Medical Specialties Commons^™

Influence Of Oral Microbiome On Longitudinal Patterns Of Oral Mucositis Severity In Patients With Squamous Cell Carcinoma Of The Head And Neck, Liangliang Zhang, Erin Marie D San Valentin, Teny M John, Robert R Jenq, Kim-Anh Do, Ehab Y Hanna, Christine B Peterson, Cielito C Reyes-Gibby

Faculty, Staff and Student Publications

Background: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck.

Methods: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit …

Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that …

Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh

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Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone.

Methods: We investigated this hypothesis …

Postprogression Therapy And Confounding For The Estimated Treatment Effect On Overall Survival In Phase Iii Oncology Trials, Alexander D Sherry, Pavlos Msaouel, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Esther J Beck, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Eugene J Koay, Clifton David Fuller, Charles R Thomas, Zachary R Mccaw, Ethan B Ludmir

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Objective: Estimations of the treatment effect on overall survival (OS) may be influenced by post-progression therapies (PPTs). It is unclear how often OS analyses account for PPT effects. The purpose of this cross-sectional analysis was to determine the prevalence of OS analyses accounting for PPT effects in phase III oncology trials.

Methods and analysis: We screened two-arm, superiority design, phase III, randomised, oncology trials reporting OS from ClinicalTrials.gov. The primary outcome was the frequency of OS analyses adjusting for PPT confounding. Logistic regressions computed ORs for the association between trial-level covariates and the outcome.

Results: A total of 334 phase …

Combination Chemotherapy Optimization With Discrete Dosing, Temitayo Ajayi, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller

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Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens; one way to alleviate this burden and better inform future trials is to build reliable models for drug administration. This paper presents a mixed-integer program for combination chemotherapy (utilization of multiple drugs) optimization that incorporates various important operational constraints and, besides dose and concentration limits, controls treatment toxicity based on its effect on the count of white blood cells. To address the uncertainty of tumor heterogeneity, we also propose chance constraints that guarantee reaching an operable tumor size with a high probability in …

The Use Of Mr-Guided Radiation Therapy For Head And Neck Cancer And Recommended Reporting Guidance, Brigid A Mcdonald, Riccardo Dal Bello, Clifton D Fuller, Panagiotis Balermpas

Faculty, Staff and Student Publications

Although magnetic resonance imaging (MRI) has become standard diagnostic workup for head and neck malignancies and is currently recommended by most radiological societies for pharyngeal and oral carcinomas, its utilization in radiotherapy has been heterogeneous during the last decades. However, few would argue that implementing MRI for annotation of target volumes and organs at risk provides several advantages, so that implementation of the modality for this purpose is widely accepted. Today, the term MR-guidance has received a much broader meaning, including MRI for adaptive treatments, MR-gating and tracking during radiotherapy application, MR-features as biomarkers and finally MR-only workflows. First studies …

Camrelizumab Combined With Apatinib And Nanoparticle Albumin-Bound Paclitaxel In Lung Adenocarcinoma (Capap-Lung): A Single-Arm Phase Ii Study, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, Bolin Chen, Xiaoping Wen, Yali Tan, Fengzhuo Cheng, Kangle Zhu, Na Li, Lin Wu

Faculty, Staff and Student Publications

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma.

Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma …

Knowledge Mapping Of Anaplastic Thyroid Cancer Treatments: A Bibliometric Analysis (2000–2023), Shiqiang Liu, Xingmin Yan, Yalong Yang, Yun Xia, Panshi Zhang

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Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.

Methodology: A systematic search was …

Considerations On Design And Analysis Of External Control In Pediatric Oncology, Jingjing Ye, Haitao Pan, Gregory Reaman, Satrajit Roychoudhury, Chengxing Lu, Lindsay A Renfro, Yuan Ji, Rong Liu, Ying Yuan, Weidong Zhang

Faculty, Staff and Student Publications

Pediatric cancer consists of a diverse group of rare diseases. Due to limited patient populations, standard randomized and controlled trials are often infeasible. As a result, single-arm trials are common in pediatric oncology and the use of external controls is often desirable or necessary to help generate actionable evidence and contextualize trial results. In this paper, we illustrate unique features in pediatric oncology clinical trials and describe their impact on the use of external controls. Various types of relevant external control data sources are described in terms of their utility and drawbacks. Statistical methodologies and design implications with external control …

Development Of The “Laser Surgical Skills Evaluation For Residents” (Laser) Scale Through A Modified Delphi Method, E Sédillot-Daniel, A Melkane, C Chiesa, N Fakhry, V N Young, L J Smith, J R Lechien, L Guertin, M J Olivier, A Maniakas, R Jun Lin, E Bissada, A Christopoulos, T Ayad, Andrée-Anne Leclerc

Faculty, Staff and Student Publications

Background: The CO2 laser is frequently used during microlaryngeal surgery (MLS) for a variety of pathology including laryngeal malignancy and stenosis. Learning how to use the laser safely is part of the curriculum for every otolaryngology resident. However, assessment of laryngoscopy technical skills can be challenging for supervisors, making it difficult to adequately provide feedback to trainees.

Objectives: "LAser Surgical skills Evaluation for Residents" (LASER) Scale aims to facilitate the evaluation of residents' performance and promote constructive feedback.

Methods: The initial evaluation grid was based on a literature review of CO2 laser laryngoscopy (with an emphasis on indications, technique, safety, …

A Review Of The Clinical Introduction Of 4d Particle Therapy Research Concepts, Barbara Knäusl, Gabriele Belotti, Jenny Bertholet, Juliane Daartz, Stella Flampouri, Mischa Hoogeman, Antje C Knopf, Haibo Lin, Astrid Moerman, Chiara Paganelli, Antoni Rucinski, Reinhard Schulte, Shing Shimizu, Kristin Stützer, Xiaodong Zhang, Ye Zhang, Katarzyna Czerska

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Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments.

Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic.

Results: Available technological capabilities …

Sample Multiplexing In Cytof: Path To Optimize Single-Cell Proteomic Profiling, Muharrem Muftuoglu, Michael Andreeff

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Sample multiplexing significantly enhanced the depth of single-cell proteomic analysis in CyTOF (Cytometry by Time-Of-Flight). New polymer-based chelators have broadened the utility of metal isotopes, enabling improved tagging and simultaneous analysis of multiple samples. These approaches minimize batch effects, streamline experiments, conserve valuable samples, reduce costs, enhance throughput, and increase the accuracy of biological data, thereby facilitating novel discoveries.

Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer

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A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of …

Author Correction: Neoadjuvant Atezolizumab For Resectable Non-Small Cell Lung Cancer: An Open-Label, Single-Arm Phase Ii Trial, Jamie E Chaft, Filiz Oezkan, Mark G Kris, Paul A Bunn, Ignacio I Wistuba, David J Kwiatkowski, Dwight H Owen, Yan Tang, Bruce E Johnson, Jay M Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S Shames, Chris Rivard, Eric Toloza, Eric B Haura, Ciaran J Mcnamee, G Alexander Patterson, Saiama N Waqar, Valerie W Rusch, David P Carbone

Faculty, Staff and Student Publications

No abstract provided.

Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam

Faculty, Staff and Student Publications

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen. In addition, cancer patients are predisposed to indirect sequela to the mediastinal vasculature from an increased risk of benign thromboembolic events, tumor thrombus, or iatrogenic complications during cancer treatments. Benign thrombus may result in partial or complete occlusion of the superior vena cava (SVC) or pulmonary artery. Vascular damage …

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

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While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …

Incidence And Impact Of Fungal Infections In Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis And Haploidentical Hematopoietic Cell Transplantation: A Center For International Blood And Marrow Transplant Research Analysis, Genovefa A Papanicolaou, Min Chen, Naya He, Michael J Martens, Soyoung Kim, Marjorie V Batista, Neel S Bhatt, Peiman Hematti, Joshua A Hill, Hongtao Liu, Sunita Nathan, Matthew D Seftel, Akshay Sharma, Edmund K Waller, John R Wingard, Jo-Anne H Young, Christopher E Dandoy, Miguel-Angel Perales, Roy F Chemaly, Marcie Riches, Celalettin Ustun

Faculty, Staff and Student Publications

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.

Methods: Patients who underwent their first …

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …

Editorial: Updates On Radiation-Induced Lymphopenia, Pim J J Damen, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Radiotherapy is a commonly employed and effective treatment for cancer, seeking to achieve an optimal balance between tumor cell death and minimizing damage to healthy tissues. Radiation-induced lymphopenia (RIL) is a common side effect due to the high radiosensitivity of lymphocytes even at low doses (< 1Gy), leading to their direct depletion (1). While the detrimental effects of radiotherapy on lymphocytes have been recognized since 1905, its influence on tumor control and survival has remained largely unclear until recently (2). Moreover, awareness and understanding of the prognostic effects of RIL remain limited in daily clinical practice.

Mri-Guided High-Dose-Rate Gynecologic Brachytherapy Using An Mr-Linac As An Mr Simulator: A Single Institutional Experience, Whitney Massock, Yusung Kim, M Alex Dresner, Wenqing Sun, Joseph Caster, Quentin Adams, Jill Jespersen, Joel St-Aubin

Faculty, Staff and Student Publications

Purpose: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development.

Methods and materials: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New …

Stereotactic Body Radiation Therapy For Gynecologic Malignancies: A Case-Based Radiosurgery Society Practice Review, Colton Ladbury, Mark H Sueyoshi, Nellie M Brovold, Ritesh Kumar, Therese Y Andraos, Emile Gogineni, Minsun Kim, Ann Klopp, Kevin Albuquerque, Charles Kunos, Eric Leung, Constantine Mantz, Tithi Biswas, Sushil Beriwal, William Small, Beth Erickson, David Gaffney, Simon S Lo, Akila N Viswanathan

Faculty, Staff and Student Publications

Purpose: The use of stereotactic body radiation therapy (SBRT) for gynecologic malignancies is controversial. We discuss certain circumstances when highly precise SBRT may be a useful tool to consider in the management of selected patients.

Methods and materials: Case selection included the following scenarios, the first 2 with palliative intent, para-aortic nodal oligorecurrence of ovarian cancer, pelvic sidewall oligorecurrence of cervical cancer, and inoperable endometrial cancer boost after intensity modulated radiation to the pelvis treated with curative intent. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a …

Editorial: Genetic And Cellular Heterogeneity In Tumors, Zishan Wang, Li Ma, Juan Xu, Chunjie Jiang

Faculty, Staff and Student Publications

No abstract provided.

Egfr, Hla-G, Cd70, C-Met, And Ny-Eso1 As Potential Biomarkers In High Grade Epithelial Ovarian Carcinoma, Duc Vo, Yan Liu, Anil K Sood, Katy Rezvani, Amir A Jazaeri, Jinsong Liu

Faculty, Staff and Student Publications

High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of …

Expert-Centered Evaluation Of Deep Learning Algorithms For Brain Tumor Segmentation, Katharina V Hoebel, Christopher P Bridge, Sara Ahmed, Oluwatosin Akintola, Caroline Chung, Raymond Y Huang, Jason M Johnson, Albert Kim, K Ina Ly, Ken Chang, Jay Patel, Marco Pinho, Tracy T Batchelor, Bruce R Rosen, Elizabeth R Gerstner, Jayashree Kalpathy-Cramer

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Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases. Results Of the surveyed articles, Dice score, sensitivity, and Hausdorff distance were the most popular metrics to report segmentation performance. Notably, only 2.8% of the articles included clinical experts' evaluation of …

Monitoring Variations In The Use Of Automated Contouring Software, Kelly A Nealon, Eun Young Han, Stephen F Kry, Callistus Nguyen, Mary Pham, Valerie K Reed, David Rosenthal, Samantha Simiele, Laurence E Court

Faculty, Staff and Student Publications

PURPOSE: Our purpose was to identify variations in the clinical use of automatically generated contours that could be attributed to software error, off-label use, or automation bias.

METHODS AND MATERIALS: For 500 head and neck patients who were contoured by an in-house automated contouring system, Dice similarity coefficient and added path length were calculated between the contours generated by the automated system and the final contours after editing for clinical use. Statistical process control was used and control charts were generated with control limits at 3 standard deviations. Contours that exceeded the thresholds were investigated to determine the cause. Moving …

Predicting Suicidality In Late-Life Depression By 3d Convolutional Neural Network And Cross-Sample Entropy Analysis Of Resting-State Fmri, Chemin Lin, Chih-Mao Huang, Wei Chang, You-Xun Chang, Ho-Ling Liu, Shu-Hang Ng, Huang-Li Lin, Tatia Mei-Chun Lee, Shwu-Hua Lee, Shun-Chi Wu

Faculty, Staff and Student Publications

BACKGROUND: Predicting suicide is a pressing issue among older adults; however, predicting its risk is difficult. Capitalizing on the recent development of machine learning, considerable progress has been made in predicting complex behavior such as suicide. As depression remained the strongest risk for suicide, we aimed to apply deep learning algorithms to identify suicidality in a group with late-life depression (LLD).

METHODS: We enrolled 83 patients with LLD, 35 of which were non-suicidal and 48 were suicidal, including 26 with only suicidal ideation and 22 with past suicide attempts, for resting-state functional magnetic resonance imaging (MRI). Cross-sample entropy (CSE) analysis …

Jointtracker: Real-Time Inertial Kinematic Chain Tracking With Joint Position Estimation, Bertram Taetz, Michael Lorenz, Markus Miezal, Didier Stricker, Gabriele Bleser-Taetz

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In-field human motion capture (HMC) is drawing increasing attention due to the multitude of application areas. Plenty of research is currently invested in camera-based (markerless) HMC, with the advantage of no infrastructure being required on the body, and additional context information being available from the surroundings. However, the inherent drawbacks of camera-based approaches are the limited field of view and occlusions. In contrast, inertial HMC (IHMC) does not suffer from occlusions, thus being a promising approach for capturing human motion outside the laboratory. However, one major challenge of such methods is the necessity of spatial registration. Typically, during a predefined …

Insights Into The Assembly And Regulation Of The Bacterial Divisome, Todd A Cameron, William Margolin

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The ability to split one cell into two is fundamental to all life, and many bacteria can accomplish this feat several times per hour with high accuracy. Most bacteria call on an ancient homologue of tubulin, called FtsZ, to localize and organize the cell division machinery, the divisome, into a ring-like structure at the cell midpoint. The divisome includes numerous other proteins, often including an actin homologue (FtsA), that interact with each other at the cytoplasmic membrane. Once assembled, the protein complexes that comprise the dynamic divisome coordinate membrane constriction with synthesis of a division septum, but only after overcoming …

Probing Membrane-Associated Cytoskeletal Oligomers Of The Bacterial Divisome By Electron Microscopy And Tomography, Bo Hu, William Margolin

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The cell division machinery or "divisome" of many bacteria, including Escherichia coli, contains homologs of tubulin (FtsZ) and actin (FtsA) that interact with each other to promote the synthesis of septal peptidoglycan. FtsA oligomers have an essential role as a track for tethering dynamically treadmilling FtsZ protofilaments to the cytoplasmic membrane. Other bacterial cytoskeletal oligomers such as MreB also assemble on and move along the membrane. Structures of these oligomers on membranes in vitro may mimic their behavior in the cell. Here, we describe a protocol to visualize FtsA oligomeric structures on membranes and their interactions with FtsZ protofilaments using …

Obesity Is Associated With Improved Progression-Free Survival In Microsatellite-Instability-High Endometrial Cancer Treated With Pembrolizumab, Laurence Bernard, Jeffrey A How, Shrina Patel, Melinda S Yates, Amir Jazaeri

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Objectives: To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas.

Methods: A retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body …