Medicine and Health Sciences Commons^™

Multidrug-Resistant Esbl-Producing Escherichia Coli Coexisting With Colistin-Resistance Genes In Pig Farms, Central Thailand, Wipawee Songsaeng, Nutthee Am-In, Nuvee Prapasarakul, Wandee Sirichokchatchawan

The Thai Journal of Veterinary Medicine

The presence of extended-spectrum beta-lactamase and colistin resistance E. coli in food-producing animals is a public health concern. This study was conducted using a rigorous methodology to survey the prevalence of ESBL-producing and colistin-resistant E. coli from pig farms in the central part of Thailand. A total of 519 samples were collected from fecal, feed, and waste in 53 farms located in central Thailand. All samples were inoculated onto selective agar, and species identification was performed using biochemical assays and MAlDI-TOF MS. Antimicrobial susceptibility was determined by broth microdilution, and ESBL production was confirmed by the combination disc diffusion method. …

Exploration Of Positive Deviance In Prevention Of Underweight In The Under-Five: A Qualitative Study On Low-Income Urban Families, Irwan Budiono, Lukman Fauzi, Dewi Sari Rochmayani

Kesmas

Children under the age of five (the under-five) from low-income families are more vulnerable to experience underweight. This nutritional vulnerability is evident in the preliminary study, where 35.1% of the under-five experience underweight, and 28.48% are low-income families. This study aimed to explore Positive Deviance (PD) behaviors in preventing underweight among the under-five. The study applied a qualitative approach with a case study design. Data collection took place in July-August 2022, focusing on low-income families in the Gunung Brintik area. Data were collected through two focus group discussions, seven in-depth interviews, and five key informant interviews. Coding, subtheme, and theme …

Risk Factors For Cognitive Impairment In Adult Population Of Coastal Area: A Cross-Sectional Study In Maringkik Island, Indonesia, Herpan Syafii Harahap, Arina Windri Rivarti, Nurhidayati Nurhidayati, Fitriannisa Faradina Zubaidi, Dini Suryani, Legis Ocktaviana Saputri, Yanna Indrayana, Athalita Andhera, Muhammad Hilam, Abiyyu Didar Haq

Kesmas

Cognitive impairment is a medical condition commonly found in elderly populations, which can be due to vascular risk factors in patients. There remains limited data on risk factors for cognitive impairment among coastal region populations. This study aimed to investigate risk factors for cognitive impairment in the adult population of Maringkik Island, West Nusa Tenggara Province, Indonesia. Data collected were age, sex, education level, hypertension, antihypertensive treatment, diabetes mellitus, cigarette smoking, and body mass index status. A total of 114 participants were recruited using a consecutive sampling method. The participants’ cognitive function assessment used the Mini-Cog instrument. The cognitive impairment …

The Icf Syndrome Protein Cdca7 Harbors A Unique Dna Binding Domain That Recognizes A Cpg Dyad In The Context Of A Non-B Dna, Swanand Hardikar, Ren Ren, Zhengzhou Ying, Jujun Zhou, John R Horton, Matthew D Bramble, Bin Liu, Yue Lu, Bigang Liu, Luis Della Coletta, Jianjun Shen, Jiameng Dan, Xing Zhang, Xiaodong Cheng, Taiping Chen

Faculty, Staff and Student Publications

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout …

Metabolite Biomarker Discovery For Lung Cancer Using Machine Learning, Ariski Fajarido, Linda Erlina, Aryo Tedjo, Fadilah Fadilah, Wawaimuli Arozal

Indonesian Journal of Medical Chemistry and Bioinformatics

Lung cancer is the leading cause of cancer death worldwide. About 2.1 million lung cancer patients were diagnosed in 2018, accounting for about 11.6% of all newly diagnosed cancer cases. For lung cancer, blood is the first choice as a source of screening biomarker candidates. Blood biomarkers provide a snapshot of the patient's entire body, including the primary tumor, metastatic disease, immune response, and peritumoral stroma. However, sputum sampling, bronchial lavage or aspiration, exhaled breath (EB), and airway epithelial sampling represent unique samples for lung cancer and other airway cancers as potential sources for alternative biomarkers. Metabolites are products of …

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …

Therapeutic Antisense Oligonucleotides In Oncology: From Bench To Bedside, Elif Çakan, Olivia D Lara, Anna Szymanowska, Emine Bayraktar, Arturo Chavez-Reyes, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Advancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification …

Active Learning Pipeline To Identify Candidate Terms For A Cdss Ontology, Xia Jing, Rohan Goli, Keerthana Komatineni, Shailesh Alluri, Nina Hubig, Hua Min, Yang Gong, Dean F Sittig, Paul Biondich, David Robinson, Christian Nøhr, Arild Faxvaag, Adam Wright, Timothy Law, Lior Rennert, Ronald Gimbel

Faculty, Staff and Student Publications

Ontology is essential for achieving health information and information technology application interoperability in the biomedical fields and beyond. Traditionally, ontology construction is carried out manually by human domain experts (HDE). Here, we explore an active learning approach to automatically identify candidate terms from publications, with manual verification later as a part of a deep learning model training and learning process. We introduce the overall architecture of the active learning pipeline and present some preliminary results. This work is a critical and complementary component in addition to manually building the ontology, especially during the long-term maintenance stage.

Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials.

Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV.

Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase …

Sexannodb, A Knowledgebase Of Sex-Specific Regulations From Multi-Omics Data Of Human Cancers, Mengyuan Yang, Yuzhou Feng, Jiajia Liu, Hong Wang, Sijia Wu, Weiling Zhao, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Background

Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited. These resources lack detailed mechanistic studies on sex-biased molecules.

Methods

In this study, we conducted a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, delving into sex-biased effects. Our analyses encompassed sex-biased competitive endogenous RNA networks, regulatory networks involving sex-biased RNA binding protein-exon skipping events, sex-biased transcription factor-gene regulatory networks, …

Challenges And Opportunities Of Artificial Intelligence In Cdss And Patient Safety, Yang Gong, Hua Min, Xia Jing, Ping Yu

Faculty, Staff and Student Publications

Ensuring patient safety in healthcare involves training professionals and implementing clinical decision support systems (CDSS) and health IT solutions to reduce errors and adverse events. The integration of artificial intelligence (AI) into health IT has revolutionized clinical settings by enabling real-time insights and personalized recommendations. However, the use of health IT can lead to unintended consequences that are not adequately addressed during training and implementation. These consequences can hinder the maximization of benefits and limit equitable access to healthcare. In this paper, we explore the impact of AI on CDSS and health IT, discuss the challenges in educating clinical informaticians, …

Loss Of Symmetric Cell Division Of Apical Neural Progenitors Drives Dennd5a-Related Developmental And Epileptic Encephalopathy, Emily Banks, Vincent Francis, Sheng-Jia Lin, Fares Kharfallah, Vladimir Fonov, Maxime Lévesque, Chanshuai Han, Gopinath Kulasekaran, Marius Tuznik, Armin Bayati, Reem Al-Khater, Fowzan S Alkuraya, Loukas Argyriou, Meisam Babaei, Melanie Bahlo, Behnoosh Bakhshoodeh, Eileen Barr, Lauren Bartik, Mahmoud Bassiony, Miriam Bertrand, Dominique Braun, Rebecca Buchert, Mauro Budetta, Maxime Cadieux-Dion, Daniel G Calame, Heidi Cope, Donna Cushing, Stephanie Efthymiou, Marwa Abd Elmaksoud, Huda G El Said, Tawfiq Froukh, Harinder K Gill, Joseph G Gleeson, Laura Gogoll, Elaine S-Y Goh, Vykuntaraju K Gowda, Tobias B Haack, Mais O Hashem, Stefan Hauser, Trevor L Hoffman, Jacob S Hogue, Akimoto Hosokawa, Henry Houlden, Kevin Huang, Stephanie Huynh, Ehsan G Karimiani, Silke Kaulfuß, G Christoph Korenke, Amy Kritzer, Hane Lee, James R Lupski, Elysa J Marco, Kirsty Mcwalter, Arakel Minassian, Berge A Minassian, David Murphy, Juanita Neira-Fresneda, Hope Northrup, Denis M Nyaga, Barbara Oehl-Jaschkowitz, Matthew Osmond, Richard Person, Davut Pehlivan, Cassidy Petree, Lynette G Sadleir, Carol Saunders, Ludger Schoels, Vandana Shashi, Rebecca C Spillmann, Varunvenkat M Srinivasan, Paria N Torbati, Tulay Tos, Maha S Zaki, Dihong Zhou, Christiane Zweier, Jean-François Trempe, Thomas M Durcan, Ziv Gan-Or, Massimo Avoli, Cesar Alves, Gaurav K Varshney, Reza Maroofian, David A Rudko, Peter S Mcpherson

Faculty, Staff and Student Publications

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells …

The Dna Repair Pathway As A Therapeutic Target To Synergize With Trastuzumab Deruxtecan In Her2-Targeted Antibody-Drug Conjugate-Resistant Her2-Overexpressing Breast Cancer, Jangsoon Lee, Kumiko Kida, Jiwon Koh, Huey Liu, Ganiraju C Manyam, Young Jin Gi, Dileep R Rampa, Asha S Multani, Jing Wang, Gitanjali Jayachandran, Dae-Won Lee, James M Reuben, Aysegul Sahin, Lei Huo, Debu Tripathy, Seock-Ah Im, Naoto T Ueno

Faculty, Staff and Student Publications

Background: Anti-HER2 therapies, including the HER2 antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpressing (HER2+) metastatic breast cancer. However, intrinsic or acquired resistance to anti-HER2-based therapies remains a clinical challenge in these patients, as there is no standard of care following disease progression. The purpose of this study was to elucidate the mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identify targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ breast cancer in vitro and in vivo. …

Transcriptome Profiling Of Pediatric Extracranial Solid Tumors And Lymphomas Enables Rapid Low-Cost Diagnostic Classification, Kofi B Opoku, Teresa Santiago, Priya Kumar, Sophia M Roush, Yuri Fedoriw, Tamiwe Tomoka, Vasiliki Leventaki, Larissa V Furtado, Nickhill Bhakta, Thomas B Alexander, Jeremy R Wang

Faculty, Staff and Student Publications

Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. …

Short-Term Hiit Impacts Hdl Function Differently In Lean, Obese, And Diabetic Subjects, Lin Zhu, Julia An, Thao Luu, Sara M. Reyna, Puntip Tantiwong, Apiradee Sriwijitkamol, Nicolas Musi, John M. Stafford

School of Medicine Publications

Introduction: High density lipoproteins (HDL) exert cardiovascular protection in part through their antioxidant capacity and cholesterol efflux function. Effects of exercise training on HDL function are yet to be well established, while impact on triacylglycerol (TG)-lowering has been often reported. We previously showed that a short-term high-intensity interval training (HIIT) program improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells in insulin-resistant subjects. The purpose of this study is to evaluate HDL function along with changes of lipoproteins after the short-term HIIT program in lean, obese nondiabetic, and obese type 2 diabetic (T2DM) subjects.

Methods: All individuals …

Preventing And Managing Equine Gastric Ulcer Syndrome, Kylie Bell, Karl Hoopes

All Current Publications

Current industry trends regarding equine management practices largely contribute to the development of equine gastric ulcer syndrome (EGUS). Research on effective medical management exists; however, we lack studies on the efficacy of equine-welfare-minded solutions. This fact sheet reviews current literature, including diagnosing, treating, and preventing EGUS. It also provides a general overview of the natural equine, promoting a greater understanding of the connection between strategies to prevent and manage EGUS.

