Digital Commons Network^™

Provider-Reported Readiness Of Chronic Healthcare Services In Saudi Arabia Under The Health Sector Transformation Program, Aseel Aldhwaihi, Saad Alghanim

Saudi Medical Journal

Objective: To assess provider-reported readiness of chronic healthcare services in Saudi Arabia within the context of the Health Sector Transformation Program (HSTP), using a validated, context-specific assessment instrument. Methods: A national cross-sectional survey was conducted between November 2024 and February 2025 among 254 healthcare providers across 5 health regions and both public and private healthcare sectors. A 34-item instrument, informed by the Chronic Care Model (CCM) and adapted to the Saudi context, assessed 7 system readiness dimensions. Descriptive statistics, independent-samples t-tests, one-way analysis of variance, and Pearson correlation analyses were performed. Results: Overall system readiness was moderately positive. Health system …

Seasonal Variation Of Diabetic Ketoacidosis Among Children And Adolescents With Type 1 Diabetes: A Single-Center Tertiary Experience, Nour Gazzaz, Fajr A Saeedi

Saudi Medical Journal

Objectives: Diabetic ketoacidosis (DKA) seasonal variations among children and adolescents with type 1 diabetes mellitus (T1DM) have been widely studied; however, findings remain inconsistent. Although several studies reported a higher incidence during colder months, others showed no consistent patterns. This study investigated whether DKA frequency and severity vary across seasons, particularly in humid cities. Methods: This retrospective cohort analyzed children and adolescents with T1DM admitted to a tertiary hospital with DKA (2015–2025). Data included demographics, seasonal admission trends, clinical severity, and outcomes. Statistical analyses involved the Chi-square and ANOVA tests. Results: A total of 369 DKA cases …

Glp-1 Receptor Agonists And Sglt-2 Inhibitors In Diabetic Nephropathy: A Comparative Study, Sara Ghadeer Alghadeer, Sama Sami Kanfar, Zakiah Dheya Algallaf, Fatimah Mudhar Alfardan, Rana Alshammrany, Maha Farhat, Cyril Cyrus

Saudi Medical Journal

Objective: To investigate the effects of glucagon-like peptide-1 receptor agonist (GLP-1RAs) on renal function in type 2 diabetes mellitus (T2DM) patients and compared their efficacy to sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in managing diabetic nephropathy. Methods: This is a retrospective cohort study conducted at King Fahad University Hospital, including 115 adults (≥ 18 years) with T2DM and baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m², treated with GLP-1RAs or SGLT-2i for over 1 year. Patients on renal replacement therapy, nephrotoxic drugs, or with incomplete records were excluded. Data were analyzed with Jeffrey's Amazing Statistics Program; the significant value …

Investigating Medical Radiation Awareness Of Saudi Arabian Cardiologists In Catheterization Labs: A Survey Study, Abdulmajeed Alotaibi, Raseel Alsallum, Reemas Alotaibi, Ali M. Aldhebaib, Noha Althubaity, Oinam Gokulchandra Singh, Zyad M. Almutlaq, Abdulaziz M. Albaraikan, Winnie Philip, Abrar M. Al-Mutairi, Mostafa Alqarras, Basma Alrowailli, Abdulrahman Alkhulaifi, Dhaifallah Ziyad Alanazi

Saudi Medical Journal

Objectives: To assess the knowledge, attitudes, and practices of interventional cardiologists in Kingdom of Saudi Arabia (KSA) regarding occupational radiation safety. Occupational radiation exposure poses significant long-term health risks for interventional cardiologists. Understanding current safety knowledge and practices is essential for guiding improvement strategies. Methods: A multicenter, cross-sectional survey was administered across several cardiac centers in KSA. The survey evaluated radiation safety awareness, use of dosimetry monitoring, and adherence to protective measures among practicing interventional cardiologists. Results: The study identified notable gaps in radiation safety knowledge and considerable inconsistencies in dosimetry monitoring. Despite these shortcomings, participants demonstrated high compliance …

Awareness Of The Mediterranean Diet And Its Perceived Effect On Cardiovascular Health In The Western Region, Saudi Arabia, Abdullah M. Alharbi, Mohammed S. Alsaedi, Mutaz S. Alharbi, Faisal F. Almutairi, Adeeb M. Aloufi, Azzam M. Alharbi, Rakan D. Alsaedi, Hatim F. Alhejaili, Motasem M. Alyamani

Saudi Medical Journal

Objective: To increase awareness of mediterranean diet (MD) and its perceived effects on cardiovascular health, enhance knowledge and inform public health efforts aimed at improving the population's health outcomes of. The MD comprises heart-healthy eating patterns high in vegetables, legumes, nuts and seeds, and fruits. Methods: This cross-sectional study involved adult participants who were living in the Western region of the Kingdom of Saudi Arabia. The data were collected online through social media platforms, then cleaned, coded, and analyzed using Statistical Package for the Social Sciences, version 21 to generate key insights. Results: A total of 390 participants were included …

Early Initiation And Dual Patterns Of Cigarette And E-Cigarette Use Among Adults In The Eastern Province, Saudi Arabia: A Cross-Sectional Study, Haidar A. Alridha, Nora A. Alafif

Saudi Medical Journal

Objectives: To explore the early initiation of cigarette and e-cigarette use and the dual patterns of usage among adults in the Eastern Province of Saudi Arabia. Methods: A cross-sectional survey was conducted from December 2024 to February 2025 among adults living in the Eastern Province. An online self-administered questionnaire collected data on sociodemographic characteristics, smoking behaviors, age of initiation, dual-use patterns, and quit attempts. Convenience sampling was applied, and a total of 551 participants were included. Descriptive statistics summarized distributions of smoking behavior and initiation age. Pearson's Chi-square tests were used to examine associations between smoking status, age of initiation, …

Multidimensional Predictors Of Disease Severity And Health Outcomes In Patients With Sickle Cell Disease: A Data-Driven Clinical Insight, Hind A. Alzahrani, Ruba Omar Mohammed Almaghrabi, Raed Alharbi, Abdulaziz Saleh Alghamdi, Mohammad A. Albanghali, Hanan E. Alyahyawi, Abdulmohsen M. Alruwetei, Besma Garah, Mohammed Alzahrani, Samar Hassan Hjar, Sana Shaker

Saudi Medical Journal

Objectives: To describe the clinical, hematologic, and therapeutic characteristics of hospitalized adults with sickle cell disease (SCD) in the Al-Baha region and to identify factors that predict hospitalization as well as transfusion frequency. Methods: A retrospective observational analysis was conducted on 117 adults with confirmed SCD who were admitted to King Fahad Hospital-Al-Baha during 2022–2024. Demographic information, hematologic parameters, clinical features, hospitalization rate, transfusion history, and treatment protocols were collected from the electronic medical records. Statistical analyses (ANOVA, Kruskal-Wallis test, Chi-square tests, and Fisher's exact Test) were performed to compare between groups where applicable. Results: The cohort had a mean …

Prevalence And Clinical Correlates Of Intraspinal And Vertebral Anomalies In Congenital, Adolescent Idiopathic, And New-Onset Scoliosis: A Comparative Study In Saudi Arabia, Faisal M Alkhunein, Mishari N Alanezi, Nwaf A Alshahir, Abdulkarim S Alsulimi, Abdulrahman H Salman, Habib Ullah Chaudhary, Abdulmajeed A Alzakri

Saudi Medical Journal

Objective: To explore the prevalence of and clinical associations between intraspinal and vertebral abnormalities in patients with congenital scoliosis (CS), adolescent idiopathic scoliosis (AIS), and early-onset scoliosis in Saudi Arabia. Methods: This retrospective cohort investigation included patients aged 18 years or younger diagnosed with CS, AIS, or new-onset idiopathic scoliosis who underwent full-spine magnetic resonance imaging between 2015 and 2025 at a tertiary center in Riyadh, Saudi Arabia. Clinical and radiological data were collected, and intraspinal and vertebral anomalies were classified. Statistical analyses included Chi-square, Fisher's exact test, and the Wilcoxon rank-sum test, with significance set at p < 0.05. Results: A …

