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Full-Text Articles in Medicine and Health Sciences

Sexually-Divergent Differentiation And Inflammatory Response To Osteoclasts, Lilijanna L. Cummings Jan 2023

Sexually-Divergent Differentiation And Inflammatory Response To Osteoclasts, Lilijanna L. Cummings

EWU Masters Thesis Collection

No abstract provided.


Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix Jan 2023

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …


Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler Jan 2023

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

Faculty, Staff and Student Publications

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …


Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang Jan 2023

Assessing The Most Vulnerable Subgroup To Type Ii Diabetes Associated With Statin Usage: Evidence From Electronic Health Record Data, Xinzhou Guo, Waverly Wei, Molei Liu, Tianxi Cai, Chong Wu, Jingshen Wang

Faculty, Staff and Student Publications

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset Type II diabetes (T2D). Nevertheless, to date, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, leveraging the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline and a novel statistical methodology that address existing limitations by (i) designing a rigorous causal …


Strengthening Deep-Learning Models For Intracranial Hemorrhage Detection: Strongly Annotated Computed Tomography Images And Model Ensembles, Dong-Wan Kang, Gi-Hun Park, Wi-Sun Ryu, Dawid Schellingerhout, Museong Kim, Yong Soo Kim, Chan-Young Park, Keon-Joo Lee, Moon-Ku Han, Han-Gil Jeong, Dong-Eog Kim Jan 2023

Strengthening Deep-Learning Models For Intracranial Hemorrhage Detection: Strongly Annotated Computed Tomography Images And Model Ensembles, Dong-Wan Kang, Gi-Hun Park, Wi-Sun Ryu, Dawid Schellingerhout, Museong Kim, Yong Soo Kim, Chan-Young Park, Keon-Joo Lee, Moon-Ku Han, Han-Gil Jeong, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Multiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance.

METHODS: We used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and …


Stem Cell Theory Of Cancer: Origin Of Metastasis And Sub-Clonality, Shi-Ming Tu, Cesar Moran, William Norton, Niki M Zacharias Jan 2023

Stem Cell Theory Of Cancer: Origin Of Metastasis And Sub-Clonality, Shi-Ming Tu, Cesar Moran, William Norton, Niki M Zacharias

Faculty, Staff and Student Publications

Metastasis may be the secret weapon cancer uses to dominate and subjugate, to persist and prevail. However, it is no longer a secret when we realize that a stem cell has the same ways and means to fulfill its own omnipotence and accomplish its own omnipresence… and when we realize that a cancer cell has its own version of stem-ness origin and stem-like nature. In this perspective, we discuss whether stem-ness enables metastasis or mutations drive metastasis. We ponder about low-grade versus high-grade tumors and about primary versus metastatic tumors. We wonder about stochasticity and hierarchy in the genesis and …


Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang Jan 2023

Analysis Of Immune Intratumor Heterogeneity Highlights Immunoregulatory And Coinhibitory Lymphocytes As Hallmarks Of Recurrence In Stage I Non-Small Cell Lung Cancer, Alejandro Francisco-Cruz, Pedro Rocha, Alexandre Reuben, Santhoshi N Krishnan, Priyam Das, Runzhe Chen, Kelly Quek, Jun Li, Edwin R Parra, Luisa M Solis, Souptik Barua, Mei Jiang, Rossana Lazcano, Chi-Wan Chow, Carmen Behrens, Curtis Gumb, Latasha Little, Junya Fukuoka, Neda Kalhor, Annikka Weissferdt, Humam Kadara, John V Heymach, Stephen Swisher, Boris Sepesi, Arvind Rao, Cesar Moran, Jianhua Zhang, J Jack Lee, Junya Fujimoto, P Andrew Futreal, Ignacio I Wistuba, Christine B Peterson, Jianjun Zhang

Faculty, Staff and Student Publications

Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between …


Case Report: Navigating The Challenges: Successful Mechanical Thrombectomy In A Case Of Persistent Primitive Hypoglossal Artery, Kamran Ahmed Khan, Irfan Amjad Lutfi, Jehangir Ali Shah, Salman Farooq, Shahnoor Ahmed, Bashir Ahmed Solangi, Ayan Ahmed Khan, Fazal Zaidi, Ali Ammar, Nadeem Qamar Jan 2023

