Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women

Purpose BRCA gene mutations (BRCAm) have an impact on patients’ characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. Methods This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). Result Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. Conclusion The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. Trial registration Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study

Background: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. Methods: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. Results: The patients’ mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18–4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48–5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). Conclusions: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons

Neuronal signal transmission depends on the frequency, pattern, and timing of spike output, each of which are shaped by spike afterhyperpolarizations (AHPs). There are classically three post-spike AHPs of increasing duration categorized as fast, medium and slow AHPs that hyperpolarize a cell over a range of 10 ms to 30 s. Intensive early work on CA1 hippocampal pyramidal cells revealed that all three AHPs incorporate activation of calcium-gated potassium channels. The ionic basis for a fAHP was rapidly attributed to the actions of big conductance (BK) and the mAHP to small conductance (SK) or Kv7 potassium channels. In stark contrast, the ionic basis for a prominent slow AHP of up to 30 s duration remained an enigma for over 30 years. Recent advances in pharmacological, molecular, and imaging tools have uncovered the expression of a calcium-gated intermediate conductance potassium channel (IK, KCa3.1) in central neurons that proves to contribute to the slow AHP in CA1 hippocampal pyramidal cells. Together the data show that the sAHP arises in part from a core tripartite complex between Cav1.3 (L-type) calcium channels, ryanodine receptors, and IK channels at endoplasmic reticulum-plasma membrane junctions. Work on the sAHP in CA1 pyramidal neurons has again quickened pace, with identified contributions by both IK channels and the Na-K pump providing answers to several mysteries in the pharmacological properties of the sAHP.

Evaluation of temporal processing skills in individuals with normal hearing

Objective: In a cumulative perspective, the aim of this study is to perform Frequency Pattern Test (FPT), Duration Pattern Test (DPT) and Gap In Noise (GIN) Test in order to determine descriptive values of these tests to evaluate central auditory processing on the individuals’ with normal hearing. Material and Methods: A total of 52 participants, as of 28 women and 24 men, with normal hearing, within the age range of 20 to 55 were included in the study. Otoscopic examination, pure tone audiometry and FPT, DPT GIN Test which are central auditory processing tests, were performed on the participants who meet the criteria of the study and voluntarily agreed to participate in the study. Results: Descriptive values were obtained as an average of 78% in FPT, 92.11% in DPT, an average of 61.22% in GIN Test and an average of 6.34 ms in Gap Detection Threshold Conclusions: It is thought that the obtained descriptive values will contribute to the clinics and the literature. Keywords: Auditory temporal tests, central auditory processing, duration pattern test, frequency pattern test, gap in noise test

Individual Stability of Pain- and Touch-Related Neuronal Gamma Oscillations

Background: The processing of brief pain and touch stimuli has been associated with an increase of neuronal oscillations in the gamma range (40-90 Hz). However, some studies report divergent gamma effects across single participants. Methods: In two repeated sessions we recorded gamma responses to pain and touch stimuli using EEG. Individual gamma responses were extracted from EEG channels and from ICA components that contain a strong gamma amplitude. Results: We observed gamma responses in the majority of the participants. If present, gamma synchronisation was always bound to a component that contained a laser-evoked response. We found a broad variety of individual cortical processing: some participants showed a clear gamma effect, others did not exhibit any gamma. For both modalities, the effect was reproducible between sessions. In addition, participants with a strong gamma response showed a similar time-frequency pattern across sessions. Conclusions: Our results indicate that current measures of reproducibility of research results do not reflect the complex reality of the diverse individual processing pattern of applied pain and touch. The present findings raise the question of whether we would find similar quantitatively different processing patterns in other domains in neuroscience: group results would be replicable but the overall effect is driven by a subgroup of the participants.

PseUdeep: RNA Pseudouridine Site Identification with Deep Learning Algorithm

Background: Pseudouridine (Ψ) is a common ribonucleotide modification that plays a significant role in many biological processes. The identification of Ψ modification sites is of great significance for disease mechanism and biological processes research in which machine learning algorithms are desirable as the lab exploratory techniques are expensive and time-consuming.Results: In this work, we propose a deep learning framework, called PseUdeep, to identify Ψ sites of three species: H. sapiens, S. cerevisiae, and M. musculus. In this method, three encoding methods are used to extract the features of RNA sequences, that is, one-hot encoding, K-tuple nucleotide frequency pattern, and position-specific nucleotide composition. The three feature matrices are convoluted twice and fed into the capsule neural network and bidirectional gated recurrent unit network with a self-attention mechanism for classification.Conclusion: Compared with other state-of-the-art methods, our model gets the highest accuracy of the prediction on the independent testing data set S-200; the accuracy improves 12.38%, and on the independent testing data set H-200, the accuracy improves 0.68%. Moreover, the dimensions of the features we derive from the RNA sequences are only 109,109, and 119 in H. sapiens, M. musculus, and S. cerevisiae, which is much smaller than those used in the traditional algorithms. On evaluation via tenfold cross-validation and two independent testing data sets, PseUdeep outperforms the best traditional machine learning model available. PseUdeep source code and data sets are available at https://github.com/dan111262/PseUdeep.

