bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta-analysis
Authors: McLaughlin John M , Khan Farid , Begier Elizabeth , Swerdlow David L , Jodar Luis , Falsey Ann R
Published: June 2022

Background

Adult respiratory syncytial virus (RSV) vaccines are in the late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making.

Methods

We performed a systematic review and meta-analysis of studies describing the incidence of medically attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab reverse transcription polymerase chain reaction (RT-PCR) results with paired serology (4-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum).

Results

We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100 000 adults ≥65 years of age was 178 (95% CI, 152‒204; n = 8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95% CI, 0‒319; n = 2) emergency department (ED) admissions, and 1519 (95% CI, 1109‒1929; n = 3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100 000 adults age ≥65 years were 267 hospitalizations (uncertainty interval [UI], 228‒306; prospective: 282; model-based: 236), 200 ED admissions (UI, 0‒478), and 2278 outpatient visits (UI, 1663‒2893). Persons <65 years with chronic medical conditions were 1.2−28 times more likely to be hospitalized for RSV depending on risk condition.

Conclusions

The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public health impact.
Tree Peony R2R3-MYB Transcription Factor PsMYB30 Promotes Petal Blotch Formation by Activating the Transcription of the Anthocyanin Synthase Gene
Authors: Luan Yuting , Tang Yuhan , Wang Xin , Xu Cong , Tao Jun , Zhao Daqiu
Published: June 2022

Petal blotches are commonly observed in many angiosperm families and not only influence plant–pollinator interactions but also confer high ornamental value. Tree peony (Paeonia suffruticosa Andr.) is an important cut flower worldwide, but few studies have focused on its blotch formation. In this study, anthocyanins were found to be the pigment basis for blotch formation of P. suffruticosa, and peonidin-3,5-di-O-glucoside (Pn3G5G) was the most important component of anthocyanins, while the dihydroflavonol-4-reductase gene was the key factor contributing to blotch formation. Then, the R2R3-myeloblastosis (MYB) transcription factor PsMYB30 belonging to subgroup 1 was proven as a positive anthocyanin regulator with transcriptional activation and nuclear expression. Furthermore, silencing PsMYB30 in P. suffruticosa petals reduced blotch size by 37.9%, faded blotch color and decreased anthocyanin and Pn3G5G content by 23.6% and 32.9%, respectively. Overexpressing PsMYB30 increased anthocyanin content by 14.5-fold in tobacco petals. In addition, yeast one-hybrid assays, dual-luciferase assays and electrophoretic mobility shift assays confirmed that PsMYB30 could bind to the promoter of the anthocyanin synthase (ANS) gene and enhance its expression. Altogether, a novel MYB transcription factor, PsMYB30, was identified to promote petal blotch formation by activating the expression of PsANS involved in anthocyanin biosynthesis, which provide new insights for petal blotch formation in plants.
The Key to the Future Lies in the Past: Insights from Grain Legume Domestication and Improvement Should Inform Future Breeding Strategies
Authors: Bohra Abhishek , Tiwari Abha , Kaur Parwinder , Ganie Showkat Ahmad , Raza Ali , Roorkiwal Manish , Mir Reyazul Rouf , Fernie Alisdair R , Smýkal Petr , Varshney Rajeev K
Published: June 2022

Crop domestication is a co-evolutionary process that has rendered plants and animals significantly dependent on human interventions for survival and propagation. Grain legumes have played an important role in the development of Neolithic agriculture some 12,000 years ago. Despite being early companions of cereals in the origin and evolution of agriculture, the understanding of grain legume domestication has lagged behind that of cereals. Adapting plants for human use has resulted in distinct morpho-physiological changes between the wild ancestors and domesticates, and this distinction has been the focus of several studies aimed at understanding the domestication process and the genetic diversity bottlenecks created. Growing evidence from research on archeological remains, combined with genetic analysis and the geographical distribution of wild forms, has improved the resolution of the process of domestication, diversification and crop improvement. In this review, we summarize the significance of legume wild relatives as reservoirs of novel genetic variation for crop breeding programs. We describe key legume features, which evolved in response to anthropogenic activities. Here, we highlight how whole genome sequencing and incorporation of omics-level data have expanded our capacity to monitor the genetic changes accompanying these processes. Finally, we present our perspective on alternative routes centered on de novo domestication and re-domestication to impart significant agronomic advances of novel crops over existing commodities. A finely resolved domestication history of grain legumes will uncover future breeding targets to develop modern cultivars enriched with alleles that improve yield, quality and stress tolerance.
Universal critical behavior of transition to chaos: Intermittency route
Authors: Okubo Ken-ichi , Umeno Ken
Published: June 2022

The robustness of the universality class concept of the chaotic transition was investigated by analytically obtaining its critical exponent for a wide class of maps. In particular, we extended the existing one-dimensional chaotic maps, thereby generalizing the invariant density function from the Cauchy distribution by adding one parameter. This generalization enables the adjustment of the power exponents of the density function and superdiffusive behavior. We proved that these generalized one-dimensional chaotic maps are exact (a stronger condition than ergodicity) to obtain the critical exponent of the Lyapunov exponent from the phase average. Furthermore, we proved that the critical exponent of the Lyapunov exponent is $\frac{1}{2}$ regardless of the power exponent of the density function and is thus universal. This result can be considered as rigorous proof of the universality of the critical exponent of the Lyapunov exponent for a countably infinite number of maps.
An amelogenin-based peptide hydrogel promoted the odontogenic differentiation of human dental pulp cells
Authors: Li Xinxin , Yu Zhaoxia , Jiang Shihui , Dai Xiaohua , Wang Guanhua , Wang Yue , Yang Zhimou , Gao Jie , Zou Huiru
Published: June 2022

