Uncommon Presentation: A Case Report on a Rare Vulvar Fibroadenoma.

Vulval fibroadenoma is an uncommon, benign tumor that originates from ectopic breast tissue or mammary-like glands in the anogenital region. Only a limited number of cases have been documented in medical literature. Typically occurring in young and middle-aged women, this condition, when surgically removed, generally exhibits a favorable prognosis with a low recurrence rate. We report a case of vulvar fibroadenoma wherein the patient exhibited a groin region mass. The mass was then excised and examined histologically. Histological examination of the polypoidal tissue section unveiled a clearly defined lesion comprising both epithelial and stromal components.

Hepatic Angiomyolipoma With Predominant Lipomatous Component: A Rare Entity.

Hepatic angiomyolipoma (HAML) is a rare benign mesenchymal tumor with varying amounts of mature adipose tissue, smooth muscle cells, and thick-walled blood vessels. We present a rare case of hepatic angiomyolipoma (AML) with predominant lipomatous components. A 42-year-old female presented to the hospital with pain in the right lumbar region. On imaging, there was a large fat-predominant mass attached to the surface of the liver extending down to the lumbar region. On small biopsy, it was reported as a well-differentiated adipocytic neoplasm, and fluorescence in situ hybridization (FISH) studies performed for MDM2 were negative. On excision, histopathological examination showed predominantly fat components, but there were few epithelioid cells between adipocytes and thick-walled blood vessels. These cells were positive for Melan-A, HMB45, and smooth muscle actin (SMA) and negative for hepatocyte paraffin-1 (Hep Par1). Angiomyolipoma is a benign tumor and has a good prognosis with surgical excision. Few cases are associated with tuberous sclerosis.

Chronic Pancreatitis-Induced Thrombosis of Celiac and Superior Mesenteric Artery.

Every year, nearly 60,000 hospitalizations occur in the United States due to chronic pancreatitis (CP). CP can cause severe chronic abdominal pain, pancreatic insufficiency, and increased risk of pancreatic cancer. While venous thrombotic complications are common, arterial thrombotic events are rarely reported in CP. This report describes a case of a 43-year-old female who presented with severe worsening abdominal pain due to CP. Diagnostic imaging disclosed thrombosis of superior mesenteric artery (SMA) and celiac artery (CA) with acute bowel wall changes reflecting ischemic changes, resulting in acute-on-chronic mesenteric ischemia. Endovascular stent placement relieved the ischemia with the resolution of pain. Arterial thrombosis should be considered as a diagnostic possibility when patients with CP present with a significant change in symptoms. Importantly, the case demonstrates that endovascular treatment with stent placement can relieve ischemia and resolve symptoms in patients with CP.

Renal Leiomyosarcoma: Unraveling the Mysteries of a Rare Malignancy.

Primary leiomyosarcoma is a rare malignant kidney tumor. The diagnosis of this disease is usually made on the basis of histological examination because it lacks specific clinical or radiological characteristics. Differentiation between leiomyosarcoma and sarcomatoid renal cell carcinoma can be challenging because spindle cell morphology is observed in both tumors. Therefore, caution should be exercised when making a diagnosis of primary renal leiomyosarcoma. Both renal sarcoma and sarcomatoid renal cell carcinoma have a worse prognosis, and nephrectomy is the treatment of choice in locally resectable tumors. An example of such a tumor is discussed in relation to its diagnostic challenges. We report a case of a 35-year-old female who presented with a left renal mass. A left radical nephrectomy was performed, and a firm, tan-white, lobulated tumor (14x8x7.5 cm) was present on gross examination. A histological diagnosis of high-grade leiomyosarcoma was made on the basis of histology, positivity for caldesmon and desmin, and negative cytokeratin immunostaining. Sarcomatoid renal cell carcinoma was ruled out based on morphological findings after extensive sampling of the tumor along with negativity for CK, CD-10, and carbonic anhydrase IX immunostaining.

HTS discovery of PARP1-HPF1 complex inhibitors in cancer.

PARP1/2 inhibitors (PARPi) are effective clinically used drugs for the treatment of cancers with BRCA deficiencies. PARPi have had limited success and applicability beyond BRCA deficient cancers, and their effect is diminished by resistance mechanisms. The recent discovery of Histone PARylation Factor (HPF1) and the role it plays in the PARylation reaction by forming a shared active site with PARP1 raises the possibility that novel inhibitors that target the PARP1-HPF1 complex can be identified. Herein we describe a simple and cost-effective high-throughput screening (HTS) method aimed at discovering inhibitors of the PARP1-HPF1 complex. Upon HTS validation, we first applied this method to screen a small PARP-focused library of compounds and then scale up our approach using robotic automation to conduct a pilot screen of 10,000 compounds and validating >100 hits. This work demonstrates for the first time the capacity to discover potent inhibitors of the PARP1-HPF1 complex, which may have utility as probes to better understand the DNA damage response and as therapeutics for cancer.

Probiotics and Fecal Transplant: An Intervention in Delaying Chronic Kidney Disease Progression?

Chronic kidney disease (CKD) is a global health challenge affecting nearly 700 million people worldwide. In the United States alone, the Medicare costs for CKD management has reached nearly USD 80 billion per year. While reversing CKD may be possible in the future, current strategies aim to slow its progression. For the most part, current management strategies have focused on employing Renin Angiotensin Aldosterone (RAS) inhibitors and optimizing blood pressure and diabetes mellitus control. Emerging data are showing that a disruption of the gut-kidney axis has a significant impact on delaying CKD progression. Recent investigations have documented promising results in using microbiota-based interventions to better manage CKD. This review will summarize the current evidence and explore future possibilities on the use of probiotics, prebiotics, synbiotics, and fecal microbial transplant to reduce CKD progression.

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review.

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007-2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau-Demjanov rearrangement, Aza-Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.

BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies.

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These bromobenzofuran-oxadiazole structural hybrids BF1-9 were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3ß, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs BF-2, BF-5, and BF-6 displayed the best anti-cancer potential and with the least cell viabilities (12.72 ± 2.23%, 10.41 ± 0.66%, and 13.08 ± 1.08%), respectively, against HepG2 liver cancer cell line, and they also showed excellent molecular docking scores against EGFR, PI3K, mTOR, and Tubulin polymerization enzymes, which are major cancer targets. Bromobenzofuran-oxadiazoles BF-2, BF-5, and BF-6 displayed excellent binding affinities with the active sites of EGFR, PI3K, mTOR, and Tubulin polymerization enzymes in the molecular docking studies as well as in MMGBSA and MM-PBSA studies. The stable bindings of these structural hybrids BF-2, BF-5, and BF-6 with the enzyme targets EGFR and PI3K were further confirmed by molecular dynamic simulations. These investigations revealed that 2,5-dimethoxy-based bromobenzofuran-oxadiazole BF-5 (10.41 ± 0.66% cell viability) exhibited excellent cytotoxic therapeutic efficacy. Moreover, computational studies also suggested that the EGFR, PI3K, mTOR, and Tubulin polymerization enzymes were the probable targets of this BF-5 scaffold. In silico approaches, such as molecular docking, molecular dynamics simulations, and DFT studies, displayed excellent association with the experimental biological data of bromobenzofuran-oxadiazoles BF1-9. Thus, in silico and in vitro results anticipate that the synthesized bromobenzofuran-oxadiazole hybrid BF-5 possesses prominent anti-liver cancer inhibitory effects and can be used as lead for further investigation for anti-HepG2 liver cancer therapy.

Large Solitary Lung Metastasis of a Matrix-Producing Metaplastic Breast Carcinoma: A Diagnostic Challenge.

Metaplastic breast carcinoma represents a diverse category of invasive breast cancers distinguished by the transformation of neoplastic epithelial cells into squamous cells or cells with mesenchymal appearance. Matrix-producing breast carcinoma is a variant of metaplastic breast carcinoma, an exceedingly uncommon malignancy accounting for less than 1% of all breast tumors. The precise origin of this tumor remains elusive; some molecular research points to a potential derivation from myoepithelial cells, while other studies emphasize the possibility of neoplastic transformation originating from multipotent stem cells. We report a case of recurrent matrix-producing breast carcinoma. The patient presented with a breast mass. The tumor cells displayed a lack of reactivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), and exhibited a Ki-67 proliferation index of approximately 40%. Additionally, the tumor cells demonstrated significant reactivity for cytokeratins and S100. The patient underwent surgery, radiation, and chemotherapy and then developed metastasis to the lower lobe of her left lung, seven years after primary diagnosis. Diagnosis of metastasis was confirmed by comparing the metastasis to the primary tumor and staining with a panel of immunohistochemical stains. The patient is currently undergoing chemotherapy and immunotherapy.

Transition Metal Catalyzed Hiyama Cross-Coupling: Recent Methodology Developments and Synthetic Applications.

Hiyama cross-coupling is a versatile reaction in synthetic organic chemistry for the construction of carbon-carbon bonds. It involves the coupling of organosilicons with organic halides using transition metal catalysts in good yields and high enantioselectivities. In recent years, hectic progress has been made by researchers toward the synthesis of diversified natural products and pharmaceutical drugs using the Hiyama coupling reaction. This review emphasizes the recent synthetic developments and applications of Hiyama cross-coupling.

A unified technique for entropy enhancement based diabetic retinopathy detection using hybrid neural network.

In this paper, a unified technique for entropy enhancement-based diabetic retinopathy detection using a hybrid neural network is proposed for diagnosing diabetic retinopathy. Medical images play crucial roles in the diagnosis, but two images representing two different stages of a disease look alike. It, consequently, make the process of diagnosis extraneous and error-prone. Therefore, in this paper, a technique is proposed to address these issues. Firstly, a novel entropy enhancement technique is devised exploiting the discrete wavelet transforms to improve the visibility of the medical images by making the subtle features more prominent. Later, we designed a computationally efficient hybrid neural network that efficiently classifies diabetic retinopathy images. To examine the effectiveness of our technique, we have chosen three datasets: Ultra-Wide Filed (UWF) dataset, Asia Pacific Tele Ophthalmology Society (APTOS) dataset, and MESSIDOR-2 dataset. In the end, we performed extensive experiments to validate the performance of our technique. In addition, the comparison of the proposed scheme - in terms of accuracy, specificity, sensitivity, precision and recall curve, and area under the curve - with some of the best contemporary schemes shows the significant improvement of our techniques in terms of diabetic retinopathy classification.