bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver disease in cystic fibrosis patients in a tertiary care center in Saudi Arabia
Authors: Banjar Hanaa , AbdulAziz Najlaa , Khader Jumana , Ghomraoui Firas , Alansari AbdulAziz , Al-Hoshan Abdulaziz , AlKaf Sara , Aldakheel Wajeeh 
Published: June 2021

Background:
Internationally, Cystic fibrosis-associated liver disease (CFLD) is considered the third leading cause of death, following lung disease and transplantation complications.

Aims:
To identify the prevalence of CFLD in cystic fibrosis (CF) patients.

Methodology:
A retrospective chart review for all patients with CF liver disease from a tertiary care center.

Result:
A total of 341 CF patients were included. The mean age at the diagnosis of liver disease is 13.5 (7.6) years. The first elevated ALT was reported in 190/341 patients (56%), elevated AST in 124 patients (36%), elevated alkaline phosphatase (ALP) in 166 patients (49.1%), elevated GGT in 57 patients (23%), and elevated bilirubin in 24 patients (7%). There was an improvement of the liver enzyme values during the follow-up period, P-value = (<0.05). Ultrasound liver assessments were performed in 258/341 patients (75.7%). One hundred and twelve patients (43%) had abnormal findings. In 14 patients (5.4%), assessment exhibited advanced liver disease (liver cirrhosis and periportal fibrosis). Out of 190 patients, who were given ursodeoxycholic acid for elevated liver enzymes, 180 (94.7%) exhibited improvement. One patient underwent liver transplant at the age of 12. Four patients were submitted for liver biopsy; periportal fibrosis was observed in 4 patients (1.6%), and liver cirrhosis by ultrasound (US) in 10 patients (4%).

Conclusion:
Patients with CF should be screened early for liver enzymes, and should undergo the US study to detect liver disease at early stages and to prevent its progression.
The Impact of the UN Guiding Principles on Business Attitudes to Observing Human Rights
Authors: MUCHLINSKI Peter 
Published: June 2021

AbstractThis contribution discusses business attitudes to human rights obligations and how the United Nations Guiding Principles on Business and Human Rights (UNGPs) have affected them. These are best understood historically through a number of periods. The first, between the mid-1970s and the end of the 1980s, coincides with intergovernmental organization-based codifications relevant to corporate social responsibility. Business representatives were highly defensive towards extensive international legal obligations not only in relation to human rights but to corporate social responsibility (CSR) more generally. This was followed by a period of ‘voluntarism’. By the 1990s, businesses had accepted that there could be a link between their operations and human rights violations but continued to reject binding legal duties. Instead, businesses opted for voluntary codes of conduct based on individual corporate, or sectoral, initiatives. It was out of this period that the UN Global Compact emerged. ‘Voluntarism’ continues into the third period, the era of the UNGPs. The UNGPs can be characterized by ‘institutionalized voluntarism’ achieved through the framework for business and human rights represented by the UNGPs. Each period will be examined followed by a concluding section that considers business attitudes to an emerging fourth period that introduces legal obligations through mandatory due diligence laws.
Advancing interprofessional education in communication
Authors: Buller Haley , Ferrell Betty R. , Paice Judith A. , Glajchen Myra , Haythorn Trace 
Published: June 2021

AbstractObjectiveThe objective of this training project is to develop and host Interprofessional Communication courses to improve interdisciplinary communication in oncology care. The initial national course was held in a virtual format and included pre- and post-course participant data. The curriculum was developed with support from the National Cancer Institute.MethodsA virtual two-day course was held to equip nurses, social workers, and chaplains with vital communication skills in oncology practice, so that they could return to their home institutions and teach communication skills to other healthcare professionals, with the intention of making improved communication a quality improvement goal. Fifty-two participants were selected through an application process to attend the virtual course in two-person interprofessional teams (e.g., nurse and chaplain, or social worker and nurse). The Interprofessional Communication Curriculum was based on the National Consensus Project for Quality Palliative Care's eight domains of quality palliative care. The six online modules developed by the investigators were presented in lectures, supplemented by discussion groups, role plays, and other methods of experiential learning.ResultsPre- and post-course results identified areas of communication, which are a priority for improvement by oncology clinicians. Participant goals identified specific strategies to be implemented by participants in their settings.Significance of resultsThe need for communication training was clearly demonstrated across professions in this national training course. Participants were able to apply course content to their goals for quality improvement in cancer settings.
Marked Seasonal Changes in the Microbial Production, Community Composition, and Biogeochemistry of Glacial Snowpack Ecosystems in the Maritime Antarctic
Authors: Hodson A. J. , Sabacka M. , Dayal A. , Edwards A. , Cook J. , Convey P. , Redeker K. , Pearce D. A. 
Published: June 2021

