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Pathology of rheumatoid meningitis: A report of 5 cases highlighting the importance of clinical correlation.

Ann Diagn Pathol

February 2025

Department of Pathology, University of Colorado Health Science Center, Anschutz Medical Campus, Aurora, CO, USA; Department of Neurosurgery, University of Colorado Health Science Center, Anschutz Medical Campus, Aurora, CO, USA; Department of Neurology, University of Colorado Health Science Center, Anschutz Medical Campus, Aurora, CO, USA.

Rheumatoid meningitis (RM) presents with sufficiently wide-ranging, but non-specific, symptoms and neuroimaging features of pachy- and/or leptomeningeal thickening that it may be indistinguishable from subacute infectious meningitis. RA diagnosis variably antedates RM and serological confirmation by rheumatoid factor and anti-citrullinated peptide antibodies may not be present preoperatively. Thus, meningeal biopsy may be undertaken.

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Spatially mapping the transcriptome and proteome in the same tissue section can significantly advance our understanding of heterogeneous cellular processes and connect cell type to function. Here, we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modality spatial omics approach that combines sequencing-based spatial transcriptomics and image-based spatial protein profiling on the same tissue section to enable both single-cell resolution cell typing and genome-scale interrogation of biological pathways. DBiTplus begins with reverse transcription for cDNA synthesis, microfluidic delivery of DNA oligos for spatial barcoding, retrieval of barcoded cDNA using RNaseH, an enzyme that selectively degrades RNA in an RNA-DNA hybrid, preserving the intact tissue section for high-plex protein imaging with CODEX.

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Perturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co-sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups.

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(Korean ginseng) is renowned for its health-promoting properties, attributed to its bioactive compounds, including saponins, polyphenols, and polysaccharides, which possess both antioxidant and anti-aging activities. This study investigated the anti-aging and anti-inflammatory effects of compounds isolated from the hot water extract of fresh roots, evaluating their resistance to TNF-α/IFN-γ-induced skin cell damage. Among 14 compounds, ginsenoside Rf (compound ) showed significant multi-target effects.

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In this paper, a high-efficiency compact power amplifier is designed and fabricated with a 0.25 μm GaN high electron mobility transistor (HEMT) to meet the demands of a high integration level and high efficiency for microwave wireless power transfer (WPT) systems. The proposed power amplifier (PA) is implemented using an internally matched method to achieve a compact circuit size.

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LCM-RNAseq Highlights Intratumor Heterogeneity and a lncRNA Signature from Archival Tissues of GH-Secreting PitNETs.

Genes (Basel)

October 2024

National Research Council (CNR)-Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" (IASI), 00185 Rome, Italy.

Background: This study explores the potential for hidden variations within seemingly uniform regions of growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs). We employed archived tissue samples using Laser Capture Microdissection Sequencing (LCM-RNAseq) to probe the molecular landscape of these tumors at a deeper level.

Methods: A customized protocol was developed to extract, process, and sequence small amounts of RNA from formalin-fixed, paraffin-embedded (FFPE) tissues derived from five patients with GH-secreting PitNETs and long-term follow-up (≥10 years).

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Background: The gene encodes ATP-dependent RNA helicase SUPV3L1, which is a part of the mitochondrial degradosome complex or SUV3. SUPV3L1 unwinds secondary structures of mitochondrial RNA (mtRNA) and facilitates the degradation of mtRNA molecules. A nonsense homozygous variant in the gene was recently associated with mitochondrial disease.

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Alzheimer's disease (AD), a prevalent neurodegenerative disorder, leads to progressive dementia, which impairs decision-making, problem-solving, and communication. While there is no cure, early detection can facilitate treatments to slow its progression. Deep learning (DL) significantly enhances AD detection by analyzing brain imaging data to identify early biomarkers, improving diagnostic accuracy and predicting disease progression more precisely than traditional methods.

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Article Synopsis
  • - Vaccine uptake among adult Medicaid beneficiaries is low, prompting a systematic review of factors influencing both patients and healthcare providers regarding vaccination practices from studies published between 2005 and 2022.
  • - The review highlights that barriers to vaccination include insurance policies, cost-sharing, access to services, and the level of vaccine-related education among both patients and providers.
  • - Recommendations to improve vaccination rates focus on reducing cost-sharing, enhancing educational outreach about vaccine safety and benefits, and ensuring better reimbursement rates comparable to other insurance plans.
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Aim Of The Study: to determine the frequency of joint lesions (JnL) in children with juvenile localized scleroderma and it's possible correlation with autoantibodies and markers of fibrosis.

Materials And Methods: 500 children with JLS (370 girls and 130 boys) were studied retrospectively for the joint lesion, using standard physical examination, ultrasound examination (UlS) X-ray, MRI. In 190 patients we investigated antinuclear antibodies (antinuclear factor (ANF), rheumatoid factor (RF), antitopoisomerase 1 and anticentomere antibodies, antibodies to DNA, autoantibodies to collagen (Cab) types I-IV, cryoglobulins (CG), serum fibronectine (FN) and hyalyronic acid (HA) levels.

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  • Neoadjuvant chemotherapy (NAC) is being increasingly utilized for breast cancer treatment, and machine learning (ML) models are being tested to predict the likelihood of a pathologic complete response (pCR) based on clinical features of patients.
  • In a study involving 499 breast cancer patients from two Singapore hospitals, various ML models were trained and evaluated, utilizing methods for addressing missing data, with the random forest model showing the highest predictive accuracy and calibration.
  • Key predictors for achieving pCR included estrogen receptor intensity, HER2 intensity, and age at diagnosis, while better handling of missing data led to improved predictive performance in terms of positive and negative predictive values.
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Article Synopsis
  • * Advanced techniques such as adeno-associated viral vectors and CRISPR-Cas9 are proving to be efficient for gene delivery and repairing genetic issues in humans.
  • * The statement reviews various gene therapy approaches for heart failure and its causes, discusses their clinical applications, and highlights safety concerns and regulatory challenges for future development.
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Purpose: Advanced urothelial cancer generally has high mortality despite modern anti-PD-1/L1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (Cancer Immunotherapy Trials Network-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses.

