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Articles 4411 - 4440 of 21606

Full-Text Articles in Medical Specialties

Severe Hypercalcemia Following Hip Joint Implantation Of Calcium Sulfate Antibiotic Beads: Case Series And Review Of Literature., Andrew P. Demidowich, Mahsa Motevalli, Kevin Yi, Atena Kamali, Kristine Batty, Kendall F. Moseley, Robert Raymond Buber, Mehdi Hashemipour`, Mihail Zilbermint Jan 2025

Severe Hypercalcemia Following Hip Joint Implantation Of Calcium Sulfate Antibiotic Beads: Case Series And Review Of Literature., Andrew P. Demidowich, Mahsa Motevalli, Kevin Yi, Atena Kamali, Kristine Batty, Kendall F. Moseley, Robert Raymond Buber, Mehdi Hashemipour`, Mihail Zilbermint

Journal of Community Hospital Internal Medicine Perspectives

Purpose: The diagnosis and management of hypercalcemia in hospitalized patients can be challenging. Hypercalcemia is often associated with significant morbidity and end-organ damage which may delay a patient’s recovery.

Methods: We report a case series of three patients who underwent orthopedic procedures with intraoperative placement of vancomycin-loaded calcium sulfate beads. Patients had no known history of malignancy or excess intake of calcium, vitamin A or vitamin D. Laboratory workup showed low parathyroid (PTH) levels and normal PTH-related peptide levels. The temporal nature of the non-PTH mediated hypercalcemia in relation to implantation of the antibiotic beads suggests causality of exogenous calcium …


Predictive Value Of Fdg Uptake On Pet For Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series, Malek Shatila, Kei Takigawa, Yang Lu, Andres Caleb Urias Rivera, Nitish Mittal, Abdullah Sagar Aleem, Sean Ngo, Eric Lu, Deanna Wu, Gabriel Sperling, Sidra Naz, Bryan Schneider, Anusha Shirwaikar Thomas, Yinghong Wang Jan 2025

Predictive Value Of Fdg Uptake On Pet For Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series, Malek Shatila, Kei Takigawa, Yang Lu, Andres Caleb Urias Rivera, Nitish Mittal, Abdullah Sagar Aleem, Sean Ngo, Eric Lu, Deanna Wu, Gabriel Sperling, Sidra Naz, Bryan Schneider, Anusha Shirwaikar Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Objectives: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis.

Methods: Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time. We included patients who had signs and symptoms of colitis and reviewed their surveillance PET/CT scans obtained 2 to 6 weeks before and up to 3 …


Couple-Based Lifestyle Intervention For Minority Prostate Cancer Survivors: A Randomized Feasibility Trial, Dalnim Cho, Yisheng Li, Karen Basen-Engquist, Chiara Acquati, Nga T T Nguyen, Hilary Ma, Curtis A Pettaway, Lorna H Mcneill Jan 2025

Couple-Based Lifestyle Intervention For Minority Prostate Cancer Survivors: A Randomized Feasibility Trial, Dalnim Cho, Yisheng Li, Karen Basen-Engquist, Chiara Acquati, Nga T T Nguyen, Hilary Ma, Curtis A Pettaway, Lorna H Mcneill

Faculty, Staff and Student Publications

Background: Black and Hispanic prostate cancer (PCa) survivors, who face a high burden of comorbid conditions and often engage in low levels of physical activity and healthy eating, remain significantly underrepresented in lifestyle intervention studies.

Purpose: Given the significance of spousal influence, we developed a culturally tailored lifestyle intervention for these survivors and their spouses and assessed its feasibility, acceptability, and impact on behavioral change.

Methods: Survivor-spouse couples were randomly assigned to an intervention group (n = 22), which received 12 health-coaching calls over 6 months, or a usual-care control group (n = 9). Assessments were conducted at baseline (T1), …


Cyclin E1/Cdk2 Activation Defines A Key Vulnerability To Wee1 Kinase Inhibition In Gynecological Cancers, Daehwan Kim, Heekyung Chung, Wen Liu, Kangjin Jeong, Tugba Y Ozmen, Furkan Ozmen, Matthew J Rames, Sangyub Kim, Xiao Guo, Nathan Jameson, Petrus R De Jong, Steven Yea, Laurie Harford, Jiali Li, Cara A Mathews, Deborah B Doroshow, Vincent J Charles, Doris Kim, Kimberlee Fischer, Ahmed A Samatar, Adrian Jubb, Kevin D Bunker, Kimberly Blackwell, Fiona Simpkins, Funda Meric-Bernstam, Gordon B Mills, Olivier Harismendy, Jianhui Ma, Mark R Lackner Jan 2025

