Deep Learning Mechanism for Predicting the Axillary Lymph Node Metastasis in Patients with Primary Breast Cancer.

The second largest cause of mortality worldwide is breast cancer, and it mostly occurs in women. Early diagnosis has improved further treatments and reduced the level of mortality. A unique deep learning algorithm is presented for predicting breast cancer in its early stages. This method utilizes numerous layers to retrieve significantly greater amounts of information from the source inputs. It could perform automatic quantitative evaluation of complicated image properties in the medical field and give greater precision and reliability during the diagnosis. The dataset of axillary lymph nodes from the breast cancer patients was collected from Erasmus Medical Center. A total of 1050 images were studied from the 850 patients during the years 2018 to 2021. For the independent test, data samples were collected for 100 images from 95 patients at national cancer institute. The existence of axillary lymph nodes was confirmed by pathologic examination. The feed forward, radial basis function, and Kohonen self-organizing are the artificial neural networks (ANNs) which are used to train 84% of the Erasmus Medical Center dataset and test the remaining 16% of the independent dataset. The proposed model performance was determined in terms of accuracy (Ac), sensitivity (Sn), specificity (Sf), and the outcome of the receiver operating curve (Roc), which was compared to the other four radiologists' mechanism. The result of the study shows that the proposed mechanism achieves 95% sensitivity, 96% specificity, and 98% accuracy, which is higher than the radiologists' models (90% sensitivity, 92% specificity, and 94% accuracy). Deep learning algorithms could accurately predict the clinical negativity of axillary lymph node metastases by utilizing images of initial breast cancer patients. This method provides an earlier diagnostic technique for axillary lymph node metastases in patients with medically negative changes in axillary lymph nodes.

Machine Learning Approach for Cardiovascular Risk and Coronary Artery Calcification Score.

Coronary artery calcification (CAC) could assist in the discovery of new risk elements for coronary artery disorder. CAC evaluation, on the other hand, is difficult due to the wide range of CAC in the populations. As a reason, evaluating and analysing data among research have become complicated. In the Research of Inherited Risk Factors for Coronary Atherosclerosis, we used CAC information to test the effects of different analytical methodologies on the correlation with recognized cardiovascular risk elements in asymptomatic patients. Cardiac computed tomography (CT) is also seeing an increase in examinations, and machine learning (ML) could assist with the growing amount of extracted data. Furthermore, there are other sectors in cardiac CT where machine learning could be crucial, including coronary calcium scoring, perfusion, and CT angiography. The establishment of risk evaluation algorithms based on information from CAC utilizing machine learning could assist in the categorization of patients undergoing cardiovascular into distinct risk groups and effectively adapt their treatments to their unique situations. Our findings imply that for forecasting CVD occurrences in asymptomatic people, age-sex segmentation by CAC percentile rank is as effective as absolute CAC scoring. Longitudinal population-based investigations are currently underway and would offer further definitive findings. While machine learning is a strong technology with a lot of possibilities, its implementations in the domain of cardiac CAC are generally in the early stages of development and are not currently commonly accessible in medical practise because of the requirement for substantial verification. Enhanced machine learning will, however, have a significant effect on cardiovascular and coronary artery calcification in the upcoming years.

A Deep Learning Framework for Earlier Prediction of Diabetic Retinopathy from Fundus Photographs.

Diabetic patients can also be identified immediately utilizing retinopathy photos, but it is a challenging task. The blood veins visible in fundus photographs are used in several disease diagnosis approaches. We sought to replicate the findings published in implementation and verification of a deep learning approach for diabetic retinopathy identification in retinal fundus pictures. To address this issue, the suggested investigative study uses recurrent neural networks (RNN) to retrieve characteristics from deep networks. As a result, using computational approaches to identify certain disorders automatically might be a fantastic solution. We developed and tested several iterations of a deep learning framework to forecast the progression of diabetic retinopathy in diabetic individuals who have undergone teleretinal diabetic retinopathy assessment in a basic healthcare environment. A collection of one-field or three-field colour fundus pictures served as the input for both iterations. Utilizing the proposed DRNN methodology, advanced identification of the diabetic state was performed utilizing HE detected in an eye's blood vessel. This research demonstrates the difficulties in duplicating deep learning approach findings, as well as the necessity for more reproduction and replication research to verify deep learning techniques, particularly in the field of healthcare picture processing. This development investigates the utilization of several other Deep Neural Network Frameworks on photographs from the dataset after they have been treated to suitable image computation methods such as local average colour subtraction to assist in highlighting the germane characteristics from a fundoscopy, thus, also enhancing the identification and assessment procedure of diabetic retinopathy and serving as a skilled guidelines framework for practitioners all over the globe.

