bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated Myeloperoxidase–Antineutrophil Cytoplasmic Antibody–Associated Hypertrophic Pachymeningitis
Authors: Maneval Jeffrey , Bryant Bronwyn , Ulano Adam , Waheed Waqar , Nevares Alana 
Published: March 2022

Abstract
A 65-year-old man with no pertinent medical history presented with 1 month of progressive holocephalic positional headaches (worse supine), photophobia, progressive gait instability resulting in multiple falls (ambulatory to walker in only 2 months), and weight loss. Testing found positive ANCA 1:160 perinuclear patter, myeloperoxidase >8.0. Cerebrospinal fluid found lymphocytic pleocytosis. We present his neuroimaging of isolated hypertrophic pachymeningitis with clinicoradiographic resolution after immunomodulatory pharmacotherapy along with histology from his meningeal biopsy. Isolated vasculitic myeloperoxidase–antineutrophil cytoplasmic antibody hypertrophic pachymeningitis is quite rare.
To Clap or Not to Clap
Authors: Díaz-Agea José L. , Pujalte-Jesús María J. , García-Méndez Juan A. , Adánez-Martínez Gracia , Jiménez-Rodríguez Diana , Leal-Costa César 
Published: March 2022

Introduction
Applause is a common behavior during simulation case learning sessions. Some simulation facilitators believe that this should not be allowed, arguing that it can mislead students when they make mistakes during simulation. This study was conducted to explore the opinions of students about spontaneous applause (initiated by the participants), as a habitual behavior in the simulation sessions, in the undergraduate and postgraduate nursing degrees.

Methods
A qualitative research study was conducted based on the content analysis of 7 focus groups composed of simulation students (N = 101, both undergraduate and graduate students). The participants were asked to conduct a debate about the following question: What is your opinion about the spontaneous applause given to participants by their peers at the completion of the scenario as they go to the debriefing, and why? An inductive method of content analysis was used to interpret the data.

Results
The majority considered applause as a sign of support; one student disapproved of the practice. For most participants, receiving spontaneous applause from their peers after finishing the simulation represented a spontaneous example of moral support that reduced the participants' stress.

Conclusions
Applause within the context of clinical simulation is a motivational act, which should not be repressed by the facilitator, as long as it is a spontaneous and genuine act by the participants once the simulation experience ends.
Sex differences associate with late microbiome alterations after murine surgical sepsis
Authors: Efron Philip Alexander , Darden Dijoia B. , Li Eric C. , Munley Jennifer , Kelly Lauren , Fenner Brittany , Nacionales Dina C. , Ungaro Ricardo F. , Dirain Marvin L. , Rincon Jaimar , Mankowski Robert T. , Leeuwenburgh Christiaan , Moore Fredrick A. , Brakenridge Scott C. , Foster Thomas C. , Laitano Orlando , Casadesus Gemma , Moldawer Lyle L. , Mohr Alicia M. , Thomas Ryan M. 
Published: March 2022

BACKGROUND
Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males.

METHODS
Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls. For this work, the results of young (3–5 months) and old (18–22 months) adult mice were analyzed by sex, independent and dependent of age. Mice were sacrificed at days 7 and 14, and 16S rRNA gene sequencing was performed on fecal bacterial DNA. α and β diversity were determined by Shannon index and Bray-Curtis with principal coordinate analysis, respectively. False discovery rate (FDR) correction was implemented to account for potential housing effect.

RESULTS
In control mice, there was no difference in α or β diversity between male and female mice (FDR, 0.76 and 0.99, respectively). However, male mice that underwent CLP with daily chronic stress had a decrease in microbiota α diversity at 7 days post-CLP (Shannon FDR, 0.005), which was sustained at 14 days post-CLP (Shannon FDR, 0.001), compared with baseline. In addition, male mice maintained differences in β diversity even at day 14 compared with controls (FDR, <0.0001). In contrast, female mice had a decreased microbiota α diversity (Shannon FDR, 0.03) and β diversity (FDR, 0.02) 7 days post-CLP but recovered their α and β diversity by post-CLP day 14 (Shannon FDR, 0.5, and FDR, 0.02, respectively). Further analysis of females revealed that only young female mice were not different (β diversity) post-CLP day 14 to controls.

CONCLUSION
Although sepsis-induced perturbations of the intestinal microbiota occur initially in both male and female C57BL/6 mice, females demonstrate different microbiota by day 14. This may be seen primarily in younger females. This difference in recovery may play a role in outcome differences between sexes after sepsis.
Animal Models in Epileptic Spasms and the Development of Novel Treatment Options
Authors: Barrett Karlene T. , Choudhary Anamika , Charkhand Behshad , Scantlebury Morris H. 
Published: March 2022

Summary:
The infantile spasms (IS) syndrome is a catastrophic developmental epileptic encephalopathy syndrome characterized by an age-specific expression of epileptic spasms that are associated with extremely abnormal, oftentimes described as chaotic, interictal EEG pattern known as hypsarrhythmia. Patients with IS generally have poor neurodevelopmental outcomes, in large part because of the frequent epileptic spasms and interictal EEG abnormalities. Current first-line treatments such as adrenocorticotropic hormone or vigabatrin are often ineffective and are associated with major toxic side effects. There is therefore a need for better and safer treatments for patients with IS, especially for the intractable population. Hope is on the horizon as, over the past 10 years, there has been robust progress in the development of etiology-specific animal models of IS. These models have been used to identify potential new treatments for IS and are beginning to provide some important insights into the pathophysiological substrates for this disease. In this review, we will highlight strengths and weaknesses of the currently available animal models of IS in addition to new insights into the pathophysiology and treatment options derived from these models.
Scoring Systems for the Evaluation of Hypsarrhythmia
Authors: Lachhwani Deepak 
Published: March 2022

Summary:
Hypsarrhythmia is a well-recognized EEG pattern and it has been long known as a feature of one of the more severe forms of epilepsy early in life with adverse consequences if not recognized and treated promptly. Yet, it has been difficult to objectively quantify its varied manifestations and link them to the clinical severity of epilepsy, implications for treatment, or the overall seizure and developmental outcome of young patients. This is not for want of effort, for there have been several approaches to score hypsarrhythmia ever since its initial recognition as a unique EEG pattern. In this article, we review the different methods proposed to score hypsarrhythmia and highlight the challenges inherent to each one of them.
Conventional polymers may unintentionally refill in vivo with unassociated drugs
Authors: Young Kathleen , Dogan Alan B. , Hernandez Christopher , Exner Agata A. , von Recum Horst A. 
Published: March 2022

AbstractPolymers used as drug delivery devices are ultimately limited by how much drug they can hold; with the device failing if the drug is depleted before the disease is cured. Our lab discovered a means to use thermodynamic driving forces to refill certain classes of polymer after implantation, for additional drug delivery windows. These same, refillable polymers can be used as additives, to provide refilling capacity to classical, non-refillable polymers such as poly(methyl methacrylate) (PMMA). In this paper, we investigated the refilling capacity of another conventional polymer: poly(lactic-co-glycolic acid) or PLGA. We explored both unmodified PLGA implants as well as implants supplemented with polymerized cyclodextrin (pCD) in microparticle form, previously shown to add refillability to poly(methyl methacrylate) (PMMA) implants which were otherwise not refillable. Assessments of in situ forming PLGA implants with and without pCD additives were made, including drug loading capacity in a liquid medium, drug refilling through a tissue-mimicking gel medium, and refilling in ex vivo and in vivo conditions. Implant cross-sections were imaged via fluorescence microscopy. Drug release from refilled implants, polymer swelling, degradation, phase inversion characteristics were assessed, and drug/monomer computational simulation studies were performed. While generally, the incorporation of cyclodextrin into implants led to significant increases in the amount of refilled drug; unexpectedly, PLGA implants with no incorporated pCD also showed refilling capability. Moreover, in two out of three in vivo conditions in rats, PLGA alone showed the potential to refill with comparable, if not greater, amounts of drug than PLGA with pCD incorporated. This contrasts predictions, since PLGA has no specifically designed affinity structure, like pCD does. We theorize that the mechanism for PLGA’s refilling depends on nano-patterning of hydrophilic and hydrophobic molecular domains, giving rise to its affinity-like behavior. The fact that PLGA implants can be refilled with unassociated drugs, gives rise to concerns about the fate of all implants made of poly alpha-hydroxy esters, and likely other polymers as well, and will likely lead to new directions of study such as of unintended polymer / drug interactions.
Fast & Scrupulous: Gesture-Based Alarms Improve Accuracy and Reaction Times Under Various Mental Workload Levels. An ERSP Study
Authors: Fabre Eve Floriane , Somon Bertille , Baragona Valeria , Uhl Quentin , Causse Mickaël 
Published: March 2022

AbstractIn high-risk environments, fast and accurate responses to warning systems are essential to efficiently handle emergency situations. The aim of the present study was twofold: 1) investigating whether hand action videos (i.e., gesture alarms) trigger faster and more accurate responses than text alarm messages (i.e., written alarms), especially when mental workload (MWL) is high; and 2) investigating the brain activity in response to both types of alarms as a function of MWL. Regardless of MWL, participants (N = 28) were found to be both faster and more accurate when responding to gesture alarms than to written alarms. Brain electrophysiological results suggest that this greater efficiency might be due to a facilitation of the action execution, reflected by the decrease in mu and beta power observed around the response time window. These results suggest that gesture alarms may improve operators’ performances in emergency situations.
Galanin Analogs Prevent Seizure-Induced Respiratory Arrest
Authors: Collard Ryley , Aziz Miriam C. , Rapp Kevin , Cutshall Connor , Duyvesteyn Evalien , Metcalf Cameron S. 
Published: March 2022

SUMMARYObjectiveSudden Unexpected Death in Epilepsy (SUDEP) accounts for 20% of mortality in those with recurrent seizures. While risk factors, monitoring systems, and standard practices are in place, the pathophysiology of SUDEP is still not well understood. Better knowledge of SUDEP and its potential mechanisms of action is crucial to reducing risk in this patient population and developing potential treatment options. Clinical studies and animal models of SUDEP suggest that diminished post-ictal respiratory control may be the dominant mechanism contributing to mortality. Recently, it was demonstrated that the depletion of the neuropeptide galanin in the amygdala occurs in human SUDEP. The amygdala plays a key role in the central integration of respiratory signaling; the depletion of galanin may represent a critical change that predisposes individuals to SUDEP.MethodsTo evaluate the potential benefit of enhancing galaninergic signaling as a means to protect against SUDEP, we studied seizure-induced respiratory arrest (S-IRA) following central (intracerebroventricular, intra-amygdala) and systemic (intraperitoneal, subcutaneous) administration of galanin agonists. Seizure naïve and seizure experienced (fully kindled) mice were tested.ResultsCentral and systemically-administered galanin analogs protect against S-IRA in naïve C57Bl/6J mice. Differential efficacy between receptor subtype-selective analogs varied based on the route of administration. Sub-chronic systemic administration at doses that reduced 6 Hz seizures also protected against S-IRA. Acute treatment benefits also extended to fully kindled mice subjected to tonic extension.SignificanceThese data demonstrate that galanin agonists may be protective against post-ictal respiratory collapse.KEY POINTSCentral and systemic galanin agonists prevent seizure-induced respiratory arrest.Efficacy was observed in three separate mouse strains under various experimental conditions.Sub-chronic administration demonstrated galanin agonist protection against respiratory arrest.Acute systemic administration also conferred protection against respiratory arrest following tonic extension.Galanin analogs may represent a novel potential therapy in SUDEP-susceptible individuals.
Integrative Analysis of Checkpoint Blockade Response in Advanced Non-Small Cell Lung Cancer
Authors: Ravi Arvind , Gainor Justin F. , Arniella Monica B. , Holton Mark , Freeman Samuel S. , Stewart Chip , Leshchiner Ignaty , Kim Jaegil , Akiyama Yo , Griffin Aaron T. , Vokes Natalie I. , Sakhi Mustafa , Kamesan Vashine , Rizvi Hira , Ricciuti Biagio , Forde Patrick M. , Anagnostou Valsamo , Riess Jonathan W. , Gibbons Don L. , Pennell Nathan A. , Velcheti Vamsidhar , Digumarthy Subba R. , Mino-Kenudson Mari , Califano Andrea , Heymach John V. , Herbst Roy S. , Brahmer Julie R. , Schalper Kurt A. , Velculescu Victor E. , Henick Brian S. , Rizvi Naiyer , Jänne Pasi A. , Awad Mark M. , Chow Andrew , Greenbaum Benjamin D. , Luksza Marta , Shaw Alice T. , Wolchok Jedd , Hacohen Nir , Getz Gad , Hellmann Matthew D. 
Published: March 2022

SUMMARYAnti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). While our understanding of the biology underlying immune checkpoint blockade in NSCLC is still incomplete, studies to date have established predictive roles for PD-L1 tumor expression and tumor mutational burden (TMB). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up 2 Cancer - Mark Foundation (SU2C-MARK) Cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including: 1) favorable (e.g., ATM altered), and unfavorable (e.g., TERT amplified) genomic subgroups, 2) distinct immune infiltration signatures associated with wound healing (unfavorable) and immune activation (favorable), and 3) a novel de-differentiated tumor-intrinsic subtype characterized by expression of endodermal lineage genes, immune activation, and enhanced response rate. Taken together, results from this cohort extend our understanding of NSCLC-specific predictors, providing a rich set of molecular and immunologic hypotheses with which to further our understanding of the biology of checkpoint blockade in NSCLC.
The gut microbiome is a significant risk factor for future chronic lung disease
Authors: Liu Yang , Teo Shu Mei , Meric Guillaume , Tang Howard H.F. , Zhu Qiyun , Sanders Jon G , Vazquez-Baeza Yoshiki , Verspoor Karin , Vartiainen Ville A , Jousilahti Pekka , Lahti Leo , Niiranen Teemu , Havulinna Aki S. , Knight Rob , Salomaa Veikko , Inouye Michael 
Published: March 2022

AbstractBackgroundThe gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.Objectives3To investigate the associations between gut microbiome and respiratory disease and to construct predictive models from baseline gut microbiome profiles for incident asthma or chronic obstructive pulmonary disease (COPD).MethodsShallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N=7,115 adults) with linked national administrative health register derived classifications for incident asthma and COPD up to 15 years after baseline. Generalised linear models and Cox regressions were utilised to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index and smoking status.ResultsA total of 695 and 392 significant microbial associations at different taxonomic levels were found with incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome predicted incident asthma and COPD with mean area under the curves of 0.608 and 0.780, respectively. For both incident asthma and COPD, the baseline gut microbiome had C-indices of 0.623 for asthma and 0.817 for COPD, which were more predictive than other conventional risk factors. The integration of gut microbiome and conventional risk factors further improved prediction capacities. Subgroup analyses indicated gut microbiome was significantly associated with incident COPD in both current smokers and non-smokers, as well as in individuals who reported never smoking.ConclusionsThe gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.
Patients’ Experiences of Using Smartphone Apps to Manage their Gestational Diabetes Diagnosis: A Systematic Review - protocol (version 1)
Authors: Anis Ali , Plüddemann Annette , Choksey Anurag , Portwood Clara , Mitra Vikram , Heneghan Carl 
Published: March 2022

AbstractBackgroundGestational diabetes is a strong predictor of type 2 diabetes onset. However, women who make healthy dietary and lifestyle choices can significantly reduce their risk. There is a need to understand the factors facilitating or preventing women from using smartphone apps that may encourage these behaviours.MethodsWe plan to conduct a systematic review of patient experiences when using mobile health applications to manage gestational diabetes. We will include primary studies of qualitative data around patient experiences of using these applications, as well as the barriers and facilitators to using technologies. We will search the following electronic databases: Medline, Embase, PsycINFO, Global Health, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), AMED and CINAHL and manually search the reference lists of included studies. We will include primary studies involving direct user interviews and where the results have been analysed using qualitative methods. To assess the quality of included studies, we will use the CASP qualitative research checklist.Expected resultsWe intend to use summary tables to report the characteristics of the study population, the overarching themes that emerged, and recommendations for research and practice.
An uncommon garden experiment: microenvironment has stronger influence on phenotypic variation than epigenetic memory in the clonal Lombardy poplar
Authors: Rodríguez Bárbara Díez , Peña Cristian , Pérez Bello Paloma , Bette Julius , Lerbs Lena , Mackenbach Tabea , Wulle Sven , De Paoli Emanuele , Verhoeven Koen J.F. , Heer Katrin , Opgenoorth Lars 
Published: March 2022

AbstractEnvironmental changes can trigger phenotypic variation in plants through epigenetic mechanisms, but strong genetic influences on epigenetic variation and phenotypes make it difficult to isolate and study these effects. We investigated phenotypic plasticity using the Lombardy poplar (Populus nigra cv. ‘Italica’ Duroi), a globaly distributed clonal tree. We surveyed 14 functional traits related to tree growth, ecophysiological and phenological processes in poplar ramets collected along a wide geographical range in Europe and planted under common garden conditions. We investigated whether phenotypic variation was related to geography and historical bioclimatic data of the ramets’ sites of origin using linear mixed effect models. We found significant differences in among ramets from different geographic origins in tree height, number of stems per ramet and duration of bud flush. However, microenvironmental variation in the common garden, captured via block effects, had an even bigger impact on phenotypic variation than the environmental conditions at the sites of origin. Our results show that phenotypic variation in the ramets might be associated to the climate origin from different climates, suggesting possible epigenetic memory. However, such legacy effects might be quickly outweighed by new environmental conditions.
Context-dependent triggering of STING-interferon signaling by CD11b agonists supports anti-tumor immunity in mouse models and human cancer patients
Authors: Liu Xiuting , Hogg Graham D. , Zuo Chong , Baer John M , Lander Varintra E. , Kang Liang , Borcherding Nicholas C. , Knolhoff Brett L. , Osterhout Robin E. , Galkin Anna V. , Bruey Jean-Marie , Carter Laura L. , Mpoy Cedric , Schwarz Julie K. , Park Haeseong , Gupta Vineet , DeNardo David G. 
Published: March 2022

AbstractChronic activation of inflammatory pathways and suppressed interferon signaling are hallmarks of myeloid cells in immunosuppressive tumors that drive poor responsiveness to conventional and immune therapies. Previous studies have identified agonistic activation of the CD11b integrin as a potential strategy to enhance anti-tumor immunity. However, the mechanisms by which CD11b-agonism reprogram tumor immunity are poorly understood, and this may impair patient selection and identification of effective treatment combinations. Herein we used a combination of in vitro systems, animal models, and samples from first in human clinical trials of the CD11b-agonist GB1275 to identify the mechanism of action of this approach and identify combinations for further testing. We found that CD11b agonism altered tumor-associated macrophage (TAM) phenotypes by simultaneously repressing NFκB/IL1-signaling and activating interferon (IFN) gene expression. Repression of NFκB/IL-1 signaling was due to rapid degradation of p65 protein by the proteosome and was not context dependent. In contrast, CD11b agonism triggered mitochondrial dysfunction to stimulate STING-induced, STAT1-mediated interferon signaling. The magnitude of CD11b agonist induction of STING/IFN signaling was dependent on the tumor microenvironment and was significantly amplified by cytotoxic therapies. Using tissues from phase I clinical trials, we demonstrated that GB1275 treatment activated STING and STAT1 signaling in TAMs in human tumors. Together, these mechanisms allowed macrophages to augment anti-tumor T cell immunity. These studies identified potential mechanism-based therapeutic strategies for CD11b agonist use and identified potential patient populations more likely to benefit from them.Statement of significanceCD11b agonists are a novel approach to reprogram myeloid cells in solid tumors. We show that GB1275, a CD11b-agonist, amplified STING/IFN signaling in TAMs to support anti-tumor immunity and this signaling is amplified further by cytotoxic therapy. These studies support new treatment strategies for advanced solid tumors with myeloid immunosuppression.