Nevin Manimala

Microrna. 2024 Apr 8. doi: 10.2174/0122115366288068240322064431. Online ahead of print.

ABSTRACT

BACKGROUND: Long non-coding RNA (lncRNA) plays a crucial role in various biolog-ical processes, and mutations or imbalances of lncRNAs can lead to several diseases, including cancer, Prader-Willi syndrome, autism, Alzheimer’s disease, cartilage-hair hypoplasia, and hear-ing loss. Understanding lncRNA-protein interactions (LPIs) is vital for elucidating basic cellular processes, human diseases, viral replication, transcription, and plant pathogen resistance. Despite the development of several LPI calculation methods, predicting LPI remains challenging, with the selection of variables and deep learning structure being the focus of LPI research.

METHODS: We propose a deep learning framework called AR-LPI, which extracts sequence and secondary structure features of proteins and lncRNAs. The framework utilizes an auto-encoder for feature extraction and employs SE-ResNet for prediction. Additionally, we apply transfer learning to the deep neural network SE-ResNet for predicting small-sample datasets.

RESULTS: Through comprehensive experimental comparison, we demonstrate that the AR-LPI ar-chitecture performs better in LPI prediction. Specifically, the accuracy of AR-LPI increases by 2.86% to 94.52%, while the F-value of AR-LPI increases by 2.71% to 94.73%.

CONCLUSION: Our experimental results show that the overall performance of AR-LPI is better than that of other LPI prediction tools.

PMID:38591194 | DOI:10.2174/0122115366288068240322064431

Med Decis Making. 2024 Apr 9:272989X241241328. doi: 10.1177/0272989X241241328. Online ahead of print.

ABSTRACT

BACKGROUND: Parameter uncertainty in EQ-5D-5L value sets often exceeds the instrument’s minimum important difference, yet this is routinely ignored. Multiple imputation (MI) accounts for parameter uncertainty in the value set; however, no valuation study has implemented this methodology. Our objective was to create a Canadian MI value set for the EQ-5D-5L, thus enabling users to account for parameter uncertainty in the value set.

METHODS: Using the Canadian EQ-5D-5L valuation study (N = 1,073), we first refit the original model followed by models with state-level misspecification. Models were compared based on the adequacy of 95% credible interval (CrI) coverage for out-of-sample predictions. Using the best-fitting model, we took 100 draws from the posterior distribution to create 100 imputed value sets. We examined how much the standard error of the estimated mean health utilities increased after accounting for parameter uncertainty in the value set by using the MI and original value sets to score 2 data sets: 1) a sample of 1,208 individuals from the Canadian general public and 2) a sample of 401 women with breast cancer.

RESULTS: The selected model with state-level misspecification outperformed the original model (95% CrI coverage: 94.2% v. 11.6%). We observed wider standard errors for the estimated mean utilities on using the MI value set for both the Canadian general public (MI: 0.0091; original: 0.0035) and patients with breast cancer (MI: 0.0169; original: 0.0066).

DISCUSSION AND CONCLUSIONS: We provide 1) the first MI value sets for the EQ-5D-5L and 2) code to construct MI value sets while accounting for state-level model misspecification. Our study suggests that ignoring parameter uncertainty in value sets leads to falsely narrow SEs.

HIGHLIGHTS: Value sets for health state utility instruments are estimated subject to parameter uncertainty; this parameter uncertainty may exceed the minimum important difference of the instrument, yet it is not fully captured using current methods.This study creates the first multiply imputed value set for a multiattribute utility instrument, the EQ-5D-5L, to fully capture this parameter uncertainty.We apply the multiply imputed value set to 2 data sets from 1) the Canadian general public and 2) women with invasive breast cancer.Scoring the EQ-5D-5L using a multiply imputed value set led to wider standard error estimates, suggesting that the current practice of ignoring parameter uncertainty in the value set leads to falsely low standard errors.Our work will be of interest to methodologists and developers of the EQ-5D-5L and users of the EQ-5D-5L, such as health economists, researchers, and policy makers.

PMID:38591189 | DOI:10.1177/0272989X241241328

J Cosmet Dermatol. 2024 Apr 9. doi: 10.1111/jocd.16308. Online ahead of print.

ABSTRACT

INTRODUCTION: Vitiligo is a common depigmenting skin disorder. This work is performed to systematically evaluate the efficacy and safety of fire needles combined with 308 nm excimer laser therapy in treating vitiligo.

METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on fire needles combined with 308 nm excimer laser therapy with 308 nm excimer laser therapy alone for vitiligo were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes.

RESULTS: In this study, 10 RCTs and 1333 patients were included. The results showed that compared with 308 nm excimer laser therapy alone, fire needle combined with 308 nm excimer laser therapy is more effective in improving clinical effective rate (RR = 1.36, 95% CI [1.24, 1.50], p < 0.00001), serum CD4+ level (MD = 3.12, 95% CI [2.50, 3.74], p < 0.00001), CD4+/CD8+ ratio (MD = 0.24, 95% CI [0.09, 0.39], p = 0.001), and quality of life measured by the Dermatology Life Quality Index (DLQI) (MD = 3.76, 95% CI [3.33, 4.19], p < 0.00001), and reducing the Vitiligo Area Score Index (VASI) (MD = -5.47, 95% CI [-6.56, -4.37], p < 0.00001). The reported adverse events, including redness, swelling, pain, blisters, and itching, were controllable, and all these events were well tolerated.

CONCLUSION: The current evidence indicates that fire needle combined with 308 nm excimer laser therapy is effective and safe for vitiligo. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

PMID:38591186 | DOI:10.1111/jocd.16308

Head Neck. 2024 Apr 9. doi: 10.1002/hed.27771. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT).

METHODS: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan-Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs.

RESULTS: Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6-82 months). There were no statistically significant differences in locoregional failure-free survival, distant metastasis-free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed.

CONCLUSIONS: In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

PMID:38591178 | DOI:10.1002/hed.27771

Am Surg. 2024 Apr 9:31348241241712. doi: 10.1177/00031348241241712. Online ahead of print.

ABSTRACT

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe.

METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test.

RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period.

DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

PMID:38591174 | DOI:10.1177/00031348241241712

Int Wound J. 2024 Apr;21(4):e14871. doi: 10.1111/iwj.14871.

ABSTRACT

Pressure ulcers including heel ulcers remain a global healthcare concern. This study comprehensively evaluates the biomechanical effectiveness of the market-popular ALLEVYN® LIFE multilayer dressing in preventing heel ulcers. It focuses on the contribution of the frictional sliding occurring between the non-bonded, fully independent layers of this dressing type when the dressing is protecting the body from friction and shear. The layer-on-layer sliding phenomenon, which this dressing design enables, named here the frictional energy absorber effectiveness (FEAE), absorbs approximately 30%-45% of the mechanical energy resulting from the foot weight, friction and shear acting to distort soft tissues in a supine position, thereby reducing the risk of heel ulcers. Introducing the novel theoretical FEAE formulation, new laboratory methods to quantify the FEAE and a review of relevant clinical studies, this research underlines the importance of the FEAE in protecting the heels of at-risk patients. The work builds on a decade of research published by our group in analysing and evaluating dressing designs for pressure ulcer prevention and will be useful for clinicians, manufacturers, regulators and reimbursing bodies in assessing the effectiveness of dressings indicated or considered for prophylactic use.

PMID:38591160 | DOI:10.1111/iwj.14871

Environ Sci Process Impacts. 2024 Apr 9. doi: 10.1039/d3em00500c. Online ahead of print.

ABSTRACT

Microplastic (MP) pollution has garnered global attention in recent years. Although anthropogenic factors have been extensively studied for their impacts on MP pollution, there is still a lack of research on the relationship between non-anthropogenic factors and MP occurrence in inland freshwater. This study investigated MP pollution in Donghu Lake, the largest urban freshwater lake in China, to examine the effects of rainfall and lakeshore soil properties on MP pollution. The MP abundance in the surface water of Donghu Lake was 5.84 ± 2.95 items per L under the equilibrium state. However, during and after rainfall, the MP abundances significantly increased to 8.27 ± 5.65 items per L and 7.60 ± 4.04 items per L, respectively (p < 0.05). This increase could be attributed to an increase in the amount of MPs transported to the lake via atmospheric deposition and rainfall runoff, as well as the re-suspension of MP debris in sediment during stronger hydrodynamics. A statistically significant negative correlation was observed between MP abundance and lakeshore soil particle size. It suggested that a high proportion of large-sized soil particles created large pores that enabled MPs to be deposited in the surface layer of soil to migrate to deeper layers. As a result, the amount of MPs in the surface soil and transported to the lake via surface runoff was low. It is of practical significance to understand the sources and distribution impact factors of MPs in urban lakes. The fate and effects of MPs retained in the inland freshwater environments should receive more attention.

PMID:38591146 | DOI:10.1039/d3em00500c

SAR QSAR Environ Res. 2024 Apr 9:1-20. doi: 10.1080/1062936X.2024.2332203. Online ahead of print.

