bluuebunny/crossref_metadata_2025_split huggingface dataset:
Main factors predicting somatic, psychological, and cognitive patient outcomes after significant injury: a pilot study of a simple prognostic tool
Authors: Gross Thomas , Amsler Felix 
Published: October 2021

Abstract

Background
There are still insufficient data on the complexity and predictability of patient-related outcomes following trauma. The aim of this study was to assess longer-term outcomes in patients with significant injury and to develop a simple scoring method to identify patients at high risk of subsequent deficits 1–2 years after injury.

Methods
We conducted a prospective cohort study of survivors of significant injury (New Injury Severity Score, NISS greater than or equal to 8), with analysis of patients’ 1- to 2-year health-related quality of life (HRQoL) and their functional outcomes based on Short Form-36 (SF-36), Trauma Outcome Profile (TOP), and Quality Of Life after Brain Injury (QOLIBRI). Documented variables suspected or known from the literature to be possible factors associated with outcome were first analysed by univariate analysis, and significant variables were entered into a stepwise logistic regression analysis. Scores predicting longer-term impaired outcome were constructed from risk factors resulting from multivariate analysis.

Results
Depending on the patient-reported outcome measure (PROM) used, up to 30 per cent of 1052 study patients (mean NISS 18.6) indicated somatic, 27 per cent psychological, and 54 per cent cognitive deficits. The investigated sociodemographic, injury-related, treatment, and early hospital outcome variables demonstrated only low associations with longer-term outcome in univariate analysis that were highest for preinjury pain or function (R = 0.4) and outcome at hospital discharge (R = 0.3). After logistic regression, the study variables explained a maximum variance of 23 per cent for somatic, 11 per cent for psychological, and 14 per cent for cognitive longer-term outcomes. The resulting Aarau trauma prognostic longer-term outcome scoring (ATPLOS) system, developed by checking eight risk factors, had a specificity of up to 80 per cent, and importantly may facilitate early detection of patients at risk of a poorer longer-term outcome.

Conclusion
Despite the high rate of deficits recorded for survivors of significant injury, particularly in loss of cognitive function, the multiple variables analysed only led to a limited characterization of patient-related longer-term outcomes. Until more is known about additional individual influencing factors, the proposed scoring system may serve well for clinical evaluation.

Registration number
NCT 02165137 (http://www.clinicaltrials.gov)
Evolutionary history of CAM photosynthesis in NeotropicalClusia: insights from genomics, anatomy, physiology and climate
Authors: Luján Manuel , Oleas Nora H , Winter Klaus 
Published: October 2021

AbstractClusia is a remarkable genus of Neotropical woody plants as its members engage in either C3 photosynthesis or employ, to varying degrees, crassulacean acid metabolism (CAM) photosynthesis. Information about the evolutionary history of CAM in Clusia is scarce. Restriction site-associated sequencing of 64 species (20% of the genus) provided strong support for most of the previously recognized nine lineages. Ancestral reconstruction using maximum parsimony or maximum likelihood under a one-rate model suggested that CAM evolved at least four times independently from a most recent common ancestor (MRCA) with C3, whereas a maximum likelihood two-rate model suggested that CAM was already present in the MRCA followed by reversions to C3 in several lineages. Phylogenetic generalized least square analysis assessed variation in seven leaf anatomical traits and CAM activity measured as δ 13C. Results indicate that CAM is highly correlated with palisade mesophyll layer thickness and cell size. In addition, correlation between 19 bioclimatic variables and δ 13C was evaluated. It was found that CAM is positively correlated with habitats with a more severe dry season and greater precipitation seasonality. Since CAM is weakly and/or only periodically expressed in many Clusia spp., and thus not readily reflected in δ 13C, future analysis of phylogenetically-informed CAM expression in Clusia must include physiological measurements such as CO2 exchange and/or diel changes in leaf acidity for each species under investigation.
Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome
Authors: Miyatake Satoko , Yoshida Kunihiro , Koshimizu Eriko , Doi Hiroshi , Yamada Mitsunori , Miyaji Yosuke , Ueda Naohisa , Tsuyuzaki Jun , Kodaira Minori , Onoue Hiroyuki , Taguri Masataka , Imamura Shintaro , Fukuda Hiromi , Hamanaka Kohei , Fujita Atsushi , Satoh Mai , Miyama Takabumi , Watanabe Nobuko , Kurita Yusuke , Okubo Masaki , Tanaka Kenichi , Kishida Hitaru , Koyano Shigeru , Takahashi Tatsuya , Ono Yoya , Higashida Kazuhiro , Yoshikura Nobuaki , Ogata Katsuhisa , Kato Rumiko , Tsuchida Naomi , Uchiyama Yuri , Miyake Noriko , Shimohata Takayoshi , Tanaka Fumiaki , Mizuguchi Takeshi , Matsumoto Naomichi 
Published: October 2021

