Digital Commons Network^™

Sahrang: Subarachnoid Hemorrhage Recovery And Galantamine: A Pilot Multicenter Randomized Placebo-Controlled Trial, Bosco Seong Kyu Yang, Jude P J Savarraj, Elena Moreno, Kevin E Immanuel, Georgene Hergenroeder, Glenda Torres, Jung Hwan Kim, Sophie Samuel, Claudia Pedroza, James C Grotta, Andrew Barreto, H Alex Choi

Faculty, Staff and Student Publications

Background: Subarachnoid hemorrhage (SAH) causes life-long neurologic dysfunction. Peripheral inflammatory processes as a reaction to brain injury have been shown to worsen outcomes after SAH. Galantamine has been shown to reduce proinflammatory microglial activities and improve synaptic connections. We hypothesize that galantamine treatment after SAH mitigates inflammation-mediated neuronal injury and improve outcomes. We conducted a pilot clinical trial to examine the tolerability and safety of galantamine in patients with SAH.

Methods: This prospective, multicenter, double-masked, randomized, placebo-controlled study contiguously screened and enrolled adult patients presenting with aneurysmal SAH with a Fisher grade of 3 within 72 h of symptom onset. …

Utility Of Serum Matrix Metalloproteinase-7 As A Biomarker In Cholestatic Infants With Congenital Heart Disease, Sindhu Pandurangi, Michael E Kim, Nicolas Noriega, Bradley Conant, Jangdong Seo, Reena Mourya, Pranavkumar Shivakumar, Anna L Peters, Andrew Misfeldt, Meghan Chlebowski

Faculty, Staff and Student Publications

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.

Methods: This is a single-center cross-sectional study including infants < 180 days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test.

Results: A total of 149 patients were included. Patients …

Chemotherapy Alone For Stage Ii-Iva Laryngeal Squamous Cell Carcinoma: A 20-Year Follow-Up, Mateus Trinconi Cunha, Matheus Sewastjanow-Silva, F Christopher Holsinger, Adam S Garden, Adel K El-Naggar, Jeffrey N Myers, Jan Lewin, Ann M Gillenwater, J Jack Lee, Fadlo R Khuri, Eduardo M Diaz, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Current treatment options for nonmetastatic laryngeal squamous cell carcinoma include radiotherapy, chemoradiotherapy, and surgery, which can result in significant morbidity. This study reports the 20-year outcomes of a single-modality chemotherapy as a larynx preservation strategy in patients with stage II-IVa laryngeal squamous cell carcinoma (LSCC).

Methods: In this single-institution, single-arm, prospective clinical trial, 31 patients with stage II-IVa LSCC received three or four cycles of paclitaxel, ifosfamide, and a platinum agent (TIP). Patients with a pathologic complete response (pCR) by biopsy assessment received three additional cycles without local therapy. Patients with a partial response underwent conservation laryngeal surgery (CLS). …

Pancreatic Cancer-Related Diabetes And Type 2 Diabetes Differ In Multiple Aspects Of Glucose Homeostasis, Frederico G S Toledo, Yisheng Li, Fuchenchu Wang, Melena D Bellin, Randall Brand, Kenneth Cusi, William Fisher, Yogish C Kudva, Walter G Park, Zeb I Saeed, Dhiraj Yadav, Robert V Considine, Sarah C Graham, Dana K Andersen, Jose Serrano, Mark O Goodarzi, Phil A Hart

Faculty, Staff and Student Publications

Aims/hypothesis: Pancreatic ductal adenocarcinoma-related diabetes mellitus (PDAC-DM) is a paraneoplastic syndrome with a poorly understood pathophysiology. PDAC-DM is often clinically confused with type 2 diabetes, resulting in delayed cancer detection and poorly individualised hyperglycaemia treatment. We investigated whether these forms of diabetes can be distinguished at the metabolic level.

Methods: Adults with either cancer treatment-naive PDAC-DM (n=28) or type 2 diabetes (n=97), and with diabetes onset within 3 years, underwent mixed-meal tolerance tests to investigate glucose metabolism. Outcomes included insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), beta cell function (oral disposition index), insulin clearance, and postprandial glucagon, glucagon-like peptide-1 …

Decoding Fibrosis In Nonresolvable Covid-19: A Role For Myeloid-Specific Hif1a Deletion, Kemly Philip, Hannah P Thompson, Scott D Collum, Isabella Lefebvre, Bindu Akkanti, Bihong Zhao, Rahat Hussain, Manish Patel, Michael R Blackburn, Tingting W Mills, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

A complication of viral lung infections is the development of pulmonary fibrosis. This phenomenon is most evident in patients with COVID-19, where in its most aggressive form patients developed nonresolvable (NR) COVID-19 requiring lung transplantation. NR-COVID-19 was characterized by the presentation of a fulminant fibrotic lung injury that progressed rapidly, even in patients with limited comorbidities. However, the mechanisms that led to this rapidly progressing form of fibrosis are not fully understood. A common clinical manifestation in the most severe cases of COVID-19 was the presence of "silent" hypoxemia. Thus, we hypothesized that a dysfunctional hypoxic response may result in …

The Role Of Neutrophils In Vasospasm And Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Is It Time For A Sah Clinical Trial Targeting Neutrophils?, William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence …

Normalization Of Temperature Effects For Quality Assurance Of Quantitative Prostate Apparent Diffusion Coefficient Imaging Across Multiple Sites, Ken-Pin Hwang, Joshua Yung, R Jason Stafford, Caroline Chung, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Background: Apparent Diffusion Coefficient (ADC) as measured by diffusion weighted imaging is known to negatively correlate with prostate tumor aggressiveness. Heterogeneity in system and protocol performance causes potential variability in ADC acquired across a large scanner network, prompting a need to evaluate quantitative ADC from a prostate-specific MR diffusion protocol as part of quality assurance (QA). Due to the temperature dependence of ADC, repeatability and reproducibility assessments typically require phantoms to maintain a temperature of 0°C, imposing a considerable burden when assessing large numbers of scanners.

Purpose: To develop a QA procedure at room temperature for assessing the reproducibility of …

Privacy-By-Design: Case Studies In Interactive Record Linkage Using A Hybrid Human-Computer System, Hye-Chung Kum, Eric Ragan, Mahin Ramezani, Gurudev Ilangovan, Theodoros Giannouchos, Qinbo Li, Adam D'Souza, Elmer V Bernstam, Jeffrey R Curtis, Alva O Ferdinand, Cason Schmit

Faculty, Staff and Student Publications

Objective: High-quality patient matching from several sources without a common identifier (ID) requires interactive record linkage (RL) using a hybrid human-computer system. MiNDFIRL (MInimum Necessary Disclosure For Interactive Record Linkage) is a hybrid prototype software system that facilitates maximizing linkage accuracy while minimizing information disclosure. We present and evaluate MiNDFIRL using two real-world case studies.

Materials and methods: Two user studies were conducted linking 10,000 data pairs from EHR data and 18,240 unique patient IDs from patient generated data. After automated RL, manual review was conducted by three teams of four reviewers (12 total) using MiNDFIRL to resolve potential matches …

A Contemporary Guide To An International Aortic Super-Fellowship For Surgical Trainees And Surgeons In The United States, Roberto G. Aru, Adam W. Beck, Stéphan Haulon

Department of Surgery Faculty Papers

Fenestrated and branched technology for endovascular aortic repair of the thoracoabdominal aorta and aortic arch has evolved significantly over the last decade. The spectrum of these devices is largely available outside the United States (US), while patient-specific company manufactured devices are limited to ten sites in the US, with ongoing expanding use of market-approved off-the-shelf devices. The necessary environment for appropriate education to ensure safe dissemination of these technologies is limited, and the current centralization of both device availability and skillsets affects trainee education. In order to refine their endovascular treatment algorithm and planning/implantation skillsets at these multidisciplinary aortic centers, …

