Digital Commons Network^™

Enhanced Dietary Monitoring Using Fecal Genomics For Childhood Malnutrition Interventions, Ammara Aqeel, Najeeha T Iqbal, Sanam Iram Soomro, Sheraz Ahmed, Teresa K Mcdonald, Olivia Osborne, Sharon Jiang, Nolan Ives, Kazi Ahsan, Fayaz Umrani, Michael J Barratt, Jeffrey I Gordon, Syed Asad Ali, Lawrence A David

2020-Current year OA Pubs

Ready-to-use therapeutic and supplementary foods (RUTF/RUSF) are a primary treatment for childhood malnutrition in Community Management of Acute Malnutrition (CMAM) programs. However, measuring intervention compliance is labor intensive and unreliable. We applied FoodSeq, a fecal genomic dietary assessment biomarker, in malnourished infants (3-15 months) from Matiari, Pakistan. FoodSeq identified a significant increase in the abundance of DNA from chickpea, a primary RUSF ingredient, during RUSF administration and captured region-specific complementary feeding practices, including age-inappropriate feeding practices such as wide-spread tea consumption. Our findings highlight the potential of dietary genomics as an empirical and scalable tool for compliance monitoring and dietary …

Herpes Simplex Virus Type 1 R-Loops Are Targets For Apobec-Mediated Mutagenesis, Márton Miskei, Dóra Varga, Lilla Hornyák, Éva Sipos, Éva Nagy, Qiuzhen Li, Zsolt Karányi, Zoltán Szabó, Rachel Deweerd, Abby M Green, Dávid Szüts, Eszter Csoma, Lóránt Székvölgyi

2020-Current year OA Pubs

APOBEC3 enzymes are key effectors of antiviral immunity that introduce mutations into viral genomes. We show that viral R-loops serve as preferred substrates for APOBEC3-mediated mutagenesis during herpes simplex virus type 1 (HSV-1) infection. APOBEC3 enzymes are recruited to viral R-loops, generating clustered C-to-T mutations in genes critical for viral assembly. Importantly, R-loops alone are not mutagenic, and APOBEC3 enzymes do not edit HSV-1 without an R-loop; mutagenesis occurs when R-loops and APOBEC3 enzymes interact. These findings identify endogenous R-loops formed during the HSV-1 life cycle as focal vulnerabilities and highlight R-loop-APOBEC3 coupling as a mechanism for antiviral mutagenesis.

Synthetic Lethality Of Decitabine Plus Atr Inhibition For Tp53-Mutated Aml, Jeremy T Baeten, Sumedha Agashe, Imene Tabet, Jack T Wooldridge, Amber Carter, Jamie N Butler, Christopher A Miller, Nicole Helton, Annabel Quinet, Kimberly B Johansson, Yichan Yang, Geoffrey L Uy, Alessandro Vindigni, Daniel C Link

2020-Current year OA Pubs

TP53 mutations are found in 10% to 15% of myeloid neoplasms and are associated with a dismal prognosis. Although hypomethylating agents (HMAs), such as decitabine, are active in TP53-mutated myeloid neoplasms (TP53-MN), mutation clearance is rarely complete and nearly all patients relapse. Molecular determinants of response to HMAs in TP53-MN are poorly understood. Here, we show that decitabine induces replicative stress with decreased replication fork progression, induction of single-strand DNA breaks, and activation of the ataxia telangiectasia mutated-Rad3-related (ATR) pathway. Resolution of decitabine-induced replication stress is impaired in TP53-mutated acute myeloid leukemia (AML) cells, representing a potential therapeutic vulnerability. Indeed, …

Adipocytes Signal To Recruit Specific Mrnas From Surrounding Cells To Restore Expression Deficits, Clair Crewe, Snigdha Tiash, Yun-Ling Pai, Marjori Russo, Saket Awadhesbhai Patel, Yi-Cian Zheng, Alex Larkin, Chun-Kan Chen, Et Al.

2020-Current year OA Pubs

Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discover that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results …

Etalanetug (E2814) In Dominantly Inherited Alzheimer's Disease: An Open-Label Phase 1b/2 Study To Assess Safety And Target Engagement In Participants With Mild To Moderate Cognitive Impairment, Erica Andreozzi, Kanta Horie, Nicolas R Barthélemy, Brian A Gordon, Shaney Flores, Tammie L S Benzinger, Eric Mcdade, Randall J Bateman, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Etalanetug (E2814) is designed to delay the clinical progression of Alzheimer's disease (AD) by binding to the microtubule binding region (MTBR) of tau implicated in seeding and spreading of tau pathology. Dominantly inherited Alzheimer's disease (DIAD) is a rare form of the disease (<  1%), having similar changes in the tau distribution and pathology to sporadic AD. Herein, we report the safety, pharmacology and biomarker results of the etalanetug Study 103 in DIAD patients.

METHODS: Study 103 enrolled participants with mild-to-moderate cognitive impairment due to DIAD who received etalanetug intravenously every 4 weeks escalating from 750 mg, 1500 mg, 3000 mg, to 4500 mg. After ascending to 4500 mg, patients received 4500 mg for up to 108 weeks. Tau pathology biomarkers, ptau217 and MTBR-tau243 were measured in CSF. Additional …

Trajectories Of Plasma And Csf Mtbr-Tau243 And Phosphorylated-Tau Species Across The Alzheimer's Disease Continuum, Lyduine E Collij, Gemma Salvadó, Kanta Horie, Nicolas R Barthélemy, Tobey J Betthauser, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Suzanne E Schindler, Rik Ossenkoppele, Shorena Janelidze, Niklas Mattsson-Carlgren, Randall J Bateman, Oskar Hansson

2020-Current year OA Pubs

To efficiently implement plasma and cerebrospinal fluid (CSF) biomarkers for staging and prognosis of Alzheimer disease (AD), we must understand their dynamics across disease progression. We analyzed participants from the Swedish BioFINDER-2 study with mass spectrometry measurements of plasma and CSF tau species, including eMTBR-tau243/MTBR-tau243 and phosphorylation occupancies (%p-tau). Disease duration was estimated using Aβ-PET and tau-PET with the SILA algorithm. Bootstrapped LOESS models showed that %p-tau217 changes earliest, increasing just before Aβ-PET positivity. Other p-tau species changed later, with smaller dynamic ranges and earlier ceiling effects. %p-tau205 and MTBR-tau243 changes aligned with tau-PET positivity onset, while MTBR-tau243-especially plasma eMTBR-tau243-tracked …

What Are The Top 10 Global Research Priorities For Perianal Crohn's Disease? The Global Perianal Crohn's Disease Priority Setting Partnership, Theo Pelly, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Perianal Crohn's disease (pCD) is a debilitating condition with a prevalence of approximately 20% in patients within 10 years of diagnosis of CD. The condition significantly impacts patient quality of life, and there remain a number of unmet needs relating to its optimal management. A global Priority Setting Partnership (PSP) was established to identify the top 10 research priorities for pCD.

METHODS: The PSP followed standard James Lind Alliance (JLA) methodology. An initial survey was circulated to gather unanswered research questions from key stakeholders. From these responses, a longlist of summary questions was formed. These questions were …

Phip Suppresses Nurd To Enable The Growth Of Swi/Snf-Mutant Cancers, Hayden A Malone, Francisca N De Luna Vitorino, Benjamin A Garcia, Et Al.

2020-Current year OA Pubs

SWI/SNF chromatin remodeling complexes are perturbed in 20% of all cancers and in several developmental disorders, yet the mechanisms by which these mutations dysregulate transcription and drive disease are poorly understood. To both elucidate these mechanisms and identify vulnerabilities caused by these mutations, we leverage genome-wide CRISPR-Cas9 screening in hundreds of cancer cell lines and identify the chromatin reader protein PHIP as a specific dependency in cancers with broadly disrupted SWI/SNF function. Mechanistically, we reveal that PHIP cooperates with SWI/SNF to facilitate transcriptional activation by ubiquitinating and suppressing subunits of the repressive Nucleosome Remodeling and Deacetylase (NuRD) complex. We demonstrate …

Ex Vivo Effect Of Apixaban On Hemostatic Biomarkers In Children With Heart Disease: A Saxophone Trial Substudy, Ghada A Aborkhees, Amy J Barr, Kevin Dietrich, Christoph Male, Zhaoqing Wang, Chen Yao, R Mark Payne, Andrew C Glatz, Paul Monagle, Kristin M Burns, Alison M Reedy, Joshua L Dyme, Peter H Schafer, Antoinette Ajavon-Hartmann, Lesley G Mitchell

2020-Current year OA Pubs

BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin.

METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for …

The Gut Microbiota Shapes The Human And Murine Breath Volatilome, Ariel J Hernandez-Leyva, Amalia Z Berna, Maggie H Bui, Yang Liu, Anne L Rosen, Michael A Lint, Samantha A Whiteside, Natalia Jaeger, Ryan T Mcdonough, Nikhilesh Joardar, Jesús Santiago-Borges, Christopher P Tomera, Wentai Luo, Audrey R Odom John, Andrew L Kau

2020-Current year OA Pubs

The gut microbiota is crucial to health, yet implementation of microbiota-based therapeutics is limited by the lack of rapid diagnostics. We hypothesize that breath contains gut microbe-derived volatile organic compounds (VOCs) reflecting microbiota composition and metabolism. In healthy children, we found that breath VOC composition (or volatilome), assessed by gas chromatography-mass spectrometry, correlates with gut microbiome composition and function. By capturing exhaled breath from human-stool-colonized and monocolonized gnotobiotic mice, we profiled breath VOCs and discovered that murine breath is also significantly influenced by the gut microbiome. VOCs from cultured gut microbes were identified in vivo in monocolonized gnotobiotic colonized mice. …

Reference Proteins To Improve Core 1 And Core 2 Alzheimer's Disease Csf And Plasma Biomarkers, Linda Karlsson, Nicolas R Barthélemy, Kanta Horie, Suzanne E Schindler, Brian A Gordon, Cyrus A Raji, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Concentration-based fluid biomarkers represent an informative and cost-effective way to detect and monitor Alzheimer's disease (AD) pathology. However, non-AD-related interindividual variation in biofluids can also affect biomarker concentrations. Here, we investigated whether normalization of CSF and plasma biomarkers to reference proteins, such as amyloid-β40 (Aβ40) and non-phosphorylated mid-region tau (np-tau), improves their robustness and reliability of representing AD pathology load. Using the Swedish BioFINDER-2 cohort [n = 1702, 50.7% male, mean (standard deviation) age 68.4 (12.2) years], we compared the associations between tau/Aβ-PET load and fluid biomarkers alone versus biomarkers in a ratio with a reference protein (Aβ40 or np-tau) …

Validate-Perianal: An International Real-World Multi-Centre Exploratory Validation Of The Topclass Definition Of A Radiologically Healed Fistula In Perianal Fistulising Crohn's Disease, Easan Anand, Thirza J Van Croonenburg, Sami Samaan, Phil Tozer, Ailsa Hart, Parakkal Deepak, David H Ballard, Jaap Stoker, Phillip Lung

2020-Current year OA Pubs

OBJECTIVES: Radiological healing on MRI is the ultimate therapeutic goal in Class 2a perianal fistulising Crohn's disease (pfCD). The TOpClass consortium recently defined radiological healing (TOpClass-RH) by the absence of T2 hyperintensity, a completely fibrotic fistula tract, and the absence of contrast enhancement when used. This study aimed to validate TOpClass-RH in real-world clinical practice.

MATERIALS AND METHODS: VALIDATE-PERIANAL was a retrospective, multi-centre international study. Patients with pfCD with a baseline MRI scan showing active disease and follow-up MRI evidence of radiological fistula healing between 2021 and 2023 were identified. Paired scans were independently reviewed by three gastrointestinal radiologists using …

Mitochondrial Presequences Harbor Variable Strengths To Maintain Organellar Function, Youmian Yan, Baigalmaa Erdenepurev, Thiago N Menezes, Ian Collinson, Natalie M Niemi

2020-Current year OA Pubs

Hundreds of mitochondrial proteins rely on N-terminal presequences for organellar targeting and import. While generally described as positively charged amphiphilic helices, presequences lack a consensus motif and thus likely promote protein import into mitochondria with variable efficiencies. Indeed, the concept of presequence strength underlies biological models such as stress sensing, yet a quantitative analysis of what dictates strong versus weak presequences is lacking. Furthermore, the extent to which presequence strength affects mitochondrial function and cellular fitness remains unclear. Here, we capitalize on the MitoLuc protein import assay to define multiple aspects of presequence strength. We find that select presequences, including …

Medicare Part D Formulary Coverage Of Disease-Modifying Therapies For Multiple Sclerosis, Pengxiang Li, Matthew J Klebanoff, John K Lin, Keya D Doshi, Salim Chahin, Jalpa A Doshi

2020-Current year OA Pubs

No abstract provided.

Eeg In Patients With Altered Mental Status In The Emergency Department, Mariama Runcie, Neal Nolan, Olivia Yoo, Robert Silbergleit, Fábio A Nascimento, Maura Kennedy, M Brandon Westover, Joshua N Goldstein

2020-Current year OA Pubs

BACKGROUND: Altered mental status is a common chief complaint in the emergency setting, and the initial evaluation often fails to find an etiology. Subclinical (electrographic) seizures and nonconvulsive status epilepticus (NCSE) are potential causes of delirium and altered mental status, but require electroencephalogram (EEG) for diagnosis. It is not clear how often subclinical seizure or NCSE is present in those with undifferentiated altered mental status, nor which patients are most likely to benefit from emergent EEG. METHODS: We performed a retrospective review of patients presenting to a single academic medical center emergency department (ED) over a one-year period with the …

Depolymerizing F-Actin Accelerates The Exit From Pluripotency To Enhance Stem Cell-Derived Islet Differentiation, Nathaniel J Hogrebe, Mason D Schmidt, Punn Augsornworawat, Sarah E Gale, Mira Shunkarova, Jeffrey R Millman

2020-Current year OA Pubs

In this study, we demonstrate that cytoskeletal state at the onset of directed differentiation impacts the exit of human pluripotent stem cells (hPSCs) from pluripotency and downstream lineage specification. In particular, depolymerizing F-actin with latrunculin A (latA) during the first 24 h of definitive endoderm formation facilitates efficient loss of pluripotency and alters Activin/Nodal, BMP, c-Jun, and WNT signaling dynamics. These signaling changes influence downstream patterning of the gut tube, leading to improved pancreatic progenitor identity and decreased expression of markers associated with other endodermal lineages. Continued differentiation generates islets containing a higher percentage of β cells that exhibit improved …

Detailed Single-Cell Mapping Of The Transcriptional Response To A Virus Infection Driven By Copy-Back Viral Genomes, Yanling Yang, Emna Achouri, Munyaradzi Tambo, Carolina B. López

2020-Current year OA Pubs

The antiviral response to several clinically significant viruses, including respiratory syncytial virus and parainfluenza virus, is driven by copy-back viral genomes (cbVGs) generated during virus replication. However, the broader impact of cbVGs on the functional states of host cells remains undefined. Here, we developed a single-cell RNA-sequencing and computational framework to map cbVG-driven host responses during Sendai virus infection. Unsupervised profiling identified distinct transcriptional states throughout the course of infection, highlighting a shift from early antiviral signaling to later inflammatory and remodeling programs. Stratifying infected cells by cbVG status demonstrated that cbVG-positive cells initiate interferon and chemokine programs, which later …

Mental Health Symptom Screening Among Adult Emergency Department Patients: A Cross-Sectional Study, Jacob Langkiet, Rachel M Ancona, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Mental health symptoms profoundly influence healthcare outcomes and utilization. Although mental health conditions are common in emergency department (ED) patients, routine, noncrisis screening is not consistently implemented; thus, problems may go unrecognized outside of psychiatric crisis presentations. We aimed to estimate the prevalence of current symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) among ED patients using validated screening tools.

METHODS: We conducted a secondary analysis of cross-sectional data from 1305 randomly selected, adult patients from 3 urban, academic EDs. Validated survey instruments included (i) Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Short Form 8a, (ii) Emotional Distress …

Preoperative Imaging For Cochlear Implantation: A Global Consensus, Farid Alzhrani, Craig Buchman, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Preoperative imaging is vital for cochlear implant surgeries, aiding diagnosis, and surgical planning. This study evaluated global practices and the value of preoperative imaging through an international survey.

METHODS: A cross-sectional survey was conducted among international cochlear implantation experts using a 112-item questionnaire. The study explored imaging modalities, anatomical targets, evaluated parameters, and different imaging approaches' perceived value and risks. Participants were recruited from a global consortium of otolaryngology, otology, neurotology, and cochlear implant surgery professionals.

RESULTS: Thirty-nine practitioners from 36 centers in 16 countries completed the survey (95.1% response rate). All used computed tomography (CT) and magnetic resonance …

Neurofibromatosis Type 1-Plexiform Neurofibromas: Integrating Treatment Across Pediatric And Adult Populations, Amy E Armstrong, Andrea M Gross, Laura J Klesse, Steven D Rhodes, Shivani Ahlawat, Verena Staedtke, Camilo A Molina, Angela C Hirbe

2020-Current year OA Pubs

Plexiform neurofibromas (PNs) are a hallmark of neurofibromatosis type 1 (NF1), affecting ∼50% of individuals with the condition. Originating from Schwann cells and other peripheral nerve sheath components, these tumors can cause significant morbidity, including functional impairment, diminished health-related quality of life, chronic pain, and malignant transformation. Managing NF1-PNs is challenging because of disease variability, differing growth rates, and age-related differences in clinical presentation and treatment tolerability. This review examines current therapeutic strategies, including surgery, medical therapies, and emerging treatments, emphasizing individualized care. Highlighted here is the need for age-specific treatment planning, particularly as disease progression, comorbidities, and side-effect profiles …

Exploring Early Antifungal Activity Of Rezafungin As A Stepping-Stone For Shorter Treatment Duration For Candidemia: Pooled Analysis Of 2 Randomized Trials, Luis Ostrosky-Zeichner, Jalal A Aram, Mark Redell, George R Thompson, Oliver A Cornely, James A Mckinnell, Andrej Spec, Peter G Pappas

2020-Current year OA Pubs

BACKGROUND: Guidelines recommend ≥2 weeks of antifungal therapy after candidemia clearance and for invasive candidiasis (IC). This post-hoc analysis evaluates Day 7 pooled data from the phase 2 STRIVE and phase 3 ReSTORE trials to explore early antifungal activity.

METHODS: Adults with candidemia and/or IC received weekly rezafungin 400/200 mg or daily caspofungin 70/50 mg for ≤4 weeks. Efficacy was evaluated in the modified intent-to-treat population via all-cause mortality (ACM; primary endpoint; 20% noninferiority margin), mycological eradication, and time to negative blood culture (TTNBC) at days 7, 14, and 30 (TTNBC assessed only in patients with candidemia). Day 7 safety …

Use Of Inverse Probability Weighting In Cardiovascular Surgical Outcomes Research: Principles, Limitations, And Recommendations, Zhongjian Liu, Wei-Guo Ma, Lei Liu, Prashanth Vallabhajosyula, Haibo Wang

2020-Current year OA Pubs

This statistical primer presents a comprehensive introduction to the use of inverse probability of treatment weighting (IPTW), a method for rebalancing group confounders at baseline in cardiovascular surgical outcomes research. We leveraged a retrospective study comparing the outcomes of 2 different surgical approaches to aortic arch pathology to illustrate the essential aspects of performing IPTW, including basic theories, application, extreme weights, underestimated variance, heterogeneity of treatment effect, and multicollinearity. The limitations of IPTW were discussed with examples of solutions. Ten practical recommendations are made on avoiding the pitfalls in the use of IPTW. Proper use of IPTW may effectively reduce …

Ten Tips On How To Prevent And Manage Post-Transplant Lymphoproliferative Disease In Kidney Transplant Recipients, Rose Mary Attieh, Armin Ghobadi, Naoka Murakami

2020-Current year OA Pubs

Post-transplant lymphoproliferative disease (PTLD) remains a challenging and high-impact complication of kidney transplantation, requiring thoughtful prevention, timely recognition, and multidisciplinary management. Key strategies include careful selection of immunosuppressive regimens, particularly avoiding belatacept in Epstein-Barr virus (EBV)-seronegative recipients and exercising caution with lymphodepleting induction in EBV-mismatched pairs, along with targeted EBV surveillance in high-risk patients. Once PTLD is suspected or confirmed, accurate staging and a stepwise treatment approach beginning with reduction of immunosuppression and escalating to rituximab, chemotherapy, or advanced cellular therapies are essential, with EBV-CTLs and chimeric antigen receptor T-cell therapy offering promising options in refractory disease. Close monitoring for …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

2020-Current year OA Pubs

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …

Mechano Responsiveness Of Neuroimmune Cross-Talk In Bone And Joints: A Narrative Review With Implications For Force-Based Manipulations, Karl J Lewis, Jennifer Bent, Per Gunnar Brolinson, Damian Keter, Ellen Lumpkin, Jan Mundo, Vitaly Napadow, William R Reed, Brent S Russell, Simon Y Tang, Mary F Barbe

2020-Current year OA Pubs

INTRODUCTION: Recent advances in osteoimmunology have illuminated the significant role of neuroimmune interactions in bone and joint health. The neuroimmune system critically regulates bone cell function through a complex network of molecular mediators - including signals from the sympathetic and parasympathetic nervous systems, pro- and anti-inflammatory cytokines, cortisol and other hormones, and growth factors. These mediators interact within a nonlinear network where each component can influence others reciprocally, with the brain serving as a central coordinator.

AIM: Our goal in this narrative review is to: 1) Provide an overview of roles the neuroimmune system is involved in bone and joint …

Accurate Predictions Of Disordered Protein Ensembles With Starling, Borna Novak, Jeffrey M Lotthammer, Ryan J Emenecker, Alex S Holehouse

2020-Current year OA Pubs

Intrinsically disordered proteins and regions (collectively IDRs) are found across all kingdoms of life and have critical roles in virtually every eukaryotic cellular process

Predictors Of Delayed Recovery In Ambulatory Advanced Endoscopic Procedures, Zoilo K Suarez, Alexandria Lenyo, Philip M Frasse, Derek J Platt, Thomas Hollander, Talwinder Nagi, Michael Dedonno, Vladimir Kushnir, Juan Reyes Genere

2020-Current year OA Pubs

BACKGROUND: There is a scarcity of data evaluating patient-related outcomes of advanced or complex endoscopy (ACE) through the post-anesthesia recovery course. Yet, gastrointestinal distress following ACE can occur commonly, and this may impact recovery length of stay and the approach to post-anesthesia care. This study aimed to describe post-procedural symptoms in patients undergoing ACE and identify factors that influence recovery time and course.

METHODS: We retrospectively reviewed a prospectively collected database of patients who underwent ambulatory ACE. Procedural-related symptoms, recovery time, dismissal rate, and adverse events (AE) were recorded. Factors associated with extended recovery time were analyzed using multiple regression …

An International Mega-Analysis Of Psychedelic Drug Effects On Brain Circuit Function, Manesh Girn, Nico Dosenbach, Et Al.

2020-Current year OA Pubs

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and …

Metabolically Reprogrammed Eosinophils Impair T Cell Immunity And Cause Chronic Skin Infection, David Barinberg, Heidi Sebald, Tobias Gold, Baplu Rai, Daniel Radtke, Dominik Lerm, David Voehringer, Jonathan Jantsch, Stefan Wirtz, Alina Ulezko Antonova, Marco Colonna, Christian Bogdan, Ulrike Schleicher

2020-Current year OA Pubs

Eosinophils exhibit antimicrobial, cytotoxic and immunoregulatory effects, but our knowledge of their transcriptional and functional heterogeneity is still limited, especially in non-intestinal tissues. Here, we used a mouse model of chronic cutaneous inflammation elicited by the protozoan pathogen Leishmania mexicana to investigate the function and transcriptional dynamics of skin eosinophils. Infection of C57BL/6 mice triggered local and systemic eosinophilia that was driven by type 2 innate lymphoid cells and interleukin-5. Genetic and pharmacological eosinophil depletion led to an enhanced Th1 response, polarization towards M1-like macrophages and resolution of clinical disease, despite an unexpected simultaneous upregulation of IL-4. Single-cell transcriptomics revealed …

Sialidosis Type I: How To Alleviate Disabling Myoclonic Seizures? - A Multicenter Analysis Of Eight Cases And Review Of The Literature, Janina Gburek-Augustat, Shao Ching Tu, Marwan Shinawi, Isabel Alfradique-Dunham, Manouela Valtcheva, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Sialidosis type I (ST-1) is an autosomal-recessive, very rare, progressive lysosomal storage disorder caused by pathogenic variants in NEU1. It is clinically characterized by progressive ataxia, myoclonic seizures (MS), bilateral tonic-clonic seizures (BTCS), and distinctive ophthalmological findings. Given the lack of curative options, in this study, we investigated symptomatic treatment strategies, with a particular focus on the efficacy of antiseizure medications (ASMs).

METHODS: We describe the clinical course of a patient followed from diagnosis to 18 years of age, and review seven additional cases from our cohort. In parallel, we conducted a narrative review of the literature (PubMed, January …