bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic stewardship in the era of precision medicine
Authors: Watkins Richard R
Published: June 2022

Antimicrobial resistance (AMR) continues to spread at an alarming rate worldwide. Novel approaches are needed to mitigate its deleterious impact on antibiotic efficacy. Antibiotic stewardship aims to promote the appropriate use of antibiotics through evidence-based interventions. One paradigm is precision medicine, a medical model in which decisions, practices, interventions, and therapies are adapted to the individual patient based on their predicted response or risk of disease. Precision medicine approaches hold promise as a way to improve outcomes for patients with myriad illnesses, including infections such as bacteraemia and pneumonia. This review describes the latest advances in precision medicine as they pertain to antibiotic stewardship, with an emphasis on hospital-based antibiotic stewardship programmes. The impact of the COVID-19 pandemic on AMR and antibiotic stewardship, gaps in the scientific evidence, and areas for further research are also discussed.
Usefulness of serum CCL2 as prognostic biomarker in prostate cancer: a long-term follow-up study
Authors: Iwamoto Hiroaki , Izumi Kouji , Nakagawa Ryunosuke , Toriumi Ren , Aoyama Shuhei , Shimada Takafumi , Kano Hiroshi , Makino Tomoyuki , Kadomoto Suguru , Yaegashi Hiroshi , Kawaguchi Shohei , Nohara Takahiro , Shigehara Kazuyoshi , Kadono Yoshifumi , Mizokami Atsushi
Published: June 2022

Objective

Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system.

Methods

Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker.

Results

Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 < 320 pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8 and chemokine (CC motif) ligand 2 ≥ 320 pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen ≥ 100 ng/mL and Gleason score ≥ 8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2 ≥ 320 pg/mL, prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively.

Conclusions

This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.
Impacts of psychological stress on high dose-rate radiation acute effects in a mouse experimental model
Authors: Nakajima Tetsuo , Ninomiya Yasuharu , Unno Keiko , Morioka Takamitsu , Nishimura Mayumi , Kakinuma Shizuko
Published: June 2022

Psychological stress affects health. Radiation workers in the medical field or astronauts living in space have possible risks of exposure to radiation, and psychological stress is considered to be easily induced in them due to activities performed in small areas or stress conditions. The impact of psychological stress on the effects of radiation was evaluated in senescence-accelerated mouse prone 10 (SAMP10) mice and ddY mice using a confrontational housing model, which makes dominant and subordinate mice in a cage live together without severe quarrel. Mice of ddY and SAMP10 have been previously demonstrated to be influenced in terms of acute and late effects, respectively, under psychological stress by this model. In SAMP10 mice, irradiation with 4 Gy induced the death of irradiated mice under psychological stress. In ddY mice, irradiation with 5 Gy X-rays alone had almost no effect on the mouse survival, but irradiation in conditions of psychological stress promoted acute death of irradiated mice. In addition, hypocellular bone marrow was also observed histopathologically in irradiated ddY mice under stress. Psychological stress may promote damage caused by radiation through modulation of radio-sensitivity in bone marrow in mice. This model would be useful for evaluation of modulation of radiation-induced various effects by psychological stress.
Simulation of winter wheat response to variable sowing dates and densities in a high-yielding environment
Authors: Dueri Sibylle , Brown Hamish , Asseng Senthold , Ewert Frank , Webber Heidi , George Mike , Craigie Rob , Guarin Jose Rafael , Pequeno Diego N L , Stella Tommaso , Ahmed Mukhtar , Alderman Phillip D , Basso Bruno , Berger Andres G , Mujica Gennady Bracho , Cammarano Davide , Chen Yi , Dumont Benjamin , Rezaei Ehsan Eyshi , Fereres Elias , Ferrise Roberto , Gaiser Thomas , Gao Yujing , Garcia-Vila Margarita , Gayler Sebastian , Hochman Zvi , Hoogenboom Gerrit , Kersebaum Kurt C , Nendel Claas , Olesen Jørgen E , Padovan Gloria , Palosuo Taru , Priesack Eckart , Pullens Johannes W M , Rodríguez Alfredo , Rötter Reimund P , Ramos Margarita Ruiz , Semenov Mikhail A , Senapati Nimai , Siebert Stefan , Srivastava Amit Kumar , Stöckle Claudio , Supit Iwan , Tao Fulu , Thorburn Peter , Wang Enli , Weber Tobias Karl David , Xiao Liujun , Zhao Chuang , Zhao Jin , Zhao Zhigan , Zhu Yan , Martre Pierre
Published: June 2022

Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change. Here, we explore the performance of a MME of 29 wheat crop models to predict the effect of changing sowing dates and rates on yield and yield components, on two sites located in a high-yielding environment in New Zealand. The experiment was conducted for 6 years and provided 50 combinations of sowing date, sowing density and growing season. We show that the MME simulates seasonal growth of wheat well under standard sowing conditions, but fails under early sowing and high sowing rates. The comparison between observed and simulated in-season fraction of intercepted photosynthetically active radiation (FIPAR) for early sown wheat shows that the MME does not capture the decrease of crop above ground biomass during winter months due to senescence. Models need to better account for tiller competition for light, nutrients, and water during vegetative growth, and early tiller senescence and tiller mortality, which are exacerbated by early sowing, high sowing densities, and warmer winter temperatures.
Functional phenomics for improved climate resilience in Nordic agriculture
Authors: Roitsch Thomas , Himanen Kristiina , Chawade Aakash , Jaakola Laura , Nehe Ajit , Alexandersson Erik
Published: June 2022

The five Nordic countries span the most northern region for field cultivation in the world. This presents challenges per se, with short growing seasons, long days, and a need for frost tolerance. Climate change has additionally increased risks for micro-droughts and water logging, as well as pathogens and pests expanding northwards. Thus, Nordic agriculture demands crops that are adapted to the specific Nordic growth conditions and future climate scenarios. A focus on crop varieties and traits important to Nordic agriculture, including the unique resource of nutritious wild crops, can meet these needs. In fact, with a future longer growing season due to climate change, the region could contribute proportionally more to global agricultural production. This also applies to other northern regions, including the Arctic. To address current growth conditions, mitigate impacts of climate change, and meet market demands, the adaptive capacity of crops that both perform well in northern latitudes and are more climate resilient has to be increased, and better crop management systems need to be built. This requires functional phenomics approaches that integrate versatile high-throughput phenotyping, physiology, and bioinformatics. This review stresses key target traits, the opportunities of latitudinal studies, and infrastructure needs for phenotyping to support Nordic agriculture.
The C2H2-type zinc finger protein PhZFP1 regulates cold stress tolerance by modulating galactinol synthesis in Petunia hybrida
Authors: Zhang Huilin , Sun Zheng , Feng Shan , Zhang Junwei , Zhang Fan , Wang Wenen , Hu Huirong , Zhang Wei , Bao Manzhu
Published: June 2022

The C2H2 zinc finger proteins (ZFPs) play essential roles in regulating cold stress responses. Similarly, raffinose accumulation contributes to freezing stress tolerance. However, the relationship between C2H2 functions and raffinose synthesis in cold tolerance remains uncertain. Here, we report the characterization of the cold-induced C2H2-type zinc finger protein PhZFP1 in Petunia hybrida. PhZFP1 was found to be predominantly localized in the nucleus. Overexpression of PhZFP1 conferred enhanced cold tolerance in transgenic petunia lines. In contrast, RNAi mediated suppression of PhZFP1 led to increased cold susceptibility. PhZFP1 regulated the expression of a range of abiotic stress responsive-genes including genes encoding proteins involved in reactive oxygen species (ROS) scavenging and raffinose metabolism. The accumulation of galactinol and raffinose, and the levels of PhGolS1-1 transcripts, were significantly increased in PhZFP1-overexpressing plants and decreased in PhZFP1-RNAi plants under cold stress. Moreover, the galactinol synthase (GolS)-encoding gene PhGolS1-1 was identified as a direct target of PhZFP1. Taken together, these results demonstrate that PhZFP1 functions in cold stress tolerance by modulation of galactinol synthesis via regulation of PhGolS1-1. This study also provides new insights into the mechanisms underlying C2H2 zinc finger protein-mediated cold stress tolerance, and has identified a candidate gene for improving cold stress tolerance.
Physical Injuries, Treatment-Seeking, and Perceived Barriers to Treatment in U.S. Army Drill Sergeants
Authors: Elliman Toby D , Cohen Bruce S , Heaton Kristin J , Proctor Susan P
Published: June 2022

Introduction

Drill sergeants work under mentally and physically challenging conditions. The current study examined self-reported rates of physical injuries in drill sergeants; rates of treatment-seeking for injuries; perceived barriers toward treatment-seeking; and associated demographic and environmental factors.

Materials and Methods

Drill sergeants from across all Army basic training locations completed self-report surveys from September to November of 2018. In total, 726 drill sergeants were included in analyses. Drill sergeants indicated whether they had acquired an injury during their time in the drill sergeant role and whether they had sought treatment for all such injuries. Furthermore, drill sergeants rated their agreement with a number of possible perceived barriers to treatment-seeking for physical injuries. Regression models examining each phenomenon included hours of sleep obtained per day; general- and health-specific leadership behaviors of the company command teams; unit cohesion; time as a drill sergeant; duty location; gender; military operational specialty; years in the military; previous combat deployments; and route of assignment. The study was approved by the Walter Reed Army Institute of Research Institutional Review Board.

Results

In total, 38% of respondents reported acquiring an injury during their time as drill sergeants. Of those who had acquired an injury, 61% reported seeking medical help for all injuries acquired. Injuries were more likely in females (49%) than in males (34%) and less likely in drill sergeants reporting at least 6 hours of sleep (27%) versus those reporting 5 hours (40%) and 4 hours or less (43%). Reported comparisons were significant after controlling for demographic and environmental variables in regression models. The most strongly endorsed perceived barriers to treatment-seeking were “Seeking help would place too much burden on the other drill sergeants” (69%) and “Seeking help would interfere with my ability to train the recruits” (60%). Both of these perceived barriers were significantly associated with reduced treatment-seeking in injured drill sergeants, after controlling for demographic and environmental variables.

Conclusions

This study is the first to examine injury occurrence, treatment-seeking, and perceived barriers to treatment-seeking in U.S. Army drill sergeants. Building on previous studies that showed the negative effects of sleep deprivation on the safety and behavioral health of drill sergeants, the current study gives further evidence of the negative effects of such sleep deprivation, this time in the domain of physical injuries. The results suggest that pursuing strategies that allow for healthier sleep duration may contribute to injury reduction.
Depression, Insomnia, and Obesity Among Post-9/11 Veterans: Eating Pathology as a Distinct Health Risk Behavior
Authors: Ramsey Christine M , Gaffey Allison E , Brandt Cynthia A , Haskell Sally G , Masheb Robin M
Published: June 2022

Introduction

Understanding the interrelationships between co-occurring chronic health conditions and health behaviors is critical to developing interventions to successfully change multiple health behaviors and related comorbidities. The objective of the present study was to examine the effects of depression, insomnia, and their co-occurrence on risk of obesity and to examine the role of health risk behaviors as potential confounders of these relationships with an emphasis on eating pathologies.

Methods

Iraq and Afghanistan conflict era veterans (n = 1,094, 51.2% women) who participated in the Women Veterans Cohort Study between July 2014 and September 2019 were categorized as having depression, insomnia, both, or neither condition. Logistic regression models were used to examine group differences in the risk of obesity. Health risk behaviors (i.e., eating pathology, physical activity, smoking, and hazardous drinking) were then assessed as potential confounders of the effects of depression and insomnia on the likelihood of obesity.

Results

Obesity was most prevalent in individuals with co-occurring insomnia and depression (53.2%), followed by depression only (44.6%), insomnia only (38.5%), and neither condition (30.1%). Importantly, maladaptive eating behaviors confounded the depression–obesity association but not the insomnia–obesity association. There was no evidence that insufficient physical activity, smoking, or hazardous drinking confounded the effects of insomnia or depression on obesity.

Conclusions

These findings exemplify the complex relationships between multiple health conditions and behaviors that contribute to obesity. Elucidating these associations can enhance the precision with which interventions are tailored to efficiently allocate resources and reduce the severe health impact of obesity among veterans.
Hazardous Non-Combat Exposures in the U.S. Department of Defense
Authors: Krahl Pamela L , Mallon Timothy M , Gaydos Joel C
Published: June 2022

Hazardous non-combat exposures are inherent to military service and occur in three settings: installation workplaces, installation environments, and deployment environments. Few military clinicians receive training in how to recognize, assess, and manage patients with these exposures, and systems improvements are needed to support clinicians with respect to exposure recognition and management. This commentary highlights key concepts surrounding military non-combat exposures by discussing three case examples of exposures occurring in each of these settings. In the workplace, well-coordinated, interdisciplinary occupational health teams improve identification of exposure-related illnesses, and these teams may be further supported by the development of automated clinical decision-support systems. Installation environmental exposures are characterized by high perceived risk, uncertainty in estimating actual risk, and a wide range of stakeholders including military family members and individuals in the surrounding community. Recognizing environmental exposure concerns, gathering a thorough environmental exposure history, and practicing exposure risk communication are vital skills to address these situations. During deployments, exposures may initially be perceived as low risk but then become a concern years later. A functional understanding of the capabilities and limitations of exposure monitoring and potential health effects of exposures helps the military clinician effectively communicate potential health risks to line leaders. For any of these exposure settings, service public health centers and OEM specialty leaders and consultants are available for consultation.
TSCat: data model and storage engine for AI-based light-curve analysis
Authors: Li Kun , Yu Ce , Zhang Yanxia , Sun Chao , Xiao Jian , Cui Chenzhou , Zhang Yajie , Mu Yifei
Published: June 2022

Light-curve data are one of the most important data sources in time domain astronomy research. With the advancement of observation facilities and the continuous accumulation of observation data, and considering the analysis needs of large sample data sets, software or tools based on new technologies, especially artificial intelligence (AI), will be indispensable for light-curve analysis. The light-curve analysis tool designed by an individual will follow its own defined data structure, which will make the tools designed and developed by different individuals incompatible. A unified light-curve data model will be able to solve this compatibility problem, similar to the traditional flexible image transport system (FITS) file format. This paper proposes a light-curve data model named TSCat, designs and implements a data storage engine. The TSCat data model defines the basic metadata and format required for storing optical curve data following the international virtual observatory alliance (IVOA) data format specification system. The TSCat storage engine implements basic operations such as importing, storing, and accessing light-curve data. The function and performance of the TSCat storage engine are evaluated through the actual observation data. The experimental results show that the TSCat data model is complete enough to support the analysis of light curves. TSCat will help support the standardization of the data access level of software and tools in the field of light-curve analysis, and provide a new reference for the specification system of astronomical scientific data formats.
Advection of accelerated electrons in radio/X-ray knots of AGN jets
Authors: Rahman Amal A , Sahayanathan S , Subha P A
Published: June 2022

