Biomarker profiling and integrating heterogeneous models for enhanced multi-grade breast cancer prognostication.

BACKGROUND: Breast cancer remains a leading cause of female mortality worldwide, exacerbated by limited awareness, inadequate screening resources, and treatment options. Accurate and early diagnosis is crucial for improving survival rates and effective treatment. OBJECTIVES: This study aims to develop an innovative artificial intelligence (AI) based model for predicting breast cancer and its various histopathological grades by integrating multiple biomarkers and subject age, thereby enhancing diagnostic accuracy and prognostication. METHODS: A novel ensemble-based machine learning (ML) framework has been introduced that integrates three distinct biomarkers-beta-human chorionic gonadotropin (ß-hCG), Programmed Cell Death Ligand 1 (PD-L1), and alpha-fetoprotein (AFP)-alongside subject age. Hyperparameter optimization was performed using the Particle Swarm Optimization (PSO) algorithm, and minority oversampling techniques were employed to mitigate overfitting. The model's performance was validated through rigorous five-fold cross-validation. RESULTS: The proposed model demonstrated superior performance, achieving a 97.93% accuracy and a 98.06% F1-score on meticulously labeled test data across diverse age groups. Comparative analysis showed that the model outperforms state-of-the-art approaches, highlighting its robustness and generalizability. CONCLUSION: By providing a comprehensive analysis of multiple biomarkers and effectively predicting tumor grades, this study offers a significant advancement in breast cancer screening, particularly in regions with limited medical resources. The proposed framework has the potential to reduce breast cancer mortality rates and improve early intervention and personalized treatment strategies.

Recent Research Trends Against Skin Carcinoma - An Overview.

Skin cancer is a prevalent and sometimes lethal cancer that affects a wide range of people. UV radiation exposure is the main cause of skin cancer. Immunosuppression, environmental factors, and genetic predisposition are other contributing variables. Fair-skinned people and those with a history of sunburns or severe sun exposure are more likely to experience this condition. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) are the three main forms. Melanoma poses a bigger hazard because of its tendency for metastasis, while SCC and BCC have limited metastatic potential. Genetic mutations and changes to signalling pathways such as p53 and MAPK are involved in pathogenesis. Early diagnosis is essential, and molecular testing, biopsy, dermoscopy, and visual inspection can all help. In addition to natural medicines like curcumin and green tea polyphenols, treatment options include immunotherapy, targeted therapy, radiation, surgery, and chemotherapy. Reducing the incidence of skin cancer requires preventive actions, including sun protection and early detection programs. An overview of skin cancers, including their forms, pathophysiology, diagnosis, and treatment, highlighting herbal therapy, is given in this review.

Neurological Wilson's disease without hepatic involvement in an adolescent female.

A female adolescent presented with a 9 month history of progressive involuntary movements, initially manifesting as finger tremors and evolving into flinging motions of the extremities, resulting in an inability to walk over the last 4 months. Concurrently, she developed dysarthria. Neurologically, she exhibited normal power, rigidity and brisk deep tendon reflexes, with a downgoing plantar reflex. Contrast-enhanced MRI revealed hyperintensity in bilateral caudate lobes, basal ganglia and pons, indicative of Wilson's disease. Liver function tests and ultrasound were normal while Kayser-Fleischer rings were confirmed by slit lamp examination. Serum ceruloplasmin was low, 24-hour urine copper was elevated (125.5 mcg) and whole exome sequencing identified a heterozygous ATP7B mutation, confirming the diagnosis. Isolated neurological involvement without hepatic involvement is an extremely rare presentation and needs clinical expertise to delineate Wilson's disease as a possible aetiology.

Understanding the novel MCM8 gene mutation: primary ovarian insufficiency and uterine hypoplasia in siblings.

This case report elucidates a scenario involving two sibling sisters born out of consanguineous marriage-one initially presenting with lower respiratory infection, concurrently exhibiting short stature and primary amenorrhoea. Investigation into the primary amenorrhoea unveiled hypergonadotropic hypogonadism, confirmed by the absence of ovaries and a hypoplastic uterus on pelvic MRI. Genetic analysis via whole exome sequencing identified a homozygous variant NM_001282717.2: c.808C>T in the MCM8 gene, located on exon 8 of chromosome 20, inherited in an autosomal recessive manner. The scarcity of primary ovarian insufficiency cases linked to MCM8 highlights the necessity of thoroughly investigating the genetic and clinical consequences of such variants.

Phytoconstituents-Based Nanotherapeutic Approach for the Effective Management of Joint Inflammatory Condition: Arthritis.