Amelogenin can induce odontogenic differentiation of human dental pulp cells (HDPCs), which has great potential and advantages in dentine-pulp complex regeneration. However, the unstability of amelogenin limits its further application. This study constructed amelogenin self-assembling peptide hydrogels (L-gel or D-gel) by heating-cooling technique, investigated the effects of these hydrogels on the odontogenic differentiation of HDPCs and explored the underneath mechanism. The critical aggregation concentration, conformation, morphology, mechanical property and biological stability of the hydrogels were characterized, respectively. The effects of the hydrogels on the odontogenic differentiation of HDPCs were evaluated via alkaline phosphatase activity measurement, quantitative reverse transcription polymerase chain reaction, western blot, Alizarin red staining and scanning electron microscope. The mechanism was explored via signaling pathway experiments. Results showed that both the L-gel and D-gel stimulated the odontogenic differentiation of HDPCs on both Day 7 and Day 14, while the D-gel showed the highest enhancement effects. Meanwhile, the D-gel promoted calcium accumulation and mineralized matrix deposition on Day 21. The D-gel activated MAPK-ERK1/2 pathways in HDPCs and induced the odontogenic differentiation via ERK1/2 and transforming growth factor/smad pathways. Overall, our study demonstrated that the amelogenin peptide hydrogel stimulated the odontogenic differentiation and enhanced mineralization, which held big potential in the dentine-pulp complex regeneration.
Linking Salience Signaling With Early Adversity and Affective Distress in Individuals at Clinical High Risk for Psychosis: Results From an Event-Related fMRI Study
Authors: Millman Zachary B , Schiffman Jason , Gold James M , Akouri-Shan LeeAnn , Demro Caroline , Fitzgerald John , Rakhshan Rouhakhtar Pamela J , Klaunig Mallory , Rowland Laura M , Waltz James A
Published: June 2022

Evidence suggests dysregulation of the salience network in individuals with psychosis, but few studies have examined the intersection of stress exposure and affective distress with prediction error (PE) signals among youth at clinical high-risk (CHR). Here, 26 individuals at CHR and 19 healthy volunteers (HVs) completed a monetary incentive delay task in conjunction with fMRI. We compared these groups on the amplitudes of neural responses to surprising outcomes—PEs without respect to their valence—across the whole brain and in two regions of interest, the anterior insula and amygdala. We then examined relations of these signals to the severity of depression, anxiety, and trauma histories in the CHR group. Relative to HV, youth at CHR presented with aberrant PE-evoked activation of the temporoparietal junction and weaker deactivation of the precentral gyrus, posterior insula, and associative striatum. No between-group differences were observed in the amygdala or anterior insula. Among youth at CHR, greater trauma histories were correlated with stronger PE-evoked amygdala activation. No associations were found between affective symptoms and the neural responses to PE. Our results suggest that unvalenced PE signals may provide unique information about the neurobiology of CHR syndromes and that early adversity exposure may contribute to neurobiological heterogeneity in this group. Longitudinal studies of young people with a range of risk syndromes are needed to further disentangle the contributions of distinct aspects of salience signaling to the development of psychopathology.
A new perspective on the evolution and diversity of the genus Amdoparvovirus (family Parvoviridae) through genetic characterization, structural homology modeling, and phylogenetics
Authors: Canuti Marta , Pénzes Judit J , Lang Andrew S
Published: June 2022

Amdoparvoviruses (genus Amdoparvovirus, family Parvoviridae) are primarily viruses of carnivorans, but recent studies have indicated that their host range might also extend to rodents and chiropterans. While their classification is based on the full sequence of the major nonstructural protein (NS1), several studies investigating amdoparvoviral diversity have been focused on partial sequences, leading to difficulties in accurately determining species demarcations and leaving several viruses unclassified. In this study, while reporting the complete genomic sequence of a novel amdoparvovirus identified in an American mink (British Columbia amdoparvovirus, BCAV), we studied the phylogenetic relationships of all amdoparvovirus-related sequences and provide a comprehensive reevaluation of their diversity and evolution. After excluding recombinant sequences, phylogenetic and pairwise sequence identity analyses allowed us to define fourteen different viruses, including the five currently classified species, BCAV, and four additional viruses that fulfill the International Committee on Taxonomy of Viruses criteria to be classified as species. We show that the group of viruses historically known as Aleutian mink disease virus (species Carnivore amdoparvovirus 1) should be considered as a cluster of at least four separate viral species that have been co-circulating in mink farms, facilitating the occurrence of inter-species recombination. Genome organization, splicing donor and acceptor sites, and protein sequence motifs were surprisingly conserved within the genus. The sequence of the major capsid protein virus protein 2 (VP2) was significantly more conserved between and within species compared to NS1, a phenomenon possibly linked to antibody-dependent enhancement (ADE). Homology models suggest a remarkably high degree of conservation of the spikes located near the icosahedral threefold axis of the capsid, comprising the surface region associated with ADE. A surprisingly high number of divergent amino acid positions were found in the luminal threefold and twofold axes of the capsid, regions of hitherto unknown function. We emphasize the importance of complete genome analyses and, given the marked phylogenetic inconsistencies across the genome, advise to obtain the complete coding sequences of divergent strains. Further studies on amdoparvovirus biology and structure as well as epidemiological and virus discovery investigations are required to better characterize the ecology and evolution of this important group of viruses.
Embryonic heat conditioning in chicks induces transgenerational heat/immunological resilience via methylation on regulatory elements
Authors: Rosenberg Tali , Marco Asaf , Kisliouk Tatiana , Haron Amit , Shinder Dmitry , Druyan Shelly , Meiri Noam
Published: June 2022

The question of whether behavioral traits are heritable is under debate. An obstacle in demonstrating transgenerational inheritance in mammals originates from the maternal environment's effect on offspring phenotype. Here, we used in ovo embryonic heat conditioning (EHC) of first‐generation chicks, demonstrating heredity of both heat and immunological resilience, confirmed by a reduced fibril response in their untreated offspring to either heat or LPS challenge. Concordantly, transcriptome analysis confirmed that EHC induces changes in gene expression in the anterior preoptic hypothalamus (APH) that contribute to these phenotypes in the offspring. To study the association between epigenetic mechanisms and trait heritability, DNA‐methylation patterns in the APH of offspring of control versus EHC fathers were evaluated. Genome‐wide analysis revealed thousands of differentially methylated sites (DMSs), which were highly enriched in enhancers and CCCTC‐binding factor (CTCF) sites. Overlap analysis revealed 110 differentially expressed genes that were associated with altered methylation, predominantly on enhancers. Gene‐ontology analysis shows pathways associated with immune response, chaperone‐mediated protein folding, and stress response. For the proof of concept, we focused on HSP25 and SOCS3, modulators of heat and immune responses, respectively. Chromosome conformational capture (3C) assay identified interactions between their promoters and methylated enhancers, with the strongest frequency on CTCF binding sites. Furthermore, gene expression corresponded with the differential methylation patterns, and presented increased CTCF binding in both hyper‐ and hypomethylated DMSs. Collectively, we demonstrate that EHC induces transgenerational thermal and immunological resilience traits. We propose that one of the mechanisms underlying inheritance depends on three‐dimensional (3D) chromatin reorganization.
The hypoxia‐induced changes in miRNA‐mRNA in RNA‐induced silencing complexes and HIF‐2 induced miRNAs in human endothelial cells
Authors: Moszyńska Adrianna , Jaśkiewicz Maciej , Serocki Marcin , Cabaj Aleksandra , Crossman David K. , Bartoszewska Sylwia , Gebert Magdalena , Dąbrowski Michał , Collawn James F. , Bartoszewski Rafal
Published: June 2022

The cellular adaptive response to hypoxia relies on the expression of hypoxia‐inducible factors (HIFs), HIF‐1 and HIF‐2. HIFs regulate global gene expression changes during hypoxia that are necessary for restoring oxygen homeostasis and promoting cell survival. In the early stages of hypoxia, HIF‐1 is elevated, whereas at the later stages, HIF‐2 becomes the predominant form. What governs the transition between the two HIFs (the HIF switch) and the role of miRNAs in this regulation are not completely clear. Genome‐wide expression studies on the miRNA content of RNA‐induced silencing complexes (RISC) in HUVECs exposed to hypoxia compared to the global miRNA‐Seq analysis revealed very specific differences between these two populations. We analyzed the miRNA and mRNA composition of RISC at 2 h (mainly HIF‐1 driven), 8 h (HIF‐1 and HIF‐2 elevated), and 16 h (mainly HIF‐2 driven) in a gene ontology context. This allowed for determining the direct impact of the miRNAs in modulating the cellular signaling pathways involved in the hypoxic adaptive response. Our results indicate that the miRNA‐mRNA RISC components control the adaptive responses, and this does not always rely on the miRNA transcriptional elevations during hypoxia. Furthermore, we demonstrate that the hypoxic levels of the vast majority of HIF‐1‐dependent miRNAs (including miR‐210‐3p) are also HIF‐2 dependent and that HIF‐2 governs the expression of 11 specific miRNAs. In summary, the switch from HIF‐1 to HIF‐2 during hypoxia provides an important level of miRNA‐driven control in the adaptive pathways in endothelial cells.
LPS stimulation stabilizes HIF‐1α by enhancing HIF‐1α acetylation via the PARP1‐SIRT1 and ACLY‐Tip60 pathways in macrophages
Authors: Chen Qiang , Cui Kun , Zhao Zengqi , Xu Xiang , Liu Yongtao , Shen Yanan , Chen Fan , Mai Kangsen , Ai Qinghui
Published: June 2022

Hypoxia and inflammatory mediators stabilize hypoxia‐inducible factor (HIF)‐1α through posttranslational modifications, such as phosphorylation and succinylation. Here, we identified sirtuin 1 (SIRT1) and 60 kDa Tat‐interactive protein (Tip60)‐mediated acetylation as another critical posttranslational modification that regulates HIF‐1α protein stability under lipopolysaccharide (LPS) stimulation. Mechanistically, DNA damage induced by excessive reactive oxygen species (ROS) activated poly (ADP‐ribose) polymerase 1 (PARP1) to consume oxidized nicotinamide adenine dinucleotide (NAD+). Correspondingly, SIRT1 activity was decreased with the decline in NAD+ levels, resulting in increased HIF‐1α acetylation. LPS also activated the ATP‐citrate lyase (ACLY)‐Tip60 pathway to further enhance HIF‐1α acetylation. Acetylation contributed to HIF‐1α stability and exacerbated LPS‐induced inflammation. Thus, inhibiting HIF‐1α stability by decreasing its acetylation could partly alleviate LPS‐induced inflammation. In conclusion, we revealed the mechanism by which LPS stabilized HIF‐1α by increasing its acetylation via the PARP1‐SIRT1 and ACLY‐Tip60 pathways in fish macrophages. This study may provide novel insights for manipulation of HIF‐1α acetylation as a therapeutic strategy against inflammation from the perspective of acetylation in vertebrates.
Cardiovascular and Pulmonary Research: The Year (2021) in Review
Authors: Ricard Paul E. H. , McHugh Hannah F. , Ramsey Stephen
Published: June 2022

Practitioners need access to and the ability to openly discuss advancement in practice and concepts as they apply to the practice of cardiovascular and pulmonary physical therapy (PT). Lack of accessibility to research literature, limited personal time, or insufficient knowledge to adequately review the breadth of literature published each year can hinder this process. This article provides a limited overview of cardiovascular and pulmonary research published in 2021 that the authors believe most important and relevant or speaks to the volume or trend of current topics in the clinical practice of cardiovascular and pulmonary PT. Each topic area is followed by brief overview of clinical relevance and was open to discussion with the participants present at the 2022 Combined Sections Meeting held on February 4, 2022.
Intradermal Botulinum Toxin A Injection Versus Topical 2% Glycopyrrolate for the Treatment of Primary Facial Hyperhidrosis: A Pilot Study and Review of Literature
Authors: Nofal Eman , Salem Somaia , Khashaba Shrook A.
Published: June 2022

BACKGROUND

Facial hyperhidrosis (HH), a common problem with both cosmetic and psychological impact, interferes with quality of life. Wide range of treatment options is available for HH. Finding the most effective and yet a safe, tolerable option is the main target.

OBJECTIVE

To evaluate and compare clinical efficacy, safety, and tolerability of topical 2% glycopyrrolate versus intradermal Botulinum toxin A injection in facial HH treatment.

MATERIALS AND METHODS

Twenty-four patients with primary facial HH were randomly divided into 2 equal groups: Group A included patients treated by intradermal Botulinum toxin A injection and Group B included patients treated by topical glycopyrrolate gel 2%. Starch iodine test was performed before and after treatment to assess response, along with Hyperhidrosis Disease Severity Scale, Dermatology Life Quality Index (DLQI), and patient satisfaction.

RESULTS

Both modalities showed complete response in 75% of cases with a longer duration of action in botulinum toxin group up to 6 months. Side effects were minor and temporary. Both Hyperhidrosis Disease Severity Scale and DLQI showed statistically significant improvement after treatment.

CONCLUSION

Topical glycopyrrolate 2% showed comparable results to Botulinum toxin A in facial HH treatment with faster onset but shorter duration of action.
The effects of pain science education plus exercise on pain and function in chronic Achilles tendinopathy: a blinded, placebo-controlled, explanatory, randomized trial
Authors: Chimenti Ruth L. , Post Andrew A. , Rio Ebonie K. , Moseley G. Lorimer , Dao Megan , Mosby Hadley , Hall Mederic , de Cesar Netto Cesar , Wilken Jason M. , Danielson Jessica , Bayman Emine O. , Sluka Kathleen A.
Published: June 2022

Exercise is the standard of care for Achilles tendinopathy (AT), but 20% to 50% of patients continue to have pain following rehabilitation. The addition of pain science education (PSE) to an exercise program may enhance clinical outcomes, yet this has not been examined in patients with AT. Furthermore, little is known about how rehabilitation for AT alters the fear of movement and central nervous system nociceptive processing. Participants with chronic AT (N = 66) were randomized to receive education about AT either from a biopsychosocial (PSE) or from a biomedical (pathoanatomical education [PAE]) perspective. Simultaneously, all participants completed an exercise program over 8 weeks. Linear mixed models indicated that there were no differences between groups in (1) movement-evoked pain with both groups achieving a clinically meaningful reduction (mean change [95% CI], PSE: −3.0 [−3.8 to −2.2], PAE = −3.6 [−4.4 to −2.8]) and (2) self-reported function, with neither group achieving a clinically meaningful improvement (Patient-Reported Outcomes Measurement Information System Physical Function-PSE: 1.8 [0.3-3.4], PAE: 2.5 [0.8-4.2]). After rehabilitation, performance-based function improved (number of heel raises: 5.2 [1.6-8.8]), central nervous system nociceptive processing remained the same (conditioned pain modulation: −11.4% [0.2 to −17.3]), and fear of movement decreased (Tampa Scale of Kinesiophobia, TSK-17: −6.5 [−4.4 to −8.6]). Linear regression models indicated that baseline levels of pain and function along with improvements in self-efficacy and knowledge gain were associated with a greater improvement in pain and function, respectively. Thus, acquiring skills for symptom self-management and the process of learning may be more important than the specific educational approach for short-term clinical outcomes in patients with AT.
Delays in Door-to-Diuretic Time and 1-Year Mortality Among Patients With Heart Failure
Authors: Dzikowicz Dillon J. , Pokhrel Bhattarai Sunita , Ng Joyce , Zemanek Arthur L. , Carey Mary G.
Published: June 2022

Background

Achieving prompt euvolemic state in heart failure (HF) is associated with reduced mortality. Time-sensitive metrics such as door-to-diuretic time, or the time between presentation and administration of intravenous diuretics, may be an important facilitator of achieving a faster euvolemic state and reducing mortality.

Objective

The aim of this study was to investigate whether reduced door-to-diuretic time was associated with lower odds of death among hospitalized patients with HF.

Methods

A retrospective chart review of patients with HF admitted to a medical center was performed between 2020 and 2021. Inclusion criteria were an International Classification of Diseases, 10th Revision code for HF with positive Framingham Criteria and the use of intravenous bolus furosemide. Exclusion criteria included ventricular assist devices, dialysis, and ultrafiltration therapy. Data collected from the medical records included demographics, echocardiography, staff notes, and medications. The end point was 1-year all-cause mortality. Descriptive statistics, t tests or median test, and multivariate logistic regression were used to describe the sample, evaluate group differences, and determine odds of mortality, respectively.

Results

Among 160 charts from patients with HF (age, 70 ± 14.4 years; 52%, n = 83, male; 53%, n = 85, ischemic cardiomyopathy; 83%, n = 134, New York Heart Association classes III–IV), 30% (n = 48) died within 1 year. The median diuretic dose was 40 mg (interquartile range, 20 mg), with a median time of administration of 247 minutes (4.12 hours) (interquartile range, 294 minutes to 4.9 hours). After covariate adjustment, prolonged door-to-diuretic time more than doubled (2.22; 95% confidence interval, 1.03–4.8; P = .04) the odds of 1-year mortality.

Conclusions

On the basis of this sample of charts from older highly symptomatic patients with HF, delayed door-to-diuretic time was associated with significantly greater odds of 1-year all-cause mortality.
Nurse Spiritual Care Therapeutics Scale
Authors: Kang Kyung-Ah , Taylor Elizabeth Johnston , Chun Jiyoung
Published: June 2022

Although clinical and empirical literature documents the variety of spiritual care interventions available to palliative care clinicians, the frequency with which they are provided is rarely and inadequately measured. Given the growing interest in implementing spiritual care across Asia, including South Korea, this study sought to cross-culturally validate the Korean version of the Nurse Spiritual Care Therapeutics Scale (NSCTS-K), a scale initially developed in the United States. The World Health Organization process for cross-cultural adaptation of scales and Polit and Yang's process for evaluating validation were implemented. With data from a sample of 252 Korean nurses providing care to patients with life-threatening illnesses, various statistical procedures for evaluating validity and reliability were applied during this cross-sectional, observational study. Exploratory factor analysis for the structural validity of the Korean scale generated 3 factors that accounted for 69.40% of the variance. The Cronbach α was 0.95. The NSCTS-K is one of the few scales available to determine the impact of nurse-provided spiritual care frequency on patient outcomes. Thus, this tool can quantify the frequency of spiritual care better and be used in quality improvement initiatives or palliative care research.
Evaluation of the Efficacy of a Hypoglycemia Protocol to Treat Severe Hypoglycemia
Authors: Gilmore Lisa , Freeman Susan , Amarasekara Sathya , Maza Alfredo , Setji Tracy
Published: June 2022

Purpose

The purpose of this quality improvement project was to evaluate the efficacy of the facility's Hypoglycemia Protocol when treating severe hypoglycemia (defined as blood glucose < 50 mg/dL).

Description

The diabetes clinical nurse specialists conducted a retrospective chart review of diabetic inpatients with severe hypoglycemia who were treated per the Hypoglycemia Protocol from October 1, 2017, through April 30, 2019. The primary outcome was achievement of euglycemia (defined as blood glucose ≥ 80 mg/dL) 15 to 30 minutes post treatment with either oral carbohydrates or intravenous dextrose.

Outcome

Two hundred twenty-two patients received treatment with oral carbohydrates versus 120 patients who received intravenous dextrose. Fifty patients receiving oral carbohydrates versus 106 patients receiving intravenous dextrose achieved euglycemia after 1 treatment. Compared with treatment with intravenous dextrose, the odds ratio of the rise in blood glucose to 80 mg/dL or greater within 15 to 30 minutes post treatment for a patient given oral carbohydrate was decreased by 97.2%.

Conclusion

Intravenous dextrose was more efficacious than oral carbohydrate treatment in patients with diabetes experiencing severe hypoglycemia. In response, the Hypoglycemia Protocol was revised to increase oral carbohydrate treatment for severe hypoglycemia and to expedite escalation from oral to intravenous treatment.
The Agile Clinical Nurse Specialist
Authors: Mamais Fotine , Jasdhaul Maninder , Gawlinski Anna , Lawanson-Nichols Mary , Kao Yuhan , Branom Raquel , Ansryan Lianna Z.
Published: June 2022

Purpose/Objectives

This article describes the contributions of the clinical nurse specialist in navigating the challenges of the COVID-19 pandemic to ensure patient and staff safety while providing science-based quality of care.

Description

The group of clinical nurse specialists using advanced practice knowledge and skills within the 3 spheres of impact (ie, patient, organization, and nurse) developed and implemented strategies that supported frontline clinicians and met emerging organizational needs during the COVID-19 pandemic.

