bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Tissue Histology for the Injectable Cellulite Treatment Collagenase Clostridium Histolyticum-aaes: Results in Swine
Authors: Shridharani Sachin M , Vijayan Saji , Napekoski Karl M , Dalton Shannon R , Bhatia Ashish C
Published: April 2023

Background

Cellulite is a common aesthetic condition that affects predominantly females. Collagenase clostridium histolyticum-aaes (CCH-aaes) injections disrupt native collagen structures, resulting in an improvement in cellulite appearance. However, injection-site bruising is a frequently occurring adverse event with CCH-aaes treatment.

Objectives

To characterize tissue histology following CCH-aaes injection in Yorkshire pigs.

Methods

In an animal study, female swine with 10 defined dosing sites on the ventral-lateral aspect received 1 or 2 CCH-aaes (0.07 mg/0.3 mL) or placebo subcutaneous injections at a single site at designated time points before tissue sampling.

Results

Injection with CCH-aaes was associated with lysis of mature, collagen-rich septa in the subcutaneous layer at and adjacent to the injection site as early as Day 1. On Day 4, an increase in inflammatory cells and a decrease in hemorrhage (vs Day 2) were observed, with inflammation and hemorrhage decreased by Day 8. By Day 21, deposition of new collagen and reorganization of fat lobules were observed. Observations with repeat CCH-aaes treatment were comparable with 1 course of CCH-aaes treatment.

Conclusions

In this animal study, targeted enzymatic subcision of collagenous bands and remodeling of subcutaneous tissue were observed following CCH-aaes injection.

Level of Evidence: 3
Vocal performance increases rapidly during the dawn chorus in Adelaide’s warbler (Setophaga adelaidae)
Authors: Vazquez-Cardona Juleyska , Bonnell Tyler R , Mower Peter C , Medina Orlando J , Jiskoot Hester , Logue David M
Published: April 2023

Many songbirds sing intensely during the early morning, resulting in a phenomenon known as the dawn chorus. We tested the hypothesis that male Adelaide’s warblers (Setophaga adelaidae) warm up their voices during the dawn chorus. If warming up the voice is one of the functions of the dawn chorus, we predicted that vocal performance would increase more rapidly during the dawn chorus compared to the rest of the morning and that high song rates during the dawn chorus period contribute to the increase in vocal performance. The performance metrics recovery time, voiced frequency modulation, and unvoiced frequency modulation were low when birds first began singing, increased rapidly during the dawn chorus, and then leveled off or gradually diminished after dawn. These changes are attributable to increasing performance within song types. Reduction in the duration of the silent gap between notes is the primary driver of improved performance during the dawn chorus. Simulations indicated that singing at a high rate during the dawn chorus period increases performance in two of the three performance measures (recovery time and unvoiced frequency modulation) relative to singing at a low rate during this period. These findings are consistent with the hypothesis that vocal warm-up is one benefit of participation in the dawn chorus.
Machine learning for RNA 2D structure prediction benchmarked on experimental data
Authors: Justyna Marek , Antczak Maciej , Szachniuk Marta
Published: April 2023

Since the 1980s, dozens of computational methods have addressed the problem of predicting RNA secondary structure. Among them are those that follow standard optimization approaches and, more recently, machine learning (ML) algorithms. The former were repeatedly benchmarked on various datasets. The latter, on the other hand, have not yet undergone extensive analysis that could suggest to the user which algorithm best fits the problem to be solved. In this review, we compare 15 methods that predict the secondary structure of RNA, of which 6 are based on deep learning (DL), 3 on shallow learning (SL) and 6 control methods on non-ML approaches. We discuss the ML strategies implemented and perform three experiments in which we evaluate the prediction of (I) representatives of the RNA equivalence classes, (II) selected Rfam sequences and (III) RNAs from new Rfam families. We show that DL-based algorithms (such as SPOT-RNA and UFold) can outperform SL and traditional methods if the data distribution is similar in the training and testing set. However, when predicting 2D structures for new RNA families, the advantage of DL is no longer clear, and its performance is inferior or equal to that of SL and non-ML methods.
Benchmarking of analytical combinations for COVID-19 outcome prediction using single-cell RNA sequencing data
Authors: Cao Yue , Ghazanfar Shila , Yang Pengyi , Yang Jean
Published: April 2023

