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Articles 1831 - 1860 of 44978

Full-Text Articles in Medical Sciences

Mechanistic Insights Into The Antimicrobial Effect Of Benzodioxane-Benzamides Against Escherichia Coli, Lorenzo Suigo, Alessia Lanzini, Valentina Straniero, William Margolin Jan 2026

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 …


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, Fabricia Petronilho Jan 2026

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, Fabricia Petronilho

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 …


Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting Jan 2026

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, 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, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, Julio F Cordero-Morales, Valeria Vásquez Jan 2026

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, Marcos Sotomayor, Alexander T Chesler, Matthew L Baker, 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, Han-Wen Li, Bin Liu, Fán Yang, Mei-Rong Chen, Mei-Ling Lu, Michael X Zhu, Fan Yang, Yi-Bei Xiao, Ye Yu Jan 2026

Structures Of Trpv1 Bound By Hyperthermia-Inducing Analgesics, Yu-Hao Gao, Yi-Zhe Huang, Zhao-Xing Li, Xiao-Ying Chen, Chang-Yan Shao, Han-Wen Li, Bin Liu, Fán Yang, 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, …


Analysis Of The Effect Of Neuro-Developmental Treatment (Ndt) On Gross Motor Function In Children With Spastic Diplegic Cerebral Palsy: A Systematic Review, Haunan Naja Izdihar, Aditya Denny Pratama Jan 2026

Analysis Of The Effect Of Neuro-Developmental Treatment (Ndt) On Gross Motor Function In Children With Spastic Diplegic Cerebral Palsy: A Systematic Review, Haunan Naja Izdihar, Aditya Denny Pratama

Jurnal Vokasi Indonesia

Effectiveness of Neurodevelopmental Treatment (NDT) in Children with Spastic Diplegia Cerebral Palsy: A Systematic Review

Background:
Neurodevelopmental Treatment (NDT) is commonly used in pediatric rehabilitation to improve motor function in children with cerebral palsy, particularly those with spastic diplegia.

Methods:
This systematic review followed PRISMA 2020 guidelines. Seven studies published between 2018 and 2024 were identified through electronic databases, including PubMed, Scopus, ProQuest, ScienceDirect, SpringerLink, Cochrane Library, Google Scholar, and Crossref.

Results:
The included studies reported improvements in gross motor function, posture, balance, and daily functional independence following NDT, particularly when combined with other therapeutic interventions. However, outcome measures and …


Assessing Predoctoral Dental Student Interest In Nutrition Education: A Study Across Two Dental Schools, Nadine M. Tassabehji, Xiaoyuan Han, Parvati Iyer Dr., Michelle Brady, Matthew Finkelman, Shafa Nathani, Anna Garrison, Annie Han Jan 2026

Assessing Predoctoral Dental Student Interest In Nutrition Education: A Study Across Two Dental Schools, Nadine M. Tassabehji, Xiaoyuan Han, Parvati Iyer Dr., Michelle Brady, Matthew Finkelman, Shafa Nathani, Anna Garrison, Annie Han

Pacific Journal of Health

The mouth is a mirror of overall health. Dentists have a vital role in the diagnosis of oral diseases, prevention, for health promotion. The purposes of our exploratory study were to investigate dental students’ attitudes and perceptions regarding nutrition education and to propose a curriculum checklist for integrating nutrition content into dental curricula.

An optional exploratory survey was distributed at two North American urban dental schools to 351 students, to compare student perspectives regarding implementation of nutrition education. The results were analyzed as a step to improve nutrition education in dental curricula. A validated stepwise checklist was developed to guide …


Changing Bodies And The History Of Anthropometrics, Moramay López-Alonso Jan 2026

Changing Bodies And The History Of Anthropometrics, Moramay López-Alonso

History of Medicine Seminar

No abstract provided.


