To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
Microsporidial stromal keratitis is rare. Conventional surgical treatment for such a condition has been penetrating keratoplasty. DALK may be considered an option for visual rehabilitation in these cases.
Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.
Primary breast lymphomas (PBLs) represent less than 1% of all breast malignancies. Intravascular large B-cell lymphoma (ILBCL) is a rare, aggressive form of extranodal lymphoma. Breast involvement has only been described in the literature once previously. ILBCL is characterized by the proliferation of tumour cells within the lumen of small vessels of involved organs, resulting in their eventual occlusion. Clinical features are often vague, diagnosis is difficult and delayed, and prognosis is usually poor. We report the first ever case of synchronous ILBCL and invasive ductal carcinoma (IDC) of the breast in a patient presenting with pyrexia of unknown origin and altered mental status who underwent modified radical mastectomy and subsequent chemotherapy, and review the literature regarding intravascular large B-cell lymphoma, PBLs and synchronous carcinomas and lymphomas of the breast.
BackgroundHeterotopic pancreas most commonly occurs in the upper gastrointestinal tract of adults, usually as an incidental finding. It seldom occurs at the umbilicus, and even rarely in the pediatric age group.Case presentationHere we present a case of heterotopic pancreatic tissue in the omphalomesenteric duct remnant of a 9-month-old baby girl. She presented with redness at the base of the umbilicus associated with occasional mild wetness. A urachal fistula was suspected by ultrasound. Histology from subsequent resection revealed fibrous tissue with heterotopic pancreatic tissue and accompanying small bowel mucosa. The patient’s umbilical redness resolved after the surgery.ConclusionsUpon literature search, we found only 17 other cases of heterotopic pancreas reported in the umbilicus. They described a high male to female ratio, frequent association with omphalomesenteric duct remnant and presentation of umbilical discharge. The Heinrich system is frequently used to classify heterotopic pancreas into 3 types, based on the presence of acini, islets and ducts. Several mechanisms have been proposed on the pathogenesis of heterotopic pancreas, including misplacement, metaplasia and totipotent cell theories. Heterotopic pancreas can manifest clinically with diseases of the pancreas, including malignant transformation, reported as high as 12.7% in a series. Awareness of this finding in the biopsy aids the suitable treatment decisions for the patient.
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