Normal Function Research Articles

Endoscopic annular chondroperichondrial tympanoplasty, technical description.

Tympanoplasty is a surgical procedure performed to cure middle ear infections and restore normal middle ear function. It is one of the most common procedures in otological surgery. Since Wullstein described tympanoplasty, the microscope has been a widely used surgical tool in otological surgery. Transcanal endoscopic ear surgery (TEES) has come to the forefront as an alternative option due to the various limitations of microscopic surgery and the development of otological surgical techniques. When reviewing the types and tecniques of grafts used in tympanoplasty in the current literature, it is clear that the ideal graft material and tecnique to meet all needs has not yet been found. The objective of this study is to describe a novel graft technique, a modification of the cartilage-perichondrium graft obtained from tragal cartilage, which is believed to represent an optimal solution for the desired graft technique at the highest level. The study included 40 patients who underwent endoscopic annular chondroperichondrial tympanoplasty at Hatay Mustafa Kemal University Hospital between 2015 and 2022. All patients underwent clinical otological examination and pure tone audiometry before and after surgery. Hearing results were expressed as pure tone mean air-bone gap (ABG) at 4 frequencies (500,1000,2000,4000Hz). For all operations, the primary surgeon was the second author. Patients with inadequate follow-up, revision surgery, inflammatory middle ear mucosa, perforation etiology other than chronic otitis media were not included in the study. No complications were observed in the patients included in the study. Accordingly, the graft was intact at the end of the 6th month in 38 of the 40 patients operated on. The graft success rate was 95%. The mean preoperative PTA-ABG was 22.1. The mean post-operative PTA-ABG was 5.7. Mean closed PTA-ABG was 16.4. In parallel with the development of otological surgical technologies, endoscopy is becoming increasingly important in tympanoplasty. We believe that our technique, endoscopic annular chondroperichondrial tympanoplasty, will be an important step in the search for the ideal grafting technique.

Etiology, clinical characteristics, genetic profile, and outcomes of children with refractory rickets at a referral center in India: a cohort study.

Limited research exists regarding the genetic profile, clinical characteristics, and outcomes of refractory rickets in children from India. Patients with refractory rickets aged ≤ 18years were enrolled. Data regarding clinical features, etiology, genotype-phenotype correlation, and estimated glomerular filtration rate (eGFR) were recorded. Seventy-two patients with refractory rickets (non-nutritional, with normal kidney function at presentation) from 65 families attending the pediatric nephrology clinic from 2005-2024 were included. Median (IQR) age at first presentation was 2 (1, 4) years. Clinical features included failure-to-thrive (49 [68.1%]), polyuria (37 [51.4%]), nephrocalcinosis (33 [45.8%]), fractures (10 [13.9%]), and hypokalemic paralysis (4 [5.6%]). Major etiologies included distal renal tubular acidosis (dRTA) [34(47.2%)], hereditary hypophosphatemic rickets (11 [15.3%]), cystinosis (9 [12.5%]), Lowe syndrome (3 [4.2%]), vitamin D-dependent rickets (4 [5.5%]), and Fanconi-Bickel syndrome (3 [4.2%]). Next-generation sequencing identified 61 variants among 71 children tested (85.9%), of which 56 variants (among 55 children) were pathogenic (P)/likely-pathogenic (LP) (77.5% diagnostic-yield). P/LP variants included SLC4A1 (n = 14), CTNS (n = 9), PHEX (n = 8), WDR72 (n = 5), OCRL (n = 2), SLC2A2 (n = 3), ATP6V0A4 (n = 4), VDR (n = 3), CLDN16 (n = 2), ATP6V1B1 (n = 1), SLC12A1 (n = 1), CLCN5 (n = 1), SLC34A3 (n = 1), ATP7B (n = 1), and KCNJ1 (n = 1). Fifteen novel P/LP variants and five novel variants-of-uncertain-significance (VUS) were identified. c.2573C > A in exon 19 among SLC4A1-dRTA (n = 14) was a recurrent mutation. Five patients with cystinosis, two patients with SLC4A1-dRTA, two with WDR72-dRTA, and two with Bartter syndrome showed progression to CKD stage 2 or greater during follow-up. dRTA, X-linked hypophosphatemic rickets, and cystinosis were common causes of refractory rickets. The c.2573C > A variant in exon 19 was a recurrent mutation in SLC4A1-dRTA.

Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real-World Data.

The liver is crucial for metabolizing the anticancer drug palbociclib, but limited information is available on the impact of hepatic impairment on its toxicity and efficacy, with no real-world data available. This study aims to evaluate how hepatic impairment affects hematological toxicity and progression-free survival (PFS) of palbociclib in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, using the National Cancer Institute scoring system, in a large real-world dataset. This multicenter retrospective observational study included female patients treated with palbociclib between August 2017 and February 2024. Regression analysis was used to compare the risk of developing grade 3/4 hematological toxicity and PFS between patients with normal and mild impaired liver function. In total, 478 female patients were included. Patients with mild hepatic impairment (n = 205) did not have an increased risk of developing grade 3/4 neutropenia compared with patients with normal hepatic function (n = 273) (hazard ratio (HR) = 1.11; 95% CI 0.83-1.47). In addition, the PFS was not significantly different between both groups (HR = 1.15; 95% CI 0.93-1.42). In real-world settings, patients with mild hepatic impairment do not have a higher risk of developing palbociclib-induced neutropenia or disease progression than patients with normal hepatic function. These findings can guide clinicians when treating breast cancer patients with mild hepatic impairment.

Atrial Fibrillation Related Titin Truncation Is Associated With Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models.

Protein-truncating mutations in the titin gene are associated with increased risk of atrial fibrillation. However, little is known about the underlying pathophysiology. We identified a heterozygous titin truncating variant (TTNtv) in a patient with unexplained early onset atrial fibrillation and normal ventricular function. We generated patient-specific atrial- and ventricular-like induced pluripotent stem cell-derived cardiomyocytes and engineered heart tissue to evaluate the impact of the TTNtv on electrophysiology, sarcomere structure, contractility, and gene expression. We demonstrate that the TTNtv increases susceptibility to pacing-induced arrhythmia, promotes sarcomere disorganization, and reduces contractile force in atrial induced pluripotent stem cell-derived cardiomyocytes compared with their CRISPR/Cas9-corrected isogenic controls. In ventricular induced pluripotent stem cell-derived cardiomyocytes, this variant was associated with abnormal electrophysiology and sarcomere organization without a reduction in contractile force compared with their isogenic controls. RNA-sequencing revealed an upregulation of cell adhesion and extracellular matrix genes in the presence of the TTNtv for both atrial and ventricular engineered heart tissues. In a patient with unexplained atrial fibrillation, induced pluripotent stem cell-derived cardiomyocytes with a TTNtv showed structural and electrophysiological abnormalities in both atrial and ventricular models, while only atrial engineered heart tissues demonstrated reduced contractility. The observed chamber-specific effect suggests that structural disorganization and reduced contractile function may be associated with atrial myopathy in the presence of truncated titin.

Effect of Target-Mediated Disposition on Iptacopan Clinical Pharmacokinetics in Participants with Normal or Impaired HepaticFunction.

Iptacopan, a first-in-class complement factor B inhibitor acting proximally in the alternative complement pathway, has been shown to be safe and effective for patients with complement-mediated diseases. Iptacopan selectively binds with high affinity to factor B, a soluble, plasma-based, hepatically produced protein. Factor B is abundant in the circulation but can be saturated at the iptacopan clinical dose of 200 mg twice daily. Iptacopan pharmacokinetics (PK) are influenced by target binding. This target-mediated drug disposition (TMDD) behavior makes PK data useful for understanding target occupancy and motivates modeling of drug-target binding to connect exposure with pharmacological effect. A phase I hepatic impairment (HI) PK study measuring both total and unbound iptacopan PK profiles provided an opportunity to characterize the effect of variation in target concentration (due to varying hepatic function) on iptacopan PK. HI caused no change in total iptacopan exposure but increased unbound iptacopan exposure 1.38- to 3.72-fold in participants with mild, moderate, or severe HI relative to demographically matched participants with normal hepatic function, with the largest increases in severe HI. A two-site competitive binding model was developed to elucidate the relationship between iptacopan PK and factor B occupancy to characterize exposure thresholds for maximal target engagement. The model was used to assess alternative dose regimens to provide insight into how to approach dose recommendations for patients with severe HI. This study provides an example of small-molecule TMDD, a behavior typically associated with targeted biologics; its importance is too often underappreciated in small-molecule drug development.

