bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractA 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

AbstractMesoscale 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

AbstractThe 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

AbstractCulturally 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

AbstractTo 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

AbstractDisruption 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

AbstractR-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

AbstractVirtually 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

AbstractProstate 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

AbstractElemental 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.
Global ecological analysis of COVID-19 mortality and comparison between “the East” and “the West”
Authors: Pablos-Méndez Ariel , Villa Simone , Monti Maria Cristina , Raviglione Mario Carlo , Tabish Hilary Brown , Evans Timothy Grant , Cash Richard Alan 
Published: March 2022

AbstractAlthough SARS-CoV-2 was first reported in China and neighbouring countries, the pandemic quickly spread around the globe. This paper explores national drivers of the pandemic and the radically different epidemiology and response in the West and in the East. We studied coronavirus disease (COVID-19) mortality until 31st December 2020, using an ecological study design, considering baseline characteristics and responses that might account for the uneven impact of the pandemic. A multivariable regression model was developed to explore key determinants. Key variables in the West were contrasted with those in the East, and speed of response was examined. Worldwide, 2.24 million COVID-19 deaths were documented in 2020. Western countries reported a median mortality 114 times that of the East (684 vs. 6.0 per million). Significant correlates of mortality in countries with at least 1 million population were median age, obesity prevalence, and democracy index; political stability and experience of SARS in 2002–2003 were protective; health system variables and income inequality were not associated. Outputs of the model were consistent when adjusted for stringency index, timeliness of stay-at-home requirements, and geographical autocorrelation. The West experiences a much higher COVID-19 mortality than the East. Despite structural advantages in the West, delays in national responses early on resulted in a loss of control over the spread of SARS-CoV-2. Although the early success of the East was sustained in the second half of 2020, the region remains extremely vulnerable to COVID-19 until enough people are immunized.
Ultrafast hot carrier transfer in WS2/graphene large area heterostructures
Authors: Trovatello Chiara , Piccinini Giulia , Forti Stiven , Fabbri Filippo , Rossi Antonio , De Silvestri Sandro , Coletti Camilla , Cerullo Giulio , Dal Conte Stefano 
Published: March 2022

AbstractCharge transfer processes in two-dimensional van der Waals heterostructures enable upconversion of low energy photons and efficient charge carriers extraction. Here we use broadband ultrafast optical spectroscopy to track charge transfer dynamics in large-area 2D heterostructures made of epitaxial single-layer tungsten disulfide (WS2) grown by chemical vapour deposition on graphene. Selective carrier photoexcitation in graphene, with tunable near-infrared photon energies as low as 0.8 eV (i.e. lower than half of the optical bandgap of WS2), results in an almost instantaneous bleaching of the WS2 excitonic peaks in the visible range, due to the interlayer charge transfer process. We find that the charge transfer signal is strongly non-linear with the pump fluence and it becomes progressively more linear at increasing pump photon energies, while the interlayer photoinjection rate is constant in energy, reflecting the spectrally flat absorbance of graphene. We ascribe the interlayer charge transfer to a fast transfer of hot carriers, photogenerated in graphene, to the semiconducting layer. The measured sub-20-fs hot-carrier transfer sets the ultimate timescale for this process. Besides their fundamental interest, our results are technologically relevant because, given the capability of large-area deterministic growth of the heterostructure, they open up promising paths for novel 2D photodetectors, also potentially scalable to industrial platforms.
ATP-sensitive inward rectifier potassium channels reveal functional linkage between salivary gland function and blood feeding in the mosquito, Aedes aegypti
Authors: Li Zhilin , Soohoo-Hui Alexander , O’Hara Flinn M. , Swale Daniel R. 
Published: March 2022

AbstractReducing saliva secretions into the vertebrate host reduces feeding efficacy by most hematophagous arthropods. However, seminal studies suggested saliva is not a prerequisite for blood feeding in Aedes aegypti. To test this paradigm, we manually transected the salivary duct of female A. aegypti and an inability to salivate was correlated to an inability to imbibe blood. These data justified testing the relevance of inwardly rectifying potassium (Kir) channels in the A. aegypti salivary gland as an antifeedant target site. Pharmacological activation of ATP-gated Kir (KATP) channels reduced the secretory activity of the salivary gland by 15-fold that led to near elimination of blood ingestion during feeding. The reduced salivation and feeding success nearly eliminated horizontal transmission and acquisition of Dengue virus-2 (DENV2). These data suggest mosquito salivation is a prerequisite for blood feeding and provide evidence that KATP channels are critical for salivation, feeding, and vector competency.