The advances of single-cell transcriptomic technologies have led to increasing use of single-cell RNA sequencing (scRNA-seq) data in large-scale patient cohort studies. The resulting high-dimensional data can be summarized and incorporated into patient outcome prediction models in several ways; however, there is a pressing need to understand the impact of analytical decisions on such model quality. In this study, we evaluate the impact of analytical choices on model choices, ensemble learning strategies and integrate approaches on patient outcome prediction using five scRNA-seq COVID-19 datasets. First, we examine the difference in performance between using single-view feature space versus multi-view feature space. Next, we survey multiple learning platforms from classical machine learning to modern deep learning methods. Lastly, we compare different integration approaches when combining datasets is necessary. Through benchmarking such analytical combinations, our study highlights the power of ensemble learning, consistency among different learning methods and robustness to dataset normalization when using multiple datasets as the model input.
Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation
Authors: Domingues Rafael R , Wiltbank Milo C , Hernandez Laura L
Published: April 2023

Maternal use of antidepressants has increased throughout the last decades; selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressants. Despite the widespread use of SSRI by women during reproductive age and pregnant women, an increasing amount of research warns of possible detrimental effects of maternal use of SSRI during pregnancy including low birthweight/small for gestational age and preterm birth. In this review, we revisited the impact of maternal use of SSRI during pregnancy, its impact on serotonin homeostasis in the maternal and fetal circulation and the placenta, and its impact on pregnancy outcomes—particularly intrauterine growth restriction and preterm birth. Maternal use of SSRI increases maternal and fetal serotonin. The increase in maternal circulating serotonin and serotonin signaling likely promotes vasoconstriction of the uterine and placental vascular beds decreasing blood perfusion to the uterus and consequently to the placenta and fetus with potential impact on placental function and fetal development. Several adverse pregnancy outcomes are similar between women, sheep, and rodents (decreased placental size, decreased birthweight, shorter gestation length/preterm birth, neonatal morbidity, and mortality) highlighting the importance of animal studies to assess the impacts of SSRI. Herein, we address the complex interactions between maternal SSRI use during gestation, circulating serotonin, and the regulation of blood perfusion to the uterus and fetoplacental unit, fetal growth, and pregnancy complications.
Shared decision-making and satisfaction with care: a population-based study in patients with acne with skin of colour in the USA
Authors: Kingston Paige , Yee Danielle , Huang Margaret Y , Korouri Edwin , Peterson Hannah , Lee Kathryn  , Agüero Rosario , Armstrong April W
Published: April 2023

Little is known about differences in shared decision-making and patient satisfaction with acne care among different ethnicities and races. We conducted a cross-sectional study to determine differences between patients with acne who are White and those with skin of colour (SOC), i.e. (i) engagement in shared decision-making, and (ii) patient satisfaction with care, using the 2009–2017 and 2019 Medical Panel Expenditure Survey. Patients with acne with SOC were nearly two times more likely to engage in high shared decision-making compared with White patients [adjusted odds ratio 1.80, 95% confidence interval (CI) 1.30–2.51, P < 0.001]. Patients with SOC with acne reported lower satisfaction with care compared with White patients (β = –0.38, 95% CI –0.69 to –0.06, P = 0.02). Patients with SOC who had acne reported higher levels of shared decision-making than White patients. However, compared with the White patients, patients with SOC report lower satisfaction with their care. There may be other factors contributing to lower satisfaction with care in patients with SOC who have acne.
Chronos: An Efficient Asynchronous Byzantine Ordered Consensus
Authors: Zhang Zongyang , Zhang Lingyue , Wang Zhuo , Li Yichen , Lu Rongxing , Yu Yong
Published: April 2023

Byzantine ordered consensus, introduced by Zhang et al. (OSDI 2020), is a new consensus primitive that additionally guarantees a correctness specification of transaction order, allowing nodes to assign fairly an ordering indicator to the committed transaction. Zhang et al. also presented a concrete Byzantine ordered consensus protocol called Pompē in the partially synchronous network model. However, Pompē cannot prevent an adversary from manipulating message delivery time. In this paper, we present Chronos, the first Byzantine ordered consensus protocol in the asynchronous network model, where an adversary can arbitrarily manipulate message delivery time. To construct Chronos, we propose a variant of asynchronous common subset called signal asynchronous common subset protocol, which guarantees the liveness of Chronos. We implement both Chronos and its baseline HoneyBadgerBFT using Go language and deploy them on 100 Amazon t3.medium instances distributed throughout 10 regions across the world. The experimental results show that Chronos is more efficient than HoneyBadgerBFT for small network, achieving peak throughput of 59 368 tx/s when the batch size is 100 000 and the number of nodes is 4, while the peak of HoneyBadgerBFT is 57 077 tx/s.
Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort
Authors: Gürgöze Muhammed T , Akkerhuis K Martijn , Oemrawsingh Rohit M , Umans Victor A W M , Kietselaer Bas , Schotborgh Carl E , Ronner Eelko , Lenderink Timo , Aksoy Ismail , van der Harst Pim , Asselbergs Folkert W , Maas Arthur C , Oude Ophuis Anton J , Krenning Boudewijn , de Winter Robbert J , The Salem H K , Wardeh Alexander J , Hermans Walter R M , Cramer G Etienne , van Gorp Ina , de Rijke Yolanda B , van Schaik Ron H N , Boersma Eric
Published: April 2023

