Biological applications of knowledge graph embedding models.

Complex biological systems are traditionally modelled as graphs of interconnected biological entities. These graphs, i.e. biological knowledge graphs, are then processed using graph exploratory approaches to perform different types of analytical and predictive tasks. Despite the high predictive accuracy of these approaches, they have limited scalability due to their dependency on time-consuming path exploratory procedures. In recent years, owing to the rapid advances of computational technologies, new approaches for modelling graphs and mining them with high accuracy and scalability have emerged. These approaches, i.e. knowledge graph embedding (KGE) models, operate by learning low-rank vector representations of graph nodes and edges that preserve the graph's inherent structure. These approaches were used to analyse knowledge graphs from different domains where they showed superior performance and accuracy compared to previous graph exploratory approaches. In this work, we study this class of models in the context of biological knowledge graphs and their different applications. We then show how KGE models can be a natural fit for representing complex biological knowledge modelled as graphs. We also discuss their predictive and analytical capabilities in different biology applications. In this regard, we present two example case studies that demonstrate the capabilities of KGE models: prediction of drug-target interactions and polypharmacy side effects. Finally, we analyse different practical considerations for KGEs, and we discuss possible opportunities and challenges related to adopting them for modelling biological systems.

Intralesional methotrexate in the treatment of localized vitiligo: A pilot study.

BACKGROUND/OBJECTIVES: Vitiligo is an immune-mediated skin disorder that targets epidermal melanocytes leading to the appearance of depigmented skin patches. Different treatment modalities have been reported with varied efficacy. We tried to evaluate the safety and efficacy of intralesional methotrexate in treating localized areas of vitiligo. METHODS: Thirty participants with localized patches of vitiligo were recruited. They were treated with intralesional injections of methotrexate every 2 weeks for a maximum of six sessions. At the end of the study, the degree of repigmentation was categorized into: excellent improvement (>75% repigmentation), good improvement (50%-75% repigmentation), fair improvement (25%-50% repigmentation) and poor improvement (<25% repigmentation). RESULTS: We included 7 males (23.3%) and 23 females (76.7%). Their mean age was 33.6 ± 8.6 years. The duration of the disease ranged from 1 to 22 years. Four patients had a family history of vitiligo. At the end of the study, there was a highly statistically significant improvement (p < 0.001) after treatment regarding repigmentation. CONCLUSIONS: This study showed that intralesional methotrexate is a safe and effective treatment option for patients with localized vitiligo lesions. Further studies on a larger scale are needed to evaluate the long-term effects of treatment and detect the ideal dose to be injected.

Outcome of redo orchidopexy after previous laparoscopic orchidopexy.

PURPOSE: Testicular reascent is a recognised complication of orchidopexy, and redo surgery may be required. In this report, we present our experience of redo orchidopexy after initial laparoscopic surgery. METHODS: Patients who had undergone redo orchidopexy following an initial vessel-sparing (VS) or non-vessel sparing (NVS) laparoscopic orchidopexy between 2005 and 2019 were identified. Outcome data, including complications and testicular size, were recorded. RESULTS: The series comprised 23 patients (5: initial bilateral surgery with reascent on one side only; 18: unilateral surgery) with a mean age at original surgery of 3.5 years (range 8 months-6 years) and at redo surgery, 4 years (range 1.5-7 years). VS surgery had been undertaken in 15 and NVS in 8. A tension-free scrotal position was achieved in all cases. There were no complications and no patient required orchidectomy. At a minimum of 6-month follow-up after redo surgery, there were no cases of reascent and there was no change in testicular size/volume (based on clinical examination). CONCLUSION: Redo orchidopexy is an effective treatment following failed laparoscopic orchidopexy and a scrotal testis can be achieved in all cases. Complete testicular atrophy did not occur, but the risk of partial atrophy could not be accurately quantified.

Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment.

