Medical Specialties Commons^™

Vitamin D Is Glucoprotective In Aging Males But Not Females, Olivia Z B Ginnard, Maria Morales, Ji Youn Youn, Yong Xu, Stephanie R Sisley

Faculty, Staff and Students Publications

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

Prevalence Of Potentially Inappropriate Medications In People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Abdulmuminu Isah, Ruth Jeminiwa, Ibraheem Abioye, Ismaeel Yunusa, Mohammed Abba-Aji, Osagie Kenneth Cole, Jamila Sani, Mukhtar Ijaiya, Chukwuemeka Nwachuya, Yusuf Ibrahim, Mustapha Usman, Duke Daniels, Oluwaseun Samuel Ilugbuhi, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

BACKGROUND: Potentially inappropriate medications (PIM) are associated with adverse health outcomes. The use of PIM among persons living with HIV (PLHIV) could be more problematic due to peculiarities such as antiretroviral toxicity and drug-disease interactions. However, PIM among PLHIV continues to receive little attention. Therefore, we aimed to systematically review and estimate the prevalence of PIM among PLHIV.

METHODS: We searched the PubMed, Scopus, and Web of Science databases to identify relevant studies from 1 January 2014 to 30 June 2024. Studies included were peer-reviewed articles that determined PIM prevalence using validated explicit or implicit tools and provided statistical information …

A Practical Primer On How To Detect And Treat Depression In Ckd, L Parker Gregg, Lynnel Goodman, Ella Q Carroll, S Susan Hedayati

Faculty, Staff and Students Publications

Detection and management of depression have special considerations in people with kidney disease. Screening should be done every 6-12 months using a self-reported questionnaire. Clinicians should rule out symptoms from medical conditions such as dialysis inadequacy or hypothyroidism and confirm the presence of sadness or anhedonia. Sertraline has shown limited efficacy and an increased risk for adverse effects such as gastrointestinal symptoms, so cautious, gradual dose titration is warranted. Cognitive behavioral therapy has potential benefit for depressive symptoms in people with kidney disease. Current trials are evaluating behavioral activation therapy. Physical activity has many benefits and likely improves depression.

Discovery Of A Novel Small Molecule Degrader Of Wild Type And Mutant Estrogen Receptors Using Dna Encoded Libraries, Anil Kumar Devakrishnan, Chandrashekhar Madasu, Yong Wang, Ramkumar Modukuri, Kurt M Bohren, Kevin R Mackenzie, Damian W Young, Suzanne A W Fuqua, Martin M Matzuk, Murugesan Palaniappan

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) variants with mutations in the ligand binding domain (LBD) are less sensitive than wild type to standard-of-care drugs that bind ERα directly. To identify novel small-molecule drugs that target ERα mutants, we screened our multibillion-compound DNA-encoded libraries against ERα LBD variants. CDD-1274, which was highly enriched with all three variants, blocked spontaneous coactivator peptide recruitment to mutant ERα LBDs and inhibited estradiol-driven proliferative markers in several ER-positive breast cancer cell lines, but not in ER-negative breast cancer cells. We demonstrated that CDD-1274 induced proteasomal degradation of ERα variants in breast cancer cell lines and caused Y537S …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Social Determinants Of Health Patterns In Children With Severe Disease Due To Sars-Cov-2 Infection-An Exploratory Approach, Joshua Prabhu, Sebastian Acosta, Fabio Savorgnan, Ananth V Annapragada, Usha Sethuraman

Faculty, Staff and Students Publications

Background/Objectives: Research on the association of adverse social determinants of health (SDOH) with severe pediatric coronavirus disease (COVID-19) is limited. We examined associations between SDOH patterns and COVID-19 severity in children.

Methods: We conducted a prospective, observational study of children (< 18 years) with symptomatic SARS-CoV-2 infection evaluated in an urban pediatric emergency department (March 2021-April 2022) in Detroit, Michigan. Caregivers completed a 34-item survey based on the Healthy People 2030 framework. Severe disease was defined as the occurrence of respiratory/cardiac failure or death within four weeks of diagnosis. Continuous and categorical variables were described using medians and percentages, respectively. Associations between disease severity and risk factors were determined using chi-square tests. Association rule mining was used for feature selection, followed by multivariate logistic regression.

