Concomitant Boost With Six Fractions of Radiation a Week in Locally Advanced Head and Neck Cancer Patients: A Prospective Study.

Background and objective Radiation therapy plays a significant role in the radical treatment of locally advanced head and neck cancers. Studies have shown the radiobiological advantage of accelerated chemoradiation over conventional chemoradiation as it reduces the chances of accelerated repopulation and decreases overall treatment time. This study aimed to assess the response and toxicities of accelerated concomitant chemoradiation in locally advanced head and neck cancer patients. Methods A total of 51 patients were enrolled and treated with accelerated concomitant chemoradiation, receiving one fraction of radiation per day, six fractions per week, with the sixth fraction as a boost on Saturdays, with weekly concurrent cisplatin at 40 mg/m2. Patients were followed up till six months after treatment completion. Radiological investigation was done to assess response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.128, and acute toxicities were assessed according to Radiation Therapy Oncology Group (RTOG) criteria. Results The median follow-up period was six months; 28 patients (62.22%) had a complete response and 17 (37.78%) had a partial response at six months post-completion of the treatment. The maximum acute toxicities developed at the completion of treatment. Grade III and IV mucositis developed in 14 patients (31.11%) and grade III dermatitis developed in one patient (2.22%), without any grade IV dermatitis during the total duration of treatment. The toxicities were manageable, and most of them resolved after three months of treatment completion. Conclusions Accelerated concomitant chemoradiation with six fractions of radiation in a week led to a decrease in overall treatment time. Of note, 62.22% of patients had complete remission, with manageable acute mucositis and dermatitis, which resolved in 82% and 67%, respectively within three months of treatment completion. However, further studies involving larger samples and longer follow-ups are needed for this regimen to be established as the standard of care in the future.

Pulmonary fibrosis and lung cancer: an analysis of the Clinical Practice Research Datalink linked to the National Cancer Registration Dataset.

We quantified the proportion of diagnoses of pulmonary fibrosis (PF) among 25 136 people with lung cancer and 250 583 matched controls and compared the natural history of lung cancer in people with and without PF. Diagnoses of PF were more common in people with lung cancer than those without (1.5% vs 0.8%, OR 1.97; 95% CI 1.77 to 2.21). Within people with PF, squamous cell carcinoma was more (22.9% vs 19.1%), and adenocarcinoma was less common (18.0% vs 21.3%). People with PF were less likely to have stage 4 disease at diagnosis (OR 0.43, 95% CI 0.28 to 0.65) but their survival was worse.

The incidence of lung cancer amongst primary care chest radiograph referrals; an evaluation of national and local datasets within the UK.

OBJECTIVES: To determine the incidence of lung cancer amongst primary care referrals for investigation with a chest radiograph (CXR). METHOD: Retrospective evaluation of datasets from the national Clinical Practice Research Datalink (CPRD) and from a single large regional centre. Data was extracted for cohorts of consecutive adults aged over 40-yrs for whom a CXR had been performed between 2016 and 2018. Using cancer registry data, the incidence of lung cancer within a two-years of the CXR referral and the variations with age, gender and smoking status were evaluated. RESULTS: A total of 291 294 CXR events were evaluated from the combined datasets. The incidence of lung cancer amongst GP CXR referrals was 1.4% in CPRD with a consistent correlation with increasing age and smoking status. The incidence of lung cancer within two-years of the CXR varied between 0.03% (95%CI 0.0-0.1) amongst never smokers aged 40-45 years to 4.8% (95%CI 4.2-5.5) amongst current-smokers aged 70-75 years. The findings were similar for the single large centre data, although cancer incidence was higher. CONCLUSIONS: A simple estimation and stratification of the risk of lung cancer amongst primary care referrals for investigation with a CXR is possible using age and smoking status. ADVANCES IN KNOWLEDGE: This is the first estimate of the incidence of lung cancer amongst primary care CXR referrals and a demonstration of how the demographic information contained within a request could be used to optimise investigations and interpret test results.

Quantitative proteomics reveals serum proteome alterations during metastatic disease progression in breast cancer patients.

BACKGROUND: Tumor recurrence and metastatic progression remains the leading cause for breast cancer related mortalities. However, the proteomes of patient- matched primary breast cancer (BC) and metastatic lesions have not yet been identified, due to the lack of clinically annotated longitudinal samples. In this study, we evaluated the global-proteomic landscape of BC patients with and without distant metastasis as well as compared the proteome of distant metastatic disease with its corresponding primary BC, within the same patient. METHODS: We performed mass spectrometry-based proteome profiling of 73 serum samples from 51 BC patients. Among the 51 patients with BC, 29 remained metastasis-free (henceforth called non-progressors), and 22 developed metastases (henceforth called progressors). For the 22 progressors, we obtained two samples: one collected within a year of diagnosis, and the other collected within a year before the diagnosis of metastatic disease. MS data were analyzed using intensity-based absolute quantification and normalized before differential expression analysis. Significantly differentially expressed proteins (DEPs; absolute fold-change ≥ 1.5, P-value < 0.05 and 30% abundance per clinical group) were subjected to pathway analyses. RESULTS: We identified 967 proteins among 73 serum samples from patients with BC. Among these, 39 proteins were altered in serum samples at diagnosis, between progressors and non-progressors. Among these, 4 proteins were further altered when the progressors developed distant metastasis. In addition, within progressors, 20 proteins were altered in serum collected at diagnosis versus at the onset of metastasis. Pathway analysis showed that these proteins encoded pathways that describe metastasis, including epithelial-mesenchymal transition and focal adhesion that are hallmarks of metastatic cascade. CONCLUSIONS: Our results highlight the importance of examining matched samples from distant metastasis with primary BC samples collected at diagnosis to unravel subset of proteins that could be involved in BC progression in serum. This study sets the foundation for additional future investigations that could position these proteins as non-invasive markers for clinically monitoring breast cancer progression in patients.

A systematic literature analysis of multi-organ cancer diagnosis using deep learning techniques.

Cancer is becoming the most toxic ailment identified among individuals worldwide. The mortality rate has been increasing rapidly every year, which causes progression in the various diagnostic technologies to handle this illness. The manual procedure for segmentation and classification with a large set of data modalities can be a challenging task. Therefore, a crucial requirement is to significantly develop the computer-assisted diagnostic system intended for the initial cancer identification. This article offers a systematic review of Deep Learning approaches using various image modalities to detect multi-organ cancers from 2012 to 2023. It emphasizes the detection of five supreme predominant tumors, i.e., breast, brain, lung, skin, and liver. Extensive review has been carried out by collecting research and conference articles and book chapters from reputed international databases, i.e., Springer Link, IEEE Xplore, Science Direct, PubMed, and Wiley that fulfill the criteria for quality evaluation. This systematic review summarizes the overview of convolutional neural network model architectures and datasets used for identifying and classifying the diverse categories of cancer. This study accomplishes an inclusive idea of ensemble deep learning models that have achieved better evaluation results for classifying the different images into cancer or healthy cases. This paper will provide a broad understanding to the research scientists within the domain of medical imaging procedures of which deep learning technique perform best over which type of dataset, extraction of features, different confrontations, and their anticipated solutions for the complex problems. Lastly, some challenges and issues which control the health emergency have been discussed.

Surgical Management of Radicular Cyst with the Application of a Natural Platelet Concentrate and Ostoden: A Case Report.

The most frequent cystic lesions that affect the jaw are radicular cysts. The current case report describes the surgical management of a radicular cyst in the periapical region of maxillary central and lateral incisors, and highlights the efficacy of natural platelet concentrate [platelet-rich fibrin (PRF)] along with Ostoden bone graft material used for postoperative healing. A 46-year-old male patient presented to the department with swelling in the palatal aspect of the maxillary anterior region. On radiographic examination, a radiolucent periapical lesion was evident in relation to the left maxillary central and lateral incisor. In the maxillary anterior region, root canal therapy was performed, followed by periapical surgery, and PRF with Ostoden bone graft was placed in the surgical site to initiate the healing at a faster rate. The patient was recalled at follow-ups after 7 days, 3, 6, and 9 months. No symptoms such as pain, inflammation, or discomfort were observed during the review period.

Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in African American and European American patients with TNBC.

Racial disparities in triple-negative breast cancer (TNBC) outcomes have been reported. However, the biological mechanisms underlying these disparities remain unclear. We integrated imaging mass cytometry and spatial transcriptomics, to characterize the tumor microenvironment (TME) of African American (AA) and European American (EA) patients with TNBC. The TME in AA patients was characterized by interactions between endothelial cells, macrophages, and mesenchymal-like cells, which were associated with poor patient survival. In contrast, the EA TNBC-associated niche is enriched in T-cells and neutrophils suggestive of an exhaustion and suppression of otherwise active T cell responses. Ligand-receptor and pathway analyses of race-associated niches found AA TNBC to be immune cold and hence immunotherapy resistant tumors, and EA TNBC as inflamed tumors that evolved a distinctive immunosuppressive mechanism. Our study revealed the presence of racially distinct tumor-promoting and immunosuppressive microenvironments in AA and EA patients with TNBC, which may explain the poor clinical outcomes.

The effect of breathing hypoxic gas (15% FIO2 ) on physiological and behavioral outcomes during simulated driving in healthy subjects.

Hypoxia is mainly caused by cardiopulmonary disease or high-altitude exposure. We used a driving simulator to investigate whether breathing hypoxic gas influences driving behaviors in healthy subjects. Fifty-two healthy subjects were recruited in this study, approved by the Science and Engineering Ethical Committee. During simulated driving experiments, driving behaviors, breathing frequency, oxygen saturation (SpO2 ), and heart rate variability (HRV) were analyzed. Each subject had four driving sessions; a 10-min practice and three 20-min randomized interventions: normoxic room air (21% FIO2 ) and medical air (21% FIO2 ) and hypoxic air (equal to 15% FIO2 ), analyzed by repeated measures ANOVA. Driving behaviors and HRV frequency domains showed no significant change. Heart rate (HR; p < 0.0001), standard deviation of the RR interval (SDRR; p = 0.03), short-term HRV (SD1; p < 0.0001), breathing rate (p = 0.01), and SpO2 (p < 0.0001) were all significantly different over the three gas interventions. Pairwise comparisons showed HR increased during hypoxic gas exposure compared to both normoxic interventions, while SDRR, SD1, breathing rate, and SpO2 were lower. Breathing hypoxic gas (15% FiO2 , equivalent to 2710 m altitude) may not have a significant impact on driving behavior in healthy subjects. Furthermore, HRV was negatively affected by hypoxic gas exposure while driving suggesting further research to investigate the impact of breathing hypoxic gas on driving performance for patients with autonomic dysfunction.

Dandelion (Taraxacum officinale): A Promising Source of Nutritional and Therapeutic Compounds.

BACKGROUND: Taraxacum officinale, commonly referred to as dandelion, is a selfgrowing plant/ weed in various parts of India and the rest of the world (particularly the northern hemisphere). The plant's chemical composition, including sesquiterpene lactones, saponins, flavonoids, phenols, and many other compounds, contributes positively to the human body, promoting overall health. AIM: This review aims to shed light on the therapeutic potential of dandelion by summarizing its nutritional benefits, phytochemical constituents, and effectiveness in addressing health conditions like diabetes, inflammation, and cancer. It also provides insights into the applications of this plant beyond the food industry to gain researchers' attention to unravel the unexplored aspects of this therapeutic plant. It will further help in laying specific considerations, which are required to be taken into account before the development of functional foods incorporated with dandelion. Scope and approach: Being rich in essential vitamins, minerals, and other phytoconstituents, dandelion is a natural remedy for various ailments. Whether consumed raw or cooked, the plant's inclusion in the diet poses potential therapeutic effects on conditions such as diabetes, inflammation, liver disease, and tumors. It also aids in immune system modulation and fights infections by targeting microbes at their root. Researchers have developed various value-added food products by incorporating different parts of dandelion. CONCLUSION: This review highlights the therapeutic potential of dandelion, emphasizing its effectiveness against various health conditions. Insights into dosage, toxicity, and diverse applications further underscore its role as a versatile and promising natural remedy.

Nutritional Significance of Wheatgrass: Cultivation Practices and Opportunities for its Processing and Preservation.

BACKGROUND: This paper aims to provide a comprehensive review of the nutritional composition and bioactive compounds found in wheatgrass, including chlorophyll, vitamins, minerals, flavonoids, and phenolic compounds, as well as their associated health benefits. The review focuses on various cultivation practices, preservation techniques, and the current utilization of wheatgrass as a whole. Additionally, the potential toxicity of wheatgrass has been discussed. Wheatgrass, a nutrient-rich grass, possesses significant pharmacological and therapeutic qualities. In the present scenario, wheatgrass is available in the form of juice, powder, and tablets, and is incorporated into various food products through different processing treatments. METHOD: Information and data regarding wheatgrass cultivation practices, processing, and preservation methods were collected from scientific sources, including Google Scholar, ResearchGate, ScienceDirect, fig, Web of Science, and Scopus databases. RESULT: Wheatgrass is a highly valuable source of diverse nutrient compounds. Various cultivation methods, such as indoor and outdoor techniques using different growing mediums, have been employed for wheatgrass production. Recent methods for wheatgrass preservation have been suggested to enhance the bioactive compounds present in wheatgrass. CONCLUSION: Numerous studies have demonstrated that the consumption of wheatgrass and wheatgrass- based products can help control diabetes, atherosclerosis, kidney and colon diseases, anemia, and certain types of cancer. The smaller size of wheatgrass allows for easier assimilation of its beneficial compounds. Creating awareness among consumers about the nutritional profile and therapeutic properties of wheatgrass is crucial in order to maximize its market potential.

A Comparative Study Evaluating the Quality of Life and Survival Outcomes in Patients Receiving Chemotherapy Versus Oral Tyrosine Kinase Inhibitor in the Third Line and Beyond Setting for Advanced NSCLC.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was -28 in the chemotherapy arm and -26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04-137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15-4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1-2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83-1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96-9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85-9.14); hazard ratio at 1.033 (95% CI: 0.80-1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

Beetroot Bioactive and its Associated Health Benefits: Considerations for Utilization of Beetroot in Value-added Products.

BACKGROUND: Beetroot is a remarkable source of nutrients needed for the improvement of human health. This paper presents a general overview of beetroot, its bioactive compounds, and its valorization. OBJECTIVE: The study aimed to understand and review the various beetroot bioactive compounds and their utilization in value-added products. METHODS: The findings and data provided in this review are based on the available research investigations and authorized articles. RESULT: Beetroot is a reliable source of a cluster of bioactive compounds, such as betalains, ascorbic acid, phenolic compounds, carotenoids, and nitrates, which have brought it into the spotlight for the preparation of various value-added products for daily consumption for better health. These beneficial compounds show a wide range of health benefits, such as antiinflammatory activity, anti-oxidant activity, anti-anemic activity, and cancer chemopreventive activity. CONCLUSION: This paper has reviewed the studies focused on the utilization of beetroot concerning its varied composition of nutraceutical components. This review briefly accounts for the different bioactive compound extraction methods that are immensely helpful in the food and health industries. The advantages and disadvantages of these extractions are also taken into consideration. There is a wide range of value-added products currently in the market that are generated from the addition of beetroot for the improvement of nutritional as well as sensory attributes of the final products.

Pomegranate Peel Phytochemistry, Pharmacological Properties, Methods of Extraction, and Its Application: A Comprehensive Review.

Pomegranate peel, derived from the processing of Punica granatum L. (pomegranate), has traditionally been considered agricultural waste. However, recent studies have revealed its potential as a rich source of bioactive compounds with diverse pharmacological effects. Pomegranate peel is a rich reservoir of antioxidants, polyphenols, dietary fiber, and vitamins, which contribute to its remarkable bioactivity. Studies have demonstrated the anti-inflammatory, cardioprotective, wound healing, anticancer, and antimicrobial properties of pomegranate peel owing to the presence of phytochemicals, such as gallic acid, ellagic acid, and punicalagin. The extraction of bioactive compounds from pomegranate peel requires a careful selection of techniques to maximize the yield and quality. Green extraction methods, including pressurized liquid extraction (PLE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzyme-assisted extraction (EAE), offer efficient and sustainable alternatives to traditional methods. Furthermore, pomegranate peel has been utilized in the food industry, where it can significantly enhance the nutritional value, organoleptic characteristics, and shelf life of food products. Pomegranate peel has the potential to be used to develop innovative functional foods, nutraceuticals, and other value-added products, providing new opportunities for the pharmaceutical, cosmetic, and food industries.

Whole-Exome Sequencing Reveals High Mutational Concordance between Primary and Matched Recurrent Triple-Negative Breast Cancers.

PURPOSE: Triple-negative breast cancer (TNBC) is a molecularly complex and heterogeneous breast cancer subtype with distinct biological features and clinical behavior. Although TNBC is associated with an increased risk of metastasis and recurrence, the molecular mechanisms underlying TNBC metastasis remain unclear. We performed whole-exome sequencing (WES) analysis of primary TNBC and paired recurrent tumors to investigate the genetic profile of TNBC. METHODS: Genomic DNA extracted from 35 formalin-fixed paraffin-embedded tissue samples from 26 TNBC patients was subjected to WES. Of these, 15 were primary tumors that did not have recurrence, and 11 were primary tumors that had recurrence (nine paired primary and recurrent tumors). Tumors were analyzed for single-nucleotide variants and insertions/deletions. RESULTS: The tumor mutational burden (TMB) was 7.6 variants/megabase in primary tumors that recurred (n = 9); 8.2 variants/megabase in corresponding recurrent tumors (n = 9); and 7.3 variants/megabase in primary tumors that did not recur (n = 15). MUC3A was the most frequently mutated gene in all groups. Mutations in MAP3K1 and MUC16 were more common in our dataset. No alterations in PI3KCA were detected in our dataset. CONCLUSIONS: We found similar mutational profiles between primary and paired recurrent tumors, suggesting that genomic features may be retained during local recurrence.

Nutritional advantages of barnyard millet and opportunities for its processing as value-added foods.

Barnyard millet (Echinochloa species) has received appreciable attention for its susceptibility to biotic and abiotic stresses, multiple harvests in a year and rich in micronutrients, fibers and phytochemicals. It is believed that the consumption of barnyard millet can possess various health benefits against diabetes, cardiovascular diseases, obesity, skin problems, cancer and celiac disease. The flour of barnyard millet is gluten-free and can be incorporated into the diet of celiac and diabetic patients. Considering the nutritional value of millet, various millet-based food products like bread, snack, baby foods, millet wine, porridge, fast foods and millet nutrition powder can be prepared. Future research and developments on barnyard millet and its products may help cope with various diseases known to humans. This paper discusses barnyard millet's nutritional and health benefits as whole grain and its value-added products. The paper also provides insights into the processing of barnyard millet and its effect on the functional properties and, future uses of barnyard millet in the field food industry as ready-to-cook and ready-to-eat products as well as in industrial uses, acting as a potential future crop contributing to food and nutritional security.

Anti-cancerous effect of corn silk: a critical review on its mechanism of action and safety evaluation.

Cancer is a broad collection of diseases that can begin in almost any organ or tissue of the body. Corn silk is the hair-like stigmata of female maize flowers which is generally discarded as waste from maize cultivation. The current study targets the anti-cancer potential of corn silk and its bioactive compounds namely, polyphenols, flavonoids, and sterols. The polyphenols and flavonoids like quercetin, rutin, apigenin and beta-sitosterol are a range of compounds from corn silk which were investigated for their anticancer effect. Corn silk showed apoptotic and antiproliferative effects in cancer cells through different signalling pathways, essentially the serine/threonine kinases (Akt)/lipid kinases (PI3Ks) pathway. The study revealed that corn silk compounds target immune cell responses, induce cell cytotoxicity, and upregulate the expression of proapoptotic genes p53, p21, caspase 9, and caspase 3 in certain cancer cell lines including HeLa cervical cancer cells, MCF-7 breast cancer cells, PANC-02 pancreatic cancer cells and Caco-2 colon cancer cells. Flavonoids derived from corn silk enhance T cell mediated immune response and decrease inflammatory factors. Corn silk bioactive compounds were found to reduce the side effects of cancer therapy. Antioxidants of corn silk, quercetin and rutin help in reducing the nephrotoxicity of chemotherapeutic drugs. The study also suggests that corn silk has anti-cancerous potential as it targets tumour suppression and inhibits metastasis A dose of 500 mg/kg body weight of corn silk has been found safe for human consumption. Corn silk extract can be used as a preventive or therapeutic step to cure cancer. The anti-cancer property, mechanism and role of corn silk in controlling cancer-related side effects have been critically reviewed providing new scope for the use of corn silk in cancer therapy.

Effectiveness of perioperative anticoagulation interruption without heparin bridging on thromboembolic events in patients with atrial fibrillation undergoing elective invasive procedures: a systematic review protocol.

OBJECTIVE: This review will determine whether withholding heparin bridging is superior to bridging in patients with atrial fibrillation requiring temporary interruption of anticoagulation therapy in the perioperative period of an elective invasive procedure. INTRODUCTION: Atrial fibrillation is the most commonly diagnosed clinical arrhythmia. It is an important cause of cardioembolic events, requiring the use of oral anticoagulation in most patients. It is unclear whether heparin bridging during temporary interruption of anticoagulants has superior outcomes compared with no bridging in the perioperative setting. INCLUSION CRITERIA: This review will consider studies that compare adults aged 18 years or older; diagnosed with atrial fibrillation; undergoing elective invasive procedures; and who have had oral anticoagulants temporarily withheld with heparin bridging with patients without heparin bridging. Participants will be excluded if they had an alternative reason for anticoagulation or were admitted for emergency surgery. Outcomes will include arterial or venous thromboembolism (including stroke, transient ischemic attack, systemic embolism), major bleeding events, non-major bleeding events, length of hospital stay, and all-cause mortality. METHODS: The review will follow the JBI methodology for systematic reviews of effectiveness. Databases including MEDLINE, Embase, CINAHL, and CENTRAL will be searched for randomized and non-randomized trials from inception until the present. Two independent reviewers will screen citations by title and abstract, and again at full text. Risk of bias will be assessed using the JBI critical appraisal instrument, and data will be extracted using a modified extraction tool. Results will be synthesized using a random effects meta-analysis and presented in a forest plot. Heterogeneity will be tested for using the standard χ 2 and I2 tests. Overall certainty of evidence will be evaluated using the GRADE approach. REVIEW REGISTRATION: PROSPERO CRD42022348538.

POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2.

Gene fusions involving EWSR1 or FUS as the 5' partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3' portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

Restoring Balance: Immune Tolerance in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic musculoskeletal disease where immune dysregulation and subsequent autoimmunity induce significant synovial joint inflammation and damage, causing pain and disability. RA disease onset is promoted through multifaceted interactions between genetic and environmental risk factors. However, the mechanisms of disease onset are not completely understood and disease-specific treatments are yet to be developed. Current RA treatments include nonspecific disease-modifying antirheumatic drugs (DMARDs) that suppress destructive immune responses and prevent damage. However, DMARDs are not curative, and relapses are common, necessitating lifelong therapy in most patients. Additionally, DMARD-induced systemic immunosuppression increases the risk of serious infections and malignancies. Herein, we review the current understanding of RA disease pathogenesis, with a focus on T and B cell immune tolerance breakdown, and discuss the development of antigen-specific RA therapeutics that aim to restore a state of immune tolerance, with the potential for disease prevention and reduction of treatment-associated adverse effects.

Spirulina- An Edible Cyanobacterium with Potential Therapeutic Health Benefits and Toxicological Consequences.

Spirulina is a blue-green algae which is cultivated not only for its maximum protein content but also due to the presence of other essential nutrients such as carbohydrates and vitamins (A, C and E). It is also a storehouse of minerals including iron, calcium, chromium, copper, magnesium, manganese, phosphorus, potassium, sodium and zinc. Simultaneously, γ- linolenic acid (an essential fatty acid), as well as pigments such as chlorophyll A and phycobiliproteins (C-phycocyanin, allophycocyanin and ß-carotene), is also a major component of its rich nutritional profile. Spirulina is known to have various promising effects on the prevention of cancer, oxidative stress, obesity, diabetes, cardiovascular diseases and anemia. Moreover, it also plays a positive role in treating muscular cramps. The safety recommended dosage of Spirulina is approximately 3-10 g/d for adults and it's biological value (BV) is 75 with a net protein utilization (NPU) of 62. Spirulina does not have pericardium due to which it does not hinder the absorption of iron by chelation with phytates or oxalates. On the contrasting note, it may have some adverse effects due to the toxins (microcystins, ß-methylamino-L-alanine (BMAA)) produced by Spirulina which might contribute to acute poisoning, cancer, liver damage as well as gastrointestinal disturbances. Its long-term consumption may also lead to the pathogenesis of Alzheimer's disease and Parkinson's disease. The current review focuses on the various aspects of spirulina including its cultivation, nutritional composition, extraction techniques, health benefits, adverse effects, industrial scope and market value which could be beneficial for its utilization in the development of value-added products and supplementary foods due to its high content of protein and bioavailability of nutrients.

• Spirulina is a nutrient-dense cyanobacterium which is composed of protein, carbohydrates, vitamins, minerals, essential fatty acids, antioxidants and pigments including chlorophyll A and Phycocyanin.• To avoid the contamination of Spirulina species by other algae, the specific pH maintenance of the media around 9-11 (alkaline) is mandatory.• Positive effects were noticed on the yield and productivity of Spirulina after its biomass was grown in polybags and greenhouse.• Its beneficial effects have been identified in particular reference to obesity, diabetes, hypertension, cardiovascular diseases, anemia, cancer, oxidative stress, arthritis, immunity as well as muscular cramps.• The toxins such as microcystins and hepatotoxins, produced by Spirulina, are accountable to cause acute poisoning, liver damage, gastrointestinal disturbances and cancer.• The safe recommended dosage of Spirulina for adults accounts to approximately 3-10 g/d, with 30 g/d being the maximum limit for consumption.