Cyclin E1/Cdk2 Activation Defines A Key Vulnerability To Wee1 Kinase Inhibition In Gynecological Cancers, Daehwan Kim, Heekyung Chung, Wen Liu, Kangjin Jeong, Tugba Y Ozmen, Furkan Ozmen, Matthew J Rames, Sangyub Kim, Xiao Guo, Nathan Jameson, Petrus R De Jong, Steven Yea, Laurie Harford, Jiali Li, Cara A Mathews, Deborah B Doroshow, Vincent J Charles, Doris Kim, Kimberlee Fischer, Ahmed A Samatar, Adrian Jubb, Kevin D Bunker, Kimberly Blackwell, Fiona Simpkins, Funda Meric-Bernstam, Gordon B Mills, Olivier Harismendy, Jianhui Ma, Mark R Lackner

Faculty, Staff and Student Publications

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib. We found that ovarian cancer cell lines with high levels of endogenous Cyclin E1 expression or forced overexpression were exquisitely sensitive to azenosertib and these results extended to in vivo models of ovarian and uterine serous carcinoma. Models with high Cyclin …


Early Treatment Discontinuation In Patients With Deficient Mismatch Repair Or Microsatellite Instability High Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio Jan 2025

Early Treatment Discontinuation In Patients With Deficient Mismatch Repair Or Microsatellite Instability High Metastatic Colorectal Cancer Receiving Immune Checkpoint Inhibitors, Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD).

Methods: To assess whether ETD is associated with similar outcomes compared …


Comprehensive Characterization Of The Transcriptional Landscape In Alzheimer’S Disease (Ad) Brains, Chengxuan Chen, Zhao Zhang, Yuan Liu, Wei Hong, Hande Karahan, Jun Wang, Wenbo Li, Lixia Diao, Meichen Yu, Andrew J Saykin, Kwangsik Nho, Jungsu Kim, Leng Han Jan 2025

Comprehensive Characterization Of The Transcriptional Landscape In Alzheimer’S Disease (Ad) Brains, Chengxuan Chen, Zhao Zhang, Yuan Liu, Wei Hong, Hande Karahan, Jun Wang, Wenbo Li, Lixia Diao, Meichen Yu, Andrew J Saykin, Kwangsik Nho, Jungsu Kim, Leng Han

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events. We additionally identified 25,351 aberrantly expressed ncRNAs and altered PTM events associated with AD …


Its Own Architect: Flipping Cardiolipin Synthase, Katsuhiro Sawasato, William Dowhan, Mikhail Bogdanov Jan 2025

Its Own Architect: Flipping Cardiolipin Synthase, Katsuhiro Sawasato, William Dowhan, Mikhail Bogdanov

Faculty, Staff and Student Publications

Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of Escherichia coli is asymmetric. However, the molecular mechanism that maintains this uneven distribution is unknown. We engineered a conditionally lethal phosphatidylethanolamine (PE)-deficient mutant in which the presence of cardiolipin (CL) on the periplasmic leaflet of the IM is essential for viability, revealing a mechanism that provides CL on the desired leaflet of the IM. CL synthase (ClsA) flips its catalytic cytoplasmic domain upon depletion of PE to supply nonbilayer-prone CL in the periplasmic leaflet of the IM …


Enhanced Motivated Behavior Mediated By Pharmacological Targeting Of The Fgf14/Nav16 Complex In Nucleus Accumbens Neurons, Nolan M Dvorak, Paul A Wadsworth, Guillermo Aquino-Miranda, Pingyuan Wang, Douglas S Engelke, Jingheng Zhou, Nghi Nguyen, Aditya K Singh, Giuseppe Aceto, Zahra Haghighijoo, Isabella I Smith, Nana Goode, Mingxiang Zhou, Yosef Avchalumov, Evan P Troendle, Cynthia M Tapia, Haiying Chen, Reid T Powell, Timothy J Baumgartner, Jully Singh, Leandra Koff, Jessica Di Re, Ann E Wadsworth, Mate Marosi, Marc R Azar, Kristina Elias, Paul Lehmann, Yorkiris M Mármol Contreras, Poonam Shah, Hector Gutierrez, Thomas A Green, Martin B Ulmschneider, Marcello D'Ascenzo, Clifford Stephan, Guohong Cui, Fabricio H Do Monte, Jia Zhou, Fernanda Laezza Jan 2025

