Medical Specialties Commons^™

Self-Powered Rapid Antigen-Specific T-Cell Response Assay For Mycobacterium Tuberculosis Infections, Bo Ning, Sutapa Chandra, Yongchun Pan, Riti Sharan, Ngan Ha, Sanjay Singh, Alexandra Portillo Varela, Lin Li, Qingli Wu, Alexander Kay, Gugu P Maphalala, Clement Adu-Gyamfi, Santiago Carrero Longlax, Anna M Mandalakas, Smriti Mehra, Christopher J Lyon, Edward A Graviss, Andrew R Dinardo, Tony Hu

Faculty, Staff and Students Publications

Interferon-gamma release assays (IGRAs) that evaluate an individual’s T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater …

Impact Of Optimal Medical Therapy In Heart Failure Certification For Hospitalists On Guideline-Directed Medical Therapy Utilization, Farhan Ishaq, Duc T Nguyen, Edward A Graviss, Ebun Ebunlomo, Arvind Bhimaraj, Nadia Fida

Faculty, Staff and Students Publications

Background: Significant gaps in guideline-directed medical therapy (GDMT) for heart failure (HF) stem from shortages of cardiologists and advanced HF providers, as well as a lack of optimal HF management knowledge among hospitalists. This study compared the impact of optimal medical therapy in HF (OMT-HF) certification on GDMT implementation and patient outcomes between an intervention group (IG) of hospitalists and a standard-of-care comparison group (SOC-CG).

Aim: To evaluate if OMT-HF has a difference in GDMT and patients in outcomes between IG and SOC-CG.

Methods: This study was implemented from November 2022 to May 2023. Hospitalized cardiology patients with HF and …

Secondary Youth-Level Mechanisms Of Change In Parent Training For Anxious Youth, Jacey L Anderberg, Kelly Barry, Blake M Upshaw, Katie H Mangen, Samuel D Spencer, Andrew G Guzick, Daphne M Ayton, Amanda D Palo, Abigail E Candelari, Eric A Storch

Faculty, Staff and Students Publications

Background: Parent-focused treatments are a promising approach for addressing youth anxiety outside of traditional therapist-delivered modalities. Supportive Parenting for Anxious Childhood Emotions (SPACE) has preliminarily demonstrated efficacy for reducing family accommodation (FA), a key treatment outcome for youth anxiety.

Objective: Since the mechanisms of SPACE remain relatively understudied, we examined youth-reported distress tolerance (DT), anxiety sensitivity (AS), and negative automatic thoughts as candidate mechanisms of SPACE using data from a previously conducted clinical trial.

Methods: In a sample of N = 68 youth (M age = 10.2; 52% male; 62% White), we examined: (a) associations among candidate mechanisms and …

Author Correction: Beta Activity In Human Anterior Cingulate Cortex Mediates Reward Biases, Jiayang Xiao, Joshua A Adkinson, John Myers, Anusha B Allawala, Raissa K Mathura, Victoria Pirtle, Ricardo Najera, Nicole R Provenza, Eleonora Bartoli, Andrew J Watrous, Denise Oswalt, Ron Gadot, Adrish Anand, Ben Shofty, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Xaq Pitkow, Kelly R Bijanki, Benjamin Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

Mapping Mave Data For Use In Human Genomics Applications, Jeremy A Arbesfeld, Estelle Y Da, James S Stevenson, Kori Kuzma, Anika Paul, Tierra Farris, Benjamin J Capodanno, Sally B Grindstaff, Kevin Riehle, Nuno Saraiva-Agostinho, Jordan F Safer, Jonathan Casper, Maximilian Haeussler, Aleksandar Milosavljevic, Julia Foreman, Helen V Firth, Sarah E Hunt, Sumaiya Iqbal, Melissa S Cline, Alan F Rubin, Alex H Wagner

Faculty, Staff and Students Publications

Background: Experimental data from functional assays have a critical role in interpreting the impact of genetic variants. Assay data must be unambiguously mapped to a reference genome to make it accessible, but it is often reported relative to assay-specific sequences, complicating downstream use and integration of variant data across resources. To make multiplexed assays of variant effect (MAVE) data more broadly available to the research and clinical communities, the Atlas of Variant Effects Alliance mapped MAVE data from the MaveDB community database to human reference sequences, creating an extensive set of machine-readable homology mappings that are incorporated into widely used …

Multimodal Imaging Directs Decision Making In Intraseptal L-Aaoca, Joseph Burns, Lindsay F Eilers, Stephen J Dolgner, Edward J Hickey, Silvana Molossi

Faculty, Staff and Students Publications

Background: Congenital coronary artery abnormalities represent an uncommon class of congenital heart disease with an associated risk of sudden cardiac death. There is a paucity of data for the evaluation and management of affected patients with an intraseptal course.