An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler Jan 2026

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …


Intouch Week Of January 26, 2026, New York Medical College Jan 2026

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry Jan 2026

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry

Faculty, Staff and Student Publications

Background: Timely reperfusion is critical in reducing mortality in ST-segment elevation myocardial infarction (STEMI). Although electrocardiography-guided cardiac catheterization laboratory (CCL) activation on the basis of first medical contact recognition improves system-level response, diagnostic uncertainty, particularly in atypical presentations, contributes to false positive activations (FPAs) and reperfusion delays.

Objectives: The aim of this study was to evaluate the diagnostic performance and operational impact of artificial intelligence (AI)-based electrocardiographic (ECG) analysis in real-world STEMI triage across a multicenter U.S. registry.

Methods: A total of 1,032 patients with suspected STEMI who triggered emergent CCL activation at 3 geographically diverse percutaneous coronary intervention centers …


High Levels Of Circulating Mir-19a-3p In Patients With Metastatic Her2 + Breast Cancer Are Associated With A Favorable Prognosis And Anti-Tumor Immune Responses, Evan N Cohen, Hui Gao, Sanda Tin, Qiong Wu, Cristina Ivan, Naoto T Ueno, Wendy A Woodward, James M Reuben, Simone Anfossi Jan 2026

High Levels Of Circulating Mir-19a-3p In Patients With Metastatic Her2 + Breast Cancer Are Associated With A Favorable Prognosis And Anti-Tumor Immune Responses, Evan N Cohen, Hui Gao, Sanda Tin, Qiong Wu, Cristina Ivan, Naoto T Ueno, Wendy A Woodward, James M Reuben, Simone Anfossi

Faculty, Staff and Student Publications

Background: Trastuzumab, combined with chemotherapy, is the current standard treatment for both metastatic and early-stage HER2-positive (HER2 +) breast cancer. One of the mechanisms of action of trastuzumab is antibody-dependent cellular cytotoxicity (ADCC), which involves engaging FcγRIIIA (CD16) on natural killer (NK) cells. A competent immune system and properly functioning NK cells are crucial for effective ADCC, as they can influence favorable clinical outcomes. Resistance to trastuzumab often develops after about one year. We previously reported that elevated levels of miR-19a-3p in the serum of patients with metastatic HER2 + breast cancer treated with trastuzumab were associated with a favorable …


Intestinal Epithelial Tlr5 Signaling Promotes Barrier-Supportive Macrophages, Ming-Ting Tsai, Ryann Callaghan, Charles Ng, Lisette Peres-Tintin, Dean B Matthews, Nikketa Stanford, Karuna Ganesh, Mary K Estes, Gretchen E Diehl Jan 2026

Intestinal Epithelial Tlr5 Signaling Promotes Barrier-Supportive Macrophages, Ming-Ting Tsai, Ryann Callaghan, Charles Ng, Lisette Peres-Tintin, Dean B Matthews, Nikketa Stanford, Karuna Ganesh, Mary K Estes, Gretchen E Diehl

Faculty, Staff and Students Publications

Intestinal macrophages are essential for epithelial barrier repair. In homeostasis, macrophages are continuously replenished by recruitment of circulating CCR2+ monocytes into the intestinal lamina propria. This requires the commensal microbiota, however, the specific microbial factors and downstream host pathways that coordinate macrophage replenishment are inadequately understood. Here, we show that colonization with an E. coli isolate increased CCR2+ macrophages in the intestine and ameliorated pathology in a colitis model. Using human colonic organoids, we showed E. coli colonization induced CCL2 secretion by intestinal epithelial stem cells which promoted monocyte migration. In vivo, protection was abolished in the absence of epithelial …


Hiv Vpr Induces Demethylation Of The Snca Antisense Promoter, Leading To Neurocognitive Impairment, Maryline Santerre, Ying Wang, Daniel Kalamarides, Jin Park, Lynn G Kirby, Jeannie Chin, Jaroslav Jelinek, Natalia Shcherbik, Bassel E Sawaya Jan 2026

Hiv Vpr Induces Demethylation Of The Snca Antisense Promoter, Leading To Neurocognitive Impairment, Maryline Santerre, Ying Wang, Daniel Kalamarides, Jin Park, Lynn G Kirby, Jeannie Chin, Jaroslav Jelinek, Natalia Shcherbik, Bassel E Sawaya

Faculty, Staff and Students Publications

Human immunodeficiency virus type 1 (HIV-1) alpha-synuclein (α-Syn) aggregation is a hallmark of neurodegenerative diseases. Accumulation and aggregation of α-Syn are often observed in individuals with HIV-1 cognitive impairments. The direct mechanistic link between α-Syn dysregulation and HIV-associated neurocognitive disorders (HAND) remains unclear. Emerging evidence suggests that epigenetic changes, particularly deoxyribonucleic acid (DNA) demethylation, influence α-Syn regulation. We show that the HIV-1 protein viral protein R (Vpr) demethylates the antisense promoter within intron 1 of the alpha-synuclein gene (SNCA), potentially contributing to increased α-Syn expression. Elevated α-Syn promotes aggregation, causing synaptic dysfunction and impaired mitochondrial transport. These processes contribute to …


De Novo Variants In The Splicing Factor Gene Sf3b1 Are Associated With Neurodevelopmental Disorders, Kevin Uguen, Tiffany Bergot, Marie-Pier Scott-Boyer, Solène Chapalain, Camille Desdouets, Séverine Commet, Changlian Zhu, Yiran Xu, Yangong Wang, Tony Roscioli, Frederic Tran-Mau-Them, Laurence Faivre, Julien Maraval, Julian Delanne, Anne-Sophie Denommé-Pichon, Antonio Vitobello, Céline Jost, Marc Planes, Susan Hiatt, Patricia Wheeler, Claudia Gonzaga-Jauregui, Heng Wang, Baozhong Xin, Valerie Sency, Michael C Kruer, Somayeh Bakhtiari, Patrick Sulem, Cynthia Curry, Trine Prescott, Gertrud Strobl-Wildemann, Theresa Brunet, Martine Doco Fenzy, Thomas Courtin, Céline Poirsier, Trine Bjørg Hammer, Christina D Fenger, Melissa Macpherson, Kosuke Izumi, Jacqueline Leonard, Dong Li, Elaine H Zackai, Ian A Glass, Scott Ward, Philippe M Campeau, Maria Carla Hermida Borroto, Laurence Le Moigno, Hilde Van Esch, Liesbeth De Waele, Daniel G Calame, James R Lupski, Giulia Barcia, Cristina Peduto, Pauline Planté-Bordeneuve, Lucie Dupuis, Roberto Mendoza-Londono, Dimitri J Stavropoulos, Jennifer Gillibert-Duplantier, Thomas Besnard, Laura Do Souto Ferreira, Benjamin Cogné, Stéphane Bézieau, Arnaud Droit, Laurent Corcos, Eric Lippert, Claude Férec, Sebastien Küry, Delphine G Bernard Jan 2026

