Publications by authors named "Ram Thapa"

Immunotherapy response is associated with the presence of conventional dendritic cells (cDCs). cDC type 1 (cDC1) is critically important for CD8+ T cell activation, cDC type 2 (cDC2) regulates CD4+ T cell responses, and mature regulatory cDCs may dampen T cell responses in the tumor microenvironment (TME). However, we lack a clear understanding of cDC distribution in the human TME, cDC prevalence in metastatic sites, and cDC differences in early- versus late-stage disease.

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Nanostructured Zincoxide thin-film is widely used as a sensing material because of its tunable surface microstructure and wide optical bandgap but synthesizing a film with desired value of resistance and reproducibility of film is challenging, particularly by chemical method. In this work, we showed how a ZnO film of arbitrary resistance can be used as a sensor without application of heat using operational amplifier. Zinc oxide thin film was synthesized by using the Sol-gel method (Spin coating) and was characterized by XRD and SEM which revealed wurtzite polycrystalline nature of Zinc oxide film with average grain size 17-25 nm.

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Background: Tunafasi is a community-based rehabilitation (CBR) programme for persons with disability, implemented by a local non-governmental organisation in Uvira, Democratic Republic of Congo, in partnership with government. To assess affordability and support discussions with the government about continued financing and implementation, Tunafasi representatives commissioned a cost-effectiveness study of the programme's health component.

Objectives: This study aimed to estimate the programme's impacts, costs, cost per disability-adjusted life year (DALY) averted and affordability of the health component implemented from February 2019 to December 2021.

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Background: The optimal treatment sequencing for patients with metastatic epidermal growth factor receptor ()-mutant non-small cell lung cancer (NSCLC) remains a subject of debate. In the United States, osimertinib is the preferred tyrosine kinase inhibitor (TKI) in the first-line setting. However, small retrospective studies suggest that alternative TKI sequencing strategies may produce similar outcomes.

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Importance: While the incidence of early-onset metastatic colorectal cancer (mCRC) has been increasing, studies on the age-related disparity in this group of patients are limited.

Objective: To evaluate the association of age with treatment-related adverse events and survival in patients with mCRC and explore the potential underlying factors.

Design, Setting, And Participants: This cohort study included 1959 individuals.

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Rationale: Adverse events (AEs) have been shown to have clinical associations, in addition to patient safety assessments of drugs of interest. However, due to their complex content and associated data structure, AE evaluation has been restricted to descriptive statistics and small AE subset for efficacy analysis, limiting the opportunity for global discovery. This study takes a unique approach to utilize AE-associated parameters to derive a set of innovative AE metrics.

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Background: Patients with relapsed and refractory solid and central nervous system (CNS) tumors have poor outcomes and need novel therapeutic options. Vincristine, irinotecan, and temozolomide (VIT) is a common chemotherapy regimen in relapsed pediatric tumors with an established toxicity profile. Metformin shows preclinical anti-cancer activity through multiple pathways.

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Article Synopsis
  • Merkel cell carcinoma is a highly aggressive and deadly skin cancer, typically treated with standard therapies like anti-PD-1 and PD-L1 monotherapy for advanced cases.
  • This study evaluated the effectiveness of combining nivolumab and ipilimumab with or without stereotactic body radiotherapy (SBRT) as a first-line treatment in patients with advanced Merkel cell carcinoma.
  • The trial involved randomly assigning adults to receive either the combination therapy alone or with SBRT, measuring treatment responses to assess the overall effectiveness through objective response rate (ORR).
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Purpose: The adenosine 2A receptor (A2AR) mediates the immunosuppressive effects of adenosine in the tumor microenvironment and is highly expressed in non-small cell lung cancer (NSCLC). Taminadenant (PBF509/NIR178) is an A2AR antagonist able to reactivate the antitumor immune response.

Patients And Methods: In this phase I/Ib, dose-escalation/expansion study, patients with advanced/metastatic NSCLC and ≥1 prior therapy received taminadenant (80-640 mg, orally, twice a day) with or without spartalizumab (anti-programmed cell death-1, 400 mg, i.

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New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME.

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Article Synopsis
  • Women with disabilities (WwDs) in Nepal face significant barriers to accessing sexual and reproductive health (SRH) services, despite goals for universal access.* -
  • A study involving 384 WwDs in Ilam district found that only 15% utilized SRH services, with major reasons for non-utilization being lack of necessity and unawareness, as well as issues like inaccessible health facilities.* -
  • Factors positively influencing SRH service utilization included being married, having a perceived need for services, and awareness of susceptibility to SRH-related conditions, with additional qualitative insights pointing to illiteracy and socioeconomic status as obstacles.*
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We conducted a prospective study of adult allogeneic hematopoietic cell transplantation (HCT) recipients to assess pre- and post-HCT physical function. Baseline measurements included a wrist actigraphy, a 6 min walk test (6MWT), an international physical activity questionnaire (IPAQ), and a Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) as well as serial post-HCT assessments of 6MWT, IPAQ, and FACT-BMT. Forty-seven patients were evaluable for functionality assessments, with a median follow-up of 54.

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Immunomodulatory properties of histone deacetylase inhibitors represent a reasonable approach for acute graft-versus-host disease (aGVHD) prevention. We report a phase 2 trial evaluating panobinostat (PANO) administered over 26 weeks, starting on day -5 (5 mg orally 3 times a week) with tacrolimus initiated on day -3 plus sirolimus on day -1, with a median patient age of 58 years (range, 19-72 years) (n = 38). Donor source consisted of HLA 8/8-matched donors, related (n = 13) or unrelated (n = 25), using granulocyte colony-stimulating factor-stimulated peripheral blood stem cells.

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Rationale: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.

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The introduction of posttransplant cyclophosphamide (PTCy) made performing allogeneic hematopoietic cell transplantation (HCT) from HLA haplotype-incompatible donors possible. In a setting of PTCy and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis, a peripheral blood (PB) graft source as compared with bone marrow reduces the relapse rate but increases acute GVHD (aGVHD) and chronic GVHD (cGVHD). This phase 2 trial assessed sirolimus and MMF efficacy following PTCy as a GVHD prophylaxis after PB haploidentical HCT (haplo-HCT).

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Introduction: Cancer sequencing efforts have revealed that cancer is the most complex and heterogeneous disease that affects humans. However, radiation therapy (RT), one of the most common cancer treatments, is prescribed on the basis of an empirical one-size-fits-all approach. We propose that the field of radiation oncology is operating under an outdated null hypothesis: that all patients are biologically similar and should uniformly respond to the same dose of radiation.

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Highly collaborative scientists are often called on to extend their expertise to different types of projects and to expand the scope and scale of projects well beyond their previous experience. For a large-scale project involving "big data" to be successful, several different aspects of the research plan need to be developed and tested, which include but are not limited to the experimental design, sample collection, sample preparation, metadata recording, technical capability, data acquisition, approaches for data analysis, methods for integration of different data types, recruitment of additional expertise as needed to guide the project, and strategies for clear communication throughout the project. To capture this process, we describe an example project in proteogenomics that built on our collective expertise and experience.

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Objectives: To establish whether clinicopathologic and genomic characteristics may explain the poor prognosis associated with advanced age in ER+/HER2- breast cancer.

Materials And Methods: The cohort included 271 consecutive post-menopausal patients with ER+/HER2- invasive breast cancer ages 55 years and older. Patients were categorized as "younger" (ages 55- < 75) and "older" (ages ≥75).

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Purpose: Histone deacetylase inhibitors (HDACi) enhance tumor immunogenicity through several mechanisms and may improve response to immune checkpoint inhibitors (ICIs). In a phase I/Ib trial, we tested the oral HDACi vorinostat combined with the programmed cell death protein 1 inhibitor pembrolizumab in advanced/metastatic non-small cell lung cancer.

Patients And Methods: Patients received intravenous pembrolizumab (200 mg every 3 weeks) plus oral vorinostat (200 or 400 mg/day).

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Article Synopsis
  • The study explores how genomic and transcriptomic changes impact the proteins expressed in lung squamous cell cancer (SCC) by analyzing data from 108 patients.
  • Three proteomic subtypes are identified: Inflamed and Redox, which together make up 87% of the tumors. The Inflamed subtype shows higher immune cell presence and PD-1 expression, while the Redox subtype is linked to specific metabolic pathways and gene alterations.
  • Although the subtypes don’t directly correlate with patient survival, the presence of B-cell-rich structures in the Inflamed subtype is linked to better survival outcomes, and the research highlights potential therapeutic targets in the Redox group related to metabolism.
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Importance: In the United States, the most used molecular test for the evaluation of cytologically indeterminate thyroid nodules is the Afirma gene expression classifier (GEC).

Objective: To evaluate the GEC's diagnostic performance through a novel approach to assess whether the findings of the initial validation study are consistent with the results of postmarketing studies.

Data Sources: PubMed was systematically searched from inception through October 26, 2017, using the terms gene expression classifier or Afirma or GEC and thyroid.

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Melanoma cells have the ability to switch to a dedifferentiated, invasive phenotype in response to multiple stimuli. Here, we show that exposure of melanomas to multiple stresses including BRAF-MEK inhibitor therapy, hypoxia, and UV irradiation leads to an increase in histone deacetylase 8 (HDAC8) activity and the adoption of a drug-resistant phenotype. Mass spectrometry-based phosphoproteomics implicated HDAC8 in the regulation of MAPK and AP-1 signaling.

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Background: Robotic pelvic lymphadenectomy (rPLND) has been demonstrated to be a safe and effective minimally invasive approach for patients with metastatic melanoma to the iliac nodes. However, the long-term oncologic benefit of this procedure remains poorly defined.

Methods: A single-institutional study comparing perioperative outcomes and survival [recurrence-free (RFS) and overall survival (OS)] between rPLND and open PLND (oPLND) for metastatic melanoma was conducted.

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Objective: Breast cancer (BC) survivors with a genetic mutation are at higher risk for subsequent cancer; knowing genetic risk status could help survivors make decisions about follow-up screening. Uptake of genetic counseling and testing (GC/GT) to determine BRCA status is low among high risk BC survivors. This study assessed feasibility, acceptability, and preliminary efficacy of a newly developed psychoeducational intervention (PEI) for GC/GT.

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Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid).

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