Maternal and perinatal outcomes in women undergoing expectant management of early-onset pre-eclampsia: A retrospective cohort study

Background. Expectant management of early-onset pre-eclampsia, with the aim of improving perinatal outcomes, may increase the risk of maternal morbidity. Objective. To study the maternal and perinatal outcomes and their association with various risk factors in women undergoing expectant management for early-onset pre-eclampsia. Methods. A retrospective cohort study was carried out in a tertiary centre in south India between April 2014 and June 2015. We studied 201 women with singleton pregnancies with pre-eclampsia diagnosed between 28 and 34 weeks' gestation. Demographic data, medication and treatment details, and delivery data were extracted from maternal charts. The primary outcomes were: (i) composite maternal outcomes, defined as the development of any of eclampsia, abruptio placentae, pulmonary oedema or renal failure; and (ii) perinatal mortality. Logistic regression was used to assess the independent association risk factors with primary outcomes, after adjusting for other variables. Results. Sixty-nine women (34.3%) had one or more of the composite adverse maternal outcomes, and there were 74 (36.8%) cases of perinatal mortality. The presence of imminent symptoms (odds ratio (OR)=2.35) and multiparity (OR=2.31) were associated with composite adverse maternal outcomes, whereas low birth weight and breech vaginal delivery were associated with perinatal mortality. Perinatal mortality was higher in women with pre-eclampsia diagnosed between 28 and 30 weeks. Gestational age at diagnosis was not found to be associated with composite adverse maternal outcomes or perinatal morbidity. Conclusion. Expectant management in early-onset pre-eclampsia can be safely considered without increasing maternal risk, after thorough counselling about outcomes, based on the available neonatal facilities in low-resource settings

Spontaneous appearance of Tay-Sachs disease in an animal model.

Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of beta-hexosaminidase A (Hex A). Deficiency of Hex A in TSD is caused by a defect of the alpha-subunit resulting from mutations of the HEXA gene. To date, there is no effective treatment for TSD. Animal models of genetic diseases, similar to those known to exist in humans, are valuable and essential research tools for the study of potentially effective therapies. However, there is no ideal animal model of TSD available for use in therapeutic trials. In the present study, we report an animal model (American flamingo; Phoenicopterus ruber) of TSD with Hex A deficiency occurring spontaneously in nature, with accumulation of G(M2)-ganglioside, deficiency of Hex A enzymatic activity, and a homozygous P469L mutation in exon 12 of the hexa gene. In addition, we have isolated the full-length cDNA sequence of the flamingo, which consists of 1581 nucleotides encoding a protein of 527 amino acids. Its coding sequence indicates approximately 71% identity at the nucleotide level and about 72.5% identity at the amino acid level with the encoding region of the human HEXA gene. This animal model, with many of the same features as TSD in humans, could represent a valuable resource for investigating therapy of TSD.

Rapid detection of three large novel deletions of the aspartoacylase gene in non-Jewish patients with Canavan disease.

Canavan disease (CD), an autosomal recessive neurodegenerative disorder, is caused by mutations in the aspartoacylase (ASPA) gene. In the present study, the ASPA gene was analyzed in 24 non-Jewish patients with CD from 23 unrelated families. Within this cohort, we found three large novel deletions of approximate 92, 56, and 12.13 kb in length, using both self-ligation of restriction endonuclease-digested DNA fragments with long-distance inverse PCR and multiplex dosage quantitative PCR analysis of genomic DNA. The 92 kb large deletion results in complete absence of the ASPA gene in one homozygous and one compound heterozygous patient, respectively. The 56 kb large deletion causes absence of the majority of the ASPA gene except for exon 1 alone in a compound heterozygous patient. The 12.13 kb deletion involves deletion of the ASPA gene from intron 3 to intron 5 including exons 4 and 5 (I3 to E4E5I5) in a compound heterozygous patient. Patients with the three large deletions clinically manifested severe symptoms at birth, including seizures. Our study showed that the combined use of long-distance inverse PCR and multiplex dosage quantitative PCR analysis of genomic DNA is a helpful and rapid technique to search for large deletions, particularly for detection of large deletions in compound heterozygous patients.

Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort.

OBJECTIVES: With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. METHODS: Demographic information and fasting blood samples were collected from 419 antiretroviral-naive HIV-1-infected patients. RESULTS: The average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/microL, the mean baseline log10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. CONCLUSIONS: Both HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied.

Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease.

The tremor rat is a spontaneous epilepsy model with a seizure phenotype caused by a deletion in the aspartoacylase (ASPA) gene. The absence of ASPA expression in these animals results in undetectable levels of enzyme activity and the accumulation of the substrate N-acetyl-aspartate (NAA) in brain, leading to generalized myelin vacuolation and severe motor and cognitive impairment. In support of human gene therapy for CD, recombinant adeno-associated viral vector (AAV-2) expressing ASPA was stereotactically delivered to the tremor rat brain and effects on the mutant phenotype were measured. AAV-ASPA gene transfer resulted in elevated aspartoacylase bioactivity compared to untreated mutant animals and elicited a significant decrease in the pathologically elevated whole-brain NAA levels. Assessment of motor function via quantitative rotorod testing demonstrated that rats injected with AAV-ASPA significantly improved on tests of balance and coordinated locomotion compared to animals receiving control vectors. This study provides evidence that AAV-2-mediated aspartoacylase gene transfer to the brain improves biochemical and behavioral deficits in tremor rat mutants (tm/tm) and supports the rationale of human gene transfer for Canavan disease.

Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy).

Umbilical cord blood (UCB) has received increasing attention as a source of unrelated hematopoietic stem cells for transplantation. Lysosomal diseases have been effectively treated and normal enzymatic activity has occurred subsequent to engraftment using UCB. The use of donor cells with normal amounts of enzyme, rather than those from carriers whose level may be 50% or less, is an obvious goal. The frequency of such heterozygotes varies from 1:10 to 1:140 or lower depending upon the disease at issue. We assayed the levels of lysosomal enzymes in normal UCB in random samples as well as those used for transplantation. We measured the following enzymatic activities: alpha-l-iduronidase (Hurler), galactocerebrosidase (globoid cell leuko- dystrophy) and arylsulfatase A (metachromatic leukodystrophy). For the latter, levels of activity in UCB are comparable to those found in adult blood. In the case of arylsulfatase B (Maroteaux-Lamy) a level lower than adult level was found. An informed choice by the transplanting physician based on the activity of the relevant enzyme in the UCB donor will provide a better opportunity for an improved prognosis for more complete correction of the recipient's primary disease. Bone Marrow Transplantation (2000) 25, 541-544.

Randomized, controlled trial of caloric supplements in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVE: To compare the efficacy of three nutritional regimens in the prevention of weight loss. DESIGN: A three-arm randomized controlled trial with primary outcome measure percent change in weight over four months. PATIENTS: A total of 536 patients with CD4 count <200 cells/mm3 and stable weight, defined as <5% weight loss as determined by a weight measurement 3 to 6 months before randomization were recruited at fourteen administrative units in the United States, each unit consisting of multiple primary care sites. INTERVENTION: The three arms were 500 kcal daily of caloric supplement with peptides and medium-chain triglycerides plus a multivitamin and mineral supplement, 500 kcal of a caloric supplement with whole protein and long-chain triglycerides plus a multivitamin and mineral supplement, and a multivitamin and mineral supplement only. RESULTS: There were no significant differences among the three regimens in the percent change in weight (p = .74) and body cell mass (p = .63). On average, 65% of the recommended 500 kcal/day of caloric supplements containing peptides with medium-chain triglycerides and 82% of the 500 kcal/day of the caloric supplement containing whole protein and long-chain triglycerides were consumed. CONCLUSIONS: Caloric supplements do not promote increases in average weight or body cell mass in weight-stable, HIV-infected adults beyond that offered by a multivitamin and mineral supplement.

Substitution of alanine543 with a threonine residue at the carboxy terminal end of the beta-chain is associated with thermolabile hexosaminidase B in a Jewish family of Oriental ancestry.

Thermolabile forms of the lysosomal enzyme beta-hexosaminidase B (Hex B), likely to result from different genetic defects, have been described. Ten individuals in five generations of a family of Oriental Jewish ancestry were identified biochemically as carriers of a thermolabile Hex B form. The beta-chain thermolability was found to be associated with the presence of a G --> A transition at nucleotide 1627 of the HEX B gene causing the substitution of Ala543 with a threonine. Oriental Jew whose Hex B was heat labile. Since thermolabile Hex B has been shown to occur more frequently among Jews of Oriental origin, the Ala543 --> Thr mutation may be the common mutation associated with beta-chain thermolability in this ethnic group.

Mucolipidosis IV: morphology and histochemistry of an autopsy case.

Mucolipidosis Type IV is a rare, autosomal recessive disorder characterized by corneal opacification, mental retardation, and delayed motor milestones. Whereas lysosomal storage material has been demonstrated in biopsied tissues and leukocytes, the complete autopsy pathology, including neuropathology, is unknown. The metabolic defect remains speculative. We report the general and neuropathologic findings of the only known autopsy. In the central nervous system, neuronal loss in the cerebral cortex, basal ganglia, deep cerebellar nuclei, and brainstem nuclei was marked by astrocytosis; the cytoplasm of residual neurons had brown granules. These granules were positive with periodic acid-Schiff, Concanavalia ensiformis, and Sudan black, but not with Luxol-fast blue. Ultrastructurally, neurons contained lysosomes laden with osmiophilic, amorphous and granular material, and few lamellated membrane structures. Hepatocytes, epithelia, endothelia, chondrocytes, and tissue macrophages also stained positively with Datura stramonium and Ricinus communis-I agglutinins, with renal glomeruli also staining with peanut agglutinin; most non-neural cells contained osmiophilic granules on toluidine blue-stained, plastic embedded sections, corresponding to lamellated membrane structures. These findings complement the previously reported ocular morphology and brain and liver biochemistry performed in the same patient, and suggest that the storage material in neurons differs from that in non-neural cells. Furthermore, the underlying defect is not likely to be a deficiency of a single enzyme (i.e. a lysosomal hydrolase).

Secondary abdominal pregnancy.

Advanced abdominal pregnancy is a rare event with a high fetal and maternal morbidity and mortality. We present 3 cases of abdominal pregnancy seen at our hospital. The perinatal mortality was 100% with no maternal deaths. Literature has been reviewed and management of abdominal pregnancy is discussed. Awareness of this condition and its clinical features is important in preventing abdominal pregnancy related morbidity, mortality. Careful clinical examination coupled with investigatory aids like X-rays and ultrasound will clinch the diagnosis. Most of the patients require early laparotomy following diagnosis and the morbidity and mortality are high particularly for the fetus.

Internal iliac artery ligation in obstetrics and gynecology. Ten years experience.

Twenty-two cases of bilateral internal iliac artery ligation done in the Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India over a period of 10 years (1981-1990) were studied. Various indications and complications were analysed. Internal iliac artery ligation is a life-saving procedure in pelvic hemorrhage. Complications are infrequents.

Adult-onset lysosomal storage disease in a Schipperke dog: clinical, morphological and biochemical studies.

An adult-onset lysosomal storage disorder was diagnosed in a 5-year-old Schipperke dog with progressive cerebellar and central vestibular signs. It was characterized by cerebellar atrophy with extensive loss of Purkinje and granular cells, and hydrocephalus. Enlarged and vacuolated neurons were observed in spinal cord and brain; pancreatic centrolobular and islet cells were also vacuolated. Ultrastructurally, enlarged secondary lysosomes laden with lamellated membrane structures were present in neurons and empty enlarged vacuoles were found in pancreatic centroacinar, ductal, and islet cells. On frozen sections neurons stained with Ricinus communis agglutinin-I and wheat germ agglutinin. On paraffin sections neurons stained with luxol fast blue, periodic acid-Schiff, Concanavalia ensiformis agglutinin, and were autofluorescent. These findings indicate an accumulation of glycolipids containing terminal beta-galactosyl and alpha-sialyl residues, and N-linked oligosaccharides. Tissue activity of lysosomal beta-galactosidase was 50% of normal and the activity of beta-hexosaminidase was elevated. Brain lipid-bound sialic acid was twice normal, with a small increase of GM1-ganglioside, but there was a significant elevation of GM2 (GD2) and GM3 (GD3). In addition, significant elevations of sialylated and non-sialylated oligosaccharides were noted. These clinical, biochemical and pathological findings are similar to those observed in human patients with adult-onset galactosialidosis.

Dysmyelinogenesis in animal model of GM1 gangliosidosis.

Magnetic resonance imaging (MRI), pathologic examinations, and biochemical analyses were performed on 2 different canine mutants with GM1 gangliosidosis (i.e., English Springer Spaniel and Portuguese Water Dog) and on age- and sex-matched controls. Serial MRI studies were also performed on a child with infantile-onset GM1 gangliosidosis. The affected dogs had abnormalities on MRI, including a relative increase in gray matter and an abnormal signal intensity of cerebral and cerebellar white matter observed on T2-weighted MRI. White matter changes on MRI were similar to white matter abnormalities observed in a 15-month-old boy with GM1 gangliosidosis. The weight ratio of white to gray matter from the frontal lobe was markedly reduced. Microscopic examination revealed characteristic ballooned neurons which stained lightly with Luxol-fast blue. The central cerebral and cerebellar folia white matter exhibited pallor and gliosis, while the corpus callosum and fornix stained normally with Luxol-fast blue. Axons appeared intact on Bodian staining. Ultrastructural studies revealed fewer myelinated axons in affected puppies. Total gangliosides in gray matter were elevated. Thin-layer chromatography demonstrated GM1 ganglioside as the predominant ganglioside. The amount of cerebrosides and sulfatides was reduced in the gray and white matter when compared to controls but the ratio in gray and white matter remained unchanged. Immunostaining of neutral glycolipids disclosed increased amounts of stage-specific embryonic antigen-1 glycolipid in gray matter. These findings suggest that canine models for GM1 gangliosidosis are associated with abnormal myelin development which may be similar to the human disease.

Canine GM1-gangliosidosis. A clinical, morphologic, histochemical, and biochemical comparison of two different models.

The clinical, morphologic, histochemical, and biochemical features of GM1-gangliosidosis in two canine models, English Springer Spaniel (ESS) and Portuguese Water Dog (PWD), have been compared. The disease onset, its clinical course, and survival period of the affected dogs were similar in both models. Skeletal dysplasia was noted radiographically at 2 months of age, whereas at 4 1/2 months of age there was progressive neurologic impairment. However, dwarfism and coarse facial features were seen only in ESS. Both models had similar deficiency in activity of lysosomal beta-galactosidase, but possessed a normal protein activator for GM1-beta-galactosidase. Both models stored GM1-ganglioside, asialo-GM1, and oligosaccharides in brain. Furthermore, only the PWD stored glycoproteins containing polylactosaminoglycans in visceral organs, and neither model stored them in the brain. Morphologically, both models demonstrated similar storage material in multiple tissues and cell types. The ultrastructure of the storage material was cell-type specific and identical in both models. However, some differences in the lectin staining pattern were noted. Our clinical, biochemical, and histochemical findings indicate that PWD and ESS may represent two different mutations of the beta-galactosidase gene. Moreover, the authors conclude that it is difficult, and inappropriate, to apply the human classification of GM1-gangliosidosis (i.e. infantile, juvenile, and adult forms) to these canine models.

Adult onset lysosomal storage disease in a Tibetan terrier: clinical, morphological and biochemical studies.

We describe a novel late-onset lysosomal lipid storage disease affecting a Tibetan terrier. The principal clinical manifestations include visual loss, progressive cerebellar ataxia and dementia. A necropsy of an affected 10-year-old dog demonstrated cerebellar atrophy. Histological analysis revealed extensive loss of retinal ganglion cells and cerebellar Purkinje cells, and mild to moderate loss of neurons in the cerebrum, basal ganglia and spinal cord. There were generalized neuronal hypertrophy and multifocal neuronal necrosis associated with the presence of enlarged macrophages. Neurons and perineuronal macrophages contained cytoplasmic granules that stained with PAS, luxol fast blue and several lectins. The granules were sudanophilic and autofluorescent. Electron microscopic analysis revealed lysosomes laden with lamellated membrane structures in neurons, pancreatic ductal and centroacinar cells and in cultured fibroblasts. These findings indicate lysosomal storage of both lipid and carbohydrate. Biochemical analysis of brain lipids and numerous lysosomal enzyme assays of leukocytes and cultured fibroblasts were unsuccessful in elucidating the underlying enzyme defect, although a generalized increase of brain gangliosides was noted.

Clinical, neurophysiological, biochemical and morphological features of eyes in Persian cats with mannosidosis.

The clinical, neurophysiological, morphological and biochemical manifestation of eyes from Persian kittens affected with alpha-mannosidosis were studied. Clinically the disease is characterized by progressive corneal and lenticular opacification. In addition there is asymmetry in shape and latency of signal conductions which were demonstrated by visual evoked potential studies. Morphological and histochemical studies revealed vacuolization of various ocular cell types which stained positively with Concanavalia ensiformis agglutinin (Con A) and wheat germ agglutinin (WGA). Biochemical studies illustrated low activity of acid alpha-mannosidase in cultured keratocytes and abnormal storage of partially degraded oligosaccharides in these cells, in vitreous humor and lens. This comprehensive study of ocular alpha-mannosidosis demonstrates enzyme deficiency which leads to abnormal storage of oligosaccharides in affected cells and is manifested by morphological alterations and functional impairment.