Sine oculis homeobox homolog family function in gastrointestinal cancer: Progression and comprehensive analysis

The sine oculis homeobox homolog (SIX) family, a group of transcription factors characterized by a conserved DNA-binding homology domain, plays a critical role in orchestrating embryonic development and organogenesis across various organisms, including humans. Comprising six distinct members, from SIX1 to SIX6 , each member contributes uniquely to the development and differentiation of diverse tissues and organs, underscoring the versatility of the SIX family. Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders, as well as in tumor initiation and progression, highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions. Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development. While the development of inhibitors targeting this gene family is still in its early stages, the significant potential of such interventions holds promise for future therapeutic advances. Therefore, this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers, focusing on its critical role in normal organ development and its implications in gastrointestinal cancers, including gastric, pancreatic, colorectal cancer, and hepatocellular carcinomas. In conclusion, this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis, prognosis, and treatment of gastrointestinal cancers.

Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy.

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis. CHF patients (n=15) underwent cardiopulmonary exercise testing with venous blood sampling at rest, peak exercise and recovery. These patients had significantly higher resting venous NPY levels compared with an age- and sex-matched control group of patients (n=16) with normal left ventricular function (40±6.9vs. 9.0±4.6 pg/mL, respectively; P<0.0001). In CHF patients, NPY levels increased significantly from baseline to peak exercise (to 93.5±42.1 pg/mL; P=0.0004) and remained elevated during recovery (86.8±44.6 pg/mL; P=0.0018). The peak (r=0.58, P=0.0222) and recovery (r=0.56, P=0.0304) NPY levels and the ability to increase NPY from baseline (r=0.53, P=0.0427) showed significant positive correlations with heart rate recovery at 1 min, but not with peak oxygen consumption. In CHF patients, the ability to increase NPY levels on exertion is correlated with heart rate recovery, a known prognostic indicator for mortality. These findings suggest that NPY dynamics during exercise might provide valuable insights into sympathetic responses and prognosis in CHF patients.

Cystic fibrosis in Pakistan: population harbouring rare variants non-responsive to CFTR modulators and the dilemma of poor health facilities.

Pathogenic mutations in the CFTR gene disrupt the normal function of the chloride ion channel CFTR protein, resulting in Cystic Fibrosis (C.F.). Pakistan's situation regarding C.F. mutation is largely unknown, complicating the disease management and treatment. This study is designed to identify the disease-causing CFTR mutations in the Pakistani C.F. cohort and perform an in silico analysis of rare/novel variants. Ninety-five C.F. patients were recruited from pediatric healthcare facilities in different regions of Pakistan. Initially, we investigated ∆F508 mutation in all patients, followed by whole exome sequencing (W.E.S.) of nineteen patients and in silico analysis of identified rare/novel mutations. Initial screening revealed that ∆F508 mutation was absent in 73.74% of cases. W.E.S. identified three novel variants (c.3036del/Q1012Hfs*11, c.488A > T/p.K163M, c.2384del/S795Yfs*8), one rare variant (c.489 + 2T > C) previously reported in two Pakistani residing in U.K. and one (c.164 + 1G > T/p.?) extremely rare in other populations. Additionally, c.1705T > G/p.Y569D, c.653T > A/p.L218X, c.2125C > T/p.R709X, and c.3484C > T/p.R1162X were also identified. Most variants in our cohort are either frameshift or nonsense, while only two are missense variants. Alarmingly, most of these variants, except ∆F508, are non-responsive to modulator drugs, while the responsiveness of c.488A > T/p.K163M is yet to be determined. High consanguinity (73.40%) and homozygous status of all mutations, except c.3036del/Q1012Hfs*11, are indicative of a high ratio of C.F. carriers in Pakistan. These findings represent the diverse pattern of CFTR mutations within the Pakistani population, highlighting the imperative need to improve earlier C.F. diagnostic and management facilities and to conduct research on treatment strategies other than modulator therapies.

Curcumin: A Potential Detoxifier Against Chemical and Natural Toxicants.

The human body gets exposed to a variety of toxins intentionally or unintentionally on a regular basis from sources such as air, water, food, and soil. Certain toxins can be synthetic, while some are biological. The toxins affect the various parts of the body by activating numerous pro-inflammatory markers, like oxidative stresses, that tend to disturb the normal function of the organs ultimately. Nowadays, people use different types of herbal treatments, viz., herbal drinks that contain different spices for detoxification of their bodies. One such example is turmeric, the most commonly available spice in the kitchen and used across all kinds of households. Turmeric contains curcumin, which is a natural polyphenol. Curcumin is a medicinal compound with different biological activities, such as antioxidant, antineoplastic, anti-inflammatory, and antibacterial. Hence, this review gives a comprehensive insight into the promising potential of curcumin in the detoxification of heavy metals, carbon tetrachloride, drugs, alcohol, acrylamide, mycotoxins, nicotine, and plastics. The review encompasses diverse animal-based studies portraying curcumin's role in nullifying the different toxic effects in various organs of the body (especially the liver, kidney, testicles, and brain) by enhancing defensive signaling pathways, improving antioxidant enzyme levels, inhibiting pro-inflammatory markers activities and so on. Furthermore, this review also argues over curcumin's safety assessment for its utilization as a detoxifying agent.

The roles of STAT1, CASP8, and MYD88 in the care of ischemic stroke.

Ischemic stroke is caused by blockage of blood vessels in brain, affecting normal function. The roles of Signal Transformer and Activator of Transcription 1 (STAT1), CASP8, and MYD88 in ischemic stroke and its care are unclear. The ischemic stroke datasets GSE16561 and GSE180470 were found from the Gene Expression Omnibus database. Batch effect removal, finding differentially expressed genes (DEGs), weighted gene co-expression network analysis, protein-protein interaction analysis, functional enrichment analysis, immune infiltration analysis, comparative toxicogenomics database analysis were carried out. Gene expression heat maps were drawn, and miRNAs were found that regulate core DEGs. A total of 1183 DEGs were obtained, which were mainly concentrated in immune effector processes, cell activation, and protein serine/threonine kinase activity, the NOD-like receptor signaling pathway, NF-kappa B signaling pathway, C-type lectin receptor signaling pathway, and P53 signaling pathway. Four core genes were identified. Heatmap revealed high expression of (CASP8, MYD88, and STAT1) in whole blood samples of ischemic stroke. Comparative toxicogenomics database analysis demonstrated (CASP8, MYD88, and STAT1) are related to cerebral hemorrhage, reperfusion injury, hypertension, and inflammation. In ischemic stroke, expression of STAT1, CASP8, and MYD88 is higher and leads to poorer prognosis.

Differences in Postoperative Disposition by Kidney Disease Severity: A Population-Based Cohort Study.

People with advanced kidney disease undergo more non-cardiac operations compared to the general population, with a higher risk of perioperative cardiac events and death. However, little is known about the associations between severity of preoperative kidney dysfunction with postoperative length of hospitalization and discharge disposition; these were the focus of this study. Population-based retrospective cohort. Adults from Alberta, Canada undergoing inpatient major noncardiac surgery between April 2005 and February 2019. Categorical preoperative outpatient estimated glomerular filtration rate (eGFR) or kidney failure status. Length of stay (LOS), days alive at home after surgery within 30 and 90 days, and discharge disposition location. Associations were estimated with unadjusted and adjusted generalized estimating equation models. 927,560 inpatient surgeries in 666,770 people (55.9% female, median age 57.4 years) were identified. People receiving dialysis had the longest LOS (11 days [95% CI 6, 29), 2 times greater than that among people with normal kidney function (adjusted incidence rate ratio [IRR] 2.21 [95% CI 2.10, 2.32]). This group also had the fewest days alive at home within the first 30 days after surgery, with an IRR of 0.69 (95% CI 0.67, 0.70) compared to people with normal eGFR. The majority of people (82.8%) were discharged home without nursing support after surgery, though people receiving dialysis were discharged to a facility with 24-hour nursing care nearly 4 times more often. There were graded increases in risks of these outcomes with lower levels of kidney function. Many people did not have preoperative kidney function assessed, reflecting standard clinical practice in the general population. After major surgery, people with kidney disease spend more time recovering in hospital and have less independence from post-discharge nursing supports than otherwise similar patients who have normal or near normal kidney function. These differences were more pronounced for those with the most severe stages of kidney disease.

Surgical approach to a biliary tract cyst in an elderly cat.

Choledochal cyst or biliary tract cyst is a pathological condition characterized by abnormal dilation of the hepatobiliary system. In veterinary medicine, case descriptions and histological characterizations of this biliary malformation are scarce, requiring reliance on data from human medicine. A presumptive diagnosis typically involves imaging studies, with histopathological examination required for confirmation. Treatment often involves surgical intervention to remove the cyst and restore normal biliary function. A 15-year-old mixed-breed domestic female cat presented with vomiting and anorexia. Ultrasonographic examination revealed a dilation adjacent to the caudal aspect of the gallbladder. The patient underwent surgical intervention, during which a sacculation in the cystic duct region was identified and completely excised. Histopathological analysis confirmed the diagnostic suspicion of a biliary tract cyst. Despite the limited veterinary literature, the success of the surgical intervention, involving complete cyst removal, was evident. The patient remains stable and fully recovered twelve months post-surgery.

Compound heterozygous TMEM67 biallelic variants including a novel frameshift mutation in two Filipino adolescent siblings with Joubert syndrome.

Joubert Syndrome (JS) is a congenital cerebellar ataxia typically inherited in an autosomal recessive pattern, although rare X-linked inheritance can occur. It is characterized by hypotonia evolving into ataxia, global developmental delay, oculomotor apraxia, breathing dysregulation, and multiorgan involvement. To date, there are 40 causative genes implicated in JS, all of which encode proteins of the primary cilium. Primary cilia play a crucial role in the normal development and function of many organs, including parts of the brain (cerebellum and brainstem), kidneys, and the retina. This likely explains the multiorgan involvement seen in JS. In this report, we present the first genetically confirmed case of JS in two Filipino adolescent siblings who had early onset ataxia, hepatomegaly, and global developmental delay. A cranial CT scan revealed the Molar Tooth Sign (MTS). Whole Exome Sequencing (WES), performed via buccal swab, showed biallelic pathogenic variants at NM_153704.6:c.2086C > T (NP_714915.3:p.Leu696Phe) and NM_153704.6:c.431del (NP_714915.3:p.Leu144CysfsTer19) in TMEM67, which are associated with Joubert Syndrome 6 (OMIM:610688) in a compound heterozygous state. The prevalence of NM_153704.6:c.2086C > T (NP_714915.3:p.Leu696Phe) in TMEM67 variant is very rare (< 0.001%), and the NM_153704.6:c.431del (NP_714915.3:p.Leu144CysfsTer19) has not been recorded. This case contributes valuable information to the expanding knowledge of JS and its related disorders.

Variability of anti-Müllerian hormone and folliculotropic hormone levels in women of reproductive age in relation to normal or impaired ovarian function

Variability of anti-Müllerian hormone and folliculotropic hormone levels in women of reproductive age in relation to normal or impaired ovarian function

Evaluating the Effect on Infants and Parents Attending the Parent-Child Psychological Support Programme®, a Community-Based Program to Promote Attachment Security.

The foremost index of caregiving quality is child attachment, as supported by attachment theory. Research supports the relevance of early parenting interventions in improving child outcomes in attachment quality to promote public health because of their long-term effects on mental health and functioning. This study aimed at evaluating the impact on both parenting and child outcomes of the Parent-Child Psychological Support Programme® (PCPS), a community-based program individually tailored to parents and their infants during periodic center-based visits to promote attachment security. The evaluation involved two cohorts from "vulnerable populations" and used the resources embedded in the program design without interfering with the normal functioning of the service. From an evaluative research approach, the effects on mothers and children were assessed using a quantitative approach. Pre- and post-test measures (parenting questionnaires) and child attachment quality assessments through the Strange Situation Procedure were examined. The equivalence of the cohorts was verified and used as a baseline for parenting outcomes. PCPS participants demonstrated increased parental competence and self-efficacy, as well as reduced levels of parenting stress. Analysis of the two cohorts showed a significant difference in the number of visits and proxies for intervention, which were associated with the expected pre-post changes in parenting dimensions. The proportion of securely attached children was significantly higher in the "medium-high intervention" group than in the "no/low intervention" group (72.7% vs 54.5%). Furthermore, compared with international baselines, this proportion showed no differences in the "no-/low-intervention" group but demonstrated expected significant differences in the "medium-high intervention" group.

Repurposing Mitochondria-Targeted Therapeutics for Kidney Diseases.

The kidney is one of the most metabolically demanding organs in the human body and requires a large amount of energy, in the form of adenosine triphosphate (ATP), to perform and maintain normal renal functions. To meet this energy demand, proximal tubule cells within the nephron segments of the renal cortex are mitochondrially dense with high oxygen consumption rates. Mitochondria are complex organelles involved in diverse cellular and molecular functions, including the production of ATP, calcium homeostasis, and phospholipid regulation. Mitochondrial dysfunction is critical in the onset and progression of kidney disease. Dysfunctional renal mitochondria have been linked with alterations in redox homeostasis, impaired bioenergetics, oxidative stress, and inflammation, all of which result in renal cell injury and death, as well as fibrotic accumulation in kidney injury and disease. As such, interest in the development and/or repurposing of mitochondria-targeted therapeutics for the potential treatment of kidney diseases has recently surged. While novel therapeutics and promising new drug targets have been identified, drug repurposing for kidney diseases offers numerous advantages over traditional drug discovery initiatives, including reduced cost, time of therapeutic development, and preclinical testing, in addition to known pharmacokinetics/pharmacodynamics and safety profiles. Here, we provide an overview of mitochondrial dysfunction in the context of kidney injury and disease and shed light on promising mitochondria-targeted therapeutic agents that display repurposing potential for the restoration of renal function and/or acceleration of renal recovery.

Coati optimization algorithm for brain tumor identification based on MRI with utilizing phase-aware composite deep neural network

ABSTRACT Brain tumors can cause difficulties in normal brain function and are capable of developing in various regions of the brain. Malignant tumours can develop quickly, pass through neighboring tissues, and extend to further brain regions or the central nervous system. In contrast, healthy tumors typically develop slowly and do not invade surrounding tissues. Individuals frequently struggle with sensory abnormalities, motor deficiencies affecting coordination, and cognitive impairments affecting memory and focus. In this research, Utilizing Phase-aware Composite Deep Neural Network Optimized with Coati Optimized Algorithm for Brain Tumor Identification Based on Magnetic resonance imaging (PACDNN-COA-BTI-MRI) is proposed. First, input images are taken from the brain tumour Dataset. To execute this, the input image is pre-processed using Multivariate Fast Iterative Filtering (MFIF) and it reduces the occurrence of over-fitting from the collected dataset; then feature extraction using Self-Supervised Nonlinear Transform (SSNT) to extract essential features like model, shape, and intensity. Then, the proposed PACDNN-COA-BTI-MRI is implemented in Matlab and the performance metrics Recall, Accuracy, F1-Score, Precision Specificity and ROC are analysed. Performance of the PACDNN-COA-BTI-MRI approach attains 16.7%, 20.6% and 30.5% higher accuracy; 19.9%, 22.2% and 30.1% higher recall and 16.7%, 21.9% and 30.8% higher precision when analysed through existing techniques brain tumor identification using MRI-Based Deep Learning Approach for Efficient Classification of Brain Tumor (MRI-DLA-ECBT), MRI-Based Brain Tumor Detection using Convolutional Deep Learning Methods and Chosen Machine Learning Techniques (MRI-BTD-CDMLT) and MRI-Based Brain Tumor Image Detection using CNN-Based Deep Learning Method (MRI-BTID-CNN) methods, respectively.