Case summary: A 27-year-old woman was found to have a single coronary trunk arising from the right sinus with a 2.7 cm intraseptal course of the left main coronary artery. She underwent stress cardiac magnetic resonance and catheterization, to assess for inducible ischemia before surgical repair with transconal unroofing. Her recovery was uneventful, and she remains free of symptoms.

Discussion: Management …

Trends In The Incidence Of Ovarian Cancer Among Premenopausal And Postmenopausal Women In The United States, 2001 To 2021, Victor Adekanmbi, Abbey B Berenson, Batul Shakir, Christine D Hsu, Thao N Hoang, Itunu O Sokale, Tolulope T Sajobi, Fangjian Guo

Faculty, Staff and Students Publications

Background: Ovarian cancer remains the deadliest and leading cause of gynecological cancer-associated mortality in the US. The aim of this study was to characterize the trends in the incidence of ovarian cancer between premenopausal and postmenopausal women to inform future targeted interventions.

Methods: This population-based cross-sectional study analyzed data from the US Cancer Statistics (USCS) database, which covered the whole of the US population between 2001 and 2021. Joinpoint regression was used to compute the average annual percentage change (APC) with 95% confidence interval (CI) and age-standardized incidence rates per 1,000,000 population.

Results: The results showed that the IR of …

Differences In Arterial Events In Vascular Ehlers-Danlos, Loeys-Dietz, And Marfan Syndrome, Ernesto Calderon-Martinez, Walter V Velasco, Dongchuan Guo, Ellen H Hostetler, Zhang Xun, Sara Stephens, Sherene Shalhub, Julie De Backer, Maral Ouzounian, Scott A Lemaire, Olivier Milleron, Nadine Hanna, Pauline Arnaud, Maria Tchitchinadze, Siddharth K Prakash, Mark Lindsay, Julien Marcadier, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Catherine Boileau, Alan C Braverman, Guillaume Jondeau, Dianna M Milewicz

Faculty, Staff and Students Publications

Background: Heritable thoracic aortic disease is due to altered genes that confer a highly penetrant risk for thoracic aortic aneurysm and dissection, and a subset of these genes also cause aneurysms and dissections of peripheral arteries beyond the aorta. Arterial aneurysms, dissections, and ruptures are associated with pathogenic variants (PVs) in COL3A1, which is responsible for vascular Ehlers-Danlos syndrome, but arterial events are rare in Marfan syndrome due to PVs in FBN1, and poorly characterized in Loeys-Dietz syndrome due to PVs in the transforming growth factor (TGF)-β pathway genes.

Objectives: This study sought to define the relative risk of arterial …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Primary Mouse Choroidal Endothelial Cell Culture, Qiuhua Yang, Yongfeng Cai, Qian Ma, Yuqing Huo

Faculty, Staff and Students Publications

The study of choroidal endothelial cells is essential for understanding the pathological mechanisms underlying choroidal neovascularization and other vision-threatening disorders. Traditional methods for isolating and culturing primary endothelial cells often yield mixed populations or require specialized equipment, limiting their widespread use. Here, we present a straightforward protocol for isolating and culturing primary mouse choroidal endothelial cells. This protocol involves enzymatic digestion of choroidal tissue, magnetic-activated cell sorting (MACS) to enrich CD31+ endothelial cells, and optimized culture conditions to promote cell proliferation and maintain endothelial phenotype. The protocol is strategic, reproducible, and requires minimal specialized equipment, making it accessible for researchers …

Risk Factors For Serious Bacterial Infections Among Young Infants With Hypothermia: Protocol For A Multicenter, Retrospective Case-Control Study, Sriram Ramgopal, Paul Aronson, Douglas Lorenz, Alexander Joseph Rogers, Andrea Tania Cruz

Faculty, Staff and Students Publications

Background: Hypothermia in young infants presenting to the emergency department (ED) may indicate a serious bacterial infection (SBI) such as a urinary tract infection, bacteremia, or bacterial meningitis. Improved understanding of the epidemiology of SBI in infants with hypothermia and the development of prediction models can help avoid unnecessary invasive procedures and antimicrobial exposure.

Objective: The aim of the study is to (1) describe the epidemiology of SBI and herpes simplex virus (HSV) among infants with hypothermia, (2) assess the role of biomarkers in predicting SBI, and (3) derive and internally validate a multivariable predictive model for SBI among infants …

Oncolytic Adeno-Immunotherapy Improves Allogeneic Adoptive Her2car-Nk Function Against Pancreatic Ductal Adenocarcinoma, Greyson Biegert, Amanda Rosewell Shaw, Daisuke Morita, Caroline Porter, Ryu Matsumoto, Lisa Jatta, Noah Crooks, Mae Woods, Qizhi Cathy Yao, Robin Parihar, Masataka Suzuki

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to conventional treatments and immunotherapy. We previously developed a binary oncolytic/helper-dependent adenovirus system (CAdTrio) that facilitated oncolysis and expressed the immunomodulatory molecule interleukin-12 and a programmed death ligand 1 (PD-L1) blocking mini-antibody. Given that CAdTrio enhanced endogenous natural killer (NK) cell anti-tumor activity in humanized mice bearing PDAC tumors and that NK cells can be adoptively transferred to patients safely in the allogeneic setting, we hypothesized that a combination of CAdTrio and allogeneic NK cells expressing a HER2-specific chimeric antigen receptor (HER2.CAR-NK) would be an effective, entirely “off-the-shelf” treatment against …

Integrating Endocannabinoid Signaling, Cck Interneurons, And Hippocampal Circuit Dynamics In Behaving Animals, Shreya Malhotra, Florian Donneger, Jordan S Farrell, Barna Dudok, Attila Losonczy, Ivan Soltesz

Faculty, Staff and Students Publications

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in …

Treatment Outcomes Of Successful M1 Versus M2 Thrombectomy For Low-Aspects Stroke Patients, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Amir Shaban, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Brian Howard, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Ramesh Grandhi, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Ergun Daglioglu, Richard Williamson, Pedro Navia, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Background

The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear.

Methods

This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders.

Results

173 patients with M1 or M2 occlusions and low ASPECTS (< 6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH.

Conclusions

Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.

Proteogenomic Analysis Of The Calgb 40601 (Alliance) Her2+ Breast Cancer Neoadjuvant Trial Reveals Resistance Biomarkers, Eric J Jaehnig, Aranzazu Fernandez-Martinez, Tanmayi D Vashist, Matthew V Holt, Laterrica Williams, Jonathan T Lei, Chang In Moon, Beom-Jun Kim, Yongchao Dou, Haoquan Zhao, Viktoriya Korchina, Richard A Gibbs, Donna Marie Muzny, Harshavardhan Doddapaneni, Charles M Perou, Lisa A Carey, Ana I Robles, Terry Hyslop, Yujia Wen, Linda Mccart, Azra Krek, Francesca Petralia, George Miles, Shyam M Kavuri, Michael A Gillette, D R Mani, Steven A Carr, Bing Zhang, Matthew J Ellis, Shankha Satpathy, Meenakshi Anurag

Faculty, Staff and Students Publications

Proteogenomic analysis is applied to samples from the CALGB 40601 (Alliance) randomized neoadjuvant trial of trastuzumab, lapatinib, or the combination to identify biomarkers associated with pathological response status. Absence of ERBB2 gene amplification and human epidermal growth factor receptor 2 (HER2) protein overexpression by proteogenomics is associated with non-pathological compete response (pCR) (p < 0.05), highlighting potential false positives from standard diagnostics. Pathway analysis in proteogenomics-confirmed HER2+ samples identifies elevated epithelial-mesenchymal transition (EMT) and WNT-β-catenin signaling in non-pCR cases before treatment. Twenty-four pCR-associated proteins reproduce in a second proteomic dataset, and four (GPRC5A, TPBG, SP140L, and NEU1) are significant in a third. A meta-analysis of ten diverse neoadjuvant anti-HER2 treatment regimens from four independent studies confirms that non-pCR cases express higher levels of mRNA for G protein-coupled receptor class C group 5 member A (GPRC5A, p = 0.0002) and trophoblast glycoprotein (TPBG, p = 0.00008). Thus, proteogenomic analysis identifies negative biomarkers for pCR and alternative plasma membrane targets for treatment-resistant HER2+ breast cancer.

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

Prognosis After Switching To E-Cigarettes: Methods Raise Doubt About Conclusion, Harold J Farber

Faculty, Staff and Students Publications

No abstract provided.

Performance Of A Novel Stool Quantitative Polymerase Chain Reaction Assay For Pediatric Tuberculosis Detection In Sub-Saharan Africa, Anca Vasiliu, Lucia Carratala-Castro, Abigail Seeger, Joanna Ehrlich, Babongile Nkala, Tara Ness, Miguel Mario Cumbe, Durbbin Mulengwa, Shilzia Munguambe, Bariki Mtafya, Edson Mambuque, Nosisa Shiba, Sozinho Acacio, Lilian Komba, Clement Gascua Adu-Gyamfi, H Lester Kirchner, Christoph Lange, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Alexander Kay

Faculty, Staff and Students Publications

Background: Children have paucibacillary tuberculosis and cannot provide expectorated sputum. Invasive specimen collection, by gastric aspiration or sputum induction, has a low diagnostic yield. In this study, we aimed to evaluate the diagnostic performance and additive yield of a novel stool-based assay in children diagnosed with tuberculosis in sub-Saharan Africa.

Methods: We conducted a prospective case-control study from October 2020 to June 2023 in Eswatini, Mozambique, and Tanzania. Children under 15 years newly diagnosed with tuberculosis completed clinical examination, chest radiography, culture, sputum Xpert Ultra, stool Xpert Ultra, and stool-based quantitative polymerase chain reaction (stool qPCR) assessment. Stool qPCR sensitivity …

Early Results With Embotrap Iii Stent Retriever: A Multicenter Us Experience, Georgios S Sioutas, Alex N Hoang, Fadi Al Saiegh, Oz Haim, Sanjana Salwi, Avi A Gajjar, Mohamed M Salem, Peter Kan, Omar Tanweer, Justin R Mascitelli, Brian T Jankowitz, Jan-Karl Burkhardt, Visish M Srinivasan

Faculty, Staff and Students Publications

Background

Mechanical thrombectomy with stent retrievers has become a standard treatment for acute ischemic stroke due to large vessel occlusion. Here we present a multicenter US experience using the EmboTrap III stent retriever, the latest iteration within its class.

Methods

We retrospectively reviewed patients with acute ischemic stroke treated with the EmboTrap III device at 4 US centers. We recorded baseline demographics, clinical characteristics, and procedural details. Outcomes included first-pass effect (FPE), modified FPE (mFPE), final mTICI scores, 90-day functional outcomes, and complications.

Results

A total of 92 patients were included, median age of 72 years, and 56.5% were women. …

Asymmetric Cingulum Bundle Connectivity Is Modulated By Paracingulate Sulcus Morphology, Isabel A Danstrom, Joshua A Adkinson, Meghan E Robinson, Lu Lin, Atul Maheshwari, Ben Shofty, Garrett Banks, Mohammed Hasen, Sameer A Sheth, Alica M Goldman, Eleonora Bartoli, Sarah R Heilbronner, Kelly R Bijanki

Faculty, Staff and Students Publications

The cingulum bundle (CB) is a group of axons supporting connectivity among several functional brain networks relevant in healthy and diseased states. The paracingulate sulcus (PCS) is present in at least one cerebral hemisphere across 70% of the population. PCS presence versus absence is linked to differences in structure and function of the anterior cingulate cortex, though the influence of PCS on the white matter of the CB remains unknown. The objective of this work was to define the CB electrographic connectivity profile and determine the impact of PCS morphology on CB engagement. Single-pulse electrical stimulation in combination with stereo-electroencephalography …

Integrating Explainable Machine Learning And Transcriptomics Data Reveals Cell-Type Specific Immune Signatures Underlying Macular Degeneration, Khang Ma, Hosei Nakajima, Nipa Basak, Arko Barman, Rinki Ratnapriya

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70–0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where …

Preoperative Dialysis Dose And Postoperative Outcomes In Patients Receiving Maintenance Hemodialysis, Vikram Fielding-Singh, Matthew W Vanneman, Arden M Morris, Wolfgang C Winkelmayer, Louise Y Sun, Pavel S Roshanov, Maria Montez-Rath, Glenn M Chertow, Eugene Lin

Faculty, Staff and Students Publications

Background: Little is known about preoperative hemodialysis dosing for patients with end-stage kidney disease. We assessed whether changes in preoperative hemodialysis dose (compared to and controlling for baseline dose) are associated with postoperative mortality in patients receiving maintenance hemodialysis.

Methods: We identified fee-for-service Medicare beneficiaries receiving hemodialysis for end-stage kidney disease who underwent surgical procedures between January 1, 2011, and November 30, 2020. Follow-up ended December 31, 2020. The primary exposure was preoperative change in Kt/Vurea, defined as the difference between the Kt/Vurea in the hemodialysis session proximal to the procedure and the mean Kt/Vurea for the preceding 180 days. …

A Family Navigator Improves Post-Discharge Treatment Adherence Among Adolescents With Anorexia Nervosa: A Pilot Study, Elizabeth V Franklin, Margaret Mathias, Duc T Nguyen, Albert C Hergenroeder, Constance M Wiemann

Faculty, Staff and Students Publications

Background: Adolescent patients with Anorexia Nervosa (AN) and Atypical Anorexia Nervosa (AAN) admitted to an inpatient medical unit are at risk of relapse if they do not receive follow up treatment. Yet treatment adherence following discharge remains poor. One possible reason for poor treatment adherence is insufficient support for parents. This pilot study explored the preliminary impact of a novel family navigator (FN) intervention on adolescent patient treatment adherence following inpatient care.

Methods: This was a pilot prospective study with a retrospective control cohort. Twenty-three adolescent patients with AN or AAN discharging from an Adolescent Medicine inpatient medical unit whose …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory And Stool Samples With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Bada Yang, Hayley Poore, Alia Razid, Brittney Sweetser, Mathias Weis Damkjær, Alexander W Kay, Johanna Åhsberg, Ruvandhi R Nathavitharana, Ian Schiller, Nandini Dendukuri, Andreas Lundh, Maunank Shah, Stephanie Bjerrum, Devan Jaganath

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular assays widely used to diagnose tuberculosis disease in children. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended for use amongst children with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM separately in children, but in clinical practice the tests may be used concurrently, i.e. in 'parallel'.

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory and stool specimens in children, and with LF-LAM on urine amongst children with HIV, versus each assay alone for detecting pulmonary tuberculosis disease.

Search …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests And Lateral Flow Urine Lipoarabinomannan Assays To Detect Tuberculosis Disease In Adults And Adolescents Living With Hiv, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Laura Olbrich, Mathias Weis Damkjær, Ruvandhi R Nathavitharana, Tobias Broger, Ioana Diana Olaru, Brittney Sweetser, Hayley Poore, Alia Razid, Alexander W Kay, Claudia M Denkinger, Ian Schiller, Nandini Dendukuri, Devan Jaganath, Andreas Lundh, Maunank Shah

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular World Health Organization (WHO)-recommended rapid diagnostic tests (also known as mWRDs) widely used to diagnose tuberculosis disease. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended by the WHO to assist in diagnosing tuberculosis disease amongst people with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM used in isolation for the detection of tuberculosis, but in clinical practice the tests may be used in parallel (i.e. LC-aNAAT in combination with LF-LAM).

