.1249/MSS.0000000000002726

J Glaucoma. 2021 Jun 10. doi: 10.1097/IJG.0000000000001882. Online ahead of print.

ABSTRACT

PRECIS: Chronic hypotony is not uncommon following deep sclerectomy, but only a minor proportion of patients develop hypotony-associated complications. Numerical hypotony does not affect the visual outcomes. This study identifies factors associated with hypotony.

PURPOSE: To investigate the incidence and risk factors of hypotony and hypotony-associated complications after deep sclerectomy (DS).

METHODS: Retrospective cohort study of 1,765 eyes (1,385 patients) undergoing DS with or without cataract extraction between 2001-2020 in two UK centers. Chronic hypotony was defined as intraocular pressure (IOP) ≤5▒mmHg in ≥2 consecutive visits lasting >90 days or as any IOP≤5▒mmHg associated with hypotony-related complications or requiring surgical intervention. Clinical hypotony was defined as the presence of: serous or hemorrhagic choroidal detachment, hypotony maculopathy, flat anterior chamber requiring reformation, decompression retinopathy. The incidence of hypotony was calculated with Kaplan-Meier statistics, and Cox regression was used to identify risk factors.

RESULTS: The median (IQR) age and follow-up were 76 (67-82) years and 45.4 (20.9-79.8) months, respectively. The incidence (95% CI) of chronic and clinical hypotony at 5 years was 13.4% (11.5-15.3%) and 5.6% (4.3-6.9%) respectively. Sixteen eyes (15.7%) with hypotony-associated complications had IOP >5▒mmHg. Male gender (HR:1.89, P=0.018), non-Caucasian ethnicity (HR:2.49, P=0.046), intraoperative bevacizumab (HR:3.96, P=0.01), pigmentary glaucoma (HR:3.59, P=0.048), previous vitreoretinal surgery (HR:5.70, P=0.009), intraoperative microperforation (HR:4.17, P<0.001) and macroperforation (HR:20.759, P<0.001), and avascular bleb (HR:1.80, P=0.036) were associated with clinical hypotony.

DISCUSSION: Chronic hypotony is not uncommon following DS, but clinical hypotony is infrequent. Hypotony associated-complications can occur in eyes without statistical hypotony.

PMID:34115726 | DOI:10.1097/IJG.0000000000001882

J Am Assoc Nurse Pract. 2021 Jun 9. doi: 10.1097/JXX.0000000000000621. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) infections have increased significantly in the United States recently, having tripled by 2014. Seventy-five percent of those with HCV are aging baby boomers, which places increased pressure on the medical system to provide treatment. There are not enough specialists available to treat everyone infected with HCV.

PURPOSE: The aim of this research was to determine whether treatment of hepatitis C with new direct-acting antivirals in primary care settings resulted in equivalent cure rates when compared with those patients treated by specialists.

METHODOLOGY: A retrospective cohort design was used. Participants were those treated for hepatitis C in specialty care at large public hospitals by gastroenterologists and/or hepatologists and those treated in two primary care community health centers in Seattle. Multivariate logistic regression was used to determine differences of sustained virologic response between those treated in primary care and those treated in specialty care. Treatment failure and those lost to follow-up were combined into one category.

RESULTS: Failure rates were only 4% in primary care and 1.1% in specialty care. After adjustment, patients treated in primary care were statistically significantly less likely to have failure/lost to follow-up than those treated in specialty care. Hepatitis C treatment can be successfully provided in primary care with equivalent treatment outcomes.

IMPLICATIONS FOR PRACTICE: Primary care advanced practice nurses are in a good position to identify and treat hepatitis C. In addition, as patients are typically more engaged with their primary care provider, follow-up rates may be better versus referring these patients to a specialty provider.

PMID:34115717 | DOI:10.1097/JXX.0000000000000621

Clin Nucl Med. 2021 Jun 10. doi: 10.1097/RLU.0000000000003738. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to evaluate the diagnostic performance of 18F-choline PET and MRI in patients with primary hyperparathyroidism. Furthermore, the additional value of software-based PET/MRI scan fusion was analyzed.

PATIENTS AND METHODS: This retrospective study includes 42 patients (38 women) with an age between 32.5 and 79.1 years. PET/CT scans were performed on a dedicated system after injection of 250 to 350 MBq 18F-choline. For the MRI examination, T1-weighted images of the cervical region were used. The image fusion was made by anatomical coregistration using an automated algorithm based on mutual information.

RESULTS: A total of 46 lesions were discovered and histologically confirmed in 42 patients. Histopathological examination revealed 38 adenomas and 8 hyperplasias. This means that, in 4 of these 42 patients, 2 lesions per patient were discovered. PET/CT also detected 46 abnormal findings, but only 43 were correctly recognized, whereas the other 3 were false-positive (FP). Six lesions could not be detected correctly: 3 were FP and 3 false-negative, which resulted in a sensitivity of 93.5% and a specificity of 97.5%. The site-specific evaluation showed 18 true-positive enlarged parathyroid glands with MRI, but also produced 13 FP findings and failed to detect 28 lesions; the sensitivity and specificity are thus 39.1% and 89.3%, respectively. The difference in detection rate between 18F-choline PET/CT and MRI was statistically significant (P < 0.001).

CONCLUSIONS: 18F-choline PET/CT is clearly superior to MRI for localization diagnostics in primary hyperparathyroidism. Image fusion of both modalities can be helpful for more precise anatomical assignment.

