Recent developments in the management of resistant hypertension: focus on endothelin receptor antagonists.

Resistant hypertension is characterized by the inability of guideline-recommended triple combination therapy to control blood pressure (BP) to target. It is associated with a significantly increased risk of adverse outcomes. Despite abundant preclinical evidence supporting the critical role of the endothelin pathway in resistant hypertension (RH), clinical implementation of endothelin antagonists for the treatment of hypertension was hindered by various factors. Recently, the novel dual endothelin-receptor antagonist aprocitentan was tested in individuals with resistant hypertension in the PRECISION trial and provided compelling evidence supporting both short and longer-term safety and clinically meaningful and sustained BP lowering efficacy. These findings resulted in the recent regulatory approval of aprocitentan by the FDA. Aprocitentan may be a particularly useful antihypertensive option for individuals with advanced age, chronic kidney disease, and albuminuria.

What is this article about? Elevated blood pressure that remains uncontrolled despite recommended drug treatment with at least three established medications including a diuretic, also known as resistant hypertension, is a worldwide health concern and leaves many patients at high risk for adverse cardiovascular consequences such as heart attacks, strokes, and chronic kidney disease. While past research suggested the potential utility of endothelin receptor antagonists in managing hypertension, their efficacy remained unconfirmed until recently.What are the results of the PRECISION study? The PRECISION study examined the safety and efficacy of a novel dual endothelin receptor antagonist aprocitentan in individuals with resistant hypertension. The trial demonstrated that aprocitentan effectively lowered blood pressure both with short- and long-term administration and that it had a favorable safety profile.What do the results of the PRECISION study mean? As a direct consequence of the trial findings, aprocitentan is now approved by the US FDA for the treatment of uncontrolled blood pressure. This drug may prove particularly useful in individuals with clinical features known to render elevated blood pressure more difficult to control such as advanced age, chronic kidney disease, and increased levels of protein in their urine.

Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

Atypical Vaginal Aggressive Angiomyxoma in a Virgin: A Case Report from South Jordan.

Aggressive angiomyxoma is a locally invasive, rarely diagnosed mesenchymal tumor that predominantly affects the perineal region of women in their reproductive years. It is typically found in areas such as the vagina, vulva, and other pelvic soft tissues, but its presentation can be highly variable. We describe a particularly unique case of aggressive angiomyxoma, presenting in an atypical manner within the vaginal region of a 31-year-old virgin woman. This case is noteworthy for the unusual growth pattern of the angiomyxoma-located strictly within the vaginal epithelium, showing no signs of invasion into surrounding tissues, which is not typical of the aggressive nature of this type of tumor. The patient presented with a mass that protruded through the hymen, an uncommon presentation that led to initial speculation about the nature of the mass. The definitive diagnosis of aggressive angiomyxoma was made by meticulous histopathological examination after surgical excision of the mass. This case emphasizes the critical importance of considering aggressive angiomyxoma in the differential diagnosis of vaginal masses, particularly those that do not exhibit invasive characteristics. The case also highlights the need for increased awareness among clinicians about the potential for atypical presentations of this rare tumor, to facilitate timely and accurate diagnosis, and to guide appropriate management strategies. This report contributes to the growing body of literature on aggressive angiomyxoma, highlighting the variability in its presentation and the need to heighten suspicion in atypical cases.

Monkeypox infection and pregnancy in lower and middle-income countries: Precautions & recommendations.

Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.

Assessment of PD-1 and PD-L1 tissue expression levels in lichen planus patients: a case-control study.

Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case-control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.

Taming resistant hypertension: The promise of novel pharmacologic approaches and renal denervation.

Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways unaddressed by guideline-recommended therapy. While spironolactone is widely considered as the preferable fourth-line drug, its broad application is limited by its side effect profile, especially off-target steroid receptor-mediated effects and hyperkalaemia in at-risk subpopulations. Recent landmark trials have reported promising safety and efficacy results for a number of novel compounds targeting relevant pathophysiologic pathways that remain unopposed by contemporary drugs. These include the dual endothelin receptor antagonist, aprocitentan, the aldosterone synthase inhibitor, baxdrostat and the nonsteroidal mineralocorticoid receptor antagonist finerenone. Furthermore, the evidence base for consideration of catheter-based renal denervation as a safe and effective adjunct therapeutic approach across the clinical spectrum of hypertension has been further substantiated. This review will summarise the recently published evidence on novel antihypertensive drugs and renal denervation in the context of resistant hypertension.

