bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare Quality for Acute Illness during the COVID-19 Pandemic: A Multisite Qualitative Analysis
Authors: Leyenaar JoAnna K. , McDaniel Corrie E. , Arthur Kimberly C. , Stevens Cathryn A. , St Ivany Amanda R. 
Published: September 2021

Introduction:
The coronavirus disease 2019 (COVID-19) pandemic incited substantial changes to acute care delivery, including the rapid scale-up of telehealth and numerous changes to in-person care. This study explored health system changes associated with the COVID-19 pandemic and their influences on pediatric acute care delivery and quality of care.

Methods:
We conducted 38 semistructured interviews May–November 2020 with families and clinicians from 3 US regions, eliciting their perspectives and experiences regarding changes to acute care delivery during the pandemic. Interviews were analyzed using a general inductive approach to identify relationships between clinical care infrastructure, care processes, and healthcare quality.

Results:
Emerging knowledge of COVID-19 epidemiology and associated restrictions influenced care-seeking behaviors and clinical infrastructure and processes. Infrastructure changes included the closure of some clinics, limited “sick visit” hours and locations, and increased resources for telehealth. Modified care processes included the assignment of clinicians to specific roles, limitations on sibling attendance, increased referrals to other clinics, and iterative development of procedures and protocols. Although intended to increase safety, these changes appear to have decreased access, timeliness, and equity of care. High-quality care was supported by telephone triage processes, in-person visits following initial assessments by telehealth, and identification of diagnoses and populations best-suited to telehealth versus in-person care.

Conclusions:
Changes in acute care delivery during the COVID-19 pandemic may have negatively impacted healthcare quality in some domains. Implementation of pediatric-specific guidelines and decision aids describing diagnoses, populations, and procedures best-suited to telehealth may improve the quality of acute care delivery.
Early-life respiratory viral infection results in impairment of adult lung function
Authors: Harb Laith H , Holt Patrick G , Strickland Deborah , Martino David , Larcombe Alexander N , Bosco Anthony 
Published: September 2021

AbstractRespiratory viral infections in early-life are linked to the development of chronic lung diseases that persist into adulthood. The aim of this study was to develop a mouse model of early-life respiratory viral infection that would lead to impaired lung function in adulthood. BALB/c pups were infected at seven days of life with one of the following respiratory viruses: influenza A/Mem/1/71 “M71”, influenza A/Puerto Rico/8/34 “PR8” or attenuated mengovirus “Mengo”. Lung function and airways responsiveness (AHR) to methacholine were assessed seven weeks later, using the forced oscillation technique, and data were compared between male and female mice. PR8 infection was associated with significantly increased responsiveness to methacholine (for airway resistance, tissue damping, tissue elastance and hystersivity) for both sexes. M71 infection resulted in less severe responses especially in adult males. Early-life Mengo infection led to significantly higher responsiveness to MCh for males only (for airway resistance and tissue damping), suggesting sex dependant effects in lung function parameters measured. In summary, we have established a murine model where respiratory viral infection on day seven of life leads to AHR in adulthood. Importantly, the model recapitulates key variations in susceptibility related to sex and nature of viral pathogen that have previously been observed in human epidemiological studies. Our findings reveal new insights into the early origins of AHR and provide a tractable model system for future studies to unlock the mechanisms that determine pathogenesis.
Multiple stressors and recruitment failure of long-lived endangered freshwater mussels with a complex life cycle
Authors: Miura Kazuki , Ishiyama Nobuo , Negishi Junjiro N. , Ito Daisetsu , Kawajiri Keita , Izumi Hokuto , Inoue Takahiro , Nakaoka Masahiro , Nakamura Futoshi 
Published: September 2021

AbstractMultiple stressors can interactively affect the population of organisms; however, the process by which they affect recruitment efficiency remains unclear for empirical populations. Recruitment efficiency can be regulated at multiple stages of life, particularly in organisms with complex life cycles. Understanding the interactive effects of multiple stressors on recruitment efficiency and determining the bottleneck life stages is imperative for species conservation.The proportion of <20-year-old juveniles of the endangered freshwater pearl mussel Margaritifera togakushiensis, which has an obligate parasitic larval stage, was investigated in 24 rivers from eastern Hokkaido, northern Japan to reveal the influence of nutrients, fine sediment, and their combined effects on juvenile recruitment efficiency. The following indices for recruitment at adult, parasitic, and post-parasitic juvenile stages were obtained from 11 of these rivers: gravid female density, glochidia density (the number of glochidia infections per stream area), and juvenile survival rate. This study explored the bottleneck stages of recruitment efficiency and the interactive effects of the two stressors on these stages.Twenty-four population status assessments determined that the proportion of juveniles ranged from 0.00 to 0.53, and juveniles were absent from four rivers. The results showed that the parasitic and post-parasitic juvenile stages were bottlenecks for recruitment efficiency. Juvenile survival rates had a more significant positive effect on recruitment efficiency in rivers with a high glochidia density. Juvenile survival rate was decreased by the synergistic interaction of nutrients and fine sediment, although factors limiting glochidia density were not found.The nutrient concentration of rivers in the study region was well explained by the proportion of agricultural land cover and urban areas in the watersheds, but no relationship was detected between fine sediment abundance and land use.This study suggests that nutrient management at a catchment scale can be effective for re-establishing the recruitment of M. togakushiensis, particularly in rivers with a high content of fine sediments. The results also emphasise the importance of considering both parasitic and post-parasitic juvenile stages of mussels to maximise the positive effects of stressor mitigation.
Probing nanomotion of single bacteria with graphene drums
Authors: Rosłoń I.E. , Japaridze A. , Steeneken P.G. , Dekker C. , Alijani F. 
Published: September 2021

AbstractMotion is a key characteristic of every form of life1. Even at the microscale, it has been reported that colonies of bacteria can generate nanomotion on mechanical cantilevers2, but the origin of these nanoscale vibrations has remained unresolved3,4. Here, we present a novel technique using drums made of ultrathin bilayer graphene, where the nanomotion of single bacteria can be measured in its aqueous growth environment. A singleE. colicell is found to generate random oscillations with amplitudes of up to 60 nm, exerting forces of up to 6 nN to its environment. Using mutant strains, we are able to pinpoint the bacterial flagella as the main source of nanomotion. By real-time tracing of changes in nanomotion upon administering antibiotics, we demonstrate that graphene drums can perform antibiotic susceptibility testing with single-cell sensitivity. These findings deepen our understanding of processes underlying cellular dynamics, and pave the way towards high throughput and parallelized rapid screening of the effectiveness of antibiotics in bacterial infections with graphene devices.
Bioactive Hydrogel Microcapsules for Guiding Stem Cell Fate Decisions by Release and Reloading of Growth Factors
Authors: Gwon Kihak , Hong Hye Jin , Gonzalez-Suarez Alan M. , Slama Michael Q. , Choi Daheui , Hong Jinkee , Baskaran Harihara , Stybayeva Gulnaz , Peterson Quinn P. , Revzin Alexander 
Published: September 2021

AbstractHuman pluripotent stem cells (hPSC) hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure. Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols. In this paper, we sought to address these challenges through the development of bioactive microcapsules. A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell. Importantly, the shell contained heparin moieties for growth factor (GF) binding and release. The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation. Specifically, we demonstrated that one-time 1h long loading of pluripotency signals, fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-β1, into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs. Furthermore, stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue, Nodal, resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol. Overall, bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.
piRNAdb: A piwi-interacting RNA database
Authors: Piuco Ricardo , Galante Pedro A. F. 
Published: September 2021

AbstractMotivationFound in several metazoan species, piwi-interacting RNAs (piRNAs) regulate the expression of a wide variety of transposable elements and genes associated with cellular development, differentiation, and growth. Despite their importance, piRNAs are not well known and are still underexplored. To facilitate piRNA research, a comprehensive and easy-to-use piRNA database is still needed.ResultsHere, we present piRNAdb, an integrative and user-friendly database designed to encompass several aspects of piRNAs. We selected piRNAs from four reliable human RNA-sequencing datasets to start our database. After data processing, we displayed these sequences, their genomic location, clustering information, putative targets on known genes and transposable elements, as well as direct links to other databases. In this first release, piRNAdb catalogues 27,329 piRNAs, as well as 23,380 genes that are putative targets and 47,060 associated gene ontology terms, both of which are organized and linked to each respective piRNA. Finally, to improve information exchange and increase the confidence of sequences, a feedback system is provided to users of piRNAdb.ConclusionThe inclusion of new features to facilitate piRNA analyses, data visualization, and integration is the major pillar of piRNAdb. Our main goal was to make this database an easy interface between the data and the user. We believe that this web tool achieves this objective by providing a streamlined and well-organized data repository for piRNAs and that it will be extremely useful to those already studying piRNAs and to the broader community.AvailabilitypiRNAdb is available freely and is compatible with smartphones and tablets: https://www.pirnadb.org/
Computationally-guided tuning of ligand sensitivity in a GPCR-based sensor
Authors: Keri Daniel , Cola Reto B. , Kagiampaki Zacharoula , Tommaso Patriarchi , Barth Patrick 
Published: September 2021

AbstractGenetically-encoded fluorescent sensors for neuromodulators are increasingly used molecular tools in neuroscience. However, these protein-based biosensors are often limited by the sensitivity of the protein scaffold towards endogenous ligands. Here, we explored the possibility of applying computational design approaches for enhancing sensor sensitivity. Using the dopamine sensor dLight1 as proof of concept, we designed two variants that boost the sensor’s potency (EC50) for dopamine and norepinephrine by up to 5- and 15-fold, respectively. Interestingly, the largest effects were obtained through improved designed allosteric transmission in the transmembrane region of the sensor. Our approach should prove generally useful for enhancing sensing capabilities of a large variety of neuromodulator sensors.
Dynamics of fibril collagen remodeling by tumor cells using individual cell-based mathematical modeling
Authors: Poonja Sharan , Damaghi Mehdi , Rejniak Katarzyna A. 
Published: September 2021

AbstractMany solid tumors are characterized by dense extracellular matrix (ECM) composed of various ECM fibril proteins that provide structural support and biological context for the residing cells. The growing tumor cell colonies are capable of remodeling the ECM structure in tumor immediate vicinity to form specific microenvironmental niches. The changes in fibril patterns of the collagen (one of the ECM proteins) surrounding the tumor can be visualized experimentally using both histology and fluorescent imaging. In particular, three diverse tumor associated collagen signatures (TACS) were identified and related to tumor behavior, such as benign growth or invasion. Here we will use an off-lattice hybrid agent-based model (MultiCell-LF) to identify the rules of cell-ECM interactions that guide the development of various patterns of alignment of the ECM fibrils.
Epidemiological rather than macro-economic factors correlate with socioeconomic inequalities in HIV testing in 16 sub-Saharan African countries
Authors: Ante-Testard Pearl Anne , Temime Laura , Jean Kévin 
Published: September 2021