A new series of sixteen new 2-arylamino-5,7-disubstituted-N-aryl-pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives was designed and synthesized. The antitumor activities of the new compounds were initially screened through the developmental therapeutics program at NCI-USA 60 cell line panel. 2-((2,4-dimethoxyphenyl)amino)-5,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7a) was identified as a potential hit with a mean percentage of growth inhibition of 48.5% over the 60-NCI cancer cell lines whereas the other fifteen compounds ranged from 0.5 to 10.72%. In MTT assay, compound 7a exhibited IC50 of 6.28 ± 0.26 µM and 17.7 ± 0.92 µM against HCT-116 colorectal cancer and WI-38 human lung fibroblast normal cell lines, respectively. In cell cycle analysis, compound 7a arrested cell cycle at G2/M phase. It was able to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyc B (Cyclin B) complex at IC50 161.2 ± 2.7 nM. The apoptosis-inducing ability of compound 7a was assessed through apoptosis detection flow-cytometry and gene expression analysis of apoptosis markers and caspase cascade which revealed that compound 7a exerts pro-apoptotic effect and increased expression of p53, Bax, cytochrome c, caspases (-3,-8, and-9), and decreased expression of Bcl-2. This suggests that the pro-apoptotic effect is exerted through the intrinsic pathway. The molecular docking study revealed a unique binding mode at the ATP binding pocket of CDK1/Cyc B/Cks2 through its 2,4-dimethoxyphenyl-amino. These results suggest that compound 7a could be a promising hit as a targeted protein kinase inhibitor which exerts its antitumor effect through CDK1 inhibition and pro-apoptotic action.

Intravenous thrombolysis before mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion; should we cross that bridge? A systematic review and meta-analysis of 36,123 patients.

BACKGROUND: The use of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a debatable subject in the field of neuro-interventional surgery. We conducted this systematic review and meta-analysis to synthesize evidence from published studies on the outcomes of IVT + MT compared with MT alone in AIS-LVO patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to January 2022 for relevant clinical trials and observational studies. Eligible studies were identified, and all relevant outcomes were pooled in the meta-analysis DerSimonian-Liard random-effects model. RESULTS: Forty-nine studies, with a total of 36,123 patients, were included in this meta-analysis. IVT + MT was significantly superior to MT alone in terms of successful recanalization (RR 1.06, 95% CI 1.03 to 1.09), mortality (RR 0.75, 95% CI 0.68-0.82), favorable functional outcome (RR 1.21, 95% CI 1.13 to 1.29), and complete recanalization (RR 1.06, 95% CI 1.00 to 1.11). There were no significant differences between the two groups in terms of improvement of the National Institute of Health Stroke Scale (NIHSS) score at 24 h or at discharge (p > 0.05). Complications including symptomatic intracranial hemorrhage, symptomatic intracerebral hemorrhage (sICH), procedure-related complications, and parenchymal hematoma were comparable between the two groups (p > 0.05). CONCLUSION: For AIS-LVO, IVT + MT is associated with slightly better rates of survival, successful and complete recanalization, and favorable functional outcome as compared with MT alone. Further clinical trials are needed to corroborate such benefits of bridging IVT.

Correction of pre-existing astigmatism with phacoemulsification using toric intraocular lens versus spherical intraocular lens and wave front guided surface ablation.

BACKGROUND: This study aimed to evaluate toric intraocular lens to correct of pre-existing astigmatism at the time of phacoemulsification compared to using of spherical intraocular lens followed by wavefront guided surface ablation. RESULTS: The patients were classified into three groups: Group A with 20 eyes of 19 patients having phacoemulsification with spherical intraocular lens only as a control group, group B with 20 eyes of 14 patients had phacoemulsification with toric intraocular lens and group C with 20 eyes of 16 patients had phacoemulsification with spherical intraocular lens and wavefront guided PRK three months later. Comparison pre-operative data for all groups showed no statistically significant difference regarding UCVA, BCVA, MRSE, and refractive astigmatism (P>0.05). Post operatively, there was a statistically significant difference for UCVA, BCVA, MRSE, and refractive astigmatism for group A compared to group B (P<0.05) and group A compared to group C but there was no statistically significant difference for group B compared to C regarding all these parameters (P>0.05). CONCLUSION: In this study, we found similar effects for both techniques in astigmatism corrected groups while both differed from the control group that was not corrected. Correcting preexisting astigmatism during cataract surgery should be in mind in every case to improve visual outcomes. Longer period of follow up are required to evaluate stability of these techniques and possibility of regression.

Discovering protein drug targets using knowledge graph embeddings.

MOTIVATION: Computational approaches for predicting drug-target interactions (DTIs) can provide valuable insights into the drug mechanism of action. DTI predictions can help to quickly identify new promising (on-target) or unintended (off-target) effects of drugs. However, existing models face several challenges. Many can only process a limited number of drugs and/or have poor proteome coverage. The current approaches also often suffer from high false positive prediction rates. RESULTS: We propose a novel computational approach for predicting drug target proteins. The approach is based on formulating the problem as a link prediction in knowledge graphs (robust, machine-readable representations of networked knowledge). We use biomedical knowledge bases to create a knowledge graph of entities connected to both drugs and their potential targets. We propose a specific knowledge graph embedding model, TriModel, to learn vector representations (i.e. embeddings) for all drugs and targets in the created knowledge graph. These representations are consequently used to infer candidate drug target interactions based on their scores computed by the trained TriModel model. We have experimentally evaluated our method using computer simulations and compared it to five existing models. This has shown that our approach outperforms all previous ones in terms of both area under ROC and precision-recall curves in standard benchmark tests. AVAILABILITY AND IMPLEMENTATION: The data, predictions and models are available at: drugtargets.insight-centre.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Accurate prediction of kinase-substrate networks using knowledge graphs.

Phosphorylation of specific substrates by protein kinases is a key control mechanism for vital cell-fate decisions and other cellular processes. However, discovering specific kinase-substrate relationships is time-consuming and often rather serendipitous. Computational predictions alleviate these challenges, but the current approaches suffer from limitations like restricted kinome coverage and inaccuracy. They also typically utilise only local features without reflecting broader interaction context. To address these limitations, we have developed an alternative predictive model. It uses statistical relational learning on top of phosphorylation networks interpreted as knowledge graphs, a simple yet robust model for representing networked knowledge. Compared to a representative selection of six existing systems, our model has the highest kinome coverage and produces biologically valid high-confidence predictions not possible with the other tools. Specifically, we have experimentally validated predictions of previously unknown phosphorylations by the LATS1, AKT1, PKA and MST2 kinases in human. Thus, our tool is useful for focusing phosphoproteomic experiments, and facilitates the discovery of new phosphorylation reactions. Our model can be accessed publicly via an easy-to-use web interface (LinkPhinder).

MONTHLY INTRAVITREAL INFLIXIMAB IN BEHÇET'S DISEASE ACTIVE POSTERIOR UVEITIS: A Long-Term Safety Study.

PURPOSE: To study the safety of extended monthly intravitreal infliximab injections in patients with active posterior uveitis in Behcet's disease. METHODS: This is a prospective, interventional, noncomparative, open-label, pilot study of 9 monthly intravitreal infliximab injections (1 mg/0.05 mL) for 22 eyes of 16 patients with active posterior uveitis in Behcet's disease. Control of inflammation and visual outcomes were assessed, and ocular complications were monitored during the study period. RESULTS: Successful treatment was achieved in 7 eyes (35%), and failure was encountered in 13 eyes (65%). Only seven eyes of six patients (35%) had completed the study and achieved complete resolution of inflammation with improved best-corrected visual acuity and no complications. Failure was either because of inability to control the inflammation in nine eyes (45%) or development of exacerbation of inflammation in four eyes (20%). Four eyes developed severe immunological reaction from the drug after first (n = 1), second (n = 2), and third (n = 1) injections and had to discontinue the injections. Kaplan-Meier survival analysis showed that the mean estimated time to failure was 3.3 ± 0.2 months, and all failed eyes required revision of their systemic immunotherapy to control the ocular inflammation. CONCLUSION: Intravitreal infliximab for active posterior uveitis in Behcet's disease was associated with a high complication rate and failure to control inflammation in most eyes. It should not be considered a substitute to systemic therapy.

