Proteomic profiling identifies muscle-invasive bladder cancers with distinct biology and responses to platinum-based chemotherapy.

Platinum-based neoadjuvant chemotherapy prior to radical cystectomy is the preferred treatment for muscle-invasive bladder cancer despite modest survival benefit and significant associated toxicities. Here, we profile the global proteome of muscle-invasive bladder cancers pre- and post-neoadjuvant chemotherapy treatment using archival formalin-fixed paraffin-embedded tissue. We identify four pre-neoadjuvant chemotherapy proteomic clusters with distinct biology and response to therapy and integrate these with transcriptomic subtypes and immunohistochemistry.

Kappa Free Light Chains in Multiple Sclerosis as a Marker of Intrathecal Humoral Response: A Sex-Disaggregated Study.

Background: Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and their agreement with the 'gold standard' of CSF IgG oligoclonal bands (OCBs).

Methods: A total of 233 patients were included in this study: 149, comprising 43 males and 106 females, had MS, and the remainder, 40 males and 44 females, had other neurological diseases (ONDs).

Phase Ib Pharmacodynamic Study of the MNK Inhibitor Tomivosertib (eFT508) Combined With Paclitaxel in Patients With Refractory Metastatic Breast Cancer.

Purpose: Preclinical data motivate clinical evaluation of inhibitors of MAPK-interacting kinases 1 and 2 (MNK1/2). We conducted a phase 1b clinical trial to study target engagement and safety of tomivosertib, a MNK1/2 inhibitor, alone and in combination with paclitaxel.

Patients And Methods: Eligible patients had metastatic breast cancer resistant to standard-of-care treatments.

Diagnostic Agreement in Whole Slide Digital Images of Cervical Cytology and Cell Blocks.

Background: Cell blocks (CB) are an established technique in non-gynecological cytology, but experience in gynecological cytology is still relatively limited. In this study, we compared the diagnostic agreement between liquid-based cytology (LBC) and CB using whole slide digital imaging (WSI).

Methods: WSI of 82 specimens (41 LBC and 41 CB) were evaluated independently by three observers.

Phytochemical analysis and investigation of analgesic, anti-inflammatory, and antispasmodic activities of hydroethanolic extracts of Alternanthera dentata, Ocimum carnosum, and Plectranthus barbatus, three species with vernacular names derived from analgesic drugs.

Ethnopharmacological Relevance: Plant vernacular names can provide clues about the popular use of a species in different regions and are valuable sources of information about the culture or vocabulary of a population. Several medicinal plants in Brazil have received names of medicines and brand-name products.

Aim Of The Study: The present work aimed to evaluate the chemical composition and pharmacological activity in the central nervous system of three species known popularly by brand names of analgesic, anti-inflammatory, antispasmodic, and digestive drugs.

Mass Spectrometry Acquisition and Fractionation Recommendations for TMT11 and TMT16 Labeled Samples.

Proteome coverage and accurate protein quantification are both important for evaluating biological systems; however, compromises between quantification, coverage, and mass spectrometry (MS) resources are often necessary. Consequently, experimental parameters that impact coverage and quantification must be adjusted, depending on experimental goals. Among these parameters is offline prefractionation, which is utilized in MS-based proteomics to decrease sample complexity resulting in higher overall proteome coverage upon MS analysis.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

Purpose: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC).

Methods: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + .

Sex Differences in Albumin Quotient and Cerebrospinal Fluid Total Protein Content Do Not Depend on Anthropometric Factors.

(1) Background: Cerebrospinal fluid (CSF)/serum albumin quotient (QAlb) and CSF total protein (TP) are more elevated in males than females, and this has been hypothesised to be due to anthropometric differences between the sexes. This study aimed to investigate QAlb and CSF TP as a function of body height, weight, and body mass index (BMI). (2) Methods: A total of 207 patients were included in the study and analysed blinded to clinical diagnosis.

Multicancer screening test based on the detection of circulating non haematological proliferating atypical cells.

Background: the problem in early diagnosis of sporadic cancer is understanding the individual's risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology.

Preoperative antibiotic prophylaxis and the incidence of surgical site infections in elective clean soft tissue surgery of the hand and upper limb: a systematic review and meta-analysis.

Background: Surgical site infections (SSI) are the most frequent early complications of hand surgeries. However, the indications still remain uncertain for antibiotic prophylaxis in elective clean soft tissue surgeries of the hand and upper limb. Therefore, a systematic review of the literature and a meta-analysis was conducted to investigate the impact of antibiotic prophylaxis on the prevention of SSI in these types of surgeries.

Characterizing the secretome of EGFR mutant lung adenocarcinoma.

Background: Lung cancer is the leading cause of cancer related death worldwide, mainly due to the late stage of disease at the time of diagnosis. Non-invasive biomarkers are needed to supplement existing screening methods to enable earlier detection and increased patient survival. This is critical to -driven lung adenocarcinoma as it commonly occurs in individuals who have never smoked and do not qualify for current screening protocols.

Regulation of mast cells by overlapping but distinct protein interactions of Siglec-6 and Siglec-8.

Background: Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 and Siglec-8 are closely related mast cell (MC) receptors with broad inhibitory activity, but whose functional differences are incompletely understood.

Methods: Proteomic profiling using quantitative mass spectrometry was performed on primary mouse MCs to identify proteins associated with Siglec-6 and Siglec-8. For functional characterization, each receptor was evaluated biochemically and in ex vivo and in vivo inhibition models of IgE and non-IgE-mediated MC activation in Siglec-6- or Siglec-8-expressing transgenic mice.

Leiomyoma or sarcoma? MRI performance in the differential diagnosis of sonographically suspicious uterine masses.

Purpose: To assess the diagnostic performance of MRI in distinguishing between leiomyomas and malignant/potentially malignant mesenchymal neoplasms in patients with rapidly enlarging/sonographically suspicious uterine masses.

Methods: IRB-approved retrospective study including 88 patients (51 ± 11 years) who underwent MRI for rapidly enlarging/sonographically suspicious uterine mass at our Institution between January 2016 and December 2021, followed by surgery or >12 months follow-up. Qualitative image analysis was independently performed by 2 radiologists and included lesion's margins (sharp/irregular), architecture (homogeneous/inhomogeneous), presence of endometrial infiltration (yes/no), necrotic areas (yes/no), hemorrhagic areas (yes/no), predominant signal intensity on T1-WI, T2-WI, CE T1-WI, DWI, and ADC map.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology.

Surface and Global Proteome Analyses Identify ENPP1 and Other Surface Proteins as Actionable Immunotherapeutic Targets in Ewing Sarcoma.

Purpose: Ewing sarcoma is the second most common bone sarcoma in children, with 1 case per 1.5 million in the United States. Although the survival rate of patients diagnosed with localized disease is approximately 70%, this decreases to approximately 30% for patients with metastatic disease and only approximately 10% for treatment-refractory disease, which have not changed for decades.

MyD88-dependent Toll-like receptor 2 signaling modulates macrophage activation on lysate-adsorbed Teflon™ AF surfaces in an biomaterial host response model.

The adsorbed protein layer on an implanted biomaterial surface is known to mediate downstream cell-material interactions that drive the host response. While the adsorption of plasma-derived proteins has been studied extensively, the adsorption of damage-associated molecular patterns (DAMPs) derived from damaged cells and matrix surrounding the implant remains poorly understood. Previously, our group developed a DAMP-adsorption model in which 3T3 fibroblast lysates were used as a complex source of cell-derived DAMPs and we demonstrated that biomaterials with adsorbed lysate potently activated RAW-Blue macrophages via Toll-like receptor 2 (TLR2).

The Classification Algorithms Applied to the Inpatient Stay for Lower Limb Surgery.

The revolutions of recent years in health care have involved several areas ranging from patient treatment to resource management. Therefore, several strategies have been put in place to increase patient value while trying to reduce spending. Several indicators have arisen to evaluate the performance of healthcare processes.

Effect of Clinical and Demographic Variables on the Hospital Stay of Patients Undergoing Total Knee Arthroplasty.

The knee is the joint most affected by osteoarthritis and in its severe form can significantly affect people's physical and functional abilities. The increased demand for surgery leads to greater attention by health care management to be able to keep costs down. A major expense item for this procedure is Length of Stay (LOS).

Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss.

SMARCA4 (BRG1) and SMARCA2 (BRM) are the two paralogous ATPases of the SWI/SNF chromatin remodeling complexes frequently inactivated in cancers. Cells deficient in either ATPase have been shown to depend on the remaining counterpart for survival. Contrary to this paralog synthetic lethality, concomitant loss of SMARCA4/2 occurs in a subset of cancers associated with very poor outcomes.