Publications by authors named "Sidharth V Puram"

To study the spatial interactions among cancer and non-cancer cells, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components.

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Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs.

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Article Synopsis
  • - The study aims to map the tonotopy (frequency organization) of the human cochlea in vivo using cochlear implant electrodes, addressing challenges of past research that relied on cadaver and animal models.
  • - Fifty patients with hearing loss underwent cochlear implantation, where their responses to sound stimuli were recorded to analyze how sound intensity and an artificial "third window" influence the tonotopic map.
  • - Results showed notable deviations from the expected Greenwood model in the frequency-position function, especially at higher sound levels, indicating complexities in how the cochlea processes sound intensity.
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Background: Given limitations in the current literature, the precise indications, techniques, and outcomes relevant to vascularized fascia lata free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature to evaluate indications, methods, and complications for vascularized fascia lata free flap reconstruction.

Methods: A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the head and neck region using vascularized fascia lata.

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Objective: To describe our experience with chimeric flaps and to assess the surgical outcomes and postoperative complications associated with chimeric flaps compared to multiple flaps.

Study Design/methods: Patients undergoing chimeric and multiple simultaneous free tissue transfer between June 2016 and October 2023 were retrospectively reviewed. The primary outcome of interest was the complication rate.

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Background: Head and neck squamous cell carcinoma (HNSCC) is the 6 leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts.

Methods: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas.

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Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined.

Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT.

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Background: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

Methods: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays.

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Objectives: To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND).

Methods: A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded.

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Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12).

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Background: Aligned with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers, in November 2021 the Commission on Cancer approved initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery for head and neck cancer (HNC) as its first and only HNC quality metric. Unfortunately, >50% of patients do not commence PORT within 6 weeks, and delays disproportionately burden racial and ethnic minority groups. Although patient navigation (PN) is a potential strategy to improve the delivery of timely, equitable, guideline-adherent PORT, the national landscape of PN for this aspect of care is unknown.

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Introduction: Coronavirus disease 2019 (COVID-19) affects the vascular system, subjecting patients to a hypercoagulable state. This is of particular concern for the success of microvascular free flap reconstruction. This study aims to report head and neck free flap complications in patients with COVID-19 during the perioperative period.

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Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples.

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Objectives: To determine the association between neighborhood socioeconomic status (nSES), race and incidence rate trends of oral cavity cancer (OCC).

Materials And Methods: We used data from the SEER (Surveillance, Epidemiology, and End Results) 18 Census Tract-level SES and Rurality Database (2006-2018) database of the National Cancer Institute to create cohorts of OCC patients between 2006 and 2018. Annual incidence rates were calculated and trends in rates were estimated using joinpoints regression.

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Article Synopsis
  • * It analyzed nine studies focusing on patients' reported and objective measures of tongue function, assessing outcomes for flap versus non-flap reconstructions.
  • * Findings suggest that for less than 20% tongue resection, non-flap methods may offer better swallowing and speech results, whereas for 40-50% resection, flap repair is more beneficial; the situation for the 20-40% range remains unclear, indicating a need for more controlled research.
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(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas.

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Objective: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT.

Data Sources: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL.

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The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC).

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About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking.

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Article Synopsis
  • Head and neck squamous cell carcinoma (HNSCC) is challenging to treat, especially with PD-1 blockade therapy, prompting researchers to explore enhancing natural killer (NK) cell therapies.
  • The study generated memory-like (ML) NK and conventional (c)NK cells, assessing their effectiveness in attacking HNSCC cells, particularly when combined with cetuximab or engineered with an anti-EphA2 CAR.
  • Results showed that ML NK cells were significantly more effective at killing HNSCC cells and that their performance improved further with cetuximab, supporting the potential of these combined therapies in clinical trials.
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Objectives: To compare taste changes after transoral robotic surgery (TORS) to taste changes in healthy controls.

Methods: Oropharyngeal cancer patients receiving TORS and healthy controls were recruited. Participants underwent posterolateral and whole-mouth psychophysical taste testing (identification, intensity, and hedonics) at baseline and at 2 weeks postoperatively (patients) or follow-up (controls).

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