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory …

A Forward Genetic Screen Identifies Potassium Channel Essentiality In Shh Medulloblastoma Maintenance, Jerry J Fan, Anders W Erickson, Julia Carrillo-Garcia, Xin Wang, Patryk Skowron, Xian Wang, Xin Chen, Guanqiao Shan, Wenkun Dou, Shahrzad Bahrampour, Yi Xiong, Weifan Dong, Namal Abeysundara, Michelle A Francisco, Ronwell J Pusong, Wei Wang, Miranda Li, Elliot Ying, Raúl A Suárez, Hamza Farooq, Borja L Holgado, Xiaochong Wu, Craig Daniels, Adam J Dupuy, Juan Cadiñanos, Allan Bradley, Anindya Bagchi, Branden S Moriarity, David A Largaespada, A Sorana Morrissy, Vijay Ramaswamy, Stephen C Mack, Livia Garzia, Peter B Dirks, Xuejun Li, Siyi Wanggou, Sean Egan, Yu Sun, Michael D Taylor, Xi Huang

Faculty, Staff and Students Publications

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo, and applied this to SHH medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver. KCNB2 governs cell volume of MB-propagating cells, with KCNB2 depletion causing osmotic swelling, decreased plasma membrane tension, and elevated endocytic internalization of EGFR, thereby mitigating proliferation of MB-propagating cells to ultimately impair MB growth. …

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

Simple And Complex Phonic Tics In Tourette Syndrome, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Tourette syndrome (TS) is the most common cause of tics. Tics are classified as motor and phonic tics. The latter (previously also referred to as “vocal tics”) are manifested by simple sounds (simple phonic tics) or complex, often semantically meaningful utterances (complex phonic tics). Methods: We compared the clinical and demographic features of consecutive patients with TS who exhibited simple and complex phonic tics. Results: There were 149 patients, 117 (78.5%) of whom were males; the mean age at evaluation was 19.61 ± 12.97 years. In total, 35 (23.5%) of these manifested complex phonic tics, and 26 (17.4%) had verbalizations. …

Fluorescence-Guided Ureteral Identification In Robotic Surgery For Advanced Endometriosis: A Comparison Of Junior Versus Senior Surgeons, Linda A Alpuing Radilla, Qiannan Yang, Daniel Y Lovell, Tamisa Koythong, Brooke Thigpen, Luis E Delgadillo Chabolla, Qianqing Wang, Xiaoming Guan

Faculty, Staff and Students Publications

Identifying the ureters in patients with advanced endometriosis and severe pelvic adhesive disease can be challenging. Adhesiolysis along the deformed pelvic sidewall may increase the risk of prolonged operative time and incidental ureteral injury. This study aimed to evaluate the safety and surgical outcomes of using Indocyanine Green (ICG) under near-infrared fluorescence for intraoperative ureteral localization and preservation during robot-assisted laparoscopic surgery (RALS) for advanced endometriosis, comparing procedures performed by two junior surgeons to those performed by one senior surgeon. This was a retrospective observational case series conducted by three minimally invasive gynecologic surgeons (X.G., T.K., B.T.) at a single …

Variants In Bsn, Encoding The Presynaptic Protein Bassoon, Result In A Distinct Neurodevelopmental Disorder With A Broad Phenotypic Range, Stacy G Guzman, Sarah M Ruggiero, Shiva Ganesan, Colin A Ellis, Alicia G Harrison, Katie R Sullivan, Zornitza Stark, Natasha J Brown, Sajel L Kana, Anabelle Tuttle, Jair Tenorio, Pablo Lapunzina, Julián Nevado, Marie T Mcdonald, Courtney Jensen, Patricia G Wheeler, Lila Stange, Jennifer Morrison, Boris Keren, Solveig Heide, Meg W Keating, Kameryn M Butler, Mike A Lyons, Shailly Jain, Mehdi Yeganeh, Michelle L Thompson, Molly Schroeder, Hoanh Nguyen, Jorge Granadillo, Kari M Johnston, Chaya N Murali, Katie Bosanko, T Andrew Burrow, Chop Birth Defects Biorepository, Penn Medicine Biobank, Syreeta Morgan, Deborah J Watson, Hakon Hakonarson, Ingo Helbig

Faculty, Staff and Students Publications

Disease-causing variants in synaptic function genes are a common cause of neurodevelopmental disorders (NDDs) and epilepsy. Here, we describe 14 individuals with de novo disruptive variants in BSN, which encodes the presynaptic protein Bassoon. To expand the phenotypic spectrum, we identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks. Clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29, 45%), febrile seizures (7/29, 25%), generalized tonic-clonic seizures (5/29, 17%), and focal-onset seizures (3/29, 10%). Behavioral phenotypes were present in almost half of all individuals (14/29, 48%), …