Frequency, Pattern, and Associations of Renal Iron Accumulation in Sickle Beta-Thalassemia

Background: Chronically transfused homozygous sickle cell disease (HbSS) patients were shown to have higher kidney iron deposition than thalassemia major patients, not associated to total body iron and mainly caused by chronic hemolysis. Kidney iron deposition has not been explored in sickle beta-thalassemia (Sβ-thal), resulting from the inheritance of both sickle cell and beta-thalssemia genes. Aim: This multi center study aimed to study frequency, pattern, and associations of renal iron accumulation in sickle beta-thalassemia. Methods: Thirty-three Sβ-thal patients (36.49±14.72 years; 13 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network were considered. Moreover, 20 healthy subjects, 14 HbSS patients and 71 thalassemia major (TM) patients were included as comparison groups. Hepatic, cardiac, pancreatic, and renal iron overload was quantified by the gradient-echo T2* technique. In each kidney T2* was measured in anterior, posterolateral, and posteromedial parenchymal regions and the global T2* value was calculated as the average of the two kidneys T2* values. Results. Global renal T2* were significantly higher in healthy subjects versus both Sβ-thal patients (49.68±10.09 ms vs 43.19±8.07 ms; P=0.013) and HbSS patients (49.68±10.09 ms vs 26.21±17.07 ms; P&lt;0.0001). Sβ-thal patients showed comparable age, sex, frequency of regular transfusion, hematochemical parameters, and hepatic, cardiac and pancreatic iron load than HbSS patients, but they had a significant lower frequency of renal iron overload (global renal T2*&lt;31 ms) (9.1% vs 57.1%; P=0.001). Regularly transfused patients (16 Sβ-thal and 10 HbSS) were compared with TM patients, homogeneous for age and sex, but TM started regular transfusions significantly earlier and they were more frequently chelated. No significant difference was detected in terms of hepatic and cardiac iron levels, but TM patients had significantly lower pancreas T2* values than both the other two groups and significantly higher global renal T2* values than HbSS patients (42.87±9.43 ms vs 24.39±15.74 ms; P=0.001). In Sβ-thal patients no significant difference was detected between T2* values in left and right kidneys, and global renal T2* values were not associated to age, gender, splenectomy, and they were comparable between regularly transfused and non transfused patients. No correlation was detected between renal T2* values and serum ferritin levels or iron load in the other organs. Global renal T2* values were not associated with serum creatinine levels but showed a significant inverse correlation with serum lactate dehydrogenase (Figure 1). Conclusion. Renal iron deposition is not common in Sβ-thal patients, with a prevalence significantly lower compared to that of HbSS patients, but with a similar underlying mechanism due to the chronic hemolysis. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees.

Selection of window functions for predicting the frequency pattern of vibrations of the technological process using an artificial neural network

The frequency pattern of the process is investigated by analyzing spectrograms constructed using the window Fourier transform. A set of window functions consists of a rectangular, membership, and windows based on atomic functions. The fulfillment of the condition for improving the time localization and energy concentration in the central part of the window allows one to select a window function. The resulting spectrograms are fed to the input of an artificial neural network to obtain a forecast. Varying the shape of the window functions allows us to analyze the proposed spectrogram prediction model.

Auditory Processing Disorder Test Battery in European Portuguese—Development and Normative Data for Pediatric Population

There is an increasing need for state-of-the-art Central Auditory Processing assessment for Portuguese native speakers, applicable as early as possible. As a contribution to answering this need, this paper presents a new battery for Central Auditory Processing assessment for European Portuguese applicable to children aged 5 and above, named BAPA-PE, providing information regarding test selection and development. The battery consists of six behavioral tests: Staggered Spondaic Words (SSW) for European Portuguese, Filtered Speech, Speech in Noise, Detection Interval in Noise, Duration, and Frequency Pattern. The normative data for children aged 5 to 12 are also reported. A sample was obtained of 217 subjects without ear pathology and with typical development. Each age group was composed of at least 30 children. All children were evaluated using pure tone audiometry, speech audiometry, impedance, and otoacoustic emissions. Normative scores are reported for each of the six auditory processing tests. The assessment is applicable to young children (aged 5 and 6). The statistical analyses showed significant effects in scores of Age for all tests and of Ear for several tests. The main result from the work presented, the Auditory Processing Assessment Battery—European Portuguese (BAPA-PE), is available for clinical use with normative data. This battery is a new tool for behaviorism assessment of European Portuguese speakers with suspected central auditory pathology and for monitoring the results of auditory training.

Frequency, Pattern and Rationale of Tooth Extractions Among Orthodontic Patients: A 10-year Tertiary Institution Experience

Background and objectives: Tooth extractions are a vital aspect of orthodontic management that enables the orthodontist to achieve good aesthetics and function as well as long term treatment stability for the patient. Extractions may be necessary for various reasons among which are tooth size arch length discrepancy (TSALD), increased overjet and facial profile. The aim of this study was to determine the prevalence, pattern and rationale of tooth extraction among orthodontic patients attending the Orthodontic Unit of the Department of Child Dental Health, University of Port Harcourt Teaching Hospital. Methods. A retrospective study of a cohort of patients who attended one of the outpatient Orthodontic Clinics in the Department of Child Dental Health, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria between 2011 and 2021. Data was collected from the patients’ records. Results. A total of 175 patients comprising 70(40%) males and 105(60%) females were included in the study. 67(38.3%) patients had at least one extraction. Twenty-eight (41.8%) extraction cases had extraction of the first premolars. Two-unit extractions of the maxillary first premolars (13, 46.4%) was the most frequent extraction pattern. Eight (29.6%) had extraction of primary canines only. Twenty-seven (40.3%) participants had extractions due to increased overjet. Over a third of the patients had extraction of at least one tooth. Conclusion. Two-unit extractions of maxillary first premolar was the commonest extraction pattern. Increased overjet was the commonest reason for extraction.