Clinical Study Data Research Articles

Novel Deep Learning Approaches for Analyzing Diffusion Imaging Data

AbstractDiffusion magnetic resonance imaging (dMRI) is developing into one of the most important non-invasive tools for clinical brain research. This development is supported by a project funded by the German Research Foundation, in which four major obstacles related to dMRI data were addressed: (1) the lack of transferability of dMRI data between clinical sites, (2) the lack of training and label data, (3) the potential of complex diffusion data, and (4) the integration of spherical signals in neural networks to improve accuracy. To overcome the problem of different MRI systems producing slightly varying data, the project developed a method for harmonizing MRI signals. To address the issue of limited ground truth data, a framework was developed to synthesize individual diffusion data and complete datasets based on important diffusion characteristics and statistics. The integration of complex signals, often discarded during acquisition, to improve reconstruction was also explored. Finally, new methods were developed to preserve the spherical character of the diffusion data in the DL model. The resulting methods are intended to improve the usability of diffusion imaging data and to enable the creation of processing pipelines for dMRI data in clinical studies and clinical practice.

Evaluating REDCap as the Central Data Collection Tool for the Hamburg City Health Study.

The collection of examination data for large clinical studies is often done with proprietary systems, which are accompanied by several disadvantages such as high cost and low flexibility. With the use of open-source tools, these disadvantages can be overcome and thereby improve data collection as well as data quality. Here we exemplary use the data collection process of the Hamburg City Health Study (HCHS), carried out at the University Medical Center Hamburg-Eppendorf (UKE). We evaluated how the recording of the examination data can be converted from an established, proprietary electronic healthcare record (EHR) system to the free-to-use Research Electronic Data Capture (REDCap) software. For this purpose, a technical conversion of the EHR system is described first. Metafiles derived from the EHR system were used for REDCap electronic case report form (eCRF) building. The REDCap system was tested by HCHS study assistants via completion of self-developed tasks mimicking their everyday study life. Usability was quantitatively evaluated via the IBM Computer System Usability Questionnaire (CSUQ) and qualitatively assessed with a semi-structured interview. With the IBM CSUQ, the study assistants rated the usage of the basic REDCap system for HCHS examination data collection with an overall score of 4.39, which represents a medium acceptance. The interview feedback was used to formulate user stories to subsequently increase the administrative sovereignty and to conceptualize a REDCap HCHS information technology (IT) infrastructure. Our work aims to serve as a template for evaluating the feasibility of a conversion from a proprietary to a free-to-use data collection tool for large clinical studies such as the HCHS. REDCap has great potential, but extensions and an integration to the current IT infrastructure are required.

Adaptability of Existing Feasibility Tools for Clinical Study Research Data Platforms.

The increasing need for secondary use of clinical study data requires FAIR infrastructures, i.e. provide findable, accessible, interoperable and reusable data. It is crucial for data scientists to assess the number and distribution of cohorts that meet complex combinations of criteria defined by the research question. This so-called feasibility test is increasingly offered as a self-service, where scientists can filter the available data according to specific parameters. Early feasibility tools have been developed for biosamples or image collections. They are of high interest for clinical study platforms that federate multiple studies and data types, but they pose specific requirements on the integration of data sources and data protection. Mandatory and desired requirements for such tools were acquired from two user groups - primary users and staff managing a platform's transfer office. Open Source feasibility tools were sought by different literature search strategies and evaluated on their adaptability to the requirements. We identified seven feasibility tools that we evaluated based on six mandatory properties. We determined five feasibility tools to be most promising candidates for adaption to a clinical study research data platform, the Clinical Communication Platform, the German Portal for Medical Research Data, the Feasibility Explorer, Medical Controlling, and the Sample Locator.

The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats.

