Digital Commons Network^™

Long-Term 3-Year Follow-Up Of Mosunetuzumab In Relapsed Or Refractory Follicular Lymphoma After ≥2 Prior Therapies, Laurie H Sehn, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Mosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 …

Fiber- And Acetate-Mediated Modulation Of Mhc-Ii Expression On Intestinal Epithelium Protects From Clostridioides Difficile Infection, José L Fachi, Tihana Trsan, Silvia Penati, Susan Gilfillan, Siyan Cao, Krzysztof L Hyrc, Xiuli Liu, Patrick Fernandes Rodrigues, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4

Handshake Antimicrobial Stewardship For Adult Surgical Patients, Abby Kosharek, Elizabeth Neuner, Emily Welch, Spenser January, Alice Bewley, Kevin Hsueh, Sena Sayood

2020-Current year OA Pubs

OBJECTIVE: Evaluate the effects of handshake stewardship on adult general surgical units.

DESIGN: Retrospective quasi-experimental pre- and post-intervention study.

SETTING: A total of 1,278 bed academic medical center with a level 1 trauma center in St. Louis, Missouri.

PATIENTS: Adults admitted to general surgery units.

INTERVENTION: Once weekly handshake antimicrobial stewardship rounds were initiated in January 2022 on adult general surgery units. The handshake stewardship team consisted of an infectious diseases (ID) physician and pharmacist who reviewed charts of patients receiving systemic antimicrobials without a formal ID consult. Antimicrobial recommendations were delivered in person to general surgery teams including trauma, …

Assessment Of Environmental, Sociocultural, And Physiological Influences On Women's Toileting Decisions And Behaviors Using "Where I Go": Pilot Study Of A Mobile App, Abigail R Smith, Elizabeth R Mueller, Cora E Lewis, Alayne Markland, Caroline Smerdon, Ariana L Smith, Siobhan Sutcliffe, Jean F Wyman, Lisa Kane Low, Janis M Miller

2020-Current year OA Pubs

BACKGROUND: Little is known about women's decisions around toileting for urination and how those decisions influence moment-to-moment behaviors to manage bladder needs. The new smartphone app "Where I Go" captures such nuanced and granular data in real-world environments.

OBJECTIVE: This study aims to describe participant engagement with "Where I Go", variation in novel parameters collected, and readiness for the data collection tool's use in population-based studies.

METHODS: "Where I Go" has three components: (1) real-time data, (2) short look-back periods (3-4 h), and (3) event location (GPS recorded at each interaction). The sample size was 44 women. Recording of real-time …

Dna Immunotherapy For Recurrent Respiratory Papillomatosis (Rrp): Phase 1/2 Study Assessing Efficacy, Safety, And Immunogenicity Of Ino-3107, Matthew P Morrow, Randal C Paniello, Et Al.

2020-Current year OA Pubs

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity …

Phgdh Inhibition And Foxo3 Modulation Drives Puma-Dependent Apoptosis In Osteosarcoma, Toshinao Oyama, Caitlyn B Brashears, Richa Rathore, Heather Benect-Hamilton, Katharine E Caldwell, Naomi Dirckx, William G Hawkins, Brian A Van Tine

2020-Current year OA Pubs

Osteosarcoma is a bone cancer that has been found to be metabolically dependent on the conversion of glucose to serine through the rate-limiting enzyme 3-phosphoglycerate dehydrogenase (PHGDH). The upregulation of PHGDH has been correlated with poor patient survival, and the inhibition of the serine synthesis pathway using targeted small-molecule inhibition of PHGDH induces a rapid metabolic adaptation that prevents cell death due to pro-survival signaling through the mammalian target of rapamycin complex 1 (mTORC1) pathway. Here, PHGDH inhibition in combination with mTORC1 signaling modulation for the treatment of osteosarcoma was evaluated. When combined with PHGDH inhibition, several non-rapalog inhibitors of …

Phosphorylation Of Cryab Induces A Condensatopathy To Worsen Post-Myocardial Infarction Left Ventricular Remodeling, Moydul Islam, David R. Rawnsley, Xiucui Ma, Walter Navid, Chen Zhao, Xumin Guan, Layla Foroughi, John T. Murphy, Honora Navid, Carla J. Weinheimer, Attila Kovacs, Jessica Nigro, Aaradhya Diwan, Ryan P. Chang, Minu Kumari, Martin E. Young, Babak Razani, Kenneth B. Margulies, Mahmoud Abdellatif, Simon Sedej, Ali Javaheri, Douglas F. Covey, Kartik Mani, Abhinav Diwan

2020-Current year OA Pubs

Protein aggregates are emerging therapeutic targets in rare monogenic causes of cardiomyopathy and amyloid heart disease, but their role in more prevalent heart-failure syndromes remains mechanistically unexamined. We observed mislocalization of desmin and sarcomeric proteins to aggregates in human myocardium with ischemic cardiomyopathy and in mouse hearts with post-myocardial infarction ventricular remodeling, mimicking findings of autosomal-dominant cardiomyopathy induced by the R120G mutation in the cognate chaperone protein CRYAB. In both syndromes, we demonstrate increased partitioning of CRYAB phosphorylated on serine 59 to NP40-insoluble aggregate-rich biochemical fraction. While CRYAB undergoes phase separation to form condensates, the phosphomimetic mutation of serine 59 …

The Foundational Capabilities Of Large Language Models In Predicting Postoperative Risks Using Clinical Notes, Charles Alba, Bing Xue, Joanna Abraham, Thomas Kannampallil, Chenyang Lu

2020-Current year OA Pubs

Clinical notes recorded during a patient's perioperative journey holds immense informational value. Advances in large language models (LLMs) offer opportunities for bridging this gap. Using 84,875 preoperative notes and its associated surgical cases from 2018 to 2021, we examine the performance of LLMs in predicting six postoperative risks using various fine-tuning strategies. Pretrained LLMs outperformed traditional word embeddings by an absolute AUROC of 38.3% and AUPRC of 33.2%. Self-supervised fine-tuning further improved performance by 3.2% and 1.5%. Incorporating labels into training further increased AUROC by 1.8% and AUPRC by 2%. The highest performance was achieved with a unified foundation model, …

Utility Of Caregiver Signaling Questions To Detect Neurocognitive Impairment In Children With Sickle Cell Disease, Christina M Dandar, Lakia Kearson, Jennifer N Longoria, Brian Potter, Allison A King, Jeffrey Gossett, Clifford M Takemoto, Jane S Hankins, Guolian Kang, Andrew M Heitzer

2020-Current year OA Pubs

The American Society of Hematology cerebrovascular guidelines for sickle cell disease (SCD) recommend surveillance using signaling questions to screen for neurocognitive difficulties, although the clinical utility of these signaling questions has yet to be established. This study aimed to determine the clinical utility of caregiver signaling questions for detecting significant neurocognitive impairment (defined as >1.5 standard deviation [SD] below the normative mean on ≥2 measures) and domain-specific impairment (defined as >1.5 SD below the normative mean) in children and adolescents with SCD. A total of 421 caregivers of children with SCD aged 8 to 17 years (62% hemoglobin SS (HbSS) …

The Tie2 Antagonist Rebastinib Reduces Ovarian Cancer Growth In A Syngeneic Murine Model, Vijayalaxmi G Gupta, Katherine F Roby, Harsh B Pathak, Andrew K Godwin, Sumedha Gunewardena, Dineo Khabele

2020-Current year OA Pubs

BACKGROUND: The receptor tyrosine kinase TIE2 and its ligands, angiopoietins (ANGPTs), promote angiogenesis. In addition to expression on vascular endothelial cells, TIE2 is expressed on M2-like pro-tumorigenic macrophages. Thus, the TIE2 inhibitor rebastinib was developed as a potential therapy to address multiple cancers. The objective of this study was to determine the effects of rebastinib alone and combined with chemotherapy in a syngeneic murine model of ovarian cancer.

METHODS: Female C57Bl6J mice were intraperitoneally injected with syngeneic ID8 ovarian cancer cells. Once tumors were established, mice were untreated (control) or treated with rebastinib, carboplatin plus paclitaxel (chemotherapy), or rebastinib plus …

Toward Equity In Cultivating A "Garden Of Mentors:" An Exploration Of Networking Experiences In An Implementation Research Training Program, Loni J Parrish, Amanda Gilbert, Kate Hoppe, Gloria D Coronado, Karen M Emmons, Amy A Eyler, Debra Haire-Joshu, Rebekah R Jacob, Alison B Hamilton, Shelly J Kannuthurai, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The Institute for Implementation Science Scholars (IS-2) is a dissemination and implementation (D&I) science training and mentoring program. A key component of IS-2 is collaborating and networking. To build knowledge on effective networking and mentoring, this study sought to 1) conduct a social network analysis to determine whether underrepresented scholars have equivalent levels of connection and 2) gain insights into the differences in networking among racial/ethnic subgroups of scholars.

METHODS: Social network survey data were used to select participants based on number of collaborative connections (highest, lowest) and racial/ ethnic category (underrepresented, not underrepresented). Interviews were recorded, transcribed, and …

2024 Physician-Scientist Trainee Diversity Summit Conference Proceedings, Jessica Weng, Cynthia Y Tang, Kyle T Enriquez, Rohini N Guin, Briana Christophers, Yentli E Soto Albrecht, Daniel B Amusin, Deborah D Rupert, Paige Cooper Byas

2020-Current year OA Pubs

The Physician-Scientist Trainee Diversity Summit, hosted by the American Physician Scientists Association and the Burroughs Wellcome Fund, was conceived in 2019 with the mission of developing strategic plans to diversify the physician-scientist community using human-centered design thinking. In June 2024, the second iteration of this conference was held in Raleigh, North Carolina, and brought together a network of scientific and medical organizations to discuss issues of justice, equity, diversity, and inclusion facing physician-scientist trainees. This article summarizes the progress made from the first meeting, the proceedings of the 2024 Summit, and a thematic analysis of the recent meeting, offering tangible …

Assessing Dynamic Cognitive Function In The Daily Lives Of Youths With And Without Type 1 Diabetes: Usability Study, Mary Katherine Ray, Jorie Fleming, Andrew Aschenbrenner, Jason Hassenstab, Brooke Redwine, Carissa Burns, Ana Maria Arbelaez, Mary Ellen Vajravelu, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Studies have shown a relationship between worse glycemic control and lower cognitive scores in youths with type 1 diabetes (T1D). However, most studies assess long-term glucose control (eg, years-decades) and cognition at a single time point. Understanding this relationship at a higher temporal resolution (eg, minutes-hours) and in naturalistic settings has potential clinical implications. Newer technology (eg, continuous glucose monitoring [CGM] and ecological momentary assessment) provides a unique opportunity to explore the glucose dynamics that influence dynamic cognition; that is, cognitive functions that fluctuate short-term and are influenced by environmental factors.

OBJECTIVE: Before we can assess this relationship, we …

Lifespan In Rodents With Myt1l Heterozygous Mutation, Allyson Schreiber, Raylynn G Swift, Leslie Wilson, Kristen L Kroll, Joseph D Dougherty, Susan E Maloney

2020-Current year OA Pubs

MYT1L syndrome is a newly recognized disorder characterized by intellectual disability, speech and motor delay, neuroendocrine disruptions, ADHD, and autism. In order to study this gene and its association with these phenotypes, our lab recently created a Myt1l heterozygous mutant mouse inspired by a clinically relevant mutation. This model recapitulates several of the physical and neurologic abnormalities seen in humans with MYT1L syndrome, such as weight gain, microcephaly, and behavioral disruptions. The majority of patients with this syndrome are young, and little is known about the impact of age on health and mortality in these patients. Using a Myt1l mutant …

Enhancing Progestin Therapy With A Glucagon-Like Peptide 1 Agonist For The Conservative Management Of Endometrial Cancer, Andrea R Hagemann, Ian S Hagemann, David G Mutch, Eric J Devor, Paige K Malmrose, Yuping Zhang, Abigail M Morrison, Kristina W Thiel, Kimberly K Leslie

2020-Current year OA Pubs

OBJECTIVE: Obesity is a major risk factor for endometrial cancer. In addition to hormone therapy with progestins, glucagon like peptide-1 receptor (GLP-1R) agonists such as semaglutide may be helpful to achieve weight loss during conservative treatment of endometrial hyperplasia or cancer.

METHODS: We theorized that the combination of semaglutide and the progestin levonorgestrel would be useful as a novel treatment or prevention regimen and tested this hypothesis using endometrial cancer cell lines and patient-derived organoids (PDOs).

RESULTS: Hec50, KLE, and Ishikawa endometrial cancer cells express GLP-1R, as determined by both qPCR and Western blotting, and GLP-1R agonist treatment induces GLP-1R …

A Neuronal Code For Object Representation And Memory In The Human Amygdala And Hippocampus, Runnan Cao, Peter Brunner, Puneeth N Chakravarthula, Krista L Wahlstrom, Cory Inman, Elliot H Smith, Xin Li, Adam N Mamelak, Nicholas J Brandmeir, Ueli Rutishauser, Jon T Willie, Shuo Wang

2020-Current year OA Pubs

How the brain encodes, recognizes, and memorizes general visual objects is a fundamental question in neuroscience. Here, we investigated the neural processes underlying visual object perception and memory by recording from 3173 single neurons in the human amygdala and hippocampus across four experiments. We employed both passive-viewing and recognition memory tasks involving a diverse range of naturalistic object stimuli. Our findings reveal a region-based feature code for general objects, where neurons exhibit receptive fields in the high-level visual feature space. This code can be validated by independent new stimuli and replicated across all experiments, including fixation-based analyses with large natural …

Cimpact-Now Update 8: Clarifications On Molecular Risk Parameters And Recommendations For Who Grading Of Meningiomas, Felix Sahm, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

Meningiomas are the most frequent primary intracranial tumors. Hence, they constitute a major share of diagnostic specimens in neuropathology practice. The 2021 WHO Classification of Central Nervous System Tumors ("CNS5") has introduced the first molecular grading parameters for meningioma with oncogenic variants in the TERT promoter and homozygous deletion of CDKN2A/B as markers for CNS WHO grade 3. However, after the publication of the new classification volume, clarifications were requested, not only on novel but also on long-standing questions in meningioma grading that were beyond the scope of the WHO "blue book." In addition, more recent research into possible new …

Swog S1815: A Phase Iii Randomized Trial Of Gemcitabine, Cisplatin, And Nab-Paclitaxel Versus Gemcitabine And Cisplatin In Newly Diagnosed, Advanced Biliary Tract Cancers, Rachna T Shroff, Benjamin Tan, Et Al.

2020-Current year OA Pubs

PURPOSE: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

METHODS: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m

RESULTS: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC. There was no significant difference in overall survival (OS) between GAP versus GC. Median …

A Synthetic Chronogenetic Gene Circuit For Programmed Circadian Drug Delivery, Lara Pferdehirt, Anna R Damato, Kristin L Lenz, Maria F Gonzalez-Aponte, Daniel Palmer, Qing-Jun Meng, Erik D Herzog, Farshid Guilak

2020-Current year OA Pubs

Circadian medicine, the delivery of therapeutic interventions based on an individual's daily rhythms, has shown improved efficacy and reduced side-effects for various treatments. Rheumatoid arthritis and other inflammatory diseases are characterized by diurnal changes in cytokines, leading to inflammatory flares, with peak disease activity in the early morning. Using a combination of synthetic biology and tissue engineering, we developed circadian-based gene circuits, termed "chronogenetics", that express a prescribed transgene downstream of the core clock gene promoter, Period2 (Per2). Gene circuits were transduced into induced pluripotent stem cells that were tissue-engineered into cartilage constructs. Our anti-inflammatory chronogenetic constructs produced therapeutic concentrations …

Bacterial Community Assembly Of Specific Pathogen-Free Neonatal Mice, Elizabeth A Kennedy, James S Weagley, Andrew H Kim, Avan Antia, Anna L Deveaux, Megan T Baldridge

2020-Current year OA Pubs

BACKGROUND: Neonatal mice are frequently used to model diseases that affect human infants. Microbial community composition has been shown to impact disease progression in these models. Despite this, the maturation of the early-life murine microbiome has not been well-characterized. We address this gap by characterizing the assembly of the bacterial microbiota of C57BL/6 and BALB/c litters from birth to adulthood across multiple independent litters.

RESULTS: The fecal microbiome of young pups is dominated by only a few pioneering bacterial taxa. These taxa are present at low levels in the microbiota of multiple maternal body sites, precluding a clear identification of …

The Tetracycline Resistome Is Shaped By Selection For Specific Resistance Mechanisms By Each Antibiotic Generation, Kevin S Blake, Yao-Peng Xue, Vincent J Gillespie, Skye R S Fishbein, Niraj H Tolia, Timothy A Wencewicz, Gautam Dantas

2020-Current year OA Pubs

The history of clinical resistance to tetracycline antibiotics is characterized by cycles whereby the deployment of a new generation of drug molecules is quickly followed by the discovery of a new mechanism of resistance. This suggests mechanism-specific selection by each tetracycline generation; however, the evolutionary dynamics of this remain unclear. Here, we evaluate 24 recombinant Escherichia coli strains expressing tetracycline resistance genes from each mechanism (efflux pumps, ribosomal protection proteins, and enzymatic inactivation) in the context of each tetracycline generation. We employ a high-throughput barcode sequencing protocol that can discriminate between strains in mixed culture and quantify their relative abundances. …

Heterogeneous Clinical Phenotypes Of Sporadic Early-Onset Alzheimer's Disease: A Neuropsychological Data-Driven Approach, Deepti Putcha, Erik Musiek, Kyle Womack, Et Al.

2020-Current year OA Pubs

BACKGROUND: The clinical presentations of early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease are distinct, with EOAD having a more aggressive disease course with greater heterogeneity. Recent publications from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) described EOAD as predominantly amnestic, though this phenotypic description was based solely on clinical judgment. To better understand the phenotypic range of EOAD presentation, we applied a neuropsychological data-driven method to subtype the LEADS cohort.

METHODS: Neuropsychological test performance from 169 amyloid-positive EOAD participants were analyzed. Education-corrected normative comparisons were made using a sample of 98 cognitively normal participants. Comparing the relative levels of …

Punch Cd3-Ols: A Phase 3 Prospective Observational Cohort Study To Evaluate The Safety And Efficacy Of Fecal Microbiota, Live-Jslm (Rebyota) In Adults With Recurrent Clostridioides Difficile Infection, Paul Feuerstadt, Teena Chopra, Whitfield Knapple, Nicholas W Van Hise, Erik R Dubberke, Brian Baggott, Beth Guthmueller, Lindy Bancke, Michael Gamborg, Theodore S Steiner, Daniel Van Handel, Sahil Khanna

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.

METHODS: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered …

Ddo-Adjuvanted Influenza A Virus Nucleoprotein Mrna Vaccine Induces Robust Humoral And Cellular Type 1 Immune Responses And Protects Mice From Challenge, Victoria Gnazzo, Hanaa Saleh, Ítalo A Castro, Adrianus C M Boon, Amelia K. Pinto, James D Brien, Carolina B López

2020-Current year OA Pubs

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8

Discordance Between 90y-Pet/Ct(Mr)-Estimated Activity And Dose Calibrator Measured Administered Activity: An International Study In Sirt Patients Treated With Resin And Glass Microspheres, Thomas Carlier, Silvano Gnesin, Justin K Mikell, Maurizio Conti, John O Prior, Niklaus Schaefer, Maria Del Sol Pérez Lago, Clément Bailly, Yuni K Dewaraja, Thiago V M Lima

2020-Current year OA Pubs

PURPOSE: Therapeutic administration of

METHODS: We analysed patient

RESULTS: Quantification ratio between calibrators and PET was significantly different from 1, regardless of the scatter correction used. In glass microspheres, the mean A

CONCLUSIONS: We observed in patients similar activity discrepancies as reported for vials, with a relative difference of 44 ± 16% between glass and resin

Advancing Mitochondrial Therapeutics: Synthesis And Pharmacological Evaluation Of Pyrazole-Based Inhibitors Targeting The Mitochondrial Pyruvate Carrier, Lingaiah Maram, Jessica M Michael, Henry Politte, Vaishnavi S Srirama, Aymen Hadji, Mohammad Habibi, Meredith O Kelly, Rita T Brookheart, Brian N Finck, Lamees Hegazy, Kyle S Mccommis, Bahaa Elgendy

2020-Current year OA Pubs

Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits arise either from the direct inhibition of mitochondrial pyruvate metabolism or from the metabolic rewiring when pyruvate entry is inhibited. However, current MPC inhibitors are either nonspecific or possess poor pharmacokinetic properties. To address this, approximately 50 pyrazole-based MPC inhibitors were synthesized to explore the structure-activity relationship for MPC inhibition, evaluated through inhibition of mitochondrial pyruvate respiration. These inhibitors were designed with increased steric hindrance around electron-deficient double bonds, allowing …

Sleep-Wake Variation In Body Temperature Regulates Tau Secretion And Correlates With Csf And Plasma Tau, Geoffrey Canet, Brendan P. Lucey, Et Al.

2020-Current year OA Pubs

Sleep disturbance is bidirectionally associated with an increased risk of Alzheimer's disease and other tauopathies. While the sleep-wake cycle regulates interstitial and cerebrospinal fluid (CSF) tau levels, the underlying mechanisms remain unknown. Understanding these mechanisms is crucial, given the evidence that tau pathology spreads through neuron-to-neuron transfer, involving the secretion and internalization of pathological tau forms. Here, we combined in vitro, in vivo, and clinical methods to reveal a pathway by which changes in body temperature (BT) over the sleep-wake cycle modulate extracellular tau levels. In mice, a higher BT during wakefulness and sleep deprivation increased CSF and plasma tau …

Toxoplasma Chitinase-Like Protein Orchestrates Cyst Wall Glycosylation To Facilitate Effector Export And Cyst Turnover, Yong Fu, Tadakimi Tomita, Louis M Weiss, Christopher M West, L David Sibley

2020-Current year OA Pubs

No abstract provided.

Metabolites And Lipid Species Mediate The Associations Of Adiposity In Childhood And Early Adulthood With Mammographic Breast Density In Premenopausal Women, Kayla R Getz, Myung Sik Jeon, Lili Liu, Lei Liu, Haixiang Zhang, Chongliang Luo, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women.

METHODS: This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Kenneth E. Remy, Jane Blood, Andrew H. Walton, Teresa Blood, Richard Hotchkiss, Et Al.

2020-Current year OA Pubs

BACKGROUND: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

METHODS: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …