Medicine and Health Sciences Commons^™

Activating Urban Spaces To Achieve Social Sustainability In Closed Residential Communities, ولاء أحمد نو زة صبحي السقا , أحمد السيد الشناوي , سارة حسني شعلان

Journal of Engineering Research

تماشيا مع توجهات الجمهورية الجديدة و رؤية مصر 2030 من أجل خلق مجتمعات سكنية مستدامة تلبي احتياجات سكانيها الاجتماعية .وقد ادي انتشار المجتمعات السكنية المغلقة الي وجود مشكلة اجتماعية لسكانها من عزلة و انحصارهم داخلها وانفصالهم عن المجتمع المحيط بهم وعن سكان باقي المدينة وبالتالي ظهرت مشاكل اجتماعية مثل العزلة و الشعور بالوحدة وفقدان الانتماء الاجتماعي وزيادة الانفصال.لذلك يتناول البحث تفعيل دور الفراغات العمرانية وتاثيرها علي العلاقة الاجتماعية بين ساكني تلك التجمعات المغلقة والتاكيد علي ضرورة تطبيق تلك المعايير التصميمية لتلبية احتياجات السكان الاجتماعية. لما للفراغ العمراني من دور مهم في ممارسة الانشطة و الفاعليات التي من شانها تحقيق التواصل …

Evaluation Of The Built Environment Performance In Light Of Sustainable And Universal Design: Criteria And Methods, N.A.Mohamed E. A. Morghany, M. E. Khalil

Journal of Engineering Research

Egypt's Vision 2030 for Sustainable Development Strategy (SDS) emphasizes social inclusion and accessibility. The concept of Universal Design (UD) is crucial in achieving the goals of SDS by facilitating utilization and access to the built environment for all.

Palm Agricultural Residues As A Sustainable Local Construction Material For Siwa House: One Click Life Cycle Assessment Perspective, Nader Mohamed Gharib,

Journal of Engineering Research

This study focuses on conducting a life cycle assessment (LCA) of using green agricultural waste as a sustainable local building material compared to conventional materials. Agricultural residues present a major waste management issue, however they can be repurposed as renewable construction resources. The aim is to quantify the environmental impacts of an experimental palm midribs roof design versus a traditional reinforced concrete roof. by using One Click LCA software to model the two design scenarios and analyze key sustainability indicators including carbon emissions. By comparing the LCA results, the study benchmarks the global warming potential and identifies opportunities to promote …

The Role Of Interior Architecture In Developing Sustainable Educational Building Spaces And Its Impact On Users In University Institutions, زينب ناجي¹ ريم الحداد

Journal of Engineering Research

يهدف البحث الى تسليط الضوء على أهمية الاستدامة في التصميم وما تحققه من جوانب ايجابية على الفرد والمجتمع، حيث أن أبنية العمارة المستدامة هي التي يتم تصميمها وإنشاءها بطرق ومواد البناء المحلية والتي لا تؤثر سلبيا على البيئة وصحة المستعملين والقائمين بالبناء وتحافظ على حقوق الأجيال القادمة، وتتناول الأبنية المستدامة العديد من الإعتبارات ومنها إستعمالات الأراضي والتأثير على الموقع والبيئة المحيطة وإستنزاف الطاقة والمياه. و يصبح المبنى الذي يبنى على أساس العمارة المستدامة مفيد لأنه يعتمد على تحسين كفاءة الطاقة المستخدمة وبالتالي توفير المال، والحد من التلوث بزيادة نقاء الهواء الذي يوفر لمستخدمي المبنى بيئة صحية سليمة بالإضافة الى المحافظة …

Opportunities And Challenges For Achieving Sustainable Architectural Education In Egypt, In Light Of Universal Design Approach., مي عيد خليل أحمد م/ هناء شعبان حسن

Journal of Engineering Research

الملخص يعتبر التعليم الجامعي هو المفتاح لتغيير الثقافة المهنية في مجالات التصميم، لذا يقع على عاتق المؤسسات التعليمية مسؤولية التعليم والتثقيف للطلاب الجامعيين، حيث يقدم التعليم المعماري حلولاً مجدية للقضايا الدولية الملحة من خلال تحقيق أهداف التنمية المستدامة والتي صاغتها الأمم المتحدة، يمكن التغلب على هذه القضايا من خلال تطبيق مفهوم التصميم العالمي (الشامل) UD والذي يسعي لتبسيط الحياه علي الجميع وتحقيق الوصول والاستخدام اليسير للجميع بغض النظر عن القدرات البدنية والأعمار.