Arthritis, a prevalent inflammatory joint condition, presents challenges for effective therapeutic interventions, with conventional treatments often limited in efficacy and associated with adverse effects. Recent years have witnessed a growing interest in exploring natural compounds, particularly phytoconstituents, renowned for their anti-inflammatory and joint-protective properties. This review aims to illuminate the potential of employing nanotherapeutic approaches with phytoconstituents for enhanced arthritis management. The integration of nanotechnology with phytoconstituents emerges as a promising strategy, addressing limitations in traditional arthritis treatments. Nanocarriers like liposomes and nanoparticles provide a platform for targeted drug delivery, improving the bioavailability of phytoconstituents. Furthermore, the combined effects of phytoconstituents can be leveraged to target multiple pathways in arthritis pathogenesis, including inflammation, oxidative stress, and cartilage degradation. Key phytoconstituents, such as curcumin, resveratrol, and quercetin, exhibit anti-inflammatory and immunomodulatory properties. Nevertheless, their therapeutic potential is often impeded by challenges like poor solubility, stability, and bioavailability. Nanocarriers offer solutions by enhancing pharmacokinetics and enabling sustained release, thereby boosting overall therapeutic efficacy. The review explores the mechanisms underlying the anti-arthritic effects of phytoconstituents and their nanoformulations, including the modulation of pro-inflammatory cytokines, inhibition of matrix metalloproteinases, and reduction of oxidative stress. In summary, the integration of phytoconstituents with nanotechnology presents a promising avenue for developing targeted and effective arthritis therapies. This comprehensive review serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking innovative approaches to address the intricate challenges associated with arthritis management.

Substrate-based synthetic strategies and biological activities of 1,3,4-oxadiazole: A review.

The five-membered 1,3,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bio-isosteric properties and an unusually wide spectrum of biological activities. After a century since 1,3,4-oxadiazole was discovered, its uncommon potential attracted medicinal chemist's attention, leading to the discovery of a few presently accessible drugs containing 1,3,4-oxadiazole units, and a large number of patents have been granted on research related to 1,3,4-oxadiazole. It is worth noting that interest in 1,3,4-oxadiazoles' biological applications has doubled in the last few years. Herein, this review presents a comprehensive overview of the recent achievements in the synthesis of 1,3,4-oxadiazole-based compounds and highlights the major advances in their biological applications in the last 10 years, as well as brief remarks on prospects for further development. We hope that researchers across the scientific streams will benefit from the presented review articles for designing their work related to 1,3,4-oxadiazoles.

Oral Health-Related Quality of Life in Rare Disorders of Congenital Facial Weakness.

Congenital facial weakness (CFW) encompasses a heterogenous set of rare disorders presenting with decreased facial movement from birth, secondary to impaired function of the facial musculature. The aim of the present study is to provide an analysis of subject-reported oral health-related quality of life (OHRQoL) in congenital facial weakness (CFW) disorders. Forty-four subjects with CFW and age- and sex- matched controls were enrolled in an Institutional Review Board (IRB)-approved study. Demographic data, medical and surgical history, comprehensive oral examination, and the Oral Health Impact Profile (OHIP-14) were obtained. Compared to unaffected controls, subjects with CFW had higher OHIP-14 scores overall (mean ± SD: 13.11 ± 8.11 vs. 4.46 ± 4.98, p < 0.0001) and within five of seven oral health domains, indicating decreased OHRQoL. Although subjects with Moebius syndrome (MBS) were noted to have higher OHIP-14 scores than those with Hereditary Congenital Facial Paresis (HCFP), there was no significant correlation in OHIP-14 score to age, sex, or specific diagnosis. An increase in OHIP-14 scores in subjects was detected in those who had undergone reanimation surgery. In conclusion, subjects with CFW had poorer OHRQoL compared to controls, and subjects with MBS had poorer OHRQoL than subjects with HCFP. This study provides better understanding of oral health care needs and quality of life in a CFW cohort and suggests that guidelines for dental treatment are required.

Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.

Neurodegenerative diseases are emerging as a global health concern in the current scenario, and their association with mitochondrial defects has been a potential area of research. Mitochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA mutations that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifically mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mitochondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structureactivity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the management of neurodegenerative diseases associated with mitochondrial defects. This review provides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

Dengue-associated longitudinally extensive transverse myelitis.

We diagnosed a patient with dengue fever who developed acute onset of sensorimotor quadriparesis with bladder involvement, and facial nerve involvement. Despite initial negative results in routine investigations and cerebrospinal fluid analysis, spinal MRI confirmed longitudinally extensive transverse myelitis. The aetiological workup was negative, prompting an investigation into the presence of dengue in the cerebrospinal fluid, which returned positive. This case underscores the importance of considering rare neurological complications in dengue, the value of advanced diagnostic techniques and the potential effectiveness of tailored interventions in challenging cases.

Citron Kinase Is a Druggable Target in Treatment-Resistant Prostate Cancer.

