bluuebunny/crossref_metadata_2025 huggingface dataset:
Domino Reaction for Synthesis of Spiro[pyrazole‐4,5′‐pyrrolo[3,4‐c]carbazoles] and Spiro[pyrrolo[3,4‐c]carbazole‐5,5′‐thiazoles]
Authors: Yan Chen , Sun Jing , Han Ying , Yan Chao‐Guo
Published: August 2021

The concentrated hydrochloride catalyzed reaction of 3‐(indol‐3‐yl)maleimides with (E)‐4‐arylidene‐5‐methyl‐2‐phenylpyrazol‐3‐ones in acetonitrile at room temperature afforded unexpected Michael addition product in high yields, which could be easily converted to the cis/trans‐diastereoisomers of spiro[pyrazole‐4,5′‐pyrrolo[3,4‐c]carbazoles] with the nearly 2 : 1 ratios by further oxidation with DDQ. On the other hand, the similar one‐pot two‐step reaction of 3‐(indol‐3‐yl)maleimides with (E)‐5‐arylidene‐2‐phenylthiazol‐4‐one predominately gave cis‐diastereoisomers of spiro[pyrrolo[3,4‐c]carbazole‐5,5′‐thiazoles] in satisfactory yields. The reaction mechanism included domino acid catalyzed Michael addition and DDQ oxidative coupling process
Cognitive impairment associated with greater care intensity during home health care
Authors: Burgdorf Julia G. , Amjad Halima , Bowles Kathryn H.
Published: August 2021

Background

In Medicare‐funded home health care (HHC), one in three patients has cognitive impairment (CI), but little is known about the care intensity they receive in this setting. Recent HHC reimbursement changes fail to adjust for patient CI, potentially creating a financial disincentive to caring for these individuals.

Methods

This cohort study included a nationally representative sample of 1214 Medicare HHC patients between 2011 and 2016. Multivariable logistic and negative binomial regressions modelled the relationship between patient CI and care intensity—measured as the number and type of visits received during HHC and likelihood of receiving multiple successive HHC episodes.

Results

Patients with CI had 45% (P < .05) greater odds of receiving multiple successive HHC episodes and received an additional 2.82 total (P < .001), 1.39 nursing (P = .003), 0.72 physical therapy (P = .03), and 0.60 occupational therapy visits (P = .01) during the index HHC episode.

Discussion

Recent HHC reimbursement changes do not reflect the more intensive care needs of patients with CI.
An Azido‐Bridged Dysprosium Chain Complex Showing Zero‐field Slow Magnetic Relaxation
Authors: Shao Dong , Yang Jiong , Yang Xiaodong , Tian Zhengfang
Published: August 2021

A one‐dimensional (1D) azido‐bridged dysprosium coordination polymer featuring a zig‐zag chain structure constructed from a halogen‐functionalized quinoline derivative and N3− ligands was structurally and magnetically characterized. Magnetic studies revealed that the chain complex exhibits zero‐field slow magnetic relaxation and a significant butterfly‐like hysteresis loop, originating from highly magnetic anisotropy of the Dy3+ ions in a D4d symmetry. This compound represents the first azido‐bridged lanthanide chain showing zero‐field slow magnetic relaxation behavior. These results highlight that the combination of high symmetric Ln3+ ions with the versatile azido bridging ligand provides an effective approach for the design and construction of advanced lanthanides molecular magnets.
“Minimal metabolism”: A key concept to investigate the origins and nature of biological systems
Authors: Lauber Nino , Flamm Christoph , Ruiz‐Mirazo Kepa
Published: August 2021

The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of “minimal metabolism”, in contrast to previous, top‐down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided. Also see the video abstract here:https://youtu.be/DP7VMKk2qpA
Adaptive neuro fuzzy evaluation of energy and non‐energy material productivity impact on sustainable development based on circular economy and gross domestic product
Authors: Petković Biljana , Zandi Yousef , Agdas Alireza Sadighi , Nikolić Ivica , Denić Nebojša , Kojić Nenad , Selmi Abdellatif , Issakhov Alibek , Milošević Slaviša , Khan Afrasyab
Published: August 2021

Circular economy represents a concept for turning of material and energy wastes into resources for other purposes in a closed loop system. The purpose of circular economy is to minimize the energy and material wastes. The effect of energy and non‐energy material productivity on the gross domestic product (GDP) was analyzed in this study. The main contribution of the investigation was to determine which sector of energy or non‐energy material productivity has the more relevance on the GDP. Energy productivity represent energy consumption sector while non‐energy material productivity represents the sector closely connected to the circular economy. The used database covers OECD members in period 1990–2020. According to the results one can determine the current status of the economic development and what needs to be improved to reduce the energy and material wastes. On the contrary GDP needs to be tracked in order determine which factor has the more influence on the GDP. For such a purpose adaptive neuro fuzzy inference system (ANFIS) was used. The metals consumption represents the most relevant factor for GDP variation and prediction. The results show also the combination of non‐energy material productivity and generated municipal waste is the best‐case scenario for the GDP prediction. The obtained results could represent the best practices for implementation of circular economy concept.
A Cyanide‐free Biocatalytic Process for Synthesis of Complementary Enantiomers of 4‐Chloro‐3‐hydroxybutanenitrile From Allyl Chloride
Authors: Zheng Daijun , Asano Yasuhisa
Published: August 2021

