Medicine and Health Sciences Commons^™

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

Aortopexy With Plication Of Kommerell Diverticulum Is An Effective Alternative To Diverticulum Resection And Reimplantation Of The Aberrant Left Subclavian Artery For Surgical Management Of Vascular Rings In Children, Adegbemisola Aregbe Perkins, Ana-Lucia Tomescu, Christopher J Knott-Craig, Umar Boston, Thomas Spentzas, Karthik Vaidyanathan Ramakrishnan

Faculty, Staff and Student Publications

Background

Right aortic arch with an aberrant left subclavian artery arising from a Kommerell diverticulum is the most common form of vascular ring. We report the outcomes of plication and pexy of the diverticulum in addition to division of the left-sided ligamentum to treat this lesion in children.

Methods

Forty-four patients were included in the study; 22 patients underwent division of the ligamentum arteriosum alone, while the other half underwent plication and/or pexy of the Kommerell diverticulum in addition to division of the ligamentum. The primary outcome of interest was reintervention for persistent symptoms following the initial operation. The other …

Polaris: Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Michael A Davies

Faculty, Staff and Student Publications

POLARIS was a study to evaluate different doses of encorafenib plus binimetinib for people with BRAF V600-mutant melanoma with brain metastasis. The first part, known as the safety lead-in, looked at a high dose of encorafenib (300 mg twice daily) combined with standard binimetinib (45 mg twice daily); in the phase 2 part, patients were given the standard dose of encorafenib (450 mg once daily) plus binimetinib. In the safety lead-in, many patients were unable to tolerate the high dose of encorafenib plus binimetinib. Despite recruitment challenges in POLARIS, in the 13 enrolled patients with unresectable metastatic BRAF V600-mutant melanoma …

Protocol To Detect M22g Modification On Single Trna Iso-Decoders By Immuno-Northern Blotting, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are highly dynamic and play crucial roles in regulating gene expression. Here, we present an assay for analyzing N2, N2-dimethylguanosine (m22G) modifications on tRNAs using an antibody-based detection approach. We describe steps for isolating tRNAs from human cells via ion-exchange chromatography, capturing specific tRNA iso-decoders on streptavidin magnetic beads, and detecting modifications through immuno-northern blotting. This approach enables researchers to investigate other tRNA modifications using specific antibodies or downstream approaches such as mass spectrometry.

Exploring Covid-19 Vaccination Behavior: A Cross-Country Study Among Pregnant And Postpartum Women In Brazil, Ghana, Kenya, And Pakistan, Rupali Limaye, Berhaun Fesshaye, Emilly Miller, Prachi Singh, Saleem Jessani, Muhammad Asim, Ferdinand Okwaro, Caroline Badzi, Emefa Amoah, Marleen Temmerman

Centre of Excellence in Women and Child Health

Pregnant women infected with SARS-CoV2 are more likely to be hospitalized and require ventilation, compared to non-pregnant women. Although the development of the COVID-19 vaccine was regarded as a scientific breakthrough among many, the pace of development in combination with delayed and unclear recommendations for maternal vaccination led to slower vaccine uptake among this population. We explored the decision-making process for COVID-19 vaccination among pregnant and postpartum women in four countries: Brazil, Ghana, Kenya, and Pakistan through 201 in-depth interviews. A grounded theory approach was used for analysis, and a socio-ecological framework was used to synthesize emerging themes. Four levels …

Covid-19 Vaccine Attitudes And Behaviors Among Pregnant Women In Nairobi, Kenya With Diverse Socio-Economic And Educational Backgrounds, Jessica Schue, Ferdinand Okwaro, Ingrid Gichere, Daizy Cherono, Mandeep Sura, Emily Miller, Berhaun Fesshaye, Prachi Singh, Grace Belayneh Belayneh, Rupali Limaye, Marleen Temmerman

Centre of Excellence in Women and Child Health

Introduction

Methods

Placental Transfer Of Sars-Cov-2 Antibodies In Mother-Neonate Pairs: A Prospective Nested Cohort Study, Alex Mugo, Angela Koech, Liberty Cantrell, Moses Mukhanya, Isaac Mwaniki, Joseph Mutunga, Merryn Voysey, Rachel Craik, Marleen Temmerman, Geoffrey Omuse

Centre of Excellence in Women and Child Health

Background: Newborns depend on the transfer of IgG across the placenta to acquire protection against pathogens. We assessed the placental transfer of SARS-CoV-2 antibodies, primarily derived from infection, from seropositive pregnant women enrolled in a pregnancy cohort in Kilifi, Kenya.

