Medicine and Health Sciences Commons^™

Cariesthe Effect Of Sweet Taste Perception On Dental Caries Experience In Relation To Age And Gender In Primary School Children, Mohammed H. Abdulaziz, Suha T. Abd

Al-Esraa University College Journal for Medical Sciences

This study aims to investigate the impact of sweet taste perception (sweet taste threshold and preference) on dental caries experience in relation to age and gender among a sample of schoolchildren. The research follows a cross-sectional observational design and includes 181 schoolchildren of both genders aged between 6 and 12 years from the Al-Risafa district of Baghdad city. The participants were divided into two age groups (6-8 and 9-12). Dental caries were assessed using the decayed, missing, and filled indices for primary and permanent teeth (dmfs, dmft, DMFS, and DMFT). Additionally, the sweet taste threshold and sweet taste preference were …

Determination The Effect Of Glucose On Btp, Lfabp Levels In The Patients With Diabetic Nephropathy, Zahraa Khalid Mahmood, Suhayr Aesa Al-Qaysi, Alaa Jafear Mahrath

Al-Esraa University College Journal for Medical Sciences

Everywhere in the globe, kidney illness is becoming more common, and there is no medication that can stop the progression of chronic kidney disease to end-stage renal disease, which is extremely expensive. Diabetes, kidney stones, accidents, and bleeding are the main contributors to kidney disease. The study was designed as a case control study. The study was involved (80) participants, only (36) were involved in this study and divided into two groups patients with nephropathy (23) and diabetic nephropathy (13) with age (20-65years) and BMI (19 -29 kg/m2). All these patients were diagnosed by nephrologist conducted in nephrology Clinic at …

Genetic Polymorphisms Of Aqp1 Rs10244884 Associated With Iron Deficiency Anemia In Baghdad City, Sawsan Hashim Hoshe, Moead E. Al Gazally, Hussein Naji Al-Shammari

Al-Esraa University College Journal for Medical Sciences

Most people throughout the world suffer from iron deficiency anemia (IDA). The morbidity rate is relatively high for such a complicated illness. Importantly, it has been identified that the aquaporin-1 polymorphism rs10244884 plays a critical role in iron homeostasis in the human body. The rs10244884 (T > C) polymorphism is significantly associated with iron levels and a variety of blood factors, leading to iron deficiency anemia (IDA). Venous blood samples were collected from (100) people in this analytical (case and control) investigation, including (50) patients with iron deficiency anemia and (50) healthy volunteers as a control group. The following parameters were …

The Concise Guide To Pharmacology 2023/24: Catalytic Receptors, Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A. Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Doris Koesling, Michaela Kuhn, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It …

Evaluation Of A Targeted Covid-19 Community Outreach Intervention: Case Report For Precision Public Health, Isela De La Cerda, Cici X Bauer, Kehe Zhang, Miryoung Lee, Michelle Jones, Arturo Rodriguez, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

BACKGROUND: Cameron County, a low-income south Texas-Mexico border county marked by severe health disparities, was consistently among the top counties with the highest COVID-19 mortality in Texas at the onset of the pandemic. The disparity in COVID-19 burden within Texas counties revealed the need for effective interventions to address the specific needs of local health departments and their communities. Publicly available COVID-19 surveillance data were not sufficiently timely or granular to deliver such targeted interventions. An agency-academic collaboration in Cameron used novel geographic information science methods to produce granular COVID-19 surveillance data. These data were used to strategically target an …

The Potential For Development Of Clinically Relevant Microbial Resistance To Rifaximin-Α: A Narrative Review, Herbert L Dupont

Faculty, Staff and Student Publications

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. …

Prt543, A Protein Arginine Methyltransferase 5 Inhibitor, In Patients With Advanced Adenoid Cystic Carcinoma: An Open-Label, Phase I Dose-Expansion Study, Renata Ferrarotto, Paul Swiecicki, Dan Zandberg, Robert Baiocchi, Robert Wesolowski, Cristina Rodriguez, Meredith Mckean, Hyunseok Kang, Varun Monga, Rajneesh Nath, Neil Palmisiano, Naveen Babbar, William Sun, Glenn Hanna

Department of Medical Oncology Faculty Papers

OBJECTIVES: Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.

