Machine learning for clinical outcome prediction in cerebrovascular and endovascular neurosurgery: systematic review and meta-analysis.

BACKGROUND: Machine learning (ML) may be superior to traditional methods for clinical outcome prediction. We sought to systematically review the literature on ML for clinical outcome prediction in cerebrovascular and endovascular neurosurgery. METHODS: A comprehensive literature search was performed, and original studies of patients undergoing cerebrovascular surgeries or endovascular procedures that developed a supervised ML model to predict a postoperative outcome or complication were included. RESULTS: A total of 60 studies predicting 71 outcomes were included. Most cohorts were derived from single institutions (66.7%). The studies included stroke (32), subarachnoid hemorrhage ((SAH) 16), unruptured aneurysm (7), arteriovenous malformation (4), and cavernous malformation (1). Random forest was the best performing model in 12 studies (20%) followed by XGBoost (13.3%). Among 42 studies in which the ML model was compared with a standard statistical model, ML was superior in 33 (78.6%). Of 10 studies in which the ML model was compared with a non-ML clinical prediction model, ML was superior in nine (90%). External validation was performed in 10 studies (16.7%). In studies predicting functional outcome after mechanical thrombectomy the pooled area under the receiver operator characteristics curve (AUROC) of the test set performances was 0.84 (95% CI 0.79 to 0.88). For studies predicting outcomes after SAH, the pooled AUROCs for functional outcomes and delayed cerebral ischemia were 0.89 (95% CI 0.76 to 0.95) and 0.90 (95% CI 0.66 to 0.98), respectively. CONCLUSION: ML performs favorably for clinical outcome prediction in cerebrovascular and endovascular neurosurgery. However, multicenter studies with external validation are needed to ensure the generalizability of these findings.

Safety and Efficacy of Outpatient Drainless Abdominoplasty: A Single-Surgeon Experience of 454 Consecutive Patients.

BACKGROUND: The incidence of seroma after abdominoplasty is accepted as approximately 10% (with a range) in the literature. Progressive tension sutures (PTS) have arisen as a means of reducing seroma, however there are conflicting data regarding their efficacy. OBJECTIVES: The primary aim of this study was to describe the incidence of postabdominoplasty seroma in the setting of drainless abdominoplasty with PTS. METHODS: A retrospective chart review was performed of all abdominoplasties (n = 454) during a 20-year period. At approximately the halfway point of this time frame, the abdominoplasty technique was changed from the use of 2 drains to the use of PTS without drains. Additionally, pulsed electromagnetic field therapy (PEMF) and liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc., Parsippany, NJ) were added as pain control adjuncts. RESULTS: There were 194 patients in the drain group and 260 patients in the PTS/no drains group. The group without drains contained a significantly higher proportion of massive weight loss patients (4.1% vs 9.2%, P = .041). The majority of the group without drains underwent outpatient surgery (89.7% vs 98.8%, P < .001). The overall complication rate was significantly lower in the no drains group (31.4% vs 13.8%, P < .001). The incidence of seroma was dramatically reduced in the group without drains (24.7% vs 0.0%, P < .001). CONCLUSIONS: PTS are highly effective in preventing seroma and can be safely employed as an alternative to drains in abdominoplasty. PEMF may play a role in seroma prevention and is also helpful for pain control. With these techniques to mitigate complications and minimize postoperative pain, abdominoplasty can be performed safely and effectively in a purely outpatient setting.

Timing of Chromosome DNA Integration throughout the Yeast Cell Cycle.

The dynamic mechanism of cell uptake and genomic integration of exogenous linear DNA still has to be completely clarified, especially within each phase of the cell cycle. We present a study of integration events of double-stranded linear DNA molecules harboring at their ends sequence homologies to the host's genome, all throughout the cell cycle of the model organism Saccharomyces cerevisiae, comparing the efficiency of chromosomal integration of two types of DNA cassettes tailored for site-specific integration and bridge-induced translocation. Transformability increases in S phase regardless of the sequence homologies, while the efficiency of chromosomal integration during a specific cycle phase depends upon the genomic targets. Moreover, the frequency of a specific translocation between chromosomes XV and VIII strongly increased during DNA synthesis under the control of Pol32 polymerase. Finally, in the null POL32 double mutant, different pathways drove the integration in the various phases of the cell cycle and bridge-induced translocation was possible outside the S phase even without Pol32. The discovery of this cell-cycle dependent regulation of specific pathways of DNA integration, associated with an increase of ROS levels following translocation events, is a further demonstration of a sensing ability of the yeast cell in determining a cell-cycle-related choice of DNA repair pathways under stress.