Methods :The study was nested within a prospective observational multi-country cohort study. All available paired maternal delivery and cord blood samples were selected. Maternal sera were tested for SARS-CoV-2 receptor binding domain (RBD) IgM/IgG total antibodies using the Wantai assay. For positive samples, maternal and corresponding cord blood samples were tested for SARS-CoV-2 IgG antibodies against the spike (anti-spike) and …

Contribution Of Maternal Adherence To The Effect Of Multiple Micronutrient Supplementation During Pregnancy: A Systematic Review And Individual Participant Data Meta-Analysis, Emily R. Smith, Filomena Gomes, Seth Adu-Afarwuah, Victor M. Aguayo, Shams El Arifeen, Zulfiqar Ahmed Bhutta, Ellen C. Caniglia, Parul Christian, Arjumand Rizvi, Sajid Bashir Soofi

Centre of Excellence in Women and Child Health

Multiple micronutrient supplements (MMS) in pregnancy reduces risk of infant low birthweight (LBW) and improves other maternal and infant outcomes compared with iron and folic acid (IFA) supplements alone. However, the impact of timing of initiation and adherence on the MMS effectiveness in real-world programs remains unclear. To address this, we conducted a 2-stage individual participant data meta-analysis that included 15 randomized trials (61,204 pregnant women) and assessed whether the relative effect of MMS differed by the following: adherence alone; adherence in combination with gestational age at initiation; and the total number of tablets taken. We also evaluated the observational …

Sex-Based Differences In The Representation Of Top Youth Athletes, Jessica J. James, Sandra K. Hunter, Elizabeth P. Bueckers, Michael J. Joyner, Jonathon W. Senefeld

Exercise Science Faculty Research and Publications

Although emerging research demonstrates that male athletes outperform female athletes before puberty, the effect of these sex-related advantages on ordinal ranking of top performances remains unclear.

Objectives

Among overall top performances of youth track and swimming athletes, we aimed to determine 1) the proportional number of male compared with female athletes represented and 2) at what age females are no longer represented.

Methods

Finishing times and sex of the top 10 and top 100 performances of youth runners and swimmers between 5 and 18 yr were abstracted from online U.S.-based databases for four running (100 m–800 m) and six freestyle …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Adapt-Marketplace - A Web-Application For Xml-Based Template Sharing In Radiation Oncology, Dennis N Stanley, Joseph Harms, Gaurav N Rathi, Joel A Pogue, Ritish Nedunoori, John B Fiveash, Richard A Popple, Carlos E Cardenas

2020-Current year OA Pubs

PURPOSE: The adaption of radiotherapy (RT) plans in response to anatomical and physiological changes during treatment marks a significant shift toward personalized cancer care. However, the complexity of Online Adaptive Radiotherapy (OART) procedures often leads to variability in treatment quality across institutions. The development of planning templates, particularly through the Ethos treatment planning system (TPS) and Intelligent Optimization Engine (IOE) (Varian Medical Systems, Palo Alto, CA), plays a crucial role in standardizing and streamlining OART. To address the challenges of sharing and optimizing treatment templates across diverse clinical environments, we developed the ADaptive rAdiotherapy Planning Template (ADAPT-) Marketplace to facilitate …

Clinical Evaluation Of The Healgen Rapid Covid-19 Antigen Test As A Point-Of-Care Diagnostic Tool, Stephen A Young, Hua Zhang, Jose Rodriguez, David Mishkin, Ward Paine, Li Seyfried, Latisha Hargrove, Dennis L Broyles, Chermaen Lindberg, Anurag Purushothaman, Stacey House

2020-Current year OA Pubs

BACKGROUND: Development of readily available Rapid COVID-19 Antigen tests essential for promptly identifying SARS-CoV2 infection and preventing its spread.

METHODS: This study evaluated the clinical performance of the Healgen Rapid COVID-19 antigen test as a point-of-care diagnostic tool with 806 evaluable subjects who were within 6 days post-symptom onset. The results from the Healgen test were compared to the results from Emergency Use Authorization (EUA) approved SARS-CoV-2 RT-PCR tests.