The X-ray emission from the knots of the kiloparsec scale jet of active galactic nuclei (AGN) suggests the high energy emission process is different from the radio/optical counterpart. Interpretation based on the inverse Compton scattering of cosmic microwave photons has been ruled out through Fermi γ-ray observations for low-redshift sources. As an alternate explanation, synchrotron emission from a different electron population is suggested. We propose a model considering the advected electron distribution from the sites of particle acceleration in AGN knots. This advected electron distribution is significantly different from the accelerated electron distribution and satisfies the requirement of the second electron population. The synchrotron emission from the accelerated and the advected electron distribution can successfully reproduce the observed radio-to-X-ray fluxes of the knots of 3C 273. For the chosen combination of the model parameters, the spectrum due to inverse Compton scattering of cosmic microwave photons falls within the Fermi γ-ray upper limits.
Prevalence of short-lived radioactive isotopes across exoplanetary systems inferred from polluted white dwarfs
Authors: Curry Alfred , Bonsor Amy , Lichtenberg Tim , Shorttle Oliver
Published: June 2022

In the Solar system, short-lived radioisotopes, such as 26Al, played a crucial role during the formation of planetary bodies by providing a significant additional source of heat. Notably, this led to early and large-scale melting and iron core formation in planetesimals and their loss of volatile elements, such as hydrogen and carbon. In the context of exoplanetary systems therefore the prevalence of short-lived radioisotopes is key to interpreting the observed bulk volatile budget and atmospheric diversity among low-mass exoplanets. White dwarfs that have accreted planetary material provide a unique means to infer the frequency of iron core formation in extrasolar planetesimals, and hence the ubiquity of planetary systems forming with high short-lived radioisotope abundances. Here, we devise a quantitative method to infer the fraction of planetary systems enriched with short-lived radionuclides upon planetesimal formation from white dwarf data. We argue that the current evidence from white dwarfs point towards a significant fraction of exoplanetesimals having formed an iron core. Although the data may be explained by the accretion of exomoon or Pluto-sized bodies that were able to differentiate due to gravitational potential energy release, our results suggest that the most likely explanation for the prevalence of differentiated material among polluted white dwarfs is that the Solar system is not unusual in being enriched in 26Al. The models presented here suggest a ubiquitous pathway for the enrichment of exoplanetary systems by short-lived radioisotopes, disfavouring short-lived radioisotope enrichment scenarios relying on statistically rare chance encounters with single nearby supernovae, Wolf–Rayet, or AGB stars.
Crystal-Liquid Segregation in Silicocarbonatite Magma Leads to the Formation of Calcite Carbonatite
Authors: Moore K R , Brady A E , Costanzo A
Published: June 2022

A suite of silicocarbonatite and lamprophyre rocks from SW Ireland, with mantle affinity and primitive composition, are used as a proxy for parental carbonated silicate magmas to model early magmatic evolution. Reconstruction of volatile ratios is validated using global occurrences. At 1200°C, the point at which melts transition from ionic liquids with exceptionally low viscosity (0.06 PaS) to covalently polymerised liquid (viscosity up to 1.3 PaS) is 33 mol% SiO2. Incremental and significant increase in magma density accompanies magma ponding, due to dehydration of magmas from model molar CO2/(CO2 + H2O) of 0.60 in plutonic settings to 0.75 for initial subvolcanic magmas. Magma-crystal density differences dictate that repeated influxes of magmas into an inflating magma chamber sustain a mechanical boundary layer between dense (silicate and oxide) mineral layers and a calcite ± phlogopite flotation assemblage. The range of critical CO2 concentration at which calcite floats (10–13 wt% CO2) may be extended by the presence of additional volatiles and fluid bubbles. The model accommodates a range of phenomena observed or inferred for alkaline/carbonatite complexes, including the following: 1, a growing calcite-dominated flotation assemblage with an apparently early magmatic mineralisation; 2, a residual liquid with high concentrations of incompatible metals; 3, variable carbonatite–pyroxenite–phoscorite rock relations; and 4, multiple phases of overprinting metasomatism.
Synergistic impacts of Montelukast and Klotho against doxorubicin-induced cardiac toxicity in Rats
Authors: Elnoury Heba A , Elgendy Salwa A , Baloza Samar H , Ghamry Heba I , Soliman Mohamed , Abdel-Aziz Eman Abdel-Mohsen
Published: June 2022

Doxorubicin (DOX) is a powerful antitumor agent with a well-known cardiaotoxic side effects. In the current study, the ameliorative combined impacts of montelukast (Mont) and Klotho against doxorubicin-induced cardiac toxicity were examined. Fifty-six adult male rats (2 months age and weighting 150–200 g) were grouped into 7 groups (8 rats per group). Animals received doxorubicin alone or in combination with either Mont or Klotho. After 2 weeks of treatments, serum samples were examined to assess the changes in cardiac activity biomarkers such as LDH, CK-MB, cardiac troponin-I (cTn-I), and heart fatty acid binding protein (H-FABP). Serum changes of IL-6, inducible nitric oxide synthase (iNOS), and caspase-3 levels were assayed. The oxidative stress biomarkers such as total antioxidant capacity (TAC) and inflammatory (rat IL-1β and rat TNF-α,) and anti-inflammatory (rat IL-10) cytokines were examined. Heart histology and transforming growth factor-β1 (TGF-β1) immunoreactivity were measured. DOX induced cardiomyopathy, which was reflected by the increases in all examined cardiac parameters. Real-time PCR confirmed that DOX upregulated the expression of TNF-α and IL-1β and decreased the expression of IL-10. Moreover, DOX showed marked elevation in the ST segment T wave complex, causing profound tachycardia. Heart histology assessments showed cardiac cell necrosis, inflammatory cell infiltration, interstitial congestion, and increased TGF-β1 immunoreactivity. Montelukast and Klotho administration ameliorated all the altered parameters when administered alone or in combination to DOX-intoxicated rats. Klotho was more effective compared with montelukast in terms of reductions in heart rate, ST segment T wave complex elevation, cardiac enzymes (lactate dehydrogenase; LDH, creatine kinase-MB; CK-MB, cardiac troponin I; cTn-I, heart fatty acid binding protein; H-FABP) cardiac histology, and caspase-3 levels and increases in TAC activity. Montelukast was more effective in reducing serum levels of IL6 and iNOS, expression of TNF-α and IL-1β, and the upregulation of IL-10 expression. The co-administration of both drugs led to significantly more synergistic results in terms of reducing cardiac toxicity. In conclusion, montelukast and Klotho either alone or in combination were confirmed to be effective in suppressing DOX-induced cardiac toxicity in rats.
Hazard identification and risk assessment of Abuja rail mass transit
Authors: Zhang Yinggui , Fom Dung D
Published: June 2022

Due to multiple advantages in terms of capacity, safety, dependability and punctuality, rail mass transit plays a vital role in easing urban traffic congestion. In addition, rail mass transit is environmentally friendly. Even though it is beneficial to passengers in urban areas, security issues have become increasingly serious in recent years. To improve the safety and dependability of the rail mass transit system to some extent and limit the loss to a bare minimum, it is necessary to identify and evaluate the hazards connected with rail mass transit in the early stages of the system's operation. Against this backdrop, this research employs a risk matrix approach to examine the dangers connected with Abuja's rail mass transit system (ARMT). The questionnaire is designed and delivered to 100 participants, including personnel and passengers, to get their perceptions of hazards at the ARMT. The questionnaire is the initial step in the research process. The four safety variables discussed in this study are human error, equipment design failure, environmental conditions and management. Human error is the most significant factor covered in this research. Understanding the source of risk stemming from these four safety variables at the early stages of rail mass transit operation can significantly improve the system's overall safety and reliability, which can be paramount. According to the findings of the investigations, human-related activity is the most significant possible cause of risk at that ARMT, with a high level of risk portrayed by the data.
SNAI1 is upregulated during muscle regeneration and represses FGF21 and ATF3 expression by directly binding their promoters
Authors: Elia Ines , Realini Giulia , Di Mauro Vittoria , Borghi Sara , Bottoni Laura , Tornambè Salvatore , Vitiello Libero , Weiss Stephen J. , Chiariello Mario , Tamburrini Annalaura , Oliviero Salvatore , Neri Francesco , Orlandini Maurizio , Galvagni Federico
Published: June 2022

During skeletal myogenesis, the zinc‐finger transcription factors SNAI1 and SNAI2, are expressed in proliferating myoblasts and regulate the transition to terminally differentiated myotubes while repressing pro‐differentiation genes. Here, we demonstrate that SNAI1 is upregulated in vivo during the early phase of muscle regeneration induced by bupivacaine injury. Using shRNA‐mediated gene silencing in C2C12 myoblasts and whole‐transcriptome microarray analysis, we identified a collection of genes belonging to the endoplasmic reticulum (ER) stress pathway whose expression, induced by myogenic differentiation, was upregulated in absence of SNAI1. Among these, key ER stress genes, such as Atf3, Ddit3/Chop, Hspa5/Bip, and Fgf21, a myokine involved in muscle differentiation, were strongly upregulated. Furthermore, by promoter mutant analysis and Chromatin immune precipitation assay, we demonstrated that SNAI1 represses Fgf21 and Atf3 in proliferating myoblasts by directly binding to multiple E boxes in their respective promoter regions. Together, these data describe a new regulatory mechanism of myogenic differentiation involving the direct repressive action of SNAI1 on ER stress and Fgf21 expression, ultimately contributing to maintaining the proliferative and undifferentiated state of myoblasts.
Calcific aortic valve stenosis and COVID-19: clinical management, valvular damage, and pathophysiological mechanisms
Authors: Bäck Magnus , Hashem Mohammed , Giani Anna , Pawelzik Sven-Christian , Franco-Cereceda Anders
Published: June 2022