Femoral versus axillary cannulation in acute type A aortic dissections: A meta-analysis.

OBJECTIVE: There has been a growing interest in antegrade cannulation techniques in type A aortic dissection surgery. Axillary cannulation has previously been reported to provide better outcomes in terms of short-term mortality and neurological event. Consensus regarding the best cannulation strategy still remains controversial. METHOD: The MEDLINE and EMBASE databases were conducted up until October 3, 2020. Data regarding mortality, stroke, reoperation for bleeding and length of hospital stay, wound infection and cardiopulmonary bypass time were extracted and submitted to a meta-analysis using random-effects modelling and the I2 -test for heterogeneity. Fourteen retrospective observational studies were included, enrolling a total of 2621 patients. RESULTS: There were a total of 2621 patients (1327 axillary cannulation and 874 femoral cannulation). Axillary cannulation was associated with reduced short term mortality (pooled odds ratio [OR] = +0.42, 95% confidence interval [CI] = +0.25 to +0.70; p = .0009) compared to femoral cannulation. Axillary cannulation was also associated with a lower incidence of neurological events (pooled OR = +0.63, 95% CI = +0.42 to +0.94; p = .02). CONCLUSION: Our meta-analyses suggests that axillary cannulation has superior outcomes in terms of mortality and stroke following emergency surgery for type A aortic dissection. However, the lack of high quality randomized controlled trials does not make this recommendation generalisable to all units.

Efficacy and Safety of Contact Lens-Assisted Corneal Crosslinking in the Treatment of Keratoconus With Thin Corneas.

OBJECTIVE: To evaluate the safety and efficacy of contact lens-assisted crosslinking (CA-CXL) in progressive keratoconus with thin corneas (350-400 µm). METHODS: Forty eyes (30 patients) underwent epithelium-off CA-CXL with iso-osmolar riboflavin and ultraviolet-A irradiation for 30 min (fluence, 3 mW/cm2). A non-ultra-violet-absorbing soft contact lens (sCL) soaked in riboflavin was applied over the cornea during irradiation. Demarcation line (DL) depth was measured 1 month postoperatively. Endothelial cell count (ECC) was measured preoperatively and 3 months postoperatively. Distance uncorrected visual acuity (UDVA) and best spectacle-corrected visual acuity (BDVA), and maximum keratometric values (K max) were evaluated preoperatively and 9 months postoperatively. RESULTS: The sCL added a mean thickness of 100.05±1.23 µm. The mean ECC was 2,982±165 cell/mm2 preoperatively and 2,955±125 cell/mm2 postoperatively (endothelial cell loss, 0.9%, P=0.21). The mean DL depth was 204.8±20.2 µm. There was significant improvement in UDVA (P<0.001) and BDVA (P=0.011) with a stable K max (P=0.06). CONCLUSION: Contact lens-assisted crosslinking was safe and effective, with endothelial loss less than 1% after 3 months and stable corneal tomography over 9 months, with improved visual acuity. Demarcation line depth was found to be shallower than conventional CXL. Therefore, the long-term efficacy of CA-CXL requires further study. CLINICAL TRIAL REGISTRY NUMBER: NCT04504578 Clinical trials.gov.

An investigative study of antitumor properties of a novel thiazolo[4,5-d]pyrimidine small molecule revealing superior antitumor activity with CDK1 selectivity and potent pro-apoptotic properties.

New thiazolo[4,5-d]pyrimidine analogues were synthesized and biologically assessed in-vitro for their antineoplastic activity. The growth inhibitory effects of these compounds were assessed through the National Cancer Institute-United States of America (NCI-USA) anticancer screening program. Compound5(7-Chloro-3-(2,4-dimethoxyphenyl)-5-methylthiazolo[4,5-d]pyrimidine-2(3H)-thione) was found to have a potent and broad-spectrum cytotoxic action against NCI panel with GI50 (50% growth inhibition concentration) mean graph midpoint (MG-MID) = 2.88 µM. MTT assay was used to determine IC50 values of the most potent agent against HCT-116 colorectal carcinoma and WI-38 human lung fibroblast cell lines; 5.33 µM ± 0.69 and 21.69 µM ± 1.04, respectively. Flow cytometric analysis revealed that compound5triggered apoptosis and G2/M cell cycle arrest. The ability of compound5to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyclin B complex was evaluated, and its IC50 value was 97 nM ± 2.33. Moreover, according to the gene expression analysis, compound5up-regulated p53, BAX, cytochrome c, caspases-3,-8 and-9 besides down-regulated Bcl-2. In conclusion, compound5exerted a potent pro-apoptotic activity through the activation of the intrinsic apoptotic pathway and arrested the cell cycle at the G2/M phase.

The expression of propionicin PLG-1 gene (plg-1) by lactic starters.

Propionicin PLG-1 is a bacteriocin produced by Propionibacterium thoenii P127. Such bacteriocin inhibits wide range of food-borne pathogens such as pathogenic Escherichia coli, Pseudomonas aeruginosa, Vibrio parahaemolyticus, Yersinia enterocolitica and a strain of Corynebacterium sp. In the present study, plg-1 gene expressing propionicin PLG-1 was isolated, sequenced for the first time and the resulting sequence was analysed using several web-based bioinformatics programs. The PCR product containing plg-1 gene was transferred to different lactic acid bacterial (LAB) strains using pLEB590 as a cloning vector to give the modified vector pLEBPLG-1. LAB transformants showed an antimicrobial activity against Esch. coli DH5α (most affected strain), Listeria monocytogenes 18116, and Salmonella enterica 25566 as model pathogenic strains. Such LAB transformants can be used in dairy industry to control the food-borne pathogens that are largely distributed worldwide and to feed schoolchildren in the poor countries where dangerous epidemic diseases and diarrhoea prevail.

Effect of fiber addition on strength and toughness of rubberized concretes.

In this paper, an experimental study was conducted to examine the static and dynamic behaviors of rubberized fiber-reinforced concrete (RFRC). Crumb rubber was partially replaced from sand at volume fractions of 0%, 5%, 10%, 15%, and 20%. Steel fibers (SFs) with fiber volume fractions (Vf%) of 0%, 0.5%, 1%, and 1.5% were used for the production of FRCs, while polypropylene fiber (PPF) with Vf% = 0.4% was adopted to produce others FRCs. A combination of 0.4% PPF and 1% SF was used for hybrid FRC. The static properties were evaluated through compression, indirect tension, and flexural tests. However, the drop weight impact test was conducted to assess the dynamic property by estimating the impact energy. It was observed that the replacement of sand with rubber reduced all mechanical properties of concrete. In the case of RFRC, a reduction in compressive strength, compared to samples without fibers, was noted, and this reduction increased with higher Vf%. Both toughness indices and fracture energy were affected slightly by increasing rubber percentages while markedly increased with higher Vf%. However, adding rubber and/or fibers enhanced the impact energy of concrete.

Efficacy of selenium on patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

INTRODUCTION: Postoperative complications pose significant challenges in cardiac surgery and with the evolution of selenium as a potential anti-inflammatory agent, some studies reported its inefficiency. Thus, we conducted our meta-analysis to evaluate the impact of selenium supplementation on cardiac surgery patients. METHODS: Different databases such as PubMed, Embase, and Cochrane Library from inception till January 2024 were searched identifying a total of seven randomized-controlled trials involving selenium supplementation after cardiac surgery. Risk ratio (RR) and Mean difference (MD) were calculated with a 95% confidence interval (CI). RESULTS: The selenium intervention significantly raised the incidence of Acute Kidney injury (RR 0.76; 95% CI: 0.59, 0.98; P = 0.04) while significantly reducing the duration of hospital stay (MD -1.33; 95% CI: -2.51, -0.16; P = 0.03) and postoperative CRP levels (SMD -0.18; 95% CI: -0.34, -0.02; P = 0.03). The effect of selenium intervention on days spent in ICU (MD -0.01; 95% CI: -0.28, 0.25; P = 0.92), mortality (RR 1.07; 95% CI: 0.84, 1.37; P = 0.57) and incidence of hospital acquired infections (RR 0.98; 95% CI: 0.76, 1.26; P = 0.88) is insignificant. CONCLUSION: Selenium supplementation did not significantly reduce major postoperative complications in cardiac surgery patients. However, its ability to modulate inflammation, as reflected in decreased C-reactive protein levels, highlights its potential role in managing the inflammatory response. Future investigations should focus on optimized selenium supplementation strategies in conjunction with other antioxidants to enhance its benefits.

COVID-19 VACCINE-INDUCED ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: CASE REPORTS.

BACKGROUND: Acute exudative polymorphous vitelliform maculopathy is a presumed retinal pigment epithelium abnormality that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear, despite the typical clinical features. PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy occurring after vaccination with a COVID-19 vaccine. CASE REPORTS: Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence, and lack of fluorescein dye leakage. Evidence of retinal pigment epithelium dysfunction was confirmed by electrooculography. CONCLUSION: Two cases of acute exudative polymorphous vitelliform maculopathy occurring after COVID-19 vaccination were reported. A relationship between the vaccine and the retinal pigment epithelial abnormality development that led to acute exudative polymorphous vitelliform maculopathy was postulate, possibly through autoantibodies against the severe acute respiratory syndrome coronavirus 2 virus structural surface glycoprotein antigens that cross react with the normal retinal pigment epithelial cells.

ACURATE neo2 Transcatheter aortic valve implantation without balloon aortic valvuloplasty - direct ACURATE neo2.

BACKGROUND: ACURATE neo2 (Neo2) implantation is performed after systematic Balloon Aortic Valvuloplasty (BAV) in most patients. No reports exist about the feasibility and safety of direct Neo2 transcatheter aortic valve implantation (TAVI) in comparison to the standard practice. AIM: We aimed to identify the patients' baseline anatomical characteristics, procedural, and early post-procedural outcomes in patients treated using Neo2 with and without BAV. METHODOLOGY: This is a retrospective multicentre analysis of 499 patients with severe aortic stenosis who underwent TAVI using Neo2. The comparison was done according to the performance or omission of BAV. Echocardiography and computed tomography were analysed by an independent Core Lab. Propensity score matching (PSM) was performed based on the annular diameter and AV calcium volume, which identified 84 matched pairs. RESULTS: Among the cohort included, 391 (78%) patients received BAV (BAV-yes) and 108 (22%) were not attempted (BAV-no or Direct TAVI). Patients in BAV-no cohort had smaller annular diameter (22.6 vs 23.4 mm; p < 0.001) and lower calcium volume (163 vs 581 mm3; p < 0.001) compared to BAV-yes cohort. In the matched cohort, VARC-3 device technical success was similar (95%) and all other outcome measures were statistically comparable between cohorts. CONCLUSION: Direct TAVI using ACURATEneo2 without pre-TAVI balloon aortic valvuloplasty in patients with mild or less valve calcifications might be feasible and associated with comparable early outcomes compared to patients with similar anatomical features undergoing systematic balloon valvuloplasty.

Predictors of Conduction Disturbances Requiring New Permanent Pacemaker Implantation following Transcatheter Aortic Valve Implantation Using the Evolut Series.