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical Trial Registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.
Bridge to recovery using an Impella 2.5 device in a 3-year-old child
Authors: Kuschnerus Kira , Starck Christoph , Potapov Evgenij , Cho Mi-Young
Published: April 2023

Mechanical support options for children and small adolescents with acute left ventricular failure are often limited to extracorporeal life support (ECLS) and subsequent left ventricular assist device implantation. We report a case of a 3-year-old child weighing 12 kg with acute humoral rejection after cardiac transplantation not adequately responding to medical therapy who presented in persistent low cardiac output syndrome. We successfully stabilized the patient by implanting a Impella 2.5 device via a 6-mm Hemashield prosthesis on the right axillary artery. The patient was bridged to recovery.
Association of body mass index with 30-day mortality and red blood cell transfusions in open heart surgery
Authors: Räsänen Jenni , Ellam Sten , Hartikainen Juha , Juutilainen Auni , Halonen Jari
Published: April 2023

OBJECTIVES

Obesity is associated with increased burden of cardiovascular risk factors, morbidity and mortality. However, several studies have counterintuitively shown better outcome after cardiac surgery in obese than in normal weight patients, a phenomenon known as obesity paradox. Furthermore, obesity has been linked with decreased need of red blood cell (RBC) transfusions. The purpose of this study was to evaluate the impact of body mass index (BMI) on 30-day mortality and RBC transfusions in patients undergoing cardiac surgery, a clinically important topic with conflicting previous data.

METHODS

We retrospectively investigated 1691 patients who underwent coronary and/or valve or aortic root surgery using cardiopulmonary bypass between 2013 and 2016. The patients were categorized by BMI based on the World Health Organization classification. For analysis, logistic regression was used with adjustment for potential confounding factors.

RESULTS

Of the patients, 28.7% were normal weight, 43.3% overweight, 20.5% mildly obese and 7.5% severely obese. Thirty-day mortality was 1.9% without significant differences between the BMI groups. 41.0% of patients received RBC transfusion. Overweight [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.56–0.99, P = 0.045], mildly (OR 0.65, 95% CI 0.46–0.92, P = 0.016) and severely obese (OR 0.41, 95% CI 0.24–0.70, P = 0.001) patients needed less frequently RBC transfusions than patients with normal weight.

CONCLUSIONS

Obesity was not associated with 30-day mortality but was associated with lower use of RBC transfusions in cardiac surgery.
The relationship of income on stroke incidence in Finland and China
Authors: Yao Honghui , Junna Liina , Hu Yaoyue , Sha Xinping , Martikainen Pekka
Published: April 2023

Background

Stroke incidence has continued to increase recently in most countries. The roles of individual-level income on the incidence of overall stroke and its subtypes are still unknown, especially in low- and middle-income countries and the cross-national evidence is also limited. We explored the association between individual-level income and stroke incidence in Finland and China.

Methods

Changde Social Health Insurance Database (N=571 843) and Finnish population register (N=4 046 205) data were used to calculate standard stroke incidence rates, which were employed to assess the absolute incidence difference between income quintiles. Cox regression was used to compare income differences in first-ever stroke incidence.

Results

The highest income quintile had lower overall and subtype stroke incidence when compared to lower-income quintiles. The relative difference was more evident in hemorrhagic stroke incidence. After adjusting for age and employment status, the disparity of stroke incidence between the lowest and highest income quintiles was high among both men and women and in Finland and China. The disparity was particularly notable among men: in Finland, the hazard ratio (HR) for hemorrhagic stroke was 0.633 [95% confidence interval (95% CI) 0.576–0.696] and HR 0.572 (95% CI 0.540–0.606) for ischemic stroke. The respective figures were HR 0.452 (95% CI 0.276–0.739) and HR 0.633 (95% CI 0.406–0.708) for China.

Conclusions

Individual-level income is related to overall and subtype stroke incidence. Future studies should explore the causal relationship between individual-level income and stroke incidence.
Epidemiology of bacterial co-infections and risk factors in COVID-19-hospitalized patients in Spain: a nationwide study
Authors: López-Herrero R , Sánchez-de Prada L , Tamayo-Velasco A , Lorenzo-López M , Gómez-Pesquera E , Sánchez-Quirós B , de la Varga-Martínez O , Gómez-Sánchez E , Resino S , Tamayo E , Álvaro-Meca A
Published: April 2023

Background

We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome.

