Digital Commons Network^™

Localization, Tissue Biology, And T Cell State — Implications For Cancer Immunotherapy, Jason M Schenkel, Kristen E Pauken

Faculty, Staff and Student Publications

Tissue localization is a critical determinant of T cell immunity. CD8+ T cells are contact-dependent killers, which requires them to physically be within the tissue of interest to kill peptide-MHC class I-bearing target cells. Following their migration and extravasation into tissues, T cells receive many extrinsic cues from the local microenvironment, and these signals shape T cell differentiation, fate and function. Because major organ systems are variable in their functions and compositions, they apply disparate pressures on T cells to adapt to the local microenvironment. Additional complexity arises in the context of malignant lesions (either primary or metastatic), and this …

Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Anju Sharma, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness …

Clinico-Genomic Profiling Of Conventional And Dedifferentiated Chondrosarcomas Reveals Tp53 Mutation To Be Associated With Worse Outcomes, Ryan A Denu, Richard K Yang, Alexander J Lazar, Shalin S Patel, Valerae O Lewis, J Andrew Livingston, Kenna R Shaw, Ravin Ratan, Maria A Zarzour, Justin Bird, Shaan Raza, Kadir C Akdemir, Jordi Rodon Ahnert, Vivek Subbiah, Shreyaskumar Patel, Anthony P Conley

Faculty, Staff and Student Publications

PURPOSE: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.

EXPERIMENTAL DESIGN: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas.

RESULTS: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising …

Multi-Omics Analysis In Developmental Bone Biology, Yuki Matsushita, Azumi Noguchi, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

Single-cell omics and multi-omics have revolutionized our understanding of molecular and cellular biological processes at a single-cell level. In bone biology, the combination of single-cell RNA-sequencing analyses and in vivo lineage-tracing approaches has successfully identified multi-cellular diversity and dynamics of skeletal cells. This established a new concept that bone growth and regeneration are regulated by concerted actions of multiple types of skeletal stem cells, which reside in spatiotemporally distinct niches. One important subtype is endosteal stem cells that are particularly abundant in young bone marrow. The discovery of this new skeletal stem cell type has been facilitated by single-cell multi-omics, …

Guidelines For Prehospital Management Of Traumatic Brain Injury 3rd Edition: Executive Summary, Halinder S Mangat

Faculty, Staff and Student Publications

Prehospital care markedly influences outcome from traumatic brain injury, yet it remains highly variable. The Brain Trauma Foundation's guidelines informing prehospital care, first published in 2002, have sought to identify and disseminate best practices. Many of its recommendations relate to the management of airway, breathing and circulation, and infrastructure for this care. Compliance with the second edition of these guidelines has been associated with significantly improved survival. A working group developed evidence-based recommendations informing assessment, treatment, and transport decision-making relevant to the prehospital care of brain injured patients. A literature search spanning May 2005 to January 2022 supplemented data contained …

Both/And: Mixed Methods Analysis Of Network Composition, Communication Patterns, And Socio-Economic Support Within Social Networks Of Transgender Women Involved In Sex Work In Lima, Peru, Eddy R Segura, Cheríe S Blair

Faculty, Staff and Student Publications

Introduction: Social networks contribute to normative reinforcement of HIV prevention strategies, knowledge sharing, and social capital, but little research has characterized the social networks of transgender women (TW) in Latin America. We conducted a mixed methods analysis of three network clusters of TW in Lima, Peru, to evaluate network composition, types of support exchanged, and patterns of communication.

Methods: We recruited TW residing in or affiliated with three "casas trans" (houses shared among TW) in Lima between April-May 2018. Eligible participants were 18 or older, self-reported HIV-negative, and reported recent intercourse with a cis-male partner. Participants completed demographic questionnaires, social …

Systematic Analysis Of Proximal Midgut- And Anorectal-Originating Contractions In Larval Zebrafish Using Event Feature Detection And Supervised Machine Learning Algorithms, Rosa A Uribe

Faculty, Staff and Student Publications

Background: Zebrafish larvae are translucent, allowing in vivo analysis of gut development and physiology, including gut motility. While recent progress has been made in measuring gut motility in larvae, challenges remain which can influence results, such as how data are interpreted, opportunities for technical user error, and inconsistencies in methods.

Methods: To overcome these challenges, we noninvasively introduced Nile Red fluorescent dye to fill the intraluminal gut space in zebrafish larvae and collected serial confocal microscopic images of gut fluorescence. We automated the detection of fluorescent-contrasted contraction events against the median-subtracted signal and compared it to manually annotated gut contraction …

Safety And Effectiveness Of The First Contact Force Ablation Catheter With A Flexible Tip, Devi Nair, Martin Martinek, B Judson Colley, Sri Sundaram, Ramesh Hariharan, Gustavo Morales, Philipp Sommer, Stewart Healy, Usman Siddiqui, Douglas Gibson, Kristina Chapman, Anne Sarver, Monica Lo

Faculty, Staff and Student Publications

Background: Catheter ablation is an established therapy for paroxysmal atrial fibrillation (PAF). The TactiFlex Ablation Catheter, Sensor Enabled (TactiFlex SE) is a next-generation radiofrequency ablation catheter incorporating fiber optics-based contact force-sensing technology with a flexible, laser-cut tip.

Objective: The study sought to evaluate the safety and effectiveness of the TactiFlex SE ablation catheter for treatment of drug-refractory PAF.

Methods: The TactiFlex AF investigational device exemption was a prospective, nonrandomized, multicenter clinical study. Enrollment began on June 26, 2020 and completed June 18, 2021. Subjects with PAF underwent de novo pulmonary vein isolation and, if indicated, ablation for typical atrial flutter. …

Firearm Injury Prevention, Kelsey A B Gastineau, Sandra Mckay

Faculty, Staff and Student Publications

Firearms are the leading cause of death for US youth, overtaking motor vehicle collisions in 2020. Approximately 65% are due to homicide, 30% are due to suicide, 3.5% are due to unintentional injuries, 2% are undetermined intent, and 0.5% are from legal interventions. In homes with firearms, the likelihood of unintentional death, suicide, and homicide is three to four times higher than those without firearms. Secure storage of firearms, having them locked, unloaded, and separate from ammunition can prevent unintentional firearm injuries.

Clinician Perspectives On Technology-Enhanced In Vivo Exposures During Prolonged Exposure Therapy For Ptsd, Delisa G Brown, Amber M Jarnecke, Tanya C Saraiya, Elizabeth Santa-Ana, Ron Acierno, Mclain Reese, Robert Adams, William Harley, Sudie E Back

Faculty, Staff and Student Publications

Objective: To investigate clinicians' perceptions regarding the use of mobile technology tools during prolonged exposure (PE) therapy to allow for monitoring and enhancing in-vivo exposures (IVEs).

Methods: Clinicians with training in PE therapy (N = 32; average of 9 years of practice) completed surveys asking about their perspectives on the utility of virtually attending IVEs with patients while simultaneously having access to real-time subjective and physiological data (i.e., heart rate, galvanic skin conductance) to guide exposure exercises and assure optimal stimulus engagement.

Results: Findings showed clinicians to have a favorable view of applying technology devices and systems to enhance IVEs …

Relapse Recovery In Relapsing-Remitting Multiple Sclerosis: An Analysis Of The Combirx Dataset, Marcus W Koch, Ester Moral, Luis Brieva, Jop Mostert, Eva Mm Strijbis, Jacynthe Comtois, Pavle Repovic, James D Bowen, Jerry S Wolinsky, Fred D Lublin, Gary Cutter

Faculty, Staff and Student Publications

Background: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.

Objective: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS).

Methods: Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time …

Incidence And Risk Factors For Neutropenia After Intra-Arterial Chemotherapy For Retinoblastoma, Debora H Lee, Richard Donkor, Matthew N Parvus, Mark J Dannenbaum, Amy C Schefler

Faculty, Staff and Student Publications

Importance: Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited.

Objective: To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia.

Design, setting, and participants: This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023.

Exposure: …

Oral Glucose Tolerance Test In Pregnancy And Subsequent Maternal Hypertension, Maged M Costantine, Madeline Murguia Rice, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, Alan T N Tita, John M Thorp, Edward K Chien, Alan M Peaceman, Sean C Blackwell

Faculty, Staff and Student Publications

Objective: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life.

Study design: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their …

Maternal And Obstetrical Factors Associated With Short Cervical Length At Midtrimester In Women With No History Of Preterm Delivery, Eleazar E Soto-Torres, Edgar Hernandez-Andrade, Erin S Huntley, Sean C Blackwell

Faculty, Staff and Student Publications

Aim: To evaluate associations between maternal characteristics and a short cervix in patients without history of preterm delivery, and to determine if these characteristics can predict the presence of a short cervix.

Materials and methods: This is a retrospective cohort study that included 18,592 women with singleton pregnancies without history of previous preterm deliveries who underwent universal transvaginal cervical length (TVCL) screening between 18 + 0 and 23 + 6 weeks/days of gestation. A short cervix was defined as a cervical length (CL) ≤25 mm, ≤20 mm, and ≤15 mm. Associations between maternal age, weight, height, body mass index (BMI), …

Hydrochlorothiazide And Prevention Of Kidney Stone Recurrence: A #Nephjc Editorial On The Nostone Trial, Jade Teakell

Faculty, Staff and Student Publications

No abstract provided.

Relapse Recovery In Relapsing-Remitting Multiple Sclerosis: An Analysis Of The Combirx Dataset, Eva Mm Strijbis, Jerry S Wolinsky, Fred D Lublin, Gary Cutter

Faculty, Staff and Student Publications

BACKGROUND: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.

OBJECTIVE: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS).

METHODS: Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to …

Biomechanical Evaluation Of Mitral Valve Repair: Virtual Chordal Transposition To Restore Anterior Leaflet Prolapse, David D Mcpherson

Faculty, Staff and Student Publications

Background: Surgical management of an anterior leaflet prolapse remains comparatively challenging and has led to the lack of any firmly established standard repair techniques, as seen in cases of posterior leaflet prolapse. Chordal transposition repair is widely acknowledged as a remarkably durable technique that utilizes the patient's native chordae. This study aims to evaluate and predict the biomechanical and functional characteristics of a normal mitral valve (MV) model and a pathological MV model featuring anterior ruptured mitral chordae tendineae (RMCT), and to assess the effectiveness of the chordal transposition repair in the pathological MV model.

Methods: There are four stages …

Empagliflozin In Patients Admitted To Hospital With Covid-19 (Recovery): A Randomised, Controlled, Open-Label, Platform Trial

Faculty, Staff and Student Publications

BACKGROUND: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

METHODS: In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge …

The Application Of Simultaneous Mainstem Bronchus Dilation With Pulmonary Artery Stenting In The Context Of Hypoplastic Left Heart Syndrome, Arun B Dutta, Daniel Gioeli

Faculty, Staff and Student Publications

The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes …

Evaluation Of The Quality Of Thyroidectomy-Related Posts On A Video-Based Social Media Platform, Daniel Kwon

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the quality of thyroidectomy-related posts on TikTok, the fastest-growing social media platform worldwide.

METHODS: Videos posted from April 2020 to September 2022 were queried on TikTok using the search terms "thyroidsurgery," "thyroidectomy," and "thyroidremoval." Two reviewers recorded thematic, demographic, and performance data of these posts. The DISCERN instrument was used to evaluate the quality and reliability of the information contained in the videos. Descriptive statistics were used to characterize post-submitter demographics and video content. Simple and multiple linear regression analyses were used to evaluate the association between DISCERN scores and video characteristics. Univariate analysis of variance was …

High School Flash Sexual Health Education Curriculum: Lgbtq Inclusivity Strategies Reduce Homophobia And Transphobia, Elizabeth Baumler

Faculty, Staff and Student Publications

Homophobic and transphobic beliefs that lead to bias-based harassment remain a critical concern for young people in the USA. The aim of the present study was to examine the impact of an inclusive comprehensive sex education program (High School FLASH) on homophobic and transphobic beliefs. Data from this study come from a randomized controlled trial that evaluated the impact of High School FLASH on students' sexual behaviors and related outcomes with 20 schools in two U.S. regions (Midwest and South). Following the baseline survey, the 20 schools were randomly assigned to receive FLASH or a comparison curriculum. Ninth and 10th …

In-Center Dialysis Versus Extended Home Hemodialysis: More Evidence To Support Extended Dialysis

Faculty, Staff and Student Publications

No abstract provided.

Sonographic Characteristics And Pathology Correlation Of Breast Imaging Reporting And Data System (Bi-Rads) Category 4 Lesions, Yasir Ali

Faculty, Staff and Student Publications

Introduction: The Breast Imaging-Reporting and Database System (BI-RADS) category 4 is designated for breast lumps that do not display the typical features of malignancy but still raise enough suspicion to warrant a recommendation for a biopsy, as malignancy cannot be ruled out through imaging alone. The main objective of this study was to investigate the sonographic characteristics and pathology correlation of BI-RADS 4 breast lesions and determine the positive predictive rate of BI-RADS 4 lesions in diagnosing breast cancer, using histopathology as the gold standard.

Methods: This was a cross-sectional study conducted at the Department of Radiology, Aga Khan University …

Resuscitative Endovascular Balloon Occlusion Of The Aorta And Resuscitative Thoracotomy Are Associated With Similar Outcomes In Traumatic Cardiac Arrest, Charles J Fox, Eileen M Bulger, David E Meyer

Faculty, Staff and Student Publications

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive alternative to resuscitative thoracotomy (RT) for patients with hemorrhagic shock. However, the potential benefits of this approach remain subject of debate. The aim of this study was to compare the outcomes of REBOA and RT for traumatic cardiac arrest.

Methods: A planned secondary analysis of the United States Department of Defense-funded Emergent Truncal Hemorrhage Control study was performed. Between 2017 and 2018, a prospective observational study of noncompressible torso hemorrhage was conducted at six Level I trauma centers. Patients were dichotomized by REBOA or RT, and baseline …

Will You Go The Distance? A Satisfaction Survey Of Telemedicine In Sexual Medicine, Charles Green

Faculty, Staff and Student Publications

BACKGROUND: The success of telemedicine depends on patient satisfaction with the care that they receive, which is impacted by the ease of use of the technology, quality of the connection, and perceived effectiveness of care.

AIM: The study sought to evaluate patient satisfaction with telemedicine services in a high-volume andrology clinic.

METHODS: We included all patients who had a telemedicine appointment between January 1, 2020, and August 22, 2022. Demographic information was gathered, and a satisfaction survey was conducted using REDCap software. Data were grouped into 2 age categories, with ≥50 years as the cutoff (19-50 years; >50 years). The …

Huntington Study Group's Neuropsychology Working Group: Implementing Non-Motor Diagnostic Criteria, Sharlet A Anderson, Adam Piccolino, Antonio L Teixeira, Julie C Stout

Faculty, Staff and Student Publications

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD.

Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD …

Comparative Study Between Antegrade Flexible Ureteroscopy And Reterograde Intrarenal Surgery In The Management Of Impacted Upper Ureteric Stones 15 Cm Or Larger, Amr S El-Dakhakhny

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm.

PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by …

Cortical Thickness Is Related To Variability In Heritage Bilingual Language Proficiency, Arturo E Hernandez

Faculty, Staff and Student Publications

Research suggests that bilingual experience is associated with gray matter changes, such that initial language gains are associated with expansion and language expertise is associated with renormalization. Previous studies on language proficiency development primarily focused on between-subjects, quasiexperimental comparisons of monolinguals and bilinguals. This study proposes a new paradigm to examine language expertise and cortical thickness within heritage bilinguals (

Nurse Care Management For Opioid Use Disorder Treatment: The Proud Cluster Randomized Clinical Trial, Jennifer Mccormack, Noorie Hyun, Abisola E Idu, Cynthia I Campbell, Andrew J Saxon, David S Liu, Andrea Altschuler, Jeffrey H Samet, Colleen T Labelle, Mohammad Zare-Mehrjerdi, Angela L Stotts, Jordan M Braciszewski, Mark T Murphy, Douglas Dryden, Julia H Arnsten, Chinazo O Cunningham, Viviana E Horigian, José Szapocznik, Joseph E Glass, Ryan M Caldeiro, Rebecca C Phillips, Mary Shea, Gavin Bart, Robert P Schwartz, Jennifer Mcneely, Jane M Liebschutz, Judith I Tsui, Joseph O Merrill, Gwen T Lapham, Megan Addis, Katharine A Bradley, Proud Trial Collaborators, Megan M Ghiroli, Leah K Hamilton, Yong Hu, Jennifer S Lahue, Amy M Loree, Sean M Murphy, Thomas F Northrup, Dikla Shmueli-Blumberg, Angela J Silva, Zoe M Weinstein, Mark Tinfook Wong, Rachael P Burganowski

Faculty, Staff and Student Publications

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments.

Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization.

Design, setting, and participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention …

The Hidden Impact Of Orthopedic Surgeries: Examining The Psychological Consequences

Faculty, Staff and Student Publications

Orthopedic surgery is commonly considered "quality of life care," as most orthopedic procedures have been shown to provide excellent pain relief and successful surgical outcomes for patients. Although orthopedic surgeries continue to improve patients' functional outcomes through modern surgical techniques and preoperative psychological screening, variation in patient function persists in current studies. Sub-optimal function in patients has been shown to be associated with emotional health burdens, such as anxiety and depression. Previous research has found that preoperative psychological conditions could negatively affect patients' functional outcomes. However, these studies were limited in that they did not examine novel psychological repercussions in …