It Is Just a Matter of Time: Balancing Homologous Recombination and Non-homologous End Joining at the rDNA Locus During Meiosis.

Ribosomal RNA genes (rDNAs) are located in large domains of hundreds of rDNA units organized in a head-to-tail manner. The proper and stable inheritance of rDNA clusters is of paramount importance for survival. Yet, these highly repetitive elements pose a potential risk to the genome since they can undergo non-allelic exchanges. Here, we review the current knowledge of the organization of the rDNA clusters in Arabidopsis thaliana and their stability during meiosis. Recent findings suggest that during meiosis, all rDNA loci are embedded within the nucleolus favoring non-homologous end joining (NHEJ) as a repair mechanism, while DNA repair via homologous recombination (HR) appears to be a rare event. We propose a model where (1) frequent meiotic NHEJ events generate abundant single nucleotide polymorphisms and insertions/deletions within the rDNA, resulting in a heterogeneous population of rDNA units and (2) rare HR events dynamically change rDNA unit numbers, only to be observed in large populations over many generations. Based on the latest efforts to delineate the entire rDNA sequence in A. thaliana, we discuss evidence supporting this model. The results compiled so far draw a surprising picture of rDNA sequence heterogeneity between individual units. Furthermore, rDNA cluster sizes have been recognized as relatively stable when observing less than 10 generations, yet emerged as major determinant of genome size variation between different A. thaliana ecotypes. The sequencing efforts also revealed that transcripts from the diverse rDNA units yield heterogenous ribosome populations with potential functional implications. These findings strongly motivate further research to understand the mechanisms that maintain the metastable state of rDNA loci.

Conservation and divergence of meiotic DNA double strand break forming mechanisms in Arabidopsis thaliana.

In the current meiotic recombination initiation model, the SPO11 catalytic subunits associate with MTOPVIB to form a Topoisomerase VI-like complex that generates DNA double strand breaks (DSBs). Four additional proteins, PRD1/AtMEI1, PRD2/AtMEI4, PRD3/AtMER2 and the plant specific DFO are required for meiotic DSB formation. Here we show that (i) MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, (ii) PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between the DSB-forming and resection machineries, (iii) DFO controls MTOPVIB foci formation and is part of a divergent RMM-like complex including PHS1/AtREC114 and PRD2/AtMEI4 but not PRD3/AtMER2, (iv) PHS1/AtREC114 is absolutely unnecessary for DSB formation despite having a conserved position within the DSB protein network and (v) MTOPVIB and PRD2/AtMEI4 interact directly with chromosome axis proteins to anchor the meiotic DSB machinery to the axis.

From Microscopy to Nanoscopy: Defining an Arabidopsis thaliana Meiotic Atlas at the Nanometer Scale.

Visualization of meiotic chromosomes and the proteins involved in meiotic recombination have become essential to study meiosis in many systems including the model plant Arabidopsis thaliana. Recent advances in super-resolution technologies changed how microscopic images are acquired and analyzed. New technologies enable observation of cells and nuclei at a nanometer scale and hold great promise to the field since they allow observing complex meiotic molecular processes with unprecedented detail. Here, we provide an overview of classical and advanced sample preparation and microscopy techniques with an updated Arabidopsis meiotic atlas based on super-resolution microscopy. We review different techniques, focusing on stimulated emission depletion (STED) nanoscopy, to offer researchers guidance for selecting the optimal protocol and equipment to address their scientific question.

Sequencing of the Arabidopsis NOR2 reveals its distinct organization and tissue-specific rRNA ribosomal variants.

Despite vast differences between organisms, some characteristics of their genomes are conserved, such as the nucleolus organizing region (NOR). The NOR is constituted of multiple, highly repetitive rDNA genes, encoding the catalytic ribosomal core RNAs which are transcribed from 45S rDNA units. Their precise sequence information and organization remain uncharacterized. Here, using a combination of long- and short-read sequencing technologies we assemble contigs of the Arabidopsis NOR2 rDNA domain. We identify several expressed rRNA gene variants which are integrated into translating ribosomes in a tissue-specific manner. These findings support the concept of tissue specific ribosome subpopulations that differ in their rRNA composition and provide insights into the higher order organization of NOR2.

Real-Life Multimarker Monitoring in Patients with Heart Failure: Continuous Remote Monitoring of Mobility and Patient-Reported Outcomes as Digital End Points in Future Heart-Failure Trials.