Methods

Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model.

Results

The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second.

Conclusions

Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.
Pain Management in Older Adults Before and During the First Year of COVID-19 Pandemic: Prevalence, Trends, and Correlates
Authors: Manhapra Ajay , Fortinsky Richard H , Berg Karina M , Ross Joseph S , Rhee Taeho Greg
Published: April 2023

Background

There is limited knowledge on whether and how health care access restrictions imposed by the coronavirus disease of 2019 pandemic have affected utilization of both opioid and nonpharmacological treatments among US older adults living with chronic pain.

Methods

We compared prevalence of chronic pain and high impact chronic pain (ie, chronic pain limiting life or work activities on most days or every day in the past 6 months) between 2019 (pre-pandemic) and 2020 (first year of pandemic) and utilization of opioids and nonpharmacological pain treatments among adults aged ≥65 years enrolled in the National Health Interview Survey, a nationally representative sample of noninstitutionalized civilian U.S. adults.

Results

Of 12 027 survey participants aged ≥65 (representing 32.6 million noninstitutionalized older adults nationally), the prevalence of chronic pain was not significantly different from 2019 (30.8%; 95% confidence interval [CI], 29.7%–32.0%) to 2020 (32.1%; 95% CI, 31.0%–33.3%; p = .06). Among older adults with chronic pain, the prevalence of high impact chronic pain was also unchanged (38.3%; 95% CI, 36.1%–40.6% in 2019 versus 37.8%; 95% CI, 34.9%–40.8% in 2020; p = .79). Use of any nonpharmacological interventions for pain management decreased significantly from 61.2% (95 CI, 58.8%–63.5%) in 2019 to 42.1% (95% CI, 40.5%–43.8%) in 2020 (p < .001) among those with chronic pain, as did opioid use in the past 12 months from 20.2% (95% CI, 18.9%–21.6%) in 2019 to 17.9% (95% CI, 16.7%–19.1%) in 2020 (p = .006). Predictors of treatment utilization were similar in both chronic pain and high-impact chronic pain.

Conclusion

Use of pain treatments among older adults with chronic pain declined in the first year of coronavirus disease of 2019 pandemic. Future research is needed to assess long-term effects of coronavirus disease of 2019 pandemic on pain management in older adults.
Clinical encounter heterogeneity and methods for resolving in networked EHR data: a study from N3C and RECOVER programs
Authors: Leese Peter , Anand Adit , Girvin Andrew , Manna Amin , Patel Saaya , Yoo Yun Jae , Wong Rachel , Haendel Melissa , Chute Christopher G , Bennett Tellen , Hajagos Janos , Pfaff Emily , Moffitt Richard
Published: April 2023

Objective

Clinical encounter data are heterogeneous and vary greatly from institution to institution. These problems of variance affect interpretability and usability of clinical encounter data for analysis. These problems are magnified when multisite electronic health record (EHR) data are networked together. This article presents a novel, generalizable method for resolving encounter heterogeneity for analysis by combining related atomic encounters into composite “macrovisits.”

Materials and Methods

Encounters were composed of data from 75 partner sites harmonized to a common data model as part of the NIH Researching COVID to Enhance Recovery Initiative, a project of the National Covid Cohort Collaborative. Summary statistics were computed for overall and site-level data to assess issues and identify modifications. Two algorithms were developed to refine atomic encounters into cleaner, analyzable longitudinal clinical visits.

Results

Atomic inpatient encounters data were found to be widely disparate between sites in terms of length-of-stay (LOS) and numbers of OMOP CDM measurements per encounter. After aggregating encounters to macrovisits, LOS and measurement variance decreased. A subsequent algorithm to identify hospitalized macrovisits further reduced data variability.

Discussion

Encounters are a complex and heterogeneous component of EHR data and native data issues are not addressed by existing methods. These types of complex and poorly studied issues contribute to the difficulty of deriving value from EHR data, and these types of foundational, large-scale explorations, and developments are necessary to realize the full potential of modern real-world data.

Conclusion

This article presents method developments to manipulate and resolve EHR encounter data issues in a generalizable way as a foundation for future research and analysis.
Using AI-generated suggestions from ChatGPT to optimize clinical decision support
Authors: Liu Siru , Wright Aileen P , Patterson Barron L , Wanderer Jonathan P , Turer Robert W , Nelson Scott D , McCoy Allison B , Sittig Dean F , Wright Adam
Published: April 2023

Objective

To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.

Methods

We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.

Results

Five clinicians analyzed 36 AI-generated suggestions and 29 human-generated suggestions for 7 alerts. Of the 20 suggestions that scored highest in the survey, 9 were generated by ChatGPT. The suggestions generated by AI were found to offer unique perspectives and were evaluated as highly understandable and relevant, with moderate usefulness, low acceptance, bias, inversion, redundancy.

Conclusion

AI-generated suggestions could be an important complementary part of optimizing CDS alerts, can identify potential improvements to alert logic and support their implementation, and may even be able to assist experts in formulating their own suggestions for CDS improvement. ChatGPT shows great potential for using large language models and reinforcement learning from human feedback to improve CDS alert logic and potentially other medical areas involving complex, clinical logic, a key step in the development of an advanced learning health system.
Nutrient profile, amino acid digestibility, true metabolizable energy, and indispensable amino acid scoring of whole hemp seeds for use in canine and feline diets
Authors: Finet Shannon , He Fei , Utterback Pam L , Parsons Carl M , de Godoy Maria R C
Published: April 2023

The use of various hemp-derived products has been rapidly growing in the human nutrition industry and has sparked great interest in using these ingredients for companion animals as well. Thorough research is needed to determine the ingredient and safety standards required for AAFCO approval of hemp ingredients. In order to be effectively incorporated into pet food products, we must determine the nutrient content, quality, and utility of these ingredients in pet species. The objective of this study was to evaluate the nutrient composition of seeds from four different varieties of hemp, NWG 452, NWG 331, NWG 2730, X-59, and determine protein quality and true metabolizable energy using a cecectomized rooster model. The seeds were similar in macronutrient composition, with small variations in acid hydrolyzed fat, crude protein, total dietary fiber and gross energy content, as well as amino acid and long-chain fatty acid profiles. All essential amino acids were present in concentrations that exceeded the NRC (2006) recommended allowances for adult dogs and cats at maintenance with the exception of tryptophan. The long-chain fatty acid profile presented a favorable ratio of omega-6 to omega-3 fatty acids of close to 3.5:1. The results of the cecectomized rooster assay indicated no significant difference in the standardized amino acid digestibility of the indispensable amino acids among the seed varieties (P > 0.05). A significant difference in the true metabolizable energy corrected for nitrogen was observed among the seeds (P < 0.05), following the pattern of higher acid hydrolyzed fat and lower total dietary fiber content resulting in higher metabolizable energy. An adapted calculation of digestible indispensable amino acid score was made to determine protein quality of the hemp seeds using AAFCO nutrient profiles and NRC recommended allowances for adult dogs and cats at maintenance as reference points. The resulting scores determined tryptophan to be the first limiting amino acid and indicate that hemp seeds alone do not meet all the amino acid requirements for adult dogs and cats at maintenance, and would need a complimentary protein source for practical use in companion animal diets. The data from this study suggest that hemp seeds may provide a beneficial source of fat, protein, and dietary fiber, with consideration to differences in nutrient profile among seed varieties. However, further investigation in vivo is needed to determine the safety and efficacy of utilizing hemp in the diets of both canines and felines.
Development of Prepositioned Burn Care-specific Disaster Resources for a Burn Mass Casualty Incident
Authors: Kearns Randy D , Flores Carl A , Arledge Frances , Hargrove Paige , Prats Rosanne , Kanter Joseph , Sittig Kevin , Barrios Joey , Phelan Herb A , Carter Jeffrey E
Published: April 2023

Disaster preparedness for a burn mass casualty incident (BMCI) must consider the needs of the first responders and community hospitals, who may be the first to receive those patients. Developing a more comprehensive statewide burn disaster program includes meeting with regional healthcare coalitions (HCCs) to identify gaps in care.

Quarterly HCC meetings, which link local hospitals, emergency medical services (EMS) agencies, and other interested parties, are held around the state. We rely on the HCC’s regional meetings to serve as a platform for conducting focus group research to identify gaps specific to a BMCI and to inform strategy development.

One of the deficiencies identified, particularly in rural areas that infrequently manage burn injuries, was a lack of burn-specific wound care dressings that could support the initial response. Relying on this process, a consensus was created for equipment types and quantities, including a kit for storage. Furthermore, maintenance, supply replacement, and scene delivery processes were developed for these kits that could augment a BMCI response.

The feedback from the focus groups reminded us that many systems report having infrequent opportunities to provide care for patients with burn injuries. In addition, several types of burn-specific dressings are expensive. With the infrequent occurrence, EMS agencies and rural hospitals reported that it was doubtful their agency/hospital would have more than a minimal stock of burn injury supplies. Therefore, developing supply caches that can be quickly mobilized and deployed to the impacted area was one of the deficiencies we identified and addressed through this process.
Species-specific differences in the egg exochorium of the sympatric taxa Triatoma costalimai and Triatoma jatai (Hemiptera: Reduviidae: Triatominae)
Authors: Müller Josiane Nogueira , Freitas Simone Patrícia Carneiro , Teves Simone Caldas , Santos-Mallet Jacenir Reis , Lopes Catarina Macedo , Gonçalves Teresa Cristina Monte
Published: April 2023

Triatoma costalimai and Triatoma jatai are related species, which occur in sympatry in Paranã, Tocantins, Brazil, in rocky outcrops and in peridomicile and intradomicile environments. This study compared morphologic and morphometric aspects of the eggs of these species using optical microscopy (OM) and scanning electron microscopy (SEM). Operculum cells (OP) and egg body (EB) were drawn and photographed, their surfaces were measured, and spots were quantified. Statistical analyses were performed using ANOVA and t-tests. OM showed an egg exochorium with spots in T. costalimai and a predominance of short lines in T. jatai. We found significant differences in egg length and width, which were larger in T. costalimai. SEM analysis showed that the operculum of both species had cells with straight and/or rounded rims, with a smooth aspect, random spots, and predominantly pentagonal shape. In the EB, hexagonal cells were predominant, with indices exceeding 60% in both species. Triatoma costalimai cells were flat, with a discrete definition of the rims, whereas T. jatai cells were smooth with well-defined rims. Statistical tests showed significant differences for EB, where T. costalimai cells were larger and have more spots than T. jatai. The eggs can thus be differentiated, thereby contributing to integrative taxonomy.
Association between APOE genotype and microglial cell morphology
Authors: Kloske Courtney M , Gearon Mary D , Weekman Erica M , Rogers Colin , Patel Ela , Bachstetter Adam , Nelson Peter T , Wilcock Donna M
Published: April 2023

APOE is the largest genetic risk factor for late-onset Alzheimer disease (AD) with E4 conferring an increased risk for AD compared to E3. The ApoE protein can impact diverse pathways in the brain including neuroinflammation but the precise impact of ApoE isoforms on inflammation remains unknown. As microglia are a primary source of neuroinflammation, this study determined whether ApoE isoforms have an impact on microglial morphology and activation using immunohistochemistry and digital analyses. Analysis of ionized calcium-binding adaptor molecule 1 (Iba1) immunoreactivity indicated greater microglial activation in both the hippocampus and superior and middle temporal gyrus (SMTG) in dementia participants versus non-demented controls. Further, only an increase in activation was seen in E3-Dementia participants in the entire SMTG, whereas in the grey matter of the SMTG, only a diagnosis of dementia impacted activation. Specific microglial morphologies showed a reduction in ramified microglia in the dementia group. For rod microglia, a reduction was seen in E4-Control patients in the hippocampus whereas in the SMTG an increase was seen in E4-Dementia patients. These findings suggest an association between ApoE isoforms and microglial morphologies and highlight the importance of considering ApoE isoforms in studies of AD pathology.
Insights into the role of PHLPP2/Akt/GSK3β/Fyn kinase/Nrf2 trajectory in the reno-protective effect of rosuvastatin against colistin-induced acute kidney injury in rats
Authors: Shafik Marihan S , El-Tanbouly Dalia M , Bishr Abeer , Attia Amina S
Published: April 2023

Objectives

Oxidative stress-mediated colistin’s nephrotoxicity is associated with the diminished activity of nuclear factor erythroid 2-related factor 2 (Nrf2) that is primarily correlated with cellular PH domain and leucine-rich repeat protein phosphatase (PHLPP2) levels. This study investigated the possible modulation of PHLPP2/protein kinase B (Akt) trajectory as a critical regulator of Nrf2 stability by rosuvastatin (RST) to guard against colistin-induced oxidative renal damage in rats.

Methods

Colistin (300,000 IU/kg/day; i.p.) was injected for 6 consecutive days, and rats were treated simultaneously with RST orally at 10 or 20 mg/kg.

Key findings

RST enhanced renal nuclear Nrf2 translocation as revealed by immunohistochemical staining to boost the renal antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH) along with a marked reduction in caspase-3. Accordingly, rats treated with RST showed significant restoration of normal renal function and histological features. On the molecular level, RST effectively decreased the mRNA expression of PHLPP2 to promote Akt phosphorylation. Consequently, it deactivated GSK-3β and reduced the gene expression of Fyn kinase in renal tissues.

Conclusions

RST could attenuate colistin-induced oxidative acute kidney injury via its suppressive effect on PHLPP2 to endorse Nrf2 activity through modulating Akt/GSK3 β/Fyn kinase trajectory.
A Bayesian feature allocation model for identifying cell subpopulations using CyTOF data
Authors: Lui Arthur , Lee Juhee , Thall Peter F , Daher May , Rezvani Katy , Basar Rafet
Published: April 2023

A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In contrast with conventional cell clustering methods, which cluster observed marker expression levels separately for each sample, the FAM-based method can be applied simultaneously to multiple samples, and also identify important cell subpopulations likely to be otherwise missed. The proposed FAM-based method is applied to jointly analyse three CyTOF datasets to study natural killer (NK) cells. Because the subpopulations identified by the FAM may define novel NK cell subsets, this statistical analysis may provide useful information about the biology of NK cells and their potential role in cancer immunotherapy which may lead, in turn, to development of improved NK cell therapies.
Social considerations in surgical management of Flood syndrome: a case report
Authors: Ekhteraei Setareh , Alsafar Ahmed
Published: April 2023

Flood syndrome, first described by Dr. Frank Flood in 1961, is a rare condition involving the leakage of ascitic fluid through a ruptured ventral hernia. Most commonly, it occurs in patients with advanced, decompensated liver cirrhosis leading to significant amounts of ascites. Currently, there is no standard of care for Flood syndrome due to its very rare nature. Our case report details the medical, surgical and social aspects of a 45-year-old unhoused male with Flood syndrome with post-surgical complications and subsequent infection. This paper aims to add to the sparse literature on Flood syndrome and to discuss some of the complications and treatment approaches for this condition.
First light and reionization epoch simulations (FLARES) XI: [O iii] emitting galaxies at 5 < z < 10
Authors: Wilkins Stephen M , Lovell Christopher C , Vijayan Aswin P , Irodotou Dimitrios , Adams Nathan J , Roper William J , Caruana Joseph , Matthee Jorryt , Seeyave Louise T C , Conselice Christopher J , Pérez-González Pablo G , Turner Jack C , Donnellan James M S , Verma Aprajita , Trussler J A A
Published: April 2023

JWST has now made it possible to probe the rest-frame optical line emission of high-redshift galaxies extending to z ≈ 9, and potentially beyond. To aid in the interpretation of these emerging constraints, in this work we explore predictions for [O iii]λλ4960, 5008 Å emission in high-redshift galaxies using the First Light and Reionization Epoch Simulations (Flares). We produce predictions for the [O iii] luminosity function, its correlation with the UV luminosity, and the distribution of equivalent widths (EWs). We also explore how the [O iii] EW correlates with physical properties including specific star formation rate, metallicity, and dust attenuation. Our predictions are largely consistent with recent observational constraints on the luminosity function, average EWs, and line ratios. However, they fail to reproduce the observed tail of high-EW sources and the number density of extreme line emitters. Possibilities to explain these discrepancies include an additional source of ionizing photons and/or greater stochasticity in star formation in the model or photometric scatter and/or bias in the observations. With JWST now rapidly building larger samples and a wider range of emission lines the answer to this remaining discrepancy should be available imminently.
Nustar observation of the binary system 4U 0114 + 65
Authors: Abdallah Mohammed H , Samir Rasha M , Leahy Denis A , Shaker Ashraf A
Published: April 2023

The high-mass X-ray binary system 4U 0114 + 65 was observed by Nustar in October 2019 and by XMM-Newton in August 2015. Here we performed spectral and timing analysis of the Nustar observation and carry out timing analysis on the XMM-Newton data. We measured the spin period of the neutron star from both observations and found a spin-up rate $\dot{p}$ = 1.54 ± 0.38 × 10−6$\mathrm{s\, s}^{-1}$ . During the Nustar observation, two flares occurred, one shortly after the start of the observation and the other near the end separated by a long period of low/quiescent state. The large and sudden flares mostly resulted from accretion of corotating interaction region (CIR) material. A common spectral model to high mass X-ray binaries (HMXBs), powerlaw with high energy cutoff and absorption at low energy, gave a good fit to both flaring and quiescent states. A fluorescent iron line was not required in fitting any of the states. On the other hand, very tentative evidence of Cyclotron Resonant Scattering Feature (CRSF) at ∼17 keV was found during fitting using cyclabs model; however, fitting improvement was not significant enough to confirm its detection, plus a very narrow width (<1 keV) was obtained for the line and its first harmonic. Visual inspection of the spectra showed a deficiency of emission near the expected first and second harmonic. Another important feature visually noticed in the spectra is the presence of hard tail above 50 keV. This could be explained by the shocked material bounding the CIR.
An ultrafast outflow in the black hole candidate MAXI J1810−222?
Authors: Del Santo M , Pinto C , Marino A , D’Aì A , Petrucci P-O , Malzac J , Ferreira J , Pintore F , Motta S E , Russell T D , Segreto A , Sanna A
Published: April 2023