Monkeypox infection and pregnancy in lower and middle-income countries: Precautions & recommendations

Abstract Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention.

Over the past decade, there have been significant developments in treatment for ovarian cancer, yet the lack of targeted therapy with few side effects still represents a major issue. The cytochrome P450 (CYP) enzyme family plays a vital role in the tumorigenesis process and metabolism of drugs and has a negative impact on therapy outcomes. Gaining more insight into CYP expression is crucial to understanding the pathophysiology of ovarian cancer since many isoforms are essential to the metabolism of xenobiotics and steroid hormones, which drive the disease's development. To the best of our knowledge, no review articles have documented the intratumoral expression of CYPs and their implications in ovarian cancer. Therefore, the purpose of this review is to provide a clear understanding of differential CYP expression in ovarian cancer and its implications for the prognosis of ovarian cancer patients, together with the effects of CYP polymorphisms on chemotherapy metabolism. Finally, we discuss opportunities to exploit metabolic CYP expression for the development of novel therapeutic methods to treat ovarian cancer.

Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients.

BACKGROUND: Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients. METHODS: A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique. RESULTS: T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes. CONCLUSION: The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

The present study revealed a positive significant association between the leptin (LEP) genetic polymorphism rs7799039, fasting blood sugar, and post-prandial blood sugar.LEP levels might be utilised to predict T2DM. The AA genotype of LEP rs7799039, 2548G/A (co-dominant model) raises the risk of diabetes compared to the GA genotype, and the A alle is considered a risk factor OR = 1.66.A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548G/A) and serum LEP in patients and controls.

Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension.

PURPOSE OF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10-15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy. RECENT FINDINGS: Despite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan. Findings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.

Obstetric Violence among Pregnant Jordanian Women: An Observational Study between the Private and Public Hospitals in Jordan.

BACKGROUND: Obstetric Violence (OV) is a public health matter that affects women and their children with an incidence rate between 18.3-75.1% globally. The delivery institution of public and private sectors represents a potential factor contributing to OV. This study aimed to assess OV existence among sample of pregnant Jordanian women and its risk factors domains between public and private hospitals. METHODOLOGY: This is a case-control study including 259 recently delivered mothers from Al-Karak Public and Educational Hospital and The Islamic Private Hospital. A designated questionnaire including demographic variables and OV domains was used for data collection. RESULTS: A significant difference was seen between patients delivering in the public sector compared to patients delivering the private sector in education level, occupation, monthly income, delivery supervision and overall satisfaction. Patients delivering in the private sector showed a significantly less physical abuse by the medical staff compared to patients delivering in the public sector, and patients delivering in a private room also showed a significantly less OV and risk of physical abuse compared to patients delivering in shared room. In public settings, medications information was lesser versus the private ones, additionally, there is significant association between performing episiotomy, physical abuse by staff and the delivery in shared rooms in private settings. CONCLUSION: This study showed that OV was less susceptible during childbirth in private settings compared to public settings. Educational status, low monthly income, occupation are risk factors for OV; also, features of disrespect and abuse like obtaining consent for episiotomy performance, delivery provision updates, care perception based on payment ability and medication information were reported.

Cytochrome 4Z1 Expression Connotes Unfavorable Prognosis in Ovarian Cancers.

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients.

Cough as a clinical manifestation of large vessel vasculitis.

Cough is not a widely recognised symptom of large vessel vasculitides. If not promptly diagnosed and treated, large vessel vasculitis can have serious clinical consequences. We present the case of a 76-year-old man who presented with a subacute history of persistent dry cough, was found to have extensive aortitis on imaging, and experienced rapid resolution of symptoms with immunosuppression.

Retinal Capillary Damage Is Already Evident in Patients With Hypertension and Prediabetes and Associated With HbA1c Levels in the Nondiabetic Range.

