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Articles 94381 - 94410 of 5209592
Full-Text Articles in Entire DC Network
Redefining The Role Of Chaperones For Dot/Icm T4bss-Mediated Substrate Translocation By Legionella Pneumophila, Sukhithasri Vijayrajratnam, Ahmet Hasanovic, Joseph P Vogel
Redefining The Role Of Chaperones For Dot/Icm T4bss-Mediated Substrate Translocation By Legionella Pneumophila, Sukhithasri Vijayrajratnam, Ahmet Hasanovic, Joseph P Vogel
2020-Current year OA Pubs
Legionella pneumophila, the etiological agent of legionnaires' disease, establishes its intracellular niche through the Dot/Icm type IVB secretion system, which translocates ∼300 effector proteins into host cells. Efficient secretion of many effectors requires the IcmS and IcmW chaperones, which interact with both substrates and the type IV coupling protein DotL. A prior model proposed that IcmSW are released from substrates during translocation by transfer to the C terminus of DotL and then recycled to the cytoplasm. This model predicts an excess cytoplasmic pool of IcmSW and their dissociation from DotL. We tested these predictions using quantitative stoichiometric analysis of Dot/Icm …
Myd88 Signaling In Myeloid Cells Induces Gastrointestinal Tract Injury And Systemic Inflammation After West Nile Virus Infection, Shih-Ching Lin, Fang R Zhao, Matthias Mack, Gabriel Mbalaviele, Michael S Diamond
Myd88 Signaling In Myeloid Cells Induces Gastrointestinal Tract Injury And Systemic Inflammation After West Nile Virus Infection, Shih-Ching Lin, Fang R Zhao, Matthias Mack, Gabriel Mbalaviele, Michael S Diamond
2020-Current year OA Pubs
Humans with autoantibodies to type I interferons (IFNs) are at higher risk for neurological disease after West Nile virus (WNV) infection. IFN signaling deficient WNV-infected mice develop greater inflammation in the brain, which correlates with loss of gut barrier integrity. Here, we investigate the immune pathways that mediate this virus-gut-brain axis of inflammation. Myd88
Dual Roles Of Trpv2 In The Innate Immune Response To Cytosolic Dna: Arresting Dormant And Boosting Activated Sting, Chen Cheng, Hsiang-Ting Lu, Shan Li, Zhongsheng You
Dual Roles Of Trpv2 In The Innate Immune Response To Cytosolic Dna: Arresting Dormant And Boosting Activated Sting, Chen Cheng, Hsiang-Ting Lu, Shan Li, Zhongsheng You
2020-Current year OA Pubs
The cGAS/STING-dependent innate immune pathway is central in the cellular response to cytosolic DNA derived from viral infections, genotoxic stress, or mitochondrial defects. While efficient activation of the pathway is crucial for defending against pathogens and cancer, maintaining its dormancy without stimuli is equally important to avoid autoimmunity. However, the precise control of the cGAS/STING pathway remains poorly understood. Here, we report that the ion channel TRPV2 regulates both the dormancy and activation of STING. TRPV2 associates with STING and suppresses spontaneous STING activation in the absence of cytoDNA but dissociates from STING and promotes its activation by releasing Ca
Distinct Contributions Of Etv2+ And Flk1+ Progenitors To Endothelial, Hematopoietic, And Cardiac Lineages, Dereck Alleyne, Minseo Kim, Jun Wu, Yoojung Kwon, Ye-Ram Kim, Ashraf Ul Kabir, Matthew Ishahak, Jeffrey R Millman, Changxu Fan, Hyung Joo Lee, Karen Krchma, Xiaoyun Xing, Kory Lavine, Ting Wang, Kyunghee Choi
Distinct Contributions Of Etv2+ And Flk1+ Progenitors To Endothelial, Hematopoietic, And Cardiac Lineages, Dereck Alleyne, Minseo Kim, Jun Wu, Yoojung Kwon, Ye-Ram Kim, Ashraf Ul Kabir, Matthew Ishahak, Jeffrey R Millman, Changxu Fan, Hyung Joo Lee, Karen Krchma, Xiaoyun Xing, Kory Lavine, Ting Wang, Kyunghee Choi
2020-Current year OA Pubs
The ETS family transcription factor ETV2, VEGFA, and its receptor FLK1 are essential for hematopoietic, vascular, and cardiac development. Here, we combine dual Etv2 and Flk1 lineage tracing with molecular profiling to define how mesoderm progenitors are allocated to hematopoietic, endothelial, cardiomyocyte, and smooth muscle lineages. We demonstrate that hematopoietic, endothelial, and cardiac valves arise from dual Etv2
Ablation Of Cd38 In Multiple Myeloma Cells Leads To An Aggressive Phenotype In A Mouse Xenograft Model, Michael R Dyer, Alex Zheleznyak, Erin N Teubner, Julie L Prior, Brad Manion, Zhenghan Jing, Amit K Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F Dipersio, Deborah Veis, Julie O'Neal, Mikhail Y Berezin, Monica Shokeen
Ablation Of Cd38 In Multiple Myeloma Cells Leads To An Aggressive Phenotype In A Mouse Xenograft Model, Michael R Dyer, Alex Zheleznyak, Erin N Teubner, Julie L Prior, Brad Manion, Zhenghan Jing, Amit K Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F Dipersio, Deborah Veis, Julie O'Neal, Mikhail Y Berezin, Monica Shokeen
2020-Current year OA Pubs
Multiple myeloma (MM) is a plasma cell malignancy characterized by bone pain and end-organ failure. A major challenge in treating MM is therapeutic resistance. CD38-targeted immunotherapies, such as daratumumab, have significantly improved outcomes; however, variable responses, resistance, and relapse remain vital challenges. We hypothesized that loss of CD38 drives a more aggressive phenotype and resistance to therapy. To test this, we developed a CD38 knockout (KO) clone of a human MM cell line and evaluated it in immunodeficient mice. Mice with CD38 KO tumors exhibited an increased tumor burden and reduced survival compared with those with CD38 wild-type (WT) tumors. …
Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang
Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang
2020-Current year OA Pubs
BACKGROUND: Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored. RESULTS: In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …
Inducible Deletion Of Dgat1 And 2 From Microglia Exacerbates Neurodegeneration And Endolysosomal Lipid Accumulation In Male Ps19 Mice, G Travis Tabor, Alexandra Litvinchuk, Yun Chen, Austin Allison, Carisa Zeng, Hao Hu, Peter B Lin, Prabal Sharma, Samira Parhizkar, Sihui Song, Xin Bao, Abhirami K Iyer, Shih Feng You, Javier Remolina Serrano, Melissa Manis, Emily Franke, Anil G Cashikar, Carla M Yuede, Celeste M Karch, Eric J Huang, Maxim Artyomov, Jason D Ulrich, David M Holtzman, Et Al.
Inducible Deletion Of Dgat1 And 2 From Microglia Exacerbates Neurodegeneration And Endolysosomal Lipid Accumulation In Male Ps19 Mice, G Travis Tabor, Alexandra Litvinchuk, Yun Chen, Austin Allison, Carisa Zeng, Hao Hu, Peter B Lin, Prabal Sharma, Samira Parhizkar, Sihui Song, Xin Bao, Abhirami K Iyer, Shih Feng You, Javier Remolina Serrano, Melissa Manis, Emily Franke, Anil G Cashikar, Carla M Yuede, Celeste M Karch, Eric J Huang, Maxim Artyomov, Jason D Ulrich, David M Holtzman, Et Al.
2020-Current year OA Pubs
Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed to be contained in lipid droplets (LDs). While studies have been performed in cell culture and Drosophila models to characterize glial LDs, the roles of microglial LD biogenesis in mammalian tauopathy are unclear. To address this issue, we induced the deletion of diacylglycerol acyltransferases (DGATs) 1 and 2, enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. Microglial DGAT double knockout (KO) exacerbated neurodegeneration and increased the abundance of brain cholesteryl esters in male PS19 …
Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.
Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.
2020-Current year OA Pubs
CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67
Mental Health And Conflicts: A Handbook For Empowerment, Dan Berstein
Mental Health And Conflicts: A Handbook For Empowerment, Dan Berstein
DRI Press
Mental health needs are universal. About half of us will end up having a diagnosable mental health issue at some point during our lives, and we all know what it is like to have a bad day. We also understand conflicts are hard and they often bring out the worst in us. There are simple ways to be ready for when mental health needs arise during conflicts. This handbook introduces different mental health perspectives, dispels common stereotypes, and provides tools for empowering mental health communication. This book is designed to help laypeople as well as professionals across all kinds of …
Future-Proofing Malaysian Graduates Through Industry-Recognised Credentials And Artificial Intelligence (Ai) Competencies: Case Studies From Industry Leaders., Yeoh Jor Ji
Student Works (2020-2029)
The evolving demands of Malaysian industries for highly skilled graduates have intensified competition and highlighted a growing skills mismatch, as academic institutions struggle to align their offerings with workforce needs. Recent data from the Department of Statistics Malaysia (DOSM) shows a 4.2% rise in the number of graduates in 2023, along with a 4.3% decrease in the unemployment rate due to the recovery of the economy after the pandemic. However, youth graduates aged 24 years and below experienced a high skill-related underemployment rate, which remained at 67.0% in 2023 compared to 62.3% in 2022. Despite an increasing number of graduates, …
Beyond The Rash: Cutaneous Peripheral T-Cell Lymphoma As A Diagnostic Pitfall In Primary Care, Jared Hensley, Aura Calderon, Blake Martin, Cristina Kochi, Andres Suarez Parraga
Beyond The Rash: Cutaneous Peripheral T-Cell Lymphoma As A Diagnostic Pitfall In Primary Care, Jared Hensley, Aura Calderon, Blake Martin, Cristina Kochi, Andres Suarez Parraga
School of Medicine Publications
Cutaneous manifestations of T-cell lymphomas may resemble common dermatologic or infectious conditions, increasing the risk of delayed recognition. We report a 78-year-old woman with known peripheral T-cell lymphoma (PTCL) who presented with a rapidly progressive, diffuse erythematous rash accompanied by cervical lymphadenopathy. Initial evaluation prioritized more common etiologies; however, inpatient medicine broadened the differential diagnosis, prompting early hematology and oncology consultation. Contrast-enhanced CT of the neck demonstrated multiple enlarged, partially necrotic left cervical lymph nodes consistent with disease progression. After multidisciplinary discussions and consideration of prognosis, the patient elected palliative-focused management with oncology follow-up. This case underscores the importance of …
Predictions Of Masses For Light Hybrid Baryons, Qi-Nan Wang, Ding-Kun Lian, Wei Chen, Hui-Min Yang, Hua-Xing Chen, Jason N.E. Ho, T. G. Steele
Predictions Of Masses For Light Hybrid Baryons, Qi-Nan Wang, Ding-Kun Lian, Wei Chen, Hui-Min Yang, Hua-Xing Chen, Jason N.E. Ho, T. G. Steele
Faculty Work Comprehensive List
Within the method of parity-projected QCD sum rules, we study the mass spectra of light hybrid baryons with 𝐼(𝐽𝑃) =1/2(1/2±),3/2(1/2±),1/2(3/2±),3/2(3/2±) by constructing the local 𝑞𝑞𝑞𝑔 interpolating currents. We calculate the correlation functions up to dimension eight condensates at the leading order of 𝛼𝑠. The stable QCD Lapalce sum rules can be established for the positive-parity 𝑁1/2+,Δ3/2+,Δ1/2+ and negative-parity 𝑁1/2−,𝑁3/2−,Δ1/2− channels to extract their mass spectra. The lowest-lying hybrid baryons are predicted to be the positive-parity 𝑁1/2+ state around 2.01 GeV. These hybrid baryons mainly decay into conventional baryon plus meson final states. We propose to search for the light hybrid …
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, Veena Kochat, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, Veena Kochat, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Faculty, Staff and Student Publications
Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, Veena Kochat, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, Veena Kochat, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting
Faculty, Staff and Student Publications
Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …
Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Alexander T Chesler, Julio F Cordero-Morales, Valeria Vásquez
Structures Of Invertebrate Pezo-1 Isoforms With A Compact Architecture And A Dispensable Pore-Distal N-Terminal Blade, Briar Bell, Angela M Jaramillo-Granada, Daniel J Orlin, Wei-Hsiang Weng, Haosheng Wen, Alexander T Chesler, Julio F Cordero-Morales, Valeria Vásquez
Faculty, Staff and Student Publications
PIEZO channels are mechanosensitive ion channels conserved from plants to humans, yet structures exist for only a few mammalian orthologs. We define the structural and functional diversity of Caenorhabditis elegans PEZO-1, a single gene with extensive alternative splicing, by determining cryo-electron microscopy structures of three representative isoforms: G (full length), K (lacking the pore-distal N-terminal blade), and L (missing most of the blade). PEZO-1G displays mechanically evoked currents yet adopts a compact, semi-flattened conformation that significantly differs from the mammalian domes. The blades exhibit a three-step slope architecture stabilized by inter-blade latching among transmembrane helical units, yielding a circular, steering-wheel-like …
Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Bin Liu, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu
Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Bin Liu, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu
Faculty, Staff and Student Publications
TRPV1, a member of the transient receptor potential vanilloid subfamily, mediates nociception and thermoregulation. TRPV1-targeting analgesics frequently induce hyperthermia, underscoring the need for structural insights to guide the development of safer compounds. Here, we determined the structures of rat TRPV1 bound to the clinical candidate analgesics AMG517, AMG9810, and SB366791. AMG517 and AMG9810 are deeply situated within the S3-S4 interface of the vanilloid pocket, where they interact with residues from the S3-S6 helices, as well as the S4-S5 linker. These interactions induce local deformations in the TRP-box and lower S6 helix, accompanied by a modest rotation of the S1-S4 bundle, …
Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello
Beyond Neurons: Impact Of Cannabidiol On Glial Cells In Ischemic Stroke, Victória Linden De Rezende, Khiany Mathias, Cinara Ludvig Gonçalves, Rafael Mariano De Bitencourt, Tatiana Barichello
Faculty, Staff and Student Publications
Ischemic stroke triggers a complex cascade of events involving inflammation, oxidative stress, and glial cell dysfunction, all of which contribute to neuronal damage and impaired recovery. Glial cells (e.g., astrocytes, microglia, and oligodendrocytes) play key roles in neuroinflammatory responses, making them attractive targets for therapeutic modulation. Cannabidiol, a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory, antioxidant, and neuroprotective properties. Preclinical evidence indicates that cannabidiol attenuates glial reactivity, reduces pro-inflammatory signaling, mitigates oxidative stress, and preserves blood-brain and intestinal barrier integrity in stroke models. Moreover, cannabidiol modulates key molecular pathways (e.g., nuclear factor-κB, tumor necrosis factor, and calcium-related signaling), contributing to …
Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin
Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin
Faculty, Staff and Student Publications
Background/Objectives: The bacterial cell division machinery is emerging as an attractive target for antimicrobial compounds. FtsZ, a highly conserved essential division protein, is the target for a number of small molecules such as benzamides. Recent studies show that benzodioxane-benzamides (BDOBs) are among the most potent inhibitors of FtsZ function in Gram-positive bacteria, although their ability to inhibit Gram-negative FtsZ, in particular Escherichia coli FtsZ, has been more controversial.
Methods: Here, we use genetic and cytological methods to demonstrate that FtsZ of efflux pump-disabled E. coli can be efficiently targeted by BDOBs.
Results: We show that engineered mutants …
Coexisting Salps Exhibit Distinct Feeding Selectivity On Microorganisms In The North Pacific Subtropical Gyre, Anne W. Thompson, Kylee Lamberson, Kelly R. Sutherland
Coexisting Salps Exhibit Distinct Feeding Selectivity On Microorganisms In The North Pacific Subtropical Gyre, Anne W. Thompson, Kylee Lamberson, Kelly R. Sutherland
Biology Faculty Publications and Presentations
Mortality mechanisms play an important role in how oceanic microorganisms contribute to global biogeochemical cycles. Salps are widespread pelagic tunicates known to remove phytoplankton from coastal and high-latitude waters, but their interaction with microorganisms in the vast tropical and subtropical gyres is not well quantified. Using quantitative measurements of six major marine microorganisms in the guts of six distinct but co-occurring salp species from the North Pacific Subtropical Gyre, we examined the impact and dynamics of salp feeding on marine microorganisms in a vast open ocean region. All salps preferentially removed prey greater than 1 μm in diameter, including marine …
Cabozantinib And Thromboembolism In Patients With Cancer: A Systematic Review, Meta-Analysis, And Retrospective Study, Raj S Kasthuri
Cabozantinib And Thromboembolism In Patients With Cancer: A Systematic Review, Meta-Analysis, And Retrospective Study, Raj S Kasthuri
Faculty, Staff and Student Publications
Antiangiogenic agents, including vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), represent an important class of treatments for a range of solid tumors. However, concerns have arisen over potential associations between antiangiogenic agents and thromboembolic events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared a frequently used VEGFR TKI, cabozantinib, with placebo or usual care. The primary outcome was the risk of any thromboembolism. Secondary outcomes included the risk of venous thromboembolism (VTE), risk of arterial thromboembolism (ATE) and progression-free survival. 14 RCTs were included with a combined total of 4204 patients, …
Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Nithya Sridhar, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee
Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Nithya Sridhar, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee
Faculty, Staff and Student Publications
Purpose: Antibody-drug conjugates (ADCs) have transformed the treatment of breast cancer. FDA-approved ADCs such as trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) have demonstrated clinical benefit; however, drug resistance will almost inevitably emerge in the metastatic setting, and there is no established strategy for selecting subsequent ADCs after disease progression to the first exposure to the ADC. This study aimed to define mechanisms of acquired resistance and evaluate rational sequencing approaches.
Experimental design: We generated breast cancer cell lines resistant to T-DXd (TDXd-R) and SG (SG-R). We assessed antigen expression, internalization, and resistance pathways, including efflux transporter …
Recurrence Of Locally Perturbed Random Walks With Long Jumps, Tamer Oraby, András Telcs
Recurrence Of Locally Perturbed Random Walks With Long Jumps, Tamer Oraby, András Telcs
School of Mathematical & Statistical Sciences Faculty Publications
We study the effect of local perturbations on the recurrence of random walks with long jumps. Such walks serve as discrete models for infinite-horizon Lorentz processes, in which a particle can take arbitrarily long steps in specific directions. Motivated by a question of Sinai in the finite-horizon case and its extension by Szász to the infinite-horizon setting, we give recurrence and transience criteria for long-jump walks on Z2 and certain classes of graphs, and we prove that local perturbations in a bounded region do not change the recurrence property. Our proofs combine the Markov chain approach with the electrical network …
Staff Education To Increase Knowledge And Awareness Of Cultural Sensitivity Among Providers, Stephanie Chiamaka Anyanwu
Staff Education To Increase Knowledge And Awareness Of Cultural Sensitivity Among Providers, Stephanie Chiamaka Anyanwu
Walden Dissertations and Doctoral Studies
This Doctor of Nursing Practice (DNP) project aimed to enhance cultural sensitivity among healthcare providers through an educational intervention in a local organization. With the U.S. foreign-born population exceeding 47 million, the need for culturally competent care has become paramount. The study involved nine participants who underwent a pretest and posttest assessment to evaluate their knowledge and awareness of cultural sensitivity. Results indicated a significant increase in knowledge, with pretest and posttest scores improving from a mean of 4.33 to 8.56 (p < 0.01). Awareness in key areas such as patient-provider relationships, cultural beliefs, and language barriers also showed marked improvement. These findings further support the necessity of ongoing cultural sensitivity training to enhance patient care and outcomes, highlighting the potential for broader application across healthcare institutions.
Digital Trust Recovery: Effective Data Breach Management Approaches, Milbert Flores Dacayana
Digital Trust Recovery: Effective Data Breach Management Approaches, Milbert Flores Dacayana
Walden Dissertations and Doctoral Studies
In the digital economy, organizations face an increasing number of data breaches that compromise sensitive information and erode consumer trust. Some organizational leaders are concerned about the lack of effective strategies to manage data breaches and restore stakeholder confidence, which threatens organizations’ reputation and financial stability, and long-term trust in digital systems. Grounded in cybersecurity risk management theory (CRMT) and situational crisis communication theory (SCCT), the purpose of this qualitative pragmatic inquiry was to explore the strategies employed by data managers in Virginia, Maryland, and Washington, DC, to manage data breaches and rebuild consumer trust. Participants were 10 experienced data …
Staff Education To Improve Nurses' Knowledge And Confidence In Suicide Risk Assessment, Sherica Mcbride
Staff Education To Improve Nurses' Knowledge And Confidence In Suicide Risk Assessment, Sherica Mcbride
Walden Dissertations and Doctoral Studies
The purpose of this Doctor of Nursing Practice staff education project was to strengthen nurses’ knowledge and confidence in suicide risk assessments. Suicide remains a crucial patient safety issue, and nurses report uncertainty in early recognition and intervention; therefore, brief, practice-proximal training is essential. The practice-focused question that informed this project’s purpose was whether a short education module with pre- and post testing improves nurses’ knowledge and confidence in suicide risk assessment. Three nurses participated in a structured session covering risk factors, warning signs, standardized screening, and safety planning. I then used descriptive analysis to compare their pre- and posttest …
Predicting Perceived Immigrant Threat To National Identity Based On Christian Nationalism, White Racial Centrality, And Social Dominance Orientation, Anna Caroline Kinney
Predicting Perceived Immigrant Threat To National Identity Based On Christian Nationalism, White Racial Centrality, And Social Dominance Orientation, Anna Caroline Kinney
Walden Dissertations and Doctoral Studies
Immigrants remain frequent targets of anti-immigrant hate speech, often amplified by right-wing media. Demographic factors such as Christian nationalism (i.e., the desire to preserve Christian symbols, beliefs, and policies preserved as the established religion of the United States), White racial centrality (i.e., an automatic association between the self and the White ingroup), and social dominance orientation (i.e., support for group-based hierarchies and inequality) significantly shape perceptions of immigrants as a threat to national identity. Although prior research has examined these factors independently, their relative importance in predicting perceived immigrant threat remains limited. Informed by intergroup threat theory, this quantitative study …
Staff Education On Metabolic Syndrome Screening In Patients Receiving Long-Acting Injectable Psychotropics, Efetze Metangpa Akana
Staff Education On Metabolic Syndrome Screening In Patients Receiving Long-Acting Injectable Psychotropics, Efetze Metangpa Akana
Walden Dissertations and Doctoral Studies
Summary This Doctor of Nursing Practice project was a staff education initiative designed to improve metabolic syndrome screening practices for patients receiving long-acting injectable psychotropic medications in an outpatient psychiatric setting. People living with serious mental illness face a heightened risk of cardiometabolic conditions, and inconsistent screening leads to delayed detection, avoidable illness, and ongoing health disparities, underscoring the importance of this practice gap within nursing practice due to nurses’ central role in medication oversight and preventive care. A key limitation of the project was the small sample size and short-term evaluation period, which limited generalizability and did not allow …
Reflective Parenting, Psychological Needs, And Parental Interpretation Of Children’S Negative Emotions, Julia Pappas
Reflective Parenting, Psychological Needs, And Parental Interpretation Of Children’S Negative Emotions, Julia Pappas
Walden Dissertations and Doctoral Studies
Parents’ ability to understand and respond effectively to children’s negative emotions plays a critical role in children’s emotional development and regulation. However, it remains unclear whether parents interpret negative emotions as potential signals of underlying psychological needs. Based in the conceptual framework of parental reflective functioning and basic psychological needs theory, and grounded in interpretivist- constructivist paradigm, the purpose of this basic qualitative study was to examine how parents interpret children’s negative emotions and how their meaning-making processes relate to basic psychological needs. Semistructured interviews were conducted with parents of children between ages 3 and 9 years old (N = …
Strategies Leaders In Structured Alternative Academic Environments Use To Improve Resource Management, Operational Efficiency, And Program Sustainability, Sean D. Clark
Walden Dissertations and Doctoral Studies
Leaders of structured alternative academic environments often struggle to sustain operations because of limited resources, fragmented leadership, and high staff turnover. This business problem is important to leaders of structured alternative academic environments because ineffective resource management and operational inefficiencies threaten program sustainability and continuity of services for at-risk student populations. Grounded in transformational leadership theory, the purpose of this qualitative pragmatic inquiry was to explore the strategies leaders in structured alternative academic environments use to improve resource management, operational efficiency, and program sustainability. The participants were six leaders from structured alternative academic programs in southeastern New Mexico. Data were …
Leadership Strategies Used By Entrepreneurial Ecosystem Resource Providers To Support Entrepreneurial Success, Sarah Niehaus
Leadership Strategies Used By Entrepreneurial Ecosystem Resource Providers To Support Entrepreneurial Success, Sarah Niehaus
Walden Dissertations and Doctoral Studies
Failure to collaborate effectively within entrepreneurial ecosystems remains a significant concern for leaders of entrepreneurial ecosystem organizations. Without clear, actionable collaboration strategies, these leaders may struggle to support entrepreneurial success and make informed decisions that enhance financial performance. Grounded in Mockler’s complex adaptive systems theory, the purpose of this qualitative pragmatic inquiry was to identify and explore effective strategies some leaders within entrepreneurial ecosystem organizations use to collaborate in a manner that supports entrepreneurial success. Participants included seven leaders of entrepreneurial ecosystem organizations located in the Midwest United States with successful experiences using such strategies. Data were collected from semistructured …