De Novo Variants In The Splicing Factor Gene Sf3b1 Are Associated With Neurodevelopmental Disorders, Kevin Uguen, Tiffany Bergot, Marie-Pier Scott-Boyer, Solène Chapalain, Camille Desdouets, Séverine Commet, Changlian Zhu, Yiran Xu, Yangong Wang, Tony Roscioli, Frederic Tran-Mau-Them, Laurence Faivre, Julien Maraval, Julian Delanne, Anne-Sophie Denommé-Pichon, Antonio Vitobello, Céline Jost, Marc Planes, Susan Hiatt, Patricia Wheeler, Claudia Gonzaga-Jauregui, Heng Wang, Baozhong Xin, Valerie Sency, Michael C Kruer, Somayeh Bakhtiari, Patrick Sulem, Cynthia Curry, Trine Prescott, Gertrud Strobl-Wildemann, Theresa Brunet, Martine Doco Fenzy, Thomas Courtin, Céline Poirsier, Trine Bjørg Hammer, Christina D Fenger, Melissa Macpherson, Kosuke Izumi, Jacqueline Leonard, Dong Li, Elaine H Zackai, Ian A Glass, Scott Ward, Philippe M Campeau, Maria Carla Hermida Borroto, Laurence Le Moigno, Hilde Van Esch, Liesbeth De Waele, Daniel G Calame, James R Lupski, Giulia Barcia, Cristina Peduto, Pauline Planté-Bordeneuve, Lucie Dupuis, Roberto Mendoza-Londono, Dimitri J Stavropoulos, Jennifer Gillibert-Duplantier, Thomas Besnard, Laura Do Souto Ferreira, Benjamin Cogné, Stéphane Bézieau, Arnaud Droit, Laurent Corcos, Eric Lippert, Claude Férec, Sebastien Küry, Delphine G Bernard

Faculty, Staff and Students Publications

SF3B1 is an essential and ubiquitous splicing factor that plays a pivotal role in the early steps of pre-mRNA splicing. Recurrent somatic missense mutations in SF3B1 are frequent in cancers, but no constitutional variant has been reported so far. We describe here a cohort of 26 individuals with neurodevelopmental disorders, harbouring SF3B1 constitutional heterozygous variants that appeared mostly de novo. Patients present with a global developmental delay, associated with variable neurological and facial dysmorphic traits. A dichotomy may emerge between patients harbouring predicted loss of function (n = 9) and missense variants (n = 17), the latter being associated with …


Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere Jan 2026

Clinical Workflow Of Spine Stereotactic Radiotherapy And Radiosurgery: Insights From A Single-Institution Physics Perspective, Dennis Mackin, Gizem Cifter, Yana Zlateva, Jihong Wang, Yao Ding, Muhammad Shafiq Ul Hassan, Zhiheng Wang, Parmeswaran Diagaradjane, Fada Guan, Travis C Salzillo, Shane Krafft, Jing Li, Martin C Tom, Amol J Ghia, Tina Marie Briere

Faculty, Staff and Student Publications

Spine stereotactic radiotherapy and radiosurgery (SSRS) techniques, encompassing both fractionated stereotactic treatments and single-fraction radiosurgery, are widely used for the management of spinal metastases due to their ability to deliver highly conformal radiation while limiting dose to adjacent critical structures. Clinical outcomes following SSRS, including durable local control and acceptable toxicity, have been reported previously in multiple institutional series. In this manuscript, we describe the clinical workflow used to deliver SSRS at a high-volume academic center, with emphasis on the medical physics processes that support routine clinical practice. Key elements of the workflow include patient selection, treatment region-specific immobilization, CT …


Tead-Independent Mechanisms Of Yap Function In Cardiomyocyte Cell Cycle Reentry, Bing Xie, Jeffrey Steimle, Vaibhav Deshmukh, Lin Liu, Chang-Ru Tsai, Todd R Heallen, Wyatt Paltzer, Yuka Morikawa, Fansen Meng, Jun Wang, James F Martin Jan 2026

Tead-Independent Mechanisms Of Yap Function In Cardiomyocyte Cell Cycle Reentry, Bing Xie, Jeffrey Steimle, Vaibhav Deshmukh, Lin Liu, Chang-Ru Tsai, Todd R Heallen, Wyatt Paltzer, Yuka Morikawa, Fansen Meng, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA …


Using The Linear References From The Pangenome To Discover Missing Autism Variants, Yang Sui, Jiadong Lin, Michelle D Noyes, Youngjun Kwon, Isaac Wong, Nidhi Koundinya, William T Harvey, Mei Wu, Kendra Hoekzema, Katherine M Munson, Gage H Garcia, Jordan Knuth, Julie Wertz, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Rafael A Polo Prieto, Rebecca Meyer-Schuman, Fisher Cherry, Davut Pehlivan, Bernhard Suter, Jonas A Gustafson, Danny E Miller, Human Pangenome Reference Consortium (Hprc), Hanna Berk-Rauch, Tomasz J Nowakowski, Aravinda Chakravarti, Huda Y Zoghbi, Evan E Eichler Jan 2026

Using The Linear References From The Pangenome To Discover Missing Autism Variants, Yang Sui, Jiadong Lin, Michelle D Noyes, Youngjun Kwon, Isaac Wong, Nidhi Koundinya, William T Harvey, Mei Wu, Kendra Hoekzema, Katherine M Munson, Gage H Garcia, Jordan Knuth, Julie Wertz, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Rafael A Polo Prieto, Rebecca Meyer-Schuman, Fisher Cherry, Davut Pehlivan, Bernhard Suter, Jonas A Gustafson, Danny E Miller, Human Pangenome Reference Consortium (Hprc), Hanna Berk-Rauch, Tomasz J Nowakowski, Aravinda Chakravarti, Huda Y Zoghbi, Evan E Eichler

Duncan NRI Faculty and Staff Publications

To better understand large-effect pathogenic variation associated with autism, we generated long-read sequencing (LRS) data to construct phased and near-complete genome assemblies (average contig N50 = 43 Mbp, QV = 56) for 189 individuals from 51 families with unsolved cases. We applied read- and assembly-based strategies to facilitate comprehensive characterization of de novo mutations, structural variants (SVs), and DNA methylation. Using LRS pangenome controls, we efficiently filtered >97% of common SVs exclusive to 87 offspring. We find no evidence of increased autosomal SV burden for probands when compared to unaffected siblings yet observe a suggestive trend toward an increased SV …


Prehospital Transfusion Strategies In Haemorrhagic Shock, Brian Burns, Brodie Nolan, Ian Ferguson, Michael Peddle, Christopher Partyka, Geoff Healy, Stacy Shackelford, Bryan Cotton Jan 2026

Prehospital Transfusion Strategies In Haemorrhagic Shock, Brian Burns, Brodie Nolan, Ian Ferguson, Michael Peddle, Christopher Partyka, Geoff Healy, Stacy Shackelford, Bryan Cotton

Faculty, Staff and Student Publications

Background: Massive transfusion protocols are established in-hospital practices for managing haemorrhagic shock, yet critical bleeding accounts for up to 40% of trauma deaths, with half occurring before hospital arrival. This has driven interest in prehospital transfusion, a concept originating in military settings where early blood product administration during prolonged evacuations demonstrated significant survival benefits. Despite compelling military evidence showing improved 24-h and 30-day survival with prehospital transfusion, civilian adoption faces substantial challenges. Global interest in this domain is increasing, particularly in regions with trauma populations remote from immediate access to major trauma centres.

Main body: Current prehospital transfusion strategies have …


Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu Jan 2026

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.


Single-Cell Atlas Of Human Lung Aging Identifies Cell Type Dyssynchrony And Increased Transcriptional Entropy, Ruben De Man, John E Mcdonough, Taylor S Adams, Fadi Nikola, Reina Rangel, Sabina Anderson, Edward P Manning, Juan Cala Garcia, Benjamin Moss, Alan Waich, Fernando Poli, Rafael Cardenas, Cristian Coarfa, Qi Song, Ziv Bar-Joseph, Bart M Vanaudenaerde, Wim A Wuyts, Laura Niklason, Micha Sam B Raredon, Xiting Yan, Ivan O Rosas, Naftali Kaminski Jan 2026

Single-Cell Atlas Of Human Lung Aging Identifies Cell Type Dyssynchrony And Increased Transcriptional Entropy, Ruben De Man, John E Mcdonough, Taylor S Adams, Fadi Nikola, Reina Rangel, Sabina Anderson, Edward P Manning, Juan Cala Garcia, Benjamin Moss, Alan Waich, Fernando Poli, Rafael Cardenas, Cristian Coarfa, Qi Song, Ziv Bar-Joseph, Bart M Vanaudenaerde, Wim A Wuyts, Laura Niklason, Micha Sam B Raredon, Xiting Yan, Ivan O Rosas, Naftali Kaminski

Faculty, Staff and Students Publications

Age is a major risk factor for lung disease. We characterized the changing cellular, transcriptional, and genomic landscape of human lung aging using single-cell RNA sequencing. We find that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest transcriptional changes. Among alveolar epithelial cells, aging is associated with a decreased relative proportion of surfactant-expressing SPChigh AT2 cells. Among alveolar capillary cells, we observed loss of differentiation and capillary function. Analysis of somatic mutations called from single-cell data revealed an increase with aging, with alveolar epithelial and endothelial cell types exhibiting greater mutation burdens. Transcriptional entropy …


The Gene Encoding Ornithine Decarboxylase For Putrescine Biosynthesis Is Essential For The Viability Of Fusobacterium Nucleatum, Shiqi Xu, Bibek G C, Alex Phan, Chenggang Wu Jan 2026

The Gene Encoding Ornithine Decarboxylase For Putrescine Biosynthesis Is Essential For The Viability Of Fusobacterium Nucleatum, Shiqi Xu, Bibek G C, Alex Phan, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum is a Gram-negative anaerobe associated with periodontitis and colorectal cancer. It secretes putrescine, a polyamine that promotes biofilm formation by oral co-colonizers and enhances the proliferation of cancer cells. However, the physiological importance of putrescine for F. nucleatum itself remains unexplored. Here, we show that putrescine biosynthesis, mediated by the ornithine decarboxylase gene oda, is essential for F. nucleatum viability. Deletion of oda was only possible when a functional copy was provided in trans, and CRISPR interference of oda expression resulted in complete growth defects. The essentiality of oda was conserved across multiple subspecies. Supplementation with …


Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi Jan 2026

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …


Association Between The 2022 Aha/Acc/Hfsa Heart Failure Staging And Cardiovascular And Kidney Outcomes In Patients With Diabetes And Kidney Disease: A Post Hoc Analysis Of The Scored Randomized Controlled Trial, Ayodele Odutayo, Deepak L Bhatt, Vikas S Sridhar, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Renato D Lopes, Benjamin M Scirica, Kausik K Ray, Michael J Davies, Phillip Banks, Manon Girard, Subodh Verma, Jacob A Udell, Bertram Pitt, Ph Gabriel Steg, David Z I Cherney Jan 2026

Association Between The 2022 Aha/Acc/Hfsa Heart Failure Staging And Cardiovascular And Kidney Outcomes In Patients With Diabetes And Kidney Disease: A Post Hoc Analysis Of The Scored Randomized Controlled Trial, Ayodele Odutayo, Deepak L Bhatt, Vikas S Sridhar, Michael Szarek, Christopher P Cannon, Lawrence A Leiter, Darren K Mcguire, Julia B Lewis, Renato D Lopes, Benjamin M Scirica, Kausik K Ray, Michael J Davies, Phillip Banks, Manon Girard, Subodh Verma, Jacob A Udell, Bertram Pitt, Ph Gabriel Steg, David Z I Cherney

Faculty, Staff and Student Publications

Background: The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) classification incorporates cardiac biomarkers to identify early risk of HF. The HF stages may also guide the prognosis and management of cardiovascular and kidney-related events.

Methods: SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) was a randomized trial in diabetes with kidney disease comparing sotagliflozin versus placebo on cardiovascular death, HF hospitalizations, and urgent HF visits. SCORED participants were grouped by HF stage post hoc. Stage A: no …


Disease-Specific And Overall Survival For Patients With Lacrimal Gland Adenoid Cystic Carcinoma In Recent Decades, Bita Esmaeli, Zhouxuan Li, Tracy J Lu, Hila Goldberg, Jing Ning, James Matthew Debnam, Steven Jay Frank, Renata Ferrarotto Jan 2026

Disease-Specific And Overall Survival For Patients With Lacrimal Gland Adenoid Cystic Carcinoma In Recent Decades, Bita Esmaeli, Zhouxuan Li, Tracy J Lu, Hila Goldberg, Jing Ning, James Matthew Debnam, Steven Jay Frank, Renata Ferrarotto

Faculty, Staff and Student Publications

Purpose: To evaluate the presenting symptoms, and the overall survival (OS) and disease-specific survival (DSS) in patients with lacrimal gland adenoid cystic carcinoma (LGACC).

Methods: This retrospective single-centre cohort study included all consecutive patients with LGACC treated by the primary author from November 1998 through August 2024. Demographic data, presenting symptoms, the histological subtype of LGACC, type of surgical treatment, adjuvant radiotherapy or chemotherapy, T category at presentation and survival data were reviewed. Correlations between histological subtypes, T-category, type of surgery (eye sparing vs orbital exenteration), and DSS and OS were analysed.

Results: 52 patients had a median age of …


Single-Photon Emission Computed Tomography Functional Liver Imaging To Facilitate Reirradiation For Liver Malignancies: A Phase I Trial, Enoch Chang, Emma B Holliday, Janio Szklaruk, William D Erwin, Ethan B Ludmir, Sonal S Noticewala, Prajnan Das, Albert C Koong, Bruce D Minsky, Grace L Smith, Gabriel O Sawakuchi, Rachael M Martin-Paulpeter, Joshua S Niedzielski, Luis A Perles, Sam Beddar, Veronica S Valino, Joshua L Nguyen, Kanwal P S Raghav, Milind Javle, Ahmed O Kaseb, Arvind N Dasari, Michael J Overman, Christine M Parseghian, Bruno C Odisio, Armeen Mahvash, Joshua D Kuban, Shu-En Shen, Xin S Wang, Aashish C Gupta, Mais M Al Taie, Kristy K Brock, Ching-Wei D Tzeng, Jean-Nicolas Vauthey, Franklin C L Wong, Eugene J Koay Jan 2026

Single-Photon Emission Computed Tomography Functional Liver Imaging To Facilitate Reirradiation For Liver Malignancies: A Phase I Trial, Enoch Chang, Emma B Holliday, Janio Szklaruk, William D Erwin, Ethan B Ludmir, Sonal S Noticewala, Prajnan Das, Albert C Koong, Bruce D Minsky, Grace L Smith, Gabriel O Sawakuchi, Rachael M Martin-Paulpeter, Joshua S Niedzielski, Luis A Perles, Sam Beddar, Veronica S Valino, Joshua L Nguyen, Kanwal P S Raghav, Milind Javle, Ahmed O Kaseb, Arvind N Dasari, Michael J Overman, Christine M Parseghian, Bruno C Odisio, Armeen Mahvash, Joshua D Kuban, Shu-En Shen, Xin S Wang, Aashish C Gupta, Mais M Al Taie, Kristy K Brock, Ching-Wei D Tzeng, Jean-Nicolas Vauthey, Franklin C L Wong, Eugene J Koay

Faculty, Staff and Student Publications

Background & aims: This phase I trial evaluated the safety of hypofractionated liver reirradiation (reRT) with preferential sparing of functional liver identified by technetium-99m sulfur colloid single-photon emission computed tomography (Tc-99m SC SPECT; hereafter SPECT) for patients previously treated with external beam radiotherapy or transarterial radioembolization.

Methods: A 3+3 design evaluated the safety of two escalating SPECT-based functional liver volumetric dose constraints. Dose-limiting toxicities (DLTs), liver segment volumes, and MRI functional liver imaging score, relative liver enhancement, and elastography were assessed.

Results: Thirteen patients were enrolled from 2018 to 2021. Median reRT gross tumor volume was 61 cm3 (range 1-677 …


Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi Jan 2026

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …


Oral Streptococcus And Vitamin B12 Deficiency In E-Cigarette Users: A Microbial–Nutrient–Neurotransmitter Axis Linking To Mood Disturbances, Maryam Sabah Naser, Ali Jabbar Abd Al-Hussain Alkawaz, Ali Abbas Hashim Almusawi, Ali Jalil Obaid, Hasanain Ayed Mohammed Al-Khafaji, Reihaneh Sabbaghzadeh Jan 2026

Oral Streptococcus And Vitamin B12 Deficiency In E-Cigarette Users: A Microbial–Nutrient–Neurotransmitter Axis Linking To Mood Disturbances, Maryam Sabah Naser, Ali Jabbar Abd Al-Hussain Alkawaz, Ali Abbas Hashim Almusawi, Ali Jalil Obaid, Hasanain Ayed Mohammed Al-Khafaji, Reihaneh Sabbaghzadeh

Karbala International Journal of Modern Science

Background: With the rising popularity of e-cigarettes, questions have emerged regarding their broader influence on oral ecology, nutrient absorption, and psychological health. Disruptions in the oral microbiome may alter vitamin B12 dynamics. This, in turn, may indirectly influence serotonin biosynthesis and mood regulation.

Methods: An observational cross-sectional study involved 150 young adults segregated into groups of 50 each as vapers, smokers, or non-users. Streptococcus sanguinis and vitamin B12 metabolism-related variable statuses methylmalonic acid and holotranscobalamin were quantified in samples, along with inflammatory markers interleukin-6, kynurenine/tryptophan ratio, and serotonin. Statistical techniques, including ANOVA and the Kruskal-Walli’s test, correlation, and serial mediation …


Early-Life Exposure To Pfas Affects Adolescent Neuroimmune Activity, Gia Marie Valdez Jan 2026

Early-Life Exposure To Pfas Affects Adolescent Neuroimmune Activity, Gia Marie Valdez

Theses and Dissertations from DePaul University

Per-/polyfluoroalkyl substances (PFAS) are persistent organic pollutants commonly used in non-stick, oil-resistant, and water-proof food packaging as well as textiles; they are detected in more than 99% of human serum. Perfluorooctane sulfonic acid (PFOS), one of the most ubiquitous PFAS, is associated with altered lipid metabolism, immunotoxicity, and neurodevelopmental disorders. These outcomes all implicate microglia, resident macrophages in the brain critical for development and sensitive to lipid signaling, as key mediators of toxicity. However, developmental effects of PFOS on microglia are not well-characterized, nor is it clear how PFOS alters microglial inflammatory responses. We hypothesized that early-life PFOS exposure alters …


Qsox1: A Mysterious Golgi-Localized Disulfide Bond Catalyst And An Emerging Cancer Regulator, Shike Wang, Guan-Yu Xiao, Xiaochao Tan Jan 2026

Qsox1: A Mysterious Golgi-Localized Disulfide Bond Catalyst And An Emerging Cancer Regulator, Shike Wang, Guan-Yu Xiao, Xiaochao Tan

Faculty, Staff and Student Publications

Quiescin sulfhydryl oxidase 1 (QSOX1) is a disulfide bond-forming enzyme with both disulfide isomerase and oxidoreductase activities. It plays an important role in protein folding, stability, and secretion. Growing evidence demonstrates that QSOX1 is upregulated in multiple cancer types and influences key behaviors of cancer cells, including proliferation, migration, invasion, and metastasis. Elevated QSOX1 expression is also associated with tumor malignancy and disease relapse. However, the molecular mechanisms by which QSOX1 drives cancer progression remain incompletely understood. In this review, we summarize current knowledge of QSOX1 expression and regulation in cancer, discuss its functional roles, and highlight key unanswered questions …