Outcomes

The clinical nurse specialist's agility was imperative in navigating the challenges of the pandemic to ensure the safety of patients and staff by providing strategies and standardization to workflow processes across the organization.

Conclusion

The group's combined clinical expertise and support of frontline nurses positioned the clinical nurse specialist to rapidly escalate the bedside nurse's concerns and provide recommendations to improve workflow while maintaining patient and staff safety.
Factors Associated With Patient Satisfaction Measured Using an Iterative Scale
Authors: Versluijs Yvonne , Fatehi Amirreza , Gonzalez Amanda I. , Reichel Lee , Laverty David , Ring David
Published: June 2022

Background and Objectives:

Patient experience measures tend to have notable ceiling effects that make it difficult to learn from gradations of satisfaction to improve care. This study tested 2 different iterative satisfaction measures after a musculoskeletal specialty care visit in the hope that they might have less ceiling effect. We measured floor effects, ceilings effects, skewness, and kurtosis of both questionnaires. We also assessed patient factors independently associated with the questionnaires and the top 2 possible scores.

Methods:

In this cross-sectional study, 186 patients completed questionnaires while seeing 1 of 11 participating orthopedic surgeons in July and August 2019; the questionnaire measured: (1) demographics, (2) symptoms of depression, (3) catastrophic thinking in response to nociception, (4) heightened illness concerns, and (5) satisfaction with the visit on 2 iterative satisfaction scales. Bivariate and multivariable analyses sought associations of the explanatory variable with the satisfaction scales.

Results:

There is a small correlation between the 2 scales (r = 0.27; P < .001). Neither scale had a floor effect and both had a ceiling effect of 45%. There is a very small correlation between greater health anxiety and lower satisfaction measured with one of the scales (r = −0.16; P = .05).

Conclusion:

An iterative satisfaction questionnaire created some spread in patient experience data, but could not limit ceiling effects. Additional strategies are needed to remove ceiling effects from satisfaction measures.
False Positive Ventilation/Perfusion SPECT/CT Mismatch Mimicking Pulmonary Embolism in a Patient With Bilateral Lung Transplant
Authors: Sandach Patrick , Kleibrink Björn , Maier Sandra , Herrmann Ken , Hautzel Hubertus
Published: June 2022

Ventilation/perfusion SPECT/CT has very high sensitivity with little false-positive findings for diagnosing pulmonary embolism (PE). However, bronchopulmonary tumors or structural changes of the lungs' vasculature infrequently mimic PE. Here, a 59-year-old man presented with acute dyspnea and acute renal failure 5 years after bilateral lung transplant. Pulmonary ventilation/perfusion SPECT/CT was performed demonstrating a lobar mismatch of the left upper lung lobe indicative for PE. Bronchoscopy revealed local hyperemia of this lobe, indicating prolonged venous blood return. Subsequent CT angiography confirmed postsurgical upper pulmonary vein obliteration as final diagnosis. In conclusion, pulmonary vein obliteration might cause false-positive ventilation/perfusion SPECT/CT.
A Systematic Review on COVID-19 Vaccine preferences using Discrete Choice Experiments
Authors: Amani Adidja , Selenguai Helen Kamo , Puepi Yolande Djike , Dairou Iyale Astadjam , Kenmoe Sebastien , Nouko Ariane , Fabrice Zobel Cheuyem Lekeumo , Ngo Um Suzanne Sap , Koki Ndombo Paul Olivier , Mbacham Wilfried , Ongolo-Zogo Pierre
Published: June 2022

Objective

To determine the attributes of COVID-19 vaccines that influence vaccine acceptance using a DCE through a systematic review.

Methods

A systematic search was carried out for articles published up to November 2021 in the PubMed, Psycinfo, Embase, Web of Science, and Global Index Medicus databases. The electronic search algorithm consisted of the terms (Covid-19) AND (Vaccine) AND (discrete choice experiment).

Findings

A total of 39 records were retrieved of which 18 duplicates were identified and removed. Of the remaining 21 records, 10 were excluded because they did not use a DCE approach. 11 studies were included in the meta-analyses with a total of 42 795 participants from three WHO regions. We examined 13 attributes of COVID-19 vaccine that influenced acceptance; cost, vaccine efficacy, number of doses, risk of side effects, proof of vaccination, vaccination setting, duration of immunity, doctor’s recommendation, proportion of acquaintances vaccinated, region of vaccine manufacture, background knowledge of herd immunity, life attenuated or mRNA, speed of vaccination development. The four attributes reported to influence COVID-19 vaccine preferences most worldwide were; high vaccine efficacy, low risk of side effects, long duration of immunity and low number of doses of the vaccine.

Conclusion

The most preferred COVID-19 vaccine attributes should be taken into account by vaccine manufacturers and public health policy makers for better introduction and acceptance of COVID-19 vaccine to the world.
Energy Landscapes from Cryo-EM Snapshots: A Benchmarking Study
Authors: Dsouza Raison , Mashayekhi Ghoncheh , Etmaadpour Roshanak , Schwander Peter , Ourmazd Abbas
Published: June 2022

Biomolecules undergo complex continuous conformational motions, a subset of which are functionally relevant. Understanding, and ultimately controlling biomolecular function are predicated on the ability to map continuous conformational motions and identify the functionally relevant conformational trajectories. For equilibrium and near-equilibrium processes, the function proceeds along minimum-energy pathways on one or more energy landscapes, because higher-energy conformations are only weakly occupied. With the growing interest in identifying functional trajectories on energy landscapes, the reliable mapping of energy landscapes has become paramount. In response, various data-analytical tools for determining structural variability are emerging. A key question concerns the veracity with which each data-analytical tool can extract functionally relevant conformational trajectories from a collection of singleparticle cryo-EM snapshots. Using synthetic data as an independently known ground truth, we benchmark the ability of four leading algorithms to determine biomolecular energy landscapes and identify the functionally relevant conformational paths on these landscapes. Such benchmarking is essential for systematic progress toward atomic-level movies of continuous biomolecular function.
Towards robust and generalizable super-resolution generative adversarial networks for magnetic resonance neuroimaging: a cross-population approach
Authors: Förster Leona Charlotte , da Costa Campos Lucas , Kocher Martin , Caspers Svenja
Published: June 2022

Magnetic resonance imaging (MRI) is fundamental to neuroscience, where detailed structural brain scans improve clinical diagnoses and provide accurate neuroanatomical information. Apart from time-consuming scanning protocols, higher image resolution can be obtained with super resolution algorithms. We investigated the generalization abilities of Super Resolution Generative Adversarial Neural Networks (SRGANs) across different populations. T1-weighted scans from three large cohorts were used, spanning older subjects, newborns, and patients with brain tumor- or treatment-induced tissue changes. Upsampling quality was validated using synthetic and anatomical metrics. Models were first trained on each cohort, yielding high image quality and anatomical fidelity. When applied across cohorts, no artifacts were introduced by the SRGANs. SRGANs that were trained on a dataset combining all cohorts also did not induce any population-based artifacts. We showed that SRGANs provide a prime example of robust AI, where application on unseen populations did not introduce artifacts due to training data bias (e.g., insertion or removal of tumor-related signals and contrast inversion). This is an important step in the deployment of SRGANs in real-world settings.
Shaping Sounds with P300 Based Brain-Computer Musical Interface
Authors: Akkaya Uğur Can , Demirel Çağatay , de Lautour Reuben , İnce Gökhan
Published: June 2022

This paper describes the development and testing of a brain-computer musical interface (BCMI) that allows a user to select and transform one element of a musical texture by paying attention to that particular element. In order to realize the BCMI system mentioned, a comprehensive testing scheme was established which uses auditory evoked potentials to elicit P300 waves via averaging various types of stimuli. Resented sound stimuli were divided into multi-channel speaker setups to have better localization of user-focused sound stimuli. A sound synthesis model was developed for transforming its sound texture based on neural oscillations that were categorized with the help of a self-organizing map algorithm. In addition, an artificial neural network was used to predict the possible P300 waves that show the attentional focus of a subject. Most of the P300 waves were classified successfully for most of the participants. Promising results were achieved concerning the developed BCMI system. A neural network model was also utilized to predict the possible P300 waves, which show the subject’s selective attention. The majority of the participants were able to correctly classify P300 waves. The proposed BCMI system yielded promising results.
Lymphatic dysfunction in lupus contributes to cutaneous photosensitivity and lymph node B cell responses
Authors: Ambler William G. , Howlander Mir , Chalasani Madhavi Latha S. , Seltzer Ethan S. , Sim JiHyun , Shin Jinyeon , Schwartz Noa , Shipman William D , Dasoveanu Dragos , Carballo Camila B. , Sevim Ecem , Siddique Salma , Rodeo Scott , Erkan Doruk , Kataru Raghu P. , Mehrara Babak , Lu Theresa T.
Published: June 2022

Photosensitivity in lupus and subsequent systemic disease flares contribute to disease burden and is incompletely understood. Skin communicates with lymphoid tissues via lymphatics and reduced lymphatic flow in murine models results in skin inflammation and autoimmunity. Here, we demonstrate that the skin of lupus patients and multiple murine lupus models are characterized by lymphatic flow dysfunction. Improving lymphatic flow in murine lupus models via manual lymphatic drainage or by utilizing a transgenic model with increased lymphatics ameliorated cutaneous photosensitivity and diminished draining lymph node germinal center B cell and plasmablast responses. Improved lymphatic flow limited B cell responses via acting on a stromal-immune circuit previously described by our lab. Increased lymphatic flow increases stromal CCL2, which modulates monocyte function and limits B cell responses. This work provides a link between cutaneous photosensitivity and systemic disease in lupus and suggests that improving lymphatic flow or targeting the lymph node microenvironment could be potential therapeutic targets.
Notch-1 mediates Epithelial-Mucosal Healing during Murine Colitis Recovery Phase
Authors: Luthra Latika , Patel Sahil R. , Bian Zhen , Liu Yuan , Merlin Didier , Garg Pallavi
Published: June 2022

Inflammatory bowel disease (IBD) is marked by inflammation mediated epithelial-mucosal damage. The intestinal epithelial forms a tight barrier displaying two contrasting functions: restricting the entry of potentially harmful substances while, on the other hand allowing the selective passage of nutrients. The damaged epithelial-mucosal barrier causes the exposure of mucosa layers to luminal inflammatory contents. This eventually leads to the leaky epithelium, exposing the immune cells, release of various cytokines, and results in loss of epithelial homeostasis. Therefore, maintenance of healthy epithelial-mucosal lining is critical during IBD recovery. Notch signaling is an evolutionarily conserved molecular pathway crucial for the development and homeostasis of most tissues. Notably, the deregulation of Notch signaling is involved in IBD (Ulcerative colitis and Crohn’s disease). Notch signaling also plays a vital role in wound healing and tissue repair. Here, we investigated the role of Notch-1 signaling in wound healing and regeneration of colonic epithelium during colitis recovery phase by using conditional deletion of Notch-1 in colonic epithelium of mice. We used colonic carcinoma cell line HCT116 transiently transfected with Notch1 intracellular domain (NICD) to support in vivo data. We observed that deletion of Notch1 among mice was associated with compromised healing after colitis. Therefore, targeting the Notch-1 pathway might provide a novel therapeutic strategy for the patients recovering from colitis.
Evidence for grid-cell-related activity in the time domain
Authors: Peters-Founshtein Gregory , Dafni-Merom Amnon , Monsa Rotem , Arzy Shahar
Published: June 2022

The relation between the processing of space and time in the brain has been an enduring cross-disciplinary question. Grid cells have been recognized as a hallmark of the mammalian navigation system, with recent studies attesting to their involvement in organization of conceptual knowledge in humans. To determine whether grid-cell-like representations support temporal processing, we asked subjects to mentally simulate changes in age and time-of-day, each constituting “trajectory” in an age-day space, while undergoing fMRI. We found that grid-cell-like representations supported trajecting across this age-day space. Furthermore, brain regions concurrently coding past-to-future orientation positively modulated the magnitude of grid-cell-like representation in the left entorhinal cortex. Our findings suggest that temporal processing may be supported by spatially modulated systems, and that innate regularities of abstract domains may interface and alter grid-cell-like representations, similarly to spatial geometry.
Hepatocellular carcinoma hosts immature neurons and cholinergic tumors that correlate with adverse molecular features and outcomes
Authors: Hernandez Charlotte A. , Verzeroli Claire , Chicherova Ievgeniia , Farca-Luna Abud-José , Tonon Laurie , Bellaud Pascale , Turlin Bruno , Fautrel Alain , Macek-Jilkova Zuzana , Decaens Thomas , Rebouissou Sandra , Viari Alain , Zoulim Fabien , Parent Romain
Published: June 2022

Background & aims

The unexplained interpatient variation in hepatocellular carcinoma (HCC) remains a major challenge. We aimed at addressing the under-explored association between the disease and the hepatic autonomic nervous system (ANS).

Methods & Results

We in-depth characterized the innervation of French biobanks HCC samples by conventional biochemistry methods. We also applied bioinformatics approaches to the TCGA dataset in order to stratify samples according to neural features and molecular correlates. We highlighted the predominant parasympathetic polarity of HCC nerves, and demonstrated that a cirrhotic rat model of aggressive HCC hosts liver neurogenesis with cholinergic features. Using the TCGA dataset, we then defined an HCC neural signature, derived from adrenergic and cholinergic receptor levels, that allowed patient stratification into two classes. Cholinergic tumors correlated with TP53 mutations (p ≤ 0.05), shorter progression-free interval (PFI) and overall survival (OS), displayed more pathogenic molecular traits (e.g., AFP-rich, proliferative tumors, mitotic functions including DNA repair, EMT, Ras, and Akt/mTOR pathways), aggressive HCC signatures and B cell accumulation. Instead, adrenergic tumors, predominant in patients aged >60 and with mutated CTNNB1, were correlated with better OS and PFI (p < 0.05), and numerous immune pathways.

Conclusions

Our results depict neural features of HCC and how the existing tumor classification may also be shaped by neural inputs. Altogether, we show that the parasympathetic branch of the ANS is implicated in the pathobiology of HCC, and advocate for the use of ANS-targeting drugs in HCC research, many of which are clinically safe and well characterized.
The differential metabolic signature of breast cancer cellular response to olaparib treatment
Authors: Berardi Domenica , Hunter Yasmin , van den Driest Lisa , Farrell Gillian , Rattray Nicholas J W , Rattray Zahra
Published: June 2022

Metabolic reprogramming and genomic instability are key hallmarks of cancer, the combined analysis of which has gained recent popularity. Given the emerging evidence indicating the role of oncometabolites in DNA damage repair and its routine use in breast cancer treatment, it is timely to fingerprint the impact of olaparib treatment in cellular metabolism. Here, we report the biomolecular response of breast cancer cell lines with DNA damage repair defects to olaparib exposure.

Following evaluation of olaparib sensitivity in breast cancer cell lines, we immunoprobed DNA double strand break foci and evaluated changes in cellular metabolism at various olaparib treatment doses using untargeted mass spectrometry-based metabolomics analysis. Following identification of altered features, we performed pathway enrichment analysis to measure key metabolic changes occurring in response to olaparib treatment.

We show a cell-line dependent response to olaparib exposure, and an increased susceptibility to DNA damage foci accumulation in triple-negative breast cancer cell lines. Metabolic changes in response to olaparib treatment were cell-line and dose-dependent, where we predominantly observed metabolic reprogramming of glutamine-derived amino acids and lipids metabolism.

Our work demonstrates the effectiveness of combining molecular biology and metabolomics studies for the comprehensive characterisation of cell lines with different genetic profiles. Follow-on studies are needed to map the baseline metabolism of breast cancer cells and their unique response to drug treatment. Fused with genomic and transcriptomics data, such readout can be used to identify key oncometabolites and inform the rationale for the design of novel drugs or chemotherapy combinations.