A biocatalyst used for selective ring scission of (±)‐5‐(chloromethyl)‐4, 5‐dihydroisoxazole to synthesize chiral (R)‐4‐chloro‐3‐hydroxybutanenitrile (90 % ee, 39 % isolated yield) and (S)‐5‐(chloromethyl)‐4, 5‐dihydroisoxazole (99 % ee, 39 % isolated yield) was developed by site‐saturated mutagenesis on aldoxime dehydratase derived from Pseudomonas chlororaphis B23 (OxdA). The positive mutant (OxdA‐L318I, E=68) improved the enantiomeric ratio E by 6‐fold as compared to the wild type enzyme (OxdA‐wild, E=11). The racemic precursor of (±)‐5‐(chloromethyl)‐4, 5‐dihydroisoxazole, used in the reaction, can be synthesized from readily available allyl chloride without utilizing highly toxic cyanide. The enantiopure (S)‐5‐(chloromethyl)‐4, 5‐dihydroisoxazole remaining in the kinetic resolution can be transformed into corresponding chiral (S)‐4‐chloro‐3‐hydroxybutanenitrile without loss of enantiomeric excess by treating it with triethylamine in acetonitrile (99 % ee, 72 % isolated yield) or catalysis of OxdA‐wild enzyme (99 % ee, 88 % isolated yield).
The Influence of the Oxygen Reduction Reaction (ORR) on Pt Oxide Electrochemistry
Authors: Rodríguez Oliver , Denuault Guy
Published: August 2021

In this study, we employed microelectrodes and scanning electrochemical microscopy (SECM) to investigate the role of molecular oxygen and local pH changes on the electrochemistry of Pt oxide. We show that in acidic media and alkaline conditions, the impact of O2 is negligible, while in unbuffered neutral media, O2 strongly affects the formation of Pt oxides. Experiments carried under hindered diffusion reveal that this is due to a high local pH arising from the oxygen reduction reaction. This is evidenced by the appearance, at very positive potentials, of a diffusion controlled wave consistent with the oxidation of OH−. The ORR produces a sufficiently alkaline environment near the electrode to promote the formation of oxide at much more negative potentials than anticipated from the bulk pH. As a result, the onset of oxide formation overlaps the onset of oxygen reduction and it is impossible to obtain a Pt surface free from oxide at potentials positive of the onset of the ORR. Thus, prior exposure of the Pt surface to dissolved oxygen does not leave irreversibly adsorbed oxygen species as previously reported by our group; instead, the ORR induces a coverage of oxide at much lower potentials than determined by the bulk pH.
Rational Design of a Confacial Pentaoctahedron: Anisotropic Exchange in a Linear ZnIIFeIIIFeIIIFeIIIZnII Complex
Authors: Walleck Stephan , Atanasov Mihail , Schnack Jürgen , Bill Eckhard , Stammler Anja , Bögge Hartmut , Glaser Thorsten
Published: August 2021

The first confacial pentaoctahedron comprised of transition metal ions namely ZnIIFeIIIAFeIIIBFeIIIAZnII has been synthesized by using a dinucleating nonadentate ligand. The face‐sharing bridging mode enforces short ZnII⋅⋅⋅FeIIIA and FeIIIA⋅⋅⋅FeIIIB distances of 2.83 and 2.72 Å, respectively. Ab‐initio CASSCF/NEVPT2 calculations provide significant negative zero‐field splittings for FeIIIA and FeIIIB with |DA|>|DB| with the main component along the C3 axis. Hence, a spin‐Hamiltonian comprised of anisotropic exchange, zero‐field, and Zeeman term was employed. This allowed by following the boundary conditions from the theoretical results the simulation in a theory‐guided parameter determination with Jxy=+0.37, Jz=−0.32, DA=−1.21, EA=−0.24, DB=−0.35, and EB=−0.01 cm−1 supported by simulations of high‐field magnetic Mössbauer spectra recorded at 2 K. The weak but ferromagnetic FeIIIAFeIIIB interaction arises from the small bridging angle of 84.8° being at the switch from anti‐ to ferromagnetic for the face‐sharing bridging mode.
A Novel Strategy to Design and Construct AIE‐active Mechanofluorochromic Materials via Regulation of Molecular Structure
Authors: Zheng Kaibo , Chen Hui , Xiao Yufeng , Liu Xiang , Yan Jiaying , Zhang Nuonuo
Published: August 2021

In this work, we first designed and synthesized tetraphenylene‐fused aryl‐imidazole derivatives TM‐1–4 via regulation of molecular structure, which were consisted of 1H‐imidazo[4,5‐f][1,10]phenanthroline, 1H‐phenanthro[9,10‐d]imidazole, 4,5‐diphenyl‐1H‐imidazole, 3,3′‐(1H‐imidazole‐4,5‐diyl)dipyridine moieties and AIE‐active tetraphenylethene units, respectively. The results illustrated that TM‐1–4 exhibited clear AIE characteristics. Meanwhile, TM‐2 and TM‐3 show excellent solid emission properties (ΦTM‐2=13.73 % and ΦTM‐3=36.21 %), whereas TM‐1 and TM‐4 exhibit the opposite properties (ΦTM‐1=1.48 % and ΦTM‐4=4.83 %). The multiple rotors (pyridine and benzene ring) causes twisted conformations of the molecule that prevents π‐π stacking and enhances solid emission(ΦTM‐2<ΦTM‐3, ΦTM‐1<ΦTM‐4). Significantly, TM‐2 and TM‐3 also exhibited reversible mechanochromic behavior (Emission red shifts: ΔλTM‐2=43 nm and ΔλTM‐3=41 nm) with color changes between blue and green emissions. The powder X‐ray diffraction (PXRD) suggested the disordered state of ground sample could be readily returned to an ordered crystalline. Therefore, the mechanochromisms of TM‐2 and TM‐3 are ascribable to the phase transformation between crystal and amorphous structure. The single crystal X‐ray analysis of TM‐2 reveals a twisted conformation for TPE moiety and the absence of π‐π intermolecular stacking. These excellent optical properties of TM‐2 and TM‐3 make them potentially applications in mechanochromic materials and imaging agents.
Ethical leadership and environment specific discretionary behaviour: The mediating role of green human resource management and moderating role of individual green values
Authors: Islam Talat , Hussain Dildar , Ahmed Ishfaq , Sadiq Misbah
Published: August 2021

This study examines the mediating role of green human resource management between ethical leadership and employees' citizenship behavior towards the environment with the moderating effect of individual green values. We collected data from 589 MBA executive students with one‐year of experience working in various organizations at two different times using a questionnaire‐based survey method. Applying structural equation modeling to the results confirmed a direct effect of ethical leadership on employees' citizenship behavior towards the environment and an indirect effect through green human resource management. Further, individual green value strengthened the association between green human resource management and employees' environmentally conscious citizenship behavior. Our study contributes to social learning and supply value‐fit theory and has implications for management.
Magnetic resonance imaging–based risk calculators optimize selection for prostate biopsy among biopsy‐naive men
Authors: Fang Andrew M. , Rais‐Bahrami Soroush
Published: August 2021

Risk calculators have been created on the basis of predictive modeling to aid clinicians and patients in deciding whether to pursue prostate biopsy. Ideally, these risk calculators would reduce the diagnosis of low‐risk prostate cancer and increase the diagnosis of clinically significant prostate cancer. However, before these prediction models are to be available for widespread use, they must be carefully validated, discriminated, and calibrated to ensure their performance and applicability.
Combining abilities and elite germplasm enhancement across U.S. public sorghum breeding programs
Authors: Fonseca Jales M. O. , Perumal Ramasamy , Klein Patricia E. , Klein Robert R. , Rooney William L.
Published: August 2021

For mature breeding programs, maintaining genetic variation in elite germplasm requires a continual assessment of the most efficient methods to maximize functional genetic variation while improving productivity. This research assessed the relative value (defined as population means and variances) derived from elite germplasm exchange between distinct public breeding programs. Ten elite A‐ and R‐lines from Texas A&M and Kansas State sorghum (Sorghum bicolor L. Moench) breeding programs were crossed in a factorial design to generate 100 hybrids. Hybrid combinations were grouped to represent hybrids within and across programs. Grain yield, plant height, and days to anthesis were measured in 10 environments over 2 yr. Combining abilities and their interactions with the environment were assessed. Combined analysis detected significant effects for all traits, but genetic effects for grain yield were not consistently significant within each group of hybrid combinations. Hybrids derived from only Texas inbreds had limited genetic variation for grain yield but the highest mean of all four groups; hybrids derived from only Kansas inbreds produced moderate genetic variation but lower grain yield potential. Maximum genetic variation for grain yield and plant height occurred when Kansas A‐lines were crossed to Texas R‐lines, whereas hybrids between Texas A‐lines and Kansas R‐lines maximized variation for days to antheses. Results demonstrated the potential benefit from crossing elite inbred parents derived from distinct breeding programs to increase genetic variation and enhance agronomic performance.
Organizations' engagement with sustainable development goals: Fromcherry‐pickingto SDG‐washing?
Authors: Heras‐Saizarbitoria Iñaki , Urbieta Laida , Boiral Olivier
Published: August 2021