Case Report: Navigating The Challenges: Successful Mechanical Thrombectomy In A Case Of Persistent Primitive Hypoglossal Artery, Kamran Ahmed Khan, Irfan Amjad Lutfi, Jehangir Ali Shah, Salman Farooq, Shahnoor Ahmed, Bashir Ahmed Solangi, Ayan Ahmed Khan, Fazal Zaidi, Ali Ammar, Nadeem Qamar

Faculty, Staff and Student Publications

Persistent primitive hypoglossal artery (PPHA) is a highly uncommon abnormal connection between the internal carotid artery (ICA) and vertebral artery (VA), with reported incidences ranging from 0.027 to 0.26%. Attempting endovascular intervention in such cases presents a considerable challenge as it carries a higher risk of embolization and other procedure-related complications that may affect a wide area of the brain. We present a case study involving the utilization of mechanical thrombectomy (MT) to treat an ischemic stroke in the M1 segment of the middle cerebral artery (MCA) despite the presence of PPHA. Performing mechanical thrombectomy in an anomalous vascular connection …


Social Protection And Foundational Cognitive Skills During Adolescence: Evidence From A Large Public Works Program, Nader Aboul-Fettouh, Kevin P Lee, Natalie Kash, Kathleen Kroger, Sirunya Silapunt Jan 2023

Social Protection And Foundational Cognitive Skills During Adolescence: Evidence From A Large Public Works Program, Nader Aboul-Fettouh, Kevin P Lee, Natalie Kash, Kathleen Kroger, Sirunya Silapunt

Faculty, Staff and Student Publications

INTRODUCTION: Reddit, a popular social media website, has numerous forums where users may discuss healthcare-related topics and request diagnostic and treatment advice for dermatologic conditions. We sought to analyze and grade user-submitted requests for dermatologic advice and their top responses on Reddit.

METHODS: User-submitted posts requesting diagnostic advice and their respective responses on two popular Reddit forums, SkinCareAddiction (ScA) and DermatologyQuestions (DQ), were reviewed by three board-certified dermatologists using a grading rubric designed for this study.

RESULTS: 300 posts and comments were reviewed. Diagnoses among all graders matched in 52.3% of posts with a mean grader confidence score of 4/5 …


Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws Jan 2023

Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws

Research outputs 2022 to 2026

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins.


Consensus Guidelines For Sarcopenia Prevention, Diagnosis And Management In Australia And New Zealand, Jesse Zanker, Marc Sim, Kate Anderson, Saliu Balogun, Sharon L. Brennan-Olsen, Elsa Dent, Gustavo Duque, Christian M. Girgis, Mathis Grossmann, Alan Hayes, Tim Henwood, Vasant Hirani, Charles Inderjeeth, Sandra Iuliano, Justin Keogh, Joshua R. Lewis, Gordon S. Lynch, Julie A. Pasco, Steven Phu, Esmee M. Reijnierse, Nicholas Russell, Lara Vlietstra, Renuka Visvanathan, Troy Walker, Debra L. Waters, Solomon Yu, Andrea B. Maier, Robin M. Daly, David Scott Jan 2023

Consensus Guidelines For Sarcopenia Prevention, Diagnosis And Management In Australia And New Zealand, Jesse Zanker, Marc Sim, Kate Anderson, Saliu Balogun, Sharon L. Brennan-Olsen, Elsa Dent, Gustavo Duque, Christian M. Girgis, Mathis Grossmann, Alan Hayes, Tim Henwood, Vasant Hirani, Charles Inderjeeth, Sandra Iuliano, Justin Keogh, Joshua R. Lewis, Gordon S. Lynch, Julie A. Pasco, Steven Phu, Esmee M. Reijnierse, Nicholas Russell, Lara Vlietstra, Renuka Visvanathan, Troy Walker, Debra L. Waters, Solomon Yu, Andrea B. Maier, Robin M. Daly, David Scott

Research outputs 2022 to 2026

Background:

Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand.