Challenges Of New And Renewable Energy In The Face Of Climate Change: An Introduction To Evaluating The Egyptian Experience, نهي أحمد عبد المنعم السيد, شاهيناز محمد علي طايع Dr, Nevine Gado Dr.

Journal of Engineering Research

أصبحت التغيرات المناخية وما يترتب عليها من المخاطر البيئية قضية من القضايا الحيوية والتي عقدت لها عدة مؤتمرات دولية مثل مؤتمر المناخ العالمي COP 27 والذي استضافته مصر في عام 2023 لوضع الحلول لتلك الأزمة. ومن أجل ذلك أصبح مردود الطاقة الجديدة والمتجددة احدى اليات وادوات التعامل مع هذه القضية الحيوية كبديل مستدام وصديق للبيئة.

The Impact Of Digital Twin On Real Estate Marketing, نوران عاطف محمد غانم Eng, مروة أحمد قمر الدولة أ.د أحمد عبد الوهاب أحمد رزق

Journal of Engineering Research

يتناول هذا البحث أولا الدراسات النظرية الأكثر حداثة التي تناولت تقنية التوأمة الرقمية وعلاقتها بالعقارات وتسويقها ونشأتها ومفهومها ومكوناتها، ثم انتقلنا الي الدراسات المخصصة لاستخداماتها في قطاع العقارات وأهميتها، ومن بعد تناولنا استخدامتها في التسويق العقاري بصفة خاصة من حيث المشاريع والبرامج. ومن ثم وضحنا أهمية تقنية التوأمة وتأثيرها علي التسويق العقاري من حيث العملاء والشركات والأسواق، وبعد ذلك تناولنا تطبيق للتسويق العقاري باستخدام تقنية التوأمة الرقمية علي التخطيط العمراني وكيفية تأثيره علي تسويق المشروع. ومن خلال القيام بدراسة استبيان لقياس أهمية تأثير تقنية التوأمة الرقمية علي أراء العملاء وتفضيلاتهم في اتخاذ القرارات واختيارهم للشركات حين ذاك، وربط تقنية التوأمة …

Sensory Garden Preferences For Autism Spectrum: Insights From Psychologists And Urban Designers, Maram Adel Ebaid

Journal of Engineering Research

Sensory gardens are outdoor environment that stimulate the senses and promote well-being for people with autism spectrum disorder (ASD). In Egypt, there is an absence of gardens, compounded by a limited understanding of the design principles aligned with the needs of people with ASD. The research explores sensory garden features and the specific challenges faced by people with ASD. To bridge this gap, the methodology depends on qualitative approach through interviews with psychology and urban design experts. The results highlight the correlation between prevalent strategies among people with ASD and the elements of sensory gardens, considering both soft and hard …

Incorporation Of Bim Techniques In The Architectural Engineering Curriculum, Ahmed Ahmed M. Saleh, Sherif S. Abdalla

Journal of Engineering Research

In this era, the age of the digital revolution, Egyptian engineering universities and academies compete by integrating new technologies such as building information modeling (BIM) inside the educational curriculum. The research aims to examine and integrate BIM techniques within the course specifications in Egyptian universities and academies, majoring in architectural engineering pathing through the four levels of credit hours system so that, teaching the BIM courses is not limited to one or two only. Furthermore, the current situation of BIM maturity levels, dimensions, and tools implementation in some architecture universities and academies curriculum will be determined and monitored. As a …

Operating Efficiency In Accommodation Units And Its Impact On The Design Of Comprehensive Single Patient Rooms In Hospitals, نهال نبيل محمد مصطفي ، احمد هلال محمد محمد ، نادي مصطفي عبد الكريم

Journal of Engineering Research

هناك الكثير من التحديات التشغيلية والتنظيمية التي تواجهها المجموعات المهنية المختلفة داخل وحدات الإقامة في المستشفيات بسبب عدم كفاية معايير التصميم الموضوعة بالاحتياجات المطلوبة خاصة بغرف المرضي، ومن اهم التحديات التي يواجهها الاطباء وفرق التمريض والفنيين وغيرهم. القدرة السلسة على دخول غرفة المريض والتفاعل مع عناصر الغرفة بشكل واضح دون حدوث تصادمات او احتكاكات، كذلك القدرة علي القيام بالأعمال التحضيرية المتعلقة بالأنشطة التمريضية المطلوبة داخل غرف المرضي وتشمل كافة الأنشطة التي يقوم بها الشخص المهني سواء اكان طبيب ام تمريض ام فني منذ لحظة دخوله غرفة المريض وحتي اداءه المهمة المطلوبة. ويجب ان تتم هذه المهام بشكل مريح وباستجابة سريعة …

Set-Based Tests For Genetic Association Studies With Interval-Censored Competing Risks Outcomes, Zhichao Xu, Jaihee Choi, Ryan Sun

Faculty, Staff and Student Publications

Over the past decade, massive genetic compendiums such as the UK Biobank have gathered extensive genetic and phenotypic data that hold the potential to provide unparalleled insight into the genetic etiologies of various complex diseases. However, much of the disease information is collected as time-to-event outcomes in interval-censored form, and conventional tools for genetic association analysis are often not available for this type of data. For example, set-based inference for common and rare variants analysis is a fundamental investigation in germline genetics studies, but there is a lack of approaches that can perform set-based testing when the interval-censored outcome of …

Dansyl Fluorophore Functionalized Hierarchically Structured Mesoporous Silica Nanoparticles As Novel Latent Fingerprint Development Agents, Lais F A M Oliveira, Lais V A T Da Silva, Artur F Sonsin, Meclycia S Alves, Cristiane V Costa, Jeane C S Melo, Nicholas Ross, Paul T Wady, Thomas Zinn, Ticiano G Do Nascimento, Eduardo J S Fonseca, Alexandro M L De Assis, A Robert Hillman, Adriana S Ribeiro

Faculty, Staff and Student Publications

A nanostructured hybrid material based on mesoporous silica nanoparticles (MCM-41) functionalized with chitosan and a fluorescent dye (dansylglycine), designated MCM-41@Ch@DnsGly, was synthesized and characterized with a view to its application for the visualization of latent fingerprints. These nanoparticles were applied as latent fingerprint developers for marks on surfaces of diverse chemical composition, topography, optical characteristics, and spatially variant nature, typical of forensically challenging evidence. For quality assessment of the enhanced fingermarks, the developed images were analyzed holistically using the UK Home Office scale, forensic protocols and, in terms of their constituent features (minutiae), using forensic software. Across a substantive collection …

Multiparametric Mri-Based Radiomic Models For Early Prediction Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Rania M Mohamed, Bikash Panthi, Beatriz E Adrada, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy Reed, Marion E Scoggins, Jong Bum Son, Alastair Thompson, Debu Tripathy, Vicente Valero, Peng Wei, Jason White, Gary J Whitman, Zhan Xu, Wei Yang, Clinton Yam, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between …

Patient-Reported Quality Of Life At Diagnosis In Adolescent And Young Adults With Cancer, Goldy C George, Clark Andersen, Xiaohui Tang, Elizabeth Rodriguez, Midhat Jafry, Maria C Swartz, Sairah Ahmed, Carlos H Barcenas, J Andrew Livingston, Michael E Roth, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: The overall landscape of health-related quality of life (HRQoL) has not been thoroughly investigated in adolescents and young adults (AYAs) with cancer. Data are also lacking on how well HRQoL at the time of cancer diagnosis can prognosticate long-term survival in AYA survivors.

Patients and methods: We included 3,497 survivors of AYA cancer (age 15-39 years at diagnosis) who completed the Short-Form 12 Health Survey (SF-12) HRQoL questionnaire at diagnosis. Physical component summary (PCS) and mental component summary (MCS) scores were generated, with scores < 50 representing poor HRQoL. Differences in HRQoL by patient characteristics and tumor type were investigated using violin plots and t tests/analysis of variance. The effect of HRQoL on overall survival was assessed using Kaplan-Meier plots and Cox proportional hazards models.