Prolonged treatment with androgen deprivation therapy (ADT) inevitably leads to castration-resistant prostate cancer (CRPC). Development of novel androgen-targeting agents and chemo/radiotherapies has resulted in improved survival. However, metastatic CRPC remains incurable. New therapeutics are greatly needed, and exploration of novel pathways such as the mechanisms underlying prostate cancer cell proliferation could potentially augment the natural course of CRPC. In the latest issue of Cancer Research, Rawat and colleagues delved deeply into the mechanistic role of citron kinase (CIT) in orchestrating prostate cancer proliferation and revealed its catalytic activity as a druggable target for treatment-resistant prostate cancer. The researchers utilized in vitro and in vivo methodologies to elucidate the function of CIT in mediating uncontrolled interphase progression and prostate cancer growth. Furthermore, the authors employed both androgen receptor-dependent and independent models to validate the significance of CIT kinase activity as a crucial factor in driving treatment-resistant prostate cancer growth. At a mechanistic level they determined that the E2F2-Skp2-p27 axis regulates CIT expression. Finally, they defined the landscape of CIT substrates in prostate cancer that encompasses a spectrum of cellular functions that spans key proliferation regulators to alternative splicing events. This comprehensive work provides insights into CIT as a potential biomarker for prostate cancer treatment resistance and disease progression and establishes the CIT kinase domain as a druggable target in CRPC. See related article by Rawat et al., p. 4142.

Diversity and seasonal fluctuation of predominant microbial communities in Bhitarkanika, a tropical mangrove ecosystem in India

Different groups of microorganisms are present in mangrove areas, and they perform complex interactions for nutrient and ecological balances. Since little is known about microbial populations in mangroves, this study analyzed the microbial community structure and function in relation to soil physico-chemical properties in Bhitarkanika, a tropical mangrove ecosystem in India. Spatial and seasonal fluctuations of thirteen important groups of microorganisms were evaluated from the mangrove forest sediments during different seasons, along with soil physico-chemical parameters. The overall microbial load (x10(5)cfu/g soil) in soil declined in the order of heterotrophic, free living N2 fixing, Gram-negative nitrifying, sulphur oxidizing, Gram-positive, spore forming, denitrifying, anaerobic, phosphate solubilizing, cellulose degrading bacteria, fungi and actinomycetes. Populations of the heterotrophic, phosphate solubilizing, sulphur oxidizing bacteria and fungi were more represented in the rainy season, while, Gram-negative, Gram-positive, nitrifying, denitrifying, cellulose decomposing bacteria and actinomycetes in the winter season. The pool size of most of other microbes either declined or maintained throughout the season. Soil nutrients such as N, P, K (Kg/ha) and total C (%) contents were higher in the rainy season and they did not follow any common trend of changes throughout the study period. Soil pH and salinity (mS/cm) varied from 6-8 and 6.4-19.5, respectively, and they normally affected the microbial population dynamics. Determination of bacterial diversity in Bhitarkanika mangrove soil by culture method showed the predominance of bacterial genera such as Bacillus, Pseudomonas, Desulfotomaculum, Desulfovibrio, Desulfomonas, Methylococcus, Vibrio, Micrococcus, Klebsiella and Azotobacter. Principal component analysis (PCA) revealed a correlation among local environmental variables with the sampling locations on the microbial community in the mangrove soil. Rev. Biol. Trop. 60 (2): 909-924. Epub 2012 June 01.

En las zonas de manglares están presentes diferentes grupos de microorganismos, los cuales presentan complejas interacciones que afectan los balances ecológicos y de nutrientes. Debido a que se sabe poco sobre las poblaciones microbianas en los manglares, este estudio analiza la estructura y función de la comunidad microbiana según las propiedades físico-químicas del suelo en Bhitarkanika, un ecosistema de manglares tropicales en la India. Se evaluaron las fluctuaciones espaciales y temporales de 13 grupos de microorganismos importantes en el sedimento de los manglares durante diferentes temporadas y parámetros físico-químicos del suelo. La carga microbiana total (x10(5)cfu/g de suelo) en el suelo se redujo en la categoría de las heterotróficas, de las bacterias libres fijadoras de N2, Gram-negativas nitrificantes, oxidativas de azufre, Gram-positivas, formadoras de esporas, desnitrificantes, anaeróbicas, las solubilizadoras de fosfato, bacterias degradadoras de celulosa, hongos y actinomicetos. Las poblaciones de heterótrofos, solubilizadoras de fosfato, oxidativas de azufre y los hongos estuvieron más representadas en la temporada lluviosa, mientras que, las Gram-negativas y Gram-positivas, nitrificantes, desnitrificantes, descomponedoras de celulosa y los actinomicetos, en la temporada de invierno. El tamaño poblacional de otros microorganismos disminuyó o se mantuvo durante toda la temporada. Los nutrientes del suelo, tales como N, P, K (Kg/ha) y el contenido total de C (%) fueron mayores en la temporada de lluvias, y no siguieron ninguna tendencia común de cambio a través del período de estudio. El pH del suelo y la salinidad (mS/cm) variaron de 6-8 y 6.4-19.5, respectivamente, lo que afectó significativamente la dinámica de la población microbiana. La determinación de la diversidad de bacterias en el suelo del manglar Bhitarkanika por el método de cultivo mostró el predominio de los géneros de bacterias como Bacillus, Pseudomonas, Desulfotomaculum, Desulfovibrio, Desulfomonas, Methylococcus, Vibrio, Micrococcus, Klebsiella y Azotobacter. El análisis de componentes principales (ACP) reveló una correlación entre las variables locales del ambiente y los sitios de muestreo en la comunidad microbiana en el suelo del manglar.