(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM at 30 days after TAVI using Evolut R/PRO/PRO+; (2) Methods: Consecutive patients who underwent TAVI with the Evolut platform between October 2019 and August 2022 at University Hospital Galway, Ireland, were included. Patients who had a prior PPM (n = 10), valve-in-valve procedures (n = 8) or received >1 valve during the index procedure (n = 3) were excluded. Baseline clinical, electrocardiographic (ECG), echocardiographic and multislice computed tomography (MSCT) parameters were analyzed. Pre-TAVI MSCT analysis included membranous septum (MS) length, a semi-quantitative calcification analysis of the aortic valve leaflets, left ventricular outflow tract, and mitral annulus. Furthermore, the implantation depth (ID) was measured from the final aortography. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal MS and ID cutoff values to predict new PPM requirements, respectively; (3) Results: A total of 129 TAVI patients were included (age = 81.3 ± 5.3 years; 36% female; median EuroSCORE II 3.2 [2.0, 5.4]). Fifteen patients (11.6%) required PPM after 30 days. The patients requiring new PPM at 30 days were more likely to have a lower European System for Cardiac Operative Risk Evaluation II, increased prevalence of right bundle branch block (RBBB) at baseline ECG, have a higher mitral annular calcification severity and have a shorter MS on preprocedural MSCT analysis, and have a ID, as shown on the final aortogram. From the multivariate analysis, pre-TAVI RBBB, MS length, and ID were shown to be predictors of new PPM. An MS length of <2.85 mm (AUC = 0.85, 95%CI: (0.77, 0.93)) and ID of >3.99 mm (area under the curve (AUC) = 0.79, (95% confidence interval (CI): (0.68, 0.90)) were found to be the optimal cut-offs for predicting new PPM requirements; (4) Conclusions: Membranous septum length and implantation depth were found to be independent predictors of new PPM post-TAVI with the Evolut platform. Patient-specific implantation depth could be used to mitigate the requirement for new PPM.

Machine Learning-Assisted Recurrence Prediction for Patients With Early-Stage Non-Small-Cell Lung Cancer.

PURPOSE: Stratifying patients with cancer according to risk of relapse can personalize their care. In this work, we provide an answer to the following research question: How to use machine learning to estimate probability of relapse in patients with early-stage non-small-cell lung cancer (NSCLC)? MATERIALS AND METHODS: For predicting relapse in 1,387 patients with early-stage (I-II) NSCLC from the Spanish Lung Cancer Group data (average age 65.7 years, female 24.8%, male 75.2%), we train tabular and graph machine learning models. We generate automatic explanations for the predictions of such models. For models trained on tabular data, we adopt SHapley Additive exPlanations local explanations to gauge how each patient feature contributes to the predicted outcome. We explain graph machine learning predictions with an example-based method that highlights influential past patients. RESULTS: Machine learning models trained on tabular data exhibit a 76% accuracy for the random forest model at predicting relapse evaluated with a 10-fold cross-validation (the model was trained 10 times with different independent sets of patients in test, train, and validation sets, and the reported metrics are averaged over these 10 test sets). Graph machine learning reaches 68% accuracy over a held-out test set of 200 patients, calibrated on a held-out set of 100 patients. CONCLUSION: Our results show that machine learning models trained on tabular and graph data can enable objective, personalized, and reproducible prediction of relapse and, therefore, disease outcome in patients with early-stage NSCLC. With further prospective and multisite validation, and additional radiological and molecular data, this prognostic model could potentially serve as a predictive decision support tool for deciding the use of adjuvant treatments in early-stage lung cancer.

Thoracoscopic excision of the sympathetic chain: an easy and effective treatment for hyperhidrosis in children.

BACKGROUND: Thoracoscopic sympathectomy (TS) is an effective treatment for hyperhidrosis. Various surgical approaches are described in the literature. We describe the technique of thoracoscopic excision of the sympathetic chain done exclusively in children younger than 13 years. METHODS: All patients younger than 13 years who underwent TS from 2006 at a single institution were prospectively identified and fully evaluated with emphasis on demographic data, age, surgical management, complications and follow-up. All patients were contacted again at the end of 2009 to complete a follow-up questionnaire. RESULTS: Twelve patients underwent TS between 2006 and 2009. Age ranged from 6 to 13 years. This involved T2-T3 excision for nine patients with isolated palmar hyperhidrosis, and T2-T3-T4 excision for three with additional axillary hyperhidrosis. Six underwent bilateral TS at the same session and six underwent unilateral TS for the dominant side. Four of them had their contralateral operation performed 2-3 months later. Dry limbs were immediately achieved in all patients. Compensatory sweating (CS) was noted in eight patients. Complications included transient ptosis in two and mild recurrence in one. CONCLUSIONS: Thoracoscopic excision of the sympathetic chain is a simple and safe procedure that relieves hyperhidrosis in all cases and significantly improves the quality of life.