OBJECTIVE: We analyzed whether any change in capillary density in the retinal circulation could be detected in patients with hypertension in the prediabetic stage. RESEARCH DESIGN AND METHODS: In a cross-sectional analysis, we assessed capillary density in the foveal (CDF) and parafoveal retinal areas using optical coherence tomography-angiography in 62 patients with hypertension and normal glucose metabolism and 40 patients with hypertension and prediabetes. RESULTS: The CDF was lower in patients with prediabetes than in those with normal glucose metabolism. Moreover, we found a correlation between CDF and HbA1c and glucose levels for the entire cohort. In patients with HbA1c <6.5% (48 mmol/mol), CDF was lower in patients with HOMA for insulin resistance (HOMA-IR) ≥2.5 than in patients with HOMA-IR <2.5. CONCLUSIONS: Patients with hypertension and prediabetes display retinal capillary changes, and an association with markers of glucose metabolism exists, even within a nondiabetic HbA1c range.

Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition.

PURPOSE OF REVIEW: The moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition. RECENT FINDINGS: SGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease. Indeed, recent experimental data in relevant animal models highlight a bidirectional interaction between sympathetic nervous system activation and SGLT2 expression, and this facilitates several of the features associated with SGLT2 inhibition observed in clinical trials including improved glucose metabolism, weight loss, increased diuresis, and lowering of blood pressure. Currently available data highlight the various levels of interaction between the sympathetic nervous system and SGLT2 expression and explores the potential for SGLT2 inhibition as a therapeutic strategy in conditions commonly characterised by sympathetic activation.

Autoencoded deep features for semi-automatic, weakly supervised physiological signal labelling.

BACKGROUND AND AIMS: Machine Learning is transforming data processing in medical research and clinical practice. Missing data labels are a common limitation to training Machine Learning models. To overcome missing labels in a large dataset of microneurography recordings, a novel autoencoder based semi-supervised, iterative group-labelling methodology was developed. METHODS: Autoencoders were systematically optimised to extract features from a dataset of 478621 signal excerpts from human microneurography recordings. Selected features were clusters with k-means and randomly selected representations of the corresponding original signals labelled as valid or non-valid muscle sympathetic nerve activity (MSNA) bursts in an iterative, purifying procedure by an expert rater. A deep neural network was trained based on the fully labelled dataset. RESULTS: Three autoencoders, two based on fully connected neural networks and one based on convolutional neural network, were chosen for feature learning. Iterative clustering followed by labelling of complete clusters resulted in all 478621 signal peak excerpts being labelled as valid or non-valid within 13 iterations. Neural networks trained with the labelled dataset achieved, in a cross validation step with a testing dataset not included in training, on average 93.13% accuracy and 91% area under the receiver operating curve (AUC ROC). DISCUSSION: The described labelling procedure enabled efficient labelling of a large dataset of physiological signal based on expert ratings. The procedure based on autoencoders may be broadly applicable to a wide range of datasets without labels that require expert input and may be utilised for Machine Learning applications if weak-labels were available.

Interaction between sodium-glucose co-transporter 2 and the sympathetic nervous system.

PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have taken centre stage in research and therapeutic efforts to modulate hard clinical outcomes in patients with heightened cardiovascular and renal risk profiles. Sympathetic nervous system (SNS) activation is a prominent feature across several cardiovascular and renal disease states. This review reflects on the remarkable clinical impact of SGLT2 inhibitors on cardiorenal outcomes, and navigates the evidence for a proposed clinically relevant interaction between SGLT2 and the SNS. RECENT FINDINGS: SGLT2 inhibitors exert several pleiotropic effects beyond glucose-lowering. These include, but are not limited to, diuresis and natriuresis, blood pressure lowering, reduction in inflammation and oxidative stress, stimulation of erythropoiesis, and improvement in cardiac energetics. Treatment with SGLT2 inhibitors is associated with significant improvement in cardiorenal outcomes irrespective of diabetes status. In addition, evidence from preclinical studies points to a strong signal of a bidirectional temporal association between SGLT2 inhibition and reduction in SNS activation. SUMMARY: Ongoing preclinical and clinical trials aimed at unravelling the proposed interaction between SGLT and SNS will enhance our understanding of their individual and/or collective contributions to cardiovascular disease progression and guide future targeted therapeutic interventions.