Methods:

A four-phase modified Delphi process involving topic experts and informed …


Causal Effect Of Pm1 On Morbidity Of Cause-Specific Respiratory Diseases Based On A Negative Control Exposure, Shiyun Lv, Xiangtong Liu, Zhiwei Li, Feng Lu, Moning Guo, Mengmeng Liu, Jing Wei, Zhiyuan Wu, Siqi Yu, Shihong Li, Xia Li, Wenkang Gao, Lixin Tao, Wei Wang, Jinyuan Xin, Xiuhua Guo Jan 2023

Causal Effect Of Pm1 On Morbidity Of Cause-Specific Respiratory Diseases Based On A Negative Control Exposure, Shiyun Lv, Xiangtong Liu, Zhiwei Li, Feng Lu, Moning Guo, Mengmeng Liu, Jing Wei, Zhiyuan Wu, Siqi Yu, Shihong Li, Xia Li, Wenkang Gao, Lixin Tao, Wei Wang, Jinyuan Xin, Xiuhua Guo

Research outputs 2022 to 2026

Background: Extensive studies have linked PM2.5 and PM10 with respiratory diseases (RD). However, few is known about causal association between PM1 and morbidity of RD. We aimed to assess the causal effects of PM1 on cause-specific RD. Methods: Hospital admission data were obtained for RD during 2014 and 2019 in Beijing, China. Negative control exposure and extreme gradient boosting with SHapley Additive exPlanation was used to explore the causality and contribution between PM1 and RD. Stratified analysis by gender, age, and season was conducted. Results: A total of 1,183,591 admissions for RD were recorded. Per interquartile range (28 μg/m3) uptick …


Differential Dna Methylation Of Steatosis And Non-Alcoholic Fatty Liver Disease In Adolescence, Phillip E. Melton, M. A. Burton, K. A. Lillycrop, K. M. Godfrey, S. Rauschert, D. Anderson, G. C. Burdge, T. A. Mori, L. J. Beilin, O. T. Ayonrinde, J. M. Craig, John K. Olynyk, J. D. Holbrook, C. E. Pennell, W. H. Oddy, E. K. Moses, L. A. Adams, R. C. Huang Jan 2023

Differential Dna Methylation Of Steatosis And Non-Alcoholic Fatty Liver Disease In Adolescence, Phillip E. Melton, M. A. Burton, K. A. Lillycrop, K. M. Godfrey, S. Rauschert, D. Anderson, G. C. Burdge, T. A. Mori, L. J. Beilin, O. T. Ayonrinde, J. M. Craig, John K. Olynyk, J. D. Holbrook, C. E. Pennell, W. H. Oddy, E. K. Moses, L. A. Adams, R. C. Huang

Research outputs 2022 to 2026

Background and aims:

Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

Approach and results:

We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at …


A Potential Role For Sirtuin-1 In Alzheimer's Disease: Reviewing The Biological And Environmental Evidence, Mehrane Mehramiz, Tenielle Porter, Eleanor K. O'Brien, Stephanie R. Rainey-Smith, Simon M. Laws Jan 2023

A Potential Role For Sirtuin-1 In Alzheimer's Disease: Reviewing The Biological And Environmental Evidence, Mehrane Mehramiz, Tenielle Porter, Eleanor K. O'Brien, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Sirtuin-1 (Sirt1), encoded by the SIRT1 gene, is a conserved Nicotinamide adenine dinucleotide (NAD+) dependent deacetylase enzyme, considered as the master regulator of metabolism in humans. Sirt1 contributes to a wide range of biological pathways via several mechanisms influenced by lifestyle, such as diet and exercise. The importance of a healthy lifestyle is of relevance to highly prevalent modern chronic diseases, such as Alzheimer's disease (AD). There is growing evidence at multiple levels for a role of Sirt1/SIRT1 in AD pathological mechanisms. As such, this review will explore the relevance of Sirt1 to AD pathological mechanisms, by describing the involvement …


Physical Education And Covid-19: What Have We Learned?, Valeria Varea, Ana Riccetti, Gustavo González-Calvo, Marcela Siracusa, Alfonso García-Monge Jan 2023

Physical Education And Covid-19: What Have We Learned?, Valeria Varea, Ana Riccetti, Gustavo González-Calvo, Marcela Siracusa, Alfonso García-Monge

Research outputs 2022 to 2026

The aim of this paper is to explore what we have learned during the COVID-19 pandemic in the field of Physical Education in three different countries: Argentina, Spain and Sweden. Data were generated through semi-structured interviews, and the concept of field agency is used to make sense of the data. Differences were found among the three countries, regarding the content of the classes, the use of resources, the emotions of teachers, and the use of physical contact. This was also a result of the regulations and resources in place. The COVID-19 pandemic has demonstrated that the nature of the field …


Externalizing Traits: Shared Causalities For Covid-19 And Alzheimer's Dementia Using Mendelian Randomization Analysis, Haotian Wang, Mingyang Cao, Yingjun Xi, Weijie Cao, Xiaoyu Zhang, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Wei Wang, Di Liu, Youxin Wang Jan 2023

Externalizing Traits: Shared Causalities For Covid-19 And Alzheimer's Dementia Using Mendelian Randomization Analysis, Haotian Wang, Mingyang Cao, Yingjun Xi, Weijie Cao, Xiaoyu Zhang, Xiaoni Meng, Deqiang Zheng, Lijuan Wu, Wei Wang, Di Liu, Youxin Wang

Research outputs 2022 to 2026

Externalizing traits have been related with the outcomes of coronavirus disease 2019 (COVID-19) and Alzheimer's dementia (AD); however, whether these associations are causal remains unknown. We used the two-sample Mendelian randomization (MR) approach with more than 200 single-nucleotide polymorphisms (SNPs) for externalizing traits to explore the causal associations of externalizing traits with the risk of COVID-19 (infected COVID-19, hospitalized COVID-19, and severe COVID-19) or AD based on the summary data. The inverse variance–weighted method (IVW) was used to estimate the main effect, followed by several sensitivity analyses. IVW analysis showed significant associations of externalizing traits with COVID-19 infection (odds ratio …


Covid-19 In Western Australia: ‘The Last Straw’ And Hopes For A ‘New Normal’ For Parents Of Children With Long-Term Conditions, Stephanie Smith, Mary Tallon, James Smith, Lauren Jones, Evalotte Mörelius Jan 2023

Covid-19 In Western Australia: ‘The Last Straw’ And Hopes For A ‘New Normal’ For Parents Of Children With Long-Term Conditions, Stephanie Smith, Mary Tallon, James Smith, Lauren Jones, Evalotte Mörelius

Research outputs 2022 to 2026

Background: Children with long-term conditions are vulnerable due to the treatments required for their conditions. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, Western Australians experienced restrictions that changed daily life activities but were able to return to some of their previous routines due to the restrictions. Aim: The study explored the stress experiences of parents caring for children with long-term conditions during COVID-19 in Western Australia. Design and Participants: The study was codesigned with a parent representative caring for children with long-term conditions to ensure essential questions were targeted. Twelve parents of children with various long-term conditions …


It's Quite Good Fun: A Qualitative Study Of A Singing/Songwriting Programme For People With Parkinson's Disease And Their Spouses, Deborah Hersh, Shi J. Kong, Jessica Smith Jan 2023

It's Quite Good Fun: A Qualitative Study Of A Singing/Songwriting Programme For People With Parkinson's Disease And Their Spouses, Deborah Hersh, Shi J. Kong, Jessica Smith

Research outputs 2022 to 2026

Background: : Group singing for people with Parkinson's disease (PD) is an established intervention not only to improve voice and speech difficulties but also for emotional and social benefit. Less is known about the experiences of group singing on the couple—the person with PD and their spouse or partner together—and studies have not specifically tracked impact through time or in combination with songwriting. Aims: : To understand the impact of group singing/songwriting on couples (participants with PD and their spouses) to unpack whether this broader view might help explain why such interventions are reported as beneficial. Using a trajectory approach, …