Enhanced Motivated Behavior Mediated By Pharmacological Targeting Of The Fgf14/Nav16 Complex In Nucleus Accumbens Neurons, Nolan M Dvorak, Paul A Wadsworth, Guillermo Aquino-Miranda, Pingyuan Wang, Douglas S Engelke, Jingheng Zhou, Nghi Nguyen, Aditya K Singh, Giuseppe Aceto, Zahra Haghighijoo, Isabella I Smith, Nana Goode, Mingxiang Zhou, Yosef Avchalumov, Evan P Troendle, Cynthia M Tapia, Haiying Chen, Reid T Powell, Timothy J Baumgartner, Jully Singh, Leandra Koff, Jessica Di Re, Ann E Wadsworth, Mate Marosi, Marc R Azar, Kristina Elias, Paul Lehmann, Yorkiris M Mármol Contreras, Poonam Shah, Hector Gutierrez, Thomas A Green, Martin B Ulmschneider, Marcello D'Ascenzo, Clifford Stephan, Guohong Cui, Fabricio H Do Monte, Jia Zhou, Fernanda Laezza

Faculty, Staff and Student Publications

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14R117, a critical residue located within a druggable pocket at the FGF14/Nav1.6 PPI interface. We found that 1028 modulates FGF14/Nav1.6 complex assembly and depolarizes the voltage-dependence of Nav1.6 channel inactivation with …


Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski Jan 2025

Dexamethasone Dose Intensity Does Not Impact Outcomes In Newly Diagnosed Multiple Myeloma: A Secondary Swog Analysis, Rahul Banerjee, Rachael Sexton, Andrew J Cowan, Aaron S Rosenberg, Sikander Ailawadhi, S Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Sagar Lonial, Brian G M Durie, Paul G Richardson, Saad Z Usmani, Antje Hoering, Robert Z Orlowski

Faculty, Staff and Student Publications

Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM), despite common toxicities, including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 mg once weekly was associated with lower mortality than higher doses. However, the performance of dexamethasone dose reductions below this threshold with regard to progression-free survival (PFS) and overall survival (OS) in NDMM has not been fully characterized. We conducted a secondary pooled analysis of the SWOG 0777 and SWOG 1211 studies of NDMM, which used lenalidomide and dexamethasone (Rd) alone, with or without bortezomib, and with or without elotuzumab. The planned …


Adverse Prehospital Events And Outcomes After Traumatic Brain Injury, Amelia W Maiga, Hsing-Hua Sylvia Lin, Stephen R Wisniewski, Joshua B Brown, Ernest E Moore, Martin A Schreiber, Bellal Joseph, Chad T Wilson, Bryan A Cotton, Daniel G Ostermayer, Brian G Harbrecht, Mayur B Patel, Jason L Sperry, Francis X Guyette, Henry E Wang Jan 2025

Adverse Prehospital Events And Outcomes After Traumatic Brain Injury, Amelia W Maiga, Hsing-Hua Sylvia Lin, Stephen R Wisniewski, Joshua B Brown, Ernest E Moore, Martin A Schreiber, Bellal Joseph, Chad T Wilson, Bryan A Cotton, Daniel G Ostermayer, Brian G Harbrecht, Mayur B Patel, Jason L Sperry, Francis X Guyette, Henry E Wang

Faculty, Staff and Student Publications

Importance: While national guidelines recommend avoidance of hypoxia, hypotension, and hypocarbia in the prehospital care of traumatic brain injury (TBI), limited data validate the association of these adverse physiologic events with TBI outcomes.

Objective: To validate the associations of prehospital hypoxia, hypotension, and hypocarbia with TBI outcomes in a US national trauma network.

Design, setting, and participants: This cohort study examined data from 8 level I trauma centers and their affiliated ground and air emergency medical services (EMS) agencies in the Linking Investigations in Trauma and Emergency Services (LITES) Network from January 1, 2017, to June 30, 2021. Adult patients …


The Role Of Iowa Gambling Task Performance In Response To Citalopram Treatment For Cocaine Use Disorder, Constanza De Dios, Robert Suchting, Charles E Green, Heather E Webber, F Gerard Moeller, Scott D Lane, Joy Schmitz Jan 2025

The Role Of Iowa Gambling Task Performance In Response To Citalopram Treatment For Cocaine Use Disorder, Constanza De Dios, Robert Suchting, Charles E Green, Heather E Webber, F Gerard Moeller, Scott D Lane, Joy Schmitz

Faculty, Staff and Student Publications

Background:

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use.

Objectives:

The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Methods:

We conducted a secondary analysis of a double-blind, placebo-controlled, randomized Bayesian adaptive trial investigating citalopram efficacy in CUD treatment-seeking adults. At baseline and mid-treatment, participants completed assessments of decision-making (Iowa Gambling Task; IGT), attention, response inhibition, and cognitive flexibility. Outcomes were longest duration of abstinence (LDA; count of consecutive …


Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu Jan 2025

Nucleus-Translocated Gclm Promotes Chemoresistance In Colorectal Cancer Through A Moonlighting Function, Jin-Fei Lin, Ze-Xian Liu, Dong-Liang Chen, Ren-Ze Huang, Fen Cao, Kai Yu, Ting Li, Hai-Yu Mo, Hui Sheng, Zhi-Bing Liang, Kun Liao, Yi Han, Shan-Shan Li, Zhao-Lei Zeng, Song Gao, Huai-Qiang Ju, Rui-Hua Xu

Faculty, Staff and Student Publications

Metabolic enzymes perform moonlighting functions during tumor progression, including the modulation of chemoresistance. However, the underlying mechanisms of these functions remain elusive. Here, utilizing a metabolic clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout library screen, we observe that the loss of glutamate-cysteine ligase modifier subunit (GCLM), a rate-limiting enzyme in glutathione biosynthesis, noticeably increases the sensitivity of colorectal cancer (CRC) cells to platinum-based chemotherapy. Mechanistically, we unveil a noncanonical mechanism through which nuclear GCLM competitively interacts with NF-kappa-B (NF-κB)-repressing factor (NKRF), to promote NF-κB activity and facilitate chemoresistance. In response to platinum drug treatment, GCLM is phosphorylated by P38 …


Cardiovascular Disease And Breast Cancer Stage At Diagnosi\S, Ivan Angelov, Allen M Haas, Elizabeth Brock, Lingfeng Luo, Jing Zhao, Benjamin D Smith, Sharon H Giordano, Nicholas J Leeper, Kevin T Nead Jan 2025

Cardiovascular Disease And Breast Cancer Stage At Diagnosi\S, Ivan Angelov, Allen M Haas, Elizabeth Brock, Lingfeng Luo, Jing Zhao, Benjamin D Smith, Sharon H Giordano, Nicholas J Leeper, Kevin T Nead

Faculty, Staff and Student Publications

Importance: Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.

Objective: To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.

Design, setting, and participants: This population-based case-control study used data from the Surveillance, Epidemiology, and End Results-Medicare linked databases from 2009 to 2020. The analysis was completed from May 2023 to August 2024. Participants were …


Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang Jan 2025

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …


Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee Jan 2025

Atrx Silences Cartpt Expression In Osteoblastic Cells During Skeletal Development, Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee

Faculty, Staff and Students Publications

ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture …


Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge Jan 2025

Meta-Ea: A Gene-Specific Combination Of Available Computational Tools For Predicting Missense Variant Effects, Panagiotis Katsonis, Olivier Lichtarge

Faculty, Staff and Students Publications

Computational methods for estimating missense variant impact suffer from inconsistent performance across genes, which poses a major challenge for their reliable use in clinical practice. While ensemble scores leverage multiple prediction methods to enhance consistency, the overrepresentation of certain genes in the training data can bias their outcomes. To address this critical limitation, we propose a gene-specific ensemble framework trained on reference computational annotations rather than on clinical or experimental data. Accordingly, we generate Meta-EA ensemble scores that achieve comparable performance to the top individual predicting method for each gene set. Incorporating the effects of splicing and the allele frequency …


In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans Jan 2025

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …


Minimally Invasive Non-Expansile Tubular Extradural Posterior Fossa Decompression (Minted Technique) For The Management Of Chiari I.5 Malformation: Historical Overview Of Surgical Techniques, Technical Note, Proof Of Concept, Illustrative Case And Case Series. Lesser Is Better, José Alberto Israel Romero Rangel, Manuel Eduardo Soto García, Sergio Soriano Solís, Carlos Raúl Rangel Morales, Gerson Reyes Rodríguez, José Antonio Soriano Sánchez Jan 2025

Minimally Invasive Non-Expansile Tubular Extradural Posterior Fossa Decompression (Minted Technique) For The Management Of Chiari I.5 Malformation: Historical Overview Of Surgical Techniques, Technical Note, Proof Of Concept, Illustrative Case And Case Series. Lesser Is Better, José Alberto Israel Romero Rangel, Manuel Eduardo Soto García, Sergio Soriano Solís, Carlos Raúl Rangel Morales, Gerson Reyes Rodríguez, José Antonio Soriano Sánchez

Archives of Neurosurgery

BACKGROUND: Chiari's Malformation surgical treatment has significantly changed since the "classical" technique description by Gardner (1950). It is probably the most commonly performed approach, even when multiple techniques are available because no substantial changes nor any clear surgical objectives have been made. OBJECTIVE: To demonstrate a new cutting-edge surgical technique mastering the advantage of each surgical procedure ever described in the history of Chiari's Malformation establishing three critical points in surgical technique: clear patient-specific surgical goals, dynamic posterior fossa reconstruction, and extradural occipitoatlantal dense-adhesions release. METHODS: A comprehensive review of historically described approaches, proof of concept of surgical technique in …


A Thermodynamic Bottleneck In The Tca Cycle Contributes To Acetate Overflow In Staphylococcus Aureus, Nabia Shahreen, Jong-Sam Ahn, Adil Alsiyabi, Niaz Bahar Chowdhury, Dhananjay Shinde, Sujata S. Chaudhari, Kenneth W. Bayles, Vinai Chittezham Thomas, Rajib Saha Jan 2025

A Thermodynamic Bottleneck In The Tca Cycle Contributes To Acetate Overflow In Staphylococcus Aureus, Nabia Shahreen, Jong-Sam Ahn, Adil Alsiyabi, Niaz Bahar Chowdhury, Dhananjay Shinde, Sujata S. Chaudhari, Kenneth W. Bayles, Vinai Chittezham Thomas, Rajib Saha

Journal Articles: Pathology and Microbiology

During aerobic growth, S. aureus relies on acetate overflow metabolism, a process where glucose is incompletely oxidized to acetate, for its bioenergetic needs. Acetate is not immediately captured as a carbon source and is excreted as waste by cells. The underlying factors governing acetate overflow in S. aureus have not been identified. Here, we show that acetate overflow is favored due to a thermodynamic bottleneck in the TCA cycle specifically involving the oxidation of succinate to fumarate by succinate dehydrogenase. This bottleneck reduces flux through the TCA cycle, making it more efficient for S. aureus to generate ATP via acetate …


Quaternized Chitosan Derivatives Inhibit Growth And Affect Biofilm Formation Of Staphylococcus Aureus, Alex Miranda, Nichole D. Brandquist, Kristen Johnson, Elena Muldiiarova, Aleksandr Fadeev, Mahboubeh Ghanbari, Jennifer L. Endres, Kenneth W. Bayles, Jason N. Mactaggart, Denis Svechkarev, Marat Sadykov, Yury Salkovskiy Jan 2025

Quaternized Chitosan Derivatives Inhibit Growth And Affect Biofilm Formation Of Staphylococcus Aureus, Alex Miranda, Nichole D. Brandquist, Kristen Johnson, Elena Muldiiarova, Aleksandr Fadeev, Mahboubeh Ghanbari, Jennifer L. Endres, Kenneth W. Bayles, Jason N. Mactaggart, Denis Svechkarev, Marat Sadykov, Yury Salkovskiy

Journal Articles: Pathology and Microbiology

Antimicrobial resistance (AMR) poses a global health threat, severely impeding the effective treatment of bacterial infections and jeopardizing the safety of routine medical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic because of its resistance to beta-lactams and the ability to form resilient biofilms. Conventional antibiotics, including last-resort options, have serious side effects and may contribute to further resistance. Chitosan, a natural biopolymer, offers a promising alternative due to its biocompatibility and antimicrobial properties, though its effectiveness against biofilms is limited. Recent studies suggest that increasing the positive charge density and adding hydrophobic moieties to chitosan, can enhance its antimicrobial …