ABSTRACT

Eight QSAR models (M1-M8) were developed from a dataset of 118 benzo-fused heteronuclear derivatives targeting VEGFR-2 by Monte Carlo optimization method of CORALSEA 2023 software. Models were generated with hybrid optimal descriptors using both SMILES and Graphs with zero- and first-order Morgan extended connectivity index from a training set of 103 derivatives. All statistical parameters for model validation were within the prescribed limits, establishing the models to be robust and of excellent quality. Among all models, split-2 of M5 was the best-fit as reflected by rvalidation2, Qvalidation2 and MAE. Mechanistic interpretation of this model assisted the identification of structural descriptors as promoters and hinderers for VEGFR-2 inhibition. These descriptors were utilized to design novel VEGFR-2 inhibitors (YS01-YS07) by bringing modifications in compound MS90 in the dataset. Docking of all designed compounds, MS90 and sorafenib with VEGFR-2 binding site revealed favourable binding interactions. Docking score of YS07 was higher than that of MS90 and sorafenib. Molecular dynamics simulation study revealed sustained interactions of YS07 with key amino acids of VEGFR-2 at a run time of 100 ns. This study concludes the development of a best fit QSAR model which can assist the design of new anticancer agents targeting VEGFR-2.

PMID:38591137 | DOI:10.1080/1062936X.2024.2332203

ACR Open Rheumatol. 2024 Apr 9. doi: 10.1002/acr2.11666. Online ahead of print.

ABSTRACT

OBJECTIVE: Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life.

METHODS: People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0^plus) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons.

RESULTS: Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of “missed doses” (two or fewer allopurinol doses missed consecutively) and “drug holidays” (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04).

CONCLUSION: Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.

PMID:38591107 | DOI:10.1002/acr2.11666

Eur Urol Open Sci. 2024 Apr 4;63:104-112. doi: 10.1016/j.euros.2024.03.013. eCollection 2024 May.

ABSTRACT

BACKGROUND AND OBJECTIVE: The Hugo RAS and DaVinci Xi systems are used for performing robot-assisted radical prostatectomy (RARP). This study aims to compare these two platforms providing granular and comprehensive data on their intraoperative performance.

METHODS: The Comparison of Outcomes of Multiple Platforms for Assisted Robotic surgery-Prostate (COMPAR-P) trial is a prospective post-market study (clinicaltrials.org NCT05766163). Enrollment began in March 2023, allocating patients to DaVinci or Hugo RAS for RARP, without selection criteria, for up to 50 consecutive cases. Two experienced console surgeons performed the procedures, following the same technique. Evaluation focused on timing, learning curves, malfunctioning events, complications, and users’ satisfaction, using standard statistical methods, including the cumulative summation analysis (CUSUM) for the learning curve assessment.

KEY FINDINGS AND LIMITATIONS: Fifty patients each were enrolled for DaVinci (DV-RARP) and Hugo RAS (H-RARP) RARP. Baseline features were balanced. DV-RARP showed significantly shorter “setup” and “console” phase durations than H-RARP (37 vs 55 min and 97 vs 126 min, respectively, p < 0.001). A longitudinal timing analysis revealed DV-RARP’s flat line, while H-RARP showed a modest decline with breakpoints at 22 and 17 procedures by CUSUM for the setup and console phases. The numbers of malfunctioning events were 4 (DV-RARP) and 20 (H-RARP). DV-RARP had high user satisfaction, while the user satisfaction of H-RARP varied. The comparison was between the first 50 H-RARP and the last 50 DV-RARP cases performed at our institution. This likely accounts for the observed differences in setup and console times between the cohorts. The specialized expertise of the surgeons involved could limit the generalizability of our findings.

CONCLUSIONS AND CLINICAL IMPLICATIONS: This prospective study compared unselected patients who underwent DV-RARP and H-RARP. More malfunctioning events occurred in case of Hugo RAS, but surgical outcomes were similar. Longer operative times for Hugo RAS were attributed to meticulous care with the novel platform. Improvement potential was evident within a few procedures, providing valuable insights for adopting this new platform.

PATIENT SUMMARY: This study compared two advanced robotic systems, DaVinci and Hugo RAS, used to remove the prostate in patients diagnosed with prostate cancer. While both systems showed similar surgical outcomes, the newer Hugo RAS system required more meticulous movements, leading to slightly longer operation times. The findings suggest that, with further experience, both systems can provide effective treatment options for patients undergoing prostate surgery.

PMID:38591096 | PMC:PMC11000201 | DOI:10.1016/j.euros.2024.03.013