Results: Overall mean PCS and MCS scores in this racially/ethnically diverse cohort (64% White, 19% …

Learning To Express Reward Prediction Error-Like Dopaminergic Activity Requires Plastic Representations Of Time, Ian Cone, Claudia Clopath, Harel Z Shouval

Faculty, Staff and Student Publications

The dominant theoretical framework to account for reinforcement learning in the brain is temporal difference learning (TD) learning, whereby certain units signal reward prediction errors (RPE). The TD algorithm has been traditionally mapped onto the dopaminergic system, as firing properties of dopamine neurons can resemble RPEs. However, certain predictions of TD learning are inconsistent with experimental results, and previous implementations of the algorithm have made unscalable assumptions regarding stimulus-specific fixed temporal bases. We propose an alternate framework to describe dopamine signaling in the brain, FLEX (Flexibly Learned Errors in Expected Reward). In FLEX, dopamine release is similar, but not identical …

Monoallelic De Novo Ajap1 Loss-Of-Function Variants Disrupt Trans-Synaptic Control Of Neurotransmitter Release, Simon Früh, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaite, Li-Yuan Chen, Diego Fernandez-Fernandez, Pascal D Rem, Daniel Ulrich, Jochen Schwenk, Ziyang Chen, Elodie Le Monnier, Thorsten Fritzius, Sabrina M Innocenti, Valérie Besseyrias, Luca Trovò, Michal Stawarski, Emanuela Argilli, Elliott H Sherr, Bregje Van Bon, Erik-Jan Kamsteeg, Maria Iascone, Alba Pilotta, Maria R Cutrì, Mahshid S Azamian, Andrés Hernández-García, Seema R Lalani, Jill A Rosenfeld, Xiaonan Zhao, Tiphanie P Vogel, Herda Ona, Daryl A Scott, Peter Scheiffele, Kristian Strømgaard, Mehdi Tafti, Martin Gassmann, Bernd Fakler, Ryuichi Shigemoto, Bernhard Bettler

Faculty, Staff and Students Publications

Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed …

A Crisis In Clinical Research, David S Hong, Patricia Lorusso, Mario Sznol

Faculty, Staff and Student Publications

The clinical research pipeline is critical to ensuring continued development of novel treatments that can offer patients with cancer safe and effective options. Unfortunately, progress has slowed since the COVID-19 pandemic due to uncovered, systemic inefficiencies across critical processes. Towards initiating discussion on how to reinvigorate clinical research, the Society for Immunotherapy of Cancer (SITC) hosted a virtual summit that characterized issues and formed potential solutions. This commentary serves to highlight the crisis facing clinical research as well as stimulate field-wide discussion on how to better serve patients into the future.

Chronic Eosinophilic Leukemia With A Novel Jak1 Mutation Responds Well To The Jak1/2 Inhibitor Ruxolitinib, Qing Wei, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Emerging Biomedical And Clinical Applications Of 3d-Printed Poly(Lactic Acid)-Based Devices And Delivery Systems, Allan John R Barcena, Prashanth Ravi, Suprateek Kundu, Karthik Tappa

Faculty, Staff and Student Publications

Poly(lactic acid) (PLA) is widely used in the field of medicine due to its biocompatibility, versatility, and cost-effectiveness. Three-dimensional (3D) printing or the systematic deposition of PLA in layers has enabled the fabrication of customized scaffolds for various biomedical and clinical applications. In tissue engineering and regenerative medicine, 3D-printed PLA has been mostly used to generate bone tissue scaffolds, typically in combination with different polymers and ceramics. PLA's versatility has also allowed the development of drug-eluting constructs for the controlled release of various agents, such as antibiotics, antivirals, anti-hypertensives, chemotherapeutics, hormones, and vitamins. Additionally, 3D-printed PLA has recently been used …

Intrinsically Disordered Membrane Anchors Of Rheb, Rhoa, And Diras3 Small Gtpases: Molecular Dynamics, Membrane Organization, And Interactions, Chase M Hutchins, Alemayehu A Gorfe

Faculty, Staff and Student Publications

Protein structure has been well established to play a key role in determining function; however, intrinsically disordered proteins and regions (IDPs and IDRs) defy this paradigm. IDPs and IDRs exist as an ensemble of structures rather than a stable 3D structure yet play essential roles in many cell-signaling processes. Nearly all Ras superfamily GTPases are tethered to membranes by a lipid tail at the end of a flexible IDR. The sequence of the IDR is a key determinant of membrane localization, and interaction between the IDR and the membrane has been shown to affect signaling in RAS proteins through the …

Psmd11 Loss-Of-Function Variants Correlate With A Neurobehavioral Phenotype, Obesity, And Increased Interferon Response, Wallid Deb, Cory Rosenfelt, Virginie Vignard, Jonas Johannes Papendorf, Sophie Möller, Martin Wendlandt, Maja Studencka-Turski, Benjamin Cogné, Thomas Besnard, Léa Ruffier, Bérénice Toutain, Léa Poirier, Silvestre Cuinat, Amy Kritzer, Amy Crunk, Janette Dimonda, Jaime Vengoechea, Sandra Mercier, Lotte Kleinendorst, Mieke M Van Haelst, Linda Zuurbier, Telma Sulem, Hildigunnur Katrínardóttir, Rún Friðriksdóttir, Patrick Sulem, Kari Stefansson, Berglind Jonsdottir, Shimriet Zeidler, Margje Sinnema, Alexander P A Stegmann, Natali Naveh, Cara M Skraban, Christopher Gray, Jill R Murrell, Sedat Isikay, Davut Pehlivan, Daniel G Calame, Jennifer E Posey, Mathilde Nizon, Kirsty Mcwalter, James R Lupski, Bertrand Isidor, François V Bolduc, Stéphane Bézieau, Elke Krüger, Sébastien Küry, Frédéric Ebstein

Faculty, Staff and Students Publications

Primary proteasomopathies have recently emerged as a new class of rare early-onset neurodevelopmental disorders (NDDs) caused by pathogenic variants in the PSMB1, PSMC1, PSMC3, or PSMD12 proteasome genes. Proteasomes are large multi-subunit protein complexes that maintain cellular protein homeostasis by clearing ubiquitin-tagged damaged, misfolded, or unnecessary proteins. In this study, we have identified PSMD11 as an additional proteasome gene in which pathogenic variation is associated with an NDD-causing proteasomopathy. PSMD11 loss-of-function variants caused early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity in 10 unrelated children. Our findings demonstrate that the cognitive impairment observed in these individuals could be …

The Multifaceted Role Of Neutrophils In Nsclc In The Era Of Immune Checkpoint Inhibitors, Shucheng Miao, Bertha Leticia Rodriguez, Don L Gibbons

Faculty, Staff and Student Publications

Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to ICIs develops over time and dampens the efficacy of ICIs in patients. Tumor-associated neutrophils (TANs) have an important role in modulating the tumor microenvironment (TME) and tumor immune response. The major challenge in the field is to characterize the TANs in NSCLC TME and understand the link between TAN-related immunosuppression with ICI treatment response. In this review, …

Tsg-6+ Cancer-Associated Fibroblasts Modulate Myeloid Cell Responses And Impair Anti-Tumor Response To Immune Checkpoint Therapy In Pancreatic Cancer, Swetha Anandhan, Shelley Herbrich, Sangeeta Goswami, Baoxiang Guan, Yulong Chen, Marc Daniel Macaluso, Sonali Jindal, Seanu Meena Natarajan, Samuel W Andrewes, Liangwen Xiong, Ashwat Nagarajan, Sreyashi Basu, Derek Ng Tang, Jielin Liu, Jimin Min, Anirban Maitra, Padmanee Sharma

Faculty, Staff and Student Publications

Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. …

Radiation Therapy With Or Without Cisplatin For Local Recurrences Of Endometrial Cancer: Results From An Nrg Oncology/Gog Prospective Randomized Multicenter Clinical Trial, Ann H Klopp, Danielle Enserro, Matthew Powell, Marcus Randall, Julian C Schink, Robert S Mannel, Laura Holman, David Bender, Christina L Kushnir, Floor Backes, Susan L Zweizig, Steven Waggoner, Kristin A Bradley, Lana Desouza Lawrence, Parviz Hanjani, Christopher J Darus, William Small, Higinia R Cardenes, Jonathan M Feddock, David S Miller

Faculty, Staff and Student Publications

Purpose: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy.

Materials and methods: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS.

Results: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to …

Inverted Triplications Formed By Iterative Template Switches Generate Structural Variant Diversity At Genomic Disorder Loci, Christopher M Grochowski, Jesse D Bengtsson, Haowei Du, Mira Gandhi, Ming Yin Lun, Michele G Mehaffey, Kyunghee Park, Wolfram Höps, Eva Benito, Patrick Hasenfeld, Jan O Korbel, Medhat Mahmoud, Luis F Paulin, Shalini N Jhangiani, James Paul Hwang, Sravya V Bhamidipati, Donna M Muzny, Jawid M Fatih, Richard A Gibbs, Matthew Pendleton, Eoghan Harrington, Sissel Juul, Anna Lindstrand, Fritz J Sedlazeck, Davut Pehlivan, James R Lupski, Claudia M B Carvalho

Faculty, Staff and Students Publications

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. …

The Cns Relapse In T-Cell Lymphoma Index Predicts Cns Relapse In Patients With T- And Nk-Cell Lymphomas, Rahul S Bhansali, Fredrik Ellin, Thomas Relander, Miao Cao, Wenrui Li, Qi Long, Nivetha Ganesan, Robert Stuver, Steven M Horwitz, Kitsada Wudhikarn, Steven R Hwang, N Nora Bennani, Julio Chavez, Lubomir Sokol, Hayder Saeed, Frank Duan, Pierluigi Porcu, Priyanka Pullarkat, Neha Mehta-Shah, Jasmine M Zain, Miguel Ruiz, Jonathan E Brammer, Rishab Prakash, Swaminathan P Iyer, Adam J Olszewski, Ajay Major, Peter A Riedell, Sonali M Smith, Caroline Goldin, Bradley Haverkos, Bei Hu, Tony Z Zhuang, Pamela B Allen, Wael Toama, Murali Janakiram, Taylor R Brooks, Deepa Jagadeesh, Nisha Hariharan, Aaron M Goodman, Gabrielle Hartman, Paola Ghione, Fatima Fayyaz, Joanna M Rhodes, Elise A Chong, James N Gerson, Daniel J Landsburg, Sunita D Nasta, Stephen J Schuster, Jakub Svoboda, Mats Jerkeman, Stefan K Barta

Faculty, Staff and Student Publications

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. …

Leukocyte Immunoglobulin-Like Receptor B1 (Lilrb1) Protects Human Multiple Myeloma Cells From Ferroptosis By Maintaining Cholesterol Homeostasis, Miao Xian, Qiang Wang, Liuling Xiao, Ling Zhong, Wei Xiong, Lingqun Ye, Pan Su, Chuanchao Zhang, Yabo Li, Robert Z Orlowski, Fenghuang Zhan, Siddhartha Ganguly, Youli Zu, Jianfei Qian, Qing Yi

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients. LILRB1 deficiency inhibits MM progression in vivo by enhancing the ferroptosis of MM cells. Mechanistic studies reveal that LILRB1 forms a complex with the low-density lipoprotein receptor (LDLR) and LDLR adapter protein 1 (LDLRAP1) to facilitate LDL/cholesterol …

Cotargeting Ebv Lytic As Well As Latent Cycle Antigens Increases T-Cell Potency Against Lymphoma, Sandhya Sharma, Naren U Mehta, Tim Sauer, Lisa A Rollins, Dirk P Dittmer, Cliona M Rooney

Faculty, Staff and Students Publications

The remarkable efficacy of Epstein-Barr virus (EBV)-specific T cells for the treatment of posttransplant lymphomas has not been reproduced for EBV-positive (EBV+) malignancies outside the transplant setting. This is because of, in part, the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely latent membrane proteins 1 and 2, EBV nuclear antigen 1, and BamHI A rightward reading frame 1 (type-2 [T2] latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies and, because several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral …

Daratumumab In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis Of Clinically Relevant Subgroups In Griffin, Ajai Chari, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a …

Self-Explainable Graph Neural Network For Alzheimer Disease And Related Dementias Risk Prediction: Algorithm Development And Validation Study, Xinyue Hu, Zenan Sun, Yi Nian, Yichen Wang, Yifang Dang, Fang Li, Jingna Feng, Evan Yu, Cui Tao

Faculty, Staff and Student Publications

Background: Alzheimer disease and related dementias (ADRD) rank as the sixth leading cause of death in the United States, underlining the importance of accurate ADRD risk prediction. While recent advancements in ADRD risk prediction have primarily relied on imaging analysis, not all patients undergo medical imaging before an ADRD diagnosis. Merging machine learning with claims data can reveal additional risk factors and uncover interconnections among diverse medical codes.

Objective: The study aims to use graph neural networks (GNNs) with claim data for ADRD risk prediction. Addressing the lack of human-interpretable reasons behind these predictions, we introduce an innovative, self-explainable method …