AbstractWe describe seasonal changes in the biogeochemistry, microbial community and ecosystem production of two glacial snowpacks in the maritime Antarctic during a cold summer. Frequent snowfall and low, intermittent melt on the glaciers suppressed surface photosynthesis and promoted net heterotrophy. Concentrations of autotrophic cells (algae and cyanobacteria) were therefore low (average: 150–500 cells mL−1), and short‐term estimates of primary production were almost negligible in early summer (<0.1 μg C L−1 d−1). However, order of magnitude increases in Chlorophyllaconcentrations occurred later, especially within the mid‐snowpack and ice layers below. Short‐term primary production increased to ca. 1 μg C L−1 d−1in mid‐summer, and reached 53.1 μg C L−1 d−1in a mid‐snow layer close to an active penguin colony. However, there were significantly more bacteria than autotrophs in the snow (typically 103cells mL−1, but >104cells mL−1in basal ice near the penguin colony). The ratio of bacteria to autotrophs also increased throughout the summer, and short‐term bacterial production rates (0.2–2000 μg C L−1 d−1) usually exceeded primary production, especially in basal ice (10–1400 μg C L−1 d−1). The basal ice represented the least diverse but most productive habitat, and a striking feature was its low pH (down to 3.3). Furthermore, all of the overlying snow cover became increasingly acidic as the summer season progressed, which is attributed to enhanced emissions from wet guano in the penguin colony. The study demonstrates that active microbial communities can be expected, even when snowmelt is intermittent in the Antarctic summer.
Heterogeneous Changes to Wetlands in the Canadian Prairies Under Future Climate
Authors: Zhang Zhe , Bortolotti Lauren E. , Li Zhenhua , Armstrong Llwellyn M. , Bell Tom W. , Li Yanping 
Published: June 2021

AbstractNumerous wetlands in the prairies of Canada provide important ecosystem services, yet are threatened by climate and land‐use changes. Understanding the impacts of climate change on prairie wetlands is critical to effective conservation planning. In this study, we construct a wetland model with surface water balance and ecoregions to project future distribution of wetlands. The climatic conditions downscaled from the Weather Research and Forecasting model were used to drive the Noah‐MP land surface model to obtain surface water balance. The climate change perturbation is derived from an ensemble of general circulation models using the pseudo global warming method, under the RCP8.5 emission scenario by the end of 21st century. The results show that climate change impacts on wetland extent are spatiotemporally heterogenous. Future wetter climate in the western Prairies will favor increased wetland abundance in both spring and summer. In the eastern Prairies, particularly in the mixed grassland and mid‐boreal upland, wetland areas will increase in spring but experience enhanced declines in summer due to strong evapotranspiration. When these effects of climate change are considered in light of historical drainage, they suggest a need for diverse conservation and restoration strategies. For the mixed grassland in the western Canadian Prairies, wetland restoration will be favorable, while the highly drained eastern Prairies will be challenged by the intensified hydrological cycle. The outcomes of this study will be useful to conservation agencies to ensure that current investments will continue to provide good conservation returns in the future.
Bayesian Detection of Streamflow Response to Earthquakes
Authors: Korup Oliver , Mohr Christian H. , Manga Michael M. 
Published: June 2021

AbstractDetecting whether and how river discharge responds to strong earthquake shaking can be time‐consuming and prone to operator bias when checking hydrographs from hundreds of gauging stations. We use Bayesian piecewise regression models to show that up to a fifth of all gauging stations across Chile had their largest change in daily streamflow trend on the day of the Mw 8.8 Maule earthquake in 2010. These stations cluster distinctly in the near field though the number of detected streamflow changes varies with model complexity and length of time window considered. Credible seismic streamflow changes at several stations were the highest detectable in eight months, with an increased variance of discharge surpassing the variance of discharge following rainstorms. We conclude that Bayesian piecewise regression sheds new and unbiased insights on the duration, trend, and variance of streamflow response to strong earthquakes, and on how this response compares to that following rainstorms.
BACE1 controls synaptic function through modulating release of synaptic vesicles
Authors: Das Brati , Singh Neeraj , Yao Annie Y. , Zhou John , He Wanxia , Hu Xiangyou , Yan Riqiang 
Published: June 2021