AbstractIn order to reach the first 95 (i.e., 95% of people living with HIV having knowledge of their status) of the 2030 UNAIDS 95-95-95 targets, it is crucial to better understand the contextual or structural factors driving socioeconomic inequalities in HIV testing uptake. It is still unclear whether they are mostly influenced by epidemiological or by macro-economic factors. Here, to shed light on this issue, we measured and decomposed socioeconomic inequalities in HIV testing in sub-Saharan Africa in relation to contextual factors using a novel method, the Recentered Influence Function decomposition method. Indeed, we found that HIV testing uptake was more concentrated among the rich in 12 of 16 sub-Saharan African countries based on population-based surveys. The level of the HIV epidemic seems to drive the level of response of HIV testing programs, rather than the per capita Gross Domestic Product of a country (i.e., national indicator of economic development). Our results suggest that when responding to the HIV epidemic, there is a need to monitor and assess inequalities in addition to monitoring HIV incidence and prevalence.
Predicting Progression Free Survival after Systemic Therapy in Advanced Head and Neck Cancer: Bayesian regression and Model development
Authors: Barber Paul R , Flores-Borja Fabian , Alfano Giovanna , Ng Kenrick , Weitsman Gregory , Dolcetti Luigi , Mustapha Rami , Wong Felix , Vicencio Jose M , Galazi Myria , Opzoomer James W , Arnold James N , Kordasti Shahram , Doyle Jana , Greenberg Jon , Dillon Magnus T , Harrington Kevin J , Forster Martin D , Coolen Anthony C C , Ng Tony 
Published: September 2021

ABSTRACTBackgroundAdvanced Head and Neck Squamous Cell Cancer (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict Progression Free Survival (PFS) with a multivariate risk prediction model.MethodsBlood samples from 56 HNSCC patients were prospectively obtained within a Phase 2 clinical trial (NCT02633800), before and after the first treatment cycle of platinum-based chemotherapy, to identify biological covariates predictive of outcome. A total of 42 baseline covariates were derived pre-treatment, which were combined with 29 covariates after one cycle of treatment. These covariates were ranked and selected by Bayesian multivariate regression to form risk scores to predict PFS, producing “baseline” and “combined” risk prediction models respectively.ResultsThe baseline model comprised of CD33+CD14+ monocytes, Double Negative B cells and age, in a weighted risk signature which predicted PFS with a concordance index (C-index) of 0.661. The combined model composed of baseline CD33+CD14+ monocytes, baseline Tregs, after-treatment changes in CD8 effector memory T cells, CD8 Central memory T cells and CD3 T Cells, along with the hypopharyngeal primary tumor subsite. This weighted risk signature exhibited an improved C-index of 0.757. There was concordance between levels of CD33+CD14+ myeloid cells in tumor tissue, as demonstrated by imaging mass cytometry, and peripheral blood in the same patients. This monocyte subpopulation also had univariate predictive value (log-rank p value = 0.03) but the C-index was inferior to the combined signature.ConclusionsThis immune-based combined multimodality signature, obtained through longitudinal peripheral blood monitoring, presents a novel means of predicting response early on during the treatment course.FundingDaiichi Sankyo Inc, Cancer Research UK, EU IMI2 IMMUCAN, UK Medical Research Council, European Research Council (335326), National Institute for Health Research and The Institute of Cancer Research.
Feasibility, Acceptability, and Barriers to Implementing Select Non-Pharmaceutical Interventions to Reduce the Transmission of Pandemic Influenza - United States, 2019
Authors: Ahmed Faruque , Qualls Noreen , Kowalczyk Shelly , Cunningham Suzanne Randolph , Zviedrite Nicole , Uzicanin Amra 
Published: September 2021

ABSTRACTObjectiveTo assess feasibility and acceptability of implementing non-pharmaceutical interventions (NPIs) reserved for influenza pandemics (voluntary home quarantine; use of face masks by ill persons; childcare facility closures; school closures; and social distancing at schools, workplaces, and mass gatherings), and the availability and usefulness of influenza surveillance data for triggering implementation of NPIs.MethodsPublic health officials in all 50 states, Washington, DC, and 8 territories, and a stratified, random sample of 822 local health departments (LHDs) were surveyed in 2019.ResultsThe response rates for the states/territories and LHDs were 75% (44/59) and 25% (206/822), respectively. About two-thirds to three-fourths of the state/territorial respondents stated that the feasibility and acceptability of implementing the NPIs were high, except for K-12 school closures lasting up to 6 weeks or 6 months. The LHD respondents also indicated that feasibility and acceptability were lowest for prolonged school closures. Compared to LHD respondents in suburban or urban areas, those in rural areas expressed lower feasibility and acceptability. Availability of influenza surveillance data in near real-time was lowest for influenza-like illness and influenza cases in schools.ConclusionsThe findings can provide insights regarding the implementation of NPIs during the Corona Virus Disease 2019 (COVID-19) pandemic.
CAR T cell therapy drives endogenous locoregional T cell dynamics in a responding patient with glioblastoma
Authors: Jonsson Vanessa D. , Ng Rachel H. , Dullerud Natalie , Wong Robyn A. , Hibbard Jonathan , Wang Dongrui , Aguilar Brenda , Starr Renate , Weng Lihong , Alizadeh Darya , Forman Stephen J. , Badie Behnam , Brown Christine E. 
Published: September 2021