Chronic kidney disease (CKD) progression is associated with persisting oxidative stress, which impairs the NO-sGC-cGMP signaling cascade through the formation of oxidized and heme-free apo-sGC that cannot be activated by NO. Runcaciguat (BAY 1101042) is a novel, potent, and selective sGC activator that binds and activates oxidized and heme-free sGC and thereby restores NO-sGC-cGMP signaling under oxidative stress. Therefore, runcaciguat might represent a very effective treatment option for CKD/DKD. The potential kidney-protective effects of runcaciguat were investigated in ZSF1 rats as a model of CKD/DKD, characterized by hypertension, hyperglycemia, obesity, and insulin resistance. ZSF1 rats were treated daily orally for up to 12 weeks with runcaciguat (1, 3, 10 mg/kg/bid) or placebo. The study endpoints were proteinuria, kidney histopathology, plasma, urinary biomarkers of kidney damage, and gene expression profiling to gain information about relevant pathways affected by runcaciguat. Furthermore, oxidative stress was compared in the ZSF1 rat kidney with kidney samples from DKD patients. Within the duration of the 12-week treatment study, kidney function was significantly decreased in obese ZSF1 rats, indicated by a 20-fold increase in proteinuria, compared to lean ZSF1 rats. Runcaciguat dose-dependently and significantly attenuated the development of proteinuria in ZSF1 rats with reduced uPCR at the end of the study by -19%, -54%, and -70% at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo treatment. Additionally, average blood glucose levels measured as HbA1C, triglycerides, and cholesterol were increased by five times, twenty times, and four times, respectively, in obese ZSF1 compared to lean rats. In obese ZSF1 rats, runcaciguat reduced HbA1c levels by -8%, -34%, and -76%, triglycerides by -42%, -55%, and -71%, and cholesterol by -16%, -17%, and -34%, at 1, 3, and 10 mg/kg/bid, respectively, compared to placebo. Concomitantly, runcaciguat also reduced kidney weights, morphological kidney damage, and urinary and plasma biomarkers of kidney damage. Beneficial effects were accompanied by changes in gene expression that indicate reduced fibrosis and inflammation and suggest improved endothelial stabilization. In summary, the sGC activator runcaciguat significantly prevented a decline in kidney function in a DKD rat model that mimics common comorbidities and conditions of oxidative stress of CKD patients. Thus, runcaciguat represents a promising treatment option for CKD patients, which is in line with recent phase 2 clinical study data, where runcaciguat showed promising efficacy in CKD patients (NCT04507061).

Psychometric properties of the dissociative subtype of posttraumatic stress disorder scale: replication and extension in two German-speaking samples

ABSTRACT Background: The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced the dissociative subtype of posttraumatic stress disorder (D-PTSD). To assess this subtype, the Dissociative Subtype of PTSD Scale (DSPS), a 15-item self-report measure to identify lifetime and current dissociative symptoms of D-PTSD, was developed. However, so far, the scale has only been validated in war veterans. Moreover, criterion validity and diagnostic utility have not been examined yet. Objective: We aimed to validate the DSPS in two samples of civilian trauma-exposed German-speaking participants. Methods: In Study 1, a pre-registered online study, participants with and without PTSD symptoms (N = 558) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, alcohol use disorder, absorption, and dissociative responding to trauma-related questionnaires. In Study 2, which used secondary data of a pre-registered clinical study, participants with a PTSD diagnosis (N = 71) answered questionnaires about traumatic experiences, dissociation, PTSD, depression, generalized anxiety disorder, somatic symptom disorder, and dissociative responding to standardized trauma exposure. Moreover, PTSD, D-PTSD, and other diagnoses were assessed with structured clinical interviews. Results: Analyses confirmed a three-factor structure as well as high internal consistency, and high convergent, discriminant, and criterion validity of the DSPS. Moreover, the scale was able to identify a latent D-PTSD group and individuals with D-PTSD diagnosis. Conclusions: The DSPS constitutes a reliable and valid tool to assess D-PTSD symptoms in clinical practice and research and thereby may contribute to a better understanding of these debilitating symptoms.

Targeting Melanoma-Associated Fibroblasts (MAFs) with Activated γδ (Vδ2) T Cells: An In Vitro Cytotoxicity Model.