MATERIALS AND METHODS: This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC …

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …

Research Priorities For Children’S Cancer: A James Lind Alliance Priority Setting Partnership In The Uk, Susie Aldiss, Rachel Hollis, Bob Phillips, Ashley Ball-Gamble, Alex Brownsdon, Julia Chisholm, Scott Crowther, Rachel Dommett, Jonathan Gower, Nigel J Hall, Helen Hartley, Jenni Hatton, Louise Henry, Loveday Langton, Kirsty Maddock, Sonia Malik, Keeley Mcevoy, Jessica Elizabeth Morgan, Helen Morris, Simon Parke, Sue Picton, Rosa Reed-Berendt, Dan Saunders, Andy Stewart, Wendy Tarplee-Morris, Amy Walsh, Anna Watkins, David Weller, Faith Gibson

Faculty, Staff and Student Publications

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda.

DESIGN: James Lind Alliance Priority Setting Partnership.

SETTING: UK health service and community.

METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities.

PARTICIPANTS: Children and …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Natalie Sirisaengtaksin, Eloise J O'Donoghue, Sara Jabbari, Andrew J Roe, Anne Marie Krachler

Faculty, Staff and Student Publications

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Effects Of Episodic Food Insecurity On Psychological And Physiological Responses In African American Women With Obesity (Responses): Protocol For A Longitudinal Observational Cohort Study, Candice A. Myers, Robbie A. Beyl, Daniel S. Hsia, Melissa N. Harris, Isabella J. Reed, Danielle D. Eliser, Lauren Bagneris, John W. Apolzan

School of Public Health Faculty Publications

Background; Food insecurity is a risk factor for multiple chronic diseases, including obesity. Importantly, both food insecurity and obesity are more prevalent in African American women than in other groups. Furthermore, food insecurity is considered a cyclic phenomenon, with episodes of food adequacy (ie, enough food to eat) and food shortage (ie, not enough food to eat). More research is needed to better understand why food insecurity is linked to obesity, including acknowledging the episodic nature of food insecurity as a stressor and identifying underlying mechanisms. Objective; The objective of this study is to investigate the episodic nature of food …

Rapidiron Trial Follow-Up Study - The Rapidiron-Kids Study: Protocol Of A Prospective Observational Follow-Up Study, Richard Derman, Roopa Bellad, Mrutyunjaya Bellad, Jesse Bradford-Rogers, Michael Georgieff, Zubair Aghai, Simal Thind, Michael Auerbach, Rupsa Boelig, Benjamin Leiby, Vanessa Short, S. Yogeshkumar, Umesh Charantimath, Manjunath Somannavar, Ashalata Mallapur, Ramesh Pol, Umesh Ramadurg, Radha Sangavi, Basavaraj Peerapur, Nasima Banu, Praveen Patil, Amaresh Patil, Subarna Roy, Phaniraj Vastrad, Dennis Wallace, Hemang Shah, Shivaprasad Goudar

Global Health Articles

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India …

Pediatric Endocrinology Milestones 20-Guide To Their Implementation, Cara V Tillotson, Imen Becetti, Katherine Hwu, Laura Page, Sowmya Krishnan, Dianne Stafford, Takara Stanley, Patricia Vuguin, Jennifer M Barker

Faculty, Staff and Students Publications

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate …

Interventricular Septal Hematoma Complicating Left Branch Bundle Lead Implantation: Treatment By Covered Stent, César Del Castillo, Jorge Van-Grieken, Marco Coello, Carlos Torres-Herrera, Barbara Clericus, Daniel Requena, Arnulfo Begazo, Franco Appiani, Boris Kuzmicic, Paola Varleta

Faculty, Staff and Students Publications

We present a female patient with heart failure with reduced ejection fraction who underwent left bundle branch cardiac resynchronization therapy. Left bundle branch lead implantation was complicated with septal branch perforation causing an iatrogenic coronary fistula complicated by septal hematoma formation and development of shock. Occlusion by covered stents was successfully achieved.

Abnormal Patterns Of Sleep And Waking Behaviors Are Accompanied By Neocortical Oscillation Disturbances In An Ank3 Mouse Model Of Epilepsy-Bipolar Disorder Comorbidity, Juan E Villacres, Nicholas Riveira, Sohmee Kim, Laura L Colgin, Jeffrey L Noebels, Angel Y Lopez

Faculty, Staff and Students Publications

ANK3 is a leading bipolar disorder (BD) candidate gene in humans and provides a unique opportunity for studying epilepsy-BD comorbidity. Previous studies showed that deletion of Ank3-1b, a BD-associated variant of Ank3 in mice leads to increased firing threshold and diminished action potential dynamic range of parvalbumin (PV) interneurons and absence epilepsy, thus providing a biological mechanism linking epilepsy and BD. To explore the behavioral overlap of these disorders, we characterized behavioral patterns of Ank3-1b KO mice during overnight home-cage activity and examined network activity during these behaviors using paired video and EEG recordings. Since PV interneurons contribute to the …

Mental Health Differences In Medical Students Based On Curriculum And Gender, Maxim Jestin, Shelly Sharma, Deval Jhaveri, Brittany Mitchell, Dean Micciche, Venkat Venkataraman, Kathryn Lambert

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The prevalence of mental health struggles among students in medical school is widely reported; however, little is known about how it is impacted by the medical school curriculum. This study aimed to evaluate differences in anxiety, depression, and emotional exhaustion in medical students based on gender, class year, and curriculum.

METHODS: An anonymous online survey consisting of questions from established, validated questionnaires about demographics, anxiety, depression, emotional exhaustion, and personal health behaviors was sent to 817 medical students who attended Rowan-Virtua School of Osteopathic Medicine during the Spring of 2021. When applying to this school, each of these students …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Traumatic Brain Injury Severity In Older Adults: Impact On Anxiety And Depression Symptoms And Community Engagement, Ashley Tomford

Theses and Graduate Projects

Background: Traumatic Brain Injury (TBI) is one of the leading causes of physical and cognitive disability worldwide. TBI can negatively impact cognitive, physical, social, and psychological functioning.

Objective: This study investigated interactions between TBI severity, mental health symptom severity, and community engagement among older adults. Specific aims included investigating 1) the relationship between TBI severity at the time of injury and psychiatric symptom severity at one-year post-TBI; 2) the relationship between TBI severity and community engagement at one-year post-TBI; and 3) whether mental health symptom severity moderated the relationship between TBI and post-injury community engagement.

Methods: Archival data was analyzed …

Accuracy Of Swept Source Biometry Device In Detecting Macular Diseases Compared With Swept Source Oct, Sidra Zafar, Taha Muneer Ahmed, Rashid Baig, Irfan Jeeva, Rehman Siddiqui

Department of Ophthalmology & Visual Sciences

Objective: To assess the diagnostic accuracy of the IOLMaster 700 foveal scans to detect foveal pathology compared with a standard swept-source optical coherence tomography (SS-OCT) device.
Results: One hundred seventy eye scans of 95 patients were included in the final analyses. Ninety-nine (58.2%) scans were classified as abnormal by SS-OCT. Mean sensitivity of the biometry device was 67.5% (range: 51-84%) and mean specificity was 69.5% (range: 44-95%). Intra-class correlation coefficients were 0.912 and 0.835, for reader 1 and 2, respectively. Area under the curve for receiver operating curve was 0.726. Foveal scans of the IOLMaster 700 can provide clinically useful …

Risk Factors For Unplanned Readmissions In Paediatric Neurosurgery: A Systematic Review Protocol, Lance Vincent Caburian Sese, Ma Celina Legaspi Guillermo

Ateneo School of Medicine and Public Health Publications

Introduction Unplanned hospital readmission (UHR) following surgical procedures reflects patient outcomes. While adult readmission studies are abundant, limited research exists in paediatric populations, especially in the context of neurosurgery. Methods and analysis This protocol outlines a systematic review aimed at identifying reasons for unplanned readmissions (30-day and 90-day readmissions) and risk factors following paediatric neurosurgical procedures. Narrative synthesis, sensitivity analyses, subgroup analyses, and meta-analysis, when appropriate, will be done. Ethics and dissemination There are no primary data involved and no access to confidential patient information. The findings aim to contribute to refining clinical practice, enhance patient counselling, and optimise healthcare …

A Broadly Reactive Antibody Targeting The N-Terminal Domain Of Sars-Cov-2 Spike Confers Fc-Mediated Protection, Lucas J Adams, Laura A Vanblargan, Zhuoming Liu, Pavlo Gilchuk, Haiyan Zhao, Rita E Chen, Saravanan Raju, Zhenlu Chong, Bradley M Whitener, Swathi Shrihari, Prashant N Jethva, Michael L Gross, James E Crowe Jr., Sean P J Whelan, Michael S Diamond, Daved H Fremont

