Digital Commons Network^™

From Bench To Bedside: Murine Models Of Inherited And Sporadic Brain Arteriovenous Malformations, Ashely R Ricciardelli, Gael Genet, Nafiisha Genet, Samuel T Mcclugage, Peter T Kan, Karen K Hirschi, Jason E Fish, Joshua D Wythe

Faculty, Staff and Students Publications

Brain arteriovenous malformations are abnormal vascular structures in which an artery shunts high pressure blood directly to a vein without an intervening capillary bed. These lesions become highly remodeled over time and are prone to rupture. Historically, brain arteriovenous malformations have been challenging to treat, using primarily surgical approaches. Over the past few decades, the genetic causes of these malformations have been uncovered. These can be divided into (1) familial forms, such as loss of function mutations in TGF-β (BMP9/10) components in hereditary hemorrhagic telangiectasia, or (2) sporadic forms, resulting from somatic gain of function mutations in genes involved in …

Characterizing The Genetic Basis For Inherited Retinal Disease: Lessons Learned From The Foundation Fighting Blindness Clinical Consortium's Gene Poll, Kari Branham, Lassana Samarakoon, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Stephen P Daiger, Patty Dhooge, Jacque L Duncan, Todd A Durham, Abigail T Fahim, Rachel M Huckfeldt, Robert B Hufnagel, Susanne Kohl, Ramiro S Maldonado, Michele Melia, Michel Michaelides, Mark E Pennesi, José-Alain Sahel, Juliana M Ferraz Sallum, Mandeep S Singh, Dror Sharon, Kimberly Stepien, Kaylie Jones, Christina Y Weng

Faculty, Staff and Students Publications

PURPOSE: The Foundation Fighting Blindness (FFB) Consortium is a collaboration of 41 international clinical centers that manage patients affected with inherited retinal diseases (IRDs). The annual Consortium gene poll was initiated in 2020 to capture the genetic cause of disease in patients with IRD and associated clinical practices of Consortium sites. Data from the 2022 gene poll are reported here.

METHODS: In 2022, academic, private practice, and government ophthalmology clinics that are members of the Consortium centers were polled to identify per-case IRD genetic causality from a list of 387 syndromic and nonsyndromic IRD genes. The survey also assessed how …

Distinct Roles Of Mtorc2 In Excitatory And Inhibitory Neurons In Inflammatory And Neuropathic Pain, Wei He, Xin Ge, Ru-Rong Ji

Faculty, Staff and Student Publications

No abstract provided.

Understanding Pediatric Bipolar Disorder Through The Investigation Of Clinical, Neuroanatomic, Neurophysiological And Neurocognitive Dimensions: A Pilot Study, Alessio Simonetti, Evelina Bernardi, Sherin Kurian, Antonio Restaino, Claudia Calderoni, Emanuela De Chiara, Francesca Bardi, Gabriele Sani, Jair C Soares, Kirti Saxena

Faculty, Staff and Student Publications

Background: Pathophysiological models of pediatric bipolar disorder (PBD) are lacking. Multimodal approaches may provide a comprehensive description of the complex relationship between the brain and behavior. Aim: To assess behavioral, neuropsychological, neurophysiological, and neuroanatomical alterations in youth with PBD.

Methods: Subjects with PBD (n = 23) and healthy controls (HCs, n = 23) underwent (a) clinical assessments encompassing the severity of psychiatric symptoms, (b) neuropsychological evaluation, (c) analyses of event-related potentials (related to the passive viewing of fearful, neutral, and happy faces during electroencephalography recording, and (d) cortical thickness and deep gray matter volume measurement using magnetic …

Deescalation Perils In Inflammatory Breast Cancer, Wendy A Woodward

Faculty, Staff and Student Publications

No abstract provided.

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

Early Tolerance And Late Persistence As Alternative Drug Responses In Cancer, Simona Punzi, Davide Cittaro, Guido Gatti, Gemma Crupi, Oronza A Botrugno, Antonino Alex Cartalemi, Alon Gutfreund, Caterina Oneto, Valentina Giansanti, Chiara Battistini, Giovanni Santacatterina, Lucrezia Patruno, Ilaria Villanti, Martina Palumbo, Daniel J Laverty, Francesca Giannese, Alex Graudenzi, Giulio Caravagna, Marco Antoniotti, Zachary Nagel, Ugo Cavallaro, Luisa Lanfrancone, Timothy A Yap, Giulio Draetta, Nathalie Balaban, Giovanni Tonon