The tumor microenvironment (TME) has gained considerable scientific attention by playing a role in immunosuppression and tumorigenesis. Besides tumor cells, TME is composed of various other cell types, including cancer-associated fibroblasts (CAFs or MAFs when referring to melanoma-derived CAFs) and tumor-infiltrating lymphocytes (TILs), a subpopulation of which is labeled as γδ T cells. Since the current anti-cancer therapies using γδ T cells in various cancers have exhibited mixed treatment responses, to better understand the γδ T cell biology in melanoma, our research group aimed to investigate whether activated γδ T cells are capable of killing MAFs. To answer this question, we set up an in vitro platform using freshly isolated Vδ2-type γδ T cells and cultured MAFs that were biobanked from our melanoma patients. This study proved that the addition of zoledronic acid (1-2.5 µM) to the γδ T cells was necessary to drive MAFs into apoptosis. The MAF cytotoxicity of γδ T cells was further enhanced by using the stimulatory clone 20.1 of anti-BTN3A1 antibody but was reduced when anti-TCR γδ or anti-BTN2A1 antibodies were used. Since the administration of zoledronic acid is safe and tolerable in humans, our results provide further data for future clinical studies on the treatment of melanoma.

Stress incontinence in women of reproductive age. modern rehabilitation methods for improving the quality of life (literature review)

The article presents the data of scientific and clinical studies of Russian and foreign authors on modern approaches to the use of nondrug technologies (behavioral therapy, Kegel exercises, electrical stimulation of the pelvic floor muscles, biofeedback, physiotherapy, reflexology) in the conservative treatment of stress incontinence in women of reproductive age.

Drug Use and Human Milk: Legal and Child Welfare Considerations.

Preventing new parents who use drugs from bonding with and bodyfeeding their babies undermines public health. Because U.S. culture treats substance use as a moral failing rather than a health concern, punitive responses to perinatal substance use continue to dominate. This is particularly true for families of color, who are more likely to be targeted by the family regulation system. These approaches fail to protect families, and cause their own, separate harm. This article will lay out existing evidence surrounding bodyfeeding. Then, it will debunk harmful mythologies about drug use and human milk, and compare the risks associated with using drugs while bodyfeeding to those inherent in family separation. Finally, it will make the case for harm-reduction approaches over criminal ones. The health risks associated with family separation are only rarely weighed against those associated with drug exposure through human milk. Our objective for this paper is to contribute new ways of framing the importance of keeping families together at birth, even when perinatal substance use is detected. This manuscript is not based upon clinical study or patient data, and exclusively references studies and research publications that have been approved by the appropriate ethics committee and which have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Significant research data support the position that the risks associated with family separation are arguably greater than those associated with exposure to substance use in human milk. Harm reduction approaches should be favored over criminal approaches when perinatal substance use is detected or confirmed.

An Overview on Phytoestrogen based antihypertensive agent for their potential Pharmacological Mechanism

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

Hereditary Angioedema With Normal C1 Inhibitor: US Survey of Prevalence and Provider Practice Patterns.

Hereditary angioedema (HAE) with normal C1-INH (HAE-nl-C1INH) is phenotypically similar to HAE resulting from C1-INH deficiency (HAE-C1INH). Confirmatory diagnostic tests for HAE-nl-C1INH are limited and few clinical study data exist regarding management of the condition. Therefore, survey studies may provide initial estimates of prevalence, diagnosis, and management patterns of this condition. To estimate the prevalence and describe current management patterns for HAE-nl-C1INH in the United States (US). We conducted an Internet-based survey of US physicians to estimate the prevalence of the HAE-nl-C1INH population in the United States. Potential participating physicians were identified from the US Hereditary Angioedema Association database and IQVIA Xponent prescription database. Eligible physicians were invited to complete an online survey between June and September2021. A total of 113 physicians provided data for the estimation of HAE-nl-C1INH prevalence and 81 physicians treating HAE-nl-C1INH patients provided data about treatment patterns. In bias-corrected analysis, we estimated 1,230 to 1,331 HAE-nl-C1INH patients within the United States between May 2019 and April 2020. Mean time to diagnosis for HAE-nl-C1INH was approximately 6 years (range, 2.4-13.5 years). Response to medication was commonly used to inform diagnosis (antihistamine response or nonresponse used by 73% of physician respondents, corticosteroids by 57%, or HAE-specific medications by 74%), and Factor XII genetic testing was used by 43%. These survey data provide estimates of HAE-nl-C1INH prevalence in the United States as well as current diagnosis and management strategies. Results may be useful for developing studies to assess treatment efficacy and safety, and potentially improve the diagnosis for and management of this patient population.

Population pharmacokinetic modeling and simulation for nirmatrelvir exposure assessment in Chinese older patients with COVID-19 infection

Nirmatrelvir is an effective component of Paxlovid, the first oral antiviral drug granted emergency use authorization by the FDA. Nirmatrelvir is prescribed extensively in older adult patients to treat the coronavirus disease 2019 (COVID-19) infection. In this study, population pharmacokinetic modeling with clinical study data was employed to explore the pharmacokinetic profile of nirmatrelvir in older adult Chinese patients with COVID-19 infection. The result suggests that the pharmacokinetic profile of nirmatrelvir can be described by a one-compartment model with first-order absorption and elimination in this study population. The calculated apparent clearance (CL/F), apparent volumes of distribution (V/F), and absorption rate constant (ka) for the typical patient were 4.16 L/h, 39.1 L, and 0.776, respectively. The area under the curve (AUC) of nirmatrelvir in the typical Chinese older adult was approximately three-fold higher than the AUCs in Chinese and Western young adult volunteers. At the same doses, the simulated AUCs were increased by 26%, 43%, 72%, and 135% in virtual populations with creatinine clearances of 60, 45, 30, and 15 mL/min, respectively. Our research provides an instructive reference for nirmatrelvir dose selection in older Chinese adults.

Historical background and modern aspects of application transcranial micropolarization in epilepsy

The purpose of this literature review is to analyze the evidence of the effectiveness of the use of electrotherapy in the treatment of epilepsy. In chronological order, the opinions of various leading scientists and doctors of antiquity, XVIII, XIX centuries, such as Avicenna, J Wesley, W Erb, etc., based on the results of their own work, are presented on the possibilities of using animal, static, galvanic current in the treatment of epilepsy. Particular attention is paid to the transcranial micropolarization method, which has been gaining popularity in recent decades, based on the effect of low-intensity direct current on the projections of selected cortical structures. The data of experimental and clinical studies conducted under the guidance of corresponding member GA Vartanyan, academician NP Bekhtereva, etc., as well as foreign authors, testifying to the effective use of micropolarization in the treatment of epilepsy are presented. Possible prospects for the development of the method for obtaining the greatest therapeutic effect are discussed. The result of such work may be the development of a method of bio-controlled micropolarization.

Non-specific low back pain: principles and algorithms for successful management of patients in real clinical practice

Non-specific low back pain (LBP) occurs in most people at least once in a lifetime. In city polyclinics, every fourth patient complains of LBP. During the COVID-19 pandemic, the prevalence of acute non-specific LBP and chronic LBP have increased due to physical inactivity, chronic stress, and anxiety. Musculoskeletal LBP is the second most common cause of disability. In this regard, it is important to consider modern principles for the diagnosis and treatment of non-specific LBP. Diagnostic algorithms, “red flags” (dangerous symptoms), “yellow flags” (chronification factors) in LBP are discussed. Own clinical cases of patients with LBP with “red flags” are presented. Effective drug and non-drug methods of treatment of LBP are considered: patient education, kinesiotherapy, cognitive-behavioral therapy, manual therapy, the use of non-steroidal anti-inflammatory drugs, muscle relaxants. The role of aceclofenac and tolperisone in the treatment of LBP is discussed, clinical studies data on the efficacy and safety of these drugs in pain syndromes are presented. We present our own clinical observation of the successful management of a patient with chronic non-specific LBP.

