Medical Specialties Commons^™

Cerebrovascular Reactivity Mapping Using Resting-State Functional Mri In Patients With Gliomas, Mei-Yu Yeh, Henry S Chen, Ping Hou, Vinodh A Kumar, Jason M Johnson, Kyle R Noll, Sujit S Prabhu, Sherise D Ferguson, Donald F Schomer, Hsu-Hsia Peng, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases.

Purpose: To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas.

Study type: Retrospective.

Population: Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas.

Field strength/sequence: Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T …

Identity-Related Experiences Of Asian American Trainees In Gynecologic Oncology, Jhalak Dholakia, Yeon Woo Lee, Karen H Lu, Warner K Huh, S Diane Yamada, Katherine C Fuh, Amanika S Kumar, Margaret I Liang, Navya Nair, Kenneth H Kim

Faculty, Staff and Student Publications

Background: Anti-Asian violence increased during the COVID-19 pandemic. Asian American/Pacific Islanders (AAPI) represent a diverse population experiencing a long history of stereotyping and exclusionism; however, this group is often left out of diversity/inclusion conversations. In academic medicine, AAPI are under-represented in leadership. We characterized the personal/professional experiences of AAPI gynecologic oncology trainees and assessed the impact of a virtual panel discussion with leaders in the field.

Methods: An anonymous survey was disseminated online to trainees in/interested in gynecologic oncology fellowship who identified as AAPI, using modified snowball sampling. A virtual session with AAPI leaders in gynecologic oncology discussed themes emerging …

Allergic Fungal Rhinosinusitis: The Role And Expectations Of Biologics, Amber U Luong, Andy Chua, Bader M Alim, Petter Olsson, Amin Javer

Faculty, Staff and Student Publications

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted …

Airway Mucus Dysfunction In Covid-19, Burton F Dickey, Jichao Chen, R Stokes Peebles

Faculty, Staff and Student Publications

No abstract provided.

Tceal1 Loss-Of-Function Results In An X-Linked Dominant Neurodevelopmental Syndrome And Drives The Neurological Disease Trait In Xq222 Deletions, Hadia Hijazi, Linda M Reis, Davut Pehlivan, Jonathan A Bernstein, Michael Muriello, Erin Syverson, Devon Bonner, Mehrdad A Estiar, Ziv Gan-Or, Guy A Rouleau, Ekaterina Lyulcheva, Lynn Greenhalgh, Marine Tessarech, Estelle Colin, Agnès Guichet, Dominique Bonneau, R H Van Jaarsveld, A M A Lachmeijer, Lyse Ruaud, Jonathan Levy, Anne-Claude Tabet, Rafal Ploski, Małgorzata Rydzanicz, Łukasz Kępczyński, Katarzyna Połatyńska, Yidan Li, Jawid M Fatih, Dana Marafi, Jill A Rosenfeld, Zeynep Coban-Akdemir, Weimin Bi, Richard A Gibbs, Grace M Hobson, Jill V Hunter, Claudia M B Carvalho, Jennifer E Posey, Elena V Semina, James R Lupski

Faculty, Staff and Student Publications

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving …

The Circadian Nobiletin-Ror Axis Suppresses Adipogenic Differentiation And Iκbα/Nf-Κb Signaling In Adipocytes, Ji Ye Lim, Eunju Kim, Collin M Douglas, Marvin Wirianto, Chorong Han, Kaori Ono, Sun Young Kim, Justin H Ji, Celia K Tran, Zheng Chen, Karyn A Esser, Seung-Hee Yoo

Faculty, Staff and Student Publications

Numerous molecular and physiological processes in the skeletal muscle undergo circadian time-dependent oscillations in accordance with daily activity/rest cycles. The circadian regulatory mechanisms underlying these cyclic processes, especially at the post-transcriptional level, are not well defined. Previously, we reported that the circadian E3 ligase FBXL21 mediates rhythmic degradation of the sarcomere protein TCAP in conjunction with GSK-3β, and Psttm mice harboring an Fbxl21 hypomorph allele show reduced muscle fiber diameter and impaired muscle function. To further elucidate the regulatory function of FBXL21 in skeletal muscle, we investigated another sarcomere protein, Myozenin1 (MYOZ1), that we identified as an FBXL21-binding protein from …

Bayesian Hierarchical Random-Effects Meta-Analysis And Design Of Phase I Clinical Trials, Ruitao Lin, Haolun Shi, Guosheng Yin, Peter F Thall, Ying Yuan, Christopher R Flowers

Faculty, Staff and Student Publications

We propose a curve-free random-effects meta-analysis approach to combining data from multiple phase I clinical trials to identify an optimal dose. Our method accounts for between-study heterogeneity that may stem from different study designs, patient populations, or tumor types. We also develop a meta-analytic-predictive (MAP) method based on a power prior that incorporates data from multiple historical studies into the design and conduct of a new phase I trial. Performances of the proposed methods for data analysis and trial design are evaluated by extensive simulation studies. The proposed random-effects meta-analysis method provides more reliable dose selection than comparators that rely …

Development Of A Distributed International Patient Data Registry For Hairy Cell Leukemia, Leslie A Andritsos, Mirela Anghelina, Jasmine Neal, James S Blachly, Puneet Mathur, Omkar Lele, Claire Dearden, Sunil Iyengar, Matthew Cross, Clive S Zent, Kerry A Rogers, Narendranath Epperla, Gerard Lozanski, Christopher C Oakes, Eric Kraut, Amy S Ruppert, Qiuhong Zhao, Seema A Bhat, Francesco Forconi, Versha Banerji, Sasanka Handunnetti, Constantine S Tam, John F Seymour, Monica Else, Robert J Kreitman, Alan Saven, Timothy Call, Sameer A Parikh, Farhad Ravandi, James B Johnston, Enrico Tiacci, Xavier Troussard, Martin S Tallman, Sascha Dietrich, Tamar Tadmor, Alessandro Gozzetti, Pier Luigi Zinzani, Tadeusz Robak, Graeme Quest, Judit Demeter, Kanti Rai, Soledad A Fernandez, Michael Grever

Faculty, Staff and Student Publications

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder, comprising only 2% of all leukemias. The Hairy Cell Leukemia Foundation (HCLF) has developed a patient data registry to enable investigators to better study the clinical features, treatment outcomes, and complications of patients with HCL. This system utilizes a centralized registry architecture. Patients are enrolled at HCL Centers of Excellence (COE) or via a web-based portal. All data are de-identified, which reduces regulatory burden and increases opportunities for data access and re-use. To date, 579 patients have been enrolled in the registry. Efforts are underway to engage additional COE's to expand …

Prognostic Impact Of Breslow Thickness In Acral Melanoma: A Retrospective Analysis, Xiaoting Wei, Yu Chen, Hong Yao, Di Wu, Hang Li, Rui Zhang, Zhihong Chi, Chuanliang Cui, Xue Bai, Lili Mao, Zhonghui Qi, Ke Li, Shijie Lan, Lizhu Chen, Rui Guo, Xinyu Yao, Bin Lian, Yan Kong, Jie Dai, Bixia Tang, Xuan Wang, Jeffrey E Gershenwald, Charles M Balch, Jun Guo, Lu Si

Faculty, Staff and Student Publications

Background: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited.

Objective: The objective of the study was to determine the prognostic impact of Breslow thickness in AM.

Methods: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression.

Results: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The …

Neoadjuvant Chemo-Immunotherapy For Lung Cancer: How Much Is Too Much?, Nathaniel Deboever, Jianjun Zhang

Faculty, Staff and Student Publications

No abstract provided.

Direct Cd32 T-Cell Cytotoxicity: Implications For Breast Cancer Prognosis And Treatment, Giuseppe Sconocchia, Giulia Lanzilli, Valeriana Cesarini, Domenico A Silvestris, Katayoun Rezvani, Roberto Arriga, Sara Caratelli, Ken Chen, Jinzhuang Dou, Carlo Cenciarelli, Gabriele Toietta, Silvia Baldari, Tommaso Sconocchia, Francesca De Paolis, Anna Aureli, Giandomenica Iezzi, Maria Irno Consalvo, Francesco Buccisano, Maria I Del Principe, Luca Maurillo, Adriano Venditti, Alessio Ottaviani, Giulio C Spagnoli

Faculty, Staff and Student Publications

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked to CD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice …

Statistical Process Control To Monitor Use Of A Web-Based Autoplanning Tool, Hunter Mehrens, Raphael Douglas, Mary Gronberg, Kelly Nealon, Joy Zhang, Laurence Court

Faculty, Staff and Student Publications

PURPOSE: To investigate the use of statistical process control (SPC) for quality assurance of an integrated web-based autoplanning tool, Radiation Planning Assistant (RPA).

METHODS: Automatically generated plans were downloaded and imported into two treatment planning systems (TPSs), RayStation and Eclipse, in which they were recalculated using fixed monitor units. The recalculated plans were then uploaded back to the RPA, and the mean dose differences for each contour between the original RPA and the TPSs plans were calculated. SPC was used to characterize the RPA plans in terms of two comparisons: RayStation TPS versus RPA and Eclipse TPS versus RPA for …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

A Recurrent Single-Exon Deletion In Tbck Might Be Under-Recognized In Patients With Infantile Hypotonia And Psychomotor Delay, Hongzheng Dai, Wenmiao Zhu, Bo Yuan, Nicole Walley, Kelly Schoch, Yong-Hui Jiang, John A Phillips, Melissa S Jones, Pengfei Liu, David R Murdock, Lindsay C Burrage, Brendan Lee, Jill A Rosenfeld, Rui Xiao

Faculty, Staff and Students Publications

Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed …

Growth Parameters In Children With Achondroplasia: A 7-Year, Prospective, Multinational, Observational Study, Ravi Savarirayan, Melita Irving, Paul Harmatz, Borja Delgado, William R Wilcox, John Philips, Natalie Owen, Carlos A Bacino, Louise Tofts, Joel Charrow, Lynda E Polgreen, Julie Hoover-Fong, Paul Arundel, Ignacio Ginebreda, Howard M Saal, Donald Basel, Rosendo Ullot Font, Keiichi Ozono, Michael B Bober, Valerie Cormier-Daire, Kim-Hanh Le Quan Sang, Genevieve Baujat, Yasemin Alanay, Frank Rutsch, Daniel Hoernschemeyer, Klaus Mohnike, Hiroshi Mochizuki, Asako Tajima, Yumiko Kotani, David D Weaver, Klane K White, Clare Army, Kevin Larrimore, Keith Gregg, George Jeha, Claire Milligan, Elena Fisheleva, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control.

Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing.

Results: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants < 1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants < 1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged < 1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward.

Conclusion: This study represents one of the largest datasets of prospectively collected …

Exome Sequencing Efficacy And Phenotypic Expansions Involving Esophageal Atresia/Tracheoesophageal Fistula Plus, Mary R Sy, Jaynee Chauhan, Katrina Prescott, Aliza Imam, Alison Kraus, Ana Beleza, Lee Salkeld, Saraswati Hosdurga, Michael Parker, Pradeep Vasudevan, Lily Islam, Himanshu Goel, Nicole Bain, Soo-Mi Park, Shehla Mohammed, Klaus Dieterich, Charles Coutton, Véronique Satre, Gaëlle Vieville, Alan Donaldson, Claire Beneteau, Jamal Ghoumid, Kris Van Den Bogaert, Anneleen Boogaerts, Elise Boudry, Clémence Vanlerberghe, Florence Petit, Laura Bernardini, Barbara Torres, Teresa Mattina, Diana Carli, Giorgia Mandrile, Michele Pinelli, Nicola Brunetti-Pierri, Katherine Neas, Rachel Beddow, Pernille M Tørring, Flavio Faletra, Beatrice Spedicati, Paolo Gasparini, Alessandro Mussa, Giovanni Battista Ferrero, Anne Lampe, Wayne Lam, Weimin Bi, Carlos A Bacino, Akela Kuwahara, Jeffrey O Bush, Xiaonan Zhao, Pamela N Luna, Chad A Shaw, Jill A Rosenfeld, Daryl A Scott

Faculty, Staff and Students Publications

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening birth defect that often occurs with other major birth defects (EA/TEF+). Despite advances in genetic testing, a molecular diagnosis can only be made in a minority of EA/TEF+ cases. Here, we analyzed clinical exome sequencing data and data from the DECIPHER database to determine the efficacy of exome sequencing in cases of EA/TEF+ and to identify phenotypic expansions involving EA/TEF. Among 67 individuals with EA/TEF+ referred for clinical exome sequencing, a definitive or probable diagnosis was made in 11 cases for an efficacy rate of 16% (11/67). This efficacy rate is significantly lower …

Genome Protection By Dna Polymerase Θ, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ) is a DNA repair enzyme widely conserved in animals and plants. Pol θ uses short DNA sequence homologies to initiate repair of double-strand breaks by theta-mediated end joining. The DNA polymerase domain of Pol θ is at the C terminus and is connected to an N-terminal DNA helicase-like domain by a central linker. Pol θ is crucial for maintenance of damaged genomes during development, protects DNA against extensive deletions, and limits loss of heterozygosity. The cost of using Pol θ for genome protection is that a few nucleotides are usually deleted or added at the …

Notch Missense Mutations In Drosophila Reveal Functions Of Specific Egf-Like Repeats In Notch Folding, Trafficking, And Signaling, Hilman Nurmahdi, Mao Hasegawa, Elzava Yuslimatin Mujizah, Takeshi Sasamura, Mikiko Inaki, Shinya Yamamoto, Tomoko Yamakawa, Kenji Matsuno

Duncan NRI Faculty and Staff Publications

Notch signaling plays various roles in cell-fate specification through direct cell–cell interactions. Notch receptors are evolutionarily conserved transmembrane proteins with multiple epidermal growth factor (EGF)-like repeats. Drosophila Notch has 36 EGF-like repeats, and while some play a role in Notch signaling, the specific functions of most remain unclear. To investigate the role of each EGF-like repeat, we used 19 previously identified missense mutations of Notch with unique amino acid substitutions in various EGF-like repeats and a transmembrane domain; 17 of these were identified through a single genetic screen. We assessed these mutants’ phenotypes in the nervous system and hindgut during …

Bob: Bayesian Optimal Design For Biosimilar Trials With Co-Primary Endpoints, Xiaohan Chi, Zhangsheng Yu, Ruitao Lin

Faculty, Staff and Student Publications

For regulatory approval of a biosimilar product, extensive evaluations should be performed by rigorous clinical trials to establish the similarity between the reference product and the proposed biosimilar in terms of both efficacy and safety. Existing designs for biosimilar trials often use a single primary efficacy endpoint in trial monitoring, and then separately evaluate the safety of the biosimilar product in a secondary analysis at the trial completion. However, ignoring the safety endpoint and the correlation between safety and efficacy in trial monitoring may lead to a high false positive rate, or it may delay the termination of the trial …

Influence Of Data Sampling Methods On The Representation Of Neural Spiking Activity In Vivo, Meike E Van Der Heijden, Amanda M Brown, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

No abstract provided.

Region-Specific Denoising Identifies Spatial Co-Expression Patterns And Intra-Tissue Heterogeneity In Spatially Resolved Transcriptomics Data, Linhua Wang, Mirjana Maletic-Savatic, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Spatially resolved transcriptomics is a relatively new technique that maps transcriptional information within a tissue. Analysis of these datasets is challenging because gene expression values are highly sparse due to dropout events, and there is a lack of tools to facilitate in silico detection and annotation of regions based on their molecular content. Therefore, we develop a computational tool for detecting molecular regions and region-based Missing value Imputation for Spatially Transcriptomics (MIST). We validate MIST-identified regions across multiple datasets produced by 10x Visium Spatial Transcriptomics, using manually annotated histological images as references. We benchmark MIST against a spatial k-nearest neighboring …

Medicc2: Whole-Genome Doubling Aware Copy-Number Phylogenies For Cancer Evolution, Tom L Kaufmann, Marina Petkovic, Thomas B K Watkins, Emma C Colliver, Sofya Laskina, Nisha Thapa, Darlan C Minussi, Nicholas Navin, Charles Swanton, Peter Van Loo, Kerstin Haase, Maxime Tarabichi, Roland F Schwarz

Faculty, Staff and Student Publications

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.

Challenges Associated With The Integration Of Immuno-Oncology Agents In Clinical Practice, Patrice Lazure, Aparna R Parikh, Neal E Ready, Marianne J Davies, Sophie Péloquin, Jeffrey M Caterino, Robert Lewandowski, Alexander J Lazar, Suzanne Murray

Faculty, Staff and Student Publications

Background: The availability of new immuno-oncology therapeutics markedly impacts oncology clinicians' treatment decision-making. To effectively support healthcare professionals (HCPs) in their practice, it is important to better understand the challenges and barriers that can accompany the introduction of these agents. This study aimed to establish the types and causes of clinical challenges posed by the introduction of new immuno-oncology agents.

Methods: The mixed-methods design included qualitative in-depth interviews and group discussions with HCPs, in which participants discussed clinical challenges and potential underlying reasons for these challenges. Qualitative findings informed a quantitative survey. This survey investigated the extent and distribution of …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Sars-Cov-2 Incubation Period According To Vaccination Status During The Fifth Covid-19 Wave In A Tertiary-Care Center In Spain: A Cohort Study, Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Faculty, Staff and Student Publications

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients. The …

Two Neuronal Peptides Encoded From A Single Transcript Regulate Mitochondrial Complex Iii In Drosophila, Justin A Bosch, Berrak Ugur, Israel Pichardo-Casas, Jordan Rabasco, Felipe Escobedo, Zhongyuan Zuo, Ben Brown, Susan Celniker, David A Sinclair, Hugo J Bellen, Norbert Perrimon

Duncan NRI Faculty and Staff Publications

Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open-reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of …

Body Mass Index And Survival After Cancer Diagnosis: A Pan-Cancer Cohort Study Of 114 430 Patients With Cancer, Huakang Tu, Jennifer L Mcquade, Michael A Davies, Maosheng Huang, Kunlin Xie, Yuanqing Ye, Wong-Ho Chow, Alma Rodriguez, Xifeng Wu

Faculty, Staff and Student Publications

The recommendation encouraging patients with cancer to keep a normal body mass index (BMI) is largely extrapolated from data on risk of developing cancer. We tested the prospective association between peri-diagnostic (within 1 year post-diagnosis) BMI and all-cause mortality in patients with incident cancers. During 7.2 years of follow-up, 42% (48,340) of the 114 430 patients with cancer died. Spline analysis revealed that compared with a BMI of 22.5, a BMI lower than 22.5 was associated with increased risk of all-cause mortality across 24 cancer types. A BMI higher than 22.5 was associated with reduced all-cause mortality, while a non-linear …

Omics Analyses Of A Somatic Trp53r245w/+ Breast Cancer Model Identify Cooperating Driver Events Activating Pi3k/Akt/Mtor Signaling, Xiaojie Yu, Yun Zhang, Shunbin Xiong, Joy M Mcdaniel, Chang Sun, Gilda P Chau, Jovanka Gencel-Augusto, Dhruv Chachad, Rhiannon L Morrissey, Xiayu Rao, Jing Wang, Guillermina Lozano

Faculty, Staff and Student Publications

Alterations of the tumor suppressor

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

Epacadostat Plus Pembrolizumab And Chemotherapy For Advanced Solid Tumors: Results From The Phase I/Ii Echo-207/Keynote-723 Study, John D Powderly, Samuel J Klempner, Aung Naing, Johanna Bendell, Ignacio Garrido-Laguna, Daniel V T Catenacci, Matthew H Taylor, James J Lee, Fred Zheng, Feng Zhou, Xiaohua Gong, Hema Gowda, Gregory L Beatty

Faculty, Staff and Student Publications

Background: Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

Methods: Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab …