bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Evidence-Based Viral Respiratory Illness Mitigation Behaviors in Pregnant Populations: Development and Validation of a Short, Single-Factor Scale During the COVID-19 Pandemic
Authors: Whipps Mackenzie D.M. , Phipps Jennifer E. , Simmons Leigh Ann
Published: May 2022

Objective:

Researchers and public health professionals need to better understand individual engagement in coronavirus disease 2019 (COVID-19) mitigation behaviors to reduce the human and societal costs of the current pandemic and prepare for future respiratory pandemics. We suggest that developing measures of individual mitigation behaviors and testing them among high-risk individuals, including pregnant people, may help to reduce overall morbidity and mortality by quickly identifying targets for messaging around mitigation until sufficient vaccination uptake is reached.

Methods:

We surveyed pregnant people in California over 2 waves of the COVID-19 pandemic to explore mitigation behaviors. We developed and validated a novel Viral Respiratory Illness Mitigation Scale (VRIMS).

Results:

Seven measures loaded onto a single factor with good psychometric properties. The overall sample scale average was high over both waves, indicating that most pregnant Californians engaged in most of the strategies most of the time. Older participants, minoritized participants, those living in more urban contexts, and those surveyed during a surge reported engaging in these strategies most frequently.

Conclusions:

Clinicians and researchers should consider using reliable, validated measures like the VRIMS to identify individuals and communities that may benefit from additional education on reducing risk for COVID-19, future respiratory pandemics, or even seasonal flu.
Prognostic Performance of Shock Index, Diastolic Shock Index, Age Shock Index, and Modified Shock Index in COVID-19 Pneumonia
Authors: Avci Mustafa , Doganay Fatih
Published: May 2022

Objective:

We aimed to compare the prognostic accuracy of shock indexes in terms of mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia.

Methods:

Hospitalized patients whose COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) test results were positive, had thoracic computed tomography (CT) scan performed, and had typical thoracic CT findings for COVID-19 were included in the study.

Results:

Eight hundred one patients were included in the study. Chronic obstructive pulmonary disease, congestive heart failure, chronic neurological diseases, chronic renal failure, and a history of malignancy were found to be chronic diseases that were significantly associated with mortality in patients with COVID-19 pneumonia. White blood cell, neutrophil, lymphocyte, C reactive protein, creatinine, sodium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, high sensitive troponin, d-dimer, hemoglobin, and platelet had a statistically significant relationship with in-hospital mortality in patients with COVID-19 pneumonia. The area under the curve (AUC) values of shock index (SI), age shock index (aSI), diastolic shock index (dSI), and modified shock index (mSI) calculated to predict mortality were 0.772, 0.745, 0.737, 0.755, and Youden Index J (YJI) values were 0.523, 0.396, 0.436, 0.452, respectively.

Conclusions:

The results of this study show that SI, dSI, mSI, and aSI are effective in predicting in-hospital mortality.
Novel Multidisciplinary Vascular Access Team Helps to Improve ICU Workflow Amidst Covid-19 Pandemic
Authors: Hackett Anna K. , Wells Celia M. , Gupta Rohit , Zhang Ziya , Brito Amy , Kirton Natalie B. , Chan Christy C. , Brown Kester , Wong Caitlin , Leonardi Kayla M. , Shittu Atinuke , Lay Cappi , Kohli-Seth Roopa
Published: May 2022

Objective:

The surge in critically ill patients has pressured hospitals to expand their intensive care unit capacities and critical care staff. This was difficult given the country’s shortage of intensivists. This paper describes the implementation of a multidisciplinary central line placement team and its impact in reducing the vascular access workload of ICU physicians during the height of the COVID-19 pandemic.

Methods:

Vascular surgeons, interventionalists, and anesthesiologists, were redeployed to the ICU Access team to place central and arterial lines. Nurses with expertise in vascular access were recruited to the team to streamline consultation and assist with line placement.

Results:

While 51 central and arterial lines were placed per 100 ICU patients in 2019, there were 87 central and arterial lines placed per 100 COVID-19 ICU patients in the sole month of April, 2020. The ICU Access Team placed 107 of the 226 vascular access devices in April 2020, reducing the procedure-related workload of ICU treating teams by 46%.

Conclusions:

The ICU Access Team was able to complete a large proportion of vascular access insertions without reported complications. Given another mass casualty event, this ICU Access Team could be reassembled to rapidly meet the increased vascular access needs of patients.
The Role of Public Health Emergency Management in Biodefense: A COVID-19 Case Study
Authors: Houser Ryan Scott
Published: May 2022

Introduction:

The emergence of the COVID-19 pandemic has had significant impact on human lives as well as economic and social stability. The United States has a complicated history with biosecurity as policy making, biodefense activities, and government transparency have historically been in contention. The terror attacks of September 11, 2001 uncovered various weaknesses in the national public health infrastructure that have persisted into the current pandemic.

Methods:

This study explores the biodefense and public health preparedness landscape for trends in federal support and capacity building. It also investigates the applicability of public health emergency management principles to the biodefense structure. A mixed method was utilized in this study to investigate the qualitative and quantitative factors of the research inquiry. Braun and Clarke’s six phase framework for thematic analysis will assist with defining the important information from a review of the literature. The concurrent triangulation design permits that use of qualitative and quantitative data to more accurately define and analyze the relationship among the variables of interest

Results:

The results included the identification of 8 common themes of failure during the COVID-19 response: (1) accountable leadership, (2) statutory authorities and policies, (3) inter-agency coordination, (4) coherent data system for situational awareness, (5) strategic national stockpile and supply chain, (6) testing and surveillance, (7) health care system surge capacity and resilience, and (8) federal funds and the role of public health emergency management in the evolving landscape of biothreats, both intentional and natural.

Discussion:

To counter the increasing biothreats, the United States must invest in revamping the biodefense infrastructure to mimic and support public health emergency preparedness initiatives which will increase our resilience to various biothreats.
Geometric morphometric analysis for the systematic elucidation of new Hylicellidae from the Jurassic of China (Hemiptera: Cicadomorpha)
Authors: Chen Jun , Zhang Qianqi , Jiang Hui , Li Yuling , Zheng Yan , Yu Shuai , Wang Xiaoli , Zhang Haichun
Published: May 2022

The extinct family Hylicellidae, as the ancestral group of modern cicadomorphans, had a wide distribution and a very high species-level biodiversity from the Triassic to Early Cretaceous. We herein report 11 new hylicellid specimens from the Jurassic Daohugou beds of Inner Mongolia, NE China, and execute geometric morphometric analysis (GMA) to elucidate their systematic position. Our GMA and subsequent morphometric statistics indicate that 10 of our new specimens can be compared to the holotype of Cycloscytina gobiensis, and one is new to science. Cycloscytina incompleta new species is erected based on this specimen, with the following discriminatory tegminal traits: C3 almost as long as and slightly narrower than C2, and the forking position of stem M distinctly migrates towards wing apex and much apicad of the stem CuA bifurcating. Additionally, Cycloscytina plachutai is herein transferred to the procercopid genus Procercopina, resulting in P. plachutai new combination. To date, just a few body structures of Hylicellidae have been revealed, and the new whole-bodied hylicellids reported herein provide some novel insights on the evolution of basal Clypeata. This study also emphasizes the use of morphometric analysis in the systematics of wing-bearing insects such as hylicellids.

UUID: http://zoobank.org/84a67eba-9b7c-4e27-a436-764802c4cdfb.
Palliative care management of head and neck cancer patients among otolaryngology surgeons: a novel national survey assessing knowledge, decision making, perceived confidence and training in the UK
Authors: Lotfallah A , Al-Hity S , Limbrick J , Khan N , Darr A
Published: May 2022

Objective

Management of head and neck cancer patients provides unique challenges. Palliation serves to optimise quality-of-life by alleviating suffering and maintaining dignity. Prompt recognition and management of suffering is paramount to achieving this. This study aimed to assess perceived confidence, knowledge and adequacy of palliative training among UK-based otolaryngologists.

Method

Eight multiple-choice questions developed by five palliative care consultants via the Delphi method were distributed over five weeks. Knowledge, perceived confidence and palliative exposure among middle-grade and consultant otolaryngologists were assessed, alongside training deficits.

Results

Overall, 145 responses were collated from middle-grade (n = 88, 60.7 per cent) and consultant (n = 57, 39.3 per cent) otolaryngologists. The mean knowledge score was 5 out of 10, with 22.1 per cent (n = 32) stating confidence in palliative management. The overwhelming majority (n = 129, 88.9 per cent) advocated further training.

Conclusion

A broad understanding of palliative care, alongside appropriate specialist involvement, is key in meeting the clinical needs of palliative patients. Curriculum integration of educational modalities such as simulation and online training may optimise palliative care.
A method to identify and rank objects and hazardous interactions affecting autonomous ships navigation
Authors: Bolbot Victor , Theotokatos Gerasimos , Wennersberg Lars Andreas
Published: May 2022

The Autonomous Navigation System (ANS) constitutes a critical key enabling technology required for operating Maritime Autonomous Surface Ships (MASS). To assure the safety of MASS operations, the effective identification of potential objects and target ships interacting with the own MASS is quintessential. This study proposes a systematic method to identify the items interacting with the own MASS. This method is based on a similar approach previously employed for the encountering items’ identification in robotics, which is customised herein for the MASS needs. The developed method is applied to a short-sea shipping MASS. The environmental features, agents and objects related to her navigation are identified and ranked based on the frequency of encounter and the potential collision consequences. The results demonstrate the ability of the method to identify additional items in comparison to Automatic Identification System based data. The interactions with the small ships are considered as the most critical, due to their potential accidental consequences and their exhibited high frequency of encounter. This study results are employed to support the ANS design and testing of the investigated ship.
Convolution and deconvolutional treatment on sample transparency aberration in Bragg–Brentano geometry
Authors: Ida Takashi
Published: May 2022

Exact and approximate mathematical models for the effects of sample transparency on the powder diffraction intensity data are examined. Application of the formula based on the first-order approximation about the deviation angle is justified for realistic measurement and computing systems. The effects of sample transparency are expressed by double convolution formulas applying two different scale transforms, including three parameters, goniometer radius R, penetration depth μ−1, and thickness of the sample t. The deconvolutional treatment automatically recovers the lost intensity and corrects the peak shift and asymmetric deformation of peak profile caused by the sample transparency.
Anxiety-specific associations with substance use: Evidence of a protective factor in adolescence and a risk factor in adulthood
Authors: Rieselbach Maya M. , Corley Robin P. , Hewitt John K. , Rhee Soo Hyun
Published: May 2022

Externalizing psychopathology is a strong risk factor for substance use, whereas the role of internalizing manifestations of distress, and anxiety in particular, in predicting substance use remains unclear. Studies have suggested that anxiety may be either a protective or risk factor for substance use. The present study aimed to clarify evidence for anxiety-specific associations with substance use, examining sex and developmental period (adolescence vs. adulthood) as potential moderators that may help explain conflicting results in the literature. In a longitudinal twin sample, cross-sectional associations of anxiety with substance use differed in adolescents and adults and in girls/women and boys/men. Controlling for externalizing psychopathology and depression, anxiety was associated with reduced substance use in adolescent girls and increased substance use in adult women. In contrast, anxiety-specific associations with substance use were not significant in boys and men. Possible explanations for these contrasting results across development and sex are discussed.
Anxiety, academic achievement, and academic self-concept: Meta-analytic syntheses of their relations across developmental periods
Authors: Brumariu Laura E. , Waslin Stephanie M. , Gastelle Marissa , Kochendorfer Logan B. , Kerns Kathryn A.
Published: May 2022

This systematic review examined how anxiety symptoms and anxiety disorders relate to academic achievement, school dropout, and academic self-concept. Studies with children or adult samples were included in seven meta-analyses (ks for number of samples ranged from 5 to 156; N’s for participants ranged from 780 to 37, 203). Results revealed significant but very small effect sizes for the relations between anxiety and overall academic achievement (r = −.06), language achievement (r = −.07), and math achievement (r = −.09), and a nonsignificant effect size for science achievement (r = −.01). Participants with greater anxiety were also significantly more likely to not complete high school (r = .11). They also had a poorer overall academic self-concept (r = −.25) and mathematics self-concept (r = −.30). Few methodological moderators (e.g., study design, age) were significant. Results show that anxiety does not strongly hinder academic achievement, but it is an important correlate of dropout and academic self-concept, which in turn could contribute to poorer life outcomes. Interventions and preventive programs need to consider ways to ameliorate the relations of anxiety with academic outcomes, especially school continuation and academic self-concept. Future studies should identify risk factors that may amplify these relations.
Does the use of proton pump inhibitors in children affect ventricular repolarisation parameters?
Authors: Tasci Onur , Kiran Tasci Ezgi
Published: May 2022

Proton pump inhibitors are widely used agents in the treatment of dyspepsia, and their effects on ventricular repolarisation through ion channels are well-known. Our aim is to evaluate the change in ventricular repolarisation parameters on electrocardiogram before and after proton pump inhibitor treatment. This study included 69 patients who had symptoms such as burning stomach pain, bloating, nausea, and heartburn for at least 3 months. Electrolyte levels of the patients were measured before and after treatment, and 12-lead electrocardiograms were taken at the initial and 1st month follow-up visit. Heart rate, QT interval, corrected QT (QTc), QT dispersion (QTd), QTc dispersion (QTcd), Tp-e measurements, and Tp-e/QT ratio were calculated and compared. Thirty-nine of the patients were girls, 30 were boys, and the mean age was 13.16 ± 3.02 years. Electrolyte levels of the patients before and after treatment were within the normal range. There was no statistically significant difference in the QTc, the Tp-e duration, or the Tp-e/QT ratio of the patients before and after treatment. We did not find a significant prolongation in the QTc duration or any other ventricular repolarisation parameters after proton pump inhibitor treatment in children with dyspepsia. We did not observe ventricular arrhythmia in our patients during follow-up. However, different results might be obtained with a larger sample and a longer follow-up period. These patients may have an increased risk of developing ventricular arrhythmias. Therefore, precaution should be taken when using drugs that prolong the QT period, and follow-up with serial electrocardiograms should be planned.
Infection preparedness of community health workers: implications for maternal and neonatal health services in Pakistan
Authors: Rizvi Jafree Sara , Khawar Amna , Momina Ain ul , Khalid Mahmood Qaisar
Published: May 2022

Aim:

This study aimed to (i) identify community health workers’ (CHWs) perceived satisfaction for maternal and neonatal health services, with respect to (1) socio-demographic characteristics; (2) coronavirus preparedness; (3) coronavirus responsiveness; and (4) employee satisfaction and (ii) investigate the interplay among study variables to identify the role of direct effects and mediation.

Background:

Women CHWs are salient providers for maternal and neonatal services at the primary level, especially in conservative regions. Service delivery is a valuable indicator for mother and newborn wellbeing. There is need for empirical evidence to understand how CHWs may be supported in delivering maternal and neonatal health services during pandemics.

Methods:

Bivariate regression was used to identify the lower odds for CHWs’ perceived satisfaction for maternal and neonatal health services. In addition, structural equation modeling was used to investigate if coronavirus responsiveness and employee satisfaction as mediating variables influence the relationship between coronavirus preparedness and maternal and neonatal health services. Data were collected telephonically from 350 CHWs. The sample was representative of 35 districts of Punjab, which is the most populated province in the country.

Findings:

We found thirty predictors with respect to coronavirus preparedness, coronavirus responsiveness and employee satisfaction which contribute to lower odds of satisfaction for maternal and neonatal health services. We also found that coronavirus preparedness has a direct effect on maternal and neonatal health service satisfaction (β = .242, P < .001) and an indirect effect on maternal health satisfaction (β = .242, P < .001) via the mediation of employee satisfaction. We conclude with four critical recommendations to support CHWs in delivering optimal services, comprising of education and training, operational support, public acceptance, and employee support and benefits. The findings are important for the planning of primary health services and governance support for CHWs and poor women clients in Pakistan and other developing countries.
The Production of Employment Conditions for Migrant Care Workers: Cross National Perspectives
Authors: Charlesworth Sara , Malone Jennifer
Published: May 2022

There is widespread scholarly recognition that migrant long-term care (LTC) workers experience relatively poorer work conditions than local LTC workers. We focus here on the ways in which migration and employment regulation intersect in formal LTC markets to produce working conditions for migrant workers. Drawing on cross-national comparisons between Australia, the Netherlands and the United Kingdom we explore: firstly, the forms of employment regulation that can protect migrant LTC workers or expose them to additional risks; and secondly, how migration regulation can work to amplify employment protection gaps for certain groups of migrant workers. We find that while historically there have been better employment protections in Australia and the Netherlands, the reshaping of work in all three LTC systems creates a context within which migration regulation can exacerbate the risks of precarious work for migrant workers and for those on temporary visas in particular.
Social vulnerability, social-ecological resilience and coastal governance
Authors: Jozaei Javad , Chuang Wen-Ching , Allen Craig R. , Garmestani Ahjond
Published: May 2022

Non-technical summary

Our analysis shows that the framing of social vulnerability is shaped by a narrow definition of resilience, focusing on post-disaster return and recovery responses. This perspective does not account for the dynamism and non-stationarity of social-ecological systems (SES) which is becoming increasingly important in the face of accelerating environmental change. Incorporating social-ecological resilience into social vulnerability analysis can improve coastal governance by accounting for adaptation and transformation, as well as scale and cross-scale interactions.

Technical summary

Social vulnerability analysis has been unable to deliver outcomes that reflect the reality of vulnerability and its consequences in an era characterised by accelerating environmental change. In this work, we used critical discourse analysis and key informant interviews to understand different framings of social vulnerability in coastal governance and management, globally and in New Zealand. We found that the framing of system vulnerability could vary depending on the definition of resilience adopted, which has critical ramifications for coastal governance of linked systems of humans and nature. We found that the framing of social vulnerability in coastal governance is mainly influenced by engineering, community and disaster resilience, focusing on return and recovery governance responses to environmental change (e.g. hurricanes, wildfires). Instead, we suggest a novel perspective based on social-ecological resilience, which more accurately reflects the dynamics of linked systems of humans and nature (SES). This revised perspective, general vulnerability, accounts for the dynamics of Earth's systems across various spatial and temporal scales in the face of accelerating environmental change. Accounting for social-ecological resilience and its core aspects (i.e. panarchy, adaptation and transformation) is essential for informing coastal governance of SES (Do we adapt? or Do we transform the SES?).

Social media summary

Social-ecological resilience is essential for social vulnerability analysis in the face of accelerating environmental change.
Compound Heterozygous Mutations Presented with Quadriparesis and Menopause. A Case Report
Authors: Noorian Shahab , Mohammadpoor Nami Sahar , Nouri Ghonbalani Zahra , Mohammadian Khonsari Nami
Published: May 2022

Mitochondrion regulates cellular metabolism with the aid of its respiratory complexes; any defect within these complexes can result in mitochondrial malfunction and various conditions. One such mutation can occur in SLC25A10, resulting in mitochondrial DNA depletion syndrome. It should be noted that the pattern of inheritance of this syndrome is autosomal recessive. However, we present a case with compound heterozygous mutations within this gene resulting in disease. An 18-year-old female was referred to our clinic due to menopause with a medical history of hearing loss, spasticity, hypotonia and quadriparesis. The child’s birth and development were uneventful until the initiation of movement reduction and hypotonia when she was 12 months old. Afterward, the hypotonia progressed to quadriparesis and spasticity throughout the years. Our patient became completely quadriplegic up to the age of 3 and became completely deaf at 10. Her puberty onset was at the age of 9, and no significant event took place until she was 17 years old when suddenly her periods, which were regular until that time, became irregular and ceased after a year; hence, a thorough evaluation began, but similar to her previous evaluations all tests were insignificant. Nonetheless, we suspected an underlying metabolic or genetic defect; thus, we ordered a whole-exome sequencing (WES) workup and found simultaneous heterozygous mutations within SLC25A10, HFE and TTN genes that could explain her condition. When all other tests fail, and we suspect an underlying genetic or metabolic cause, WES can be of great value.
Characteristic Depths, Fluxes, and Timescales for Greenland's Tidewater Glacier Fjords From Subglacial Discharge‐Driven Upwelling During Summer
Authors: Slater D. A. , Carroll D. , Oliver H. , Hopwood M. J. , Straneo F. , Wood M. , Willis J. K. , Morlighem M.
Published: May 2022

Greenland's glacial fjords are a key bottleneck in the earth system, regulating exchange of heat, freshwater and nutrients between the ice sheet and ocean and hosting societally important fisheries. We combine recent bathymetric, atmospheric, and oceanographic data with a buoyant plume model to show that summer subglacial discharge from 136 tidewater glaciers, amounting to 0.02 Sv of freshwater, drives 0.6–1.6 Sv of upwelling. Bathymetric analysis suggests that this is sufficient to renew most major fjords within a single summer, and that these fjords provide a path to the continental shelf that is deeper than 200 m for two‐thirds of the glaciers. Our study provides a first pan‐Greenland inventory of tidewater glacier fjords and quantifies regional and ice sheet‐wide upwelling fluxes. This analysis provides important context for site‐specific studies and is a step toward implementing fjord‐scale heat, freshwater and nutrient fluxes in large‐scale ice sheet and climate models.
The Tides of Enceladus' Porous Core
Authors: Rovira‐Navarro Marc , Katz Richard F. , Liao Yang , van der Wal Wouter , Nimmo Francis
Published: May 2022

The inferred density of Enceladus' core, together with evidence of hydrothermal activity within the moon, suggests that the core is porous. Tidal dissipation in an unconsolidated core has been proposed as the main source of Enceladus' geological activity. However, the tidal response of its core has generally been modeled assuming it behaves viscoelastically rather than poroviscoelastically. In this work, we analyze the poroviscoelastic response to better constrain the distribution of tidal dissipation within Enceladus. A poroviscoelastic body has a different tidal response than a viscoelastic one; pressure within the pores alters the stress field and induces a Darcian porous flow. This flow represents an additional pathway for energy dissipation. Using Biot's theory of poroviscoelasticity, we develop a new framework to obtain the tidal response of a spherically symmetric, self‐gravitating moon with porous layers and apply it to Enceladus. We show that the boundary conditions at the interface of the core and overlying ocean play a key role in the tidal response. The ocean hinders the development of a large‐amplitude Darcian flow, making negligible the Darcian contribution to the dissipation budget. We therefore infer that Enceladus' core can be the source of its geological activity only if it has a low rigidity and a very low viscosity. A future mission to Enceladus could test this hypothesis by measuring the phase lags of tidally induced changes of gravitational potential and surface displacements.
Sensitivity of the Arctic Sea Ice Cover to the Summer Surface Scattering Layer
Authors: Smith Madison M. , Light Bonnie , Macfarlane Amy R. , Perovich Don K. , Holland Marika M. , Shupe Matthew D.
Published: May 2022

The “surface scattering layer” (SSL) is the highly‐scattering, coarse‐grained ice layer that forms on the surface of melting, drained sea ice during spring and summer. Ice of sufficient thickness with an SSL has an observed persistent broadband albedo of ∼0.65, resulting in a strong influence on the regional solar partitioning. Experiments during the Multidisciplinary drifting Observatory for the Study of the Arctic Climate expedition showed that the SSL re‐forms in approximately 1 day following manual removal. Coincident spectral albedo measurements provide insight into the SSL evolution, where albedo increased on sunny days with higher solar insolation. Comparison with experiments in radiative transfer and global climate models show that the sea ice albedo is greatly impacted by the SSL thickness. The presence of SSL is a significant component of the ice‐albedo feedback, with an albedo impact of the same order as melt ponds. Changes in SSL and implications for Arctic sea ice within a warming climate are uncertain.
Record Low Arctic Sea Ice Extent in 2012 Linked to Two‐Year La Niña‐Driven Sea Surface Temperature Pattern
Authors: Jeong Hyein , Park Hyo‐Seok , Stuecker Malte F. , Yeh Sang‐Wook
Published: May 2022

Arctic summer sea ice decline accelerated from the mid‐2000s to 2012, with the 2012 record low remaining unbroken. While frequent La Niña events during this period have been suggested as a driver of this trend acceleration, no convincing evidence has been presented. Here, using a climate model nudged to observed pan‐tropical sea surface temperatures (SST), we show that the back‐to‐back La Niña events during 2010–2011, followed by a North Pacific cooling and a marginal El Niño, were a key contribution to the 2012 record low. Specifically, the La Niña events in 2010–2011 warmed the Arctic Pacific sector, whereas tropical SST anomalies in 2012 strengthened the Greenland high pressure, leading to an Arctic dipole‐like pressure pattern and strengthening of transpolar ice drift. These Arctic temperature and circulation anomalies led to the record low sea ice extent in 2012, highlighting the strong influence of tropical SSTs on Arctic climate.
Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis
Authors: Luo Kui , Wang Zhifei , Zhuang Kai , Yuan Shishan , Liu Fei , Liu Aihua
Published: May 2022

Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.
Predicted cardiovascular disease risk and prescribing of antihypertensive therapy among patients with hypertension in Australia using MedicineInsight
Authors: Roseleur Jacqueline , Gonzalez-Chica David A. , Karnon Jonathan , Stocks Nigel P.
Published: May 2022

Hypertension guidelines recommend that absolute cardiovascular disease (CVD) risk guide the management of hypertensive patients. This study aimed to assess the proportion of patients with diagnosed hypertension with sufficient data to calculate absolute CVD risk and determine whether CVD risk is associated with prescribing of antihypertensive therapies. This was a cross-sectional study using a large national database of electronic medical records of patients attending general practice in 2018 (MedicineInsight). Of 571,492 patients aged 45–74 years without a history of CVD, 251,733 [40.6% (95% CI: 39.8–41.2)] had a recorded hypertension diagnosis. The proportion of patients with sufficient recorded data available to calculate CVD risk was higher for patients diagnosed with hypertension [51.0% (95% CI: 48.0–53.9)] than for patients without a diagnosis of hypertension [38.7% (95% CI: 36.5–41.0)]. Of those patients with sufficient data to calculate CVD risk, 29.3% (95% CI: 28.1–30.6) were at high risk clinically, 6.0% (95% CI: 5.8–6.3) were at high risk based on their CVD risk score, 12.8% (95% CI: 12.5–13.2) at moderate risk and 51.8% (95% CI: 50.8–52.9) at low risk. The overall prevalence of antihypertensive therapy was 60.9% (95% CI: 59.3–62.5). Prescribing was slightly lower in patients at high risk based on their CVD risk score [57.4% (95% CI: 55.4–59.4)] compared with those at low [63.3% (95% CI: 61.9–64.8)] or moderate risk [61.8% (95% CI: 60.2–63.4)] or at high risk clinically [64.1% (95% CI: 61.9–66.3)]. Guideline adherence is suboptimal, and many patients miss out on treatments that may prevent future CVD events.
An epigenetic association analysis of childhood trauma in psychosis reveals possible overlap with methylation changes associated with PTSD
Authors: Løkhammer Solveig , Stavrum Anne-Kristin , Polushina Tatiana , Aas Monica , Ottesen Akiah A. , Andreassen Ole A. , Melle Ingrid , Le Hellard Stephanie
Published: May 2022

Patients with a severe mental disorder report significantly higher levels of childhood trauma (CT) than healthy individuals. Studies have suggested that CT may affect brain plasticity through epigenetic mechanisms and contribute to developing various psychiatric disorders. We performed a blood-based epigenome-wide association study using the Childhood Trauma Questionnaire-short form in 602 patients with a current severe mental illness, investigating DNA methylation association separately for five trauma subtypes and the total trauma score. The median trauma score was set as the predefined cutoff for determining whether the trauma was present or not. Additionally, we compared our genome-wide results with methylation probes annotated to candidate genes previously associated with CT. Of the patients, 83.2% reported CT above the cutoff in one or more trauma subtypes, and emotional neglect was the trauma subtype most frequently reported. We identified one significant differently methylated position associated with the geneTANGO6for physical neglect. Seventeen differentially methylated regions (DMRs) were associated with different trauma categories. Several of these DMRs were annotated to genes previously associated with neuropsychiatric disorders such as post-traumatic stress disorder and cognitive impairments. Our results support a biomolecular association between CT and severe mental disorders. Genes that were previously identified as differentially methylated in CT-exposed subjects with and without psychosis did not show methylation differences in our analysis. We discuss this inconsistency, the relevance of our findings, and the limitations of our study.
POH1/Rpn11/PSMD14: a journey from basic research in fission yeast to a prognostic marker and a druggable target in cancer cells
Authors: Spataro Vito , Buetti-Dinh Antoine
Published: May 2022

POH1/Rpn11/PSMD14 is a highly conserved protein in eukaryotes from unicellular organisms to human and has a crucial role in cellular homoeostasis. It is a subunit of the regulatory particle of the proteasome, where it acts as an intrinsic deubiquitinase removing polyubiquitin chains from substrate proteins. This function is not only coupled to the translocation of substrates into the core of the proteasome and their subsequent degradation but also, in some instances, to the stabilisation of ubiquitinated proteins through their deubiquitination. POH1 was initially discovered as a functional homologue of the fission yeast gene pad1+, which confers drug resistance when overexpressed. In translational studies, expression of POH1 has been found to be increased in several tumour types relative to normal adjacent tissue and to correlate with tumour progression, higher tumour grade, decreased sensitivity to cytotoxic drugs and poor prognosis. Proteasome inhibitors targeting the core particle of the proteasome are highly active in the treatment of myeloma, and recently developed POH1 inhibitors, such as capzimin and thiolutin, have shown promising anticancer activity in cell lines of solid tumours and leukaemia. Here we give an overview of POH1 function in the cell, of its potential role in oncogenesis and of recent progress in developing POH1-targeting drugs.
Types of necroinflammation, the effect of cell death modalities on sterile inflammation
Authors: Mázló Anett , Jenei Viktória , Burai Sára , Molnár Tamás , Bácsi Attila , Koncz Gábor
Published: May 2022

Distinct types of immune responses are activated by infections, which cause the development of type I, II, or III inflammation, regulated by Th1, Th2, Th17 helper T cells and ILC1, ILC2 and ILC3 cells, respectively. While the classification of immune responses to different groups of pathogens is widely accepted, subtypes of the immune response elicited by sterile inflammation have not yet been detailed. Necroinflammation is associated with the release of damage-associated molecular patterns (DAMP) from dying cells. In this review, we present that the distinct molecular mechanisms activated during apoptosis, necroptosis, pyroptosis, and ferroptosis lead to the release of different patterns of DAMPs and their suppressors, SAMPs. We summarize the currently available data on how regulated cell death pathways and released DAMPs and SAMPs direct the differentiation of T helper and ILC cells. Understanding the subtypes of necroinflammation can be crucial in developing strategies for the treatment of sterile inflammatory diseases caused by cell death processes.
Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank
Authors: Hay Rachel , Cullen Breda , Graham Nicholas , Lyall Donald M. , Aman Alisha , Pell Jill P. , Ward Joey , Smith Daniel J. , Strawbridge Rona J.
Published: May 2022

The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10−4). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r2 = 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.
Noise reduction by upstream open reading frames
Authors: Wu Ho-Wei , Fajiculay Erickson , Wu Jing-Fen , Yan Ching-Cher Sanders , Hsu Chao-Ping , Wu Shu-Hsing
Published: May 2022

Gene expression is prone to burst production, making it a highly noisy process that requires additional controls. Upstream open reading frames (uORFs) are widely present in the 5′ leader sequences of 30–50% of eukaryotic messenger RNAs1–3. The translation of uORFs can repress the translation efficiency of the downstream main coding sequences. Whether the low translation efficiency leads to a different variation, or noise, in gene expression has not been investigated, nor has the direct biological impact of uORF-repressed translation. Here we show that uORFs achieve low but precise protein production in plant cells, possibly by reducing the protein production rate. We also demonstrate that, by buffering a stable TIMING OF CAB EXPRESSION 1 (TOC1) protein production level, uORFs contribute to the robust operation of the plant circadian clock. Our results provide both an action model and the biological impact of uORFs in translational control to mitigate transcriptional noise for precise protein production.
Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR
Authors: Ahn Sung Gwe , Bae Soong June , Kim Yoonjung , Ji Jung Hwan , Chu Chihhao , Kim Dooreh , Lee Janghee , Cha Yoon Jin , Lee Kyung-A , Jeong Joon
Published: May 2022

We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.
Connector theory for reusing model results to determine materials properties
Authors: Vanzini Marco , Aouina Ayoub , Panholzer Martin , Gatti Matteo , Reining Lucia
Published: May 2022

The success of Density Functional Theory (DFT) is partly due to that of simple approximations, such as the Local Density Approximation (LDA), which uses results of a model, the homogeneous electron gas, to simulate exchange-correlation effects in real materials. We turn this intuitive approximation into a general and in principle exact theory by introducing the concept of a connector: a prescription how to use results of a model system in order to simulate a given quantity in a real system. In this framework, the LDA can be understood as one particular approximation for a connector that is designed to link the exchange-correlation potentials in the real material to that of the model. Formulating the in principle exact connector equations allows us to go beyond the LDA in a systematic way. Moreover, connector theory is not bound to DFT, and it suggests approximations also for other functionals and other observables. We explain why this very general approach is indeed a convenient starting point for approximations. We illustrate our purposes with simple but pertinent examples.
Sugars dominate the seagrass rhizosphere
Authors: Sogin E. Maggie , Michellod Dolma , Gruber-Vodicka Harald R. , Bourceau Patric , Geier Benedikt , Meier Dimitri V. , Seidel Michael , Ahmerkamp Soeren , Schorn Sina , D’Angelo Grace , Procaccini Gabriele , Dubilier Nicole , Liebeke Manuel
Published: May 2022

Seagrasses are among the most efficient sinks of carbon dioxide on Earth. While carbon sequestration in terrestrial plants is linked to the microorganisms living in their soils, the interactions of seagrasses with their rhizospheres are poorly understood. Here, we show that the seagrass, Posidonia oceanica excretes sugars, mainly sucrose, into its rhizosphere. These sugars accumulate to µM concentrations—nearly 80 times higher than previously observed in marine environments. This finding is unexpected as sugars are readily consumed by microorganisms. Our experiments indicated that under low oxygen conditions, phenolic compounds from P. oceanica inhibited microbial consumption of sucrose. Analyses of the rhizosphere community revealed that many microbes had the genes for degrading sucrose but these were only expressed by a few taxa that also expressed genes for degrading phenolics. Given that we observed high sucrose concentrations underneath three other species of marine plants, we predict that the presence of plant-produced phenolics under low oxygen conditions allows the accumulation of labile molecules across aquatic rhizospheres.
Multi-omics single-cell data integration and regulatory inference with graph-linked embedding
Authors: Cao Zhi-Jie , Gao Ge
Published: May 2022

Despite the emergence of experimental methods for simultaneous measurement of multiple omics modalities in single cells, most single-cell datasets include only one modality. A major obstacle in integrating omics data from multiple modalities is that different omics layers typically have distinct feature spaces. Here, we propose a computational framework called GLUE (graph-linked unified embedding), which bridges the gap by modeling regulatory interactions across omics layers explicitly. Systematic benchmarking demonstrated that GLUE is more accurate, robust and scalable than state-of-the-art tools for heterogeneous single-cell multi-omics data. We applied GLUE to various challenging tasks, including triple-omics integration, integrative regulatory inference and multi-omics human cell atlas construction over millions of cells, where GLUE was able to correct previous annotations. GLUE features a modular design that can be flexibly extended and enhanced for new analysis tasks. The full package is available online at https://github.com/gao-lab/GLUE.