Prognostic And Predictive Value Of Metformin In The European Organisation For Research And Treatment Of Cancer 1325/Keynote-054 Phase Iii Trial Of Pembrolizumab Versus Placebo In Resected High-Risk Stage Iii Melanoma, Oliver J. Kennedy, Michal Kicinski, Sara Valpione, Sara Gandini, Stefan Suciu, Christian U. Blank, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Marye Boers-Sonderen, Anna M. Di Giacomo, Alfonsus J. M. Van Der Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C. J. Van Akkooi, Caroline Robert, Alexander M. M. Eggermont, Paul Lorigan, Mario Mandala Jan 2023

Prognostic And Predictive Value Of Metformin In The European Organisation For Research And Treatment Of Cancer 1325/Keynote-054 Phase Iii Trial Of Pembrolizumab Versus Placebo In Resected High-Risk Stage Iii Melanoma, Oliver J. Kennedy, Michal Kicinski, Sara Valpione, Sara Gandini, Stefan Suciu, Christian U. Blank, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Marye Boers-Sonderen, Anna M. Di Giacomo, Alfonsus J. M. Van Der Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C. J. Van Akkooi, Caroline Robert, Alexander M. M. Eggermont, Paul Lorigan, Mario Mandala

Research outputs 2022 to 2026

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 randomised controlled trial. Methods: Patients with resected high-risk stage IIIA, IIIB, or IIIC melanoma received 200 mg of pembrolizumab (n = 514) or placebo (n = 505) every 3 weeks for twelve months. Pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at approximately 42 months …


Association Between Immunoglobulin G N-Glycosylation And Lupus Nephritis In Female Patients With Systemic Lupus Erythematosus: A Case-Control Study, Xinxia Lu, Liangao Wang, Meng Wang, Yuejin Li, Qinqin Zhao, Yanjun Shi, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li Jan 2023

Association Between Immunoglobulin G N-Glycosylation And Lupus Nephritis In Female Patients With Systemic Lupus Erythematosus: A Case-Control Study, Xinxia Lu, Liangao Wang, Meng Wang, Yuejin Li, Qinqin Zhao, Yanjun Shi, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography …


Machine-Learning Assessed Abdominal Aortic Calcification Is Associated With Long-Term Fall And Fracture Risk In Community-Dwelling Older Australian Women, Jack Dalla Via, Abadi Gebre, Cassandra Smith, Zulqarnain Gilani, David Suter, Naeha Sharif, Pawel Szulc, John T. Schousboe, Douglas P. Kiel, Kun Zhu, William D. Leslie, Richard L. Prince, Joshua R. Lewis, Marc Sim Jan 2023

Machine-Learning Assessed Abdominal Aortic Calcification Is Associated With Long-Term Fall And Fracture Risk In Community-Dwelling Older Australian Women, Jack Dalla Via, Abadi Gebre, Cassandra Smith, Zulqarnain Gilani, David Suter, Naeha Sharif, Pawel Szulc, John T. Schousboe, Douglas P. Kiel, Kun Zhu, William D. Leslie, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the …


Ketone Bodies Mediate Alterations In Brain Energy Metabolism And Biomarkers Of Alzheimer’S Disease, Matin Ramezani, Malika Fernando, Shaun Eslick, Prita R. Asih, Sina Shadfar, Ekanayaka M. S. Bandara, Heidi Hillebrandt, Silochna Meghwar, Maryam Shahriari, Pratishtha Chatterjee, Rohith Thota, Cintia B. Dias, Manohar L. Garg, Ralph N. Martins Jan 2023

Ketone Bodies Mediate Alterations In Brain Energy Metabolism And Biomarkers Of Alzheimer’S Disease, Matin Ramezani, Malika Fernando, Shaun Eslick, Prita R. Asih, Sina Shadfar, Ekanayaka M. S. Bandara, Heidi Hillebrandt, Silochna Meghwar, Maryam Shahriari, Pratishtha Chatterjee, Rohith Thota, Cintia B. Dias, Manohar L. Garg, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta () plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including A , phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and …


Plasma Aβ42/40 Ratio, P-Tau181, Gfap, And Nfl Across The Alzheimer's Disease Continuum: A Cross-Sectional And Longitudinal Study In The Aibl Cohort, Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Doré, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins, Aibl Research Group Jan 2023

Plasma Aβ42/40 Ratio, P-Tau181, Gfap, And Nfl Across The Alzheimer's Disease Continuum: A Cross-Sectional And Longitudinal Study In The Aibl Cohort, Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Doré, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Introduction:

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking.

