bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction
Authors: Tromp Jasper , Ouwerkerk Wouter , Teng Tiew-Hwa K , Cleland John G F , Bamadhaj Sahiddah , Angermann Christiane E , Dahlstrom Ulf , Tay Wan Ting , Dickstein Kenneth , Ertl Georg , Hassanein Mahmoud , Perrone Sergio V , Ghadanfar Mathieu , Schweizer Anja , Obergfell Achim , Collins Sean P , Filippatos Gerasimos , Lam Carolyn S P 
Published: February 2022

Abstract

Background
Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines.

Methods and results
This analysis assessed prescription rates and doses of renin–angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.
Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level.

Conclusion
Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.
Changes in the phyllosphere and rhizosphere microbial communities of soybean in the presence of pathogens
Authors: Díaz-Cruz Gustavo A , Cassone Bryan J 
Published: February 2022

Abstract
Soybean (Glycine max L.) is host to an array of foliar- and root-infecting pathogens that can cause significant yield losses. To provide insights into the roles of microorganisms in disease development, we evaluated the bacterial and fungal communities associated with the soybean rhizosphere and phyllosphere. For this, leaf and soil samples of healthy, Phytophthora sojae-infected and Septoria glycines-infected plants were sampled at three stages during the production cycle, and then subjected to 16S and Internal Transcribed Spacer (ITS) amplicon sequencing. The results indicated that biotic stresses did not have a significant impact on species richness and evenness regardless of growth stage. However, the structure and composition of soybean microbial communities were dramatically altered by biotic stresses, particularly for the fungal phyllosphere. Additionally, we cataloged a variety of microbial genera that were altered by biotic stresses and their associations with other genera, which could serve as biological indicators for disease development. In terms of soybean development, the rhizosphere and phyllosphere had distinct microbial communities, with the fungal phyllosphere most influenced by growth stage. Overall, this study characterized the phyllosphere and rhizosphere microbial communities of soybean, and described the impact of pathogen infection and plant development in shaping these bacterial and fungal communities.
A Mixed-methods Assessment of the Impact of Insurance Issues on the Emotional and Physical Health of Patients With Inflammatory Bowel Disease
Authors: Philippou Alicia , Birhanu Beselot , Biello Anthony , Keefer Laurie , Gorbenko Ksenia 
Published: February 2022

Abstract

Background
In patients with inflammatory bowel disease (IBD), failure to adhere to treatment regimens due to insurance issues can lead to disease complications. Our aim was to examine patients’ perceptions of the impact of insurance issues on their health.

Methods
Twenty-nine patients with IBD at a large US academic center and an insurance issue participated in a mixed-methods study. Retrospective chart review and an online questionnaire were completed to collect demographic information, IBD characteristics, and validated resilience scores. Semistructured interviews were completed for insurance experiences, which were coded independently by 2 coders for themes.

Results
Twenty-nine patients completed the interview, and 24 completed the online survey. Sixteen had Crohn’s disease, 13 had ulcerative colitis, and 66% were female. The most common insurance issue was lapsed insurance. Many experienced physical consequences, with 58% having flares, 14% undergoing surgery, and 14% developing antibodies. All emotional responses were negative, with the majority feeling stressed (38%). Providers were uninformed of insurance issues in 28% of cases. When asked about perceived resilience, 41% felt incapable of managing the situation, and 45% gave up trying to solve the problem. When asked how to improve going forward, 38% requested an easily accessible advocate to guide them.

Conclusions
A large proportion of our cohort chose not to inform their provider, felt incapable of managing on their own, and gave up on resolving their insurance issue. This highlights the need to consider restructuring the insurance system, to identify those at risk for insurance issues, and to make advocates available to avoid devastating consequences.
Heavy metals in the blueband hermit crab, Pagurus samuelis (Stimpson, 1857) (Decapoda: Anomura: Paguridae), from two Southern California habitats
Authors: dos Santos Tyler S , Boskovic Danilo S , Shih Wendy , Dunbar Stephen G 
Published: February 2022