The transient X-ray source MAXI J1810−222 was discovered in 2018 and has been active ever since. A long combined radio and X-ray monitoring campaign was performed with Australia Telescope Compact Array and Swift, respectively. It has been proposed that MAXI J1810−222 is a relatively distant black hole X-ray binary, albeit showing a very peculiar outburst behaviour. Here, we report on the spectral study of this source making use of a large sample of NICER observations performed between 2019 February and 2020 September. We detected a strong spectral absorption feature at ∼1 keV, which we have characterized with a physical photoionization model. Via a deep scan of the parameters space, we obtained evidence for a spectral-state dependent outflow, with mildly relativistic speeds. In particular, the soft and intermediate states point to a hot plasma outflowing at 0.05–0.15c. This speeds rule-out thermal winds and hence, they suggest that such outflows could be radiation pressure or (most likely) magnetically driven winds. Our results are crucial to test current theoretical models of wind formation in X-ray binaries.
Beginner's Guide on the Use of PAML to Detect Positive Selection
Authors: Álvarez-Carretero Sandra , Kapli Paschalia , Yang Ziheng
Published: April 2023

The CODEML program in the PAML package has been widely used to analyze protein-coding gene sequences to estimate the synonymous and nonsynonymous rates (dS and dN) and to detect positive Darwinian selection driving protein evolution. For users not familiar with molecular evolutionary analysis, the program is known to have a steep learning curve. Here, we provide a step-by-step protocol to illustrate the commonly used tests available in the program, including the branch models, the site models, and the branch-site models, which can be used to detect positive selection driving adaptive protein evolution affecting particular lineages of the species phylogeny, affecting a subset of amino acid residues in the protein, and affecting a subset of sites along prespecified lineages, respectively. A data set of the myxovirus (Mx) genes from ten mammal and two bird species is used as an example. We discuss a new feature in CODEML that allows users to perform positive selection tests for multiple genes for the same set of taxa, as is common in modern genome-sequencing projects. The PAML package is distributed at https://github.com/abacus-gene/paml under the GNU license, with support provided at its discussion site (https://groups.google.com/g/pamlsoftware). Data files used in this protocol are available at https://github.com/abacus-gene/paml-tutorial.
Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis
Authors: Sarnak Mark J , Agarwal Rajiv , Boudville Neil , Chowdhury Pradip C P , Eckardt Kai-Uwe , Gonzalez Carlos R , Kooienga Laura A , Koury Mark J , Ntoso Kwabena A , Luo Wenli , Parfrey Patrick S , Vargo Dennis L , Winkelmayer Wolfgang C , Zhang Zhiqun , Chertow Glenn M
Published: April 2023

Background

Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.

Methods

We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24–36).

Results

Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was −0.10 g/dL (95% CI −0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively.

Conclusions

In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.
Shuangqing Forum on carbon neutrality in construction and architecture
Authors: Zhu He
Published: April 2023

The Natural Science Foundation of China (NSFC) held the 326th Shuangqing Forum on 22 February 2023. As the first forum of 2023 and one of the first in-person activities post-COVID, a topic of national and global significance was chosen: the challenges, for basic sciences, of reaching carbon neutrality in construction and architecture. National Science Review (NSR) attended this forum, as several presentations related to materials science and information science would appeal to the broad audience of NSR. In the plenary session, four members of the Chinese Academy of Engineering (CAE), Profs. Jiaping Liu, Jianguo Wang, Weimin Zhuang and Hongyuan Mei, provided an overview of the challenges facing construction and architecture industries in the run-up to carbon neutrality.
Theorising Evidence Law
Authors: Roberts Paul
Published: April 2023

Abstract—

What does it mean for a specialist department of legal studies, such as the Law of Evidence, to have, or to acquire, ‘philosophical foundations’? In what sense are the theoretical foundations of procedural scholarship and teaching distinctively or uniquely philosophical? The publication of Philosophical Foundations of Evidence Law (OUP, 2021), edited by Christian Dahlman, Alex Stein and Giovanni Tuzet, presents a valuable opportunity to reflect on these existential questions of disciplinary constitution, methodology and design. This review article critically examines the volume’s idiosyncratic selection of topics, structural taxonomy, epistemological priorities, and enigmatic thesis that modern evidence law is turning from rules to reasons as its organising intellectual framework. Whilst the volume is impressively interdisciplinary and cosmopolitan in authorship and outlook, some doubts are expressed about its implicit US orientation, limited engagement with institutional or doctrinal details, and marginalisation of normative criminal jurisprudence.