RESULTS: Out of the 806 evaluable subjects, 140 tested positive and 640 tested negative for SARS-CoV-2 with the Healgen COVID-19 test, showing good agreement with the EUA RT-PCR results. There were …

Dna Methylation Epitypes Of Burkitt Lymphoma With Distinct Molecular And Clinical Features, Nicole Thomas, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

UNLABELLED: The genetic subtypes of Burkitt lymphoma have been defined, but the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by the Epstein-Barr virus status or mutation status, leading to two epitypes described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression, and mutational differences between the epitypes …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Antonina I Frolova, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Covid-19-Associated Pulmonary Aspergillosis In Mechanically Ventilated Patients At 7 Us Hospitals: Epidemiology And Estimated Likelihood Of Invasive Pulmonary Aspergillosis-Results Of The Prospective Msg-017 Study, M Hong Nguyen, Sixto M Leal, Luis Ostrosky-Zeichner, Andrej Spec, George R Thompson, Thomas F Patterson, John Baddley, Rachel Mcmullen, Drashti Shah, Cornelius J Clancy, Gerald Mcgwin, Peter G Pappas

2020-Current year OA Pubs

BACKGROUND: There is no prospective, US multicenter study of COVID-19-associated pulmonary aspergillosis (CAPA). CAPA definitions do not differentiate invasive aspergillosis (IPA) from colonization. Validity of single mycologic test results is unclear.

METHODS: We performed a prospective 7-center US study of mechanically ventilated adults with COVID-19 (April 2021-May 2022). Mycoses Study Group (MSGERC) CAPA criteria include host and clinical factors, imaging and test results (histopathology; bronchoalveolar lavage [BAL] culture and/or BAL or serum galactomannan-immunoassay). Proven, putative, and unlikely IPA were defined by clinical criteria. CAPA-unlikely IPA criteria included survival or negative autopsy following no/limited antifungal treatment. IPA likelihood was estimated using …

Genetic Structuring And Estimation Of Reproductive Adults In Onchocerca Volvulus: A Genome-Wide Analysis Across Hosts And Regions, Pawan Kumar, Young-Jun Choi, Kerstin Fischer, Shannon M. Hedtke, Anusha Kode, Nicholas Opoku, Lincoln Gankpala, Tony O. Ukety, Jöel Lonema Mande, Timothy J. C. Anderson, Warwick N. Grant, Peter U. Fischer, Makedonka Mitreva

2020-Current year OA Pubs

Genomic analysis of parasites can deepen our understanding of their transmission, population structure, and important biological characteristics. Onchocerciasis (river blindness), caused by the parasitic nematode Onchocerca volvulus, involves adult worms residing in subcutaneous nodules that produce larval-stage microfilariae (mf), which are routinely detected in the skin for diagnosis. Whole-genome studies of mf are limited; most analyses have focused on the mitochondrial genome. We conducted a genome-wide analysis with 94% median nuclear genome coverage, analyzing 171, 37, and 98 mf from 16, 3, and 5 individuals from Ghana, Liberia, and the Democratic Republic of Congo, respectively. These data were used to …

Soft Tissue Stabilization Of Midcarpal Instability In Ehlers-Danlos Patients Using A Cadaveric Tendon Graft, Mohammed Muneer, Fadi Bouri, Kjell Van Royen, Saif Badran, Jorge I. Quintero, Tuna Ozyurekoglu

2020-Current year OA Pubs

Ehlers-Danlos syndrome (EDS) is a group of hereditary disorders that affects collagen synthesis. In the wrist, pain and midcarpal laxity may affect up to 70% of EDS patients. The mainstay treatment of midcarpal instability in patients with ligamentous injury but not EDS includes orthotics, physiotherapy, and activity modification. These methods of conservative treatment may be unsuccessful in controlling instability in the longer term. Using autologous tendon for reconstructing midcarpal instability in patients with EDS carries the risk of loosening over time due to intrinsic abnormalities in collagen metabolism. In this article, we present a novel surgical technique using a cadaveric …

Robust Photogrammetric Scalp Morphology Estimation For Functional Optical Neuroimaging, Abigail L Magee, Calamity Svoboda, Tessa G George, Alvin A Agato, Edward J Richter, Joseph P Culver, Adam T Eggebrecht

2020-Current year OA Pubs

SIGNIFICANCE: Optical functional neuroimaging relies upon accurate anatomical models to provide optimal data registration and image reconstruction.

AIM: We establish and validate a robust photogrammetric algorithm for scalp morphology that utilizes 3-dimensional (3D) imaging with a photogrammetric cap to provide individualized scalp morphology estimation through hair in the absence of magnetic resonance imaging (MRI).

APPROACH: The scalp morphology estimation uses a flexible, neoprene cap and 3D-printed photogrammetric modules with fiducials. We create a sparse scalp sampling and align the MNI152 atlas to generate the scalp morphology estimation. We used the international 10 to 20 electroencephalogram positions for alignment and calculated …

Sleep Variability And Time To Achieving Pregnancy: Findings From A Pilot Cohort Study Of Women Desiring Pregnancy, Peinan Zhao, Emily S Jungheim, Bronwyn S Bedrick, Leping Wan, Patricia T Jimenez, Ronald Mccarthy, Jessica Chubiz, Justin C Fay, Erik D Herzog, Siobhan Sutcliffe, Sarah K England

2020-Current year OA Pubs

OBJECTIVE: To determine whether chronodisruption is associated with achieving pregnancy.

DESIGN: Pilot prospective cohort study.

SETTING: Academic Medical Center.

SUBJECTS: One hundred eighty-three women desiring pregnancy were recruited from the local community of an academic medical center located in the Midwest and provided sleep information between February 1, 2015, and November 30, 2017.

EXPOSURE: Sleep and activity data were obtained via actigraphy watches worn continuously for 2 weeks to assess measures of chronodisruption, including sleep period onset, offset, midtime, and duration; as well as variability in each of these measures.

MAIN OUTCOME MEASURES: Time to becoming pregnant over 1-year of …

Projection-Tags Enable Multiplex Projection Tracing And Multi-Modal Profiling Of Projection Neurons, Lite Yang, Fang Liu, Hannah Hahm, Takao Okuda, Xiaoyue Li, Yufen Zhang, Vani Kalyanaraman, Monique R Heitmeier, Vijay K Samineni

2020-Current year OA Pubs

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged …

Molecular Profile Of Adult Primary Leptomeningeal Gliomatosis Aligns With Glioblastoma, Idh-Wildtype, Yi Zhu, Darin D Carabenciov, Derek R Johnson, Jorge A Trejo-Lopez, Aivi T Nguyen, Aditya Raghunathan, Giuseppe Lanzino, Cristiane M Ida, Cinthya J Zepeda-Mendoza, Surendra Dasari, Emilie Russler-Germain, Sonika Dahiya, Martha Quezado, Kenneth Aldape, Caterina Giannini

2020-Current year OA Pubs

Adult primary leptomeningeal gliomatosis (PLG) is a rare, rapidly progressive and fatal disease characterized by prominent leptomeningeal infiltration by a glial tumor without an identifiable parenchymal mass. The molecular profile of adult PLG has not been well-characterized. We report the clinical, pathological, and molecular findings of six adult PLG patients (five males and one female), median age 58 years. All cases exhibited pathological leptomeningeal enhancement at presentation. Leptomeningeal biopsy was diagnostic in five (of six) cases, revealing infiltration by an astrocytic glioma with mitotic activity, lacking microvascular proliferation or necrosis. One case was diagnosed at autopsy. All tumors were IDH-wildtype, …

Automated Assignment Grading With Large Language Models: Insights From A Bioinformatics Course, Pavlin G Poličar, Martin Špendl, Tomaž Curk, Blaž Zupan

Faculty, Staff and Students Publications

Motivation: Providing students with individualized feedback through assignments is a cornerstone of education that supports their learning and development. Studies have shown that timely, high-quality feedback plays a critical role in improving learning outcomes. However, providing personalized feedback on a large scale in classes with large numbers of students is often impractical due to the significant time and effort required. Recent advances in natural language processing and large language models (LLMs) offer a promising solution by enabling the efficient delivery of personalized feedback. These technologies can reduce the workload of course staff while improving student satisfaction and learning outcomes. Their …

Glioblastoma-Instructed Astrocytes Suppress Tumour-Specific T Cell Immunity, Camilo Faust Akl, Brian M Andersen, Zhaorong Li, Federico Giovannoni, Martin Diebold, Liliana M Sanmarco, Michael Kilian, Luca Fehrenbacher, Florian Pernin, Joseph M Rone, Hong-Gyun Lee, Gavin Piester, Jessica E Kenison, Joon-Hyuk Lee, Tomer Illouz, Carolina M Polonio, Léna Srun, Jazmin Martinez, Elizabeth N Chung, Anton Schüle, Agustin Plasencia, Lucinda Li, Kylynne Ferrara, Mercedes Lewandrowski, Craig A Strathdee, Lorena Lerner, Christophe Quéva, Iain C Clark, Benjamin Deneen, Judy Lieberman, David H Sherr, Jack P Antel, Michael A Wheeler, Keith L Ligon, E Antonio Chiocca, Marco Prinz, David A Reardon, Francisco J Quintana

Faculty, Staff and Students Publications

Glioblastoma is the most common and aggressive primary brain cancer and shows minimal response to therapies. The immunosuppressive tumour microenvironment in glioblastoma contributes to the limited therapeutic response. Astrocytes are abundant in the central nervous system and have important immunoregulatory roles. However, little is known about their role in the immune response to glioblastoma1. Here we used single-cell and bulk RNA sequencing of clinical glioblastoma samples and samples from preclinical models, multiplexed immunofluorescence, in vivo CRISPR-based cell-specific genetic perturbations and in vitro mouse and human experimental systems to address this gap in knowledge. We identified an astrocyte subset …

Bispecific Antibodies In Follicular Lymphoma, Imran A. Nizamuddin, Nancy L. Bartlett

2020-Current year OA Pubs

Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm for multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at 2 years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige K Boneski, Hiromi Sesaki, Ruteja A Barve, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Exploitable Mechanisms Of Antibody And Car Mediated Macrophage Cytotoxicity, Tianyi Liu, Alexander B Kim, Young Ah Goo, Minsoo Son, Jaenyeon Kim, Carl J Deselm, Et Al.

2020-Current year OA Pubs

Macrophages infiltrate solid tumors and either support survival or induce cancer cell death through phagocytosis or cytotoxicity. To uncover regulators of macrophage cytotoxicity towards cancer cells, we perform two co-culture CRISPR screens using CAR-macrophages targeting different tumor associated antigens. Both identify ATG9A as an important regulator of this cytotoxic activity. In vitro and in vivo, ATG9A depletion in cancer cells sensitizes them to macrophage-mediated killing. Proteomic and lipidomic analyses reveal that ATG9A deficiency impairs the cancer cell response to macrophage-induced plasma membrane damage through defective lysosomal exocytosis, reduced ceramide production, and disrupted caveolar endocytosis. Depleting non-cytotoxic macrophages using CSF1R inhibition …

Participation In Activities Among People With Long-Term Spinal Cord Injury In Sweden And The Usa - An Explorative Study Using Secondary Data Analysis, Jessica L Dashner, Ulrica Antepohl

2020-Current year OA Pubs

STUDY DESIGN: Secondary data analysis.

OBJECTIVE: To explore differences in participation, secondary health complications, and the use of assistive devices and personal assistance among people with long-term SCI in Sweden and the USA.

SETTING: Community dwelling individuals with SCI in Sweden and USA.

METHODS: Secondary analysis of data collected via PARTS-Mv3 among individuals living with SCI in Sweden (n = 73) and in the USA (n = 45). Descriptive analyses provided information regarding the participants, their participation in activities, and secondary health complications, together with the use of assistive devices and personal assistance.

RESULTS: Both samples included more males than …

Incident Depression After Breast Cancer Among Older Asian, Native Hawaiian, And Pacific Islander Women, Alzina Koric, Chun-Pin Esther Chang, Yuan-Chin Amy Lee, Mei Wei, Catherine Lee, Jing Wang, Mia Hashibe

2020-Current year OA Pubs

BACKGROUND: Longitudinal studies examining mental health outcomes among older (≥66 years) Asian, Native Hawaiian, and Pacific Islander (ANHPI) women diagnosed with breast cancer are limited. We evaluated incident depression after breast cancer among specific groups of older ANHPI compared with older non-Hispanic White (NHW) women. Predictors of depression and the risk of death following early onset of depression after breast cancer were also evaluated.

METHODS: A cohort of 26 776 older ANHPI women in the United States diagnosed with breast cancer between 2000 and 2017 was identified from the SEER-Medicare linked claims. There were 6694 older ANHPI and 20 082 …

Sexually Dimorphic Impact Of Prenatal Hyperandrogenism On Offspring Growth Trajectory In Sheep, Eylem Topaktas, Joseph Ciarelli, Stephanie Domke, Brooke Pallas, Adel Ghnenis, Mansi Agarwal, Charles Goss, Kevin Cho, Leah P Shriver, Gary J Patti, Vasantha Padmanabhan, Arpita Kalla Vyas

2020-Current year OA Pubs

In a translationally relevant ovine model of gestational hyperandrogenism we have previously reported cardiometabolic disruption in female offspring (males were not extensively studied). We hypothesized that gestational hyperandrogenism would lead to sex-specific disruption in offspring's growth, cytokine and metabolic milieu, potential mediators of cardiometabolic disease (CMD). 100 mg Testosterone propionate (T) or vehicle (C) was administered intramuscularly twice weekly between gestational days (GD) 30-90. Two cohorts of offspring were generated, including both males and females. Fetal weight and systemic metabolomics were analyzed in the fetal cohort (GD120). Growth trajectory, systemic cytokines, and metabolomics were analyzed in the postnatal cohort. Data …