Results: We analyzed data from 354 children [6-12 years: 31.1%, Female: 51.1%, Black: 59%, not Hispanic: 84.7%, public insurance: 77.1%, chronic condition: 27.4%]. Of the total, 113 children had severe disease. Most caregivers were 30-44 years old (53.1%), had less than a college degree (70.4%), and income < USD 50,000 (75.2%). Adverse SDOH reported included food/housing insecurity (24.6%), no support (64.7%), unmet childcare needs (35.9%), and lack of transportation (12.7%). After controlling for age, sex, medical history, income, and obesity, severe disease was associated with caregiver use of drugs/alcohol (OR:5.92, p < 0.001) and social discrimination/lack of support (OR: 1.74, p = 0.030).

Conclusions: Two SDOH patterns (caregiver use of drugs/alcohol …

Standardizing And Scaffolding Health Care Ai-Chatbot Evaluation: Systematic Review., Yining Hua, Winna Xia, David Bates, George Hartstein, Hyungjin Tom Kim, Michael Li, Benjamin Nelson, Charles Stromeyer Iv, Darlene King, Jina Suh, Li Zhou, John Torous

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Health care chatbots are rapidly proliferating, while generative artificial intelligence (AI) outpaces existing evaluation standards.

OBJECTIVE: We aimed to develop a structured, stakeholder-informed framework to standardize evaluation of health care chatbots.

METHODS: PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)-guided searches across multiple databases identified 266 records; 152 were screened, 21 full texts were assessed, and 11 frameworks were included. We extracted 356 questions (refined to 271 by deduplication and relevance review), mapped items to Coalition for Health AI constructs, and organized them with iterative input from clinicians, patients, developers, epidemiologists, and policymakers.

RESULTS: We developed the Health …

Pathways And Challenges In The Clinical Translational Of Radiopharmaceuticals For Pediatric Investigations, Erik Stauff, Hanieh Karimi, Heidi H. Kecskemethy, Thomas H. Shaffer, Reza Vali, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical development and clinical translation face numerous scientific, ethical, and regulatory challenges, particularly within the pediatric population. Although molecular imaging holds significant promise for improving diagnosis and treatment across a spectrum of diseases, including pediatric-specific conditions like Kawasaki disease, autism spectrum disorders, attention-deficit/hyperactivity disorder, and neuroblastoma, the path from discovery to clinical application remains problematic. The U.S. Food and Drug Administration (FDA) provides three primary pathways-traditional Investigational New Drug (IND) applications, exploratory Investigational New Drug application (eIND), and the Radioactive Drug Research Committee (RDRC) mechanism-to facilitate clinical translation of radiotracers. However, these frameworks are not specifically tailored to pediatric needs. …

Use Of An Expert Panel For Symptomatic Patients With Grade I Degenerative Lumbar Spondylolisthesis: A Randomized Clinical Trial, Zoher Ghogawala, Tasneem Rizvi, Zhibang Lin, Adam Kanter, Praveen Mummaneni, Erica Bisson, Todd Albert, Daniel Resnick, Michael Wang, Steven Glassman, David Polly, Mohamad Bydon, Subu Magge, Luis Tumialan, Michael Fehlings, Michael Steinmetz, Robert Whitmore, Vedantam Rajshekhar, James Harrop, Roger Härtl, Elnasri Ahmed, Dom Coric, Paul Mccormick, Richard Assaker, Abdul Msaddi, Langston Holly, Yoshiharu Kawaguchi, Asdrubal Falavigna, Fred Barker, Edward Benzel

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The appropriate utilization of lumbar fusion when performing laminectomy for lumbar spondylolisthesis is uncertain. The objective was to determine whether the use of a surgical expert review panel recommending fusion might improve patient selection, possibly reducing surgical failures.

METHODS: Randomized clinical trial of patients with symptomatic degenerative lumbar stenosis with spondylolisthesis enrolled from 14 North American hospitals was conducted with patients randomized to receive an expert panel review of their case or not. Spinal expert review consisted of 10 to 15 surgeons' review of patient images and clinical data with voting on the appropriateness of fusion. Primary …

Mutant P53 Variants Differentially Impact Replication Initiation And Activate Cgas-Sting To Affect Immune Checkpoint Inhibition, Kang Liu, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

Prior research shows that Akt-dependent phosphorylation of TopBP1 in S phase results in the switch of TopBP1/Treslin binding to TopBP1/E2F1 binding, which is important to prevent replication re-initiation in late S and G2 phases. Here, we demonstrate that contact, but not conformational, mutant p53 can override this switch by binding to both TopBP1 and Treslin, thereby facilitating persistent TopBP1/Treslin interaction in late S and G2 phases, which ultimately leads to over-firing of replication initiation. This increases micronuclei formation, which is further enhanced by genotoxic stressors such as doxorubicin, PARP inhibitors, or ATR inhibitors. Consequently, contact mutant p53 increases the sensitivity …

Disparate Leukemia Mutations Converge On Nuclear Phase-Separated Condensates, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting …

Serum Response Factor Is Essential For Endometrial Function And Prevention Of Inflammatory Fibrosis, Ryan M Marquardt, Sara A Grimm, San-Pin Wu, Peter F Lais, Shu-Yun Li, Xin Xu, Erin Smithberger, David Cunefare, Charan Ganta, David Olson, Eunhee M Jeong, Jae-Wook Jeong, Bruce A Lessey, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Pregnancy requires a supportive uterine environment facilitated by steroid hormone–regulated differentiation of endometrial stromal fibroblasts into decidual cells and tight control of inflammation. Serum response factor (SRF) is a widely expressed transcription factor essential for mesenchymal cell growth and differentiation with noted roles in hormonal regulation of muscle tissues but little characterization in reproductive organs. Here, we reveal that endometrial SRF is dysregulated in human endometriosis and is critical for female reproductive success in mice through regulation of endometrial stromal and epithelial cells. Immunohistochemical analysis identified decreased endometrial SRF expression in infertile endometriosis patient tissues. RNAi-based SRF knockdown in human …

Giant Cell Arteritis After Mrna Covid Vaccines: Concerning Or A False Alarm?-A Retrospective Cohort Study, Syed M. F. Zabiullah, Rutwik Pradeep Sharma, Roshan Subedi, Viqarunnisa Faaiza Zahid, Yasir Loai, Sarathlal Mannumbethlal, Aatifa Aatifa

Advances in Clinical Medical Research and Healthcare Delivery

Background: The coronavirus disease (COVID-19) pandemic led to the first large-scale rapid deployment of novel messenger RNA (mRNA) vaccines. Although the effectiveness and safety of these vaccines were rigorously studied, post-vaccination adverse events such as giant cell arteritis (GCA) continue to be reported. More than two hundred and sixty three cases of new-onset GCA occurring after mRNA vaccine administration are listed in the Vaccine Adverse Events Reporting System as of October 2024. We aimed to explore the incidence of GCA after mRNA vaccines among patients in our health system and study their characteristics and outcomes.

Methods: We conducted a …

Evaluation Of Integrative Oncology Modalities For Symptom Management: A Mascc/Sio Global Survey, Alexandre Chan, Reem Nasr, Daniela Arcos, Dalia Kagramanov, Chioma Asuzu, Ting Bao, Yin Ting Cheung, Jung Hye Kwon, Judith Lacey, Richard T. Lee, Maryam Lustberg, Beatrice M. Ohaeri, Santosh Rao, Enrique Soto-Perez-De-Celis, Claudia M. Witt, Ana M. Lopez

Kimmel Cancer Center Faculty Papers

BACKGROUND: With growing evidence pointing towards the potential of integrative oncology modalities (IOM) in addressing cancer and cancer-treatment related symptoms, research on IOM utilization and implementation is warranted. This study examines global stakeholder perspectives on integrative oncology (IO) utilization for supportive cancer care.

METHODS: Members of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) completed a survey on the utilization of IOM for supportive cancer care. Descriptive statistics were used to assess demographic data, IOM usage patterns, IOM education, and financial considerations for utilizing IOM.

RESULTS: Among 344 participants representing eight geographical …

National Alliance Of Sickle Cell Centers Consensus Recommendations On Sickle Cell Disease Health Maintenance: A Consensus Statement, Seethal A. Jacob, Melissa Frei-Jones, Sana Saif-Ur-Rehman, Monica L. Hulbert, Andrew R. W. O'Brien, Crawford Strunk, Anthony Villella, Ravi Talati, Amma Owusu-Ansah, Francis Coyne, Patrick T. Mcgann, Parul Rai, Robin Miller, Angeli Rampersad, Vishwas Sakhalkar, Neha Bhasin, Deepa Manwani, Sophie Lanzkron, Julie Kanter

Cardeza Foundation for Hematologic Research

IMPORTANCE: The most common inherited blood disorder in the world, sickle cell disease (SCD) is a known global health concern. While survival of children into adulthood has improved significantly over the last few decades in high-resource countries, substantial gaps in care standards and limited practice harmonization persist.

OBJECTIVE: To provide up-to-date recommendations for preventive care and treatment of all people living with SCD and its related comorbidities.

EVIDENCE REVIEW: As part of the National Alliance of Sickle Cell Centers (NASCC), 41 pediatric and adult sickle cell disease experts developed consensus standards and recommendations based on available evidence and expert consensus …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

Burden Of Central Nervous System Cancer In The United States, 1990-2021, Hyun Jin Han, Yun Seo Kim, Seoyeon Park, Jae Il Shin, Min Seo Kim, Ju Hyung Moon, Yong Bae Kim, Hazim S Ababneh, Ahmed Abu-Zaid, Demelash Areda, Santhosh Arul, Ahmed Y Azzam, Mainak Bardhan, Mohammad Amin Bayat Tork, Babak Behnam, Gokce Belge Bilgin, Prarthna V Bhardwaj, Soumitra S Bhuyan, Nima Broomand Lomer, Meng Xuan Chen, Suma Sri Chennapragada, Xiaochen Dai, Frances E Dean, Sindhura Deekonda, Xueting Ding, Ojas Prakashbhai Doshi, Abdel Rahman E'Mar, Muhammed Elhadi, Jawad Fares, Patrick Fazeli, James L Fisher, Maryam Fotouhi, Ali Gholamrezanezhad, Fidelia Ida, Chidozie Declan Iwu, Mohamed Jalloh, Chinmay T Jani, Rizwan Kalani, Samuel Berchi Kankam, Foad Kazemi, Ariz Keshwani, Atulya Aman Khosla, Stephen S Lim, Riffat Mehboob, Tomislav Mestrovic, Ali H Mokdad, Christopher J L Murray, Gurudatta Naik, Zuhair S Natto, Dang Nguyen, Fred Nugen, Atakan Orscelik, Romil R Parikh, Louise Penberthy, Richard G Pestell, Disha Prabhu, Jagadeesh Puvvula, Shakthi Kumaran Ramasamy, Cameron John Sabet, Austin E Schumacher, Yigit Can Senol, Sunder Sham, Samendra P Sherchan, Gizeaddis Lamesgin Simegn, Jasvinder A Singh, Ranjan Solanki, Bahadar S Srichawla, Jabeen Taiba, Manoj Tanwar, Mike Tuffour Amirikah, Anjul Verma, Ismaeel Yunusa, David X Zheng, Dong Keon Yon, Keun Young Park

Faculty, Staff and Students Publications

Importance: Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States.

Objective: To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI).

Design, setting, and participants: This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Integrative Proteogenomics And Forward Genetics Reveal A Novel Mitotic Vulnerability In Triple-Negative Breast Cancer, Nicholas J Neill, Shankha Satpathy, Karsten Krug, Jitendra K Meena, Nivetha Ramesh Babu, Cheyenne Calderon, Desmon Reed, Marcus J Weber, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Meenakshi Anurag, Kimberly R Holloway, Chen Huang, Suhas Vasaikar, Maria F Cardenas, Beom-Jun Kim, Doug W Chan, Shayan C Avanessian, Siddhartha Tyagi, Mayra Orellana, Sufeng Mao, Heyuan Li, Fade Gong, Sarah J Kurley, Kristen L Meerbrey, Calla M Olson, Amritha Nair, Tingting Sun, Hsiang-Ching Chung, Elizabeth A Bowling, Jarey H Wang, Pengju Zhang, Peng Xiao, Duxiao Yang, Fabio Stossi, Mei-Yin C Polley, Alexander B Saltzman, Filip Mundt, D R Mani, Michael A Gillette, Susan G Hilsenbeck, George Miles, Carolina Gutierrez, C Kent Osborne, Charles Y Lin, Nathanael S Gray, Jinpeng Sun, David A Wheeler, Charles M Perou, Anna Malovannaya, Michael T Lewis, Bing Zhang, Matthew J Ellis, Steven A Carr, Thomas F Westbrook

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent …

Neonatal Unit Human Resources: Coverage For Six Cadres And Trends For Staff-To-Baby Ratios In 65 Neonatal Units Implementing With Nest360 In Kenya, Malawi, Nigeria, And Tanzania, Rebecca Penzias, Eric Ohuma, Opeyemi Odedere, Olabisi Dosunmu, George Okello, Hannah Mwaniki, Robert Tillya, Josephine Shabani, Vincent Ochieng, Ekran Rashid, William Macharia

Paediatrics and Child Health, East Africa

Background: Implementing small and sick newborn care (SSNC) requires skilled health workers; however, there is a shortage, adversely impacting patient outcomes and health worker wellbeing. There are limited data and no cur‑ rent World Health Organization (WHO) standards for staftobaby ratios in neonatal units in low and middleincome countries (LMICs) to inform policy, planning, and investment.

Methods: In 65 neonatal units (36 in Malawi, 13 in Kenya, 7 in Tanzania, and 9 in Nigeria), a health facility assessment (HFA) for SSNC and governmentled quality improvement (QI) processes were implemented. Stafng data were col‑ lated from baseline HFA (Sept 2019–March 2021) …

Implementation And Evaluation Of Infection Prevention And Control Training In Sub-Saharan Africa, David Odada, James Ndai, Ruth Thuku, Philip Adebayo

Internal Medicine, East Africa

No abstract provided.

Age-Specific Distribution Of Cervical Precancer And Cancer Among Women Living With Hiv Across Seven Countries: A Systematic Review And An Individual Patient Data Meta-Analysis, Shona Dalal, Karin Sundström, Ronaldo Silva, Katayoun Taghavi, Helen Cejtin, Michael Chung, Sharon Greene, Smita Joshi, Helen Kelly, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Background Women living with HIV have an elevated risk for cervical cancer, present earlier, and have more recurrent human papillomavirus (HPV) infections compared with women without HIV. To update WHO recommendations on screening and treatment to prevent cervical cancer, we aimed to identify whether women living with HIV should be screened for cervical cancer at a specific age, the optimal screening interval following a negative cervical screen, and the screening interval following treatment.

Methods We conducted a systematic literature review on cervical cancer and HIV by searching MEDLINE, Embase, CENTRAL, the Cochrane Library, and clinical trial registries covering Jan 1, …

Implementation Of The Multicountry Who Covid-19 Pregnancy Cohort Study: Challenges And Lessons Learned During The Pandemic, Maria Costa, Renato Souza, Jose Cecatti, Sami Gottlieb, Marie Delnord, Soe Soe Thwin, Ndema Habib, Marleen Temmerman, Ingrid Gichere, Beth Maina

Obstetrics and Gynaecology, East Africa

Introduction A generic research protocol was developed for a prospective cohort study to allow systematic, harmonized data collection of the impact of SARS-CoV-2 infection and vaccination during pregnancy on maternal, obstetric, and neonatal outcomes across different settings. This article describes the study conception, development, implementation, challenges, and key lessons learned within study sites across the world.

Methods The protocol was implemented in 43 facilities in 10 countries during the pandemic, involving consecutive recruitment of over 16,000 pregnant or postpartum women. We evaluated selection of study sites, ethical approvals, staff recruitment and training, recruitment and follow-up, and incorporation of new elements …

Neonatal Unit Human Resources: Coverage For Six Cadres And Trends For Staff-To-Baby Ratios In 65 Neonatal Units Implementing With Nest360 In Kenya, Malawi, Nigeria, And Tanzania, Rebecca Penzias, Eric Ohuma, Opeyemi Odedere, Olabisi Dosunmu, George Okello, Hannah Mwaniki, Robert Tillya, Vincent Ochieng, Ekran Rashid, William Macharia

Paediatrics and Child Health, East Africa

Background Implementing small and sick newborn care (SSNC) requires skilled health workers; however, there is a shortage, adversely impacting patient outcomes and health worker well-being. There are limited data and no current World Health Organization (WHO) standards for staff-to-baby ratios in neonatal units in low- and middle-income countries (LMICs) to inform policy, planning, and investment.

Methods In 65 neonatal units (36 in Malawi, 13 in Kenya, 7 in Tanzania, and 9 in Nigeria), a health facility assessment (HFA) for SSNC and government-led quality improvement (QI) processes were implemented. Staffing data were collated from baseline HFA (Sept 2019–March 2021) and mid-2023 …

Identifying Sex- And Gender-Specific Endocrinological, Lifestyle, Psychosocial, And Socio-Cultural Targets For Alzheimer's Disease Prevention In Africans: The Female Brain Health And Endocrine Research In Africa (Fember-Africa) Project, Chinedu Momoh, Benard Aliwa, Lukoye Atwoli, Karen Blackmon, Edna Bosire, Samuel Gitau, Harrison Kaleli, Ciru Kamanda, Linda Khakali, Rachel Maina, Peter Mativo, Sylvia Mbugua, Zul Merali, Kendi Muchungi, Anne Njogu, Douglas Nyankira, Alice Ondieki, Catherine Onyancha, Stanely Onyango, Jasmit Shah, Sheena Shah, Cynthia Smith, Dilraj Sokhi, Sheila Waa, Thomas Thesen

Brain and Mind Institute

Dementia rates are rising globally, with the burden increasing most rapidly in low- tomiddle-income countries. Despite this, research into Alzheimer’s disease and relateddementias (ADRD) among African populations remains limited, with existing modelsbased on Western cohorts that overlook sex-, gender-, and ancestry-specific factors.The Female Brain Health and Endocrine Research in Africa (FemBER-Africa) project,hosted at the Brain and Mind Institute, Aga Khan University, Kenya, will establish adeeply phenotyped cohort of 250 African individuals across the ADRD spectrum. Itwill assess sex-specific risk factors linked to ethnicity, lifestyle, and endocrinologicalvariables using fluid-based biomarkers (blood and saliva), neuroimaging (magneticresonance imaging and positron emission tomography), and …

Prevalence And Determinants Of Nomophobia Among Healthcare Workers In Nepal: A Cross-Sectional Study, Prakash Banjade, Asmita Itani, Munish Sharma, Reena Shah, Jasmit Shah, Aakansha Singh, Rahul Kashyap, Salim Surani

Brain and Mind Institute

Introduction: Nomophobia, the fear of being without a mobile phone, has become a significant concern in the current digital age. Healthcare professionals rely heavily on mobile devices for communication and information access. This cross-sectional study aimed to assess the prevalence and determinants of nomophobia among healthcare workers in Nepal.

Methods: A modified Nomophobia Questionnaire (NMP-Q) was used to determine nomophobia scores. Demographic characteristics such as age, gender, race, type of smartphone, hours spent on a smartphone, and type of medical specialty were considered to evaluate nomophobia in diverse groups of healthcare workers. Summary statistics were presented as frequencies …

Evaluating The Impact Of Alcohol On Dementia: Evidence From 13 Developing Countries, Cyprian Mostert

Brain and Mind Institute

Background: The 2024 Lancet Commission on Dementia Prevention identified alcoholconsumption as a risk factor contributing to a global increase in dementia cases by onepercent.

Method: We used a panel VAR model to analyze the impact of alcohol consumption ondementia prevalence in 13 developing countries with different alcohol tax systems.

Result: In countries with progressive alcohol tax systems, an increase in taxes onbeer and spirits leads to a 10 percent reduction in per capita alcohol consumption.This decline corresponds to a 4 percent reduction in dementia prevalence within fouryears. In countries with hybrid alcohol tax systems, a combination of alcohol bansand tax …

Small For Gestational Age Subgroups Have Differential Morbidity, Growth, And Neurodevelopment At Age 2: The Interbio-21st Newborn Study, Aris T. Papageorghiou, María C. Restrepo-Ménde, Rose Mcgready, Fernando C. Barros, Francois Nosten, Shama Munim, Roseline Ochieng, Rachel Craik, Hellen C. Barsosio, Zulfiqar Ahmed Bhutta

Department of Obstetrics & Gynaecology

Background: Small for gestational age is a complex perinatal syndrome associated with increased neonatal morbidity, mortality, and impaired childhood growth and neurodevelopment. Current classifications rely primarily on birthweight, which does not capture the heterogeneity of the condition nor predict long-term health outcomes. Here we aim to identify and characterize distinct small for gestational age subgroups and assess their neonatal and early childhood health trajectories.
Objective: To refine the classification of small for gestational age by identifying subgroups based on maternal, fetal, and environmental factors and evaluating their associations with neonatal morbidity, growth, and neurodevelopment at age 2.
Study design: Prospective …