Оцінка системних і органотоксичних ефектів, спричинених дією сучасних синтетичних опіоїдів: клінічні та судово-медичні аспекти

ABSTRACT. Establishing the cause of death in modern drug poisonings (overdoses) is not always a simple task. The systemic toxic effects resulting from the consumption of opioid drugs of the new generations are extremely diverse and extend far beyond the nervous system. The causes of death and mechanisms of tonatogenesis are also quite diverse, so their establishment is based on a wide range of data that can be obtained both during life and in the process of forensic research. Aim. Analysis of the causes of death due to drug poisoning (opioids-related) in adults according to the data of clinical and pathohistological studies. Materials and Methods. A retrospective analysis of the medical records of 164 patients who died in the hospital as a result of opioid poisoning during the period 2017–2021 was carried out; analyzed the data of sectional and microscopic studies of tissues (lungs, kidneys, myocardium, brain, liver, spleen) of 28 people with drug overdoses involving opioids who died outside hospitals during the same period. The preparations were examined using an Olympus CX 41 microscope in transmitted light, at magnifications of 40, 100, and 400 times. Results. Clinical, functional and laboratory tests carried out in the hospital's admissions department and in the intensive care unit revealed the following pathological conditions: cerebral coma, brain edema – 158 (96.3 %); respiratory failure – 73 cases (44.5 %); liver failure – 23 (13.4 %); kidney failure, including anuria – 14 (8.5 %); syndrome of prolonged compression of soft tissues and rhabdomyolysis – 9 (5.4 %); cardiopulmonary failure, including pulmonary edema – 19 (11.5 %); the presence of thrombophlebitis, purulent wounds, sepsis – 24 (14.6 %). According to examination data, toxicological anamnesis, and information from patients' relatives, the structure of concomitant pathology was determined in accordance with ICD-10 codes. According to the data of sectional and histological studies, in 89 cases (54.2 %), changes characteristic of a systemic inflammatory reaction and a chronic inflammatory process, including sepsis, were detected. The results of clinical and pathohistological studies show that drug users have various concomitant pathologies of many organs and systems (lungs, heart, liver, kidneys, etc.), which increases the toxic effect of drugs and conditions the features of tonatogenesis. Conclusions. The study of clinical and histological parallels in cases of sudden death due to drug overdoses will allow us to increase the level of our knowledge about the mechanisms of tonatogenesis and contribute to the determination of effective measures to prevent premature mortality of the population. Keywords: drugs, overdose, mortality, lethality, forensic medicine.

Development and Validation of txSim: A Model of Advanced Lung Cancer Treatment in Australia.

Since 2016, new therapies have transformed the standard of care for lung cancer, creating a need for up-to-date evidence for health economic modelling. We developed a discrete event simulation of advanced lung cancer treatment to provide estimates of survival outcomes and healthcare costs in the Australian setting that can be updated as new therapies are introduced. Treatment for advanced lung cancer was modelled under a clinician-specified treatment algorithm for Australia in 2022. Prevalence of lung cancer subpopulations was extracted from cBioPortal and the Sax Institute's 45 and Up Study, a large prospective cohort linked to cancer registrations. All costs were from the health system perspective for the year 2020. Pharmaceutical and molecular diagnostic costs were obtained from public reimbursement fees, while other healthcare costs were obtained from health system costs in the 45 and Up Study. Treatment efficacy was obtained from clinical trials and observational study data. Costs and survival were modelled over a 10-year horizon. Uncertainty intervals were generated with probabilistic sensitivity analyses. Overall survival predictions were validated against real-world studies. Under the 2022 treatment algorithm, estimated mean survival and costs for advanced lung cancer 10years post-diagnosis were 16.4months (95% uncertainty interval [UI]: 14.7-18.1) and AU$116,069 (95% UI: $107,378-$124,933). Survival and costs were higher assuming optimal treatment utilisation rates (20.5 months, 95% UI: 19.1-22.5; $154,299, 95% UI: $146,499-$161,591). The model performed well in validation, with good agreement between predicted and observed survival in real-world studies. Survival improvements for advanced lung cancer have been accompanied by growing treatment costs. The estimates reported here can be used for budget planning and economic evaluations of interventions across the spectrum of cancer control.

Nutriative Support Strategy in the Catering of Preschool Children with the Food Intolerance

Catering in child welfare institutions, considering the individual characteristics of food tolerance, is an urgent problem. The research aims at substantiating and optimizing the preschool children diet with food intolerance scientifically. The authors assessed diets of children with food intolerance – pupils of a specialized preschool institution located in the ecologically unfavorable territory of the Sverdlovsk region. A man developed scientifical ly based diets in accordance with the physiological needs and clinical and immunological children profile. 97.8 % of the children included in the study demonstrated food intoler ance, and each child had the recommendation to exclude from 1 to 29 products. The diets developed by the immunologist in preschool had an unreasonably limited range of food products, did not meet the physiological need for energy, macronutrients, vitamins B1, B2, calcium. A man relates eggs, milk and fish intolerance to a permeability violation of the natural intestinal mucosa barriers. The diet modeling in the preschool institutions relied on the clinical and immunological studies data, adaptive-compensatory and detoxification mechanisms of food substances action. The developed hypoallergenic menu enables to optimize the diet in terms of nutrient and amino acid composition, in particular by imple menting foods with increased nutritional and biological value. A man adjusted the diet to the physiological needs of children, strengthened the protective-compensatory and detoxification orientation to reduce the morbidity risk. The initially formed elimination nutrition model in preschool leads to a protein-energy deficit, dietary fiber, B vitamins and minerals (calcium) deficiency, which affected the physical children development, and the metals elimination, decrease in the protective and adaptive body functions, worsening atopic dermatitis symptoms.

Natural products and Hypertension: Scope and role in Antihypertensive Therapy

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

TransFAIR study: a European multicentre experimental comparison of EHR2EDC technology to the usual manual method for eCRF data collection

PurposeRegulatory authorities including the Food and Drug Administration and the European Medicines Agency are encouraging to conduct clinical trials using routinely collected data. The aim of the TransFAIR experimental comparison...

Early detection of Alzheimer’s Disease using MRI images and deep learning techniques

AbstractBackgroundAlzheimer’s is a neurodegenerative disease that diminishes the capability of individuals to perform their daily activities. It is an irreversible disease once it is started not able to stop it but early detection of the disease can help to slow down the progression of it by starting early treatment. In this experiment, we use MRI images and clinical study data available at the Alzheimer’s Disease Neuroimaging Initiative data set to detect the different stages of Alzheimer’s and forecast the duration required for the conversion from mild cognitive impairment to Alzheimer’s. The clinical signs of Alzheimer’s disease are portrayed by Age, patient education details, the progression rate of disease, and cognitive information. Done experiment by using Machine learning and Deep learning techniques like multi perceptron networks, Random forest, SVM, and decision tree classifiers to do binary and multi‐classification of Alzheimer’s Disease(AD), Late Mild cognitive impairment (MCI), Early cognitive impairment (EMCI), and Cognitive control(CN).MethodDeep learning techniqueResultan average the model achieved 91.25% of precision indicates 91.25% total positive images are correctly classified, 91.25% of sensitivity indicates 91.25% of total images are detected remaining are not, and achieved 95.52% of accuracyConclusionAlzheimer’s is a neuron degenerative disease. Currently no treatment is available to cure AD or to stop progress of disease. But detection of dementia at its early stage might help individual family to think about their future regarding financial issues. In this work we tried our best to categorize the different phases of AD. We used a deep neural network and achieved an accuracy of 95.52%.

Stem Cell Therapy for Complex Anal Fistula in Crohn`s Disease: Current Evidence and Future Perspectives

Despite progress in multidisciplinary diagnostic and therapeutic strategies, complex anal fistulas associated with Crohn's disease remain a challenge for both medical and surgical management. Conventional surgical techniques such as flap procedures or LIFT are still associated with considerable persistence and recurrence rates. Based on this background, results of stem cell therapy for Crohn's anal fistula have shown promising results and are a sphincter-preserving technique. In particular, adipose-derived, allogeneic stem cell therapy (Darvadstrocel) has shown encouraging healing rates within the randomised controlled ADMIRE-CD trial, which were reproducible in "real world" data of limited clinical studies. The current evidence has led to the integration of allogeneic stem cell therapy into international guidelines. To date, the definitive status of allogeneic stem cells in the multidisciplinary treatment algorithm for complex anal fistulas associated with Crohn's disease cannot be evaluated.