Biomedical subjects

Robert Ferris

Publications and source records attributed to Robert Ferris.

9 recordsLinked to original sources

PubMed2026

Toward a Better Paradigm for Head and Neck Cancer Treatment Applying AI (HNC-TACTIC): Protocol for an International Cohort Study of Electronic Health Records.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) cause considerable morbidity and mortality. Multimodal treatment strategies can cause significant toxicity, and therapy options are limited for recurrent disease. Immunotherapy has emerged as a promising approach. However, patient response variability underscores the need for better predictive markers. OBJECTIVE: This study aims to use artificial intelligence to develop two predictive models in patients with HNSCC to assess (1) progression or recurrence following primary curative treatment and (2) long-term survival after immunotherapy schemes in recurrent and metastatic disease. This study will also describe the characteristics of patients with early, locally advanced, and recurrent or metastatic cancers. METHODS: This is a retrospective, observational study of data captured in electronic health records (EHRs) from participating hospitals between January 1, 2014, and December 31, 2021. This study's population comprises adults diagnosed with HNSCC at any stage. Study variables, including demographics, comorbidities, clinical variables, treatments, and outcomes, will be extracted using EHRead, a technology that applies natural language processing and machine learning to extract and analyze structured and unstructured clinical information in deidentified EHRs. Predictive models based on dynamic risk stratification for treatment response and progression or recurrence will be developed using multivariable logistic regressions, decision tree classifiers, and random forest approaches. Descriptive and outcome analyses will be shown for different anatomic subsites and stratified by stage and treatment. RESULTS: This study began enrolling sites in July 2021 and is currently ongoing. By December 2025, data from 10 centers has been collected, comprising a total of 151,934,990 EHRs from 2,159,719 patients. CONCLUSIONS: Development of predictive models using artificial intelligence will advance clinical understanding of HNSCC to improve patient outcomes.

Humans↗

PubMed2006

Reconstruction of the lateral mandibulectomy defect: management based on prognosis and location and volume of soft tissue resection.

OBJECTIVE: To examine how the accompanying soft tissue resection of the oral cavity, oropharynx, neck, or face affects the reconstructive management of the lateral mandibulectomy defect. STUDY DESIGN: Retrospective review of 76 consecutive patients. METHODS: Patient and tumor variables were extracted from the medical records. Outcomes that were examined included method of reconstruction, medical complications, flap complications, and survival. RESULTS: Age greater than 70 years (P = .03), moderate or severe comorbidity (P = .01), and tumor involvement of the base of tongue (P = .03) were significantly associated with decreased use of a free flap and with decreased 3-year survival rates. For choice of free (osteocutaneous radial forearm free flap or fibula vs. rectus abdominis) and regional flaps (pectoralis or cervicodeltopectoral), lateral defects could be classified into one of three types: type 1 (n = 60), lateral defect with a soft tissue resection limited to the oral cavity and oropharynx; type 2 (n = 11), lateral defect with a through and through defect of the lower one third of the face (skin overlying the mandible) or neck; and type 3 (n = 5), lateral defect with an associated large-volume resection of the midface, parotid, or cheek skin. CONCLUSION: When the lateral mandible is resected with an accompanying large soft tissue defect of the neck or face (type 2 or type 3 defect), the reconstructive challenge becomes the determination of how best to cover the planned bony reconstruction or whether to perform only a soft tissue reconstruction. When placed in the context of expected prognosis, the proposed classification system based on the location and volume of the associated soft tissue resection can help guide the reconstructive options for these decisions.

Aged↗

PubMed2006

Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138.

Lys101Glu is a drug resistance mutation in reverse transcriptase clinically observed in HIV-1 from infected patients treated with the non-nucleoside inhibitor (NNRTI) drugs nevirapine and efavirenz. In contrast to many NNRTI resistance mutations, Lys101(p66 subunit) is positioned at the surface of the NNRTI pocket where it interacts across the reverse transcriptase (RT) subunit interface with Glu138(p51 subunit). However, nevirapine contacts Lys101 and Glu138 only indirectly, via water molecules, thus the structural basis of drug resistance induced by Lys101Glu is unclear. We have determined crystal structures of RT(Glu138Lys) and RT(Lys101Glu) in complexes with nevirapine to 2.5 A, allowing the determination of water structure within the NNRTI-binding pocket, essential for an understanding of nevirapine binding. Both RT(Glu138Lys) and RT(Lys101Glu) have remarkably similar protein conformations to wild-type RT, except for significant movement of the mutated side-chains away from the NNRTI pocket induced by charge inversion. There are also small shifts in the position of nevirapine for both mutant structures which may influence ring stacking interactions with Tyr181. However, the reduction in hydrogen bonds in the drug-water-side-chain network resulting from the mutated side-chain movement appears to be the most significant contribution to nevirapine resistance for RT(Lys101Glu). The movement of Glu101 away from the NNRTI pocket can also explain the resistance of RT(Lys101Glu) to efavirenz but in this case is due to a loss of side-chain contacts with the drug. RT(Lys101Glu) is thus a distinctive NNRTI resistance mutant in that it can give rise to both direct and indirect mechanisms of drug resistance, which are inhibitor-dependent.

Anti-HIV Agents↗

PubMed2006

Frameless stereotactic radiosurgery for recurrent head and neck carcinoma.

The aim of this study was to assess the feasibility and toxicity of stereotactic radiosurgery (CK-SRS) using the CyberKnife Frameless Radiosurgery System (Accuray Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of the head and neck region (SCCHN). Between November 2001 and February 2004, 22 patients with recurrent, previously irradiated SCCHN were treated with CK-SRS. The following endpoints were assessed post-CK-SRS: local control (LC), cause-specific survival (CSS), overall survival (OS), symptom relief, and acute and late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS, and OS rates. Clinical symptoms were graded as "improved," "stable," or "progressed" after CK-SRS. Acute and late toxicity were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0. Seventeen patients were followed until their death. The median follow-up in the remaining five patients was 19 months (range 11-40 months). The median survival time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC, CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms were improved or stable in all but one patient who reported increasing pain. The treatment was well tolerated, with one case each of Grade 2 and 3 mucositis. There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible and safe in the setting of high doses of prior irradiation. The majority of patients experienced palliation of disease without excess toxicity.

Adult↗

PubMed2005

Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo.

Breast and kidney-expressed chemokine (BRAK) CXCL14 is a new CXC chemokine with unknown function and receptor selectivity. The majority of head and neck squamous cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous epithelium. In this study, we demonstrate that the loss of CXCL14 in HNSCC cells and at HNSCC primary tumor sites was correlated with low or no attraction of dendritic cell (DC) in vitro, and decreased infiltration of HNSCC mass by DC at the tumor site in vivo. Next, we found that recombinant human CXCL14 and CXCL14-positive HNSCC cell lines induced DC attraction in vitro, whereas CXCL14-negative HNSCC cells did not chemoattract DC. Transduction of CXCL14-negative HNSCC cell lines with the human CXCL14 gene resulted in stimulation of DC attraction in vitro and increased tumor infiltration by DC in vivo in chimeric animal models. Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation of the expression of DC maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR. Activation of DC with recombinant human CXCL14 was accompanied by up-regulation of NF-kappaB activity. These data suggest that CXCL14 is a potent chemoattractant and activator of DC and might be involved in DC homing in vivo.

Animals↗

PubMed2005

Chronic loss of subcutaneous adipose tissue in HIV-associated lipodystrophy may not be associated with accelerated apoptosis.