Dietary Fat Intake And Its Influence On The Association Between Liver Fat And Brain Choline Metabolism In Young Saudi Women, Halima S. Hawesa, Mansour E. Shanawani, Haya A. Alshegri, Mahasin G. Hassan, Amal I. Alorainy, Nouf A. Alroqaiba, Shanoo G. A. Sheikh

Saudi Medical Journal

Objective: Fat-rich nutrition may influence the neurochemical consequences of hepatic lipid accumulation. This study examined whether percent energy from fat modifies the association between liver fat and the brain (Cho/Cr) ratio in healthy young women. Methods: A total of 109 healthy Saudi women aged 18–25 years underwent brain magnetic resonance spectroscopy (¹H-MRS) to quantify Cho/Cr ratios. Liver fat was estimated using MRI-based proton density fat fraction (PDFF), and lipid intake was assessed using a validated food frequency questionnaire. Multivariable regression models tested the interaction between liver fat and fat-derived energy intake, followed by simple slopes analysis, regression …

Artificial Intelligence In Pharmaceutical Care: Transforming Drug Discovery, Development, And Patient-Care Delivery, Abdulrahman G. Alharbi, Abdulrahman A. Aljabri

Saudi Medical Journal

The integration of artificial intelligence (AI) into pharmaceutical care represents a paradigm shift in healthcare delivery, offering unprecedented opportunities to revolutionize medication management, accelerate drug development, and enhance patient outcomes. This comprehensive review synthesized evidence from global literature (2021–2025) examining AI applications across drug discovery and development, clinical trials optimization, medication therapy management, and pharmacy operations. The AI demonstrated prediction accuracies of 86–98% in drug discovery, 80% improvement in clinical trial recruitment efficiency, and 32.7% increase in medication adherence over standard care. The global AI drug discovery market, valued at \$1.5 billion (2023), is projected to reach \$11.8 billion by …

Emerging Strategies For Cardio-Renal Protection Beyond Raas Blockade: Emphasis On Non-Diabetic Ckd And Resistant Hypertension, Fahad S. Alrashidi

Saudi Medical Journal

Non-diabetic chronic kidney disease (ND-CKD) complicated by resistant hypertension remains a high-risk phenotype even when renin–angiotensin system blockade is optimized. This review synthesizes contemporary evidence for cardio-renal protection beyond traditional renin-angiotensin-aldosterone system inhibition (RAASi), with emphasis on mechanisms, clinical trial data, and pragmatic sequencing. Sodium–glucose cotransporter 2 inhibitors provide hemodynamic and tubular benefits that translate into renal and heart failure risk reduction in many patients with ND-CKD. Non-steroidal mineralocorticoid receptor antagonism (MRA) like finerenone targets inflammatory and fibrotic signaling and may add incremental benefit when potassium is proactively managed. The GLP-1 receptor agonists offer cardiometabolic advantages with emerging kidney signals, …

The Use Of Platelet-Rich Plasma For De Quervain's Tenosynovitis: A Systematic Review With Limited Meta-Analysis, Abdullah W. Abumadian, Mohanad I. Binibrahim, Abdurrahman H. Sultan, Mohammed A. Addas, Hattan Y. Bamagaus, Sultan K. Alhaddad, Motasem O. Bamabad, Bayan A. Ghalimah