This article analyzes the organizational engagement with the United Nations sustainable development goals (SDGs), an initiative for corporate social responsibility also referred to as the 2030 Agenda. Engagement with the SDGs by organizations all around the world, whatever their sector and size, has attracted a lot of media interest and heightened expectations. Nevertheless, there is a lack of empirical work that sheds light on the commitment to this initiative at the organizational level. In order to fill this gap, this article examines the characteristics of engagement with the SDGs of 1370 organizations from 97 countries, taking data from their sustainability reports. The study looks at how and why organizations engage with the SDGs, as well as the priority they assign to them. The findings point to a superficial engagement with the SDGs for the vast majority of organizations, which suggests a process of “SDG‐washing”. Implications for managers, public policy makers and other stakeholders are analyzed.
Head injury is associated with tau deposition on PET in MCI and AD patients
Authors: Risacher Shannon L. , West John D. , Deardorff Rachael , Gao Sujuan , Farlow Martin R. , Brosch Jared R. , Apostolova Liana G. , McAllister Thomas W. , Wu Yu‐Chien , Jagust William J. , Landau Susan M. , Weiner Michael W. , Saykin Andrew J. ,   for the Alzheimer's Disease Neuroimaging Initiative#
Published: August 2021

Introduction

Head injuries (HI) are a risk factor for dementia, but the underlying etiology is not fully known. Understanding whether tau might mediate this relationship is important.

Methods

Cognition and tau deposition were compared between 752 individuals with (impaired, n = 302) or without cognitive impairment (CN, n = 450) with amyloid and [18F]flortaucipir positron emission tomography, HI history information, and cognitive testing from the Alzheimer's Disease Neuroimaging Initiative and the Indiana Memory and Aging Study.

Results

Sixty‐three (38 CN, 25 impaired) reported a history of HI. Higher neuropsychiatric scores and poorer memory were observed in those with a history of HI. Tau was higher in individuals with a history of HI, especially those who experienced a loss of consciousness (LOC). Results were driven by impaired individuals, especially amyloid beta‐positive individuals with history of HI with LOC.

Discussion

These findings suggest biological changes, such as greater tau, are associated with HI in individuals with cognitive impairment. Small effect sizes were observed; thus, further studies should replicate and extend these results.
Per‐oral endoscopic myotomy as treatment for Killian–Jamieson diverticulum
Authors: Shimamura Yuto , Fujiyoshi Mary Raina Angeli , Fujiyoshi Yusuke , Nishikawa Yohei , Ono Masashi , Owada Kaori , Ikeda Haruo , Onimaru Manabu , Inoue Haruhiro
Published: August 2021

Killian–Jamieson diverticulum (KJD) is a rare type of esophageal diverticulum less commonly encountered compared with Zenker's diverticulum (ZD). Endoscopic approach for these diverticula has been rapidly evolving. Currently, a flexible endoscopic septum division is considered the first‐line treatment for symptomatic ZD patients, however reported recurrence rates are over 10% according to recent literature. With the advent of submucosal tunneling technique established by per‐oral endoscopic myotomy for achalasia, it has been applied to treat ZD named as Zenker's diverticulum per‐oral endoscopic myotomy (Z‐POEM) as a minimally invasive treatment. Although there are very few reports utilizing submucosal tunneling approach to KJD, we have opted to perform Z‐POEM in order to safely perform complete dissection of the muscle septum while maintaining mucosal integration. Due to the difficulty of anatomical location of KJD, we created mucosal incision and subsequent submucosal tunnel directly at the level of the septum as opposed to creating a submucosal tunnel few centimeters proximal to the septum as being previously proposed. We report a case in which this technique was successfully performed with complete resolution of dysphagia without any adverse event. This technique permits to perform complete myotomies without the fear of causing perforation. Although larger cohorts are required to assess its safety and efficacy, Z‐POEM to treat KJD seems to be promising.
Beyond the single index: Investigating ecological mechanisms underpinning ecosystem multifunctionality with network analysis
Authors: Siwicka Ewa , Gladstone‐Gallagher Rebecca , Hewitt Judi E. , Thrush Simon F.
Published: August 2021

Ecosystems simultaneously deliver multiple functions that relate to both the activities of resident species and environmental conditions. One of the biggest challenges in multifunctionality assessment is balancing analytical simplicity with ecosystem complexity. As an alternative to index‐based approaches, we introduce a multivariate network analysis that uses network theory to assess multifunctionality in terms of the relationships between species' functional traits, environmental characteristics, and functions. We tested our approach in a complex and heterogeneous ecosystem, marine intertidal sandflats. We considered eight ecosystem function, five macrofaunal functional trait groups derived from 36 species, and four environmental characteristics. The indicators of ecosystem functions included the standing stock of primary producers, oxygen production, benthic oxygen consumption, DIN (ammonium and NOx efflux) and phosphate release from the sediments, denitrification, and organic matter degradation at the sediment surface. Trait clusters included functional groups of species that shared combinations of biological traits that affect ecosystem function: small mobile top 2 cm dwellers, suspension feeders, deep‐dwelling worms, hard‐bodied surface dwellers, and tube‐forming worms. Environmental characteristics included sediment organic matter, %mud, %shell hash, and %sediment water content. Our results visualize and quantify how multiple ecosystem elements are connected and contribute to the provision of functions. Small mobile top 2 cm dwellers (among trait clusters) and %mud (among environmental characteristics) were the best predictor for multiple functions. Detailed knowledge of multifunctionality relationships can significantly increase our understanding of the real‐world complexity of natural ecosystems. Multivariate network analysis, as a standalone method or applied alongside already existing single index multifunctionality methods, provides means to advance our understanding of how environmental change and biodiversity loss can influence ecosystem performance across multiple dimensions of functionality. Embedding such a detailed yet holistic multifunctionality assessment in environmental decision‐making will support the assessment of multiple ecosystem services and social‐ecological values.
Temperature affects the repeatability of evolution in the microbial eukaryote Tetrahymena thermophila
Authors: Tarkington Jason , Zufall Rebecca A.
Published: August 2021

Evolutionary biologists have long sought to understand what factors affect the repeatability of adaptive outcomes. To better understand the role of temperature in determining the repeatability of adaptive trajectories, we evolved populations of different genotypes of the ciliate Tetrahymena thermophila at low and high temperatures and followed changes in growth rate over 6,500 generations. As expected, growth rate increased with a decelerating rate for all populations; however, there were differences in the patterns of evolution at the two temperatures. The growth rates of the different genotypes tended to converge as evolution proceeded at both temperatures, but this convergence was quicker and more pronounced at the higher temperature. Additionally, over the first 4,000 generations we found greater repeatability of evolution, in terms of change in growth rate, among replicates of the same genotype at the higher temperature. Finally, we found limited evidence of trade‐offs in fitness between temperatures, and an asymmetry in the correlated responses, whereby evolution in a high temperature increases growth rate at the lower temperature significantly more than the reverse. These results demonstrate the importance of temperature in determining the repeatability of evolutionary trajectories for the eukaryotic microbe Tetrahymena thermophila and may provide clues to how temperature affects evolution more generally.
Inhibition of aluminum‐silicon alloy dust explosion and flame byKH2PO4/montmorillonite composite powder
Authors: Xiao Qin , Meng Xiangbao , Li Zhiyong , Ma Xuesong , Yan Ke , Wang Zheng
Published: August 2021

To obtain a good explosive suppressant, KH2PO4/montmorillonite composite powder was prepared by the solvent‐antisolvent method by using montmorillonite as the carrier and KH2PO4as the supported particles. Flame propagation inhibition and explosion inhibition of aluminum‐silicon alloy dust by the KH2PO4/montmorillonite composite powder were investigated in a vertical quartz glass combustion tube and 20‐L spherical explosive tank, respectively. The results showed that the flame propagation of aluminum‐silicon alloy dust was basically suppressed as the inerting ratio of KH2PO4/montmorillonite composite powder was 1.2, and the explosion of aluminum‐silicon alloy dust was basically inhibited as the inerting ratio of KH2PO4/montmorillonite composite powder was 1.8. The flame and explosion inhibition mechanism of KH2PO4/montmorillonite composite powder on aluminum‐silicon alloy dust was further analyzed in this paper.
Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I
Authors: Riva Matteo , Martorana Davide , Uliana Vera , Caleffi Edoardo , Boschi Elena , Garavelli Livia , Ponti Giovanni , Sangiorgi Luca , Graziano Claudio , Bigoni Stefania , Rocchetti Luca Maria , Madeo Simona , Soli Fiorenza , Grosso Enrico , Carli Diana , Goldoni Matteo , Pisani Francesco , Percesepe Antonio
Published: August 2021

Neurofibromatosis type I, a genetic condition due to pathogenic variants in the NF1 gene, is burdened by a high rate of complications, including neoplasms, which increase morbidity and mortality for the disease. We retrospectively re‐evaluated the NF1 gene variants found in the period 2000–2019 and we studied for genotype/phenotype correlations of disease complications and neoplasms 34 variants, which were shared by at least two unrelated families (range 2–11) for a total 141 of probands and 21 relatives affected by Neurofibromatosis type I. Recurrent variants could be ascribed to the most common mutational mechanisms (C to T transition, microsatellite slippage, non‐homologous recombination). In genotype/phenotype correlations, the variants p.Arg440*, p.Tyr489Cys, and p.Arg1947*, together with the gross gene deletions, displayed the highest rates of complications. When considering neoplasms, carriers of variants falling in the extradomain region at the 5′ end of NF1 had a lower age‐related cancer frequency than the rest of the gene sequence, showing a borderline significance (p = 0.045), which was not conserved after correction with covariates. We conclude that (1) hotspots in NF1 occur via different mutational mechanisms, (2) several variants are associated with high rates of complications and cancers, and (3) there is an initial evidence toward a lower cancer risk for carriers of variants in the 5′ end of the NF1 gene although not significant at the multivariate analysis.
Thermotectonic constraints on the geodynamic evolution of the Pindos fold‐and‐thrust‐belt by low‐temperature (U–Th)/He thermochronometry
Authors: Athanassas Constantin D. , Papanikolaou Dimitrios I. , Falkowski Sarah , Papanikolaou Ioannis D. , Ntokos Dimitrios
Published: August 2021

This study presents new thermochronometric data to constrain the cooling history of the Pindos fold‐and‐thrust‐belt (PFTB) on the NW Peloponnese, and the timing of nappe stacking in the external Hellenides in western Greece. Low‐temperature thermochronology was performed on apatite and zircon minerals extracted from basal exposures of the PFBT in Mt. Erymanthos (NW Peloponnese) using the (U‐Th)/He system. Three bedrock samples collected from a profile across the strike of the PFBT returned thermochronometric ages for the apatite (AHe) between 15 and 9 Ma, while for the zircon (ZHe) the ages are interpreted as unreset (or partially reset). The AHe ages are interpreted as cooling ages related to the Cenozoic geodynamic evolution of the PFTB. Thermal models generated in this research demonstrate two phases of geodynamic evolution of the PFBT during the Cenozoic: an early one associated with the heating of the fold‐and‐thrust belt during 40–20 Ma and a later one associated with fast cooling from 20 Ma onwards. Heating is attributed to the structural thickening of the PFTB while cooling is associated with enhanced uplift and exhumation, which became widespread in Erymanthos by 9 Ma. The initiation of cooling on Mt. Erymanthos echoes the substantial geometric remodelling that underwent the Hellenic arc during the Middle Miocene, associated with slab rollback and arc extension, and is connected to the underplating of the internal segments of the external platform (Gavrovo‐Tripolis unit) by the external metamorphic segments (Mani and Arna units). The current inverse thermal modelling offers the first continuous description of the geodynamic evolution of the most prominent fold‐and‐thrust belt of the Hellenides, from the oceanic stage through basin inversion to uplift and orogen decay.
Noninvasive magnetic resonance imaging techniques in mild traumatic brain injury research and diagnosis
Authors: Lunkova Ekaterina , Guberman Guido I. , Ptito Alain , Saluja Rajeet Singh
Published: August 2021

Mild traumatic brain injury (mTBI), frequently referred to as concussion, is one of the most common neurological disorders. The underlying neural mechanisms of functional disturbances in the brains of concussed individuals remain elusive. Novel forms of brain imaging have been developed to assess patients postconcussion, including functional magnetic resonance imaging (fMRI), susceptibility‐weighted imaging (SWI), diffusion MRI (dMRI), and perfusion MRI [arterial spin labeling (ASL)], but results have been mixed with a more common utilization in the research environment and a slower integration into the clinical setting. In this review, the benefits and drawbacks of the methods are described: fMRI is an effective method in the diagnosis of concussion but it is expensive and time‐consuming making it difficult for regular use in everyday practice; SWI allows detection of microhemorrhages in acute and chronic phases of concussion; dMRI is primarily used for the detection of white matter abnormalities, especially axonal injury, specific for mTBI; and ASL is an alternative to the BOLD method with its ability to track cerebral blood flow alterations. Thus, the absence of a universal diagnostic neuroimaging method suggests a need for the adoption of a multimodal approach to the neuroimaging of mTBI. Taken together, these methods, with their underlying functional and structural features, can contribute from different angles to a deeper understanding of mTBI mechanisms such that a comprehensive diagnosis of mTBI becomes feasible for the clinician.
Modeling the Covid‐19 epidemic using time series econometrics
Authors: Goliński Adam , Spencer Peter
Published: August 2021

The classic “logistic” model has provided a realistic model of the behaviour of Covid‐19 in China and many East Asian countries. Once these countries passed the peak, the daily case count fell back, mirroring its initial climb in a symmetric way, just as the classic model predicts. However, in Italy and Spain and most other Western countries, the first wave of the epidemic was very different. The daily count fell back gradually from the peak but remained stubbornly high. The reason for the divergence from the classical model remain unclear. We take an empirical stance on this issue and develop a model framework based upon the statistical characteristics of the time series. With the possible exception of China, the workhorse logistic model is decisively rejected against more flexible alternatives.
Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
Authors: Iwamoto Junichi , Honda Akira , Miyazaki Teruo , Monma Tadakuni , Ueda Hajime , Morishita Yukio , Yara Sho‐ichiro , Hirayama Takeshi , Ikegami Tadashi
Published: August 2021

Western‐style high‐fat/high‐sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD‐induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild‐type (WT) and human‐like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography–tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD‐induced change of gut microbiota inhibited BA deconjugation and 7α‐dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human‐like hydrophobic BA composition.
Cognitive Impairment and Physical Frailty in Patients With Cirrhosis
Authors: Berry Kacey , Duarte‐Rojo Andres , Grab Joshua D. , Dunn Michael A. , Boyarsky Brian J. , Verna Elizabeth C. , Kappus Matthew R. , Volk Michael L. , McAdams‐DeMarco Mara , Segev Dorry L. , Ganger Daniel R. , Ladner Daniela P. , Shui Amy , Tincopa Monica A. , Rahimi Robert S. , Lai Jennifer C. ,   from the Multi‐Center Functional Assessment in Liver Transplantation (FrAILT) Study
Published: August 2021

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance‐based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; “frail,” LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous “impaired cognition” was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, “impaired cognition” was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait‐list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10‐second NCT increase associated with a 0.08‐LFI increase (95% confidence interval [CI], 0.07‐0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43‐1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04‐1.10) associated with wait‐list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait‐list mortality (sHR, 1.55; 95% CI, 1.33‐1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%‐16.4%) of the total effect of frailty on 1‐year wait‐list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait‐list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.
Globo H Is a Promising Theranostic Marker for Intrahepatic Cholangiocarcinoma
Authors: Hung Tsai‐Hsien , Hung Jung‐Tung , Wu Chiao‐En , Huang Yenlin , Lee Chien‐Wei , Yeh Chau‐Ting , Chung Yi‐Hsiu , Lo Fei‐Yun , Lai Li‐Chun , Tung John K. , Yu John , Yeh Chun‐Nan , Yu Alice L.
Published: August 2021

Recent studies support the development of cancer therapeutics to target Globo H‐ceramide, the most prevalent tumor‐associated carbohydrate antigen in epithelial cancers. Herein, we evaluated the expression of Globo H and its prognostic significance in intrahepatic cholangiocarcinoma (ICC) and conducted preclinical studies to assess the antitumor activity of Globo H–specific antibody in thioacetamide (TAA)–induced ICC in rats. Globo H–ceramide in tumor specimens was detected by immunohistochemistry (IHC) and mass spectrometry. Antitumor efficacy of anti–Globo H mAbVK9 was evaluated in TAA‐induced ICC in rat. Natural killer (NK) cells and their related genes were analyzed by IHC and quantitative real‐time polymerase chain reaction. Data mining revealed that B3GALT5 and FUT2, the key enzymes for Globo H biosynthesis, were significantly up‐regulated in human ICC. In addition, Globo H expression was detected in 41% (63 of 155) of ICC tumor specimens by IHC staining, and validated by mass spectrometric analysis of two IHC‐positive tumors. Patients with Globo H positive tumors had significantly shorter relapse‐free survival (RFS) and overall survival (P = 0.0003 and P = 0.002, respectively). Multivariable Cox regression analysis identified Globo H expression as an independent unfavorable predictor for RFS (hazard ratio: 1.66, 95% confidence interval: 1.08‐2.36, P = 0.02) in ICC. Furthermore, gradual emergence of Globo H in liver tissues over 6 months in TAA‐treated rats recapitulated the multistage progression of ICC in vivo. Importantly, administration of anti‐Globo H mAbVK9 in rats bearing TAA‐induced ICC significantly suppressed tumor growth with increased NK cells in the tumor microenvironment. Conclusion: Globo H is a theranostic marker in ICC.
Role of Cholesterol‐Associated Steatohepatitis in the Development of NASH
Authors: Horn Christian L. , Morales. Amilcar L. , Savard Christopher , Farrell Geoffrey C , Ioannou George N.
Published: August 2021

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD‐related cirrhosis in the United States and globally highlights the need to better understand the mechanisms causing progression of hepatic steatosis to fibrosing steatohepatitis and cirrhosis in a small proportion of patients with NAFLD. Accumulating evidence suggests that lipotoxicity mediated by hepatic free cholesterol (FC) overload is a mechanistic driver for necroinflammation and fibrosis, characteristic of nonalcoholic steatohepatitis (NASH), in many animal models and also in some patients with NASH. Diet, lifestyle, obesity, key genetic polymorphisms, and hyperinsulinemia secondary to insulin resistance are pivotal drivers leading to aberrant cholesterol signaling, which leads to accumulation of FC within hepatocytes. FC overload in hepatocytes can lead to ER stress, mitochondrial dysfunction, development of toxic oxysterols, and cholesterol crystallization in lipid droplets, which in turn lead to hepatocyte apoptosis, necrosis, or pyroptosis. Activation of Kupffer cells and hepatic stellate cells by hepatocyte signaling and cholesterol loading contributes to this inflammation and leads to hepatic fibrosis. Cholesterol accumulation in hepatocytes can be readily prevented or reversed by statins. Observational studies suggest that use of statins in NASH not only decreases the substantially increased cardiovascular risk, but may ameliorate liver pathology. Conclusion: Hepatic FC loading may result in cholesterol‐associated steatohepatitis and play an important role in the development and progression of NASH. Statins appear to provide significant benefit in preventing progression to NASH and NASH‐cirrhosis. Randomized controlled trials are needed to demonstrate whether statins or statin/ezetimibe combination can effectively reverse steatohepatitis and liver fibrosis in patients with NASH.
Identification and functional analysis of the mitochondrial cysteine synthase TtCsa2 from Tetrahymena thermophila
Authors: Lv Hongrui , Hu Lina , Xu Jing , Bo Tao , Wang Wei
Published: August 2021

Cysteine is a crucial component for all organisms and plays a critical role in the structure, stability, and catalytic functions of many proteins. Tetrahymena has reverse transsulfuration and de novo pathways for cysteine biosynthesis. Cysteine synthase is involved in the de novo cysteine biosynthesis and catalyzes the production of cysteine from O‐acetylserine. The novel cysteine synthase TtCSA2 was identified from Tetrahymena thermophila. The TtCSA2 showed high expression levels at the log‐phase and the sexual development stage. The TtCsa2 was localized on the outer mitochondrial membrane throughout different developmental stages. However, the truncated N‐terminal signal peptide mutant TtCsa2‐ΔN23 was localized into the mitochondria. His‐TtCsa2 was expressed in Escherichia coli and purified using affinity chromatography. The His‐TtCsa2 showed O‐acetylserine sulfhydrylase and serine sulfhydrylase activities. Cysteine and glutathione contents decreased in the csa2KD mutant. Furthermore, mutant cells were sensitive to cadmium and copper stresses. This study indicated that the TtCSA2 was involved in the cysteine synthesis in mitochondria and related to heavy metal stresses resistance in Tetrahymena.
Evaluation of point‐of‐care testing device for anemia detection: A cross‐sectional method comparison study from Thailand
Authors: Chantkran Wittawat , Jamnarnwej Pitipat , Sritanabutr Pipat , Arnutti Pasra
Published: August 2021

Background

A comparison study is crucial before launching a new medical device; therefore, we compared the Mission Ultra Hb Testing System with the Sysmex XN‐3000 automated hematology analyzer in Thai adult males and non‐pregnant adult females.

Methods

Parallel studies were conducted using discarded venous K2‐ethylenediaminetetraacetic acid samples from participants requiring hematological investigations. According to the World Health Organization criteria, the participants were categorized as overall, anemia, and non‐anemia for analysis.

Results

Three hundred participants were included in this study. In all participants, near‐perfect correlation and agreement were observed between the two methods for Hb measurement (r = 0.963, p < 0.001) with an interclass correlation coefficient (ICC) of 0.981 (95% confidence interval [CI]: 0.976–0.985) and Hct measurement (r = 0.941, p < 0.001) with an ICC of 0.965 (95% CI: 0.956–0.972). The sensitivity and specificity of the device in detecting anemia were 86.2% (95% CI: 79.7–91.2) and 98.6% (95% CI: 95.2–99.8), respectively. The area under the curve was 0.976 (95% CI: 0.963–0.989). The device showed average biases of 0.76 g/dl (95% limits of agreement [LOA]: −1.03 to 2.54) for Hb measurement and −2.73% (95% LOA: −9.28 to 3.82) for Hct measurement in all participants.

Conclusion

Agreement between the Mission Ultra Hb Testing System and Sysmex XN‐3000 was observed. The device was excellent for detecting anemia. However, the essential evidence showing biases of the Hb and Hct measurements obtained from the device was revealed. Laboratory interpretation should be carefully performed, particularly at the near cut‐off values.
Preventing Indigenous youth homelessness in Canada: A qualitative study on structural challenges and upstream prevention in education
Authors: Ansloos Jeffrey Paul , Wager Amanda Claudia , Dunn Nicole Santos
Published: August 2021

Drawing on a partnership with a group of Indigenous youth experiencing homelessness in Vancouver, Canada, this study identifies four structural challenges that have impacted them and four actionable upstream strategies to further prevent youth housing precarity. As a secondary analysis of a community‐engaged study with youth experiencing homelessness, we conducted a thematic analysis with qualitative data, which included qualitative interviews with five young people and researcher observations. The results reflect the racial, colonial, and economic concerns that impact Indigenous youth experiencing homelessness. The four actionable upstream solutions highlight human rights‐based approaches to homelessness, ranging from advancing and strengthening public services, transitional justice processes, and cultural and socioeconomic safety. This study provides strategies to promote Indigenous youth wellbeing and decrease risk of housing precarity, while centering and drawing from youth knowledge production. Strengths and limitations of the study are also discussed.
Opportunities to improve behavioral health crisis response: Results of a large urban county's community status assessment
Authors: Flynn Karen Coen , Riske‐Morris Michelle , Hussey David L.
Published: August 2021

A comprehensive community status assessment of an Ohio urban county's crisis response (CR) system explored the experiences of its behavioral health services' clients and providers to surface themes characterizing the system's responsiveness and identifying opportunities for improvements. Forty‐eight focus groups and two online surveys were conducted. Data were analyzed using qualitative content analysis and descriptive statistics. The greatest areas of needed improvement ascertained by this effort are in increased CR system resources, more efficient use of resources, and capacity enhancements in nine areas: the mobile crisis team, CR protocols, psychiatric inpatient and crisis stabilization beds, stabilization admission for eligible persons, stabilization services for in‐crisis but admission‐ineligible persons, continuity of care, research into child versus adult CR systems, Provider Emergency Support Program, and first responder crisis intervention training. The assessment provides a foundation for the county to identify further opportunities for system scale‐up.