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Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification-amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two-Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure-Function Linkage Database, SFLD) self-identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self-identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well-curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP-identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F-measure and performance analysis on the enolase search results and comparison to GEMMA and SCI-PHY demonstrate that TuLIP avoids the over-division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results.

Introduction: Identifying suitable predictive biomarkers is critical for preventing recurrence and improving the survival rate in individuals with Oral Squamous Cell Carcinomas (OSCC). HOTAIR is a novel type of long non-coding RNA (lncRNA) that has been linked to initiation and progression in OSCC. Most previous studies on HOTAIR have included a small number of OSCC cohorts, only a few studies have performed multivariate analyses adjusting for confounding factors, and there has been little emphasis on HOTAIR's potential to predict loco-regional recurrence. Methodology: The study included 96 OSCC Formalin Fixed Paraffin Embedded (FFPE) tissue samples and gender and age-matched 30 normal mucosa who had received surgical therapy. HOTAIR expression in OSCC was analysed using qRT-PCR and correlated with clinic-pathological variables, risk practices, loco-regional recurrence, and Overall Survival (OS). Results: HOTAIR was overexpressed in OSCC compared to NM. High HOTAIR expression was related to regional lymph node metastases, perineural invasion, and locoregional recurrence. The Kaplan-Meier curve followed by Log-rank test survival estimates revealed a significantly associated with high HOTAIR expression and poor OS (p<0.05). In multivariate analysis, lymph node metastasis (Hazard ratio 4.39, p ≤ 0.001, 95% confidence interval, 1.775-10.886) and high HOTAIR expression (Hazard ratio 3.337, p ≤ 0.001, 95% confidence interval, 1.396-7.973) were the independent predictors of poor OS. Age, TNM staging, and high HOTAIR expression were all independent predictors of loco regional recurrence. Conclusion: The current study establishes HOTAIR as a novel prognostic marker for OSCC and suggests a therapeutic strategy for targeted therapy of OSCC. [ABSTRACT FROM AUTHOR]

Purpose To compare the effect of 'intermittent' central venous oxygen saturation (ScvO.sub.2) monitoring with 'continuous' ScvO.sub.2 monitoring on shock resolution and mortality in children with septic shock. Methods Primary outcome was the achievement of therapeutic goals or shock resolution in the first 6 h. We randomly assigned children < 17 years' age with septic shock to 'intermittent ScvO.sub.2' or 'continuous ScvO.sub.2' groups. All children were subjected to subclavian/internal jugular line insertion and managed as per Surviving Sepsis Campaign Guidelines. To guide resuscitation, we used ScvO.sub.2 estimated at other clinical and laboratory parameters were monitored similarly in both groups. Results We enrolled 75 and 77 children [median (IQR) age: 6 (1.5-10) years] in the 'intermittent' and 'continuous' groups, respectively. Baseline characteristics were comparable between the groups. When compared to the 'continuous' group, fewer children in the 'intermittent' group achieved shock resolution within first 6 h [19% vs. 36%; relative risk (RR) 0.51; 95% CI 0.29-0.89; risk difference - 18.0%; 95% CI - 32.0 to - 4.0]. The lower bound of confidence interval, however, crossed the pre-specified non-inferiority margin. There was no difference in the proportion of children attaining shock resolution within 24 h (63% vs. 69%; RR 0.86; 95% CI 0.68-1.08) or risk of mortality between the groups (47% vs. 43%; RR 1.06; 95% CI 0.74-1.51). Conclusions Given that a greater proportion of children attained therapeutic end points in the first 6 h, continuous monitoring of ScvO.sub.2 should preferably be used to titrate therapy in the first few hours in children with septic shock. In the absence of such facility, intermittent monitoring of ScvO.sub.2 can be used to titrate therapy in these children, given the lack of difference in the proportion of patients achieving shock resolution at 24 h or in risk of mortality between the intermittent and continuous groups., Author(s): Jhuma Sankar [sup.1], Man Singh [sup.1], Kiran Kumar [sup.1], M. Jeeva Sankar [sup.1], Sushil Kumar Kabra [sup.1], Rakesh Lodha [sup.1] Author Affiliations: (1) grid.413618.9, 0000 0004 1767 6103, Department [...]

Background: The need for mobile-based ambulatory heart rhythm monitoring arises from its potential to provide convenient and continuous tracking of heart rhythms, improving early detection and management of cardiac issues while accommodating patients' active lifestyles. The present study aims to compare and validate the 24 h ECG monitoring between the traditional Holter and Vigo Heart wearable patch. Method: One hundred and nineteen patients with a workup of pre-diagnosed arrhythmias or suspicious arrhythmic episodes were evaluated. Each participant wore both devices simultaneously, and the cardiac rhythm was monitored for 24 h. Selective ECG parameters were compared between the two devices and the cardiologist independently compared the diagnoses of each device. Results: The indication for ECG monitoring in the ent study was patients who were presented with suspicious arrhythmia-related symptoms (47.8%). The Vigo Heart ECG showed a negligible amount of mean noise percentage (1.94 ±6.68%) when compared with the traditional Holter 17.84±23.95% of the total recording time. For the maximum heart rate, there was significant correlation between the Holter monitoring and Vigo Heart patch (129.69 ± 22.5 vs. 113.31 ± 23.6 beats/min, p = 0.02). The results also showed significant correlation for the average heart rates (74.85 ± 10.8 vs. 76 ± 10.3 beats/min, p = 0.02) and minimum heart rates (47.94 ± 9.5 vs. 59.21 ± 8.9 beats/min, p = 0.02), for the Vigo Heart ECG and Holter monitoring, respectively. The cardiologist made coherent clinical diagnoses for all the 119 study participants using both the ECG monitoring devices. The findings also revealed comparable coherent detection of cardiac arrhythmias in both the ECG monitoring devices. Conclusion: The single-lead adhesive device presents itself as a viable and acceptable alternative for conducting ambulatory ECG monitoring in individuals with arrhythmia or suspicious symptoms of arrhythmias. [ABSTRACT FROM AUTHOR]