Abstract
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied.
To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION.
We identified 16 patients from 11 families, of whom seven had ACAGG expansions [(ACAGG)exp/(ACAGG)exp] (ACAGG homozygotes), two had ACAGG and AAGGG expansions [(ACAGG)exp/(AAGGG)exp] (ACAGG/AAGGG compound heterozygotes) and seven had AAGGG expansions [(AAGGG)exp/(AAGGG)exp] (AAGGG homozygotes). The overall detection rate was 5.2% (11/212 families including one family having two expansion genotypes). Long-read sequencers revealed the entire sequence of both AAGGG and ACAGG repeat expansions at the nucleotide level of resolution. Clinical assessment and neuropathology results suggested that patients with ACAGG expansions have similar clinical features to previously reported patients with homozygous AAGGG expansions, although motor neuron involvement was more notable in patients with ACAGG expansions (even if one allele was involved). Furthermore, a later age of onset and slower clinical progression were implied in patients with ACAGG/AAGGG compound heterozygous expansions compared with either ACAGG or AAGGG homozygotes in our very limited cohort.
Our study clearly shows the occurrence of repeat conformation heterogeneity, with possible different impacts on the affected nervous systems. The difference in disease onset and progression between compound heterozygotes and homozygotes might also be suspected but with very limited certainty due to the small sample number of cases in our study. Studies of additional patients are needed to confirm this.
Lessons Learned from Coronavirus Disease 2019 (COVID-19) Therapies: Critical Perspectives From the Infectious Diseases Society of America (IDSA) COVID-19 Treatment Guideline Panel
Authors: Bhimraj Adarsh , Morgan Rebecca L , Shumaker Amy Hirsch , Baden Lindsey , Chi-Chung Cheng Vincent , Edwards Kathryn M , Gandhi Rajesh T , Gallagher Jason C , Muller William J , O’Horo John C , Shoham Shmuel , Wollins Dana Swartzberg , Falck-Ytter Yngve 
Published: October 2021

Abstract
Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained.
Informed decision-making in delivery of dialysis: combining clinical outcomes with sustainability
Authors: Apel Christian , Hornig Carsten , Maddux Frank W , Ketchersid Terry , Yeung Julianna , Guinsburg Adrian 
Published: October 2021

ABSTRACTAs the prevalence of chronic kidney disease is expected to rise worldwide over the next decades, provision of renal replacement therapy (RRT), will further challenge budgets of all healthcare systems. Most patients today requiring RRT are treated with haemodialysis (HD) therapy and are elderly. This article demonstrates the interdependence of clinical and sustainability criteria that need to be considered to prepare for the future challenges of delivering dialysis to all patients in need. Newer, more sustainable models of high-value care need to be devised, whereby delivery of dialysis is based on value-based healthcare (VBHC) principles, i.e. improving patient outcomes while restricting costs. Essentially, this entails maximizing patient outcomes per amount of money spent or available. To bring such a meaningful change, revised strategies having the involvement of multiple stakeholders (i.e. patients, providers, payers and policymakers) need to be adopted. Although each stakeholder has a vested interest in the value agenda often with conflicting expectations and motivations (or motives) between each other, progress is only achieved if the multiple blocs of the delivery system are advanced as mutually reinforcing entities. Clinical considerations of delivery of dialysis need to be based on the entire patient disease pathway and evidence-based medicine, while the non-clinical sustainability criteria entail, in addition to economics, the societal and ecological implications of HD therapy. We discuss how selection of appropriate modes and features of delivery of HD (e.g. treatment modalities and schedules, selection of consumables, product life cycle assessment) could positively impact decision-making towards value-based renal care. Although the delivery of HD therapy is multifactorial and complex, applying cost-effectiveness analyses for the different HD modalities (conventional in-centre and home HD) can support in guiding payability (balance between clinical value and costs) for health systems. For a resource intensive therapy like HD, concerted and fully integrated care strategies need to be urgently implemented to cope with the global demand and burden of HD therapy.
Ideal Vial Size for Infliximab in the Treatment of Inflammatory Bowel Disease: An Analysis of Pharmaceutical Waste and Physician Opinions
Authors: Schachne Jonathan M , Durbin Laura L , Lacher Corey R , Sangha Maheep , Mone Anjali , Swaminath Arun 
Published: October 2021

Abstract

Background
Infliximab is a weight-based prescription for multiple autoimmune diseases and is dispensed only in single-use, 100mg vials. We aim to compute the quantity of infliximab waste at our site and in an ideal world where weight-based prescribing practices are followed. We estimate hypothetical waste reduction and cost-savings if a smaller vial is dispensed. We also surveyed gastroenterologists to study prescription rounding practices for infliximab.

Methods
A pre-existing registry of 426 inflammatory bowel disease patients identified 112 individuals who had received a total of 1003 infliximab administrations from December 2013 to May 2019. We calculated infliximab wastage per administration for the real world and an ideal (weight-based) world. Analysis of potential waste reduction and cost-savings was computed with the hypothetical creation of 50 and 25mg vials. Infliximab-prescribing gastroenterologists completed an online survey, determining reasons for rounding of weight-based prescription, rounding practices, and biosimilar use.

Results
At our site, the total value of infliximab wasted was between $112738.08 and $243209.50. Utilizing 50 and 25mg vials would reduce this waste by 92.2% and 99.4%, respectively. If prescriber guidelines were followed precisely, the total value of waste was between $132781.08 and $286448.19. Utilizing 50 and 25mg vials would reduce waste by 50.39% and 75.34%, respectively. The physician survey revealed that 68.1% rounded doses while only 31.9% prescribed exact weight-based doses.

Conclusions
Infliximab-prescribing gastroenterologists considered reducing drug waste as a common reason in their rounding practices. Our analysis demonstrates significant waste reduction and cost-savings are possible with the introduction of 50 and 25mg vials.
Post-pericardiotomy syndrome: insights into neglected postoperative issues
Authors: Maranta Francesco , Cianfanelli Lorenzo , Grippo Rocco , Alfieri Ottavio , Cianflone Domenico , Imazio Massimo 
Published: October 2021

Abstract Abstract OBJECTIVESPericardial effusion is a common complication after cardiac surgery, both isolated and in post-pericardiotomy syndrome (PPS), a condition in which pleuropericardial damage triggers both a local and a systemic inflammatory/immune response. The goal of this review was to present a complete picture of PPS and pericardial complications after cardiac surgery, highlighting available evidence and gaps in knowledge.METHODSA literature review was performed that included relevant prospective and retrospective studies on the subject.RESULTSPPS occurs frequently and is associated with elevated morbidity and significantly increased hospital stays and costs. Nevertheless, PPS is often underestimated in clinical practice, and knowledge of its pathogenesis and epidemiology is limited. Several anti-inflammatory drugs have been investigated for treatment but with conflicting evidence. Colchicine demonstrated encouraging results for prevention.CONCLUSIONSWider adoption of standardized diagnostic criteria to correctly define PPS and start early treatment is needed. Larger studies are necessary to better identify high-risk patients who might benefit from preventive strategies.
Efficient production of shinorine, a natural sunscreen material, from glucose and xylose by deleting HXK2 encoding hexokinase in Saccharomyces cerevisiae
Authors: Jin Chaeyeon , Kim Sojeong , Moon Seokjun , Jin Hyunbin , Hahn Ji-Sook 
Published: October 2021

ABSTRACT
Mycosporine-like amino acids (MAAs), microbial secondary metabolites with ultraviolet (UV) absorption properties, are promising natural sunscreen materials. Due to the low efficiency of extracting MAAs from natural producers, production in heterologous hosts has recently received attention. Shinorine is a well characterized MAA with strong UV-A absorption property. Previous, we developed Saccharomyces cerevisiae strain producing shinorine by introducing four shinorine biosynthetic genes from cyanobacterium Nostoc punctiforme. Shinorine is produced from sedoheptulose 7-phosphate (S7P), an intermediate in the pentose phosphate pathway. Shinorine production was greatly improved by using xylose as a co-substrate, which can increase the S7P pool. However, due to a limited xylose-utilizing capacity of the engineered strain, glucose was used as a co-substrate to support cell growth. In this study, we further improved shinorine production by attenuating glucose catabolism via glycolysis, which can redirect the carbon flux from glucose to the pentose phosphate pathway favoring shinorine production. Of the strategies we examined to reduce glycolytic flux, deletion of HXK2, encoding hexokinase, was most effective in increasing shinorine production. Furthermore, by additional expression of Ava3858 from Anabaena variabilis, encoding a rate-limiting enzyme 2-demethyl 4-deoxygadusol synthase, 68.4 mg/L of shinorine was produced in an optimized medium containing 14 g/L glucose and 6 g/L xylose, achieving a 2.2-fold increase compared with the previous strain.
Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513
Authors: Kiel Christina , Strunz Tobias , Hasler Daniele , Meister Gunter , Grassmann Felix , Weber Bernhard H F 
Published: October 2021

AbstractMicroRNAs (miRNAs) are small post-transcriptional regulators that offer promising targets for treating complex diseases. To this end, hsa-miR-4513 is an excellent candidate as this gene harbors within its conserved heptametrical seed sequence a frequent polymorphism (rs2168518), which has previously been associated with several complex phenotypes. So far, little is known about the biological mechanism(s) underlying these associations. In an initial step, we now aimed to identify allele-specific target genes of hsa-miR-4513. We performed RNA sequencing in a miRNA overexpression model in human umbilical vein endothelial cells transfected with separated hsa-miR-4513 alleles at rs2168518, namely hsa-miR-4513-G and hsa-miR-4513-A. Genes specifically regulated by the rs2168518 alleles were independently verified by quantitative reverse transcription PCR (qRT-PCR), western blot analysis and allele-specific miRNA binding via a luciferase reporter assay. By a text-based search publicly available databases such as Online Mendelian Inheritance in Man and Mouse Genome Informatics were utilized to link target genes of hsa-miR-4513 to previously described phenotypes. Overall, we identified 23 allele-specific hsa-miR-4513 target genes and replicated 19 of those independently via qRT-PCR. Western blot analysis and luciferase reporter assays conducted for an exemplary subsample further confirmed the allele-specific regulation of these genes by hsa-miR-4513. Remarkably, multiple allele-specific target genes identified are linked via text retrieval to several phenotypes previously reported to be associated with hsa-miR-4513. These genes offer promising candidates for ongoing research on the functional pathobiological impact of hsa-miR-4513 and its seed polymorphism rs2168518. This could give rise to therapeutic applications targeting this miRNA.
Risking Children: The Implications of Predictive Risk Analytics Across Child Protection and Policing for Vulnerable and Marginalized Children
Authors: Sacher Sarah 
Published: October 2021

Abstract
Predictive risk models (‘PRMs’) are increasingly utilized in policing and child protection contexts to monitor, flag and assess children ‘at risk’ of victimization and/or offending. Policing and child protection PRMs focus on similar vulnerable and marginalized cohorts, strengthening the power of the State’s gaze over these groups. An analysis of the overlap between these PRMs reveals problematic State constructions of vulnerability and risk, exposing porous lines between welfare and policing agendas. This Article contends that these PRMs may result in the criminalization of vulnerable and marginalized children, thus undermining objectives of the United Nations Convention on the Rights of the Child (UNCRC). The UNCRC is applied to assess implications for privacy, discrimination and child justice principles, in context with positive obligations to protect children and promote their best interests. The Article also addresses the UNCRC through a critical lens, identifying shortcomings that may undermine its potential to confront relevant harms.
It’s Good to Be Different: How Diversity Impacts Judgments of Moral Behavior
Authors: Khan Uzma , Kalra Ajay 
Published: October 2021

AbstractRecently, conversation on diversity and inclusion has been at the forefront in the media as well as the workplace. Though research has examined how diversity impacts organizational culture and decision-making, little attention has been given to how corporate diversity impacts consumers’ responses to the firm. This article establishes a link between diversity and the perceived morality of market actors. A series of studies demonstrate that greater diversity (racial, gender, or national) in a corporate team leads to perceptions of greater morality of the firm and its representatives and, as a consequence, results in more favorable consumer attitudes and behavior toward the firm. This positive effect arises because consumers perceive diverse teams as possessing higher perspective-taking abilities. Since marketplace morality is concerned with the greater good, we argue that higher perceptions of perspective-taking signal that the team will safeguard the broad interests of the community rather than serve narrow interest groups. The findings have broad implications since consumers are increasingly concerned with moral consumption. Our research suggests that diversity in the workforce is not only important for team performance and social equity but can shape consumers’ sentiments and behavior toward the firm.
Cosmic metal density evolution in neutral gas: insights from observations and cosmological simulations
Authors: Yates Robert M , Péroux Céline , Nelson Dylan 
Published: October 2021

ABSTRACT
We contrast the latest observations of the cosmic metal density in neutral gas ($\rho _{ {met,neu}}$) with three cosmological galaxy evolution simulations: L-Galaxies 2020, TNG100, and EAGLE. We find that the fraction of total metals that are in neutral gas is &lt;40 per cent at 3 ≲ $z$ ≲ 5 in these simulations, whereas observations of damped Lyman-α (DLA) systems suggest ≳ 85 per cent. In all three simulations, hot, low-density gas is also a major contributor to the cosmic metal budget, even at high redshift. By considering the evolution in cosmic SFR density ($\rho _{ {\rm {\small {sfr}}}}$), neutral gas density ($\rho _{ {HI}}$), and mean gas-phase metallicity ($[\langle {} {M/H}\rangle ]_{ {neu}}$), we determine two possible ways in which the absolute $\rho _{ {met,neu}}$ observed in DLAs at high redshift can be matched by simulations: (i) the $\rho _{ {\rm {\small {sfr}}}}$ at $z$ ≳ 3 is greater than inferred from current FUV observations, or (ii) current high-redshift DLA metallicity samples have a higher mean host mass than the overall galaxy population. If the first is correct, TNG100 would match the ensemble data best, however there would be an outstanding tension between the currently observed $\rho _{ {\rm {\small {sfr}}}}$ and $\rho _{ {met,neu}}$. If the second is correct, L-Galaxies 2020 would match the ensemble data best, but would require an increase in neutral gas mass inside subhaloes above $z$ ∼ 2.5. If neither is correct, EAGLE would match the ensemble data best, although at the expense of overestimating $[\langle {} {M/H}\rangle ]_{ {neu}}$. Modulo details related to numerical resolution and H i mass modelling in simulations, these incompatibilities highlight current tensions between key observed cosmic properties at high redshift.