AIMS: Heart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.g., 6-min walking distance [6MWD], blood biomarkers, Kansas City Cardiomyopathy Questionnaire [KCCQ], and echocardiography). METHODS: REALIsM-HF is an ongoing, 12-week, observational study enrolling 80-100 patients aged ≥45 years with HF with preserved ejection fraction (HFpEF; EF ≥45%) or reduced EF (HFrEF; EF ≤35%). Statistical analyses will include examining the association between data from wearables (the AVIVO© mobile patient management patch or VitalPatch© biosensor, and the DynaPort MoveMonitor©), daily ePROs, and conventional HF metrics (e.g., serum/plasma biomarkers, 6MWD, KCCQ, and echocardiographic parameters). The feasibility of and patient compliance with at-home devices will be documented, and the data captured for the purpose of establishing reference values in patients with HFpEF or HFrEF will be summarized. CONCLUSIONS: The REALIsM-HF study is to evaluate the longitudinal daily activity profiles of patients with HF and correlate these with changes in serum/plasma biomarker profiles, symptoms, quality of life, and cardiac function and morphology to inform the use of wearable activity monitors for developing novel therapies and managing patients.

Characteristics and outcomes of patients with normal left atrial pressure undergoing transcatheter mitral valve repair.

OBJECTIVE: A subset of patients at the time of transcatheter mitral valve repair (TMVR) will have normal left atrial pressure (LAP) (<13 mm Hg) despite having severe mitral regurgitation (MR). The goal of this study was to determine clinical characteristics and outcomes in patients with normal LAP undergoing TMVR. METHODS: A single-centre retrospective cohort of consecutive patients who underwent transcatheter edge-to-edge mitral valve clip and continuous LAP monitoring between 5/1/2014 and 5/1/2018 was analysed. One-year mortality was compared by Kaplan-Meier survival curves. Multivariable analysis was performed to identify predictors of normal LAP and 1 year mortality. RESULTS: Of the 204 patients undergoing TMVR, 65% were men and the mean age was 81. Of these patients, 31 (15%) had normal LAP (mean LAP 10.5 mm Hg, mean V wave 16.5 mm Hg) and 173 had elevated LAP (mean LAP 19 mm Hg, mean V wave 32.5 mm Hg). The prevalence of severe MR was not different between groups, although the normal LAP group had significantly lower effective regurgitant orifice area and regurgitant volume. Other notable baseline characteristics including prior cardiac surgery, atrial fibrillation, hypertension, diabetes, congestive heart failure, body mass index, mechanism of MR and ejection fraction were similar between groups. However, there was an increased prevalence of chronic lung disease (CLD) (45.2% vs 17.3%, p<0.001) in the normal LAP group. On multivariate analysis, the only significant predictor of normal LAP was the presence of CLD (OR 4.79 (1.83-12.36), p=0.001) and 1-year mortality was significantly higher in the normal LAP group (32.3% vs 12.7%, p=0.006). After adjustment for comorbidities, normal LAP was no longer a predictor of 1-year mortality (RR 1.62 (0.64-4.06), p=0.32); however, CLD (RR 3.44 (1.37-8.67), p=0.01) remained a statistically significant predictor. CONCLUSION: Normal LAP at the time of TMVR is associated with a higher incidence of CLD which independently predicts increased 1-year mortality. In patients with CLD and apparently severe MR, measurement of LAP may help identify those with lower likelihood of benefit from TMVR.

Targeted Analysis of Chromatin Events (TACE).

Visualization of meiotic chromatin from pollen mother cells has become an essential technique to study meiosis in the model plant Arabidopsis thaliana. Here we present an advanced cytogenetic method that combines improved immunocytology with chromosome painting, thereby generating a tool to quantitatively analyze localization of proteins to any given genomic region. Proteins involved in different processes such as DNA double-strand break formation and recombinational repair can be visualized on meiotic chromatin with the additional feature of assessing their abundance at specific chromosomal locations.

Whole-Mount Immuno-FISH on Arabidopsis Meiocytes (WhoMI-FISH).

Imaging cells, nuclei, and DNA in their natural spatial contexts and configurations is challenging yet required to understand the biology of genome organization, maintenance, and transmission. Live-cell imaging allows capturing dynamic changes of chromosomes in their nuclear and cellular context but lacks resolution. In contrast, imaging of fixed, spread chromosome samples provides unmatched resolution but potentially distorts configurations and spatial relations. Fixed whole-mount samples preserve chromosome configurations and cellular contexts and allow high-resolution imaging. Importantly the latter method allows simultaneous visualization of specific genomic regions (via fluorescent in situ hybridization-FISH) and proteins (via immune-localization using antibodies or tags). Here we present an advanced "whole-mount immuno-FISH" (WhoMI-FISH) method based on the published protocol by Bey Till et al. (Methods Mol Biol 1675:467-480, 2018) specifically optimized for pollen mother cells (PMCs) of Arabidopsis thaliana. It focuses on (1) specimen preparation that maintains meiocyte nuclei positions and genome organization in anthers and also on (2) simultaneous detection of specific genomic regions and meiotic proteins.