Faculty, Staff and Student Publications

Bacteria withstand antibiotic treatment through three alternative mechanisms: resistance, persistence or tolerance. While resistance and persistence have been described, whether drug-induced tolerance exists in cancer cells remains largely unknown. Here, we show that human cancer cells elicit a tolerant response when exposed to commonly used chemotherapy regimens, propelled by the pervasive activation of autophagy, leading to the comprehensive activation of DNA damage repair pathways. After prolonged drug exposure, such tolerant responses morph into persistence, whereby the increased DNA damage repair is entirely reversed. The central regulator of mitophagy PINK1 drives this reduction in DNA repair via the cytoplasmic relocalization of …

Plant-Nanoparticles Enhance Anti-Pd-L1 Efficacy By Shaping Human Commensal Microbiota Metabolites, Yun Teng, Chao Luo, Xiaolan Qiu, Jingyao Mu, Mukesh K Sriwastva, Qingbo Xu, Minmin Liu, Xin Hu, Fangyi Xu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Maiying Kong, Zhanxu Liu, Xiang Zhang, Raobo Xu, Jun Yan, Michael L Merchant, Craig J Mcclain, Huang-Ge Zhang

Faculty, Staff and Student Publications

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Antitumor Activity And Biomarker Analysis For Trop2 Antibody-Drug Conjugate Datopotamab Deruxtecan In Patient-Derived Breast Cancer Xenograft Models, Funda Meric-Bernstam, Erkan Yuca, Kurt W Evans, Ming Zhao, Takanori Maejima, Tsuyoshi Karibe, Maria Gabriela Raso, Ximing Tang, Xiaofeng Zheng, Yasmeen Qamar Rizvi, Argun Akcakanat, Stephen M Scott, Bailiang Wang, Lauren A Byers, Debu Tripathy, Daisuke Okajima, Senthil Damodaran

Faculty, Staff and Student Publications

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is a humanized anti-trophoblast cell-surface antigen-2 (TROP2) IgG1 mAb linked to a potent topoisomerase I inhibitor payload (DXd). Dato-DXd has already shown antitumor activity in breast cancer; however, the determinants of response, including the importance of TROP2 expression, remain unclear. We tested the activity of Dato-DXd in a panel of breast cancer patient-derived xenografts (BCX) varying in TROP2 expression.

EXPERIMENTAL DESIGN: The antitumor activity of Dato-DXd and isotype-control-DXd (IgG-DXd) was assessed against 11 BCXs varying in TROP2 expression, 10 representing tumors postneoadjuvant chemotherapy. Pharmacodynamic effects were assessed at 24 and 72 hours. The effects of TROP2 …

Cardiovascular Disease In Adults With Osteogenesis Imperfecta: Clinical Characteristics, Care Recommendations, And Research Priorities Identified Using A Modified Delphi Technique, Lars Folkestad, Siddharth K Prakash, Sandesh C S Nagamani, Niels Holmark Andersen, Erin Carter, Jannie Dahl Hald, Riley J Johnson, Bente Langdahl, Eleanor M Perfetto, Cathleen Raggio, Stuart H Ralston, Robert A Sandhaus, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Student Publications

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the …

Investigating The In Vivo Effects Of Anti-Prion Protein Nanobodies On Prion Disease With Aav Vector, Jingjing Zhang, Mengfei Wang, Dan Wang, Xiangyi Zhang, Yue Ma, Els Pardon, Jan Steyaert, Romany Abskharon, Fei Wang, Jiyan Ma

Faculty, Staff and Student Publications

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, and the central pathogenic event is the conversion of normal prion protein (PrPC) into the pathogenic PrPSc isoform. Previous studies have identified nanobodies that specifically recognize PrPC and inhibit the PrPC to PrPSc conversion in vitro. In this study, we investigated the potential for in vivo expression of anti-PrPC nanobodies and evaluated their impact on prion disease. The coding sequences of three nanobodies were packaged into recombinant adeno-associated virus (rAAV) and were administered via intracerebroventricular (ICV) injection in newborn mice. We found that the expression of these nanobodies remained robust …

Pharmacogenetic And Microrna Mechanisms Of Beta Blocker Use On Bone, Christine W Lary, Elizabeth J Atkinson, Jennifer Spillane, Zannatun Nayema, Tyler A Roy, Rebecca Peters, Griffin T Scott, Hongyu Chen, Archana Nagarajan, Aaron Brown, Katherine J Motyl, David G Monroe, Sundeep Khosla

Faculty, Staff and Students Publications

Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/d), or nebivolol (5 mg/d) to determine changes in bone turnover markers (BTMs) and in BMD over 20 wk. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial. We genotyped all participants and …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Defining The Role Of Adjuvant Radiotherapy For Biliary Tract Cancers: A Site-Specific Propensity-Matched Analysis, Yongwoo David Seo, Belkacem Acidi, Andrew Newton, Antony Haddad, Yi-Ju Chiang, Rainna Coelho, Timothy E Newhook, Ching-Wei D Tzeng, Yun Shin Chun, Ethan B Ludmir, Eugene J Koay, Milind Javle, Jean Nicolas Vauthey, Hop S Tran Cao

Faculty, Staff and Student Publications

Background: Biliary tract cancers (BTCs) have distinct tumor biology but share a poor prognosis, with a 5-year-survival-rate of 5-19%. Surgical resection is the only potential cure, but recurrences are common. The role of adjuvant radiotherapy (XRT) remains unclear.

Methods: Using the National Cancer Database (2006-2018), we analyzed resected non-metastatic BTCs. Patients who survived beyond 90 days post-surgery were included, while those with R2 resections or neoadjuvant therapy were excluded. Propensity matching was performed based on predictors of adjuvant radiation, age, and sex. Survival outcomes were compared between no adjuvant therapy, chemotherapy alone, and XRT ± chemotherapy.

Results: …

Lab Protocols And Experiments To Reduce Your Research Time, Joanne Romano

TMC Library Newsletter (2023-)

Lab Protocols and Experiments to Reduce your Research Time!

Find your favorite protocol or experiment using a keyword search in our library catalog, or by entering the database name into our A to Z list of databases.

A Statistical Framework Of Watermarks For Large Language Models: Pivot, Detection Efficiency And Optimal Rules, Xiang Li, Feng Ruan, Huiyuan Wang, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

Since ChatGPT was introduced in November 2022, embedding (nearly) unnoticeable statistical signals into text generated by large language models (LLMs), also known as watermarking, has been used as a principled approach to provable detection of LLM-generated text from its human-written counterpart. In this paper, we introduce a general and flexible framework for reasoning about the statistical efficiency of watermarks and designing powerful detection rules. Inspired by the hypothesis testing formulation of watermark detection, our framework starts by selecting a pivotal statistic of the text and a secret key-provided by the LLM to the verifier-to control the false positive rate (the …

Synaptic Alterations In Pyramidal Cells Following Genetic Manipulation Of Neuronal Excitability In Monkey Prefrontal Cortex, Guillermo Gonzalez-Burgos, Takeaki Miyamae, Yosuke Nishihata, Olga L Krimer, Kirsten Wade, Kenneth N Fish, Dominique Arion, Zhao-Lin Cai, Mingshan Xue, William R Stauffer, David A Lewis

Duncan NRI Faculty and Staff Publications

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

Revisiting What Constitutes A Neglected Tropical Disease?, Paul J Brindley, Peter J Hotez, Shaden Kamhawi

Center for Medical Ethics and Health Policy Staff Publications

PLOS Neglected Tropical Diseases (PLOS NTDs) publishes research devoted to pathogenesis and other clinical aspects, epidemiology, prevention, diagnosis, treatment, and control of the neglected tropical diseases (NTDs), as well as work relevant to public health policy. We define NTDs as poverty-promoting infectious diseases that can negatively impact the quality of life in rural areas and poor urban areas of low- and middle-income countries but which can also affect specific communities within high-income countries. The poverty-inducing effects of the NTDs operate by impairing child health and development, pregnancy outcomes for both mother and child, worker productivity, and quality of life. The …

Resilience And Coping: A Qualitative Analysis Of Cognitive And Behavioral Factors In Adults With Osteogenesis Imperfecta, Hannah E Cho, Whitney S Shepherd, Gianna M Colombo, Andrew D Wiese, W Conor Rork, Kristin M Kostick, Dianne Nguyen, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Justin H Qian, Brendan Lee, V Reid Sutton, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The aim of this qualitative study was to investigate resilience among adults with Osteogenesis Imperfecta (OI).

Materials and methods: Semi-structured interviews were conducted with 15 adults with OI. Transcripts were coded and subsequently abstracted, yielding themes specific to resilience and coping. Interview guides covered broad topics including pain challenges specific to OI, mental health issues related to OI, and priorities for future interventions for individuals with OI.

Results: Participants described resilience in the context of OI as the ability to grow from adversity, adapt to challenges resulting from OI-related injuries, and find identities apart from their condition. Psychological coping …

Subendocardial Ischemia: Does Cmd Really Exist?, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress. Second, rare patients indeed have ischemic signs or symptoms due solely to reduced flow attributable to …

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers, Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Methods: Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The Gene …

Multi-Institutional Retrospective Study On Opioid Prescribing Patterns Of Oral And Maxillofacial Surgeons, Steven J D Zbarsky, Issa A Hanna, Je Dong Ryu, Audra Boehm, Simon Young, Gary Yu, Minh Phuong Dong, Minh Chau Joe Tran, Alan Herford, Samuel Young, Chi T Viet

Faculty, Staff and Student Publications

BACKGROUND: The opioid epidemic is a serious crisis in the United States. It has been proposed that opioid prescriptions after dental procedures are a major contributor to opioid use and abuse. The American Dental Association has been working to educate dental care providers about safe opioid prescribing practices. The authors hypothesized that oral and maxillofacial surgeons, following the efforts and publications from the American Dental Association, have been prescribing fewer postoperative opioids.

METHODS: This was a multi-institutional retrospective study with a total of 3,710 patients from Loma Linda University and University of Texas Health Science Center at Houston undergoing ambulatory …

Identifying Mechanisms Of Action For Implementation Strategies Using A Retrospective Implementation Mapping Logic Model Approach, Timothy J Walker, Funlola Are, Natalia I Heredia, Kempson Onadeko, Emma E Saving, Eunyoung Kang, Maria E Fernandez

Faculty, Staff and Student Publications

Understanding causal mechanisms for implementation strategies is a priority for implementation and health promotion research. Logic models are helpful for understanding and illustrating mechanisms through which implementation strategies operate. Little guidance exists for developing logic models for existing implementation strategies. We demonstrate how to use Implementation Mapping (IM) in a retrospective manner to develop an IMap Logic Model for a social-emotional learning program implemented at Boys & Girls Clubs of Greater Houston (BGCGH). To inform logic model development, we used qualitative interview data (from implementers) and conversations with program organizers. To develop the logic model, we specified the most accessible …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Evidence For Alpha-Synuclein Aggregation In Older Individuals With Hyposmia: A Cross-Sectional Study, Kenneth Marek, David S Russell, Luis Concha-Marambio, Seung Ho Choi, Danna Jennings, Michael C Brumm, Christopher S Coffey, Ethan Brown, John Seibyl, Matthew Stern, Claudio Soto, Andrew Siderowf

Faculty, Staff and Student Publications

Background: Synuclein pathology in neurodegenerative diseases, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur.

Methods: Data from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA.

Findings: CSF α-syn SAA was positive in 48% …

Bmj Case Reports, Joanne Romano

TMC Library Newsletter (2015-)

The TMC Library subscription to BMJ Case Reports provides a fellowship benefit that allows affiliated authors to publish in BMJ Case Reports at no cost, once the author submission is approved by the BMJ editorial team.

Check the Scholarly Publishing Support LibGuide for information on other publishers.

Lab Protocols And Experiments To Reduce Your Research Time, Joanne Romano

TMC Library Newsletter (2015-)

Lab Protocols and Experiments to Reduce your Research Time!

Find your favorite protocol or experiment using a keyword search in our library catalog, or by entering the database name into our A to Z list of databases.

A Switch Protein Adapter For Anti-Lilrb4 Car-T Cells, Ryan Huang, Heyu Chen, Jingjing Xie, Qi Lou, Lingxiao Tan, Ningyan Zhang, Zhiqiang An, Samuel John, Cheng Cheng Zhang

The Brown Foundation: Institute of Molecular Medicine

Chimeric antigen receptor-T cell (CAR-T) immunotherapy has shown remarkable results for the treatment of certain hematologic malignancies. A redirection strategy that utilizes clinically relevant CAR-T cells in combination with adapter proteins may be an effective strategy to target other hematologic and solid cancers. We established a fusion antibody-based strategy with flexibility to target multiple tumor types in combination with a novel anti-leukocyte immunoglobulin-like receptor-B 4 (LILRB4) CAR-T cell. Specifically, we engineered switch protein (SwP) adapters containing the LILRB4 extracellular domain fused to either an anti-CD19 or anti-CD20 single-chain variable fragment (scFv). These SwPs were sufficient to stimulate anti-LILRB4 CAR-T cells …