AbstractCAR T cell therapy has transformed clinical care and management of patients with certain hematological cancers. However, it remains unclear whether the success of CAR T cell therapy relies solely on CAR T cell engagement with tumor antigen, or if it also requires the stimulation of an individual patient’s endogenous T cell response. Here, we performed combined analysis of longitudinal, single cell RNA and T cell receptor sequencing on glioblastoma tumors, peripheral blood (PB), and cerebrospinal fluid (CSF) from a patient with recurrent multifocal glioblastoma that underwent a remarkable response followed by recurrence on IL13RA2-targeted CAR T cell therapy (Brown et al. 2016). Single cell analysis of a tumor resected prior to CAR T cell therapy revealed the existence of an inflamed tumor microenvironment including a CD8+ cytotoxic, clonally expanded and antigen specific T cell population that disappeared in the recurrent setting. Longitudinal tracking of T cell receptors uncovered distinct T cell dynamics classes in the CSF during CAR T cell therapy. These included T cell clones with transient dynamics, representing intraventricular CAR T cell delivery and endogenous T cell recruitment from the PB into the CSF; and a group of T cells in the cerebrospinal fluid, that tracked with clonally expanded tumor resident T cells and whose dynamics contracted concomitantly with tumor volume. Our results suggest the existence of an endogenous T cell population that was invigorated by intraventricular CAR T cell infusions, and combined with the therapy to produce a complete response.
Mitochondrial stress-induced GDF15-GFRAL axis promotes anxiety-like behavior and CRH-dependent anorexia
Authors: Gil Carla Igual , Coull Bethany M. , Jonas Wenke , Lippert Rachel , Ost Mario , Klaus Susanne 
Published: September 2021

AbstractGrowth differentiation factor 15 (GDF15) is a stress-induced cytokine that modulates food intake and energy metabolism. Until now, most mechanistic studies on GDF15 rely on pharmacological interventions using exogenous GDF15, but little is known about its mode of action when induced both chronically and endogenously. Mitochondrial stress is one of the most described physiological conditions that induces GDF151, and therefore an important model to study the underlying mechanisms of endogenous GDF15’s action. Here, using a mouse model of mitochondrial dysfunction via elevated respiratory uncoupling in skeletal muscle, we show a circadian oscillation of muscle-derived GDF15 to promote a daytime-restricted anorexia without signs of nausea or reduced physical activity, contrary to findings using recombinant GDF152–5. We find that mitochondrial stress-induced GDF15 associates with increased anxiety and hypothalamic corticotropin releasing hormone (CRH) induction, without further activation of the hypothalamic-pituitary-adrenal (HPA) axis and corticosterone response. Strikingly, the daytime-restricted anorexia, lean phenotype, systemic shift in substrate metabolism and anxiety-like behavior are completely abolished in conditions of mitochondrial stress coupled with genetic ablation of the GDF15 receptor GDNF receptor alpha-like (GFRAL), which is predominantly expressed in the hindbrain. Finally, we demonstrate that stress-induced GDF15-GFRAL signaling is required for hypothalamic CRH induction to control diurnal food intake in a CRH-receptor 1 (CRHR1)-dependent manner. With this, we uncover for the first time a molecular target of the GDF15-GFRAL axis that links anxiolytic and anorectic behavior as downstream effects of the chronic activation of this pathway by mitochondrial stress.