A Prognostic Classification System For Extent Of Resection In Idh-Mutant Grade 2 Glioma: An International, Multicentre, Retrospective Cohort Study With External Validation By The Rano Resect Group, Philipp Karschnia, Jacob S Young, Maarten M J Wijnenga, Tommaso Sciortino, Nico Teske, Alba Corell, Arthur Wagner, Gilbert Youssef, Yae Won Park, Levin Häni, Stephanie T Jünger, Antonio Dono, Felix Ehret, Eduardo E Mendoza Mireles, Nicolas Neidert, Francesco Bruno, Chad A Tuchek, Thijs Van Der Vaart, Marco Rossi, Marco Conti Nibali, Lorenzo Gay, Alfred Gramelt, Nitin Tandon, Sung Soo Ahn, Jong Hee Chang, Michael Weller, Arnaud J P E Vincent, Roland Goldbrunner, Daniel P Cahill, Raymond Y Huang, Andreas Raabe, Bernhard Meyer, Juergen Beck, Annette M Molinaro, Susan M Chang, Michael A Vogelbaum, Roberta Rudà, Einar O Vik-Mo, Jorg Dietrich, Yoshua Esquenazi, Stefan J Grau, Patrick Y Wen, Asgeir S Jakola, Oliver Schnell, Lorenzo Bello, Martin J Van Den Bent, Shawn Hervey-Jumper, Mitchel S Berger, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Background: The efficacy of resection in IDH-mutant grade 2 gliomas remain controversial since terminology for the extent of resection has been inconsistently applied across studies. We aimed to establish a standardised classification for the extent of resection and assess the association between supramaximal resection and survival across molecular subtypes.

Methods: In this international, multicentre, retrospective study, patients aged 18 years and older with newly diagnosed grade 2 IDH-mutant glioma were identified from institutional databases across 16 centres in the USA, Europe, and Asia between between Sept 1, 1993, and May 10, 2024. We used Cox proportional hazard regressions to analyse …

Peripheral Blood Gene Expression Profiling And Prognostic Significance For The Course Of Interstitial Lung Disease In Patients With Systemic Sclerosis, Shervin Assassi, Christopher P Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan

Faculty, Staff and Student Publications

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated …

Impact Of Propofol Or Sevoflurane On The Renoprotective Effect Of Remote Ischaemic Preconditioning In Cardiac Surgery: The Hypnorenalrip Randomised Clinical Trial, Alexander Zarbock, Ludwig Maximilian Schöne, John A Kellum, Joachim Gerss, Raphael Weiss, Hendrik Booke, Melanie Meersch

Faculty, Staff and Student Publications

Background: Remote ischaemic preconditioning (RIPC) might reduce acute kidney injury after cardiac surgery. Protective effects appear to be restricted to patients with early and transient increases in two cell cycle arrest markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), in urine. Studies suggest that propofol can attenuate the preconditioning effect on the myocardium. This study investigated whether propofol diminishes the renoprotective effect associated with the early transient increases in TIMP-2 and IGFBP7.

Methods: This was a single-centre, prospective randomised double-blind 2×2 factorial clinical trial of high-risk patients undergoing cardiac surgery. Patients were randomised to receive …

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells For Parkinson's Disease: A Randomized Trial., Mya C Schiess, Jessika Suescun, Juan D Martinez-Lemus, Charles Green, Tia S Thomas, Mohammad Shahnawaz, Emily Tharp, Nikunj B Satani, Jerome G Saltarrelli, Christopher Adams, Marie-Francoise Doursout, Vanessa Thyne, Rula Abuamouneh, Elsa M Rodarte, Sean I Savitz, Timothy M Ellmore

Faculty, Staff and Student Publications

Background: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo-hMSCs) may reduce neuroinflammation and improve motor symptoms.

Objectives: To evaluate the efficacy of repeated intravenous doses of 10 × 106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP).

Methods: In this phase 2, randomized, placebo-controlled trial (November 2020-July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants …

Prospective Trial Of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage Via Lumbar Catheter Extension (Pillar-Xt), Spiros L Blackburn, Marc A Babi, Andrew W Grande, Omar A Choudhri, Erik F Hauck, Christopher P Kellner, Michael C Giordano, Shivanand P Lad, Aaron R Mccabe

Faculty, Staff and Student Publications

Background: There is a growing consensus that blood in the cerebrospinal fluid (CSF) is deleterious to outcomes in patients with aneurysmal subarachnoid hemorrhage. The extracorporeal filtration of subarachnoid hemorrhage via spinal catheter extension study evaluated the safety, tolerability, and filtration curve of blood and its lysis products from hemorrhagic CSF using the Neurapheresis CSF Management System.

Methods: After aneurysm repair, a dual-lumen intrathecal catheter was inserted into the study participant's spinal canal. CSF was extracorporeally filtered for up to 72 h, removing blood products from the lumbar cistern, and reintroducing filtered CSF to the thoracic subarachnoid space. Neurological examinations were …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy B Grossman, Zhen Zhao

Faculty, Staff and Student Publications

Background: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

Patients/materials and methods: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Developing Consensus For A More Provider-Friendly Next-Generation Sequencing Molecular Biomarker Report: A Joint Consensus Recommendation Of The Association For Molecular Pathology And College Of American Pathologists, Jane Gibson, Hanadi El Achi, Dana Altenburger, Noah Brown, Amy S Clark, Joshua Coleman, Rajyasree Emmadi, Amber M Fussell, Meera Hameed, Danielle Jordan, Jennifer Laudadio, Anthony Provenzano, Robyn L Temple-Smolkin, Christopher G Suciu

Faculty, Staff and Student Publications

Despite the increasing availability of next-generation sequencing (NGS) gene panel analysis for cancers, published reports suggest underutilization of testing, citing the shortage of credentialed professionals available to assist with the interpretation of test results among the key barriers. Obtaining a multidisciplinary consensus regarding a shared best practice NGS molecular biomarker reporting section template may facilitate introduction and/or increased testing for institutions that adopt similar report structures by improving report effectiveness and efficiency for both health care providers and laboratory professionals, leading to improved patient care. To address this challenge, the Association for Molecular Pathology convened a multidisciplinary collaborative expert working …

Early Identification For Spasticity Patient Referral Needs: An Inter-Rater Reliability Study Of The Post-Stroke Spasticity Referral Tool, Jorg Wissel, Atul Patel, Ganesh Bavikatte, Xiao Li, Sophie L Musson, Elizabeth Torres, Nabilah Alibhai, Tiziana Musacchio, Gerard E Francisco

Faculty, Staff and Student Publications

Background: The post-stroke spasticity (PSS) Referral Tool was developed to assist health care professionals in the early identification of patient referral needs. An inter-rater reliability (IRR) study using videos of patients with different stages of or without predictors of PSS was performed to validate its utility in clinical practice.

Research design and methods: This prospective study had 3 parts: patient video production (Part A); expert panel classification of patient videos into PSS Referral Tool categories (Part B; Urgent Referral [UR; red], Routine Referral [RR; yellow], Periodic Monitoring [PM; green]), and an IRR analysis from global clinician raters (Part C). IRR …

Real-World Disease Burden And Health Care Resource Utilization For Patients With Barth Syndrome, Lindsay Marjoram, Yonglin Huang, Mary Kay Koenig, Bruce H Cohen, Eric Anderson

Faculty, Staff and Student Publications

Background: Barth syndrome (BTHS) is an ultra-rare, X-linked genetic disorder for which there is limited economic data. Because compiling such data that target rare indications is difficult, we assessed real-world data to increase understanding of the cost of BTHS based on disease burden and health care resource utilization (HCRU).

Methods: A search of the published medical literature identified individual case studies and registry data used to assess the burden of disease and potential costs associated with BTHS, including the potential ability of developing treatments to positively impact those costs. In addition, a claims database analysis was conducted to assess HCRU …

Whipple Disease Initial Presentation As Supraclavicular Lymphadenopathy In A Patient With Rheumatoid Arthritis: A Diagnostic Challenge, Sara E Amin, Swati Gite, Audrey Wanger, Violeta Chavez, Jacob Armstrong, Beenu Thakral, Patricia Navarro, Jennifer Makhoul, Amer Wahed, Navneet Narula, Karan Saluja

Faculty, Staff and Student Publications

Whipple disease is a rare systemic disease caused by Tropheryma whipplei. It can present with a wide range of nonspecific symptoms that might overlap with underlying medical conditions, posing a diagnostic challenge. We present a 61-year-old man with a past medical history of rheumatoid arthritis and chronic inflammatory demyelinating polyneuropathy, who presented with persistent leukocytosis and supraclavicular lymphadenopathy. A positron emission tomography scan revealed hypermetabolic activity in the supraclavicular, abdominal, and pelvic lymph nodes along with a myocardial hypermetabolic lesion, concerning a lymphoproliferative disorder versus sarcoidosis. A supraclavicular lymph node excisional biopsy revealed complete architectural effacement by a diffuse foamy …

Nocturnal Oxygen Therapy For Central Sleep Apnea In Patients With Heart Failure: A Multisite, Double-Blind, Sham-Controlled Randomized Clinical Trial (Loft-Hf), Susan Redline, Dongdong Li, Shahrokh Javaheri, Sanjay R Patel, Sairam Parthasarathy, James C Fang, Lee K Brown, Mark Dunlap, M Safwan Badr, Neomi Shah, Luqi Chi, Ruckshanda Majid, Mihaela Teodorescu, Garrick Stewart, Eileen Hsich, Tamar Polonsky, Justin Vader, Maryl R Johnson, Dennis Auckley, Henry Klar Yaggi, Andrew Kao, Ali Azarbarzin, Raichel Alex, Michael Rueschman, Lisa Wolfe, Daniel J Gottlieb, Scott A Sands, Phyllis C Zee, Reena Mehra, Babak Mokhlesi, Rami Khayat, Eldrin F Lewis, William T Abraham, Rui Wang

Faculty, Staff and Student Publications

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF but has not been rigorously studied. Objectives: To compare NOT with sham NOT (control) in heart failure (HF) patients receiving guideline-based HF therapy on the composite outcome of first occurrence of either mortality due to any cause, a lifesaving cardiovascular intervention, or an unplanned hospitalization for worsening HF, together with other secondary outcomes.

Methods: A multisite, double-blind, sham-controlled randomized clinical trial was conducted …

Revisiting Soluble Guanylate Cyclase Pharmacology: Additive Potential Of Stimulators And Activators, Alexandra Petraina, Mahmoud H Elbatreek, Christopher T Neullens, Theodora Saridaki, Vu Thao-Vi Dao, Rebecca D Szepanowski, Emil Martin, Wolfgang Sippl, Ana I Casas, Harald H H W Schmidt

Faculty, Staff and Student Publications

Nitric oxide (NO) is a key gasotransmitter that binds to soluble guanylate cyclase (sGC), thereby stimulating cGMP production. Under disease conditions, reactive oxygen species disrupt this signaling by either: (1) scavenging NO, or (2) promoting heme-free, NO-insensitive apo-sGC due to impaired heme incorporation or oxidative damage. To counteract these conditions, two pharmacological approaches have emerged: sGC stimulators, which allosterically enhance sGC sensitivity to low NO levels; and sGC activators, which directly activate apo-sGC (heme-free sGC) by binding to its empty heme pocket, inducing a conformation that mimics NO-bound sGC. Thus, sGC stimulators are thought to target only sGC. Instead, we …

Fam13a Polymorphism Is Associated With A Usual Interstitial Pneumonia Pattern In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Elana J Bernstein, Francesco Boin, Brett Elicker, Yiming Luo, Yawen Ren, Meng Zhang, John Varga, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and …

Utilizing Functional Neuroimaging To Study Early Language Development, Halie A Olson, Trevor K M Day, Kelly J Hiersche, Brittany L Manning, Holly Bradley, Soujin Choi, Gavkhar Abdurokhmonova, Sarah A Mccormick, Amy L Conrad, Dustin Scheinost, Kelly A Vaughn

Faculty, Staff and Student Publications

Language develops rapidly over the infant and toddler period and has been a key area of research within the field of developmental cognitive neuroscience. Understanding the neural basis of early language development may help us predict delays or disorders, recommend early interventions, and provide a deeper mechanistic understanding of how the brain supports language learning. While the ontogeny of many cognitive functions can be studied in animal models, language development can only be studied in human children. Thus, functional neuroimaging is critical for uncovering the neural basis of language in early development. The purpose of this review is to take …

Social Media Listening Study To Understand The Journey And Unmet Needs Of Patients Living With Post-Stroke Spasticity, Stefano Carda, Jörg Wissel, Damon Hoad, Gerard E Francisco, Monica Verduzco-Gutierrez, Daniela Gallardo, Matteo Vacchelli, Jorge Jacinto

Faculty, Staff and Student Publications

Purpose: Stroke survivors may develop spasticity (post-stroke spasticity [PSS]) that can challenge activity and participation. Recognising the needs and expectations of people with PSS is crucial for enhancing care. This study is the first to employ social media listening to explore the experiences, unmet needs, and quality of life (QoL) of people with PSS.

Materials and methods: A subset of 417 patient-centric PSS-related posts published on major social media platforms was identified for analysis from 31 600 retrieved.

Results: Posts mainly discussed patient journey (centred around treatment options and management techniques), the impact of PSS on QoL, and patient interactions …

Navigating Health Literacy: Comparison Of Assessment Tools In A Surgical Safety-Net Population, Mokunfayo O Fajemisin, Stephanie Martinez Ugarte, Gabrielle E Hatton, Jackson G Burns, Lillian S Kao, Krislynn M Mueck

Faculty, Staff and Student Publications

Health literacy as measured by three validated assessment tools.

Breakwater Phase Iii: Results For Encorafenib And Cetuximab Plus Mfolfox6 In First-Line Braf V600e-Mutant Metastatic Colorectal Cancer, Scott Kopetz, Josep Tabernero, Elena Élez

Faculty, Staff and Student Publications

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E – mutant metastatic colorectal cancer. The study showed significantly improved objective response rate by blinded independent central review, and significantly longer progression-free survival by blinded independent central review and overall survival in patients treated with first-line encorafenib and cetuximab plus mFOLFOX6 compared with chemotherapy with or without bevacizumab. The safety profiles were consistent with those known for each agent. These results led to the approval of encorafenib and cetuximab plus mFOLFOX6 for the …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Knowledge Mapping And Visualized Analysis Of Research Progress In Onconephrology: A Bibliometric Analysis, Yiwei Wang, Shuling Fan, Wei Wang

Faculty, Staff and Student Publications

Objectives: Onconephrology is an expanding subspecialty focused on the management of cancer patients with renal injury. This study used a comprehensive bibliometric analysis to emphasize the need for cooperation between oncologists and nephrologists, exploring current trends and future research areas in onconephrology.

Methods: Relevant literature on onconephrology published between 1 January 2000 and 27 April 2024 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection, followed by manual screening. Bibliometric analyses were performed using CiteSpace, VOSviewer, and Bibliometrix software.

Results: A total of 1,853 publications, including 1,647 articles and 206 reviews, by 11,606 authors …

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …