bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrofauna communities across a seascape of seagrass meadows: environmental drivers, biodiversity patterns and conservation implications
Authors: Rodil Iván F. , Lohrer Andrew M. , Attard Karl M. , Hewitt Judi E. , Thrush Simon F. , Norkko Alf
Published: July 2021

Similar to other coastal biogenic habitats (e.g. tidal marshes, kelp forests, mangroves and coral reefs), a key function of seagrass meadows is the enhancement of biodiversity. Variability at multiple spatial scales is a driver of biodiversity, but our understanding of the response of macrofauna communities to variability of seagrass meadows is limited. We examined the macrofauna community structure (abundance and biomass) and diversity patterns (α- and β-diversity) across a seascape gradient of eleven seagrass meadows differing in the number, composition and density of plant species. The variability of the macrobenthic communities was regulated by a combination of sedimentary (mainly for the infauna) and macrophyte (mainly for the epifauna) predictors. We demonstrate that the natural occurrence of drifting algae trapped in the aboveground complexity of the meadows benefits seagrass macrofauna. Seagrass-associated macrofauna showed a clear increase in abundance and α-diversity metrics with increasing habitat complexity attributes (i.e. shoot density, plant biomass and canopy height). Furthermore, partitioning of β-diversity (i.e. the variation of species composition between sites) implied the replacement of some species by others between sites (i.e. spatial turnover) instead of a process of species loss (or gain) from site to site (i.e. nestedness). Therefore, the enhancement of macrofauna diversity across an increasing gradient of seagrass complexity, and the dominance of the turnover component suggest that devoting conservation efforts on many different types of meadows, including the less diverse, should be a priority for coastal habitat-management.
Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank
Authors: Watts Eleanor L. , Perez-Cornago Aurora , Doherty Aiden , Allen Naomi E. , Fensom Georgina K. , Tin Tin Sandar , Key Timothy J. , Travis Ruth C.
Published: July 2021

Purpose

Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods

Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results

The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion

Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.
Effectiveness of Positive Discipline Parenting Program on Parenting Style, and Child Adaptive Behavior
Authors: Carroll Paul
Published: July 2021

In this study, a community sample of parents attending free 7-week Positive Discipline parenting workshops were recruited, as well as a non-randomized community control. Both samples consisted of primarily Hispanic parents with similar demographic information and attrition rates (initial N = 91), as well as children of similar age (mean age 6.89 and 6.95 years) and gender. Parenting stress, parenting style, and parent-reported child adaptive behavior were assessed at baseline and after three months. Longitudinal analysis was performed using mixed-effects regression modeling. Results indicate that attendance in Positive Discipline parenting workshops was related to a decrease in authoritarian parenting style, a decrease in permissive parenting style, and a decrease in parental stress. It was also related to an increase in child academic competence, and a decrease in externalizing-hyperactive behavior (both parent-report). These results suggest that positive discipline parenting workshops may alter parenting style and may positively impact children of parents who attend.
A Meta-Analysis Investigating the Association Between Metacognition and Math Performance in Adolescence
Authors: Muncer Gemma , Higham Philip A. , Gosling Corentin J. , Cortese Samuele , Wood-Downie Henry , Hadwin Julie A.
Published: July 2021

Poor math and numeracy skills are associated with a range of adverse outcomes, including reduced employability and poorer physical and mental health. Research has increasingly focused on understanding factors associated with the improvement of math skills in school. This systematic literature review and meta-analysis investigated the association between metacognition and math performance in adolescence (11–16-year-olds). A systematic search of electronic databases and grey literature (to 04.01.2020) highlighted 31 studies. The quantitative synthesis of 74 effect sizes from 29 of these studies (30 independent populations) indicated a significantly positive correlation between metacognition and math performance in adolescence (r = .37, 95% CI = [.29, .44], p < .001). There was significant heterogeneity between studies. Consideration of online (versus offline) measures of metacognition and more complex (versus simple) measures of math performance, and their combination, was associated with larger effect sizes; however, heterogeneity remained high for all analyses.
A continuum mechanics model for the Fåhræus-Lindqvist effect
Authors: Farina Angiolo , Rosso Fabio , Fasano Antonio
Published: July 2021

The decrease in apparent relative viscosity that occurs when blood is made to flow through a tube whose diameter is less than about 0.3 mm is a well-known and documented phenomenon in physiology, known as the Fåhræus-Lindqvist effect. However, since the historical work of Fåhræus and Lindqvist (Amer. J. Physiol. 96(3): pp. 562–568, 1931), the underlying physical mechanism has remained enigmatic. A widely accepted qualitative explanation was provided by Haynes (Amer. J. Physiol. 198, pp. 1193–1200, 1960) according to which blood flows in microvessels with a core-annulus structure, where the erythrocytes concentrate within a central core surrounded by a plasma layer. Although sustained by observations, this conjecture lacks a rigorous deduction from the basic principles of continuum dynamics. Moreover, relations aimed to reproduce the blood apparent relative viscosity, extensively used in micro-circulation, are all empirical and not derived from the analysis of the fluid mechanical phenomena involved. In this paper, we apply the recent results illustrated in Guadagni and Farina (Int. J. Nonlinear Mech. 126, p. 103587, 2020), with the purpose of showing that Haynes’ conjecture, slightly corrected to make it more realistic, can be proved and can be used to reach a sound explanation of the Fåhræus-Lindqvist effect based on continuum mechanics. We propose a theoretical model for the blood apparent relative viscosity which is validated by matching not only the original experimental data reported by Fåhræus and Lindqvist (Amer. J. Physiol. 96(3), pp. 562–568, 1931), but also those provided by several subsequent authors.
The Opacity of Law: On the Hidden Impact of Experts’ Opinion on Legal Decision-making
Authors: Canale Damiano
Published: July 2021

It is well known that experts’ opinion and testimony take on a decisive weight in judicial fact-finding, raising issues and perplexities that have long been under scholarly scrutiny. In this paper I argue that expert’s opinions have a much wider impact on legal decision-making. In particular, they may generate a problem that I will call ‘the opacity of law’. A legal text, such as a statute or regulation, becomes opaque if a legal authority is not able to grasp its full linguistic content but is nevertheless in a position to use it, thanks to an expert’ opinion, in legal decision-making. When this occurs, not only do experts contribute to fact-finding but also to determining the content of the law. In the paper I analyse the linguistic and cognitive sources of this phenomenon, its characteristics and troublesome consequences, and the different kinds of opacity that may affect legal decision-making.
Concurrent predictors of word reading and reading comprehension for 9-year-olds with Williams syndrome
Authors: Mervis Carolyn B. , Greiner de Magalhães Caroline , Cardoso-Martins Cláudia
Published: July 2021

We examined the cognitive, language, and instructional factors associated with reading ability in Williams syndrome (WS). Seventy 9-year-olds with WS completed standardized measures of real-word reading, pseudoword decoding, reading comprehension, phonological skills, listening comprehension, nonverbal reasoning, visual-spatial ability, verbal working memory, rapid naming, and vocabulary. Reading instruction method was determined from school records and interviews with parents and teachers. Similar to prior findings for individuals with WS, reading ability varied widely, ranging from inability to read any words to reading comprehension at age level. Multiple regression analyses indicated that the primary concurrent predictor of word reading ability was reading instruction method, with a systematic phonics approach associated with considerably better performance than other reading instruction approaches. Phonological processing skills—as assessed by a composite of phonological awareness and verbal short-term memory—also contributed significant unique variance to word reading ability, as did visual-spatial ability. The concurrent predictors of reading comprehension were single-word reading and listening comprehension. These findings indicate that the factors that predict concurrent early word reading and reading comprehension abilities for children with WS are consistent with previous findings for typically developing children and that the Simple View of Reading applies to children with WS. Children with WS benefit strongly from systematic phonics instruction regardless of IQ. Instruction focused on improving listening comprehension is likely to improve reading comprehension, especially as word reading skills increase.
Key CO2 capture technology of pure oxygen exhaust gas combustion for syngas-fueled high-temperature fuel cells
Authors: Wang Hanlin , Lei Qilong , Li Pingping , Liu Changlei , Xue Yunpeng , Zhang Xuewei , Li Chufu , Yang Zhibin
Published: July 2021

Integrated gasification fuel cells (IGFCs) integrating high-temperature solid oxide fuel cell technology with CO2 capture processes represents highly-efficient power systems with negligible CO2 emissions. Flame burning with pure oxygen is an ideal method for fuel cell exhaust gas treatment, and this report describes experimental and numerical studies regarding an oxy-combustor for treating the exhaust gas of a 10 kW IGFC system anode. The applied simulation method was verified based on experiments, and the key performance indices of the combustor were studied under various conditions. It was determined that 315 K was the ideal condensation temperature to obtain flame stability. Under these pure oxygen flame burning conditions, CO was almost completely converted, and the dry mole fraction of CO2 after burning was ≥ 0.958 when there was up to 5% excess O2. Overall, 5% excess O2 was recommended to maximize CO2 capture and promote other environmental considerations. Additionally, the optimal tangential fuel jet angle to control the liner temperature was approximately 25°. The total fuel utilization had to be high enough to maintain the oxygen flame temperature of the anode exhaust gas below 1800 K to ensure that the system was environmentally friendly. The results presented herein have great value for designing IGFCs coupled with CO2 capture systems.
Willenbring Receives 2020 Earth and Planetary Surface Processes Marguerite T. Williams Award
Authors:   AGU
Published: July 2021

Jane K. Willenbring received the inaugural Marguerite T. Williams Award at AGU’s virtual Fall Meeting 2020. The award is given in recognition of “significant contributions to research and community-building by a mid-career scientist in the field of Earth and planetary surface processes.”
Evidence for a Highly Dynamic West Antarctic Ice Sheet During the Pliocene
Authors: Gohl Karsten , Uenzelmann‐Neben Gabriele , Gille‐Petzoldt Johanna , Hillenbrand Claus‐Dieter , Klages Johann P. , Bohaty Steven M. , Passchier Sandra , Frederichs Thomas , Wellner Julia S. , Lamb Rachel , Leitchenkov German ,   IODP Expedition 379 Scientists
Published: July 2021

Major ice loss in the Amundsen Sea sector of the West Antarctic Ice Sheet (WAIS) is hypothesized to have triggered ice sheet collapses during past warm periods such as those in the Pliocene. International Ocean Discovery Program (IODP) Expedition 379 recovered continuous late Miocene to Holocene sediments from a sediment drift on the continental rise, allowing assessment of sedimentation processes in response to climate cycles and trends since the late Miocene. Via seismic correlation to the shelf, we interpret massive prograding sequences that extended the outer shelf by 80 km during the Pliocene through frequent advances of grounded ice. Buried grounding zone wedges indicate prolonged periods of ice‐sheet retreat, or even collapse, during an extended mid‐Pliocene warm period from ∼4.2–3.2 Ma inferred from Expedition 379 records. These results indicate that the WAIS was highly dynamic during the Pliocene and major retreat events may have occurred along the Amundsen Sea margin.
Spatial Extents of Tropical Droughts During El Niño in Current and Future Climate in Observations, Reanalysis, and CMIP5 Models
Authors: Perez Arango Juan D. , Lintner Benjamin R. , Carvalho Leila M. V. , Lyon Bradfield
Published: July 2021

Drought conditions significantly impact human and natural systems in the Tropics. Here, multiple observational and reanalysis products and ensembles of simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) are analyzed with respect to drought areal extent over tropical land regions and its past and future relationships to the El Niño/Southern Oscillation (ENSO). CMIP5 models forced with prescribed sea surface temperatures compare well to observations in capturing the present day time evolution of the fraction of tropical land area experiencing drought conditions and the scaling of drought area and ENSO, that is, increasing tropical drought area with increasing ENSO warm phase (El Niño) strength. The ensemble of RCP8.5 simulations suggests lower end‐of‐the‐century El Niño strength‐tropical drought area sensitivity. At least some of this lower sensitivity is attributable to atmosphere‐ocean coupling, as historic coupled model simulations also exhibit lower sensitivity compared to the observations.
Statistics on Omega Band Properties and Related Geomagnetic Variations
Authors: Vokhmyanin M. , Apatenkov S. , Gordeev E. , Andreeva V. , Partamies N. , Kauristie K. , Juusola L.
Published: July 2021

Using the list of the omega structures based on the Magnetometers‐Ionospheric Radars‐All‐sky Cameras Large Experiment network (Partamies et al., 2017, https://doi.org/10.5194/angeo-35-1069-2017), we obtained a number of important statistical characteristics describing the surface magnetic field. Based on 438 events, typical magnetic variations associated with the passage of the single omega were obtained. The typical variation, obtained using superposed epoch analysis, is associated with a local bending of the westward electrojet and statistically confirms the distribution of equivalent ionospheric currents obtained in earlier observations of single omegas. It was found that during low and moderate geomagnetic activity, the appearance of the omega structures in the dark morning magnetic local time (MLT) sector results in two times higher than average dB/dt on the ground surface. Also, the velocity, direction of movement, and area of omega structures were calculated. It is shown that faster and bigger omegas produce larger time derivatives of the ground magnetic field. Furthermore, we demonstrate that in the 03–08 MLT sector, superposed magnetic variations for the arbitrary events of very high time derivatives |dB/dt| > 10 nT/s, reveal magnetic signatures similar to omegas. Our findings, together with the results described by Apatenkov et al. (2020, https://doi.org/10.1029/2019gl086677), emphasize the important role of omega structures in the formation of large geomagnetically induced currents.
Changes in sleep phase and body weight of mobile health App users during COVID-19 mild lockdown in Japan
Authors: Tahara Yu , Shinto Takae , Inoue Kosuke , Roshanmehr Farnaz , Ito Akito , Michie Mikiko , Shibata Shigenobu
Published: July 2021

Objective and method

The stay-at-home order during the COVID-19 pandemic has restricted individuals’ social behaviors, and therefore, effected their lifestyle including sleep, diet, and physical activity. Using the cross-sectional study design with a large sample size (N = 30,275) from the mobile health App users in Japan, we show age-dependent lifestyle changes during a nonpunitive “mild lockdown” (from April to May 2020).

Results

Sleep onset and offset were delayed on work-days but not on free-days with increased sleep duration and decreased social jetlag, and the changes were more evident in the younger population. Although average weight change was close to none because of the users’ characteristic (95% of App users try to lose weight), we investigated an association between lifestyle change and body-weight change. Participants who reported advanced sleep phase during mild lockdown described a weight decrease. In contrast, the delayed sleep phase reported a weight gain. The results were significant after adjustment of confounding factors including physical activity and meal changes.

Conclusions

Although there is cumulative evidence showing a relationship between late chronotype and obesity, it is still unclear about the potential benefit of the chronotype management to control body weight. Thus, to the best of our knowledge, this is the first study investigating the association between chronotype and weight changes by leveraging a large cohort.
SFPQ promotes an oncogenic transcriptomic state in melanoma
Authors: Bi O. , Anene C. A. , Nsengimana J. , Shelton M. , Roberts W. , Newton-Bishop J. , Boyne J. R.
Published: July 2021

The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.
FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis
Authors: Ruan Dan-Yun , Li Ting , Wang Ying-Nan , Meng Qi , Li Yang , Yu Kai , Wang Min , Lin Jin-Fei , Luo Li-Zhi , Wang De-Shen , Lin Jun-Zhong , Bai Long , Liu Ze-Xian , Zhao Qi , Wu Xiang-Yuan , Ju Huai-Qiang , Xu Rui-Hua
Published: July 2021

Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasis both in vitro and in vivo. Mechanistically, FTO exerted a tumor suppressive role by inhibiting metastasis-associated protein 1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A “reader”, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA. Together, our findings highlight the critical role of FTO in CRC metastasis and reveal a novel epigenetic mechanism by which the hypoxic tumor microenvironment promotes CRC metastasis.
Steroid-refractory chronic graft-versus-host disease: treatment options and patient management
Authors: Wolff Daniel , Fatobene Giancarlo , Rocha Vanderson , Kröger Nicolaus , Flowers Mary E.
Published: July 2021

Chronic graft-versus-host disease (cGVHD) is one of the major causes of late mortality after allogenic hematopoietic stem cell transplantation. Moderate-to-severe cGVHD is associated with poor health-related quality of life and substantial disease burden. While corticosteroids with or without calcineurin inhibitors comprise the first-line treatment option, the prognosis for patients with steroid-refractory cGVHD (SR-cGVHD) remains poor. The mechanisms underlying steroid resistance are unclear, and there are no standard second-line treatment guidelines for patients with SR-cGVHD. In this review, we provide an overview on current treatment options of cGVHD and use a series of theoretical case studies to elucidate the rationale of choices of second- and third-line treatment options for patients with SR-cGVHD based on individual patient profiles.
Integrated analysis of long non-coding RNAs and mRNAs associated with malignant transformation of gastrointestinal stromal tumors
Authors: Yin Xiaonan , Yin Yuan , Dai Lei , Shen Chaoyong , Chen Na , Li Junshu , Cai Zhaolun , Jiang Zhiyuan , Wang Jian , Zhao Zhou , Chen Xin , Deng Hongxin , Zhang Bo
Published: July 2021

Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Collectively, these results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.
Photophysical and NMR studies of encapsulation of 2-cyano-6-hydroxy benzothiazole in p-sulfonatocalix[6]arene and its biological applications
Authors: Jadhav Ankita S. , Chaudhari Ashvini U. , Kodam Kisan M. , Malkhede Dipalee D.
Published: July 2021

Study of inclusion complexation of 2-cyano-6-hydroxy benzothiazole and p-sulfonatocalix[6]arene by UV-visible absorption spectroscopy, steady-state fluorescence spectroscopy, HR-MS, FT-IR, NMR, 2D NMR, and FESEM analysis and its biological activity.
Probing the solute-drag effect and its role in stabilizing the orthorhombic phase in bulk La-doped HfO2 by X-ray and gamma ray spectroscopy
Authors: Banerjee D. , Dey C. C. , Kumar Ravi , Sewak R. , Jha S. N. , Bhattacharyya D. , Acharya R. , Pujari P. K.
Published: July 2021

The orthorhombic phase is shown to be stabilized in bulk HfO2 by the La-dopant and the mechanism for nucleation of orthorhombic phase is explained by the solute drag model.
Suitable claw shape design for improving the magnetic properties of forged claw pole parts in generator
Authors: Zhao Jiaxin , Hu Chengliang , Zhao Zhen , Tang Minjun , Tang Xiaofeng
Published: July 2021

High power‐generation efficiency can be achieved by optimising the shape of the claw pole used as automobile generators. The working process of the stator and rotor in the claw pole generator was simulated using the finite‐element method. First, one of the eight typical claw pole types commonly used in industry was selected. Then, orthogonal optimisation was performed based on the simulation results, yielding an optimal claw shape design. To examine the adaptability of the designed claw pole to shape change, the non‐destructive test for evaluating the magnetic properties of claw pole (NDTEM) was employed. Finally, a claw pole with an optimal shape was forged, and its magnetic induction intensity was assessed using the NDTEM. The results indicated that compared with the unoptimised claw pole, the magnetic induction intensity of the optimised claw pole increased by a maximum of 8.11% and its weight reduced by 4.86%. This optimisation effectively improved the efficiency of power generation and achieved the lightweight of the claw pole.
Improve adaptive cruise control under driver distraction: Time headway compensation based on a random‐effect crash risk model
Authors: Li Penghui , Hu Mengxia , Chen Feng , Xu Chengliang , Dong Chunjiao , Li Yibing
Published: July 2021

Human drivers conduct compensatory behaviour to counteract the increased risk while being distracted. This kind of compensation strategy should be learned for a safer and smart design of adaptive cruise control system (ACC). Hence, a simulator study was conducted, requiring performance visual, cognitive, and combined secondary tasks during a car following scenario. An increased time headway (THW) was found in all of the three distraction conditions, which confirmed that drivers compensated an extra THW to counteract the increased crash risk. Furthermore, crash probability models using binary logistic regression with random intercept were constructed where driver distraction and dynamic traffic situations were embodied as inputs. Results showed that crash risk increased with reduced THW, increased lead vehicle deceleration, and unopened brake light of the lead vehicle. Besides, visual‐related distractions increased crash risk, while pure cognitive distraction lowered crash risk in low THW (lower than 1.8 s) condition and increased crash risk in high THW (larger than 1.8 s) condition. Based on the authors' proposed models, theoretical compensation in THW to fully counteract the increased crash risk by distraction was derived, which could be used for the design of a human‐like ACC with automatic adjustment of THW setting considering driver distraction.
Recent Advances in the Transition-Metal-Free Arylation of Hetero­arenes
Authors: Uçar Sefa , Daştan Arif
Published: July 2021

Transition-metal-free arylation reactions have attracted considerable attention for economic and environmental reasons over the past 40 years. In recent years, much effort has been made to develop efficient transition-metal-free approaches for the arylation of heteroarenes. Covering the literature from 2015 to early 2021, this review aims to provide a thorough overview of the synthetic and mechanistic aspects of these atom-economical and environmentally benign reactions.

1 Introduction

2 Arylation of Pre-functionalized Heteroarenes

2.1 Arylation of Heteroaryl Halides

2.2 Decarboxylative Arylation of Heteroarenes

3 Direct C–H Arylation of Heteroarenes

3.1 C(sp2)–H Arylation

3.2 C(sp3)–H Arylation

4 N-Arylation of Heteroarenes

5 Summary and Outlook
Visible-Light Photocatalytic Ugi/Aza-Wittig Cascade towards 2-Aminomethyl-1,3,4-oxadiazole Derivatives
Authors: Giustiniano Mariateresa , Russo Camilla , Cannalire Rolando , Luciano Paolo , Brunelli Francesca , Tron Gian Cesare
Published: July 2021

A new visible-light photocatalytic multicomponent reaction (MCR) involving N-alkyl-N-methylanilines, N-isocyanoiminotriphenylphosphorane, and carboxylic acids leading to 1,3,4-oxadiazole derivatives is reported. The developed mild reaction conditions enable a broad substrate scope and good functional group tolerance, as further highlighted in the late-stage functionalization of amino acids and drugs. Additionally, a two-step one-pot protocol for the synthesis of non-symmetrical diacylhydrazines is also reported.
Contusion Index is an Important Tool for the Management of Traumatic Intracerebral Hematoma
Authors: Khaliq Adnan , Ali Mumtaz , Azam Farooq , Gul Nayab , Chaurasia Bipin
Published: July 2021

Objective This article evaluates outcome of traumatic intracerebral hematomas in terms of Glasgow Coma Scale (GCS) after medical or surgical management according to contusion index.

Materials and Methods This descriptive study was conducted in the Department of Neurosurgery, Lady Reading Hospital, Peshawar, Pakistan from January 2017 to December 2018. Total number of patients with traumatic intracerebral contusions included in this study was 60 with age between 5 and 75 years. Both male and female were included. Patients with other coexisting traumatic intracranial hematomas like extradural hematoma, subdural hematoma, and polytrauma were excluded from this study. Contusion index of patients were calculated by noncontrast-enhanced computed tomography brain. On arrival patient GCS was documented. The management protocol, that is, conservative or surgical, was provided to individual patient according to contusion index as calculated. Outcome of management was assessed in terms of GCS.

Results Patients with contusion index of 0 to 4 were managed conservatively. Patients with contusion index of 6 were offered surgical management. Patients with contusion index of 9 had poor outcome with both conservative and surgical management.

Conclusion Contusion index can be used reliably as a tool for management of isolated traumatic intracerebral hematomas
Modernism’s Others: Literary Realisms in an Age of Incomplete Emancipation
Authors: Holbo Christine
Published: July 2021

Modernism’s Others explores how a transformation in traditions of realist representation laid the grounds for the emergence of the multicultural and avant-garde constructions of modern American literature. At the heart of this investigation is the way the “right to privacy” articulated at the end of the nineteenth century reshaped visions of separate spheres, differential rights, and public duties. It examines a moment at which writers placed, at the heart of literature’s ethics and its epistemology, the right to not be known. Tracing the career of this idea from its roots in late nineteenth-century realism through the emerging canons of modernist and multicultural literature, this project explores the interplay between new categories of legal right, new categories of social analysis, and new measures of literary value.

“Selling somebody out” slouches into American literature, more or less, on the heels of Bartley Hubbard.
Contribution of the microbiota and their secretory products to inflammation and colorectal cancer pathogenesis: the role of toll-like receptors
Authors: Sheikh Aadil , Taube Joseph , Greathouse K Leigh
Published: July 2021

Alterations in diversity and function of the gut microbiome are associated with concomitant changes in immune response, including chronic inflammation. Chronic inflammation is a major risk factor for colorectal cancer (CRC). An important component of the inflammatory response system are the toll-like receptors (TLRs). TLRs are capable of sensing microbial components, including nucleic acids, lipopolysaccharides and peptidoglycans, as well as bacterial outer membrane vesicles (OMV). OMVs can be decorated with or carry as cargo these TLR activating factors. These microbial factors can either promote tolerance or activate signaling pathways leading to chronic inflammation. Herein we discuss the role of the microbiome and the OMVs that originate from intestinal bacteria in promoting chronic inflammation and the development of colitis-associated CRC. We also discuss the contribution of TLRs in mediating the microbiome-inflammation axis and subsequent cancer development. Understanding the role of the microbiome and its secretory factors in TLR response may lead to the development of better cancer therapeutics.
Does gut microbiota affect atrial rhythm? Causalities and speculations
Authors: Linz Dominik , Gawałko Monika , Sanders Prashanthan , Penders John , Li Na , Nattel Stanley , Dobrev Dobromir
Published: July 2021

Dietary intake has been shown to change the composition of gut microbiota and some changes in microbiota (dysbiosis) have been linked to diabetes, hypertension, and obesity, which are established risk factors for atrial fibrillation (AF). In addition, intestinal dysbiosis generates microbiota-derived bioactive metabolites that might exert proarrhythmic actions. Although emerging preclinical investigations and clinical observational cohort studies suggest a possible role of gut dysbiosis in AF promotion, the exact mechanisms through which dysbiosis contributes to AF remain unclear. This Viewpoint article briefly reviews evidence suggesting that abnormalities in the intestinal microbiota play an important and little-recognized role in the pathophysiology of AF and that an improved understanding of this role may open up new possibilities in the management of AF.
Behavioral Research in Cancer Prevention and Control: Emerging Challenges and Opportunities
Authors: Klein William M P , O’Connell Mary E , Bloch Michele H , Czajkowski Susan M , Green Paige A , Han Paul K J , Moser Richard P , Nebeling Linda C , Vanderpool Robin C
Published: July 2021

It is estimated that behaviors such as poor diet, alcohol consumption, tobacco use, sedentary behavior, and excessive ultraviolet exposure account for nearly one-half of all cancer morbidity and mortality. Accordingly, the behavioral, social, and communication sciences have been important contributors to cancer prevention and control research, with methodological advances and implementation science helping to produce optimally effective interventions. To sustain these contributions, it is vital to adapt to the contemporary context. Efforts must consider ancillary effects of the 2019 coronavirus disease pandemic, profound changes in the information environment and public understanding of and trust in science, renewed attention to structural racism and social determinants of health, and the rapidly increasing population of cancer survivors. Within this context, it is essential to accelerate reductions in tobacco use across all population subgroups; consider new models of energy balance (diet, physical activity, sedentary behavior); increase awareness of alcohol as a risk factor for cancer; and identify better communication practices in the context of cancer-related decisions such as screening and genetic testing. Successful integration of behavioral research and cancer prevention depends on working globally and seamlessly across disciplines, taking a multilevel approach where possible. Methodological and analytic approaches should be emphasized in research training programs and should use new and underused data sources and technologies. As the leadership core of the National Cancer Institute’s Behavioral Research Program, we reflect on these challenges and opportunities and consider implications for the next phase of behavioral research in cancer prevention and control.
A novel circular RNA, circPUS7 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating Kirsten rat sarcoma viral oncogene homolog expression via sponging miR-770
Authors: Pan Shuya , Wang Qin , Zhang Qian , Zhou Mei , Li Luyao , Zhou Xue
Published: July 2021

Cadmium is a human carcinogen, which induces cancers by mechanisms that are not fully understood. Induction of oxidative stress, apoptosis resistance, genotoxic effects, and epigenetic modulations have been indicated to regulate cadmium-induced carcinogenesis. Circular RNAs are epigenetic regulators that have been recognized to play essential roles in carcinogenesis. Yet, the involvement of circular RNAs in cadmium carcinogenesis remains unclear. In this study, a novel circular RNA, circPUS7, was identified and described for the first time. CircPUS7 was significantly upregulated at week 12, 16, and 20 during the cadmium-induced transformation of human bronchial epithelial BEAS-2B cells. Knockdown of circPUS7 in cadmium-transformed BEAS-2B (T-BEAS-2B) cells significantly attenuated transformation markers including cell proliferation, migration, invasion, and anchorage-independent growth. Moreover, circPUS7 promoted malignant phenotypes by competitively binding with miR-770. Overexpression of miR-770 significantly inhibited the transformation properties of T-BEAS-2B cells while inhibition of miR-770 potently reversed the inhibitory effects of circPUS7 knockdown in proliferation, migration, invasion, and anchorage-independent growth of the T-BEAS-2B cells. Kirsten rat sarcoma viral oncogene homolog (KRAS), which was increased synchronically with circPUS7 during cadmium-induced cell transformation, was regulated by circPUS7 through sponging miR-770. In summary, our findings demonstrate that circPUS7 promotes cadmium-induced cell transformation through sponging miR-770 to regulate KRAS expression, providing a new perspective with the involvement of circular RNAs to further understand the mechanisms of cadmium carcinogenesis.
The IDentif.AI 2.0 Pandemic Readiness Platform: Rapid Prioritization of Optimized COVID-19 Combination Therapy Regimens
Authors: Blasiak Agata , Truong Anh T.L. , Remus Alexandria , Hooi Lissa , Seah Shirley Gek Kheng , Wang Peter , Chye De Hoe , Lim Angeline Pei Chiew , Ng Kim Tien , Teo Swee Teng , Tan Yee-Joo , Allen David Michael , Chai Louis Yi Ann , Chng Wee Joo , Lin Raymond T.P. , Lye David C.B. , Wong John Eu-Li , Tan Gek-Yen Gladys , Chan Conrad En Zuo , Chow Edward Kai-Hua , Ho Dean
Published: July 2021

Objectives

We aimed to harness IDentif.AI 2.0, a clinically actionable AI platform to rapidly pinpoint and prioritize optimal combination therapy regimens against COVID-19.

Methods

A pool of starting candidate therapies was developed in collaboration with a community of infectious disease clinicians and included EIDD-1931 (metabolite of EIDD-2801), baricitinib, ebselen, selinexor, masitinib, nafamostat mesylate, telaprevir (VX-950), SN-38 (metabolite of irinotecan), imatinib mesylate, remdesivir, lopinavir, and ritonavir. Following the initial drug pool assessment, a focused, 6-drug pool was interrogated at 3 dosing levels per drug representing nearly 10,000 possible combination regimens. IDentif.AI 2.0 paired prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus (propagated, original strain, B.1.351 and B.1.617.2 variants) and Vero E6 assay with a quadratic optimization workflow.

Results

Within 3 weeks, IDentif.AI 2.0 realized a list of combination regimens, ranked by efficacy, for clinical go/no-go regimen recommendations. IDentif.AI 2.0 revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived.

Conclusions

IDentif.AI 2.0 rapidly revealed promising drug combinations for clinical translation. It pinpointed dose-dependent drug synergy behavior to play a role in trial design and realizing positive treatment outcomes. IDentif.AI 2.0 represents an actionable path towards rapidly optimizing combination therapy following pandemic emergence.

Graphical Abstract

Highlights

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When novel pathogens emerge, the immediate strategy is to repurpose drugs.

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Good drugs delivered together in suboptimal combinations and doses can yield low or no efficacy, leading to misperception that the drugs are ineffective.

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IDentif.AI 2.0 does not use in silico modeling or pre-existing data.

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IDentif.AI 2.0 pairs optimization with prospectively acquired experimental data using a SARS-CoV-2/Vero E6 assay.