Telomerase RNAs in land plants.

To elucidate the molecular nature of evolutionary changes of telomeres in the plant order Asparagales, we aimed to characterize telomerase RNA subunits (TRs) in these plants. The unusually long telomere repeat unit in Allium plants (12 nt) allowed us to identify TRs in transcriptomic data of representative species of the Allium genus. Orthologous TRs were then identified in Asparagales plants harbouring telomere DNA composed of TTAGGG (human type) or TTTAGGG (Arabidopsis-type) repeats. Further, we identified TRs across the land plant phylogeny, including common model plants, crop plants, and plants with unusual telomeres. Several lines of functional testing demonstrate the templating telomerase function of the identified TRs and disprove a functionality of the only previously reported plant telomerase RNA in Arabidopsis thaliana. Importantly, our results change the existing paradigm in plant telomere biology which has been based on the existence of a relatively conserved telomerase reverse transcriptase subunit (TERT) associating with highly divergent TRs even between closely related plant taxa. The finding of a monophyletic origin of genuine TRs across land plants opens the possibility to identify TRs directly in transcriptomic or genomic data and/or predict telomere sequences synthesized according to the respective TR template region.

Meiotic DNA Repair in the Nucleolus Employs a Nonhomologous End-Joining Mechanism.

Ribosomal RNA genes are arranged in large arrays with hundreds of rDNA units in tandem. These highly repetitive DNA elements pose a risk to genome stability since they can undergo nonallelic exchanges. During meiosis, DNA double-strand breaks (DSBs) are induced as part of the regular program to generate gametes. Meiotic DSBs initiate homologous recombination (HR), which subsequently ensures genetic exchange and chromosome disjunction. In Arabidopsis (Arabidopsis thaliana), we demonstrate that all 45S rDNA arrays become transcriptionally active and are recruited into the nucleolus early in meiosis. This shields the rDNA from acquiring canonical meiotic chromatin modifications and meiotic cohesin and allows only very limited meiosis-specific DSB formation. DNA lesions within the rDNA arrays are repaired in an RAD51-independent but LIG4-dependent manner, establishing that nonhomologous end-joining maintains rDNA integrity during meiosis. Utilizing ectopically integrated rDNA repeats, we validate our findings and demonstrate that the rDNA constitutes an HR-refractory genome environment.

Utility of cardiac computed tomography scanning in the diagnosis and pre-operative evaluation of patients with infective endocarditis.

Transesophageal echocardiography (TEE) is the gold standard imaging study used in the diagnosis of infective endocarditis (IE). Computed tomography angiography (CTA) has undergone rapid advancement as a cardiac imaging technique and has previously shown promise in small non-randomized studies for evaluation of IE. We hypothesized that cardiac CTA would perform similarly to TEE in the detection of endocarditic lesions and that there would be no difference in clinical outcomes whether the coronary arteries were evaluated by CTA or invasive coronary angiography (ICA). 255 adults who underwent surgery for IE at the Mayo Clinic Rochester between January 1, 2006 and June 1, 2014 were identified retrospectively. 251 patients underwent TEE and 34 patients underwent cardiac CTA. TEE had statistically higher detection of vegetations (95.6 vs. 70.0%, p < 0.0001) and leaflet perforations (81.3 vs. 42.9%, p = 0.02) as compared to cardiac CTA. For detection of abscess/pseudoaneurysm TEE had a similar sensitivity to cardiac CTA (90.5 vs. 78.4%, p = 0.21). There was no significant difference in peri-operative outcomes whether coronary arteries were evaluated by CTA or ICA. The greatest advantage of cardiac CT in the setting of IE is its ability to couple the detection of complex cardiac anatomic abnormalities with coronary artery delineation, serving two important components of the diagnostic evaluation, particularly among patients who will require surgical intervention due to IE complications. Cardiac CTA may be considered as an alternate coronary artery imaging modality in IE patients with low to intermediate risk of disease but meet guideline recommendations for coronary artery imaging.

Arabidopsis thaliana FANCD2 Promotes Meiotic Crossover Formation.