Abstract
Although heavy metal concentrations naturally vary in the environment, anthropogenic sources of heavy metals can mask and override such fluctuations. Indicator species can be used to determine environmental concentrations of certain metals and evaluate the impacts of metals from associated anthropogenic sources. We sought to determine if the hermit crab Pagurus samuelis (Stimpson, 1857) may play a role as an indicator species along the Southern California coast. Seawater and P. samuelis samples were collected from both Cabrillo Beach and White Point Beach rocky intertidal locations and analyzed for concentrations of cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), and zinc (Zn) using microwave plasma-atomic emission spectrometry (MP-AES). Lead concentrations were higher in seawater at Cabrillo Beach compared to White Point Beach, whereas Zn concentrations were higher at White Point Beach than at Cabrillo Beach. All other metals were not significantly different between these locations. Cd was higher in hermit crabs collected from Cabrillo Beach than those from White Point Beach, whereas Cr was higher in crabs collected from White Point Beach compared with those from Cabrillo Beach. In comparisons of seawater with samples of hermit crabs, seawater had higher concentrations of Zn and Cd, whereas hermit crabs had higher concentrations of Cu at both locations, and higher levels of Cr at White Point Beach. While this study does not provide conclusive evidence that P. samuelis is an indicator species, it does demonstrate differences in metal concentrations between tested locations and populations of P. samuelis. Although P. samuelis may not be negatively impacted by the heavy metal concentrations we found, the risks of potential bioaccumulation at higher trophic levels is of concern.
Prognostic Relevance of Transforming Growth Factor-β Receptor Expression and Signaling in Glioblastoma, Isocitrate Dehydrogenase-Wildtype
Authors: Togni Claudio , Rom Emanuel , Burghardt Isabel , Roth Patrick , Rushing Elisabeth J , Weller Michael , Gramatzki Dorothee 
Published: February 2022

Abstract
The transforming growth factor (TGF)-β signaling pathway has been recognized as a major factor in promoting the aggressive behavior of glioblastoma, isocitrate dehydrogenase-wildtype. However, there is little knowledge about the expression of TGF-β receptors in glioblastoma. Here, we studied the expression patterns of TGF-β receptor II (TGFβRII), type I receptors activin receptor-like kinase (ALK)-5, and ALK-1, as well as of the transcriptional regulators inhibitor of differentiation (Id) 2, Id3, and Id4 in human glioblastoma. The expression of TGFβRII, ALK-5, and ALK-1 varied greatly, with TGFβRII and ALK-5 being the most abundant and ALK-1 being the least expressed receptor. None of the 3 receptors was preferentially expressed by tumor vasculature as opposed to the tumor bulk, indicating tumor bulk-governed mechanisms of TGF-β signaling with regard to glioblastoma-associated angiogenesis. A positive correlation was found between ALK-1 and Id2, suggesting that Id2, broadly expressed in the tumor cells, is a downstream target of this receptor-dependent pathway. Furthermore, there was a trend for high expression of ALK-5 or Id2 to be associated with inferior overall survival. Hence, we propose that ALK-5 may be used for patient stratification in future anti-TGF-β treatment trials and that Id2 might be a potential target for anti-TGF-β interventions.
Effects of internal exposure to neutron-activated 56MnO2 powder on locomotor activity in rats
Authors: Otani Keiko , Ohtaki Megu , Fujimoto Nariaki , Uzbekov Darkhan , Kairkhanova Ynkar , Saimova Aisulu , Chaizhunusova Nailya , Habdarbaeva Dariya , Azhimkhanov Almas , Zhumadilov Kassym , Stepanenko Valeriy , Hoshi Masaharu 
Published: February 2022