Simultaneously measured inter-arm blood pressure difference is not associated with pulse wave velocity in a clinical dataset of at-risk hypertensive patients.

Recent analysis of systolic inter-arm differences in blood pressure from the INTERPRESS-IPD Collaboration suggest an association with increased all-cause mortality, cardiovascular mortality and cardiovascular events. Previous studies have demonstrated associations with other risk parameters. We aimed to reproduce these associations in a cohort of 199 treated, at-risk hypertensive patients with pulse wave velocity (PWV) as a surrogate marker of cardiovascular (CV) damage. Simultaneously measured inter-arm blood pressure (BP) differences, 24 hour ambulatory BP and PWV were measured in 199 treated patients from a tertiary hospital hypertension outpatient clinic. Associations between systolic inter-arm BP difference and PWV were analyzed with uni- and multi-variate regression models. Out of 199 participants, 90 showed an inter-arm BP difference of more than 5 mmHg. The inter-arm difference was not associated with PWV. Furthermore, neither observed single BP measurements nor 24 hour ambulatory BP was associated with inter-arm BP differences. In our clinical patient cohort we failed to observe an association between inter-arm BP differences and PWV. Mode of assessment, study design and the sample characteristics of this treated, hypertensive cohort may have contributed to the negative findings. The limited sample size of the study poses a challenge to the detection of smaller effects in our study.

K-means panning - Developing a new standard in automated MSNA signal recognition with a weakly supervised learning approach.

BACKGROUND: Accessibility of labelled datasets is often a key limitation for the application of Machine Learning in clinical research. A novel semi-automated weak-labelling approach based on unsupervised clustering was developed to classify a large dataset of microneurography signals and subsequently used to train a Neural Network to reproduce the labelling process. METHODS: Clusters of microneurography signals were created with k-means and then labelled in terms of the validity of the signals contained in each cluster. Only purely positive or negative clusters were labelled, whereas clusters with mixed content were passed on to the next iteration of the algorithm to undergo another cycle of unsupervised clustering and labelling of the clusters. After several iterations of this process, only pure labelled clusters remained which were used to train a Deep Neural Network. RESULTS: Overall, 334,548 individual signal peaks form the integrated data were extracted and more than 99.99% of the data was labelled in six iterations of this novel application of weak labelling with the help of a domain expert. A Deep Neural Network trained based on this dataset achieved consistent accuracies above 95%. DISCUSSION: Data extraction and the novel iterative approach of labelling unsupervised clusters enabled creation of a large, labelled dataset combining unsupervised learning and expert ratings of signal-peaks on cluster basis in a time effective manner. Further research is needed to validate the methodology and employ it on other types of physiologic data for which it may enable efficient generation of large labelled datasets.

Impact of Adjuvant Radiotherapy in Patients with Central Neurocytoma: A Multicentric International Analysis.

BACKGROUND: Central neurocytoma (CN) is a rare tumor accounting for <0.5% of all intracranial tumors. Surgery ± radiotherapy is the mainstay treatment. This international multicentric study aims to evaluate the outcomes of CNs patients after multimodal therapies and identify predictive factors. PATIENTS AND METHODS: We retrospectively identified 33 patients with CN treated between 2005 and 2019. Treatment characteristics and outcomes were assessed. RESULTS: All patients with CN underwent surgical resection. Radiotherapy was delivered in 19 patients. The median radiation dose was 54 Gy (range, 50-60 Gy). The median follow-up time was 56 months. The 5-year OS and 5-year PFS were 90% and 76%, respectively. Patients who received radiotherapy had a significantly longer PFS than patients without RT (p = 0.004) and a trend towards longer OS. In addition, complete response after treatments was associated with longer PFS (p = 0.07). CONCLUSIONS: Using RT seems to be associated with longer survival rates with an acceptable toxicity profile.