bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the impact of a very low-cost intervention to increase practices’ engagement with data and change prescribing behaviour: a randomized trial in English primary care
Authors: Curtis Helen J , Bacon Seb , Croker Richard , Walker Alex J , Perera Rafael , Hallsworth Michael , Harper Hugo , Mahtani Kamal R , Heneghan Carl , Goldacre Ben 
Published: March 2021

Abstract

Background
Unsolicited feedback can solicit changes in prescribing.

Objectives
Determine whether a low-cost intervention increases clinicians’ engagement with data, and changes prescribing; with or without behavioural science techniques.

Methods
Randomized trial (ISRCTN86418238). The highest prescribing practices in England for broad-spectrum antibiotics were allocated to: feedback with behavioural impact optimization; plain feedback; or no intervention. Feedback was sent monthly for 3 months by letter, fax and email. Each included a link to a prescribing dashboard. The primary outcomes were dashboard usage and change in prescribing.

Results
A total of 1401 practices were randomized: 356 behavioural optimization, 347 plain feedback, and 698 control. For the primary engagement outcome, more intervention practices had their dashboards viewed compared with controls [65.7% versus 55.9%; RD 9.8%, 95% confidence intervals (CIs): 4.76% to 14.9%, P &lt; 0.001]. More plain feedback practices had their dashboard viewed than behavioural feedback practices (69.1% versus 62.4%); but not meeting the P &lt; 0.05 threshold (6.8%, 95% CI: −0.19% to 13.8%, P = 0.069). For the primary prescribing outcome, intervention practices possibly reduced broad-spectrum prescribing to a greater extent than controls (1.42% versus 1.12%); but again not meeting the P &lt; 0.05 threshold (coefficient −0.31%, CI: −0.7% to 0.1%, P = 0.104). The behavioural impact group reduced broad-spectrum prescribing to a greater extent than plain feedback practices (1.63% versus 1.20%; coefficient 0.41%, CI: 0.007% to 0.8%, P = 0.046). No harms were detected.

Conclusions
Unsolicited feedback increased practices’ engagement with data, with possible slightly reduced antibiotic prescribing (P = 0.104). Behavioural science techniques gave greater prescribing effects. The modest effects on prescribing may reflect saturation from similar initiatives on antibiotic prescribing.

Clinical Trial Registration
ISRCTN86418238.
Glucose-induced internalization of the S. cerevisiae galactose permease Gal2 is dependent on phosphorylation and ubiquitination of its aminoterminal cytoplasmic tail
Authors: Tamayo Rojas Sebastian A , Schmidl Sina , Boles Eckhard , Oreb Mislav 
Published: March 2021

ABSTRACT
The hexose permease Gal2 of Saccharomyces cerevisiae is expressed only in the presence of its physiological substrate galactose. Glucose tightly represses the GAL2 gene and also induces the clearance of the transporter from the plasma membrane by ubiquitination and subsequent degradation in the vacuole. Although many factors involved in this process, especially those responsible for the upstream signaling, have been elucidated, the mechanisms by which Gal2 is specifically targeted by the ubiquitination machinery have remained elusive. Here, we show that ubiquitination occurs within the N-terminal cytoplasmic tail and that the arrestin-like proteins Bul1 and Rod1 are likely acting as adaptors for docking of the ubiquitin E3-ligase Rsp5. We further demonstrate that phosphorylation on multiple residues within the tail is indispensable for the internalization and possibly represents a primary signal that might trigger the recruitment of arrestins to the transporter. In addition to these new fundamental insights, we describe Gal2 mutants with improved stability in the presence of glucose, which should prove valuable for engineering yeast strains utilizing complex carbohydrate mixtures present in hydrolysates of lignocellulosic or pectin-rich biomass.
Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions
Authors: Wu Harry , Mach John , Gemikonakli Gizem , Tran Trang , Allore Heather , Gnjidic Danijela , Howlett Susan E , de Cabo Rafael , Le Couteur David G , Hilmer Sarah N 
Published: March 2021