Fanconi anemia (FA) is a human autosomal recessive disorder characterized by chromosomal instability, developmental pathologies, predisposition to cancer, and reduced fertility. So far, 19 genes have been implicated in FA, most of them involved in DNA repair. Some are conserved across higher eukaryotes, including plants. The Arabidopsis thaliana genome encodes a homolog of the Fanconi anemia D2 gene (FANCD2) whose function in DNA repair is not yet fully understood. Here, we provide evidence that AtFANCD2 is required for meiotic homologous recombination. Meiosis is a specialized cell division that ensures reduction of genomic content by half and DNA exchange between homologous chromosomes via crossovers (COs) prior to gamete formation. In plants, a mutation in AtFANCD2 results in a 14% reduction of CO numbers. Genetic analysis demonstrated that AtFANCD2 acts in parallel to both MUTS HOMOLOG4 (AtMSH4), known for its role in promoting interfering COs and MMS AND UV SENSITIVE81 (AtMUS81), known for its role in the formation of noninterfering COs. AtFANCD2 promotes noninterfering COs in a MUS81-independent manner and is therefore part of an uncharted meiotic CO-promoting mechanism, in addition to those described previously.

Clinical, Radiographic, and Microbiologic Features of Infective Endocarditis in Patients With Hypertrophic Cardiomyopathy.

Infective endocarditis (IE) is an infection of the inner lining of the heart with high morbidity and mortality despite medical and surgical advancements in recent decades. Hypertrophic cardiomyopathy (HC) is one of several medical conditions that have been linked to an increased risk of IE, but there is a paucity of data on this association. We therefore sought to define the clinical phenotype of IE in patients with HC at a single tertiary care center. A retrospective cohort of 30 adult patients with HC diagnosed with IE between January 1, 2006 and December 31, 2016 at Mayo Clinic Rochester were identified. Similar rates of aortic (n = 14) and mitral (n = 16) valve involvement by IE were noted (47% vs 53%). This finding persisted even in patients with left-ventricular outflow tract obstruction and systolic anterior motion of the mitral valve. Symptomatic embolic complications occurred in 10 cases (33%). Surgical intervention was performed in 11 cases (37%). One-year mortality was remarkably low at 7%. In conclusion, in the largest single-center cohort of IE complicating HC, there were similar rates of both mitral and aortic valve involvement regardless of the presence of left ventricular outflow tract obstruction, which is contrary to a long-standing tenet regarding the association of HC and IE. Moreover, no "high risk" IE subset was identified based on HC-related parameters.

Postoperative dyspnoea.

CLINICAL INTRODUCTION: A man in his 50s presented with abscessed aortic valve methicillin-sensitive Staphylococcus aureus endocarditis, received intravenous antibiotics and underwent bioprosthetic aortic valve replacement with removal of all infected tissues. He returned 18 days later with severe dyspnoea, subjective fever and bilateral lower extremity oedema. Physical examination revealed tachypnoea and tachycardia without fever, prominent neck CV waves visible at 90°, left parasternal heave, 3/6 holosystolic murmur across the precordium, lung rales and severe peripheral oedema. C reactive protein was 211 mg/L (normal <8 mg/L). Blood cultures were obtained. ECG showed sinus tachycardia and right axis deviation. Transthoracic echocardiogram (TTE) parasternal zoomed short-axis systolic frame (figure 1A, B), apical four-chamber systolic frame (figure 1C) and subcostal continuous wave (CW) Doppler (figure 1D), are shown. QUESTION: Given the clinical presentation and TTE findings, what is the diagnosis?Severe tricuspid regurgitation due to extension of endocarditisAortic valve obstruction resulting in severe pulmonary hypertensionAcquired Gerbode defectAortic valve dehiscence with severe paraprosthetic regurgitation.

Post-translocational adaptation drives evolution through genetic selection and transcriptional shift in Saccharomyces cerevisiae.

Adaptation by natural selection might improve the fitness of an organism and its probability to survive in unfavorable environmental conditions. Decoding the genetic basis of adaptive evolution is one of the great challenges to deal with. To this purpose, Saccharomyces cerevisiae has been largely investigated because of its short division time, excellent aneuploidy tolerance and the availability of the complete sequence of its genome with a thorough genome database. In the past, we developed a system, named bridge-induced translocation, to trigger specific, non-reciprocal translocations, exploiting the endogenous recombination system of budding yeast. This technique allows users to generate a heterogeneous population of cells with different aneuploidies and increased phenotypic variation. In this work, we demonstrate that ad hoc chromosomal translocations might induce adaptation, fostering selection of thermo-tolerant yeast strains with improved phenotypic fitness. This "yeast eugenomics" correlates with a shift to enhanced expression of genes involved in stress response, heat shock as well as carbohydrate metabolism. We propose that the bridge-induced translocation is a suitable approach to generate adapted, physiologically boosted strains for biotechnological applications.