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A Flexible, Quantitative Plasmonic-Fluor Lateral Flow Assay For The Rapid Detection Of Orthoebolavirus Zairense And Orthoebolavirus Sudanense, Abraham J Qavi, Qisheng Jiang, M Javad Aman, Hong Vu, Larry Zetlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Frederick Holtsberg, Scott L Crick, Gaya K Amarasinghe Jan 2024

A Flexible, Quantitative Plasmonic-Fluor Lateral Flow Assay For The Rapid Detection Of Orthoebolavirus Zairense And Orthoebolavirus Sudanense, Abraham J Qavi, Qisheng Jiang, M Javad Aman, Hong Vu, Larry Zetlin, John M Dye, Jeffrey W Froude, Daisy W Leung, Frederick Holtsberg, Scott L Crick, Gaya K Amarasinghe

2020-Current year OA Pubs

Filoviruses comprise a family of single-stranded, negative-sense RNA viruses with a significant impact on human health. Given the risk for disease outbreaks, as highlighted by the recent outbreaks across Africa, there is an unmet need for flexible diagnostic technologies that can be deployed in resource-limited settings. Herein, we highlight the use of plasmonic-fluor lateral flow assays (PF-LFA) for the rapid, quantitative detection of an Ebolavirus-secreted glycoprotein, a marker for infection. Plasmonic fluors are a class of ultrabright reporter molecules that combine engineered nanorods with conventional fluorophores, resulting in improved analytical sensitivity. We have developed a PF-LFA for


Inhibition Of Autocrine Hgf Maturation Overcomes Cetuximab Resistance In Colorectal Cancer, Vivian Truong Jones, Vishnu C Damalanka, James W Janetka, Et Al. Jan 2024

Inhibition Of Autocrine Hgf Maturation Overcomes Cetuximab Resistance In Colorectal Cancer, Vivian Truong Jones, Vishnu C Damalanka, James W Janetka, Et Al.

2020-Current year OA Pubs

Although amplifications and mutations in receptor tyrosine kinases (RTKs) act as bona fide oncogenes, in most cancers, RTKs maintain moderate expression and remain wild-type. Consequently, cognate ligands control many facets of tumorigenesis, including resistance to anti-RTK therapies. Herein, we show that the ligands for the RTKs MET and RON, HGF and HGFL, respectively, are synthesized as inactive precursors that are activated by cellular proteases. Our newly generated HGF/HGFL protease inhibitors could overcome both de novo and acquired cetuximab resistance in colorectal cancer (CRC). Conversely, HGF overexpression was necessary and sufficient to induce cetuximab resistance and loss of polarity. Moreover, HGF-induced …


Overview Of Covid-19 Infection, Treatment, And Prevention In Children, Carol M Kao Jan 2024

Overview Of Covid-19 Infection, Treatment, And Prevention In Children, Carol M Kao

2020-Current year OA Pubs

Coronavirus disease 2019 (COVID-19), caused by the novel respiratory virus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was declared a global pandemic by the World Health Organization on 11 March 2020. Since then, substantial gains have been made in our understanding of COVID-19 epidemiology, disease presentation, and management. While children tend to have less severe disease courses compared to adults, children can still develop severe COVID-19 infections, particularly in those with underlying medical conditions such as obesity, chronic lung disease, or prematurity. In addition, children are at risk of severe complications of COVID-19 infection, such as multisystem inflammatory syndrome in children (MIS-C) …


Single-Cell Multi-Omic Analysis Of The Vestibular Schwannoma Ecosystem Uncovers A Nerve Injury-Like State, Thomas F Barrett, Bhuvic Patel, Riley D Z Mullins, Aldrin K Y Yim, Sangami Pugazenthi, Tatenda Mahlokozera, Gregory J Zipfel, Jacques A Herzog, Cameron C Wick, Nedim Durakovic, Joshua W Osbun, Matthew Shew, Craig A Buchman, Sidharth V Puram, Albert H Kim, Et Al. Jan 2024

Single-Cell Multi-Omic Analysis Of The Vestibular Schwannoma Ecosystem Uncovers A Nerve Injury-Like State, Thomas F Barrett, Bhuvic Patel, Riley D Z Mullins, Aldrin K Y Yim, Sangami Pugazenthi, Tatenda Mahlokozera, Gregory J Zipfel, Jacques A Herzog, Cameron C Wick, Nedim Durakovic, Joshua W Osbun, Matthew Shew, Craig A Buchman, Sidharth V Puram, Albert H Kim, Et Al.

2020-Current year OA Pubs

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, …


Neuroactive Steroid Effects On Autophagy In A Human Embryonic Kidney 293 (Hek) Cell Model, Sofia V Salvatore, Ma Xenia G Ilagan, Hongjin Shu, Peter M Lambert, Ann Benz, Mingxing Qian, Douglas F Covey, Charles F Zorumski, Steven Mennerick Jan 2024

Neuroactive Steroid Effects On Autophagy In A Human Embryonic Kidney 293 (Hek) Cell Model, Sofia V Salvatore, Ma Xenia G Ilagan, Hongjin Shu, Peter M Lambert, Ann Benz, Mingxing Qian, Douglas F Covey, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP …


The Chromatin Landscape Of Healthy And Injured Cell Types In The Human Kidney, Debora L Gisch, Jeannine Basta, Reetika Ghag, Charles Lu, Lisa Stout, Bo Zhang, Amanda Knoten, Shamim Mollah, Sanjay Jain, Michael Rauchman, Et Al. Jan 2024

The Chromatin Landscape Of Healthy And Injured Cell Types In The Human Kidney, Debora L Gisch, Jeannine Basta, Reetika Ghag, Charles Lu, Lisa Stout, Bo Zhang, Amanda Knoten, Shamim Mollah, Sanjay Jain, Michael Rauchman, Et Al.

2020-Current year OA Pubs

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, …


Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A. Huggins, Evan M. Gordon, Et Al. Jan 2024

Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A. Huggins, Evan M. Gordon, Et Al.

2020-Current year OA Pubs

No abstract provided.


Multiple Pathways For Glucose Phosphate Transport And Utilization Support Growth Of Cryptosporidium Parvum, Rui Xu, Wandy L Beatty, Valentin Greigert, William H Witola, L David Sibley Jan 2024

Multiple Pathways For Glucose Phosphate Transport And Utilization Support Growth Of Cryptosporidium Parvum, Rui Xu, Wandy L Beatty, Valentin Greigert, William H Witola, L David Sibley

2020-Current year OA Pubs

Cryptosporidium parvum is an obligate intracellular parasite with a highly reduced mitochondrion that lacks the tricarboxylic acid cycle and the ability to generate ATP, making the parasite reliant on glycolysis. Genetic ablation experiments demonstrated that neither of the two putative glucose transporters CpGT1 and CpGT2 were essential for growth. Surprisingly, hexokinase was also dispensable for parasite growth while the downstream enzyme aldolase was required, suggesting the parasite has an alternative way of obtaining phosphorylated hexose. Complementation studies in E. coli support a role for direct transport of glucose-6-phosphate from the host cell by the parasite transporters CpGT1 and CpGT2, thus …


Implementing Integrated Hypertension And Diabetes Management Using The World Health Organization's Hearts Model: Protocol For A Pilot Study In The Guatemalan National Primary Care System, Irmgardt Alicia Wellmann, Luis Fernando Ayala, José Javier Rodríguez, Timothy C Guetterman, Vilma Irazola, Eduardo Palacios, Mark D Huffman, Peter Rohloff, Michele Heisler, Manuel Ramírez-Zea, David Flood Jan 2024

Implementing Integrated Hypertension And Diabetes Management Using The World Health Organization's Hearts Model: Protocol For A Pilot Study In The Guatemalan National Primary Care System, Irmgardt Alicia Wellmann, Luis Fernando Ayala, José Javier Rodríguez, Timothy C Guetterman, Vilma Irazola, Eduardo Palacios, Mark D Huffman, Peter Rohloff, Michele Heisler, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The HEARTS technical package was developed by the World Health Organization to address the implementation gap in cardiovascular disease prevention in low- and middle-income countries. Guatemala is a middle-income country that is currently implementing HEARTS. National authorities in Guatemala are interested in exploring how hypertension and diabetes management can be integrated in HEARTS implementation. The objective of this study is to conduct a feasibility and acceptability pilot trial of integrated hypertension and diabetes management based on HEARTS in the publicly funded primary care system in Guatemala.

METHODS: A single-arm pilot trial for 6 months will be carried out in …


Age-Related Differences In Motor Skill Transfer With Brief Memory Reactivation, Kylie B Tomlin, Brian P Johnson, Kelly P Westlake Jan 2024

Age-Related Differences In Motor Skill Transfer With Brief Memory Reactivation, Kylie B Tomlin, Brian P Johnson, Kelly P Westlake

2020-Current year OA Pubs

Motor memories can be strengthened through online practice and offline consolidation. Offline consolidation involves the stabilization of memory traces in post-practice periods. Following initial consolidation of a motor memory, subsequent practice of the motor skill can lead to reactivation and reconsolidation of the memory trace. The length of motor memory reactivation may influence motor learning outcomes; for example, brief, as opposed to long, practice of a previously learned motor skill appears to optimize intermanual transfer in healthy young adults. However, the influence of aging on reactivation-based motor learning has been scarcely explored. Here, the effects of brief and long motor …


Clinical Outcomes Of Older And Younger Patients Treated With Loncastuximab Tesirine In The Lotis-2 Clinical Trial, Mehdi Hamadani, Brad Kahl, Et Al. Jan 2024

Clinical Outcomes Of Older And Younger Patients Treated With Loncastuximab Tesirine In The Lotis-2 Clinical Trial, Mehdi Hamadani, Brad Kahl, Et Al.

2020-Current year OA Pubs

No abstract provided.


Postnatal Meningeal Csf Transport Is Primarily Mediated By The Arachnoid And Pia Maters And Is Not Altered After Intraventricular Hemorrhage-Posthemorrhagic Hydrocephalus, Shelei Pan, Joshua P Koleske, Gretchen M Koller, Grace L Halupnik, Abdul-Haq O Alli, Shriya Koneru, Dakota Defreitas, Sruthi Ramagiri, Jennifer M Strahle Jan 2024

Postnatal Meningeal Csf Transport Is Primarily Mediated By The Arachnoid And Pia Maters And Is Not Altered After Intraventricular Hemorrhage-Posthemorrhagic Hydrocephalus, Shelei Pan, Joshua P Koleske, Gretchen M Koller, Grace L Halupnik, Abdul-Haq O Alli, Shriya Koneru, Dakota Defreitas, Sruthi Ramagiri, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: CSF has long been accepted to circulate throughout the subarachnoid space, which lies between the arachnoid and pia maters of the meninges. How the CSF interacts with the cellular components of the developing postnatal meninges including the dura, arachnoid, and pia of both the meninges at the surface of the brain and the intracranial meninges, prior to its eventual efflux from the cranium and spine, is less understood. Here, we characterize small and large CSF solute distribution patterns along the intracranial and surface meninges in neonatal rodents and compare our findings to meningeal CSF solute distribution in a rodent …


Associations Between Coordination And Wearable Sensor Variables Vary By Recording Context But Not Assessment Type, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang Jan 2024

Associations Between Coordination And Wearable Sensor Variables Vary By Recording Context But Not Assessment Type, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang

2020-Current year OA Pubs

Motor coordination is an important driver of development and improved coordination assessments could facilitate better screening, diagnosis, and intervention for children at risk of developmental disorders. Wearable sensors could provide data that enhance the characterization of coordination and the clinical utility of that data may vary depending on how sensor variables from different recording contexts relate to coordination. We used wearable sensors at the wrists to capture upper-limb movement in 85 children aged 6-12. Sensor variables were extracted from two recording contexts.


Gene-Sgan: Discovering Disease Subtypes With Imaging And Genetic Signatures Via Multi-View Weakly-Supervised Deep Clustering, Zhijian Yang, John C Morris, Pamela Lamontagne, Daniel S Marcus, Tammie L S Benzinger, Et Al. Jan 2024

Gene-Sgan: Discovering Disease Subtypes With Imaging And Genetic Signatures Via Multi-View Weakly-Supervised Deep Clustering, Zhijian Yang, John C Morris, Pamela Lamontagne, Daniel S Marcus, Tammie L S Benzinger, Et Al.

2020-Current year OA Pubs

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first …


Phase I Dose-Escalation Study Of The Safety And Pharmacokinetics Of Ags15e Monotherapy In Patients With Metastatic Urothelial Carcinoma, Daniel P Petrylak, Joel Picus, Et Al. Jan 2024

Phase I Dose-Escalation Study Of The Safety And Pharmacokinetics Of Ags15e Monotherapy In Patients With Metastatic Urothelial Carcinoma, Daniel P Petrylak, Joel Picus, Et Al.

2020-Current year OA Pubs

PURPOSE: Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADC) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen.

PATIENTS AND METHODS: This was a multicenter, single-arm, phase I dose-escalation and expansion trial of AGS15E in patients with mUC (NCT01963052). During dose escalation, AGS15E was administered intravenously at six levels (0.10, 0.25, 0.50, 0.75, 1.00, 1.25 mg/kg), employing a continual reassessment method to determine dose-limiting toxicities (DLT) and the recommended …


Dgidb 5.0: Rebuilding The Drug-Gene Interaction Database For Precision Medicine And Drug Discovery Platforms, Matthew Cannon, James Stevenson, Kathryn Stahl, Rohit Basu, Adam Coffman, Susanna Kiwala, Joshua F Mcmichael, Kori Kuzma, Dorian Morrissey, Kelsy Cotto, Elaine R Mardis, Obi L Griffith, Malachi Griffith, Alex H Wagner Jan 2024

Dgidb 5.0: Rebuilding The Drug-Gene Interaction Database For Precision Medicine And Drug Discovery Platforms, Matthew Cannon, James Stevenson, Kathryn Stahl, Rohit Basu, Adam Coffman, Susanna Kiwala, Joshua F Mcmichael, Kori Kuzma, Dorian Morrissey, Kelsy Cotto, Elaine R Mardis, Obi L Griffith, Malachi Griffith, Alex H Wagner

2020-Current year OA Pubs

The Drug-Gene Interaction Database (DGIdb, https://dgidb.org) is a publicly accessible resource that aggregates genes or gene products, drugs and drug-gene interaction records to drive hypothesis generation and discovery for clinicians and researchers. DGIdb 5.0 is the latest release and includes substantial architectural and functional updates to support integration into clinical and drug discovery pipelines. The DGIdb service architecture has been split into separate client and server applications, enabling consistent data access for users of both the application programming interface (API) and web interface. The new interface was developed in ReactJS, and includes dynamic visualizations and consistency in the display of …


Updates To The Modern Diagnosis Of Gerd: Lyon Consensus 2.0, C Prakash Gyawali, Et Al. Jan 2024

Updates To The Modern Diagnosis Of Gerd: Lyon Consensus 2.0, C Prakash Gyawali, Et Al.

2020-Current year OA Pubs

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes …


The Low-Density Lipoprotein Receptor Promotes Infection Of Multiple Encephalitic Alphaviruses, Hongming Ma, Lucas J Adams, Saravanan Raju, Alan Sariol, Natasha M Kafai, Hana Janova, William B Klimstra, Daved H Fremont, Michael S Diamond Jan 2024

The Low-Density Lipoprotein Receptor Promotes Infection Of Multiple Encephalitic Alphaviruses, Hongming Ma, Lucas J Adams, Saravanan Raju, Alan Sariol, Natasha M Kafai, Hana Janova, William B Klimstra, Daved H Fremont, Michael S Diamond

2020-Current year OA Pubs

Members of the low-density lipoprotein receptor (LDLR) family, including LDLRAD3, VLDLR, and ApoER2, were recently described as entry factors for different alphaviruses. However, based on studies with gene edited cells and knockout mice, blockade or abrogation of these receptors does not fully inhibit alphavirus infection, indicating the existence of additional uncharacterized entry factors. Here, we perform a CRISPR-Cas9 genome-wide loss-of-function screen in mouse neuronal cells with a chimeric alphavirus expressing the Eastern equine encephalitis virus (EEEV) structural proteins and identify LDLR as a candidate receptor. Expression of LDLR on the surface of neuronal or non-neuronal cells facilitates binding and infection …


Inhibiting Metabotropic Glutamate Receptor 5 After Stroke Restores Brain Function And Connectivity, Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Byungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch Jan 2024

Inhibiting Metabotropic Glutamate Receptor 5 After Stroke Restores Brain Function And Connectivity, Jakob Hakon, Miriana J Quattromani, Carin Sjölund, Daniela Talhada, Byungchan Kim, Slavianka Moyanova, Federica Mastroiacovo, Luisa Di Menna, Roger Olsson, Elisabet Englund, Ferdinando Nicoletti, Karsten Ruscher, Adam Q Bauer, Tadeusz Wieloch

2020-Current year OA Pubs

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative …


Self-Sampling Tools To Increase Cancer Screening Among Underserved Patients: A Pilot Randomized Controlled Trial, Jennifer L Moss, Juliette Entenman, Kelsey Stoltzfus, Jiangang Liao, Tracy Onega, Paul L Reiter, Lisa M Klesges, George Garrow, Mack T Ruffin Jan 2024

Self-Sampling Tools To Increase Cancer Screening Among Underserved Patients: A Pilot Randomized Controlled Trial, Jennifer L Moss, Juliette Entenman, Kelsey Stoltzfus, Jiangang Liao, Tracy Onega, Paul L Reiter, Lisa M Klesges, George Garrow, Mack T Ruffin

2020-Current year OA Pubs

BACKGROUND: Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients.

METHODS: We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated …


Low Rna Disruption During Neoadjuvant Chemotherapy Predicts Pathologic Complete Response Absence In Patients With Breast Cancer, Marina Elena Cazzaniga, Foluso Ademuyiwa, Et Al. Jan 2024

Low Rna Disruption During Neoadjuvant Chemotherapy Predicts Pathologic Complete Response Absence In Patients With Breast Cancer, Marina Elena Cazzaniga, Foluso Ademuyiwa, Et Al.

2020-Current year OA Pubs

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in …


Liquefied Petroleum Gas Or Biomass Cooking And Severe Infant Pneumonia, Eric D. Mccollum, Victor G. Davila-Roman, Lindsay J. Underhill, Et Al. Jan 2024

Liquefied Petroleum Gas Or Biomass Cooking And Severe Infant Pneumonia, Eric D. Mccollum, Victor G. Davila-Roman, Lindsay J. Underhill, Et Al.

2020-Current year OA Pubs

No abstract provided.


Effects Of Cooking With Liquefied Petroleum Gas Or Biomass On Stunting In Infants, William Checkley, Lindsay J Underhill, Victor G Dávila-Román, Et Al. Jan 2024

Effects Of Cooking With Liquefied Petroleum Gas Or Biomass On Stunting In Infants, William Checkley, Lindsay J Underhill, Victor G Dávila-Román, Et Al.

2020-Current year OA Pubs

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown.

METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length …


Sensory Neurons Promote Immune Homeostasis In The Lung, Masato Tamari, Aaron M Ver Heul, Masato Hoshi, Anna M Trier, Ting-Lin Yang, Sanjay Jain, Steven Van Dyken, Et Al. Jan 2024

Sensory Neurons Promote Immune Homeostasis In The Lung, Masato Tamari, Aaron M Ver Heul, Masato Hoshi, Anna M Trier, Ting-Lin Yang, Sanjay Jain, Steven Van Dyken, Et Al.

2020-Current year OA Pubs

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1


Heterozygous Mutations In The C-Terminal Domain Of Copa Underlie A Complex Autoinflammatory Syndrome, Selket Delafontaine, Tarin M. Bigley, Megan A. Cooper, Et Al. Jan 2024

Heterozygous Mutations In The C-Terminal Domain Of Copa Underlie A Complex Autoinflammatory Syndrome, Selket Delafontaine, Tarin M. Bigley, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular …


Sarm1 Knockout Prevents Type 1 Diabetic Bone Disease In Females Independent Of Neuropathy, Jennifer M. Brazill, Ivana R. Shen, Clarissa S. Craft, Kristann L. Magee, Jay S. Park, Madelyn Lorenz, Amy Strickland, Natalie K. Wee, Xiao Zhang, Alec T. Beeve, Gretchen A. Meyer, Jeffrey Milbrandt, Aaron Diantonio, Erica L. Scheller Jan 2024

Sarm1 Knockout Prevents Type 1 Diabetic Bone Disease In Females Independent Of Neuropathy, Jennifer M. Brazill, Ivana R. Shen, Clarissa S. Craft, Kristann L. Magee, Jay S. Park, Madelyn Lorenz, Amy Strickland, Natalie K. Wee, Xiao Zhang, Alec T. Beeve, Gretchen A. Meyer, Jeffrey Milbrandt, Aaron Diantonio, Erica L. Scheller

2020-Current year OA Pubs

Patients with diabetes have a high risk of developing skeletal diseases accompanied by diabetic peripheral neuropathy (DPN). In this study, we isolated the role of DPN in skeletal disease with global and conditional knockout models of sterile-α and TIR-motif-containing protein-1 (Sarm1). SARM1, an NADase highly expressed in the nervous system, regulates axon degeneration upon a range of insults, including DPN. Global knockout of Sarm1 prevented DPN, but not skeletal disease, in male mice with type 1 diabetes (T1D). Female wild-type mice also developed diabetic bone disease but without DPN. Unexpectedly, global Sarm1 knockout completely protected female mice from T1D-associated bone …


Pathways To Care For Psychosis In Rural Uganda: Mixed-Methods Study Of Individuals With Psychosis, Family Members, And Local Leaders, Yang Jae Lee, Sophie Waimon, Et Al. Jan 2024

Pathways To Care For Psychosis In Rural Uganda: Mixed-Methods Study Of Individuals With Psychosis, Family Members, And Local Leaders, Yang Jae Lee, Sophie Waimon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Low- and middle-income countries (LMICs) bear a disproportionate burden of mental illness, with limited access to biomedical care. This study examined pathways to care for psychosis in rural Uganda, exploring factors influencing treatment choices.

METHODS: We conducted a mixed-methods study in Buyende District, Uganda, involving 67 in-depth interviews and 4 focus group discussions (data collection continued until thematic saturation was reached) with individuals with psychotic disorders, family members, and local leaders. Structured questionnaires were administered to 41 individuals with psychotic disorders.

RESULTS: Three main themes emerged: (1) Positive attitudes towards biomedical providers, (2) Barriers to accessing biomedical care (3) …


Proteo-Genomics Of Soluble Trem2 In Cerebrospinal Fluid Provides Novel Insights And Identifies Novel Modulators For Alzheimer's Disease, Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al. Jan 2024

Proteo-Genomics Of Soluble Trem2 In Cerebrospinal Fluid Provides Novel Insights And Identifies Novel Modulators For Alzheimer's Disease, Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer's disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an …


An Applicable Framework For Understanding Successful Aging Of People Living With Hiv And Comorbid Chronic Obstructive Pulmonary Disease, Jun Y. Byun, Crystal Chapman Lambert, Pariya L. Fazeli, Burel R. Goodin, Anand S. Iyer, Mirjam-Colette Kempf, Jenni M. Wise, Yookyong Lee, David Scott Batey, David E. Vance Jan 2024

An Applicable Framework For Understanding Successful Aging Of People Living With Hiv And Comorbid Chronic Obstructive Pulmonary Disease, Jun Y. Byun, Crystal Chapman Lambert, Pariya L. Fazeli, Burel R. Goodin, Anand S. Iyer, Mirjam-Colette Kempf, Jenni M. Wise, Yookyong Lee, David Scott Batey, David E. Vance

2020-Current year OA Pubs

No abstract provided.


Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer Jan 2024

Surveillance And Selective Treatment Of Brugia Malayi Filariasis Eleven Years After Stopping Mass Drug Administration In Belitung District, Indonesia, Taniawati Supali, Yenny Djuardi, Santoso, Lita Renata Sianipar, Nungki Hapsari Suryaningtyas, Rahmat Alfian, Yossi Destani, Elisa Iskandar, Hendri Astuty, Noviani Sugianto, Peter U Fischer

2020-Current year OA Pubs

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This …