AbstractBACE1 initiates production of β-amyloid peptides (Aβ), which is associated with cognitive dysfunction in Alzheimer’s disease (AD) due to abnormal oligomerization and aggregation. While BACE1 inhibitors show strong reduction in Aβ deposition, they fail to improve cognitive function in patients, largely due to its role in synaptic function. We show that BACE1 is required for optimal release of synaptic vesicles. BACE1 deficiency or inhibition decreases synaptic vesicle docking in the synaptic active zones. Consistently, BACE1-null mice or mice treated with clinically tested BACE1 inhibitors Verubecestat and Lanabecestat exhibit severe reduction in hippocampal LTP and learning behaviors. To counterbalance this synaptic deficit, we discovered that BACE1-null mice treated with positive allosteric modulators (PAMs) of metabotropic glutamate receptor 1 (mGluR1), whose levels were reduced in BACE1-null mice and significantly improved long-term potentiation and cognitive behaviors. Similarly, mice treated with mGluR1 PAM showed significantly mitigated synaptic deficits caused by BACE1 inhibitors. Together, our data suggest that a therapy combining BACE1 inhibitors for reducing amyloid deposition and an mGluR1 PAM for counteracting BACE1-mediated synaptic deficits appears to be an effective approach for treating AD patients.
Site selective C–H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy
Authors: Bhowmik Srijita , Galeta Juraj , Havel Václav , Nelson Melissa , Faouzi Abdelfattah , Bechand Benjamin , Ansonoff Mike , Fiala Tomas , Hunkele Amanda , Kruegel Andrew C. , Pintar John. E. , Majumdar Susruta , Javitch Jonathan A. , Sames Dalibor 
Published: June 2021

AbstractMitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material “kratom”, which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.
An actionable anti-racism plan for geoscience organizations
Authors: Ali Hendratta N. , Sheffield Sarah L. , Bauer Jennifer E. , Caballero-Gill Rocío P. , Gasparini Nicole M. , Libarkin Julie , Gonzales Kalynda K. , Willenbring Jane , Amir-Lin Erika , Cisneros Julia , Desai Dipa , Erwin Maitri , Gallant Elisabeth , Gomez Kiara Jeannelle , Keisling Benjamin A. , Mahon Robert , Marín-Spiotta Erika , Welcome Leiaka , Schneider Blair 
Published: June 2021

AbstractGeoscience organizations shape the discipline. They influence attitudes and expectations, set standards, and provide benefits to their members. Today, racism and discrimination limit the participation of, and promote hostility towards, members of minoritized groups within these critical geoscience spaces. This is particularly harmful for Black, Indigenous, and other people of color in geoscience and is further exacerbated along other axes of marginalization, including disability status and gender identity. Here we present a twenty-point anti-racism plan that organizations can implement to build an inclusive, equitable and accessible geoscience community. Enacting it will combat racism, discrimination, and the harassment of all members.
Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry
Authors: Kulkarni Amit , Ferreira Tiago , Bretscher Clemens , Grewenig Annabel , El-Andaloussi Nazim , Bonifati Serena , Marttila Tiina , Palissot Valérie , Hossain Jubayer A. , Azuaje Francisco , Miletic Hrvoje , Ystaas Lars A. R. , Golebiewska Anna , Niclou Simone P. , Roeth Ralf , Niesler Beate , Weiss Amélie , Brino Laurent , Marchini Antonio 
Published: June 2021

AbstractH-1 parvovirus (H-1PV) is a promising anticancer therapy. However, in-depth understanding of its life cycle, including the host cell factors needed for infectivity and oncolysis, is lacking. This understanding may guide the rational design of combination strategies, aid development of more effective viruses, and help identify biomarkers of susceptibility to H-1PV treatment. To identify the host cell factors involved, we carry out siRNA library screening using a druggable genome library. We identify one crucial modulator of H-1PV infection: laminin γ1 (LAMC1). Using loss- and gain-of-function studies, competition experiments, and ELISA, we validate LAMC1 and laminin family members as being essential to H-1PV cell attachment and entry. H-1PV binding to laminins is dependent on their sialic acid moieties and is inhibited by heparin. We show that laminins are differentially expressed in various tumour entities, including glioblastoma. We confirm the expression pattern of laminin γ1 in glioblastoma biopsies by immunohistochemistry. We also provide evidence of a direct correlation between LAMC1 expression levels and H-1PV oncolytic activity in 59 cancer cell lines and in 3D organotypic spheroid cultures with different sensitivities to H-1PV infection. These results support the idea that tumours with elevated levels of γ1 containing laminins are more susceptible to H-1PV-based therapies.
Physical constraints and functional plasticity of cellulases
Authors: Kari Jeppe , Molina Gustavo A. , Schaller Kay S. , Schiano-di-Cola Corinna , Christensen Stefan J. , Badino Silke F. , Sørensen Trine H. , Røjel Nanna S. , Keller Malene B. , Sørensen Nanna Rolsted , Kolaczkowski Bartlomiej , Olsen Johan P. , Krogh Kristian B. R. M. , Jensen Kenneth , Cavaleiro Ana M. , Peters Günther H. J. , Spodsberg Nikolaj , Borch Kim , Westh Peter 
Published: June 2021

AbstractEnzyme reactions, both in Nature and technical applications, commonly occur at the interface of immiscible phases. Nevertheless, stringent descriptions of interfacial enzyme catalysis remain sparse, and this is partly due to a shortage of coherent experimental data to guide and assess such work. In this work, we produced and kinetically characterized 83 cellulases, which revealed a conspicuous linear free energy relationship (LFER) between the substrate binding strength and the activation barrier. The scaling occurred despite the investigated enzymes being structurally and mechanistically diverse. We suggest that the scaling reflects basic physical restrictions of the hydrolytic process and that evolutionary selection has condensed cellulase phenotypes near the line. One consequence of the LFER is that the activity of a cellulase can be estimated from its substrate binding strength, irrespectively of structural and mechanistic details, and this appears promising for in silico selection and design within this industrially important group of enzymes.
Decoupling between calorimetric and dynamical glass transitions in high-entropy metallic glasses
Authors: Jiang Jing , Lu Zhen , Shen Jie , Wada Takeshi , Kato Hidemi , Chen Mingwei 
Published: June 2021

AbstractGlass transition is one of the unresolved critical issues in solid-state physics and materials science, during which a viscous liquid is frozen into a solid or structurally arrested state. On account of the uniform arrested mechanism, the calorimetric glass transition temperature (Tg) always follows the same trend as the dynamical glass transition (or α-relaxation) temperature (Tα) determined by dynamic mechanical analysis (DMA). Here, we explored the correlations between the calorimetric and dynamical glass transitions of three prototypical high-entropy metallic glasses (HEMGs) systems. We found that the HEMGs present a depressed dynamical glass transition phenomenon, i.e., HEMGs with moderate calorimetric Tg represent the highest Tα and the maximum activation energy of α-relaxation. These decoupled glass transitions from thermal and mechanical measurements reveal the effect of high configurational entropy on the structure and dynamics of supercooled liquids and metallic glasses, which are associated with sluggish diffusion and decreased dynamic and spatial heterogeneities from high mixing entropy. The results have important implications in understanding the entropy effect on the structure and properties of metallic glasses for designing new materials with plenteous physical and mechanical performances.
Leveraging bipolar effect to enhance transverse thermoelectricity in semimetal Mg2Pb for cryogenic heat pumping
Authors: Chen Zhiwei , Zhang Xinyue , Ren Jie , Zeng Zezhu , Chen Yue , He Jian , Chen Lidong , Pei Yanzhong 
Published: June 2021

AbstractToward high-performance thermoelectric energy conversion, the electrons and holes must work jointly like two wheels of a cart: if not longitudinally, then transversely. The bipolar effect — the main performance restriction in the traditional longitudinal thermoelectricity, can be manipulated to be a performance enhancer in the transverse thermoelectricity. Here, we demonstrate this idea in semimetal Mg2Pb. At 30 K, a giant transverse thermoelectric power factor as high as 400 μWcm−1K−2 is achieved, a 3 orders-of-magnitude enhancement than the longitudinal configuration. The resultant specific heat pumping power is ~ 1 Wg−1, higher than those of existing techniques at 10~100 K. A large number of semimetals and narrow-gap semiconductors making poor longitudinal thermoelectrics due to severe bipolar effect are thus revived to fill the conspicuous gap of thermoelectric materials for solid-state applications.
Structural basis of substrate recognition and translocation by human ABCA4
Authors: Xie Tian , Zhang Zike , Fang Qi , Du Bowen , Gong Xin 
Published: June 2021

AbstractHuman ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3–3.4 Å. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common ‘lateral access and extrusion’ mechanism for ABCA-mediated lipid transport.
UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair
Authors: Ngo Greg H. P. , Grimstead Julia W. , Baird Duncan M. 
Published: June 2021

AbstractDNA-RNA hybrid structures have been detected at the vicinity of DNA double-strand breaks (DSBs) occurring within transcriptional active regions of the genome. The induction of DNA-RNA hybrids strongly affects the repair of these DSBs, but the nature of these structures and how they are formed remain poorly understood. Here we provide evidence that R loops, three-stranded structures containing DNA-RNA hybrids and the displaced single-stranded DNA (ssDNA) can form at sub-telomeric DSBs. These R loops are generated independently of DNA resection but are induced alongside two-stranded DNA-RNA hybrids that form on ssDNA generated by DNA resection. We further identified UPF1, an RNA/DNA helicase, as a crucial factor that drives the formation of these R loops and DNA-RNA hybrids to stimulate DNA resection, homologous recombination, microhomology-mediated end joining and DNA damage checkpoint activation. Our data show that R loops and DNA-RNA hybrids are actively generated at DSBs to facilitate DNA repair.