Abstract
Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6–8/group) for 4–6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p &lt; .001). Old animals had a greater decline in nesting score (p &lt; .05) and midzone distance (p &lt; .001) than young animals. Grip strength declined more in males than females (p &lt; .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes.
Cellular Immune Phenotypes and Worsening Scores of Frailty-Associated Parameters Over an 18-Month Period in the Very Old
Authors: Goldeck David , Adriaensen Wim , Oettinger Lilly , Vaes Bert , van Pottelbergh Gijs , Degryse Jean-Marie , Hamprecht Klaus , Matheï Catharina , Pawelec Graham 
Published: March 2021

Abstract
Frailty has been related to inflammaging and certain immune parameters. In previous analyses of participants older than 80 years of age in the longitudinal BELFRAIL cohort study, the main focus was on T-cell phenotypes and the association with cytomegalovirus (CMV) serostatus and survival, finding that a CD4:CD8 ratio greater than 5 was associated with frailty, impaired activities of daily living (ADLs), and mortality (but only in women). Here, we phenotyped peripheral blood immune cells via multicolor flow cytometry and correlated these with the dynamics of changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery from baseline values over 18 months follow-up. We found that higher frequencies of B cells and late-differentiated CD8+ T cells at 18 months from baseline were associated with ADL impairment that had worsened over the preceding 18 months. There were no significant associations with monocyte, dendritic cell, or natural killer (NK) cell phenotypes. No associations with the Geriatric Depression Scale, the Mini-Mental State Examination, or the Short Physical Performance Battery were found. Thus, while these results do not establish causality, they suggest that certain adaptive immune, but not innate immune, parameters are associated with a worsened ADL in the very old.
Finding opportunity in the COVID-19 crisis: prioritizing gender in the design of social protection policies
Authors: Perri Melissa , Metheny Nick , Matheson Flora I , Potvin Kelly , O’Campo Patricia 
Published: March 2021

SummaryThe COVID-19 pandemic is highlighting the harm perpetuated by gender-blind programs for marginalized citizens, including sexual and gender minorities (SGMs) and cisgender women. Gender-blind programs are known to augment harms associated with violence and structural stigmatization by reinforcing rather than challenging unequal systems of power. The intersecting marginalization of these populations with systems of class, race, and settler-colonialism is exacerbating the impact that policies such as physical distancing, school closures, and a realignment of healthcare priorities are having on the wellbeing of these populations. The overarching reasons why women and SGM are marginalized are well known and stem from a hegemonic, patriarchal system that fails to fully integrate these groups into planning and decision making regarding public health programming—including the response to COVID-19. In this perspective, we aim to highlight how the exclusion of cisgender women and SGM, and failure to use a gender redistributive/transformative approach, has (i) hampered the recovery from the pandemic and (ii) further entrenched the existing power structures that lead to the marginalization of these groups. We also argue that COVID-19 represents a once-in-a-century opportunity to realign priorities regarding health promotion for cisgender women and SGM by using gender redistributive/transformative approaches to the recovery from the pandemic. We apply this framework, which aims to challenge the existing power structures and distribution of resources, to exemplars from programs in health, housing, employment, and incarceration to envision how a gender redistributive/transformative approach could harness the COVID-19 recovery to advance health equity for cisgender women and SGM.
Characterization of Klebsiella pneumoniae complex isolates from pigs and humans in farms in Thailand: population genomic structure, antibiotic resistance and virulence genes
Authors: Leangapichart Thongpan , Lunha Kamonwan , Jiwakanon Jatesada , Angkititrakul Sunpetch , Järhult Josef D , Magnusson Ulf , Sunde Marianne 
Published: March 2021

Abstract

Objectives
To define characteristics of Klebsiella pneumoniae complex (hereafter KP) isolates from healthy pigs, farm workers and their household members in Thailand.

Methods
A total of 839 individual rectal swabs from pigs on 164 farms and 271 faecal samples of humans working on pig farms and persons living in the same household in Khon Kaen, Thailand were screened for gut colonization by KP. Genomic sequences were investigated for antibiotic resistance and virulence genes. Phylogenetic analyses were performed in addition to comparison with isolates from previous studies from Thailand.

Results
KP was detected in approximately 50% of pig and human samples. In total, 253 KP isolates were obtained: 39% from pigs, 34% from farmers and 26% from individuals living on the same farm but without animal contact. MLST revealed high genetic diversity with 196 different STs distributed over four phylogroups (Kp1 to Kp4). Low prevalence of ESBL-KP (7.5%) and colistin-resistant KP (3.2%) was observed among pigs and humans. Remarkably, four convergent MDR and hypervirulent strains were observed: one from pigs (ST290) and three from humans [ST35, ST3415 (strain 90CP1), ST17 (strain 90CM2)]. Sharing of KP clones among pigs and humans was identified for some STs including ST4788, ST661, ST3541 and ST29.

Conclusions
The study indicated a low prevalence of ESBL and mcr genes among KP isolated from pigs and healthy humans in Thailand and suggested the possibility of zoonotic transmission for a subset of circulating KP clones.
The Impact of a Two-Step Choice Process on Trade-Off Decisions
Authors: Lei Jing , Zhang Ying 
Published: March 2021

Abstract
Trade-offs between attributes are common when making product choices. Prior research suggests that consumers tend to avoid the extremes and opt for the middle options when they make a trade-off decision between two key product attributes (e.g., tastiness and healthiness of food items) in one step. In this research, we examine how consumers make such trade-off decisions in a two-step choice process in which consumers first choose between product categories competing on two key attributes and then make a final choice within the chosen category. In three studies, we show that when holding the actual choice options unchanged, consumers are more likely to make a more extreme final choice, prioritizing a single attribute rather than compromising when they follow a two-step choice process instead of a one-step process.
Alterations in the Expression of the Genes Responsible for the Synthesis of Heparan Sulfate in Brains With Alzheimer Disease
Authors: Pérez-López Natalia , Martín Carla , García Beatriz , Solís-Hernández Maria Pilar , Rodríguez David , Alcalde Ignacio , Merayo Jesús , Fernández-Vega Iván , Quirós Luis M 
Published: March 2021

Abstract
The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.
High-altitude tree growth responses to climate change across the Hindu Kush Himalaya
Authors: Zheng Lili , Gaire Narayan Prasad , Shi Peili 
Published: March 2021

AbstractAimsRapid warming at high altitudes may lead to a higher sensitivity in tree growth to temperature. The key factors constraining tree radial growth and to what extent regional tree growth has suffered from climatic changes are unclear.MethodsTree-ring width data were collected from 73 sites across the Hindu Kush Himalaya (HKH), including three dominant genera (Abies, Juniperus and Picea) at high altitudes over 3000 m. Dynamic time warping was introduced to develop subregional chronologies by considering the synchrony of annual tree growth among different sites. We quantified the contribution of the climate variables, and analyzed the spatiotemporal variation of the growth–climate relationship.Important FindingsThe site chronologies were grouped into three clusters, corresponding to the three distinct bioclimatic zones, i.e. the western HKH, central-eastern HKH and southeastern Tibetan Plateau (TP). Tree growth was positively correlated to winter and spring precipitation in the drier western HKH, and to winter temperature and spring precipitation in the humid southeastern TP. Tree growth was markedly constrained by the minimum temperature, especially in winter, with its importance increasing from the west toward the east. As shown by moving correlation analysis, the signal of winter temperature in tree growth was weakened in the western and central-eastern HKH, while it was enhanced in the southeastern TP following rapid warming since the 1980s. Our results highlight that continuous warming may cause forest recession due to warming-induced moisture deficit in the western HKH, but forest expansion in the southeastern TP.
Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction
Authors: Yamada Takahiro , Takao Seishin , Koyano Hidenori , Nihongi Hideaki , Fujii Yusuke , Hirayama Shusuke , Miyamoto Naoki , Matsuura Taeko , Umegaki Kikuo , Katoh Norio , Yokota Isao , Shirato Hiroki , Shimizu Shinichi 
Published: March 2021

Abstract
In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.
Emergency Neurology
Authors: LaHue Sara , Levin Morris 
Published: March 2021

Abstract
Neurological emergencies, either presenting in the emergency department, arising in hospitalized patients, or presenting in the field are among the most worrisome of all medical situations. Neurologists are trained in best approaches to these emergencies, which include such diverse presentations as severe headache, transient neurologic deficits, altered consciousness and coma, severe vertigo and balance problems, uncontrolled seizures, radicular and facial pain, and posttraumatic conditions. However, as time is often “the enemy” as ER physicians commonly say, diagnostic and treatment dilemmas are particularly challenging in the field of emergency neurology. This volume attempts, as do all the offerings in Oxford University Press’s What Do I Do Now series, to present straightforward but thorough roadmaps for handling the most common and worrisome impasses faced by neurologists and other providers in the topic area. Illustrative cases in cerebrovascular, epileptic, infectious, inflammatory, metabolic, traumatic, neoplastic, and structural conditions are presented with recommendations for best approaches to differential diagnosis, diagnostic testing, and management decision-making in important challenges faced in both adult and pediatric cases. Each case contains a brief summary of key information. The reader is encouraged to imagine the case under discussion, formulate a differential diagnosis, plan diagnostic testing, and begin thinking about best management approaches. Then read Drs. LaHue’s and Levin’s approach to the situation. At the end of each chapter is a list of key points to remember in the topic and a selection of resources for further reading.
Acute coronary syndrome: STEMI and NSTEMI
Authors: Prasad Abhiram , Raphael Claire 
Published: March 2021

Abstract
Management of acute coronary syndrome (ACS) is dictated by clinical features and electrocardiographic findings. Morphine is used for pain relief. Sublingual or intravenous nitrates are administered to relieve ischaemia. Patients should be treated with dual antiplatelet medications, usually aspirin and one of clopidogrel, prasugrel, or ticagrelor. For ST-segment elevation myocardial infarction, reperfusion therapy is with primary percutaneous coronary intervention (PPCI) or thrombolysis for those presenting to non-PPCI centres who cannot have timely access to PPCI. For non-ST-segment elevation myocardial infarction and unstable angina, timing of angiography, and revascularization if indicated, is determined by the severity of ischaemia. All patients with ACS should be treated with secondary prevention medications, including antiplatelet therapy, statins, beta-blockers, and renin–angiotensin system inhibitors.
A novel approach to investigate chemical inhomogeneities in GRB host galaxies: theZabs–Zemiss relation
Authors: Metha Benjamin , Cameron Alex J , Trenti Michele 
Published: March 2021

ABSTRACTModels of chemical enrichment and inhomogeneity in high-redshift galaxies are challenging to constrain observationally. In this work, we discuss a novel approach to probe chemical inhomogeneities within long gamma-ray burst (GRB) host galaxies, by comparing the absorption metallicity, Zabs, from the GRB afterglow (which probes the environment along the line of sight) with the emission-line metallicity, Zemiss, measured via slit spectroscopy. Using the IllustrisTNG simulation, the theoretical relationship between these metallicity metrics is explored for a range of GRB formation models, varying the GRB progenitor metallicity threshold. For galaxies with fixed Zemiss, the median value of Zabs depends strongly on the GRB progenitor threshold metallicity, with Zabs significantly lower than Zemiss for high-metallicity hosts. Conversely, at fixed Zabs, the median value of Zemiss depends primarily on the metallicity distribution of galaxies in IllustrisTNG and their chemical inhomogeneities, offering a GRB model-independent way to constrain these processes observationally. Currently, only one host galaxy has data for both absorption and emission metallicities (GRB121014A). We re-analyse the emission spectrum and compare the inferred metallicity Zemiss to a recent Bayesian determination of Zabs, finding $\log (Z_{\rm emiss}/Z_{\odot }) = \log (Z_{\rm abs}/Z_{\odot }) +0.35^{+ 0.14}_{- 0.25}$, within ∼2 standard deviations of predictions from the IllustrisTNG simulation. Future observations with the James Webb Space Telescope will be able to measure Zemiss for four other GRB hosts with known Zabs values, using ∼2-h observations. While small, the sample will provide preliminary constraints on the Zabs–Zemiss relation to test chemical enrichment schemes in cosmological simulations.