Patients with corona virus disease (COVID)-19 are prone to a variety of myocardial and vascular complications. Recent studies suggest that cardiac valves are also potential targets for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease. Severe COVID-19 has been associated with main risk factors for CAVS, including male sex, older age, cardiovascular co-morbidities, obesity, hypertension, diabetes, and chronic kidney disease. Prognostic implications for concomitant CAVS and SARS-CoV-2 infection have been reported. Changes in CAVS diagnostic, interventional, and follow-up clinical processes have occurred during the COVID-19 pandemic. SARS-CoV-2 may damage aortic valves via both direct injury and indirect mechanisms that include hyperinflammation, oxidative stress, and valve thrombosis. The injury is often acute but may be irreversible and thus favor future CAVS development. Rheumatic heart disease, which develops as a sequel of rheumatic fever, is one example of a possible relation between an acute infection and chronic valvular heart disease. A persistent prothrombotic state, prolonged endothelial dysfunction, and incomplete resolution of inflammation after COVID-19 convalescence may expose the aortic valves to chronic stimulation toward CAVS. Priority of CAVS management in COVID-19 includes avoiding treatment delay and managing underlying pathophysiological state that promotes CAVS.
Aldehyde dehydrogenase 2-associated metabolic abnormalities and cardiovascular diseases: current status, underlying mechanisms, and clinical recommendations
Authors: Xu Lei , Cui Xiao-Tong , Chen Zhang-Wei , Shen Ling-Hong , Gao Xiu-Fang , Yan Xiao-Xiang , Wang Cong , Zhang Xiao-Kai , Hu Kai , Ge Jun-Bo , Sun Ai-Jun
Published: June 2022

Cardiovascular diseases originate from various pathogeneses, among which metabolic abnormalities are common. An integrated metabolic disturbance in common cardiovascular diseases has been suggested, particularly in the Asian population. This speculation is supported by the finding that aldehyde dehydrogenase 2 (ALDH2) gene mutations are present in nearly half of the Asian population. ALDH2 mutations significantly reduce ALDH2 enzyme activity and increase production of toxic aldehydes, including 4-hydroxynonenal, and are involved in the pathophysiology of several cardiovascular disorders such as atherosclerosis and myocardial infarction. Additionally, individuals with ALDH2 mutations are more susceptible to hypertension and diabetes, and these mutations are significantly correlated with heart failure. Until now there are no actionable clinical recommendations with regards to screening for ALDH2 mutations. A comprehensive understanding of the relationship between ALDH2 and these etiologies may greatly help in better prevention and treatment of cardiovascular diseases in populations, especially Asian, where ALDH2 mutations are common.
Signaling pathways of inflammation in myocardial ischemia/reperfusion injury
Authors: Hu Shi-Yu , Yang Ji-E , Zhang Feng
Published: June 2022

Primary percutaneous coronary intervention is the current standard treatment for myocardial infarction, but is associated with ischemia/reperfusion injury for which inflammation is an important part. This review summaries the recent findings in the study of pro- and anti-inflammatory signaling pathways (eg, TLR4/Myd88/NF-κB, MAPKs/NF-κB, NLRP3 inflammasome, JAK2/STAT3, and Nrf2/HO-1) in myocardial ischemia/reperfusion injury, as well as relevant drug development efforts. Despite of the vast body of literature, no concrete advances have been made in translating the new knowledge into clinical practice, but we do anticipate major breakthroughs in the foreseeable future.
Maternal and fetal health outcomes of cesarean sections (CS) in Ethiopia: results from retrospective cross-sectional study of Southern Ethiopia Gurage Zone Governmental Hospitals
Authors: Belay Helina M. , Kassa Roza T. , Negeri Haweni A. , Woldesenbet Ermiyas B. , Belachew Fitsum K.
Published: June 2022

Background:

The most common obstetric surgery performed nowadays is a cesarean section (CS). Even though cesarean delivery is the safest mode of delivery in high-risk scenarios, it also appears to have a higher risk of maternal and newborn morbidity and mortality than vaginal delivery, and in low-resource settings, the risks are doubled. In this study we investigated fetal and maternal outcomes following CS in southern Ethiopia, specifically in the Gurage region, to better understand and quantify the prevalence of these outcomes and to provide recommendations based on the findings.

Methods:

Institutional based retrospective cross-sectional study was conducted in Gurage Zone in 5 governmental hospitals from February 21, 2021 to March 13, 2021, on the hospital medical records of mothers who delivered by CS from February 2019 to January 2021. The collected data was entered and analyzed using STATA version 15. Binary and Multiple Logistic regressions were used to identify associated factors for maternal outcome and fetal outcome.

Results:

Among the 368 mothers included in the study, 86 (23.4%) had poor maternal outcomes, and the 3 most common causes were postop infection 19 (25.6%), the need for blood transfusion 16 (21.6%), and anesthesia-related complications 9 (12.1%). On the other hand, from the 384 neonates studied, 75 (19.74%) had poor outcomes with 16 (4.2%) perinatal death, and 60 (15,6%) had low first-minute APGAR scores needing close monitoring. Obstetric complications, medical diseases, and AntePartum Hemorrhage as an indication for CS were statistically significant factors for poor maternal outcomes. Similarly, medical disease and cephalic pelvic disproportion as an indication for CS were statistically significant factors for poor fetal outcomes.

Conclusion and recommendation:

The numbers are not uniformly high or low when compared with other regions of Ethiopia, but they are closely related, suggesting a need for immediate collaborative evidence-based interventions to improve hospital capacities and preoperative optimization strategies, since pregnancy-related complications, preoperative hemorrhages, and preoperative medical conditions all contributed to poor maternal and neonatal outcomes.
Risk factors for ocular neovascularization after central retinal artery occlusion
Authors: Lo Wen-Jung , Lin Yu-Ching , Chang Hsin-Yi , Chen Mei-Ju
Published: June 2022

Background:

To report the incidence and risk factors associated with ocular neovascularization (NV) in patients with central retinal artery occlusion (CRAO).

Methods:

This retrospective study included patients diagnosed with acute CRAO in a single tertiary center. Medical charts were reviewed for ocular NV occurrences. We analyzed systemic and ocular conditions on first visit and demographic data.

Results:

Eighty-seven eyes were eligible for this study. Among these, 13 eyes had ocular NV after CRAO, with an incidence of 15%. The prevalences of hypertension, diabetes mellitus, history of stroke, chronic kidney disease (CKD), and age at first visit were higher among patients with ocular NV than among patients without ocular NV after CRAO. Moreover, most patients with CKD in the ocular NV group had undergone dialysis. A multivariate regression analysis revealed that CKD (hazard ratio [HR]: 9.27, 95% CI, 1.87-46.05, p = 0.006) and glaucoma history (HR: 7.52, 95% CI, 1.14-49.46, p = 0.036) were significant risk factors for developing ocular NV among patients with CRAO.

Conclusion:

CKD and glaucoma history were significant risk factors for developing ocular NV after CRAO, particularly among patients that underwent dialysis.
Recalcitrant cutaneous mastocytosis treated with genetically informed targeted therapy
Authors: Gleason Laura , Tekmen Volkan , Cohen Alexa , Bhatti Safiyyah , Beksac Burcu , Cha Jisun , Porcu Pierluigi , Nikbakht Neda
Published: June 2022

Introduction:

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from skin-limited lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.

We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.

Case Presentation:

We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms.

Discussion:

The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy.

Conclusion:

Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.
Livedoid Vasculopathy Secondary to Protein C Deficiency: A Case Successfully Treated With Rivaroxaban
Authors: Chaisrimaneepan Nattanicha , Tienthavorn Tanongkiet
Published: June 2022

Introduction:

Livedoid vasculopathy is a chronic noninflammatory skin disease secondary to hypercoagulable states. No therapeutic guideline has yet been established for livedoid vasculopathy.

We herein report a case of livedoid vasculopathy secondary to protein C deficiency that was successfully treated with rivaroxaban.

Case presentation:

A 31-year-old Thai woman who had been diagnosed with livedoid vasculopathy 10 years previously presented with a 2-month history of worsening leg ulcers and failure to respond to aspirin, colchicine, and pentoxifylline. Further investigations confirmed protein C deficiency. Rivaroxaban was initiated, and clinical improvement was achieved in 8 weeks.

Discussion:

When livedoid vasculopathy is confirmed by skin biopsy, additional investigations for hypercoagulable states should be performed to exclude secondary causes. Identification of the causes of livedoid vasculopathy can direct physicians to therapeutic options based on previously reported cases of successful treatment. Our patient, whose livedoid vasculopathy was caused by protein C deficiency, responded well to rivaroxaban.

Conclusion:

Protein C deficiency results in a hypercoagulable state, and affected patients can present with livedoid vasculopathy. The anticoagulant rivaroxaban has been beneficial in the treatment of livedoid vasculopathy.
Meeting the need for nurse practitioner clinicals: A survey of practitioners
Authors: Gigli Kristin H. , Gonzalez John D.
Published: June 2022

Background:

The increase in the number of nurse practitioner (NP) students requires increased clinical practice sites and prepared preceptors.

Purpose:

This study describes NPs' clinical experiences as a student and their current practices as an NP preceptor.

Methodology:

A descriptive study design used a 38-item web-based survey conducted in June and July 2021.