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Unlabelled: The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton & Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives.

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  • This study investigates the connection between oxidative stress and the survival prognosis of elderly patients with esophageal squamous cancer (ESCC), utilizing machine learning models due to a lack of existing research in this area.
  • The researchers included elderly ESCC patients who underwent surgery from 2013 to 2020 and analyzed data through Cox regression, ultimately developing an oxidative stress score (OSS) to predict 3-year overall survival rates.
  • Among the 485 patients analyzed, key factors influencing survival were identified, and the random forest machine-learning model showed the best predictive performance for survival outcomes in the training cohort.
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Article Synopsis
  • * Between 2004 and 2022, MRI awarded scholarships to 405 individuals, and those who received funding had significantly lower dropout rates compared to national averages: 0% for graduate students and 2.2% for medical students.
  • * The initiative also showed that awardees were more likely to stay in the hematology-oncology field than national minority averages, with 14.4% of medical students and 88.5% of early-career
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Cerebral Blood Flow Dynamics in Neurogenic Orthostatic Hypotension: A Systematic Review and Meta-Analysis.

Hypertension

January 2025

Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Alberta, Canada (J.R.B., S.I.R., A.P., S.R.R.).

Background: Neurogenic orthostatic hypotension (nOH) causes pathological falls in standing blood pressure that may or may not be symptomatic. nOH also raises the risk of poor neurological outcomes irrespective of symptom presence, possibly reflecting subclinical cerebral hypoperfusion. Dynamic changes in cerebral blood flow velocity (CBFv) help infer how blood pressure fluctuations influence CBFv and cerebral autoregulation.

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Article Synopsis
  • Brain metastases (BMs) in extensive-stage small cell lung cancer (ES-SCLC) lead to poor survival rates, making it vital to identify high-risk patients early.
  • The study analyzed data from 4,716 ES-SCLC patients using four machine learning algorithms, finding that the random forest (RF) model was the most accurate in predicting the risk of BMs.
  • Key risk factors for BMs included bone and liver metastases, age, tumor size, and treatment history, which the RF model can help physicians use to improve patient care and potentially enhance survival outcomes.
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Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

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Long-Term Cognitive, Functional, and Patient-Reported Outcomes in Patients With Anti-NMDAR Encephalitis.

Neurology

December 2024

From the Department of Neurology (J.B., C.J.R., I.K., A.E.M.B., Y.S.C., C.N.K., J.C.P.V., A.A.G.T., B.T., L.P.K., M.A.A.M.d.B., M.R.M., J.K., R.W.v.S., J.M.d.V., R.F.N., P.A.E.S.S., M.J.T.), Erasmus University Medical Center, Rotterdam; Department of Neurology (S.H.C.O.), Amsterdam University Medical Center; Department of Immunology (S.V.), Erasmus University Medical Center, Rotterdam; Laboratory of Medical Microbiology and Immunology Microvida (M.W.J.S.), Tilburg; and Department of Neurology & Alzheimer Center (E.v.d.B.), Erasmus University Medical Center, Rotterdam, the Netherlands.

Background And Objectives: Anti-NMDA receptor (anti-NMDAR) encephalitis generally manifests in young adults. Although 80%-90% returns to independence, the majority experience persistent cognitive and psychosocial difficulties. Studies have demonstrated that cognitive recovery may continue for years; the temporal trajectory is largely unknown, as are factors influencing cognitive/psychosocial recovery.

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Purpose Of Review: In this review, we discuss which patients with metastatic clear cell renal cell carcinoma (mRCC) may be most suitable for frontline tyrosine kinase inhibitor (TKI) monotherapy, a treatment option supported by emerging long-term efficacy data including overall survival and quality of life. We specifically focus on tivozanib, a potent and selective inhibitor of vascular endothelial growth factor receptor, which has comparable efficacy to other single-agent TKIs in frontline treatment for mRCC while exhibiting fewer off-target side effects.

Recent Findings: Combination therapy with TKIs and checkpoint inhibitors (CPIs) and CPI/CPI combination therapies, as well as TKI monotherapy are recommended frontline treatment options for mRCC.

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Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by persistent joint inflammation, pain, and tissue degradation. This study evaluates the therapeutic potential of Norisoboldine (NOR), an isoquinoline alkaloid from Lindera aggregata, in a rat model of RA.

Methods: Rats were divided into five groups: normal control (G1), RA model (G2), NOR-treated groups at 15 mg/kg (G3) and 30 mg/kg (G4), and methotrexate-treated group (G5).

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Background: Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures.

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The resolvin D2 and omega-3 polyunsaturated fatty acid as a new possible therapeutic approach for inflammatory bowel diseases.

Sci Rep

November 2024

Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil.

Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies' adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation.

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Statin-associated regulation of hepatic PNPLA3 in patients without known liver disease.

J Intern Med

January 2025

Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Background And Objectives: Statins are used for metabolic dysfunction-associated steatotic liver disease (MASLD) (NAFLD) treatment, but their role in this context is unclear. Genetic variants of patatin-like phospholipase domain containing 3 (PNPLA3) are associated with MASLD susceptibility and statin treatment efficacy. Access to liver biopsies before established MASLD is limited, and statins and PNPLA3 in early liver steatosis are thus difficult to study.

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