HIV-associated lipodystrophy (HIV-LD) is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue (SAT). The present study examined the rate of apoptosis in SAT with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV-LD were compared with HIV-infected subjects without LD and subjects without HIV disease. Although apoptosis was observed in subjects with HIV-LD, there was no difference in the incidence of individuals with apoptosis among those with HIV-LD (10 of 22 subjects), those with HIV but no LD (13 of 25 subjects), and those without HIV disease (13 of 27 subjects). These data suggest that HIV-related chronic loss of SAT may not always be associated with increased frequency of adipocyte apoptosis.

Adipocytes↗

PubMed2005

Loss of subcutaneous adipose tissue in HIV-associated lipodystrophy is not due to accelerated apoptosis.

HIV-associated lipodystrophy is characterized by a loss of adipose tissue from the subcutaneous compartment. Previously reported data suggested that this loss of adipose tissue was the result of an increased rate of apoptosis in subcutaneous adipose tissue. The present study examined the rate of apoptosis in subcutaneous adipose tissue with a sensitive ligase-mediated polymerase chain reaction technique to amplify DNA ladders. Individuals with HIV lipodystrophy were compared with HIV-infected subjects without lipodystrophy and subjects without HIV disease. Although apoptosis was observed in subjects with HIV lipodystrophy, there was no difference in the frequency of individuals with apoptosis among those with HIV lipodystrophy (10/22), those with HIV but no lipodystrophy (13/25), and subjects without HIV disease (13/27).

Adipocytes↗

PubMed2005

Task-based optimization and performance assessment in optical coherence imaging.

Optimization of an optical coherence imaging (OCI) system on the basis of task performance is a challenging undertaking. We present a mathematical framework based on task performance that uses statistical decision theory for the optimization and assessment of such a system. Specifically, we apply the framework to a relatively simple OCI system combined with a specimen model for a detection task and a resolution task. We consider three theoretical Gaussian sources of coherence lengths of 2, 20, and 40 microm. For each of these coherence lengths we establish a benchmark performance that specifies the smallest change in index of refraction that can be detected by the system. We also quantify the dependence of the resolution performance on the specimen model being imaged.

Algorithms↗

PubMed2002

Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action.

Benzimidazole nucleosides have been shown to be potent inhibitors of human cytomegalovirus (HCMV) replication in vitro. As part of the exploration of structure-activity relationships within this series, we synthesized the 2-isopropylamino derivative (3322W93) of 1H-beta-D-ribofuranoside-2-bromo-5,6-dichlorobenzimidazole (BDCRB) and the biologically unnatural L-sugars corresponding to both compounds. One of the L derivatives, 1H-beta-L-ribofuranoside-2-isopropylamino-5,6-dichlorobenzimidazole (1263W94), showed significant antiviral potency in vitro against both laboratory HCMV strains and clinical HCMV isolates, including those resistant to ganciclovir (GCV), foscarnet, and BDCRB. 1263W94 inhibited viral replication in a dose-dependent manner, with a mean 50% inhibitory concentration (IC(50)) of 0.12 +/- 0.01 microM compared to a mean IC(50) for GCV of 0.53 +/- 0.04 microM, as measured by a multicycle DNA hybridization assay. In a single replication cycle, 1263W94 treatment reduced viral DNA synthesis, as well as overall virus yield. HCMV mutants resistant to 1263W94 were isolated, establishing that the target of 1263W94 was a viral gene product. The resistance mutation was mapped to the UL97 open reading frame. The pUL97 protein kinase was strongly inhibited by 1263W94, with 50% inhibition occurring at 3 nM. Although HCMV DNA synthesis was inhibited by 1263W94, the inhibition was not mediated by the inhibition of viral DNA polymerase. The parent benzimidazole D-riboside BDCRB inhibits viral DNA maturation and processing, whereas 1263W94 does not. The mechanism of the antiviral effect of L-riboside 1263W94 is thus distinct from those of GCV and of BDCRB. In summary, 1263W94 inhibits viral replication by a novel mechanism that is not yet completely understood.

Antiviral Agents↗