Results:

A total of 334 NPs practicing in Texas responded; most had been NPs for 10 or fewer years (58.2%) and in their positions less than 5 years (50.3%). A plurality of respondents was required to find their own clinical placements (46%). The most common challenge in obtaining clinical placements was finding preceptors (33%). Nurse practitioners reported excellent clinical experiences (39.3%) as a student and believed that they were generally well prepared for the NP role (38.9%) and to care for their specialty patient population (46.1%) upon graduation. Sixty percent of respondents reported not currently precepting, 37.6% had never been asked to precept, whereas 32.8% reported that employers restricted precepting. Family NPs were the least likely to precept.

Conclusions:

Nurse practitioners report positive clinical experiences that prepare them for NP careers. Multiple opportunities exist to enlist additional NPs as preceptors for NP students.

Implications:

There is capacity within the current NP workforce to meet the clinical educational needs of NP students. Future work should examine best practices to engage NPs who are not currently preceptors. As policies change NP education, research should examine the implications of the preparation for NP roles at the time of graduation, organizational outcomes, and quality of care.
Online Self-Directed Learning Module
Authors: Kuttner Winchell Rodriguez
Published: June 2022

The lack of dedicated time and standardized education for stroke coordinators focusing on program disease-specific care certification standards has led to undue added stress prior to survey. The purpose of this literature review is to provide staff development educators an alternative method to train stroke coordinators. Findings suggest that online self-directed learning modules are useful in acquiring knowledge, gaining clinical competency, improving confidence, and meeting the learners’ needs and satisfaction.
Provider Communication and Fever Protocol for Children With Sickle Cell Disease in the Emergency Department
Authors: Awe Mofoluwake , Robbins Adelaide , Chandi Mohit , Cortright Lindsay , Tumin Dmitry , Whitfield Andrea
Published: June 2022

Objective

We assessed whether prior communication between pediatric hematologists and emergency department (ED) providers reduced time to administration of parenteral antibiotics for children with sickle cell disease presenting with fever.

Methods

Patients 2 months to 21 years of age were retrospectively identified if they were followed up at our center's pediatric hematology clinic and presented to the pediatric ED with fever. Emergency department–hematology communication before patient arrival was ascertained by chart review. The primary outcome was time to administration of parenteral antibiotics after ED arrival, with 60 minutes being the recommended maximum.

Results

Forty-nine patients were included in the analysis. Prior communication occurred in 43% of cases, with a median time to antibiotic administration of 79 minutes in this group (interquartile range, 59–142), compared with 136 minutes for patients without prior communication (interquartile range, 105–181 minutes; P = 0.012). The groups did not differ in hospital length of stay at the index visit.

Conclusions

Advance communication between the pediatric hematologist and ED physician was associated with reduced time to antibiotic administration for febrile children with sickle cell disease. Further interventions should be explored to achieve timely antibiotics administration within 60 minutes of ED arrival.
Care Pattern for Fontan-Associated Liver Disease by Academic Pediatric Hepatologists in Canada
Authors: Kehar Mohit , Jimenez-Rivera Carolina
Published: June 2022

Background:

Fontan-Associated Liver Disease (FALD) is a common extracardiac complication seen in patients following the Fontan procedure. There are no consensus guidelines on screening and management of children with FALD.

Objective:

The current study aims to determine academic pediatric hepatologists’ practices and identify variability in management provided to children with FALD in Canada.

Methods:

Using the infrastructure of the Canadian Pediatric Hepatology Research Group, a nationwide survey was distributed electronically to all pediatric hepatologists practicing in university-affiliated hospitals.

Results:

Twelve pediatric hepatologists from 12 of 13 academic centers (92%) responded to the survey. The institutions of only 2 (17%) physicians offer post-Fontan care with a multidisciplinary team, both from different provinces. The screening for other comorbidities, use of noninvasive modality, and timing of liver biopsy for estimation of liver fibrosis and screening for esophageal varices differ from program to program. The frequency of outpatient clinic follow-up varies significantly. Education and counseling concerning liver health are generally used as treatment; only 58% of academic centers have a formal adult care transition plan.

Conclusions:

Significant discrepancies exist in the care provided to children with FALD by hepatologists practicing in academic centers across Canada. Future study is needed to develop a standardized protocol for managing and following children and youth with FALD.
Giant Meckel’s Diverticulum in a 9-Year-Old Boy: An Unusual Presentation With Isolated Faltering Growth
Authors: Rout Alexandra , Morreau Phil , Bird Helen , Roberts Amin
Published: June 2022

Meckel’s diverticulum is the most common congenital gastrointestinal abnormality. Clinical presentation is normally in childhood with either hemorrhage or an acute surgical abdomen. The much rarer giant Meckel’s diverticulum is associated with a more varied clinical presentation. In this case report, we provide a unique example of presentation with isolated faltering growth related to a giant Meckel’s diverticulum in a young boy. We discuss the diagnostic process, imaging modalities, and subsequent surgical procedure.