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IDentif.AI 2.0 pinpoints EIDD-1931 as a foundation for optimized anti-SARS-CoV-2 combination therapies.
The Genetic Architecture of Amygdala Nuclei
Authors: Mufford Mary S. , van der Meer Dennis , Kaufmann Tobias , Frei Oleksandr , Ramesar Raj , Thompson Paul M. , Jahanshad Neda , Morey Rajendra A. , Andreassen Ole A. , Stein Dan J. , Dalvie Shareefa
Published: July 2021

Background

Whereas a number of genetic variants influencing total amygdala volume have been identified in previous research, genetic architecture of its distinct nuclei have yet to be thoroughly explored. We aimed to investigate whether increased phenotypic specificity through segmentation of the nuclei aids genetic discoverability and sheds light on the extent of shared genetic architecture and biological pathways between the nuclei and disorders associated with the amygdala.

Methods

T1-weighted brain MRI scans (n=36,352, mean age= 64.26 years, 52% female) of trans-ancestry individuals from the UK Biobank were segmented into nine amygdala nuclei with FreeSurfer v6.1, and genome-wide association analyses were performed on the full sample and a European-only subset (n=31,690). We estimated heritability using Genome-wide Complex Trait Analysis, derived estimates of polygenicity, discoverability and power using MiXeR, and determined genetic correlations and shared loci between the nuclei using Linkage Disequilibrium Score Regression, followed by functional annotation using FUMA.

Results

The SNP-based heritability of the nuclei ranged between 0.17-0.33, and the central nucleus had the greatest statistical power for discovery. Across the whole amygdala and the nuclei volumes, 38 novel significant (p < 5×10−9) loci were identified, with most loci mapped to the central nucleus. The mapped genes and associated pathways revealed both unique and shared effects across the nuclei, and immune-related pathways were particularly enriched across several nuclei.

Conclusions

These findings indicate that the amygdala nuclei volumes have significant genetic heritability, increased power for discovery compared to whole amygdala volume, may have unique and shared genetic architectures, and a significant immune component to their aetiology.
Alzheimer’s Disease Assessments Optimised for Diagnostic Accuracy and Administration Time
Authors: McCombe Niamh , Ding Xuemei , Prasad Girijesh , Gillespie Paddy , Finn David P. , Todd Stephen , McClean Paula L. , Wong-Lin KongFatt ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2021

Objective

Despite the potential of machine learning techniques to improve dementia diagnostic processes, research outcomes are often not readily translated to or adopted in clinical practice. Importantly, the time taken to administer diagnostic assessment has yet to be taken into account in feature-selection based optimisation for dementia diagnosis. We address these issues by considering the impact of assessment time as a practical constraint for feature selection of cognitive and functional assessments in Alzheimer’s disease diagnosis.

Methods

We use three different feature selection algorithms to select informative subsets of dementia assessment items from a large open-source dementia dataset. We use cost-sensitive feature selection to optimise our feature selection results for assessment time as well as diagnostic accuracy. To encourage clinical adoption and further evaluation of our proposed accuracy-vs-cost optimisation algorithms, we also implement a sandbox-like toolbox with graphical user interface to evaluate user-chosen subsets of assessment items.

Results

We find that there are subsets of accuracy-cost optimised assessment items that can perform better in terms of diagnostic accuracy and/or total assessment time than most other standard assessments.

Discussion

Overall, our analysis and accompanying sandbox tool can facilitate clinical users and other stakeholders to apply their own domain knowledge to analyse and decide which dementia diagnostic assessment items are useful, and aid the redesigning of dementia diagnostic assessments. Clinical Impact (Clinical Research): By optimising diagnostic accuracy and assessment time, we redesign predictive and efficient dementia diagnostic assessments and develop a sandbox interface to facilitate evaluation and testing by clinicians and non-specialists.
The Role of the Human Brain Neuron-Glia-Synaptic Composition in Forming Resting State Functional Connectivity Networks
Authors: Kahali Sayan , Raichle Marcus E. , Yablonskiy Dmitriy A.
Published: July 2021

While significant progress has been achieved in studying resting state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain’s cellular constituents remain open. Herein we use quantitative Gradient-Recalled-Echo (qGRE) MRI for mapping human brain cellular composition, and BOLD (blood oxygen level dependent) MRI to explore how the brain cellular constituents relate to resting state functional networks. Results show that the BOLD-signal-defined synchrony of connections between cellular circuits in network-defined individual functional units is mainly associated with the regional neuronal density, while the between-functional-units connectivity strength is also influenced by the glia and synaptic components of brain tissue cellular constituents. These mechanisms lead to a rather broad distribution of resting state functional networks properties. Visual networks with the highest neuronal density (but lowest density of glial cells and synapses) exhibit the strongest coherence of BOLD signal, as well as the strongest intra-network connectivity. The Default Mode Network (DMN) is positioned near the opposite part of the spectrum with relatively low coherence of the BOLD signal but a remarkably balanced cellular content enabling DMN prominent role in the overall organization of the brain and the hierarchy of functional networks.