Abstract
At the detonation of the atomic bombing in Hiroshima and Nagasaki, a significant amount of radionuclides was produced by the neutron induced activation. The residual radiation from the explosion is crucial to the health risk of the people who entered these cities after the bombing and might have inhaled these radioactive materials. Because 56Mn is one of the major radionuclides produced in soil and have not been studied until now, we had conducted a series of experiments using rats to investigate the biological impacts of exposure of 56MnO2 particles. In these experiments, the rats’ spontaneous locomotor activity was also assessed to examine the possible effects of 56Mn on their behavior. However, the locomotor activity data obtained from an individual experiment failed to identify radiation effects due to the large variation among animals and the small sample size. In the present study, all available data from our previous studies on 56MnO2 exposure (0.02–0.15 Gy of whole-body doses) as well as 60Co-γ exposure (at 2–5 Gy of whole-body doses) were pooled. Our statistical method, which takes into account individual differences and daily fluctuations, successfully identified a decrease in locomotor activity caused by 56MnO2 exposure, where the changes were gradual and reached the maximum reduction around 2 weeks after exposure. In contrast, exposure to 60Co-γ rays produced the highest decline of activity within one day. These results suggest that internal exposure to 56Mn at whole-body doses of even less than 0.15 Gy may have a long-lasting impact on locomotor activity.
Serratia marcescensPLR enhances lateral root formation through supplying PLR-derived auxin and enhancing auxin biosynthesis in Arabidopsis
Authors: Zhang Chunlei , Yu Zipeng , Zhang Mengyue , Li Xiaoxuan , Wang Mingjing , Li Lixin , Li Xugang , Ding Zhaojun , Tian Huiyu 
Published: February 2022

AbstractPlant growth promoting rhizobacteria (PGPR) refer to bacteria that colonize the rhizosphere and contribute to plant growth or stress tolerance. To further understand the molecular mechanism by which PGPR exhibit symbiosis with plants, we performed a high-throughput single colony screening from the rhizosphere, and uncovered a bacterium (named promoting lateral root, PLR) that significantly promotes Arabidopsis lateral root formation. By 16S rDNA sequencing, PLR was identified as a novel sub-species of Serratia marcescens. RNA-seq analysis of Arabidopsis integrated with phenotypic verification of auxin signalling mutants demonstrated that the promoting effect of PLR on lateral root formation is dependent on auxin signalling. Furthermore, PLR enhanced tryptophan-dependent indole-3-acetic acid (IAA) synthesis by inducing multiple auxin biosynthesis genes in Arabidopsis. Genome-wide sequencing of PLR integrated with the identification of IAA and its precursors in PLR exudates showed that tryptophan treatment significantly enhanced the ability of PLR to produce IAA and its precursors. Interestingly, PLR induced the expression of multiple nutrient (N, P, K, S) transporter genes in Arabidopsis in an auxin-independent manner. This study provides evidence of how PLR enhances plant growth through fine-tuning auxin biosynthesis and signalling in Arabidopsis, implying a potential application of PLR in crop yield improvement through accelerating root development.
FRB 121102: Drastic changes in the burst polarization contrasts with the stability of the persistent emission
Authors: Plavin A , Paragi Z , Marcote B , Keimpema A , Hessels J W T , Nimmo K , Vedantham H K , Spitler L G 
Published: February 2022

ABSTRACT
We study milliarcsecond-scale properties of the persistent radio counterpart to FRB 121102 and investigate the spectro-polarimetric properties of a bright burst. For the former, we use European VLBI Network (EVN) observations in 2017 at 1.7 and 4.8 GHz. For the latter, we reanalyse the 1.7-GHz data from the 100-m Effelseberg telescope taken in 2016. These observations predate other polarimetric studies of FRB 121102, and yield the highest burst Faraday rotation measure (RM) to date, RM = 1.27 · 105 rad m−2, consistent with the decreasing RM trend. The fractional polarization of the burst emission is 15 per cent at 1.7 GHz. This can be reconciled with the high-fractional polarization at higher frequencies if the Faraday width of the burst environment is 150 rad m−2 – a bare 0.1 per cent of the total Faraday rotation. The width may originate from minor non-uniformities in the Faraday screen, or from effects in the emitting region itself. The upper limit on the persistent source size is 1 pc, barely consistent with a young supernova (SN) scenario. The flux variability limit of $\lt 10{{\ \rm per\ cent}}$ is not in favour of the young SN scenario, and challenges other interpretations as well. The fractional polarization of the faint persistent source is constrained at $\lt 25{{\ \rm per\ cent}}$ at 4.8 GHz ruling out a common origin with the highly polarized individual bursts.
Antispacer peptide nucleic acids for sequence-specific CRISPR-Cas9 modulation
Authors: Economos Nicholas G , Quijano Elias , Carufe Kelly E W , Perera J Dinithi R , Glazer Peter M 
Published: February 2022

Abstract
Despite the rapid and broad implementation of CRISPR-Cas9-based technologies, convenient tools to modulate dose, timing, and precision remain limited. Building on methods using synthetic peptide nucleic acids (PNAs) to bind RNA with unusually high affinity, we describe guide RNA (gRNA) spacer-targeted, or ‘antispacer’, PNAs as a tool to modulate Cas9 binding and activity in cells in a sequence-specific manner. We demonstrate that PNAs rapidly and efficiently target complexed gRNA spacer sequences at low doses and without design restriction for sequence-selective Cas9 inhibition. We further show that short PAM-proximal antispacer PNAs achieve potent cleavage inhibition (over 2000-fold reduction) and that PAM-distal PNAs modify gRNA affinity to promote on-target specificity. Finally, we apply antispacer PNAs for temporal regulation of two dCas9-fusion systems. These results present a novel rational approach to nucleoprotein engineering and describe a rapidly implementable antisense platform for CRISPR-Cas9 modulation to improve spatiotemporal versatility and safety across applications.
ZMYM2 restricts 53BP1 at DNA double-strand breaks to favor BRCA1 loading and homologous recombination
Authors: Lee Doohyung , Apelt Katja , Lee Seong-Ok , Chan Hsin-Ru , Luijsterburg Martijn S , Leung Justin W C , Miller Kyle M 
Published: February 2022

Abstract
An inability to repair DNA double-strand breaks (DSBs) threatens genome integrity and can contribute to human diseases, including cancer. Mammalian cells repair DSBs mainly through homologous recombination (HR) and nonhomologous end-joining (NHEJ). The choice between these pathways is regulated by the interplay between 53BP1 and BRCA1, whereby BRCA1 excludes 53BP1 to promote HR and 53BP1 limits BRCA1 to facilitate NHEJ. Here, we identify the zinc-finger proteins (ZnF), ZMYM2 and ZMYM3, as antagonizers of 53BP1 recruitment that facilitate HR protein recruitment and function at DNA breaks. Mechanistically, we show that ZMYM2 recruitment to DSBs and suppression of break-associated 53BP1 requires the SUMO E3 ligase PIAS4, as well as SUMO binding by ZMYM2. Cells deficient for ZMYM2/3 display genome instability, PARP inhibitor and ionizing radiation sensitivity and reduced HR repair. Importantly, depletion of 53BP1 in ZMYM2/3-deficient cells rescues BRCA1 recruitment to and HR repair of DSBs, suggesting that ZMYM2 and ZMYM3 primarily function to restrict 53BP1 engagement at breaks to favor BRCA1 loading that functions to channel breaks to HR repair. Identification of DNA repair functions for these poorly characterized ZnF proteins may shed light on their unknown contributions to human diseases, where they have been reported to be highly dysregulated, including in several cancers.
Âcimowin Waspison: Cultivating curiosity, sharing stories, and taking steps forward in Canada’s ‘Calls to Action’
Authors: MacNairn Ian Adam Smith , Al-Ani Abdullah 
Published: February 2022

AbstractWe have yet to fully walk the path of the Calls to Action put forth by the Truth & Reconciliation Commission of Canada within our health care system. In this piece, we offer a suggestion of enhanced and increased curiosity and empathy in our practice as health care providers, particularly in regard to Call 22. This encouragement is exemplified through sharing learning we received around an Indigenous way of knowing and traditional health practice: waspison, known in English as, ‘moss bag’. Waspison is a sacred prenatal and postnatal practice used since time immemorial and carrying through to today, across Canada and the USA. It is a novel teaching example not previously discussed in medical literature. Our intention is to stoke greater interest in practicing deep caring for our patients in ways that are culturally humble, safe, and as competent as possible. That is, learning more about our patients through curiosity and empathy.
The Impact of Active Bystander Training on Officer Confidence and Ability to Address Ethical Challenges
Authors: Taniguchi Travis , Vovak Heather , Cordner Gary , Amendola Karen , Yang Yukun , Hoogesteyn Katherine , Bartness Martin 
Published: February 2022

Abstract
Active bystandership (AB) training in the Baltimore Police Department (titled Ethical Policing is Courageous, (EPIC)) was designed to (1) prevent misconduct, (2) avoid mistakes, and (3) promote healthy officers. AB training promotes an organizational culture where officers feel empowered to intervene when noticing their colleagues are or are about to, engage in dangerous, unwanted, or inappropriate behaviour. It focuses on direct intervention in an informal capacity rather than formalized reporting. Self-report surveys (n = 1,753) were collected immediately post-completion of EPIC training. Survey domains included perceived impact of the training on behaviour, application to the job, confidence in ability to intervene, and ability to address ethical challenges. A large majority of respondents indicated greater likelihood of intervening after the training and having confidence in their ability to intervene with peers and supervisors; write-in responses suggested that the biggest perceived challenge was in intervening with supervisors.
Post-COVID-19 HSV encephalitis: a review
Authors: Gupta S , Dutta A , Chakraborty U , Kumar R , Das D , Ray B K 
Published: February 2022

Summary

Background
Herpes simplex virus encephalitis (HSVE) is one of the most common infectious causes of sporadic encephalitis. Coronavirus disease (COVID-19) has been associated with immune dysregulation of the host that might increase the risk of infections like HSVE following SARS-CoV-2 infection. There is paucity of literature on post COVID-19 HSVE. This study was conducted with the aim of analyzing the clinical presentation, brain imaging, and outcome of patients presenting with HSVE within 6 weeks of COVID-19 and providing a comprehensive review on the possible mechanisms of post-COVID-19 HSVE.

Methods
This observational study included patients who had laboratory-confirmed HSVE (type 1 or type 2) and a history of COVID-19 within the previous 6 weeks. Patients were followed up for 3 months.

Results
Eight patients were included and all of them had type 1 HSVE. The mean latency of onset of neurological symptoms from being diagnosed with COVID-19 is 23.87 days and a majority of the patients have received injectable steroids with a mean duration of 6.5 days. Behavioral abnormality was the commonest neurological presentation and typical brain imaging involved T2 FLAIR hyperintensities of the medial temporal lobes. All patients received intravenous acyclovir 10 mg/kg every eight hourly for atleast 14 days. One patient with concomitant rhinocerebral mucormycosis succumbed while the majority had a complete recovery.

Conclusion
Possible immune dysregulation in COVID-19 may increase the susceptibility of HSVE in patients with a history of recent SARS-CoV-2 infection. The clinical manifestations and laboratory findings of HSVE in such patients are similar to typical HSVE.
Increased Belief Instability in Psychotic Disorders Predicts Treatment Response to Metacognitive Training
Authors: Hauke D J , Roth V , Karvelis P , Adams R A , Moritz S , Borgwardt S , Diaconescu A O , Andreou C 
Published: February 2022

AbstractBackground and HypothesisIn a complex world, gathering information and adjusting our beliefs about the world is of paramount importance. The literature suggests that patients with psychotic disorders display a tendency to draw early conclusions based on limited evidence, referred to as the jumping-to-conclusions bias, but few studies have examined the computational mechanisms underlying this and related belief-updating biases. Here, we employ a computational approach to understand the relationship between jumping-to-conclusions, psychotic disorders, and delusions.Study DesignWe modeled probabilistic reasoning of 261 patients with psychotic disorders and 56 healthy controls during an information sampling task—the fish task—with the Hierarchical Gaussian Filter. Subsequently, we examined the clinical utility of this computational approach by testing whether computational parameters, obtained from fitting the model to each individual’s behavior, could predict treatment response to Metacognitive Training using machine learning.Study ResultsWe observed differences in probabilistic reasoning between patients with psychotic disorders and healthy controls, participants with and without jumping-to-conclusions bias, but not between patients with low and high current delusions. The computational analysis suggested that belief instability was increased in patients with psychotic disorders. Jumping-to-conclusions was associated with both increased belief instability and greater prior uncertainty. Lastly, belief instability predicted treatment response to Metacognitive Training at the individual level.ConclusionsOur results point towards increased belief instability as a key computational mechanism underlying probabilistic reasoning in psychotic disorders. We provide a proof-of-concept that this computational approach may be useful to help identify suitable treatments for individual patients with psychotic disorders.