2020-Current year OA Pubs

Most neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) target the receptor binding domain (RBD) of the spike (S) protein. Here, we characterize a panel of mAbs targeting the N-terminal domain (NTD) or other non-RBD epitopes of S. A subset of NTD mAbs inhibits SARS-CoV-2 entry at a post-attachment step and avidly binds the surface of infected cells. One neutralizing NTD mAb, SARS2-57, protects K18-hACE2 mice against SARS-CoV-2 infection in an Fc-dependent manner. Structural analysis demonstrates that SARS2-57 engages an antigenic supersite that is remodeled by deletions common to emerging variants. In neutralization escape studies with SARS2-57, this NTD site accumulates mutations, including …

The Federal Government Must Revise Public Housing Policies To Protect Vulnerable Populations From Evictions, Caroline Grabowski

Population Health Research Brief Series

Over 100,000 Americans are now dying from drug overdoses annually, signifying that the goal of the 1986 Anti-Drug Abuse Act (ADAA) to end illicit drug use has not been achieved. What’s more, numerous statutes within the ADAA have created or worsened housing instability among people who use drugs and their families. This is because the ADAA allows public housing officials to use their own discretion when determining evictions and lease refusals and has disproportionately harmed individuals in public housing who did not participate in the drug-related activities that led to their eviction. This brief describes how the ADAA negatively affects …

The 50 Most Cited Papers On Rugby Since 2000 Reveal A Focus Primarily On Strength And Conditioning In Elite Male Players, Katherine J. Hunzinger, Eric Schussler

Department of Exercise Science Faculty Papers

We sought to conduct a bibliometric analysis and review of the most cited publications relating to rugby since 2000 in order to identify topics of interest and those that warrant further investigations. Clarivate Web of Science database was used to perform a literature search using the search term "rugby." The top 200 papers by citation count were extracted and reviewed for the inclusion criteria: all subjects were rugby players. The top 50 manuscripts were included for analysis of author, publication year, country of lead authors, institution, journal name and impact factor, topic, participant sex, and level of rugby. The total …

The Pharmacological Deprescription In Elderly Patients, Chelsey Ali, Daniel Huang, Charlene Tugwete, Stefano Del Canale, Vittorio Maio

College of Population Health Faculty Papers

No abstract provided.

Intragenic Egfr::Egfre1e8 Fusion (Egfrviii) In 4331 Solid Tumors, Lan Zheng, Rajyalakshmi Luthra, Hector A Alvarez, F Anthony San Lucas, Dzifa Y Duose, Ignacio I Wistuba, Gregory N Fuller, Leomar Y Ballester, Sinchita Roy-Chowdhuri, Keith J Sweeney, Asif Rashid, Richard K Yang, Wei Chen, Audrey Liu, Yun Wu, Constance Albarracin, Keyur P Patel, Mark J Routbort, Aysegul A Sahin, Qingqing Ding, Hui Chen

Faculty, Staff and Student Publications

Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2-7) is a recurrent intragenic EGFR::EGFR.E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII in other solid tumors has not been well characterized. We retrospectively reviewed advanced malignant solid tumor cases tested by a custom hybrid capture 610-gene next-generation sequencing platform from 2021 to 2022. EGFRvIII was identified in 17 of 4331 (0.4%) cases, including 16 of 238 (7%) brain tumors and 1/301 (0.3%) breast tumors. EGFRvIII-positive brain tumors were all glioblastoma IDH-wildtype, most with concurrent TERT promoter mutation (14 of 16), EGFR amplification (13 of …

Blue-Shift Photoconversion Of Near-Infrared Fluorescent Proteins For Labeling And Tracking In Living Cells And Organisms, Francesca Pennacchietti, Jonatan Alvelid, Rodrigo A Morales, Martina Damenti, Dirk Ollech, Olena S Oliinyk, Daria M Shcherbakova, Eduardo J Villablanca, Vladislav V Verkhusha, Ilaria Testa

Faculty, Staff and Student Publications

Photolabeling of intracellular molecules is an invaluable approach to studying various dynamic processes in living cells with high spatiotemporal precision. Among fluorescent proteins, photoconvertible mechanisms and their products are in the visible spectrum (400-650 nm), limiting their in vivo and multiplexed applications. Here we report the phenomenon of near-infrared to far-red photoconversion in the miRFP family of near infrared fluorescent proteins engineered from bacterial phytochromes. This photoconversion is induced by near-infrared light through a non-linear process, further allowing optical sectioning. Photoconverted miRFP species emit fluorescence at 650 nm enabling photolabeling entirely performed in the near-infrared range. We use miRFPs as …

Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo

Department of Microbiology and Immunology Faculty Papers

Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …