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Bending The Patient Safety Curve: How Much Can Ai Help?, David C Classen, Christopher Longhurst, Eric J Thomas Jan 2023

Bending The Patient Safety Curve: How Much Can Ai Help?, David C Classen, Christopher Longhurst, Eric J Thomas

Faculty, Staff and Student Publications

This paper reviews the current state of patient safety and the application of artificial intelligence (AI) techniques to patient safety. This paper defines patient safety broadly, not just inpatient care but across the continuum of care, including diagnostic errors, misdiagnosis, adverse events, injuries, and measurement issues. It outlines the major current uses of AI in patient safety and the relative adoption of these techniques in hospitals and health systems. It also outlines some of the limitations of these AI systems and the challenges with evaluation of these systems. Finally, it outlines the importance of developing a proactive agenda for AI …


Cissus Quadrangularis (Hadjod) Inhibits Rankl-Induced Osteoclastogenesis And Augments Bone Health In An Estrogen-Deficient Preclinical Model Of Osteoporosis Via Modulating The Host Osteoimmune System, Zaffar Azam, Leena Sapra, Kalpana Baghel, Niharika Sinha, Rajesh K Gupta, Vandana Soni, Chaman Saini, Pradyumna K Mishra, Rupesh K Srivastava Jan 2023

Cissus Quadrangularis (Hadjod) Inhibits Rankl-Induced Osteoclastogenesis And Augments Bone Health In An Estrogen-Deficient Preclinical Model Of Osteoporosis Via Modulating The Host Osteoimmune System, Zaffar Azam, Leena Sapra, Kalpana Baghel, Niharika Sinha, Rajesh K Gupta, Vandana Soni, Chaman Saini, Pradyumna K Mishra, Rupesh K Srivastava

Faculty, Staff and Student Publications

Osteoporosis is a systemic skeletal disease characterised by low bone mineral density (BMD), degeneration of bone micro-architecture, and impaired bone strength. Cissus quadrangularis (CQ), popularly known as Hadjod (bone setter) in Hindi, is a traditional medicinal herb exhibiting osteoprotective potential in various bone diseases, especially osteoporosis and fractures. However, the cellular mechanisms underpinning its direct effect on bone health through altering the host immune system have never been elucidated. In the present study, we interrogated the osteoprotective and immunoporotic (the osteoprotective potential of CQ via modulating the host immune system) potential of CQ in preventing inflammatory bone loss under oestrogen-deficient …


Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K Mishra, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade Jan 2023

Obesity Is Associated With Altered Tumor Metabolism In Metastatic Melanoma, Andrew W Hahn, Ashley V Menk, Dayana B Rivadeneira, Ryan C Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K Mishra, Tuba N Gide, Camelia Quek, Yan Zang, Christine N Spencer, Alexander M Menzies, Carrie R Daniel, Courtney W Hudgens, Theodore Nowicki, Lauren E Haydu, M A Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M Burton, Jared Malke, Julie M Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E Woodman, Y N Vashisht Gopal, Renato Guerrieri, Grant M Fischer, Jian Wang, Khalida M Wani, John F Thompson, Jeffrey E Lee, Patrick Hwu, Nadim Ajami, Jeffrey E Gershenwald, Georgina V Long, Richard A Scolyer, Michael T Tetzlaff, Alexander J Lazar, Dirk Schadendorf, Jennifer A Wargo, John M Kirkwood, Ralph J Deberardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S Wilmott, Weiyi Peng, Michael A Davies, Greg M Delgoffe, Yana G Najjar, Jennifer L Mcquade

Faculty, Staff and Student Publications

PURPOSE: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI).

EXPERIMENTAL DESIGN: Associations between BMI [normal (NL < 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371).

RESULTS: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased …


Silicone Gel Sheeting For Treating Keloid Scars, Fan Tian, Qingling Jiang, Junjie Chen, Zhenmi Liu Jan 2023

Silicone Gel Sheeting For Treating Keloid Scars, Fan Tian, Qingling Jiang, Junjie Chen, Zhenmi Liu

Faculty, Staff and Student Publications

BACKGROUND: Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring.

OBJECTIVES: To assess …


Radiation Therapy For Retroperitoneal Sarcomas: A Strass-Ful Situation, Ahsan S Farooqi, B Ashleigh Guadagnolo, Devarati Mitra, Andrew J Bishop Jan 2023

Radiation Therapy For Retroperitoneal Sarcomas: A Strass-Ful Situation, Ahsan S Farooqi, B Ashleigh Guadagnolo, Devarati Mitra, Andrew J Bishop

Faculty, Staff and Student Publications

Locoregional recurrence (LRR) is the predominant pattern of relapse and often the cause of death in patients with retroperitoneal sarcomas (RPS). As a result, reducing LRR is a critical objective for RPS patients. However, unlike soft tissue sarcomas (STS) of the superficial trunk and extremity where the benefits of radiation therapy (RT) are well-established, the role of RT in the retroperitoneum remains controversial. Historically, preoperative or postoperative RT, either alone or in combination with intraoperative radiation (IORT), was commonly justified for RPS based on extrapolation from the superficial trunk and extremity STS literature. However, long-awaited results were recently published from …


Prevalence And Concordance Of Oral And Genital Hpv By Sexual Orientation Among Us Men, Kalyani Sonawane, Shiang Shiuan Shyu, Haluk Damgacioglu, Ruosha Li, Alan G Nyitray, Ashish A Deshmukh Jan 2023

Prevalence And Concordance Of Oral And Genital Hpv By Sexual Orientation Among Us Men, Kalyani Sonawane, Shiang Shiuan Shyu, Haluk Damgacioglu, Ruosha Li, Alan G Nyitray, Ashish A Deshmukh

Faculty, Staff and Student Publications

The objective of our study was to describe oral and genital human papillomavirus (HPV) infection prevalence and concordance by sexual orientation among US men using a nationally representative sample. We conducted a retrospective cross-sectional analysis of the 2013-2016 National Health and Nutrition Examination Survey. The survey conducts a physical examination and collects oral rinse and genital swab specimens; demographic and health behaviors are self-reported. We used descriptive statistics and multivariate regression models to estimate HPV infection prevalence and the likelihood of HPV infection, respectively. All analyses were adjusted for National Health and Nutrition Examination Survey design and weights, and statistical …


Microenvironmental Ammonia Enhances T Cell Exhaustion In Colorectal Cancer, Hannah N Bell, Amanda K Huber, Rashi Singhal, Navyateja Korimerla, Ryan J Rebernick, Roshan Kumar, Marwa O El-Derany, Peter Sajjakulnukit, Nupur K Das, Samuel A Kerk, Sumeet Solanki, Jadyn G James, Donghwan Kim, Li Zhang, Brandon Chen, Rohit Mehra, Timothy L Frankel, Balázs Győrffy, Eric R Fearon, Marina Pasca Di Magliano, Frank J Gonzalez, Ruma Banerjee, Daniel R Wahl, Costas A Lyssiotis, Michael Green, Yatrik M Shah Jan 2023

Microenvironmental Ammonia Enhances T Cell Exhaustion In Colorectal Cancer, Hannah N Bell, Amanda K Huber, Rashi Singhal, Navyateja Korimerla, Ryan J Rebernick, Roshan Kumar, Marwa O El-Derany, Peter Sajjakulnukit, Nupur K Das, Samuel A Kerk, Sumeet Solanki, Jadyn G James, Donghwan Kim, Li Zhang, Brandon Chen, Rohit Mehra, Timothy L Frankel, Balázs Győrffy, Eric R Fearon, Marina Pasca Di Magliano, Frank J Gonzalez, Ruma Banerjee, Daniel R Wahl, Costas A Lyssiotis, Michael Green, Yatrik M Shah

Faculty, Staff and Student Publications

Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor development, progression, and treatment resistance is unclear. We generated an autochthonous metastatic mouse model of CRC and used unbiased multi-omic analyses to reveal a robust accumulation of tumoral ammonia. The high ammonia levels induce T cell metabolic reprogramming, increase exhaustion, and decrease proliferation. CRC patients have increased serum ammonia, and the ammonia-related gene signature correlates with altered T cell response, adverse patient outcomes, and …


Revision Of The Melanocytic Pathology Assessment Tool And Hierarchy For Diagnosis Classification Schema For Melanocytic Lesions: A Consensus Statement, Raymond L Barnhill, David E Elder, Michael W Piepkorn, Stevan R Knezevich, Lisa M Reisch, Megan M Eguchi, Boris C Bastian, Willeke Blokx, Marcus Bosenberg, Klaus J Busam, Richard Carr, Alistair Cochran, Martin G Cook, Lyn M Duncan, Rosalie Elenitsas, Arnaud De La Fouchardière, Pedram Gerami, Iva Johansson, Jennifer Ko, Gilles Landman, Alexander J Lazar, Lori Lowe, Daniela Massi, Jane Messina, Daniela Mihic-Probst, Douglas C Parker, Birgitta Schmidt, Christopher R Shea, Richard A Scolyer, Michael Tetzlaff, Xiaowei Xu, Iwei Yeh, Artur Zembowicz, Joann G Elmore Jan 2023

Revision Of The Melanocytic Pathology Assessment Tool And Hierarchy For Diagnosis Classification Schema For Melanocytic Lesions: A Consensus Statement, Raymond L Barnhill, David E Elder, Michael W Piepkorn, Stevan R Knezevich, Lisa M Reisch, Megan M Eguchi, Boris C Bastian, Willeke Blokx, Marcus Bosenberg, Klaus J Busam, Richard Carr, Alistair Cochran, Martin G Cook, Lyn M Duncan, Rosalie Elenitsas, Arnaud De La Fouchardière, Pedram Gerami, Iva Johansson, Jennifer Ko, Gilles Landman, Alexander J Lazar, Lori Lowe, Daniela Massi, Jane Messina, Daniela Mihic-Probst, Douglas C Parker, Birgitta Schmidt, Christopher R Shea, Richard A Scolyer, Michael Tetzlaff, Xiaowei Xu, Iwei Yeh, Artur Zembowicz, Joann G Elmore

Faculty, Staff and Student Publications

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).

Evidence review: Practicing dermatopathologists recruited from 40 US states participated in the 2-year REMI study …


Distribution Pattern Of Antibiotic Resistance Genes In Escherichia Coli Isolated From Colibacillosis Cases In Broiler Farms Of Egypt, Mona A A Abdel-Rahman, Engy A Hamed, May F Abdelaty, Hend K Sorour, Heba Badr, Wafaa M Hassan, Azhar G Shalaby, Ahmed Abd-Elhalem Mohamed, Mohamed A Soliman, Heba Roshdy Jan 2023

Distribution Pattern Of Antibiotic Resistance Genes In Escherichia Coli Isolated From Colibacillosis Cases In Broiler Farms Of Egypt, Mona A A Abdel-Rahman, Engy A Hamed, May F Abdelaty, Hend K Sorour, Heba Badr, Wafaa M Hassan, Azhar G Shalaby, Ahmed Abd-Elhalem Mohamed, Mohamed A Soliman, Heba Roshdy

Faculty, Staff and Student Publications

BACKGROUND AND AIM: Multidrug resistance (MDR) of

MATERIALS AND METHODS: Samples from 938 broiler farms were bacteriologically examined for

RESULTS:

CONCLUSION: The study showed a high prevalence of


Psychotic Symptom, Mood, And Cognition-Associated Multimodal Mri Reveal Shared Links To The Salience Network Within The Psychosis Spectrum Disorders, Chuang Liang, Godfrey Pearlson, Juan Bustillo, Peter Kochunov, Jessica A Turner, Xuyun Wen, Rongtao Jiang, Zening Fu, Xiao Zhang, Kaicheng Li, Xijia Xu, Daoqiang Zhang, Shile Qi, Vince D Calhoun Jan 2023

Psychotic Symptom, Mood, And Cognition-Associated Multimodal Mri Reveal Shared Links To The Salience Network Within The Psychosis Spectrum Disorders, Chuang Liang, Godfrey Pearlson, Juan Bustillo, Peter Kochunov, Jessica A Turner, Xuyun Wen, Rongtao Jiang, Zening Fu, Xiao Zhang, Kaicheng Li, Xijia Xu, Daoqiang Zhang, Shile Qi, Vince D Calhoun

Faculty, Staff and Student Publications

Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP. Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability …


Vessel Patency And Associated Factors Of Drug-Coated Balloon For Femoropopliteal Lesion, Yoshimitsu Soga, Mitsuyoshi Takahara, Osamu Iida, Yusuke Tomoi, Daizo Kawasaki, Akiko Tanaka, Yasutaka Yamauchi, Kazuki Tobita, Amane Kozuki, Masahiko Fujihara, Kenji Ando Jan 2023

Vessel Patency And Associated Factors Of Drug-Coated Balloon For Femoropopliteal Lesion, Yoshimitsu Soga, Mitsuyoshi Takahara, Osamu Iida, Yusuke Tomoi, Daizo Kawasaki, Akiko Tanaka, Yasutaka Yamauchi, Kazuki Tobita, Amane Kozuki, Masahiko Fujihara, Kenji Ando

Faculty, Staff and Student Publications

Background Although clinical trials have reported favorable outcomes after drug-coated balloon (DCB) therapy for femoropopliteal lesions, their real-world performance and predictors have not been well evaluated. This study aimed to elucidate 1-year freedom from restenosis and to explore the associated factors after a DCB for femoropopliteal lesions in clinical settings. Methods and Results This multicenter, prospective cohort registered 3165 de novo or restenotic femoropopliteallesions (mean lesion length, 13.5±9.3 cm; chronic total occlusion, 25.9%; severe calcification, 14.6%) that underwent successful DCB (Lutonix [24.2%] and IN.PACT Admiral [75.8%]) treatment between March 2018 and December 2019. Patency was assessed at 12±2 months. The …


Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan Jan 2023

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan

Faculty, Staff and Student Publications

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a …


Radiofrequency Ablation Remodels The Tumor Microenvironment And Promotes Neutrophil-Mediated Abscopal Immunomodulation In Pancreatic Cancer, Erika Y Faraoni, Baylee J O'Brien, Lincoln N Strickland, Baron K Osborn, Victoria Mota, Jarod Chaney, Constance Lynn Atkins, Putao Cen, Julie Rowe, Jessica Cardenas, Kyle L Poulsen, Curtis J Wray, Nirav C Thosani, Jennifer M Bailey-Lundberg Jan 2023

Radiofrequency Ablation Remodels The Tumor Microenvironment And Promotes Neutrophil-Mediated Abscopal Immunomodulation In Pancreatic Cancer, Erika Y Faraoni, Baylee J O'Brien, Lincoln N Strickland, Baron K Osborn, Victoria Mota, Jarod Chaney, Constance Lynn Atkins, Putao Cen, Julie Rowe, Jessica Cardenas, Kyle L Poulsen, Curtis J Wray, Nirav C Thosani, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong …


Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Yuqi Kang, Jianhua Zhang, Alberto Briganti, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola Jan 2023

Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Yuqi Kang, Jianhua Zhang, Alberto Briganti, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola

Faculty, Staff and Student Publications

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor-expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward …


Longitudinal Developmental Outcomes Of Infants And Toddlers With Traumatic Brain Injury, Heather T Keenan, Amy Clark, Rich Holubkov, Linda Ewing-Cobbs Jan 2023

Longitudinal Developmental Outcomes Of Infants And Toddlers With Traumatic Brain Injury, Heather T Keenan, Amy Clark, Rich Holubkov, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

IMPORTANCE: Among children, infants and toddlers have some of the highest rates of traumatic brain injury (TBI), but longitudinal information on their developmental outcomes to guide postinjury surveillance is sparse.

OBJECTIVE: To evaluate infants' and toddlers' development over 3 years following TBI compared with those with orthopedic injury (OI).

DESIGN, SETTING, AND PARTICIPANTS: A longitudinal observational cohort study was conducted at 2 level 1 pediatric trauma centers from January 20, 2013, to September 30, 2015; data analysis was performed from May 12 to October 20, 2021. Participants included children injured when younger than 31 months with TBI or OI who …


Evaluation Of Proton Therapy Reirradiation For Patients With Recurrent Head And Neck Squamous Cell Carcinoma, Anna Lee, Robbie Woods, Amgad Mahfouz, Sarin Kitpanit, Olivia Cartano, Nader Mohamed, Irini Youssef, Kathryn Marqueen, Kevin Sine, Dennis Mah, Brian Neal, Kaveh Zakeri, Jung J Kang, Nadeem Riaz, Yao Yu, Sean M Mcbride, Linda D Chen, C Jillian Tsai, Daphna Y Gelblum, Robert H Press, Loren S Michel, Eric J Sherman, David Pfister, Lara A Dunn, Alan L Ho, James Fetten, Richard J Wong, Jay O Boyle, Bhuvanesh Singh, Jennifer R Cracchiolo, Ian Ganly, Marc A Cohen, Nancy Y Lee Jan 2023

Evaluation Of Proton Therapy Reirradiation For Patients With Recurrent Head And Neck Squamous Cell Carcinoma, Anna Lee, Robbie Woods, Amgad Mahfouz, Sarin Kitpanit, Olivia Cartano, Nader Mohamed, Irini Youssef, Kathryn Marqueen, Kevin Sine, Dennis Mah, Brian Neal, Kaveh Zakeri, Jung J Kang, Nadeem Riaz, Yao Yu, Sean M Mcbride, Linda D Chen, C Jillian Tsai, Daphna Y Gelblum, Robert H Press, Loren S Michel, Eric J Sherman, David Pfister, Lara A Dunn, Alan L Ho, James Fetten, Richard J Wong, Jay O Boyle, Bhuvanesh Singh, Jennifer R Cracchiolo, Ian Ganly, Marc A Cohen, Nancy Y Lee

Faculty, Staff and Student Publications

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret.

Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma.

Design, setting, and participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and …


The Phytophthora Sojae Nuclear Effector Psavh110 Targets A Host Transcriptional Complex To Modulate Plant Immunity, Xufang Qiu, Liang Kong, Han Chen, Yachun Lin, Siqun Tu, Lei Wang, Zhiyuan Chen, Mengzhu Zeng, Junhua Xiao, Peiguo Yuan, Min Qiu, Yan Wang, Wenwu Ye, Kaixuan Duan, Suomeng Dong, Yuanchao Wang Jan 2023

The Phytophthora Sojae Nuclear Effector Psavh110 Targets A Host Transcriptional Complex To Modulate Plant Immunity, Xufang Qiu, Liang Kong, Han Chen, Yachun Lin, Siqun Tu, Lei Wang, Zhiyuan Chen, Mengzhu Zeng, Junhua Xiao, Peiguo Yuan, Min Qiu, Yan Wang, Wenwu Ye, Kaixuan Duan, Suomeng Dong, Yuanchao Wang

Faculty, Staff and Student Publications

Plants have evolved sophisticated immune networks to restrict pathogen colonization. In response, pathogens deploy numerous virulent effectors to circumvent plant immune responses. However, the molecular mechanisms by which pathogen-derived effectors suppress plant defenses remain elusive. Here, we report that the nucleus-localized RxLR effector PsAvh110 from the pathogen Phytophthora sojae, causing soybean (Glycine max) stem and root rot, modulates the activity of a transcriptional complex to suppress plant immunity. Soybean like-heterochromatin protein 1-2 (GmLHP1-2) and plant homeodomain finger protein 6 (GmPHD6) form a transcriptional complex with transcriptional activity that positively regulates plant immunity against Phytophthora infection. To suppress plant immunity, the …


Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim Jan 2023

Fn14-Directed Dart Nanoparticles Selectively Target Neoplastic Cells In Preclinical Models Of Triple-Negative Breast Cancer Brain Metastasis, Christine P Carney, Anshika Kapur, Pavlos Anastasiadis, Rodney M Ritzel, Chixiang Chen, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA−PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane—an FDA-approved paclitaxel nanoformulation—following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association …


Evaluating The Impact Of Using A Wound-Specific Oral Nutritional Supplement To Support Wound Healing In A Rehabilitation Setting, Rya K Clark, Argyrios Stampas, Kirk W Kerr, Jeffrey L Nelson, Suela Sulo, Luis Leon-Novelo, Esther Ngan, Dehuti Pandya Jan 2023

Evaluating The Impact Of Using A Wound-Specific Oral Nutritional Supplement To Support Wound Healing In A Rehabilitation Setting, Rya K Clark, Argyrios Stampas, Kirk W Kerr, Jeffrey L Nelson, Suela Sulo, Luis Leon-Novelo, Esther Ngan, Dehuti Pandya

Faculty, Staff and Student Publications

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein-energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non-healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound-specific oral nutritional supplementation (WS-ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard …


A Umls-Based Investigation Of Laterality In Biomedical Terminologies, Rashmie Abeysinghe, Xubing Hao, Licong Cui, Guo-Qiang Zhang Jan 2023

A Umls-Based Investigation Of Laterality In Biomedical Terminologies, Rashmie Abeysinghe, Xubing Hao, Licong Cui, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Laterality is an important anatomic directional property indicating the sidedness of body structures, diseases, and procedures. Errors in laterality could have catastrophic consequences in patient care. In this paper, we investigate how different biomedical terminologies organize terms indicating laterality. We leverage the Unified Medical Language System (UMLS) to identify lateral terms in different terminologies. For each lateral term, we attempt to obtain other matched lateral terms and further analyze how they are interrelated. Our results indicated that only 1.68% of the matched lateral term-pairs are hierarchically related. It was also seen that 44.24% of matched-pairs were siblings. We found that …


Extracting Temporal Expressions Of First Seizure Onset From Epilepsy Patient Discharge Summaries, Shiqiang Tao, Rashmie Abeysinghe, Blanca Talavera De La Esperanza, Samden Lhatoo, Guo-Qiang Zhang, Licong Cui Jan 2023

Extracting Temporal Expressions Of First Seizure Onset From Epilepsy Patient Discharge Summaries, Shiqiang Tao, Rashmie Abeysinghe, Blanca Talavera De La Esperanza, Samden Lhatoo, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Early onset of seizure is a potential risk factor for Sudden Unexpected Death in Epilepsy (SUDEP). However, the first seizure onset information is often documented as clinical narratives in epilepsy monitoring unit (EMU) discharge summaries. Manually extracting first seizure onset time from discharge summaries is time consuming and labor-intensive. In this work, we developed a rule-based natural language processing pipeline for automatically extracting the temporal information of patients’ first seizure onset from EMU discharge summaries. We use the Epilepsy and Seizure Ontology (EpSO) as the core knowledge resource and construct 4 extraction rules based on 300 randomly selected EMU discharge …


Literature Review: Pericranial Nerve Blocks For Chronic Migraines, Stephanie Wahab, Saurabh Kataria, Parker Woolley, Naanama O'Hene, Chima Odinkemere, Rosa Kim, Ivan Urits, Alan D Kaye, Jamal Hasoon, Cyrus Yazdi, Christopher L Robinson Jan 2023

Literature Review: Pericranial Nerve Blocks For Chronic Migraines, Stephanie Wahab, Saurabh Kataria, Parker Woolley, Naanama O'Hene, Chima Odinkemere, Rosa Kim, Ivan Urits, Alan D Kaye, Jamal Hasoon, Cyrus Yazdi, Christopher L Robinson

Faculty, Staff and Student Publications

Purpose of review: Headaches, especially migraines, are one of the most pervasive neurological disorders affecting up to 15.9% of the population. Current methods of migraine treatment include lifestyle changes, pharmacologic, and minimally invasive techniques such as peripheral nerve stimulation (PNS) and pericranial nerve blocks (PNB).

Recent findings: PNBs are used to treat and prevent migraines and involves injection of local anesthetics with or without corticosteroids. PNBs include the greater occipital, supraorbital, supratrochlear, lesser occipital, auriculotemporal, sphenopalantine ganglion, and cervical root nerve blocks. Of the PNBs, the most extensively studied is the greater occipital nerve block (GONB) which has been shown …


Multi-Model Order Spatially Constrained Ica Reveals Highly Replicable Group Differences And Consistent Predictive Results From Resting Data: A Large N Fmri Schizophrenia Study, Xing Meng, Armin Iraji, Zening Fu, Peter Kochunov, Aysenil Belger, Judy M Ford, Sara Mcewen, Daniel H Mathalon, Bryon A Mueller, Godfrey Pearlson, Steven G Potkin, Adrian Preda, Jessica Turner, Theo G M Van Erp, Jing Sui, Vince D Calhoun Jan 2023

Multi-Model Order Spatially Constrained Ica Reveals Highly Replicable Group Differences And Consistent Predictive Results From Resting Data: A Large N Fmri Schizophrenia Study, Xing Meng, Armin Iraji, Zening Fu, Peter Kochunov, Aysenil Belger, Judy M Ford, Sara Mcewen, Daniel H Mathalon, Bryon A Mueller, Godfrey Pearlson, Steven G Potkin, Adrian Preda, Jessica Turner, Theo G M Van Erp, Jing Sui, Vince D Calhoun

Faculty, Staff and Student Publications

Brain functional networks identified from resting functional magnetic resonance imaging (fMRI) data have the potential to reveal biomarkers for brain disorders, but studies of complex mental illnesses such as schizophrenia (SZ) often yield mixed results across replication studies. This is likely due in part to the complexity of the disorder, the short data acquisition time, and the limited ability of the approaches for brain imaging data mining. Therefore, the use of analytic approaches which can both capture individual variability while offering comparability across analyses is highly preferred. Fully blind data-driven approaches such as independent component analysis (ICA) are hard to …


Lipids And Lipoproteins May Play A Role In The Neuropathology Of Alzheimer’S Disease, Omer Akyol, Sumeyya Akyol, Mei-Chuan Chou, Shioulan Chen, Ching-Kuan Liu, Salih Selek, Jair C Soares, Chu-Huang Chen Jan 2023

Lipids And Lipoproteins May Play A Role In The Neuropathology Of Alzheimer’S Disease, Omer Akyol, Sumeyya Akyol, Mei-Chuan Chou, Shioulan Chen, Ching-Kuan Liu, Salih Selek, Jair C Soares, Chu-Huang Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the …


Oral/Oropharyngeal “Selfies” In Gay And Bisexual Men: A Pilot Study Exploring Oropharyngeal Screening For Hpv-Related Possible Malignancies, Michael W Ross, Sarah L Bennis, C Mark Nichols, I Niles Zoschke, J Michael Wilkerson, B R Simon Rosser, Cyndee L Stull, Alan G Nyitray, Charlene Flash, Samir S Khariwala Jan 2023

Oral/Oropharyngeal “Selfies” In Gay And Bisexual Men: A Pilot Study Exploring Oropharyngeal Screening For Hpv-Related Possible Malignancies, Michael W Ross, Sarah L Bennis, C Mark Nichols, I Niles Zoschke, J Michael Wilkerson, B R Simon Rosser, Cyndee L Stull, Alan G Nyitray, Charlene Flash, Samir S Khariwala

Faculty, Staff and Student Publications

Objectives: This study aims to determine the potential uptake and quality of oropharyngeal "selfies" taken by gay/bisexual men as a screening approach for HPV-associated oropharyngeal cancer.

Methods: From 1,699 gay/bisexual men in the US, surveyed about knowledge and attitudes to HPV-associated oropharyngeal cancer, a random sample of 320 men were invited to take an oropharyngeal "selfie" by smartphone and send it to the study website: 113 (35.5%) did so. Images were rated for quality by three healthcare professional raters blinded to each other's rating, with an otolaryngologist as the gold standard. In the second wave, those whose images were rated …


Roles Of Specialized Pro-Resolving Mediators And Omega-3 Polyunsaturated Fatty Acids In Periodontal Inflammation And Impact On Oral Microbiota, Chun-Teh Lee, Gena D Tribble Jan 2023

Roles Of Specialized Pro-Resolving Mediators And Omega-3 Polyunsaturated Fatty Acids In Periodontal Inflammation And Impact On Oral Microbiota, Chun-Teh Lee, Gena D Tribble

Faculty, Staff and Student Publications

Periodontitis is a chronic inflammatory disease induced by dysbiotic dental biofilms. Management of periodontitis is primarily anti-bacterial via mechanical removal of bacterial biofilm. The successful resolution requires wound healing and tissue regeneration, which are not always achieved with these traditional methods. The discovery of specialized pro-resolving mediators (SPMs), a class of lipid mediators that induce the resolution of inflammation and promote local tissue homeostasis, creates another option for the treatment of periodontitis and other diseases of chronic inflammation. In this mini-review, we discuss the host-modulatory effects of SPMs on periodontal tissues and changes in the taxonomic composition of the gut …


Serum Neurofilament Light-Chain Levels And Long-Term Treatment Outcomes In Relapsing-Remitting Multiple Sclerosis Patients: A Post Hoc Analysis Of The Randomized Combirx Trial, Gary Cutter, Richard A Rudick, Carl De Moor, Carol M Singh, Elizabeth Fisher, Thijs Koster, Fred D Lublin, Jerry S Wolinsky, Henry Mcfarland, Steven Jacobson, Maria L Naylor Jan 2023

Serum Neurofilament Light-Chain Levels And Long-Term Treatment Outcomes In Relapsing-Remitting Multiple Sclerosis Patients: A Post Hoc Analysis Of The Randomized Combirx Trial, Gary Cutter, Richard A Rudick, Carl De Moor, Carol M Singh, Elizabeth Fisher, Thijs Koster, Fred D Lublin, Jerry S Wolinsky, Henry Mcfarland, Steven Jacobson, Maria L Naylor

Faculty, Staff and Student Publications

BACKGROUND: CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies.

OBJECTIVE: This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse.

METHODS: RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. …


Pharmacokinetics And Pharmacodynamics Of Intranasal And Intramuscular Administration Of Naloxone In Working Dogs Administered Fentanyl, Ciara A Barr, Joanne Haughan, Giacomo Gianotti, Kelley Varner, Kenneth J Drobatz, Darko Stefanovski, Mary Robinson, Mark Pennington, Amanda Mcguire, Cynthia M Otto Jan 2023

Pharmacokinetics And Pharmacodynamics Of Intranasal And Intramuscular Administration Of Naloxone In Working Dogs Administered Fentanyl, Ciara A Barr, Joanne Haughan, Giacomo Gianotti, Kelley Varner, Kenneth J Drobatz, Darko Stefanovski, Mary Robinson, Mark Pennington, Amanda Mcguire, Cynthia M Otto

Faculty, Staff and Student Publications

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field.

OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs.

ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg.

METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after …


Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Srihari V Chari, Eric R Cui, Haylie E Fehl, Antonio R Fernandez, Jane H Brice, Mehul D Patel Jan 2023

Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Srihari V Chari, Eric R Cui, Haylie E Fehl, Antonio R Fernandez, Jane H Brice, Mehul D Patel

Faculty, Staff and Student Publications

OBJECTIVE: Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.

METHODS: This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based …


High-Definition Transcranial Direct Current Stimulation For Upper Extremity Rehabilitation In Moderate-To-Severe Ischemic Stroke: A Pilot Study, Jordan N Williamson, Shirley A James, Dorothy He, Sheng Li, Evgeny V Sidorov, Yuan Yang Jan 2023

High-Definition Transcranial Direct Current Stimulation For Upper Extremity Rehabilitation In Moderate-To-Severe Ischemic Stroke: A Pilot Study, Jordan N Williamson, Shirley A James, Dorothy He, Sheng Li, Evgeny V Sidorov, Yuan Yang

Faculty, Staff and Student Publications

Introduction: Previous studies found that post-stroke motor impairments are associated with damage to the lesioned corticospinal tract (CST) and hyperexcitability of the contralesional cortico-reticulospinal tract (CRST). This proof-of-concept study aims to develop a non-invasive brain stimulation protocol that facilitates the lesioned CST and inhibits the contralesional CRST to improve upper extremity rehabilitation in individuals with moderate-to-severe motor impairments post-stroke.

Methods: Fourteen individuals (minimum 3 months post ischemic stroke) consented. Physician decision of the participants baseline assessment qualified eight to continue in a randomized, double-blind cross-over pilot trial (ClinicalTrials.gov Identifier: NCT05174949) with: (1) anodal high-definition transcranial direct stimulation (HD-tDCS) over …