bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of glycosaminoglycans in cirrhotic liver and hepatocellular carcinoma—a pilot study including etiology
Authors: Tóth Gábor , Pál Domonkos , Sugár Simon , Kovalszky Ilona , Dezső Katalin , Schlosser Gitta , Drahos László , Turiák Lilla
Published: March 2022

Chronic liver diseases have both high incidence and mortality rates; therefore, a deeper understanding of the underlying molecular mechanisms is essential. We have determined the content and sulfation pattern of chondroitin sulfate (CS) and heparan sulfate (HS) in human hepatocellular carcinoma and cirrhotic liver tissues, considering the etiology of the diseases. A variety of pathological conditions such as alcoholic liver disease, hepatitis B and C virus infections, and primary sclerosing cholangitis were studied. Major differences were observed in the total abundance and sulfation pattern of CS and HS chains. For example, the 6-O-sulfation of CS is fundamentally different regarding etiologies of cirrhosis, and a 2–threefold increase in HS N-sulfation/O-sulfation ratio was observed in hepatocellular carcinoma compared to cirrhotic tissues.

Graphical abstract
Depression, anxiety and stress in women with breech pregnancy compared to women with cephalic presentation—a cross-sectional study
Authors: Schauer Madeleine , Latartara Elisabetta , Alonso-Espias Maria , Rossetti Emma , Gebert Pimrapat , Henrich Wolfgang , Hinkson Larry
Published: March 2022

Purpose

This study aims to evaluate the level of psychological distress for women with
breech compared to cephalic presentation. We hypothesized, that women with breech presentation have higher levels of depression, stress and anxiety. Secondary objectives were to analyze potential demographic risk factors and comorbidity of psychological distress in breech pregnancy.

Methods

The breech study group was formed by 379 women with breech presentation. A sample of 128 women with cephalic presentation was recruited during routine clinical care. Depression, anxiety and stress symptoms were ascertained by means of the Depression–Anxiety–Stress-Score (DASS)-21 questionnaire. Categorial data was analyzed with Chi-square or exact test, continuous data with unpaired t test or Mann–Whitney U test. Demographic risk factors were identified using a binary logistic regression model.

Results

Prevalence of psychological distress among women with breech was not higher compared to those of other pregnant women. Symptomatic depression, anxiety and stress affected 5.8%, 14.5% and 11.9% of women with breech, respectively. Decreasing age was identified as a risk factor for anxiety (p = 0.006). Multiparity increased risk for depression (p = 0.001), for anxiety (p = 0.026) and for perinatal stress (p = 0.010). More than 80% of women with depressive symptoms had comorbidities of psychological distress.

Conclusions

Breech presentation compared to cephalic presentation was not associated with higher levels of psychological distress. However, breech pregnancies are affected by symptoms of potential mental disorder. Multiparous women and younger women may need additional support and would benefit from a standardized screening tool for the assessment of perinatal psychological distress.

Clinical trial registration

Ethical approval (EA2/241/18) was granted by the Ethics Commission of the Charité University Hospital on the 23.01.2019 (ClinicalTrials.gov Identifier: NCT03827226).
Handling unobserved confounding in the relation between prenatal risk factors and child outcomes: a latent variable strategy
Authors: Gustavson Kristin , Davey Smith George , Eilertsen Espen M.
Published: March 2022

Background

Several studies have examined maternal health behavior during pregnancy and child outcomes. Negative control variables have been used to address unobserved confounding in such studies. This approach assumes that confounders affect the exposure and the negative control to the same degree. The current study introduces a novel latent variable approach that relaxes this assumption by accommodating repeated measures of maternal health behavior during pregnancy.

Methods

Monte Carlo simulations were used to examine the performance of the latent variable approach. A real-life example is also provided, using data from the Norwegian Mother, Father, and Child Study (MoBa).

Results

Simulations: Regular regression analyses without a negative control variable worked poorly in the presence of unobserved confounding. Including a negative control variable improved result substantially. The latent variable approach provided unbiased results in several situations where the other analysis models worked poorly. Real-life data: Maternal alcohol use in the first trimester was associated with increased ADHD symptoms in the child in the standard regression model. This association was not present in the latent variable approach.

Conclusion

The current study showed that a latent variable approach with a negative control provided unbiased estimates of causal associations between repeated measures of maternal health behavior during pregnancy and child outcomes, even when the effect of the confounder differed in magnitude between the negative control and the exposures. The real-life example showed that inferences from the latent variable approach were incompatible with those from the standard regression approach. Limitations of the approach are discussed.
Determinants of Household Savings: A Cross-Country Analysis
Authors: Fredriksson Cajsa , Staal Klaas
Published: March 2022

This paper analyses determinants of household savings in a model based on an extension of the disequilibrium savings theory. These extensions follow from the life-cycle and permanent-income theories. Based on panel data for 14 countries spanning the period 2000–2018, fixed-effect least squares and two-stage least squares estimation procedures were used. In line with previous studies, there is strong and robust evidence for the hypotheses of disequilibrium savings theory, specifically, positive effects of unanticipated income changes, unanticipated inflation and the lagged savings rate. There is also robust evidence for the income uncertainty hypothesis that uncertainty has a positive effect on savings. The analysis presents some evidence that social security suppresses savings, but finds no significant effects on the interest rate or old-age dependency ratio. Unexpectedly, the participation rate of the elderly has a significant positive effect in some specifications. These findings contribute to the debate on whether and how governments can influence saving behavior.
Advances in application of machine learning to life cycle assessment: a literature review
Authors: Ghoroghi Ali , Rezgui Yacine , Petri Ioan , Beach Thomas
Published: March 2022

Purpose

Life Cycle Assessment (LCA) is the process of systematically assessing impacts when there is an interaction between the environment and human activity. Machine learning (ML) with LCA methods can help contribute greatly to reducing impacts. The sheer number of input parameters and their uncertainties that contribute to the full life cycle make a broader application of ML complex and difficult to achieve. Hence a systems engineering approach should be taken to apply ML in isolation to aspects of the LCA. This study addresses the challenge of leveraging ML methods to deliver LCA solutions. The overarching hypothesis is that: LCA underpinned by ML methods and informed by dynamic data paves the way to more accurate LCA while supporting life cycle decision making.

Methods

In this study, previous research on ML for LCA were considered, and a literature review was undertaken.

Results

The results showed that ML can be a useful tool in certain aspects of the LCA. ML methods were shown to be applied efficiently in optimization scenarios in LCA. Finally, ML methods were integrated as part of existing inventory databases to streamline the LCA across many use cases.

Conclusions

The conclusions of this article summarise the characteristics of existing literature and provide suggestions for future work in limitations and gaps which were found in the literature.
Policing the Gaps: Legitimacy, Special Obligations, and Omissions in Law Enforcement
Authors: Hadjimatheou Katerina , Nathan Christopher
Published: March 2022

The ethics of policing currently neglects to provide a framework for analysing the morality of deliberate inactions to prevent harm, even though these are often adopted tactically by police as a means of preventing greater harms. In this paper we argue (a) that police have special moral obligations to prevent harm, grounded both in a contractarian account of police legitimacy and in the interpersonal morality of associations and (b) that police are morally culpable for failures to fulfil these special obligations when these are neither proportionate nor necessary to the prevention of greater crime-related harms. Our claims have implications both for the morality of policing and for its regulation and governance under human rights legislation, which we argue should be reformed so as to recognise police culpability not only for inflictions of harm, but also for failures to prevent it.
A Survey on Quantum Computational Finance for Derivatives Pricing and VaR
Authors: Gómez Andrés , Leitao Álvaro , Manzano Alberto , Musso Daniele , Nogueiras María R. , Ordóñez Gustavo , Vázquez Carlos
Published: March 2022

We review the state of the art and recent advances in quantum computing applied to derivative pricing and the computation of risk estimators like Value at Risk. After a brief description of the financial derivatives, we first review the main models and numerical techniques employed to assess their value and risk on classical computers. We then describe some of the most popular quantum algorithms for pricing and VaR. Finally, we discuss the main remaining challenges for the quantum algorithms to achieve their potential advantages.
Non-conventional Stabilization for Fruit and Vegetable Juices: Overview, Technological Constraints, and Energy Cost Comparison
Authors: Vignali Giuseppe , Gozzi Mario , Pelacci Massimiliano , Stefanini Roberta
Published: March 2022

This study will provide an overview and a description of the most promising alternatives to conventional thermal treatments for juice stabilization, as well as a review of the literature data on fruit and vegetable juice processing in terms of three key parameters in juice production, which are microbial reduction, enzyme inactivation, and nutrient-compound retention. The alternatives taken into consideration in this work can be divided, according to the action mechanism upon which these are based, in non-conventional thermal treatments, among which microwave heating (MWH) and ohmic heating (OH), and non-thermal treatments, among which electrical treatments, i.e., pulsed electric fields (PEF), high-pressure processing (HPP), radiation treatments such as ultraviolet light (UVL) and high-intensity pulsed light (PL), and sonication (HIUS) treatment, and inert-gas treatments, i.e., the pressure change technology (PCT) and supercritical carbon dioxide (SC-CO2) treatments. For each technology, a list of the main critical process parameters (CPP), advantages (PROS), and disadvantages (CONS) will be provided. In addition, for the non-thermal technologies, a summary of the most relevant published result of their application on fruit and vegetable juices will be presented. On top of that, a comparison of typical specific working energy costs for the main effective and considered technologies will be reported in terms of KJ per kilograms of processed product.
Lateral- or prone-position video-assisted thoracic surgery for dumbbell-type posterior mediastinal tumors: pros and cons
Authors: Matsumura Yuki , Yamaguchi Hikaru , Watanabe Kazuyuki , Suzuki Hiroyuki
Published: March 2022

Surgery for dumbbell-type posterior mediastinal tumors (D-PMTs) is difficult because surgeons should confirm the tumor’s extension into the spinal cord and pay attention to the Adamkiewicz artery. We describe two patients of D-PMTs who underwent lateral- or prone-position video-assisted thoracic surgery (VATS). In patient 1 (a 70-year-old woman), the tumor extended to the spinal canal through the fourth thoracic intervertebral foramen. After hemi-laminectomies, she was moved to the lateral position, and the tumor was resected. In patient 2 (a 16-year-old boy), the tumor extended to the spinal canal through the seventh thoracic intervertebral foramen. Additionally, 320-row high-resolution computed tomography showed Adamkiewicz arteries running through the sixth and eighth thoracic intervertebral foramina. After laminectomy, the tumor was resected without repositioning. Prone-position VATS is a useful approach for D-PMTs because it provides a better view of the vertebrae compared with the lateral position. We discuss the advantages and disadvantages of both approaches.
SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2021)
Authors: Majem Margarita , de las Peñas Ramon , Virizuela Juan Antonio , Cabezón-Gutiérrez Luís , Cruz Patricia , Lopez-Castro Rafael , Méndez Miriam , Mondéjar Rebeca , Muñoz María del Mar , Escobar Yolanda
Published: March 2022

Among the side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) is one of the most feared given its high prevalence, affecting up to 40% of patients. It can impair patient’s quality of life and provoke low adherence to cancer treatment or chemotherapy dose reductions that can comprise treatment efficacy. Suffering CINV depends on factors related to the intrinsic emetogenicity of antineoplastic drugs and on patient characteristics. CINV can appear at different times regarding the administration of antitumor treatment and the variability of risk according to the different antitumor regimens has, as a consequence, the need for a different and adapted antiemetic treatment prophylaxis to achieve the desired objective of complete protection of the patient in the acute phase, in the late phase and in the global phase of emesis. As a basis for the recommendations, the level of emetogenicity of anticancer treatment is considered and they are classified as high, moderate, low and minimal emetogenicity and these recommendations are based on the use of antiemetic drugs with a high therapeutic index: anti 5-HT, anti-NK and steroids. Despite having highly effective treatments, clinical reality shows that they are not applied enough, so evidence-based recommendations are needed to show the best options and help in decision-making. To cover all the antiemetic prophylaxis options, we have also included recommendations for oral treatments, multiday regimens and radiation-induced emesis prevention.
A novel optimized design of a piezoelectric-driven 4-stage amplified compliant microgripper using a 2-step multi-objective algorithm
Authors: Haghshenas Gorgani Hamid , Shabani Sharif , Honarmand Mohammadmahdi
Published: March 2022

Advancements in microscale technologies have prompted a demand for high precision micro-manipulation. Microgrippers are the primary means of conducting micro-scale operations, and they significantly affect the procedure's performance. This paper presents a novel optimized design for compliant microgrippers, intending to enhance functionality and durability. The mainframe of the proposed microgripper is based on a compact flexure-based compliant structure with four stages of movement amplification. Experiments were designed based on the L25 Taguchi orthogonal arrays. The experiments were conducted using the finite element method in Abaqus 6.14 workbench. Range of motion and maximum created mechanical stress are selected as the two fundamental goals of the optimization. A variety of designs are achieved using the proposed algorithm. The use of Analytical Hierarchy Process has led to the presentation of an efficient and well-defined algorithm to perform decisions. The decision process can be performed with regard to specific requirements of various applications. The presented design process of microgrippers has the potential for customized manufacturing for specific applications.

Article Highlights

Finding correlations between design parameters and outputs (Amplification factor & Stress), using Taguchi's method in design of experiments (DOE).

Optimization of dimensional inputs using a multi-objective genetic algorithm process to achieve an optimal Pareto-front instead of a single design point.

Selecting the desirable point on the optimal Pareto-front for specific applications using Analytic Hierarchy Process (AHP) to prevent possible decision-making errors.
Real fracture toughness of FRC and FGC: size and boundary effects
Authors: Elakhras A. A. , Seleem M. H. , Sallam H. E. M.
Published: March 2022

The present dilemma is how to simulate the real crack in full depth (FD) fiber-reinforced concrete (FRC), FD FRC, to get the actual fracture toughness of such fibrous composites, i.e., through-thickness pre-cracks are inappropriate for such materials. To overcome this dilemma, a new technique was adopted to create a pre-matrix crack (MC) without cutting the fibers bridging the two surfaces of the pre-crack. The main objective of the present work is to study the size and boundary effects on the real fracture toughness of MC-FD FRC and functionally graded concrete (FGC). Forty-eight MC-FD FRC and MC-FGC beams with three different span to depth ratios L/d equal 4, 5, and 6, and three different beam depths of the same beam span have been tested under three-point bending. All beams have the same pre-MC length to beam depth ratio (a
o/d) of 1/3. Hooked end steel fibers of 1% fiber volume fraction produced FRC. FGC beams consist of three equal layers, FRC layer at the tension side, normal strength concrete layer at the middle of the beam, and high strength concrete layer at the compression side. The applied load versus all beams' crack mouth opening displacement (CMOD) curves have been analyzed. The present load/CMOD results showed that beams having constant L/d ratios are recommended to capture independent size effect parameters. The size effect law (SEL) and boundary effect model (BEM) are good candidates to predict the size effect. According to the maximum non-damaged defect concept, the SEL is more reliable in predicting MC FD FRC fracture toughness than BEM.
Crafting granular stories with child-like embodied, affective and sensory encounters that attune to the world’s differential becoming
Authors: Osgood Jayne , Odegard Nina
Published: March 2022

In this paper we explore what decentring the child in posthumanism does to our research practices, to our conceptualisations of and relationalities to the child. Crucially, we explore the imperative for other ways to encounter the child – that pursue a decolonising and de/recentralising agenda. We pursue tentacular lines of enquiry through a series of interwoven stories – some more familiar than others. It is by queering old narratives that new and unexpected stories concerning pedagogical documentation, sustainability and environmental education, and the child’s contaminated connection to ‘nature’ begin to emerge. This paper attempts to mobilise ‘the posthuman child’ as feral, an uncomfortable in-between that invites us to grapple with the disease of life on a damaged planet. Central to our storytelling is recycled, ‘natural’ materials found in a Reggio Emilia kindergarten in Norway. Specifically, cork has guided us; insisting that we take the non-innocence of matter to the heart of enquiries. We do this to illustrate the potential of feminist new materialism to respond with situated, embodied, affective insights and provocations that might offer ways to consume, cohabit and wrestle in more care-full ways with the Anthropocene ecologies that we are intricately and endlessly enmeshed in.
Analysis of ice-sheet temperature profiles from low-frequency airborne remote sensing
Authors: Jezek Kenneth C. , Yardim Caglar , Johnson Joel T. , Macelloni Giovanni , Brogioni Marco
Published: March 2022

Ice internal temperature and basal geothermal heat flux (GHF) are analyzed along a study line in northwestern Greenland. The temperatures were obtained from a previously reported inversion of airborne microwave brightness-temperature spectra. The temperatures vary slowly through the upper ice sheet and more rapidly near the base increasing from ~259 K near Camp Century to values near the melting point near NorthGRIP. The flow-law rate factor is computed from temperature data and analytic expressions. The rate factor increases from ~1 × 10−8to 8 × 10−8kPa−3a−1along the line. A laminar flow model combined with the depth-dependent rate factor is used to estimate horizontal velocity. The modeled surface velocities are about a factor of 10 less than interferometric synthetic aperture radar (InSAR) surface velocities. The laminar velocities are fitted to the InSAR velocities through a factor of 8 enhancement of the rate factor for the lower 25% of the column. GHF values retrieved from the brightness temperature spectra increase from ~55 to 84 mW m−2from Camp Century to NorthGRIP. A strain heating correction improves agreement with other geophysical datasets near Camp Century and NEEM but differ by ~15 mW m−2in the central portion of the profile.
The Persistence in Gendering: Work-Family Policy in Britain since Beveridge
Authors: CHANFREAU JENNY
Published: March 2022

Understanding the historical policy pathways that have led to the constellation of policies that both reflect and shape the current gender order can reveal reasons for the persistence of gender inequality in paid work and unpaid family care. Bringing together existing research and policy critique with Carol Bacchi’s framework of policy as ‘gendering practices’, this paper focuses on the role of policy as a process that constructs and upholds an unequal gender order. The discussion traces how UK social policies have since the establishment of the post-war welfare state articulated and positioned gendered possibilities for combining paid work and childrearing, shaping gendered and classed work-family life courses. The analysis illustrates that British social policy has not been consistently committed to a more equal gender regime but instead maintained a heteronormative family ideal and thus, despite various policy changes, the gendering of ‘the worker’ and ‘the parent’ as conceptualised in UK policy has persisted over the last several decades.
Social Policy and Queer Lives: Coming Out of the Closet?
Authors: GREGORY LEE , MATTHEWS PETER
Published: March 2022

Social Policy as an academic discipline has been at the forefront of many progressive movements in society, exploring problems of poverty, hardship, exclusion and suffering, government intervention, and the critical appraisal of those interventions. Yet it has been strangely silent on issues of sexual identity and gender identity and the inequities faced by the LGBTQ+ community. In this article we draw upon lesbian and gay studies, and queer studies, to, first, unpack how heteronormativity is reinforced in social policy in practice and in its analysis within Social Policy as a discipline. This illustrates how the family, as a core basis for welfare in societies, has meant that, reflexively, the base unit of analysis within Social Policy has been the heterosexual family, without a full interrogation of what this means for different groups. Second, we review the limited evidence available around the inequalities LGBTQ+ people face, primarily in the UK (and wider global North), highlighting how the years of oppression have made “counting” this group of people difficult within our usual survey instruments. Thus, while Social Policy has aimed to achieve a universal social citizenship for all, it has inadvertently remained silent on how to include LGBTQ+ in its analysis.
Narratives of Social Conflict in the Merstallinger Trial, 1883
Authors: Pajakowski Philip
Published: March 2022

The robbery of Viennese shoe manufacturer Josef Merstallinger on 4 July 1882 led to a political trial of social radicals the following year. When Merstallinger's assailants were arrested, they admitted to the crime and professed to have carried it out to raise funds for the radical socialist movement. In response, the police arrested dozens of radical activists and eventually charged twenty-nine people with crimes including high treason. The authorities, including the chief of the Vienna police and state's attorney, characterized the robbery as part of an international anarchist conspiracy that threatened violent revolution against the basis of Austrian and European civilization. The trial was thus intended to cripple the radical organization and demonstrate the dangers socialist politics posed to the public. A counternarrative for the defendants stressed the relative harmlessness of the radical movement, general harmony of Austrian social relations, and rights of the accused to free speech and to protection from arbitrary treatment by the police. A public jury trial suggested the greater persuasiveness of the latter narrative, as the jury acquitted the defendants of all charges except those directly related to the robbery.
Social robots as depictions of social agents
Authors: Clark Herbert H. , Fischer Kerstin
Published: March 2022

Social robots serve people as tutors, caretakers, receptionists, companions, and other social agents. People know that the robots are mechanical artifacts, yet they interact with them as if they were actual agents. How is this possible? The proposal here is that people construe social robots not as social agentsper se, but asdepictionsof social agents. They interpret them much as they interpret ventriloquist dummies, hand puppets, virtual assistants, and other interactive depictions of people and animals. Depictions as a class consist of three physical scenes with part-by-part mappings between them: (a) a base scene (the raw physical artifact), (b) the depiction proper (the artifact construed as a depiction), and (c) the scene depicted (the scene people are to imagine). With social robots, evidence shows people form the same three scenes plus mappings: They perceive the raw machinery of a robot, construe it as a depiction of a character, and, using the depiction as a guide, engage in the pretense that they are interacting with the character depicted. With social robots, people also recognize three classes of agents – the characters depicted, the intended recipients of the depictions (those who view or interact with the robots), and the authorities responsible for the robots (the designers, makers, and owners). Construing social robots as depictions, we argue, accounts for many phenomena not covered by alternative models.
Public health implications of plasmid-mediated quinolone and aminoglycoside resistance genes in Escherichia coli inhabiting a major anthropogenic river of India
Authors: Singh Nambram Somendro , Singhal Neelja , Kumar Manish , Virdi Jugsharan Singh
Published: March 2022

Presence of antimicrobial resistance (AMR) genes in Escherichia coli inhabiting anthropogenic rivers is an important public health concern because plasmid-mediated AMR genes can easily spread to other pathogens by horizontal gene transfer. Besides β-lactams, quinolones and aminoglycosides are the major antibiotics against E. coli. In the present study, we have investigated the presence of plasmid-mediated quinolone resistance (PMQR) and aminoglycoside resistance genes in E. coli isolated from a major river of northern India. Our results revealed that majority of the strains were phenotypically susceptible for fluoroquinolones and some aminoglycosides like amikacin, netilmicin, tobramycin and gentamicin. However, 16.39% of the strains were resistant for streptomycin, 8.19% for kanamycin and 3.30% for gentamicin. Of the various PMQR genes investigated, only qnrS1 was present in 24.59% of the strains along with ISEcl2. Aminoglycoside-resistance genes like strA-strB were found to be present in 16.39%, aphA1 in 8.19% and aacC2 in only 3.30% of the strains. Though, no co-relation was observed between phenotypic resistance for fluorquinolones and presence of PMQR genes, phenotypic resistance for streptomycin, kanamycin and gentamicin exactly co-related with the presence of the genes strA-strB, aphA1 and aacC2, respectively. Moreover, all the AMR genes discerned in aquatic E. coli were found to be situated on conjugative plasmids and, thus easily transferrable. Our study accentuates the importance of routine surveillance of urban rivers to curtail the spread of AMR genes in aquatic pathogens.
The identification of abnormalities on radiotherapy CT planning scans: a retrospective audit
Authors: Cameron Josie
Published: March 2022

Introduction:

Therapeutic radiographers are an essential part of a cancer patient’s journey and play a vital and changing role in the delivery of radiotherapy services. This retrospective audit highlights the number of incidental abnormalities found by a Breast Advanced Practitioner on radiotherapy computed tomography (CT) planning scans and their subsequent management.

Methods:

This retrospective audit investigated the incidental abnormalities found by the Breast Advanced Practitioner on routine CT planning scans for breast cancer patients 2016–2021. Any breast cancer patient found to have an abnormality had their planning scan uploaded to the national picture archiving and communication systems (PACS) system for radiology review. Further formal CT imaging was requested or direct referral to an appropriate multi-disciplinary team meeting.

Results:

Sixty-three significant abnormalities were found over the five-year period, of these thirty seven were malignant and the majority of these were lung lesions. Seven patients went on to have surgery alone, surgery plus chemoradiation or stereotactic ablative radiotherapy for their newly diagnosed lung primaries. Five patients were found to have liver metastases that unfortunately changed their treatment plan to palliative.

Conclusion:

This retrospective audit has demonstrated that CT planning for radiotherapy offers an opportunity to identify malignant abnormalities at a potentially early stage, thereby improving prognosis and survival. Radiographers have a duty of care to appraise these CT scans to ensure any abnormalities can be addressed in a timely manner.
Good versus poor prescribers: the comparison of prescribing competencies in primary care
Authors: Atac Omer , Aydin Volkan , Karabey Selma , Hayran Osman , Akici Ahmet
Published: March 2022

Aim:

To compare the competencies of primary care physicians (PCPs) with poor and good prescribing performance in frequently encountered indications.

Background:

Primary care centers are one of the mostly visited health facilities by the population for different health issues.

Methods:

In this cross-sectional study, we analyzed 6 125 487 prescriptions generated by 1431 PCPs which were selected by systematic sampling in 2016 in Istanbul. We defined PCPs as poor prescriber (n = 227) or good prescriber (n = 210) in terms of their prescribing performance per WHO/INRUD criteria. We compared solo diagnosis prescriptions of these two groups in ‘percentage of prescriptions in compliance with clinical guidelines’ and also rational prescribing indicators.

Findings:

Poor prescribers and good prescribers significantly differed in each of the prescribing indicators for their all solo diagnosis prescriptions. Hypertension had the highest difference of the average cost per encounter (Δ = 284.2%) between poor prescribers (US$43.99 ± 63.05) and good prescribers (US$11.45 ± 45.0), whereas headache had the highest difference between the groups in the percentage encounters with an antibiotic (14.9% vs. 1.5%). Detailed analysis of the prescribing performances showed significantly higher values of each WHO/INRUD indicators for all examined diagnoses. We found significantly higher percentages of guideline-compliant drugs in good prescribers compared to that in poor prescribers in hypertension (40.8% vs 34.8%), tonsillopharyngitis (57.9% vs 50.7%), and acute sinusitis (46.4% vs 43.6%).

Conclusion:

This study shows that the prescribing performances of PCPs are not rational enough in terms of drug selection and prescription content. Furthermore, even the physicians who have good prescribing practice appear as not satisfactorily rational in compliance with current pharmacotherapy competencies.
On the Intermittent Occurrence of Open‐Ocean Polynyas in a Multi‐Century High‐Resolution Preindustrial Earth System Model Simulation
Authors: Diao Xiliang , Stössel Achim , Chang Ping , Danabasoglu Gokhan , Yeager Stephen G. , Gopal Abishek , Wang Hong , Zhang Shaoqing
Published: March 2022

A 500‐year‐long high‐resolution Community Earth System Model simulation under preindustrial radiative forcing produces Maud Rise Polynyas (MRPs) and Weddell Sea Polynya (WSP) events intermittently from decadal (MRP) to multidecadal (WSP) timescales. This periodicity is correlated with the variation of a regional Southern Annular Mode (SAM) index (evaluated regionally instead of circum‐Antarctic) with corresponding variations of precipitation and winds over the Weddell Sea. A negative index causes the upper‐ocean salinity to increase over multiple decades. Ultimately, brine rejection during seasonal sea‐ice formation superimposed on the multidecadal increase raises the upper‐ocean salinity beyond the tipping point for triggering deep convection that leads to polynyas. The initiation of polynya events is thus controlled by surface properties while the location of initiation is determined by bathymetric features. The persistent Taylor column effect, which is well represented by the high‐resolution model topography of the Maud Rise seamount, preconditions this region for MRP initiation. Therefore, MRPs form more frequently than WSPs in the simulation. When the upper‐ocean salinity is high, deep convection in the MRP region tends to be stronger, in which case MRPs are also more likely to grow into WSPs. Once WSPs emerge, they affect the regional atmospheric circulation and associated variables. We propose a regional coupled ocean‐atmosphere mechanism to explain both the periodic emergence of polynyas and the periodic variation of the regional SAM index. Although the temperature and salinity of Weddell Deep Water show upward trends due to model drift, these density‐compensating changes do not affect the frequency of polynya formation.
Mesoscale Convective Systems Simulated by a High‐Resolution Global Nonhydrostatic Model Over the United States and China
Authors: Na Ying , Fu Qiang , Leung L. Ruby , Kodama Chihiro , Lu Riyu
Published: March 2022

Mesoscale convective systems (MCSs) contribute a large fraction of warm‐season precipitation and generate hazardous weather with substantial socioeconomic impacts. Uncertainties in convection parameterizations in climate models limit our understanding of MCS characteristics and reliability of future projection. We examine MCSs simulated by the global 14 km Nonhydrostatic ICosahedral Atmospheric Model (NICAM) without cumulus parameterization against satellite observation from Global Precipitation Measurement during 2001–2008. We focus on MCSs over the central United States and eastern China where MCSs are prevalent from March to August. A process‐oriented tracking method incorporating both cloud and precipitation criteria is used to identify and track MCSs. About 140/100 MCSs initiate in the central United States/eastern China per warm season and most of them initiate in the east of high mountains and in coastal regions. The frequency distribution of MCS lifetime is well captured by NICAM. However, the simulated MCSs have stronger precipitation, smaller precipitation area, and larger cold cloud system than that observed in both regions, which may be caused by weak entrainment as it is not well resolved at 14 km resolution. The simulated MCS number is also underestimated in summer. By examining the climatological and MCS large‐scale environments, the significant underestimation of MCS number in summer over the central United States may be attributed to the large climatological dry bias in the atmosphere. For China, mean moisture in summer is well simulated but deficiency in capturing the dynamic condition related to the coastal topography for triggering convection may have contributed to underestimation of MCS even in a sufficiently moist environment.
Induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma: an update
Authors: Bazarbachi Abdul Hamid , Al Hamed Rama , Malard Florent , Bazarbachi Ali , Harousseau Jean-Luc , Mohty Mohamad
Published: March 2022

The current standard of care model for newly diagnosed fit multiple myeloma (NDMM) patients is the sequential treatment of induction, high dose melphalan, autologous stem cell transplantation (ASCT), and maintenance. Adequate induction is required to achieve good disease control and induce deep response rates while minimizing toxicity as a bridge to transplant. Doublet induction regimens have greatly fallen out of favor, with current international guidelines favoring triplet or quadruplet induction regimens built around the backbone of the proteasome inhibitor bortezomib and dexamethasone (Vd). In fact, the updated 2021 European Haematology Association (EHA) and European Society for Medical Oncology (ESMO) clinical practice guidelines recommend the use of either lenalidomide-Vd (VRd), or daratumumab-thalidomide-Vd (Dara-VTd) as first-line options for transplant-eligible NDMM patients, and when not available, thalidomide-Vd (VTd) or cyclophosphamide-Vd (VCd) as acceptable alternatives. Quadruplet regimens featuring anti-CD38 monoclonal antibodies are extremely promising and remain heavily investigated, as is the incorporation of more recent proteasome inhibitors such as carfilzomib. This review will focus on induction therapies prior to ASCT examining the latest data and guidelines on triplet and quadruplet regimens.
Machine learning reveals cryptic dialects that explain mate choice in a songbird
Authors: Wang Daiping , Forstmeier Wolfgang , Farine Damien R. , Maldonado-Chaparro Adriana A. , Martin Katrin , Pei Yifan , Alarcón-Nieto Gustavo , Klarevas-Irby James A. , Ma Shouwen , Aplin Lucy M. , Kempenaers Bart
Published: March 2022

Culturally transmitted communication signals – such as human language or bird song – can change over time through cultural drift, and the resulting dialects may consequently enhance the separation of populations. However, the emergence of song dialects has been considered unlikely when songs are highly individual-specific, as in the zebra finch (Taeniopygia guttata). Here we show that machine learning can nevertheless distinguish the songs from multiple captive zebra finch populations with remarkable precision, and that ‘cryptic song dialects’ predict strong assortative mating in this species. We examine mating patterns across three consecutive generations using captive populations that have evolved in isolation for about 100 generations. We cross-fostered eggs within and between these populations and used an automated barcode tracking system to quantify social interactions. We find that females preferentially pair with males whose song resembles that of the females’ adolescent peers. Our study shows evidence that in zebra finches, a model species for song learning, individuals are sensitive to differences in song that have hitherto remained unnoticed by researchers.
Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology
Authors: Sajuthi Satria P. , Everman Jamie L. , Jackson Nathan D. , Saef Benjamin , Rios Cydney L. , Moore Camille M. , Mak Angel C. Y. , Eng Celeste , Fairbanks-Mahnke Ana , Salazar Sandra , Elhawary Jennifer , Huntsman Scott , Medina Vivian , Nickerson Deborah A. , Germer Soren , Zody Michael C. , Abecasis Gonçalo , Kang Hyun Min , Rice Kenneth M. , Kumar Rajesh , Zaitlen Noah A. , Oh Sam ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Rodríguez-Santana José , Burchard Esteban G. , Seibold Max A.
Published: March 2022

To identify genetic determinants of airway dysfunction, we performed a transcriptome-wide association study for asthma by combining RNA-seq data from the nasal airway epithelium of 681 children, with UK Biobank genetic association data. Our airway analysis identified 102 asthma genes, 58 of which were not identified by transcriptome-wide association analyses using other asthma-relevant tissues. Among these genes wereMUC5AC, an airway mucin, andFOXA3, a transcriptional driver of mucus metaplasia. Muco-ciliary epithelial cultures from genotyped donors revealed that theMUC5ACrisk variant increases MUC5AC protein secretion and mucus secretory cell frequency. Airway transcriptome-wide association analyses for mucus production and chronic cough also identifiedMUC5AC. These cis-expression variants were associated with trans effects on expression; theMUC5ACvariant was associated with upregulation of non-inflammatory mucus secretory network genes, while theFOXA3variant was associated with upregulation of type-2 inflammation-induced mucus-metaplasia pathway genes. Our results reveal genetic mechanisms of airway mucus pathobiology.
A computational model of neurodegeneration in Alzheimer’s disease
Authors: Jones D. , Lowe V. , Graff-Radford J. , Botha H. , Barnard L. , Wiepert D. , Murphy M. C. , Murray M. , Senjem M. , Gunter J. , Wiste H. , Boeve B. , Knopman D. , Petersen R. , Jack C.
Published: March 2022

Disruption of mental functions in Alzheimer’s disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.
Structural basis of R-loop recognition by the S9.6 monoclonal antibody
Authors: Bou-Nader Charles , Bothra Ankur , Garboczi David N. , Leppla Stephen H. , Zhang Jinwei
Published: March 2022

R-loops are ubiquitous, dynamic nucleic-acid structures that play fundamental roles in DNA replication and repair, chromatin and transcription regulation, as well as telomere maintenance. The DNA-RNA hybrid–specific S9.6 monoclonal antibody is widely used to map R-loops. Here, we report crystal structures of a S9.6 antigen-binding fragment (Fab) free and bound to a 13-bp hybrid duplex. We demonstrate that S9.6 exhibits robust selectivity in binding hybrids over double-stranded (ds) RNA and in categorically rejecting dsDNA. S9.6 asymmetrically recognizes a compact epitope of two consecutive RNA nucleotides via their 2′-hydroxyl groups and six consecutive DNA nucleotides via their backbone phosphate and deoxyribose groups. Recognition is mediated principally by aromatic and basic residues of the S9.6 heavy chain, which closely track the curvature of the hybrid minor groove. These findings reveal the molecular basis for S9.6 recognition of R-loops, detail its binding specificity, identify a new hybrid-recognition strategy, and provide a framework for S9.6 protein engineering.
Dynamics of ranking
Authors: Iñiguez Gerardo , Pineda Carlos , Gershenson Carlos , Barabási Albert-László
Published: March 2022

Virtually anything can be and is ranked; people, institutions, countries, words, genes. Rankings reduce complex systems to ordered lists, reflecting the ability of their elements to perform relevant functions, and are being used from socioeconomic policy to knowledge extraction. A century of research has found regularities when temporal rank data is aggregated. Far less is known, however, about how rankings change in time. Here we explore the dynamics of 30 rankings in natural, social, economic, and infrastructural systems, comprising millions of elements and timescales from minutes to centuries. We find that the flux of new elements determines the stability of a ranking: for high flux only the top of the list is stable, otherwise top and bottom are equally stable. We show that two basic mechanisms — displacement and replacement of elements — capture empirical ranking dynamics. The model uncovers two regimes of behavior; fast and large rank changes, or slow diffusion. Our results indicate that the balance between robustness and adaptability in ranked systems might be governed by simple random processes irrespective of system details.
An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method
Authors: Nordin Elise , Steffensen Stine K. , Laursen Bente B. , Andersson Sven-Olof , Johansson Jan-Erik , Åman Per , Hallmans Göran , Borre Michael , Stærk Dan , Hanhineva Kati , Fomsgaard Inge S. , Landberg Rikard
Published: March 2022

Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.
Non-destructive 3D imaging method using muonic X-rays and a CdTe double-sided strip detector
Authors: Chiu I-Huan , Takeda Shin’ichiro , Kajino Meito , Shinohara Atsushi , Katsuragawa Miho , Nagasawa Shunsaku , Tomaru Ryota , Yabu Goro , Takahashi Tadayuki , Watanabe Shin , Takeshita Soshi , Miyake Yasuhiro , Ninomiya Kazuhiko
Published: March 2022

Elemental analysis based on muonic X-rays resulting from muon irradiation provides information about bulk material composition without causing damage, which is essential in the case of precious or otherwise unreachable samples, such as in archeology and planetary science. We developed a three-dimensional (3D) elemental analysis technique by combining the elemental analysis method based on negative muons with an imaging cadmium telluride double-sided strip detector (CdTe-DSD) designed for the hard X-ray and soft $$\gamma$$
γ
-ray observation. A muon irradiation experiment using spherical plastic samples was conducted at the Japan Proton Accelerator Research Complex (J-PARC); a set of projection images was taken by the CdTe-DSD, equipped with a pinhole collimator, for different sample rotation angles. The projection images measured by the CdTe-DSD were utilized to obtain a 3D volumetric phantom by using the maximum likelihood expectation maximization algorithm. The reconstructed phantom successfully revealed the 3D distribution of carbon in the bulk samples and the stopping depth of the muons. This result demonstrated the feasibility of the proposed non-destructive 3D elemental analysis method for bulk material analysis based on muonic X-rays.