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Pomaded and unctuous- spindle cell lipoma

Published on: 17th March, 2023

Spindle cell lipoma and pleomorphic lipoma emerge as benign, adipocytic neoplasms representing a morphologic continuum of a singular neoplasm. In addition to myofibroblastoma and cellular angiofibroma, spindle cell lipoma or pleomorphic lipoma configures as a constituent of chromosome 13q/RB1 family of tumors. Initially scripted by Enzinger and Harvey in 1975 with an obsolete terminology of dendritic fibromyxolipoma, aforesaid adipocytic neoplasms articulate an estimated 1.5% of lipomatous tumors. In contrast to conventional lipoma, spindle cell lipoma or pleomorphic lipoma is an uncommonly discerned variant, demonstrating a proportion of 1: 60.
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Development of qualitative GC MS method for simultaneous identification of PM-CCM a modified illicit drugs preparation and its modern-day application in drug-facilitated crimes

Published on: 28th March, 2023

Prescriptions for psychoactive substances such as Pregabalin, Methamphetamine, Caffeine, Clonazepam and Mirtazapine (PM-CCM) are common in the treatment of a variety of disorders. Indeed, the PM-CCM has been used in different therapeutic areas, including insomnia, anxiety, seizure disorders, etc. Unfortunately, these psychoactive substances are present in the illegal street market, leading to a lot of drug abuse among some addicted users, road insecurity and suicide. Hence, it has become essential to validate and develop a rapid and effective method to analyze the PM-CCM, a modified illicit drug, for drug abuse in the forensic sciences. A simple, rapid, specific and sensitive Gas Chromatography-Mass Spectrometry(GC-MS) method has been developed for the identification of Pregabalin, Methamphetamine, Caffeine, Clonazepam and Mirtazapine (PM-CCM) in forensic exhibits. At room temperature, the sample was ultrasonicated for 5 minutes before being extracted with methanol. A highly precise auto-injector is used to inject a very small quantity of samples for analysis. Helium is used as a carrier gas with a flow rate of 1 ml/min. The separation of PM-CCM was performed on SH-RXi-5 MS, ID.25 mm, film thickness. 25 µm, length of 30 m column. The constituents of PM-CCM were identified by the mass-to-charge ratio (m/z ratio) of fragments of the parent compound by comparing them with the NIST-17 MS Library. Separation and identification of PM-CCM were achieved within a 15-minute run. The proposed method has been successfully used for the routine analysis of PM-CCM in complex illicit drug preparations and in forensic exhibits as well. The application of above discussed qualitative analysis method and screening of PM-CCM, modified illicit drug samples demonstrates the potential and applicability of the technique to the fast chemical profiling of illicit samples.  
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Nuclear science and magnetic carbon: a promising way from a chemical method to detect and fight cancer and tumors/neoplasms

Published on: 17th April, 2023

In 2005 we reported for the first time on a chemical route aiming to synthesize stable magnetic carbon/graphite. By using the Nuclear Magnetic Resonance (NMR) technique we have verified that its magnetism is an intrinsic property of this synthesized material and not originated from ferromagnetic impurities of any kind. Through direct measurement of the local magnetic field using Carbon-13, we have concluded that its magnetism originated from defects in the structure. From its biocompatibility, we have been working on the use of magnetic carbon/graphite to deliver many compounds aiming to fight different diseases. Despite all the scientific and technological advances of the present day, cancer is a multifactorial and difficult-to-treat disease, killing hundreds of thousands of people a year worldwide. Therefore, the development of a new and efficient drug delivery system to fight cancer – among other diseases - is as important as the discovery of a novel active molecule. In this review of our own work, we show the drug delivery system named MAGUS® (an acronym for Magnetic Graphite Universal System) we have built based on nanostructured magnetic carbon/graphite. This is an innovative and promising system composed of a biocompatible nanostructured particle of magnetic carbon/graphite functionalized with different molecules and materials. MAGUS®, depending on what we link to its structure, is so versatile and can be used to detect a wide range of specimens, from tumors and cancers to chemical and biological agents used as non-conventional weapons. That is why we call it universal. In the present work, MAGUS® will be acting as a biosensor, where the magnetic carbon/graphite is functionalized with radioactive particles of Iodine-131 and antibodies of different types of cancer. Then, by focusing on both the antigen-antibody interaction and the spatial guiding through an external magnetic field we are providing our drug delivery system a double way to detect and reach just the target. Based on these strategies, the functionalized magnetic carbon/graphite will reach only the neoplasm and not the surrounding healthy cells around. In a general view, it means that we are giving specificity to the MAGUS® drug delivery system as a pioneering and effective way to detect and treat cancers. We are also working on this unprecedented and efficient drug delivery system using the principles of Boron Neutron Capture Therapy (BNCT) with Boron-10 instead of Iodine-131. BNCT technique uses neutrons as the external source and is frequently employed to treat specific tumors that are radio resistant or very difficult to kill using conventional radiation therapy. In summary, we show here for the first time that our Magnetic Graphite Universal System associated with nuclear techniques can be successfully used as a biosensor to detect and fight cancers and tumors with powerful features that conventional delivery drug systems and other treatments do not have at all.
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Update in the Understanding, Diagnosis, and Management of Sturge Weber Syndrome: Case Report

Published on: 24th August, 2023

Sturge-Weber Syndrome (SWS) is a congenital, vascular, neurocutaneous, uncommon disease associated with facial angiomas port wine birthmark (PWB) or “nevus flammeus”, cerebral vascularity alterations (leptomeningeal vascular malformation), and ocular disorders. It is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis. GNAQ R183Q is the most frequent related mutation, caused by a postzygotic, somatic, gain-of-function. 75% of patients present seizures during the first year of life, mainly focal motor seizures, with or without consciousness impairment.We present the case of a 33-year-old female with a diagnosis of SWS, with refractory seizures that started at 4 months of age. In this admission, she presented upper and lower respiratory tract infections that culminated in a convulsive status epilepticus (CSE), the reason for which she required sedation and advanced airway management with adjustment of the anti-seizure medication (ASM). An electroencephalogram (EEG) was performed that reported epileptic activity, as well as an imaging study with data suggestive of calcification in the frontal and right parietal region, compatible with vascular malformation.
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High-Grade Endometrial Mesenchymal Sarcoma: Current Status and Future Trends

Published on: 19th September, 2023

Endometrial Stromal Sarcoma (ESS) is a rare gynecological malignancy originating from endometrial stromal tissue. Representing only a tenth of uterine malignant tumors, ESS is categorized into Low-Grade (LGESS) and High-Grade (HGESS) based on nuclear division. Interestingly, prognostic studies have found no strong correlation between ESS prognosis and nuclear division activity. Undifferentiated Uterine Sarcoma (UUS) represents a spectrum of tumors with varied morphological, clinical, and prognostic features, and lacks a standardized naming convention. In 2014, the World Health Organization grouped ESS into LGESS, HGESS, and UUS based on clinical and pathological attributes. HGESS, despite its rarity, is notorious for its poor prognosis and low survival rate. Its early detection is complicated due to its asymptomatic presentation and ambiguous pathogenesis, leading to debates over treatment approaches. This article delves into the recent research developments concerning HGESS.
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A Rare Coexistence: Breast Cancer, Pheochromocytoma and Von Recklinghausen Disease

Published on: 11th December, 2023

Breast cancer associated with type-1 neurofibromatosis is a rare clinical entity. These patients have a higher risk of developing various types of cancers, especially tumors derived from the embryogenic neural crest, such as pheochromocytoma. This publication aims to add to the literature a rare association between Type-1 Neurofibromatosis, breast cancer, and pheochromocytoma.We present a rare case of a 51-year-old Tunisian woman with neurofibromatosis who was diagnosed with breast cancer and pheochromocytoma. The breast tumor was classified as T4b N1M0, and the discovery of the pheochromocytoma was incidental to thoracic-abdominal-pelvic CT. She underwent surgery to remove the adrenal gland and was referred to medical oncologists to receive chemotherapy for her breast cancer. Type-1 Neurofibromatosis disorder is a benign disease but can expose patients to numerous neoplasms. The challenging diagnosis at an early stage can worsen the prognosis and make medical care more difficult.
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Mechanism of Action and Validation of the Traditional Medicinal use of Grewia Tenax Fruits in Sudan to Encounter Iron Deficiency Anemia

Published on: 27th December, 2023

Introduction: In Sudan, Grewia tenax fruits, are known commonly as Goddaim. The fruit’s pericarp is used traditionally for a long time as a juice or a porridge to treat iron deficiency anemia (IDA). Traditional Goddaim users have a very strong belief in its effectiveness. However, the pattern of hemoglobin improvement follows an initial fast increase followed by a decline upon continuing its use. Some previous studies have attributed its effect to high iron content, while the iron quantity was too small. This work attempts to find an explanation for its mechanism of action by screening the fruit extract and its respective fractions for secondary metabolites, minerals, vitamins, and fibre. Methods: Entailed three methodologies: Chemical analysis to identify quantified minerals, ascorbic acid and non-digestible fibers, Phytochemical Analysis to separate and identify secondary metabolites using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS technique), and estimation of radical scavenging activities of crude fruit extract and its respective chloroform and ethyl acetate fractions by inhibition of the 2,2-diphenylpicrylhydrazyl (DPPH).Results: Ascorbic acid and indigestible fibres were revealed in the aqueous extract. Secondary metabolites were flavonoids (e.g., quercetin, kaempferol), organic acids (e.g., ferulic acid, chlorogenic acid), β-carboline alkaloids (e.g., 3-hydroxy-tetrahydroharman) identified in the chloroform, and ethyl acetate fractions. The in vitro antioxidant activity of G. tenax fruit extract was confirmed spectrophotometrically. Conclusion: It can be concluded that the initial enhancement of iron absorption through ascorbic acid and fibres, followed by iron uptake inhibition, could be explained by iron chelation by the chelators in the fruits. This paradoxical effect may qualify G. tenax fruits as a safety gauge for improving haemoglobin levels without compromising iron excess once iron stores are filled by keeping the oxidative stress in check. This may present G. tenax fruits as a good and safe remedy that optimizes the treatment of IDA.
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Treatment Outcome in Patients with Myofascial Orofacial Pain: A Randomized Clinical Trial

Published on: 18th January, 2024

Background: Temporomandibular Disorder (TMD) pain attributed to myalgia is a common condition and patients should get advice on the best treatment option. Objectives: The aim was to evaluate the effect of two different exercise programs, or bite splint therapy, respectively, in patients with chronic frequent primary myofascial orofacial pain. Methods: The study was a randomized clinical trial including patients fulfilling criteria of chronic frequent primary myofascial orofacial pain with a reported pain intensity of ≥ 4 on a numerical rating scale (0-10). Ninety subjects were randomized to either bite splint, home exercises, or a supervised exercise program. Two examiners blinded to the treatment modality examined the same subject at baseline and a 3-month follow-up. Non-parametric statistical methods were applied for the outcome of treatment in intended-to-treat analyses. A P-value <0.05 was considered statistically significant. Results: The pain severity index was significantly reduced (p < 0.001) in all treatment groups. Jaw opening capacity improved significantly (p < 0.05) for those randomized to bite splint and for those in the home exercise program. About 70% of the participants reported improvement in their TMD pain severity with no significant difference between treatments. Both exercise groups improved in jaw function at the 3-month follow-up compared to baseline. Those who had a bite splint reported significantly more improvement in their headaches compared to those in the exercise programs. Conclusion: Jaw exercise programs and bite splint treatments had similar positive effects on TMD pain severity attributed to myalgia after 3 months.
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Management and use of Ash in Britain from the Prehistoric to the Present: Some implications for its Preservation

Published on: 23rd January, 2024

The properties that make the wood of fast-grown Ash pliable, strong, and resilient have been exploited by man for thousands of years, and are illustrated by reference to the probable use of Ash timber for tools, arms, and transport by the Roman Army of Occupation in Britain two thousand years ago. Militarily organized and disciplined, the Roman Army was responsible for changing the face of Britain with huge infrastructure projects that required significant numbers of tools, equipment, and fuel, in addition to the arms it used to maintain control over the fractious tribes of the north. The extent to which it maintained supplies of this valuable resource by managing its woods, possibly by coppicing, is discussed and raises the question as to the degree of genetic selection involved in coppicing.Ash: Fraxinus excelsior: extinction: prehistoric and historic uses: Roman army military use of Ash.
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Next Generation Tools in mRNA Purification: The Role of Continuous Raman Spectroscopy Testing with Pretreatment of the Sample

Published on: 29th March, 2024

In the biopharmaceutical production field, the purification process is a crucial step in order to obtain Drugs with an impurity profile according to the regulatory agency requirement.The aim of this work is to verify some relevant and recent literature and after analysis to submit to the researcher new Solutions in order to improve global safety and the toxicological profile: Submit a project related to the continuous testing of the purified materials using Raman spectroscopy – with pre-treatment of the sample: using solvents.Nanolipis Payload of Biopharmaceutical is not efficiently detected by direct Raman spectroscopy allowed by the regulatory agency for PAT process analytical technology.
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Preparation of Healthy Cookies from Germinated Flour Blends of Finger Millet and Pearl Millet Sweetened with Jaggery

Published on: 2nd April, 2024

Millets are physiologically and therapeutically healthy with high nutritious value and are in rising demand in emerging markets like India, China, Africa, and other developing countries including the Western world. Germinated Millets have high digestibility and are used as healthy food for children’s growth and development. Climate change resilience technology, high nutritional value, and the announcement of the year 2023 as “International Millet Year” have made it very popular. Bakery items based on Millet, particularly cookies, are becoming more popular in both urban and rural areas. Jaggery is raw sugar prepared from sugarcane juice and is considered superior to white sugar. It offers numerous nutritional and therapeutic benefits, including anti-carcinogenic with antitoxic actions. Hence, this study aimed to prepare healthy food items with germinated finger and pearl Millets for better nutritional quality that are attracting the attention of health-conscious people on a worldwide scale. Cookies made from blends of germinated wheat flour (GWF), germinated finger millet flour (GFMF), and germinated pearl millet flour (GPMF) were examined for their physicochemical qualities, in vitro digestibility, antioxidant activity, and overall acceptability by consumers. In vitro protein digestibility (62.24-82.34%), starch digestibility (47.48-62.41%), total phenolic content (11.45–49.12 mg GAE/100 g), and antioxidant activities significantly increased as the proportion of GFMF and GPMF flour increased in the cookie samples, whereas total starch, dietary fiber, carbohydrate, and phytic acid decreased. The physical qualities of the cookies were also improved by the addition of GFMF and GPMF flours. Cookies with acceptable sensory properties, including taste, aroma, appearance, mouthfeel, crispiness, and overall acceptability, were produced by blending 60% GWF, 20% GFMF, and 20% GPMF (T2). This study demonstrated that GFMF and GPMF flour blends may be used as functional ingredients to create superior goods.
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Contrast-enhanced Susceptibility Weighted Imaging (CE-SWI) for the Characterization of Musculoskeletal Oncologic Pathology: A Pictorial Essay on the Initial Five-year Experience at a Cancer Institution

Published on: 2nd April, 2024

Susceptibility-weighted imaging (SWI) is based on a 3D high-spatial-resolution, velocity-corrected gradient-echo MRI sequence that uses magnitude and filtered-phase information to create images. It SWI uses tissue magnetic susceptibility differences to generate signal contrast that may arise from paramagnetic (hemosiderin), diamagnetic (minerals and calcifications) and ferromagnetic (metal) molecules. Distinguishing between calcification and blood products is possible through the filtered phase images, helping to visualize osteoblastic and osteolytic bone metastases or demonstrating calcifications and osteoid production in liposarcoma and osteosarcoma. When acquired in combination with the injection of an exogenous contrast agent, contrast-enhanced SWI (CE-SWI) can simultaneously detect the T2* susceptibility effect, T2 signal difference, contrast-induced T1 shortening, and out-of-phase fat and water chemical shift effect. Bone and soft tissue lesion SWI features have been described, including giant cell tumors in bone and synovial sarcomas in soft tissues. We expand on the appearance of benign soft-tissue lesions such as hemangioma, neurofibroma, pigmented villonodular synovitis, abscess, and hematoma. Most myxoid sarcomas demonstrate absent or just low-grade intra-tumoral hemorrhage at the baseline. CE-SWI shows superior differentiation between mature fibrotic T2* dark components and active enhancing T1 shortening components in desmoid fibromatosis. SWI has gained popularity in oncologic MSK imaging because of its sensitivity for displaying hemorrhage in soft tissue lesions, thereby helping to differentiate benign versus malignant soft tissue tumors. The ability to show the viable, enhancing portions of a soft tissue sarcoma separately from hemorrhagic/necrotic components also suggests its utility as a biomarker of tumor treatment response. It is essential to understand and appreciate the differences between spontaneous hemorrhage patterns in high-grade sarcomas and those occurring in the therapy-induced necrosis process in responding tumors. Ring-like hemosiderin SWI pattern is observed in successfully treated sarcomas. CE-SWI also demonstrates early promising results in separating the T2* blooming of healthy iron-loaded bone marrow from the T1-shortened enhancement in bone marrow that is displaced by the tumor.SWI and CE-SWI in MSK oncology learning objectives: SWI and CE-SWI can be used to identify calcifications on MRI.Certain SWI and CE-SWI patterns can correlate with tumor histologic type.CE-SWI can discriminate mature from immature components of desmoid tumors.CE-SWI patterns can help to assess treatment response in soft tissue sarcomas.Understanding CE-SWI patterns in post-surgical changes can also be useful in discriminating between residual and recurrent tumors with overlapping imaging features.
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Using Isomets as a Foundation, a Connection Factor between Nucleation and Atomic Physics

Published on: 10th June, 2024

The radioactive isomer was initially used to characterize persistent excited atomic states, much like molecular isomers, more than a century ago. Otto Hahn made the first atomic isomer discovery in 1921.  Subsequently, it was gradually discovered that there are several kinds of nuclear isomers, such as spin isomer, K isomer, seniority isomer, and “shape and fission” isomer.  Isomers are essential to the nucleosynthesis of astrophysical materials. High-accuracy nuclear reaction rate inputs are anticipated while carrying out a celestial nucleosynthesis net computation, even though a single reaction rate can have a significant impact on the whole astronomical evolutionary network. The isotopes are often considered to be in their initial state or to have levels populated in accordance with the thermal-equilibrium distribution of chances when computing nuclear synthesis rates. After all, certain isomers may have lives that reach millions of years or perhaps beyond the age of the cosmos. Thus, in an astrophysics event, such isomers might not be thermally equilibrium. Some atomic isomers—that is, astrometry—should be considered special isotopes since they are crucial to nucleosynthesis. Nuclear batteries can also be produced using nuclear isomers. Similar to the weak force, in certain specific cases such as isomer decays, the electromagnetic force could be crucial for nuclear changes. It is important to note that radioactive isomer states and radioactive ground states are not the same thing.  Durable nuclear states of excitement provide insight into the nuclear framework and potential uses. Atomic and molecular changes become interconnected when the connection to the electrons in atoms is made possible by the existence of em decay routes from isomers. Notably renowned chemical decay process is inner conversion. Its inverted, nuclear excitement by free capture of electrons has been observed; however, it is debatable and needs more investigation. This study describes the connection connecting radioactive and molecular changes and discusses instances of manipulating nuclear moves related to isomers using external electromagnetic fields.
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A Comparative Analysis of Traditional Latent Fingerprint Visualization Methods and Innovative Silica Gel G Powder Approach

Published on: 19th September, 2024

Latent fingerprints are a common source of information for forensic experts and law enforcement agencies. The thin layer chromatography (TLC) plates that are prepared in this work are made with silica gel G powder. Latent fingerprint remnants are made up of secretions from the nose, palm, and sebaceous, apocrine, and eccrine glands (sweat). However, the quest for more versatile and effective techniques persisted, leading to the emergence of innovative approaches like Silica Gel G powder. The silicon atoms are linked to –OH groups at the silica gel’s surface. A latent fingerprint is an imprint left by direct contact with a surface or object that is not apparent to the unaided eye. The advantages of using Silica Gel G powder for latent fingerprint visualization underscore its significance as an innovative technique in forensic science. The latent fingerprints were developed on each of the several substrates using Merck Specialties Private Limited’s white-coloured silica gel G powder. There are several techniques in the literature for creating latent fingerprints. The emergence of Silica Gel G powder in forensic science represents a significant breakthrough in the visualization of latent fingerprints. The process of using Silica Gel G powder for latent fingerprint visualization exemplifies the precision and attention to detail required in forensic investigations.
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Fibrothecal Tumors of the Ovary - Case Report

Published on: 11th November, 2024

Fibrothecal tumors of the ovary are rare neoplasms, comprising less than 4% of all ovarian tumors and primarily affecting post-menopausal women. These benign tumors arise from the stromal tissue of the ovary and may produce hormones, particularly estrogen. Their diagnosis presents considerable challenges, frequently leading to misclassification as malignant ovarian tumors or uterine myomas. This report describes the case of a 59-year-old woman who presented with abdominal distension and pelvic pain. Clinical examination revealed a large, lobulated mass and imaging studies classified the right ovarian mass as ORADS 4. An exploratory laparotomy confirmed the absence of metastasis, resulting in total hysterectomy, bilateral adnexectomy, and omentectomy. The anatomopathological analysis identified the latero-ovarian mass as a fibrothecoma. Generally, fibrothecal tumors are benign with a favorable prognosis following surgical intervention. Common symptoms include pelvic pain and abdominal distension, and diagnosis typically relies on imaging techniques such as ultrasound and CT, with definitive confirmation achieved through histopathological examination. Given their potential to mimic malignant ovarian cancer, accurate diagnosis is critical and necessitates a multidisciplinary approach.
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Efficient Sequential Chromatographic Purification of a Recombinant Nanobody-Fc Fusion Designed for Treatment of Severe Fever with Thrombocytopenia Syndrome

Published on: 29th January, 2025

Severe fever with thrombocytopenia syndrome (SFTS) is caused by a virus that induces acute infections. Despite its expansion beyond China, where it first appeared in 2009, no specific drug exists to treat the disease. The discovery that antibodies targeting the SFTS virus surface glycoprotein (Glycoprotein N, GN) significantly enhance patient survival has driven the development of antibodies, particularly nanobodies. Nanobodies targeting the GN protein are a promising therapeutic approach. This paper presents a systematic study of the purification process for a recombinant nanobody-Fc fusion designed to treat the SFTS virus HB29. The study evaluated a sequential purification approach using affinity (AFF), ion exchange (IEC), and hydrophobic interaction chromatography (HIC) techniques to gradually remove impurities. The results demonstrate that this approach achieves an overall yield of more than 50% and a total purity of 95%. Efficient nanobody purification methods, as outlined here, can pave the way for novel treatments to manage this disease.
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Clinical and Histopathological Mismatch: A Case Report of Acral Fibromyxoma

Published on: 7th April, 2025

Background: Acral Fibromyxoma (AFM) is a rare benign soft tissue tumour which is described as a fibromatous and myxoid tumour of skin and soft tissue. Case details: A 40-year-old  male presented to the Dermatology outpatient department with swelling over the wrist of one year duration. The swelling was associated with mild pain, and it gradually increased in size to reach its present size. Cutaneous examination revealed a 2x2 cm mobile, cystic to firm, non-tender swelling over the dorsum of the right wrist. Based on its location and clinical features, it was provisionally diagnosed as a ganglion cyst  and excision biopsy was done. Histology showed stellate-shaped cells in a myxoid background with round to oval nuclei having a small, inconspicuous nucleolus. Acral fibromyxoma presents a distinct histopathology including a myxoid stroma and spindle-shaped cells, which are essential for accurate diagnosis and management.
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The Color of Diseases and Herbs-chromatic Illustrating the Yin-yang Regulation Theory in Traditional Chinese Medicine

Published on: 9th May, 2025

Traditional Chinese medicine (TCM) has been used to serve people since antiquity in China, and still has an important role in today’s healthcare. As the outbreak of coronavirus disease 2019 (COVID-19) globally, TCM has played an important role in the fight against COVID-19 in China and other countries. However, scientists outside China doubted TCM. The philosophy of TCM in the description of diseases and the use of herbal medicines is difficult to understand for Western scientists. This article explains the philosophy of TCM using chromatic analogies to make it easily understandable and visually intuitive.
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Detection of Transferrin Oxidative Modification In vitro and In vivo by Mass Spectrometry. Hereditary Hemochromatosis is a Model

Published on: 27th May, 2025

Hereditary Hemochromatosis (HH) is an inherited recessive autosomal disorder characterized by the accumulation of excess iron. When iron-binding proteins become saturated, concentrations of free or Non-transferrin-bound iron (NTBI) rise, a condition thought to be responsible for the adverse effects associated with HH. To investigate whether disturbing iron homeostasis plays a role in free radical injury in HH, protein carbonyls were found to be 1-7 times higher in patients with HH than in controls, with the greatest increases observed in untreated HH patients with high ferritin and > 90% transferrin saturation with iron. An unpaired t-test revealed a p value of 0.0278 (p < 0.05), which is considered statistically significant.In vitro oxidation of transferrin standards with hydrogen peroxide and excess iron, followed by immobilized trypsin digestion (Poroszyme), high-resolution LC-MS/MS analysis (Q-TOF Ultima, Waters), and MS/MS data processing (PEAKS, Bioinformatics Solution), identified several tryptic peptides containing oxidized Methionine (Met), Tryptophan (Trp), and Histidine (His) residues. Using the same methodology, oxidized residues were subsequently detected in transferrin isolated from plasma samples of patients severely affected by HH. Comparison of MS/MS spectra of in vitro oxidized samples with the most fragment ion peaks in common with oxidized peptide MS/MS spectra from patient samples revealed a strong correlation between the two. These data show that elevated NTBI may be involved in the oxidative modification of transferrin and that such modifications may play a significant role in the pathophysiology of HH.
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