Saudi Medical Journal

Introduction: De Quervain's tenosynovitis (DQT) is a painful wrist condition that impairs daily activities. Corticosteroid (CS) injections are commonly used for symptom relief, but their effects may diminish over time. Platelet-rich plasma (PRP) has emerged as a regenerative alternative that promotes tissue healing rather than merely suppressing inflammation. This systematic review and limited meta-analysis compare the efficacy and safety of PRP versus CS injections in DQT. A limited meta-analysis was chosen due to the high heterogeneity between studies (I² = 98.7%). Methodology: A comprehensive literature search identified six studies comparing PRP and CS injections. Pain and functional outcomes …

Healthcare-Associated Infection Causes And Mitigation Strategies: A Systematic Review, Mohammad Irfan, Nahed Alquwez

Saudi Medical Journal

Objective: To describe the landscape of healthcare-associated infections (HAI) and, in particular, to pay attention to the types of infection that are usually seen, the most common infectious agents involved and the effective prevention strategies. Methods: A detailed search was performed using Google and PubMed, and studies that exclusively addressed healthcare associated infections or their mitigation. Studies published since 2000 were included. Data from individual articles were extracted and categorized by study focus, type of infection, causes and contributing factors, and documented mitigation strategies. Editorials, reviews, case studies, meta-analyses, and systematic reviews were excluded. Results: The analysis showed that infections …

Clinical Outcomes Of Decompression Versus Decompression With Instrumented Fusion For Lumbar Spinal Stenosis Secondary To Degenerative Spondylolisthesis: A Systematic Review And Meta-Analysis, Lama N. Alqahtani, Ahmed K. Alzahrani, Razan A. Almutairi, Abdulaziz M. Salah, Shahad F. Khan, Mohammad G. Sindi, Khalid E. Fassi, Abdulrahman M. Alshami, Ibrahim A. Hakami

Saudi Medical Journal

Objective: To compare decompression alone with decompression with fusion in patients with degenerative lumbar spondylolisthesis. Methods: PubMed, Google Scholar, Ovid, and Web of Science databases were searched up to March 2025 for randomized controlled trials (RCTs). The primary outcomes were the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) scores. The secondary outcomes included operative time, length of hospital stay, intraoperative blood loss, reoperation, complications, and cost. Pooled analysis was performed using a random-effects model in Review Manager following Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. The quality of included randomized trials was evaluated using the …

Single-Nucleotide Rna M6a Mapping In Bovine Preimplantation Development Reveals Site-Specific Regulation Of Rpl12 At Zygotic Genome Activation, Rajan Iyyappan, Yichi Niu, Yang Li, Hao Ming, Kinga Pajdzik, Noah R Rakestraw, Piyush K Jain, Chuan He, Chenghang Zong, Zongliang Jiang

Faculty, Staff and Students Publications

RNA N6-methyladenosine (m6A) is a key regulator of gene expression during early embryogenesis. Using SAC-seq (m6A-selective allyl chemical labeling and sequencing), an antibody-independent m6A profiling method, we generated the first single-nucleotide-resolution m6A map of bovine oocytes and preimplantation embryos. We observed both coordinated and uncoupled relationships between m6A modification and expression of protein-coding and noncoding genes. Integrative analysis of the transcriptome, m6A epitranscriptome, and translatome revealed dynamic m6A remodeling, particularly in ribosomal protein genes. Functional interrogation of a specific m6A site within the RPL12 transcript demonstrated that loss of this modification reduces protein synthesis, disrupts translation-related gene expression, impairs zygotic …

Reducing Communicable-Disease Risk After Earthquakes: Vaccination And Prevention Lessons For Venezuela's Doublet, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Adriana Sucari, Wendy Moncada, Lili Vanessa Hernández-Serrano, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Bernal Cordero, Virgilio Lezcano, Amanda Guerrero, Herberth Maldonado, Luis Cuellar, Ines Ceron, Yori Roque, Melisa Florentin, Rosa Infante, Ana Carvajal, Lily M Soto-Ávila, Marbelys Hernández, Hector Villaroel, Gianmary Miozzi, Rafael Navas, Moraima Hernández, Carlos Pérez-Vega, Manuela Mérida, David A Forero-Peña, Juan-Carlos Navarro, Claudia Beltrán-Arroyave, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Krisha Shah, Rubén Herzog, Alan C Swann, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Elective Genomic Sequencing For Adults In Research, Clinical And Commercial Contexts, Michael D Linderman, Sophia M Adelson, Tala M Berro, Jennifer L Anderson, Scott D Crawford, Tshaka J Cunningham, Edward D Esplin, Altovise T Ewing-Crawford, Daiva E Nielsen, Stacey Pereira, Tara Schmidlen, Heather Andrighetti, Steven B Bleyl, George M Church, Eden V Haverfield, Madhuri Hegde, Lazaridis N Konstantinos, Paul Kruszka, Debra Leonard, Thomas May, Molly Mcginniss, Vaibhav Pandya, Eric E Schadt, Bastian Greshake Tzovaras, Bethany Zettler, Amy L Mcguire, Robert C Green

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants' motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers.

Methods: We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms.

Results: We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire …

Multiplexed Plasmon-Enhanced Lateral Flow Assay For Early Diagnosis Of Acute Kidney Injury, Heng Guo, Yuxiong Liu, Ravi Jada, Ying Liu, Carissa Ng, Aquiles Payte, Jiaying Xu, Connor Malone, Jie Zhao, Kedhareswara Sairam Pasupuleti, Arda Aidan Arikan, Sameer Thadani, Srikanth Singamaneni, Ayse Akcan Arikan, Limei Tian

Faculty, Staff and Students Publications

Early diagnosis of acute kidney injury (AKI) remains a major clinical challenge due to the delayed and insensitive nature of conventional markers such as serum creatinine. Urinary protein biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC), provide earlier and complementary information on kidney injury, but their clinical translation is limited by the lack of rapid, quantitative, and multiplexed point-of-care (POC) diagnostic tests. Here, we report a multiplexed plasmonic-fluor-based lateral flow assay (p-LFA) that enables sensitive, quantitative, and simultaneous detection of NGAL and CysC. By harnessing ultrabright plasmonic-fluor nanolabels and ratiometric fluorescence analysis, the p-LFA achieves picogram-per-milliliter analytical sensitivity …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

Assessing Hpv And Hpv Vaccine Awareness And Perception Amongst Undergraduate Students, Maura Hawkins

Honors Theses

Human Papillomavirus (HPV) is one of the most common sexually transmitted infections in the United States. Vaccination rates remain low among college-aged students despite an effective vaccine being available. This study investigates HPV and HPV vaccination-related knowledge, beliefs, and perceptions among undergraduate students to inform targeted intervention strategies. Participants included undergraduate students (n = 19) who attended one of three focus groups conducted in April 2025 at the University of South Alabama. Structured interview guides explored HPV knowledge, perceived risk and severity, attitudes towards vaccination, autonomy in health decision-making, trust in health information sources, and preferred educational strategies. Discussions were …

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

Nano-Bio Interfacial Effects Modulating Protein Adsorption In Dialdehyde Lentinan-Crosslinked Polysaccharide Sponges Reinforced With Zein Nanoflowers, Dorota Chelminiak-Dudkiewicz, Miloslav Machacek, Hana Janová, Klara Konecna, Ondrej Jandourek, Jana Kejmarová, Kinga Mylkie, Aleksander Smolarkiewicz-Wyczachowski, Marta Ziegler-Borowska

The Brown Foundation: Institute of Molecular Medicine

The interfacial organization of porous biomaterials critically influences protein adsorption and subsequent cell-material interactions at hydrated biointerfaces relevant to wound-contacting environments. Herein, hybrid sponges were developed by rationally assembling chitosan, lentinan, levan, and fucoidan into a covalently defined macromolecular network featuring nano-bio interfacial effects. The materials were designed to modulate interfacial biological performance via engineered pore-wall structures, with protein-layer formation at sponge interfaces associated with downstream cell-material responses. A dialdehyde lentinan was deliberately employed to establish a chemically defined pore-wall interface via dense Schiff-base junctions with chitosan. The incorporation of zein nanoflowers introduced additional nanoscale structure features, providing additional anchoring …

Cost Utility Analysis Of Fluticasone Exhalation Delivery System Versus Budesonide Nasal Irrigation For Chronic Rhinosinusitis With Nasal Polyps, Daniel Xiao, Martin J Citardi, William C Yao, Amber U Luong

The Brown Foundation: Institute of Molecular Medicine

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is managed after sinus surgery with topical corticosteroids. Given limited distribution of nasal steroid sprays, patients have the option of either steroid nasal irrigation (SNI) or exhalation delivery system with fluticasone (EDS-FLU). This study evaluates the cost-effectiveness of EDS-FLU compared to SNI for CRSwNP.

Methods: A cohort-style Markov decision-tree economic model with a 33-year time horizon was developed in TreeAgePro. Because EDS-FLU is not currently covered by Medicare, costs of medications were estimated using retail pricing. A willingness-to-pay threshold of $50,000/quality adjusted life year (QALY) was used to determine cost-effectiveness. One-way and probabilistic …

Functional Characterization Of Uhrf1 Variants In Facilitating Dna Methylation, Bigang Liu, Kaila Nayvelt, Swanand Hardikar, Kimie Kondo, Marcos R Estecio, Xiaodong Cheng, Taiping Chen

The Brown Foundation: Institute of Molecular Medicine

Ubiquitin-like with plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) is essential for DNA methylation inheritance. However, the functional impacts of several natural and engineered UHRF1 variants are either insufficiently characterized or obscured by conflicting results, with some discrepancies likely stemming from cellular toxicity and adaptive responses induced by DNA methylation changes. In this study, we utilized mouse embryonic stem cells (mESCs)-which uniquely tolerate the complete loss of DNA methylation-to evaluate the functional consequences of clinical mutations, isoform variation, and epitope tagging. Using rescue experiments in Uhrf1-deficient mESCs, we characterized two UHRF1 mutations identified in …

The Effects Of Abstinence Status And Sleep Quality On Resting State Alpha Power In Cocaine Use Disorder, Heather E Webber, Danielle A Kessler, Joy M Schmitz, Scott D Lane, Robert Suchting

Faculty, Staff and Student Publications

Rationale

Substance use disorders are associated with notable sleep disturbances. Electroencephalogram (EEG) alpha power occurs during wakeful rest, is associated with sleepiness, and indicates neural deactivation.

Objectives

The goal of the current study was to assess the effects of abstinence on the relationship between alpha power and subjective sleep quality in participants with cocaine use disorder (CUD).

Methods

Participants with CUD (n = 32) who were recently or non-abstinent completed a resting-state EEG paradigm (90 s eyes open/closed). Absolute alpha power was calculated using the fast Fourier transform and by averaging within the power spectra of the alpha band (8–13 …

Does Antibiotic Therapy Affect Multiplex Pcr Results In Community-Acquired Bacterial Meningitis?, Caroline Reckart, Elizabeth Aguilera, Audrey Wanger, Rafael Bravo-Santos, Rodrigo Hasbun

Faculty, Staff and Student Publications

No abstract provided.

Relationship Of Early Rapid Weight Loss To Efficacy And Safety Of Tirzepatide And Semaglutide For Obesity: Surmount-5 Post Hoc Analysis, Louis J Aronne, Deborah B Horn, Alexander D Kokkinos, Beverly L Falcon, Hui Wang, Hunter T Hoffmann, Clare J Lee, Julia P Dunn

Faculty, Staff and Student Publications

Background: A knowledge gap remains in how the rate of body weight reduction impacts efficacy and safety of obesity management medications. This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.

Methods: Rapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively. Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed. End-of-study safety and gastrointestinal adverse events measures were summarized.

Results: Overall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%). The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders. Safety trends for tirzepatide and semaglutide were similar between …