Interferon-Gamma Receptor Signaling Regulates Innate Immunity During Staphylococcus Aureus Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Rachel W. Fallet, Tammy Kielian Jan 2025

Interferon-Gamma Receptor Signaling Regulates Innate Immunity During Staphylococcus Aureus Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Rachel W. Fallet, Tammy Kielian

Journal Articles: Pathology and Microbiology

A craniotomy is a neurosurgical procedure performed to access the intracranial space. In 3-5% of cases, infections can develop, most caused by Staphylococcus aureus biofilm formation on the skull surface. Medical management of this infection is difficult, as biofilm properties confer immune and antimicrobial recalcitrance to the infection and necessitate additional surgical procedures. Furthermore, treatment failure rates can be appreciably high. These factors, compounded with rapidly expanding rates of antimicrobial resistance, highlight the need to develop alternative treatment strategies to target and reverse the immune dysfunction that occurs during biofilm infection. Our recent work has identified CD4+ Th1 and Th17 …


High-Grade Avm. Educational Vignette And Clinical Cases, Marcos Devanir Silva Da Costa, Marcelo Augusto Acosta Goiri, Daniela Coelho, Juan Alberto Paz Archila, Talita Helena Martins Sarti, Feres Chaddad-Neto Jan 2025

High-Grade Avm. Educational Vignette And Clinical Cases, Marcos Devanir Silva Da Costa, Marcelo Augusto Acosta Goiri, Daniela Coelho, Juan Alberto Paz Archila, Talita Helena Martins Sarti, Feres Chaddad-Neto

Archives of Neurosurgery

The arteriovenous malformation (AVM) is a vascular malformation characterized by fistulas between arteries and veins forming a nidus, without interposition of capillary vessels and of which early draining vein is identified at the digital angiography. Potential reports of its existence date from the second century AD. Spetzler and Martin (S-M) proposed a classification considering three features and Lawton then added new predictors. A maximum of 10 score can be achieved by applying the modified S-M grade system. This classification guides decision-making and the possible choice of the multimodal treatment (surgery, radiosurgery and embolization). We discuss historical, pathological, clinical and therapeutic …


Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian Jan 2025

Cd4+ T Cell-Innate Immune Crosstalk Is Critical During Staphylococcus Aureus Craniotomy Infection, Gunjan Kak, Zachary A. Van Roy, Rachel W. Fallet, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. Staphylococcus aureus accounts for half of craniotomy infections, increasing morbidity in a medically fragile patient population. T cells preferentially traffic to the brain during craniotomy infection; however, their functional importance is unknown. Using a mouse model of S. aureus craniotomy infection, CD4+ T cells were critical for bacterial containment, as treatment of WT animals with anti-CD4 exacerbated infection that was similar to phenotypes in Rag1-/- mice. Single-cell RNA-Seq (scRNA-Seq) revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent that displayed …


Reproductive Autonomy In Immunological Intervention: Ethical Boundaries In Maternal-Fetal Immune Therapy, Marium Z. Rizvi Jan 2025

Reproductive Autonomy In Immunological Intervention: Ethical Boundaries In Maternal-Fetal Immune Therapy, Marium Z. Rizvi

Journal of Health Ethics

Recent advances in immunology have broken barriers in reproductive medicine through immune-modulating therapies that support fertility and pregnancy. Treatments such as intravenous immunoglobulin (IVIG) and intralipid infusions are increasingly offered to patients with Recurrent Implantation Failure (RIF) or Recurrent Pregnancy Loss (RPL), conditions that result in miscarriages and failed IVF treatments (Pillarysetti et al., 2023). Maternal-fetal immunology reveals a delicate interplay between immune tolerance and defense: the maternal system must accept a genetically foreign fetus while preserving immunological protection. Disruptions in this balance are implicated in implantation disorders and pregnancy failure. As a result, immune-based therapies have emerged as promising …


An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen Jan 2025

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …


Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot Jan 2025

Pgc-1Α Activation To Enhance Macrophage Immune Function In Mycobacterial Infections, Joel R. Frandsen, Zhihong Yuan, Brahmchetna Bedi, Zohra Prasla, Seoung-Ryoung Choi, Prabagaran Narayanasamy, Ruxana Sadikot

Journal Articles: Pathology and Microbiology

Nontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a …


Extracellular Adherence Proteins Reduce Matrix Porosity And Enhance Staphylococcus Aureus Biofilm Survival During Prosthetic Joint Infection, Mohini Bhattacharya, Tyler D. Scherr, Jessica Lister, Tammy Kielian, Alexander R. Horswill Jan 2025

Extracellular Adherence Proteins Reduce Matrix Porosity And Enhance Staphylococcus Aureus Biofilm Survival During Prosthetic Joint Infection, Mohini Bhattacharya, Tyler D. Scherr, Jessica Lister, Tammy Kielian, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Biofilms are a cause of chronic, non-healing infections. Staphylococcus aureus is a proficient biofilm-forming pathogen commonly isolated from prosthetic joint infections that develop following primary arthroplasty. Extracellular adherence protein (Eap), previously characterized in planktonic or non-biofilm populations as being an adhesin and immune evasion factor, was recently identified in the exoproteome of S. aureus biofilms. This work demonstrates that Eap and its two functionally orphaned homologs EapH1 and EapH2 contribute to biofilm structure and prevent macrophage invasion and phagocytosis in these communities. Biofilms unable to express Eap proteins demonstrated increased porosity and reduced biomass. We describe the role of Eap …


Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning, Ritika Gupta, Aayushi Laliwala, Elena Muldiiarova, Kenneth W. Bayles, Denis Svechkarev, Marat Sadykov, Aaron M. Mohs Jan 2025

Species-Specific Discrimination Of Bacterial Biofilms Using A Ratiometric Fluorescence Sensor Array And Machine Learning, Ritika Gupta, Aayushi Laliwala, Elena Muldiiarova, Kenneth W. Bayles, Denis Svechkarev, Marat Sadykov, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Biofilms are intricate bacterial communities encased in a self-produced extracellular matrix (ECM) of DNA, lipids, proteins, and polysaccharides. The diverse ECM composition across bacterial species significantly influences the progression of biofilm-associated infections, making precise identification crucial for effective treatment. Traditional methods such as biochemical assays, MALDI-TOF mass spectrometry, DNA sequencing and culturing provide valuable insights but have notable drawbacks, including time-consuming procedures, high costs, and the need for specialized equipment and trained personnel. These limitations hinder the rapid and widespread adoption of biofilm identification in clinical settings, underscoring the need for more streamlined, accurate, and accessible methods. In this study, …


Semaglutide Vs Liraglutide For Weight Loss In Adults With Obesity, Orian Bar Jan 2025

Semaglutide Vs Liraglutide For Weight Loss In Adults With Obesity, Orian Bar

The PA Department Journal of Medical Science

Introduction: Obesity is a growing chronic condition worldwide with limited effective and safe treatment options. Semaglutide and liraglutide are two GLP-1a medications with encouraging outcomes for the treatment of obesity. The purpose of this paper is to compare semaglutide to liraglutide for weight loss and obesity

Methods: Pubmed was searched for randomized controlled trials, systematic reviews, and meta- analyses from 2019 to 2024 to assess efficacy of semaglutide and liraglutide. Five articles were selected for clinical review.

Results: In 4 out of the 5 studies there was a greater reduction in weight in patients receiving semaglutide compared to liraglutide. Statistically …


Improving Knowledge And Confidence Of Family Nurse Practitioners In Offering The Hpv Vaccine, Leni Terano Fisher Jan 2025

Improving Knowledge And Confidence Of Family Nurse Practitioners In Offering The Hpv Vaccine, Leni Terano Fisher

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Abstract

Introduction

Despite the recommendations of the United States Advisory Committee on Immunization Practices, HPV immunization lags behind other routine vaccines by up to 31%. Although there are many reasons for the low vaccine rate, provider hesitancy and lack of confidence significantly contribute to suboptimal HPV vaccine uptake.

Objectives

This project aimed to utilize evidence-driven interventions to increase family nurse practitioners' (FNPs) knowledge and confidence in offering the HPV vaccine.

Methods

Participants were given pre- and post-questionnaire surveys. The Wilcoxon Rank Test was used to compare, quantify, and measure the results of the eight-week data collection.

Results

The subjects were …