Gait patterns in unstable older patients related with vestibular hypofunction. Preliminary results in assessment with time-frequency analysis

Background Gait instability and falls significantly impact life quality and morbi-mortality in elderly populations. Early diagnosis of gait disorders is one of the most effective approaches to minimize severe injuries. Objective To find a gait instability pattern in older adults through an image representation of data collected by a single sensor. Methods A sample of 13 older adults (71-85 years old) with instability by vestibular hypofunction is compared to a sample of 19 adults (21-75 years old) without instability and normal vestibular function. Image representations of the gait signals acquired on a specific walk path were generated using a continuous wavelet transform and analyzed as a texture using grey level co-occurrence matrix metrics as features. A support vector machine (SVM) algorithm was used to discriminate subjects. Results First results show a good classification performance. According to analysis of extracted features, most information relevant to instability is concentrated in the medio-lateral acceleration (X axis) and the frontal plane angular rotation (Z axis gyroscope). Performing a ten-fold cross-validation through the first ten seconds of the sample dataset, the algorithm achieves a 92,3 F1 score corresponding to 12 true-positives, 1 false positive and 1 false negative. Discussion This preliminary report suggests that the method has potential use in assessing gait disorders in controlled and non-controlled environments. It suggests that deep learning methods could be explored given the availability of a larger population and data samples.

The Cul3 ubiquitin ligase engages Insomniac as an adaptor to impact sleep and synaptic homeostasis.

Mutations of the Cullin-3 (Cul3) E3 ubiquitin ligase are associated with autism and schizophrenia, neurological disorders characterized by sleep disturbances and altered synaptic function. Cul3 engages dozens of adaptor proteins to recruit hundreds of substrates for ubiquitination, but the adaptors that impact sleep and synapses remain ill-defined. Here we implicate Insomniac (Inc), a conserved protein required for normal sleep and synaptic homeostasis in Drosophila, as a Cul3 adaptor. Inc binds Cul3 in vivo, and mutations within the N-terminal BTB domain of Inc that weaken Inc-Cul3 associations impair Inc activity, suggesting that Inc function requires binding to the Cul3 complex. Deletion of the conserved C-terminus of Inc does not alter Cul3 binding but abolishes Inc activity in the context of sleep and synaptic homeostasis, indicating that the Inc C-terminus has the properties of a substrate recruitment domain. Mutation of a conserved, disease-associated arginine in the Inc C-terminus also abolishes Inc function, suggesting that this residue is vital for recruiting Inc targets. Inc levels are negatively regulated by Cul3 in neurons, consistent with Inc degradation by autocatalytic ubiquitination, a hallmark of Cullin adaptors. These findings link Inc and Cul3 in vivo and support the notion that Inc-Cul3 complexes are essential for normal sleep and synaptic function. Furthermore, these results indicate that dysregulation of conserved substrates of Inc-Cul3 complexes may contribute to altered sleep and synaptic function in autism and schizophrenia associated with Cul3 mutations.

Usefulness of radiomics and kidney volume based on non-enhanced computed tomography in chronic kidney disease - initial report.

Chronic kidney disease (CKD) is classified according to the estimated glomerular filtration rate (eGFR), but kidney volume (KV) can also provide meaningful information. Very few radiomics (RDX) studies on CKD have used computed tomography (CT). This study aimed to determine whether non-enhanced computed tomography-based (NECT) RDX can be useful in evaluation of patients with CKD and to compare it with KV. The NECT scans of 64 subjects with impaired kidney function classified based on < 60 ml/min/1,73 m2 and 60 with normal kidney function as controls were retrospectively analyzed. Kidney segmentation, volume measurements and RDX features extraction were performed. Machine learning models (RDX) were constructed to classify the kidneys as having structural markers of impaired or normal function. The median KV in the impaired kidney function group was 114.83 mL vs 159.43 mL (p < 0.001) in the control group. There was a statistically significant strong positive correlation between KV and eGFR (rs = 0.579, p < 0.001), and a strong negative correlation between KV and serum creatinine level (rs = -0.514, p < 0.001). The KV-based models achieved the best area under the curve (AUC) of 0.746, whereas the RDX-based models achieved the best AUC of 0.878. RDX can be useful in identifying patients with impaired kidney function on NECT. RDX-based models perform better than KV-based models. RDX has the potential to identify patients with a higher risk of CKD based on imaging, which, as we believe, can indirectly assist in clinical decision-making.