PMID:34115700 | DOI:10.1097/RLU.0000000000003738

J Addict Nurs. 2021 Jun 10. doi: 10.1097/JAN.0000000000000410. Online ahead of print.

ABSTRACT

BACKGROUND: The challenges experienced by mothers supporting an adult child with substance use problems suggest intervention is needed to improve such mothers’ psychosocial well-being through adaptive coping.

AIMS: This study examined beliefs about journaling as well as changes in stress, cortisol levels, and mental health after a 6-week intervention by mothers whose adult children had substance use problems. In addition, the study explored coping methods used and the experience of writing among these mothers.

METHODS: A purposeful sample of 17 mothers completed the pretest and posttest. Participating mothers were asked to make journal entries at least 3 times per week for 6 weeks.

RESULTS: The mothers used diverse adaptive coping methods to manage stress. In particular, they frequently used religious and meaning-focused coping. The mothers perceived journaling as a highly valuable coping method for daily stress. The findings of paired t tests indicated no statistically significant differences in the stress, mental health variables, and cortisol levels between pretest and posttest. However, participants shared the positive experiences of journaling: emotional well-being, stress management, perspective changes, focus, self-regulation, clarity, and gratitude.

CONCLUSION: The present finding suggests journaling is a practical means to promoting adaptive coping in mothers with adult children who have substance use problems.

PMID:34115696 | DOI:10.1097/JAN.0000000000000410

J Clin Gastroenterol. 2021 Jun 11. doi: 10.1097/MCG.0000000000001571. Online ahead of print.

ABSTRACT

BACKGROUND AND GOALS: There is variation in polypectomy techniques for resection of small polyps. Aim was to compare techniques for 4 to 6 mm polyps for recurrent adenoma, efficiency, and adverse events and to establish methodological factors for definitive trial.

MATERIALS AND METHODS: The study was a randomized controlled trial. Outpatients with ≥1, 4 to 6 mm polyps were randomized to cold forceps (CF), cold snare (CS), and hot snare (HS). Polypectomy site was marked with SPOT to assess for recurrence at the original polypectomy site during surveillance colonoscopy. To assess feasibility of a definitive trial we measured (1) rates of patient refusal, participation, ineligibility; (2) retention; (3) recurrent neoplasia; and (4) sample size for a definitive trial.

RESULTS: Three hundred fifty-three patients were randomized to 1 of the 3 polypectomy techniques, of whom 260 (73.6%) completed the initial colonoscopy (mean age 57 y, 50.4% women), with 91, 87, and 82 patients randomized to CF, CS, and HS polypectomy, respectively. Mean time for polyp resection for CF, CS, and HS were 198.8, 58.5, and 96.8 seconds, respectively, with CS and HS requiring less time than CF (P<0.001). One hundred sixty-four (63.1%) completed surveillance colonoscopy. Polyp recurrences were 9 (14.5%) with CF, 5 (9.6%) with CS, and 0 (0%) with HS. Although the recurrence relative risks with CF and CS polypectomy were 1.84 and 1.65 as compared with HS, respectively, neither was statistically significant.

CONCLUSIONS: CS and HS polypectomy require less time than CF. HS polypectomy may have a lower risk for recurrent neoplasia. High attrition rate is a challenge in conducting randomized controlled trial with polyp recurrence as endpoint.

PMID:34115660 | DOI:10.1097/MCG.0000000000001571

Coron Artery Dis. 2021 Jun 10. doi: 10.1097/MCA.0000000000001080. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have reported that prophylactic dialysis can reduce the mortality of non-dialysis-dependent chronic kidney disease (CKD) patients after cardiac surgery. However, the results of complications in these randomized controlled trials (RCTs) were not consistent. We aimed to perform a meta-analysis to systematically evaluate the effect of prophylactic dialysis in these non-dialysis-dependent CKD patients.

METHODS: We systematically searched Medline, Embase, Cochrane’s Library and other online sources for related RCTs. Effects of prophylactic dialysis on the incidence of 30 days’ mortality and postoperative complications were analyzed.

RESULTS: Four RCTs comprising 395 patients were included, all of them treated by coronary artery bypass grafting. Treatment of preoperative and intraoperative prophylactic dialysis significantly reduced the rate of 30-day all-cause mortality (risk ratio [RR]: 0.27, 95% confidence interval [CI], 0.13-0.58, P < 0.001, I2 = 0%) and the incidence of pulmonary complications (RR: 0.39, 95% CI, 0.20-0.77, P = 0.007, I2 = 0%), low cardiac output (RR: 0.29, 95% CI, 0.09-0.99, P = 0.05, I2 = 0%), and acute kidney injury (RR: 0.19, 95% CI: 0.07-0.52, P = 0.001, I2 = 0%). However, there were no statistically significant differences between the dialysis group and the control group in gastrointestinal bleeding, sepsis or multiple organ failure, wound infection, arrhythmia, transient neurologic deficit, stroke and re-exploration for bleeding.

CONCLUSION: Prophylactic dialysis can improve the 30-day clinical outcomes of non-dialysis-dependent CKD patients undergoing cardiac surgery, it was associated with the 30-day mortality benefit and led to a decrease in the incidence of pulmonary complications, as well as low cardiac output, and acute kidney injury.

PMID:34115642 | DOI:10.1097/MCA.0000000000001080