Methods:

Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross-sectionally across the AD continuum, wherein Aβ-PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ-PET–positive participants across the AD continuum (CU Aβ+, n = …


Diabetic Retinopathy And The Role Of Vegf, Aishwarya Gatiganti, Laura Valdez, Andrew Tsin Ph.D. Jan 2023

Diabetic Retinopathy And The Role Of Vegf, Aishwarya Gatiganti, Laura Valdez, Andrew Tsin Ph.D.

School of Medicine Publications

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. It works by disrupting the neural and vascular components in the retina and leads to loss of neural interaction/function, vascular permeability, and angiogenesis. It can be classified into two general stages: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). DR can also lead to vascular leakage and cause diabetic macular edema (DME), the most common cause of vision loss in DR (Duh, Sun et al. 2017). There are currently a wide range of therapies, but they are limited in their efficacy and side effects. None of …


Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache Jan 2023

Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache

Faculty, Staff and Student Publications

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively.

STUDY DESIGN: Retrospective analysis of prospective cohort.

SETTING: Tertiary care Veterans Health Administration (VHA) medical center.

METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively …


Validity And Diagnostic Performance Of Computing Fractional Flow Reserve From 2-Dimensional Coronary Angiography Images, Vahid Mohammadi, Massoud Ghasemi, Reza Rahmani, Maryam Mehrpooya, Hamidreza Babakhani, Akbar Shafiee, Mohammad Sadeghian Jan 2023

Validity And Diagnostic Performance Of Computing Fractional Flow Reserve From 2-Dimensional Coronary Angiography Images, Vahid Mohammadi, Massoud Ghasemi, Reza Rahmani, Maryam Mehrpooya, Hamidreza Babakhani, Akbar Shafiee, Mohammad Sadeghian

The Texas Heart Institute Journal

BACKGROUND: Measurement of fractional flow reserve (FFR) is the gold standard for determining the physiologic significance of coronary artery stenosis, but newer software programs can calculate the FFR from 2-dimensional angiography images.

METHODS: A retrospective analysis was conducted using the records of patients with intermediate coronary stenoses who had undergone adenosine FFR (aFFR). To calculate the computed FFR, a software program used simulated coronary blood flow using computational geometry constructed using at least 2 patient-specific angiographic images. Two cardiologists reviewed the angiograms and determined the computational FFR independently. Intraobserver variability was measured using κ analysis and the intraclass correlation coefficient. …


Surgical Reconstruction Of The Anomalous Left Coronary Artery From The Pulmonary Artery, Slobodan Micovic, Petar Milacic, Miroslav Milicic, Milica Brkovic, Petar Vukovic, Igor Zivkovic Jan 2023

Surgical Reconstruction Of The Anomalous Left Coronary Artery From The Pulmonary Artery, Slobodan Micovic, Petar Milacic, Miroslav Milicic, Milica Brkovic, Petar Vukovic, Igor Zivkovic

The Texas Heart Institute Journal

The anomalous left coronary artery from the pulmonary artery is a rare congenital disease. Early surgical reconstruction is mandatory to prevent adverse cardiac events. Direct coronary button transfer, vein graft interposition, ligation, and coronary artery bypass construction are the most commonly used techniques. This case report presents a modified technique of Dacron graft interposition and reimplantation anomalous left coronary artery from the pulmonary artery on the ascending aorta.


Investigation Of Lower Extremity Neuromuscular Function In Individuals With And Without Diabetes, Roya Hoveizavi Jan 2023

Investigation Of Lower Extremity Neuromuscular Function In Individuals With And Without Diabetes, Roya Hoveizavi

Theses and Dissertations--Kinesiology and Health Promotion

Background: Diabetes mellitus is associated with notable neuromuscular and motor dysfunctions that could lead to an increased risk of plantar ulcers and amputations. Several contributing factors, including increased muscle-tendon stiffness and abnormal muscle activation pattern may influence the kinematics and kinetics of walking in people with diabetes and promote formation of plantar ulcers. Hyperglycemia and the resultant accelerated rate of glycation have been recognized as the leading cause of muscle and tendon degeneration, yet the precise mechanisms by which diabetes affects the biomechanical properties of the muscle-tendon unit remains unclear. Altered muscle activity during gait is observed in people with …


Genetic Sequencing Of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections In Fully Vaccinated Healthcare Workers, Sara Haddad, John Zurlo, Zi-Xuan Wang, Bonnie Richards, Nitika Badjatia, Dagan Coppock Jan 2023

Genetic Sequencing Of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infections In Fully Vaccinated Healthcare Workers, Sara Haddad, John Zurlo, Zi-Xuan Wang, Bonnie Richards, Nitika Badjatia, Dagan Coppock

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Introduction

Since the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several efforts have been made to prevent infection, culminating in the development of highly effective vaccines. However, as genetic variants of the virus have emerged, concerns have arisen regarding potential limitations of available vaccines.

Methods

In this article, we evaluated SARS-CoV-2 breakthrough infections among 520 healthcare workers in a 950-bed hospital from March 1, 2021, to October 31, 2021, and stratified them according to the type of vaccine received. We tested for associations between Alpha and Delta strains of SARS-CoV-2 and clinical characteristics.

Results

During the study period, …


A Multicenter Cross-Sectional Study In Infants With Congenital Heart Defects Demonstrates High Diagnostic Yield Of Genetic Testing But Variable Evaluation Practices, Matthew D Durbin, Lindsey R Helvaty, Ming Li, William Border, Sara Fitzgerald-Butt, Vidu Garg, Gabrielle C Geddes, Benjamin M Helm, Seema R Lalani, Kim L Mcbride, Alexis Mcentire, Dana K Mitchell, Chaya N Murali, Stephanie B Wechsler, Benjamin J Landis, Stephanie M Ware Jan 2023

A Multicenter Cross-Sectional Study In Infants With Congenital Heart Defects Demonstrates High Diagnostic Yield Of Genetic Testing But Variable Evaluation Practices, Matthew D Durbin, Lindsey R Helvaty, Ming Li, William Border, Sara Fitzgerald-Butt, Vidu Garg, Gabrielle C Geddes, Benjamin M Helm, Seema R Lalani, Kim L Mcbride, Alexis Mcentire, Dana K Mitchell, Chaya N Murali, Stephanie B Wechsler, Benjamin J Landis, Stephanie M Ware

Faculty, Staff and Students Publications

PURPOSE: For patients with congenital heart disease (CHD), the most common birth defect, genetic evaluation is not universally accepted, and current practices are anecdotal. Here, we analyzed genetic evaluation practices across centers, determined diagnostic yield of testing, and identified phenotypic features associated with abnormal results.

METHODS: This is a multicenter cross-sectional study of 5 large children's hospitals, including 2899 children ≤14 months undergoing surgical repair for CHD from 2013 to 2016, followed by multivariate logistics regression analysis.

RESULTS: Genetic testing occurred in 1607 of 2899 patients (55%). Testing rates differed highly between institutions (42%-78%, P < .001). Choice of testing modality also differed across institutions (ie, chromosomal microarray, 26%-67%, P < .001). Genetic testing was abnormal in 702 of 1607 patients (44%), and no major phenotypic feature drove diagnostic yield. Only 849 patients were seen by geneticists (29%), ranging across centers (15%-52%, P < .001). Geneticist consultation associated with increased genetic testing yield (odds ratio: 5.7, 95% CI 4.33-7.58, P < .001).

CONCLUSION: Genetics …