Analysis Of Serum Exosome Metabolites Identifies Potential Biomarkers For Human Hepatocellular Carcinoma, Tingting Zhao, Yan Liang, Xiaolan Zhen, Hong Wang, Li Song, Didi Xing, Hui Li

Faculty, Staff and Student Publications

Currently, the clinical cure rate for primary liver cancer remains low. Effective screening and early diagnosis of hepatocellular carcinoma (HCC) remain clinical challenges. Exosomes are intimately associated with tumor development and their contents have the potential to serve as highly sensitive tumor-specific markers. A comprehensive untargeted metabolomics study was conducted using exosome samples extracted from the serum of 48 subjects (36 HCC patients and 12 healthy controls) via a commercial kit. An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) strategy was used to identify the metabolic compounds. A total of 18 differential metabolites were identified using the non-targeted metabolomics approach of UPLC-QTOF-MS/MS. …

Teacher Implementation Profiles: A Response To Top-Down Mandate Of Movement Integration, Zack Beddoes, Jeanne Barcelona, Darla Castelli

International Journal of Physical Activity and Health

This study examined teacher implementation practices to meet a state mandate requiring 135 minutes of student physical activity (PA) weekly. Teachers were required to implement a video-based movement integration (MI) program. Using an embedded mixed-methods design, provider characteristics of 42 teachers and the organizational capacity of six schools were developed from interviews, surveys, observations, and artifacts. Data analysis revealed three teacher profiles (a) Dynamic Experientialists, (b) Coachable Constructivists, and (c) Cautious Behaviorists, and three school profiles (a) Whole Child Approach, (b) Grade Level Champions, and (c) Back to Basics. Findings suggest that school, teacher, …

Bp1003 Decreases Stat3 Expression And Its Pro-Tumorigenic Functions In Solid Tumors And The Tumor Microenvironment, Maria Gagliardi, Rhonda Kean, Bingbing Dai, Jithesh Augustine, Michael Roberts, Jason Fleming, D. Craig Hooper, Ana Ashizawa

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2⁺, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in …

Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Cell-based medicinal products are a breakthrough that has been proven to treat previously incurable diseases, making them a topic of global interest. This review delves into the current state and progress of cell therapy, highlighting the remarkable therapeutic effects of various types of cell-based medicinal products. We specifically explore the potential development of cell-based medicinal products in China, focusing on promoting clinical translation and commercialization. We propose necessary actions to achieve these goals, such as fostering cutting-edge basic research, innovative therapeutic approaches, scalable manufacturing processes, and policy changes.

Structural Basis For Substrate Binding And Selection By Human Mitochondrial Rna Polymerase, Karl Herbine, Ashok Nayak, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

The mechanism by which RNAP selects cognate substrates and discriminates between deoxy and ribonucleotides is of fundamental importance to the fidelity of transcription. Here, we present cryo-EM structures of human mitochondrial transcription elongation complexes that reveal substrate ATP bound in Entry and Insertion Sites. In the Entry Site, the substrate binds along the O helix of the fingers domain of mtRNAP but does not interact with the templating DNA base. Interactions between RNAP and the triphosphate moiety of the NTP in the Entry Site ensure discrimination against nucleosides and their diphosphate and monophosphate derivatives but not against non-cognate rNTPs and …

Clinical And Genomic-Based Decision Support System To Define The Optimal Timing Of Allogeneic Hematopoietic Stem-Cell Transplantation In Patients With Myelodysplastic Syndromes, Cristina Astrid Tentori, Caterina Gregorio, Marie Robin, Nico Gagelmann, Carmelo Gurnari, Somedeb Ball, Juan Carlos Caballero Berrocal, Luca Lanino, Saverio D'Amico, Marta Spreafico, Giulia Maggioni, Erica Travaglino, Elisabetta Sauta, Manja Meggendorfer, Lin-Pierre Zhao, Alessia Campagna, Victor Savevski, Armando Santoro, Najla Al Ali, David Sallman, Francesc Sole, Guillermo Garcia-Manero, Ulrich Germing, Nicolaus Kroger, Shahram Kordasti, Valeria Santini, Guillermo Sanz, Wolfgang Kern, Uwe Platzbecker, Maria Diez-Campelo, Jaroslaw P Maciejewski, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Amer M Zeidan, Gastone Castellani, Rami Komrokji, Francesca Ieva, Matteo Giovanni Della Porta, Genomed4all And Synthema Consortiums

Faculty, Staff and Student Publications

Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M).

Patients and methods: We studied a retrospective population of 7,118 patients, stratified into training and validation …

Impacts Of Interleukin-10 Promoter Genotypes On Prostate Cancer, Yu-Ting Chin, Chung-Lin Tsai, Hung-Huan Ma, Da-Chuan Cheng, Chia-Wen Tsai, Yun-Chi Wang, Hou-Yu Shih, Shu-Yu Chang, Jian Gu, Wen-Shin Chang, Da-Tian Bau

Faculty, Staff and Student Publications

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of …

Association Of Social Determinants, Lifestyle, And Metabolic Factors With Mortality In Chinese Adults: A Nationwide 10-Year Prospective Cohort Study, Jieli Lu, Mian Li, Jiang He, Yu Xu, Ruizhi Zheng, Jie Zheng, Guijun Qin, Yingfen Qin, Yuhong Chen, Xulei Tang, Zhen Ye, Min Xu, Tiange Wang, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Zhiyun Zhao, Qin Wan, Gang Chen, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Hong Qiao, Yinfei Zhang, Tianshu Zeng, Chunyan Hu, Qiuyu Cao, Xiaojing Jia, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Hongyan Qi, Xueyan Wu, Di Zhang, Meng Dai, Donghui Li, Shenghan Lai, Lulu Chen, Jiajun Zhao, Yiming Mu, Weiguo Hu, Guang Ning, Ruying Hu, Yufang Bi, Weiqing Wang, 4c Study Group

Faculty, Staff and Student Publications

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high …

Effect Of The Implementation Of A Multiple-Behavior Self-Monitoring Intervention On Dietary Intake In Type 2 Diabetes: Secondary Data Analysis, Jisook Ko, Jing Wang, Ngozi Mbue, Susan Schembre, Stanley Cron

Faculty, Staff and Student Publications

Background: An electronic diary embedded in a mobile device to monitor lifestyle can be as effective as traditional methods. However, the efficacy of self-monitoring multiple behaviors for dietary intake has not been well studied in people with diabetes.

Objective: This study aimed to compare the effect of using technology-assisted self-monitoring versus paper diaries on changes in dietary intake.

Methods: This is a secondary analysis of data collected from 39 people with type 2 diabetes as part of a 3-month pilot clinical trial. Changes in energy intake and the contribution of total fat intake and total carbohydrate intake to total calories …

The Complex Molecular Epileptogenesis Landscape Of Glioblastoma, Victoria Soeung, Ralph B Puchalski, Jeffrey L Noebels

Faculty, Staff and Students Publications

The cortical microenvironment surrounding malignant glioblastoma is a source of depolarizing crosstalk favoring hyperexcitability, tumor expansion, and immune evasion. Neosynaptogenesis, excess glutamate, and altered intrinsic membrane currents contribute to excitability dyshomeostasis, yet only half of the cases develop seizures, suggesting that tumor and host genomics, along with location, rather than mass effect, play a critical role. We analyzed the spatial contours and expression of 358 clinically validated human epilepsy genes in the human glioblastoma transcriptome compared to non-tumor adult and developing cortex datasets. Nearly half, including dosage-sensitive genes whose expression levels are securely linked to monogenic epilepsy, are strikingly enriched …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

08.19.2024 Orsp Connect, Liz Williamson

ORED Newsletter

Lei Cao NSF award

FDP Meeting Summaries Available

August LINC Lunch

Collaboration Opportunities

Simulation Of Crispr-Cas9 Editing On Evolving Barcode And Accuracy Of Lineage Tracing, Fengshuo Liu, Xiang Zhang, Yipeng Yang

Faculty, Staff and Students Publications

We designed a simulation program that mimics the CRISPR-Cas9 editing on evolving barcode and double strand break repair procedure along with cell divisions. Emerging barcode mutations tend to build upon previously existing mutations, occurring sequentially with each generation. This process results in a unique mutation profile in each cell. We sample the barcodes in leaf cells and reconstruct the lineage, comparing it to the original lineage tree to test algorithm accuracy under different parameter settings. Our computational simulations validate the reasonable assumptions deduced from experimental observations, emphasizing that factors such as sampling size, barcode length, multiple barcodes, indel probabilities, and …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …