bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation as Experimentalism
Authors: Lee Tong King
Published: July 2022

This Element argues for a perspective on literary translation based around the idea of ludification, using concrete poetry as a test case. Unlike rational-scientific models of translating, ludic translation downplays the linear transmission of meaning from one language into another. It foregrounds instead the open-ended, ergodic nature of translation, where the translator engages with and responds to an original work in an experimental and experiential manner. Focusing on memes rather than signs, ludic translation challenges us to adopt an oblique lens on literary texts and deploy verbal as well as nonverbal resources to add value to an original work. Such an approach is especially amenable to negotiating apparently untranslatable writing like concrete poems across languages, modes, and media. This Element questions assumptions about translatability and opens the discursive space of literary writing to transgressive articulation and multimodal performance. This title is also available as Open Access on Cambridge Core.
On local weak limit and subgraph counts for sparse random graphs
Authors: Kurauskas Valentas
Published: July 2022

We use an inequality of Sidorenko to show a general relation between local and global subgraph counts and degree moments for locally weakly convergent sequences of sparse random graphs. This yields an optimal criterion to check when the asymptotic behaviour of graph statistics, such as the clustering coefficient and assortativity, is determined by the local weak limit.

As an application we obtain new facts for several common models of sparse random intersection graphs where the local weak limit, as we see here, is a simple random clique tree corresponding to a certain two-type Galton–Watson branching process.
JORDFALLET AT BOHUS: REINTERPRETING THE14C DATING OF A MEDIEVAL LANDSLIDE EVENT
Authors: Larsson Anton , Dury Jack P R
Published: July 2022

Radiocarbon (14C) dating has, since its inception, become an integral part of disciplines such as geology and archaeology, underpinning many key findings made by researchers in the past seven decades. As14C dating develops, the need arises to revisit older findings and legacy data which may well contain laboratory errors or post-analysis misinterpretations. In this paper we examine one such finding from Sweden, namely the 195814C dating of the great Jordfallet (“the Earthfall”) landslide, which was published in the very first volume ofRadiocarbonin 1959. We further trace how the results of this14C dating were misunderstood in a time prior to modern radiocarbon calibration, and the impact which this mistake has had throughout academic publications, state reports and local heritage literature through the course of over sixty years. Because of this flawed interpretation the credible date of 1249 AD given to the landslide by historical sources has been overlooked. Instead, a series of dates from the mid-12th and early 13th centuries have been attributed to the landslide event based on erroneous radiocarbon analysis, a mistake which has substantial implications for the understanding of both regional and international history in medieval Scandinavia.
Accountability and corruption displacement: evidence from Italy
Authors: Woodhouse Eleanor Florence
Published: July 2022

One of the reasons for which corruption is so difficult to eradicate is because the actors involved are skilled in adapting their behaviour to changing institutional landscapes. However, surprisingly little is known about how corruption displacement functions across multiple levels of government. Using novel multilevel data on a political scandal in Italy and a Difference-in-Differences estimation strategy, I provide within-country evidence that a sudden increase in accountability fornationaldeputies can impact negatively upon the behaviour oflocal-level public officials and politicians. In treated districts, where there is an increase in the indictment rate of national deputies, local-level corruption increases significantly as compared to nontreated districts. My results show how, in contexts characterised by systemic corruption, changes intended to enhance accountability can trigger a series of mechanisms within the political machine that exploit different levels of government.
Response to Mass-Casualty Incidents and Outbreaks: A Prehospital Disaster Training Package Developed for the National Emergency Medical Service in Sierra Leone
Authors: Caviglia Marta , da Silva-Moniz José Alberto , Venturini Francesco , Jambai Amara , Vandy Matthew Jusu , Wurie Abdul Rahman , Sartie Moi T. , Putoto Giovanni , Ragazzoni Luca
Published: July 2022

Sierra Leone is a country highly prone to disasters, still recovering from the catastrophic 2014 Ebola epidemic. In 2018, the country launched its first National Emergency Medical Service (NEMS) aiming to strengthen the provision of essential health services to the population with the long-term goal of creating a resilient health system able to effectively respond to and recover from emergencies. The Center for Research and Training in Disaster Medicine, Humanitarian Aid, and Global Health (CRIMEDIM), together with the Italian NGO Doctors with Africa (CUAMM), under the direct supervision of the Ministry of Health and Sanitation (MoHS), developed a prehospital Disaster Training Package (DTP) to be delivered to all NEMS personnel to boost the prehospital management of mass-casualty incidents (MCIs) and outbreaks. The DTP included a first phase in which NEMS local trainers underwent a training-of-trainers (ToT) course, enabling them to deliver cascade trainings to 16 district ambulance supervisors, 441 paramedics, 441 ambulance drivers, and 36 operators working in the NEMS operation center. This on-going training package represents the first Disaster Medicine training course for prehospital health professionals in Sierra Leone.
Painting in the Fatimid Period: A Reconsideration
Authors: BLOOM JONATHAN M.
Published: July 2022

The libraries of the Fatimid caliphs in Egypt (r. 969–1171) are known to have been extraordinarily large, containing hundreds of thousands of volumes on all branches of knowledge. Of these fabled manuscripts, only a handful are known to survive. It has long been assumed that a substantial number of the secular manuscripts would have been illustrated, as many later Islamic manuscripts are illustrated, but no examples are known to have survived, although somewhat more than 150 paper fragments bearing images have been attributed to the period, as well as representations in other media, ranging from carved ivories to ceramics. In the absence of surviving illustrated manuscripts, scholars have deployed several strategies to attempt to reconstruct the lost art of painting in the Fatimid period, most notably Richard Ettinghausen in his seminal 1942 article “Painting in the Fatimid Period” and Ernst Grube in a subsequent series of articles and chapters. This article examines the evidence and explores how scholars have interpreted it within the broader contexts of representation and manuscript illustration in Islamic art.
Speech Related Anxiety in Adults Who Stutter
Authors: Bayat Masoumeh , Boostani Reza , Sabeti Malihe , Yadegari Fariba , Taghavi Mahsa , Pirmoradi Mohammadreza , Chakrabarti Prasun , Nami Mohammad
Published: July 2022

Abstract. The relationship between anxiety and stuttering has always been a topic of debate with a great emphasis on research focused on examining whether speech-related anxiety can exacerbate stuttering. This investigation compares some speech-related anticipatory anxiety indices in fluent and dysfluent utterances in adults who stutter (AWS). We scored the level of cognitive speech-related anxiety (anticipatory anxiety) using a self-reporting method and also evaluated the autonomic aspects of anxiety (state anxiety) through recording changes in Galvanic Skin Response (GSR) signals. Explaining the link between stuttering and anxiety is expected to assist practitioners in stuttering assessment and subsequent treatment strategies. Phasic GSR values of six events related to answering the verbal stimuli through fluent and dysfluent responses were registered to measure sympathetic arousal as an index of state anxiety in 20 AWS ( Mage= 35 ± 4 years, range: 21–42). To quantitatively examine the cognitive aspects of speech-related anticipatory anxiety, two questionnaires were rated by participants addressing the stuttering anticipation and semantic difficulty of verbal stimuli. GSR measures of fluent events were significantly higher than dysfluent counterparts within time windows before and during answering aloud the verbal stimuli ( p < .001). Later in the experiment, GSR values of dysfluent events were found to be higher than their fluent counterparts ( p < .001). Stuttering anticipation yielded a weak negative meaningful correlation with the scores of fluency ( r = −0.283, p = .046) and a positive yet nonsignificant correlation with the stuttering scores. The semantic difficulty had a moderately significant correlation with stuttering anticipation ( r = 0.354, p = .012) but not a meaningful correlation with fluency state. Autonomic and cognitive indices of speech-related anticipatory anxiety are not robust predictors of fluency. Anxiety seems to be more of a consequence of stuttering than a cause.
The Impact of Pain on Subsequent Effort and Cognitive	Performance
Authors: Silvestrini Nicolas , Corradi-Dell’Acqua Corrado
Published: July 2022

Abstract: Theoretical accounts of pain and empirical evidence indicate that pain and cognitive control share common neurocognitive processes. Numerous studies have examined the interactions between pain and cognitive performance when they occur simultaneously, typically showing analgesic effects on task performance and impaired performance due to pain. However, the sequential impact of pain on cognitive control and effort remains less clear. This study investigated the influence of a first task, including painful vs. non-painful thermal stimuli, on effort-related cardiac response and performance in a subsequent moderately difficult cognitive task. Drawing on the hypothesis that experiencing pain should recruit cognitive resources (such as attention and working memory) and reduce perceived ability, we predicted lower task performance and/or stronger compensatory effort in the subsequent cognitive task after the painful than after the non-painful first task. Results support our predictions regarding the effect of pain on subsequent cognitive performance, which was moderately lower after the painful task. However, such a decrease in task proficiency was not associated with a comparable decrease in perceived capacity or increase in effort-related cardiac reactivity. Nevertheless, further correlational analyses indicated that effort and perceived capacity were significantly related to pain ratings. Moderate pain was associated with stronger effort during the cognitive task, whereas high pain led to disengagement, that is, a low effort. Moreover, in line with our predictions, higher pain ratings were associated with a lower self-reported capacity to perform the cognitive task. We discuss these findings regarding the relationship between effort and performance, the impact of fatigue on motivation, and interindividual variability in these after-effects.
How a Few Inconsistent Respondents Can Confound the Structure of Personality Survey Data
Authors: Arias Víctor B. , Ponce Fernando P. , Martínez-Molina Agustín
Published: July 2022

Abstract: In survey data, inconsistent responses due to careless/insufficient effort (C/IE) can lead to problems of replicability and validity. However, data cleaning prior to the main analyses is not yet a standard practice. We investigated the effect of C/IE responses on the structure of personality survey data. For this purpose, we analyzed the structure of the Core-Self Evaluations scale (CSE-S), including the detection of aberrant responses in the study design. While the original theoretical model of the CSE-S assumes that the construct is unidimensional ( Judge et al., 2003 ), recent studies have argued for a multidimensional solution (positive CSE and negative CSE). We hypothesized that this multidimensionality is not substantive but a result of the tendency of C/IE data to generate spurious dimensions. We estimated the confirmatory models before and after removing highly inconsistent response vectors in two independent samples (6% and 4.7%). The analysis of the raw samples clearly favored retaining the two-dimensional model. In contrast, the analysis of the clean datasets suggested the retention of a single factor. A mere 6% C/IE response rate showed enough power to confound the results of the factor analysis. This result suggests that the factor structure of positive and negative CSE factors is spurious, resulting from uncontrolled wording variance produced by a limited proportion of highly inconsistent response vectors. We encourage researchers to include screening for inconsistent responses in their research designs.
Training Considerations for Providers Engaged in Refugee Mental Health Care
Authors: Mattar Sandra , Ipekci Bediha , Louis Elizabeth F. , Taknint Joelle T.
Published: July 2022

Abstract. More people than ever in history are being displaced and becoming refugees due to political conflict, climate change, and persecution, among others. Meeting the mental health care needs of refugees has become a global priority. This population’s needs are unique due to the multiple traumatic experiences of refugees, their difficulties in navigating various systemic barriers, and the minimal specialized cultural training in refugee care. In order to improve the health of refugees, it is important to examine how care is delivered and the provider and systemic factors that perpetuate inequities and cultural misunderstandings in providing care. Most of the refugee literature focuses on refugee factors that limit access to care but falls short on discussing providers’ lack of training in refugee care. In the following paper, we present refugee mental health training considerations for providers. These considerations are based on the lessons learned from direct clinical work in a refugee clinic located in a major public academic hospital in the New England area (United States of America). The authors discuss the particular context of caring for refugee populations, the skills needed to work with this population, and considerations for navigating provider and systemic barriers that arise in refugee care. We believe that training mental health providers can have significant implications for refugee mental health care utilization, patient improved treatment outcomes, and on refugees’ increased sense of self-determination.
CMIP5 and CMIP6 Model Projection Comparison for Hydrological Impacts Over North America
Authors: Martel J.‐L. , Brissette F. , Troin M. , Arsenault R. , Chen J. , Su T. , Lucas‐Picher P.
Published: July 2022

A warmer climate impacts streamflows and these changes need to be quantified to assess future risk, vulnerability, and to implement efficient adaptation measures. The climate simulations from the fifth phase of the Coupled Model Intercomparison Project (CMIP5), which have been the basis of most such assessments over the past decade, are being gradually superseded by the more recent Coupled Model Intercomparison Project Phase 6 (CMIP6). Our study portrays the added value of the CMIP6 ensemble over CMIP5 in a first North America wide comparison using 3,107 catchments. Results show a reduced spread of the CMIP6 ensemble compared to the CMIP5 ensemble for temperature and precipitation projections. In terms of flow indicators, the CMIP6 driven hydrological projections result in a smaller spread of future mean and high flow values, except for mountainous areas. Overall, we assess that the CMIP6 ensemble provides a narrower band of uncertainty of future climate projections, bringing more confidence for hydrological impact studies.
Turbulent Mechanisms for the Deep Convective Boundary Layer in the Taklimakan Desert
Authors: Zhang Lu , Zhang Hongsheng , Li Qianhui , Wei Wei , Cai Xuhui , Song Yu , Mamtimin Ali , Wang Minzhong , Yang Fan , Wang Yu , Zhou Chenglong
Published: July 2022

The deep convective boundary layer (CBL) in the Taklimakan Desert plays an important role in the climate system in East Asia. Based on the observation experiment and large‐eddy simulation, turbulent mechanisms for its formation were revealed in this study. This explained why the daily maximum CBL depth was independent of surface heating. In the late‐morning, there was a weak temperature inversion and a near‐neutral residual layer (RL) above the CBL. With the development of the CBL, stronger convection could penetrate the RL and even overshoot the top of the RL. The distinctive boundary‐layer process entrained free‐tropospheric air to warm the RL and then promoted the entrainment of the warmed air in the RL into the CBL. This extra energy supply effectively contributed to the growth of the CBL. With further positive feedback between the CBL and RL depths, a deeper CBL would form in consecutive fair‐weather conditions.
ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis
Authors: Xiang Yaoxian , Dai Junxi , Li Yao , You Zongqi , Zhang Junpeng , Huang Xinying , Nie Shuqi , Chen Yujie , Xu Lei , Liu Fengming , Jiang Junjian , Xu Jianguang
Published: July 2022

Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy.
LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis
Authors: Xie Tao , Du Kunpeng , Liu Wei , Liu Chunshan , Wang Baiyao , Tian Yunhong , Li Rong , Huang Xiaoting , Lin Jie , Jian Haifeng , Zhang Jian , Yuan Yawei
Published: July 2022

Background

Distant metastasis and recurrence remain the main obstacle to nasopharyngeal carcinoma (NPC) treatment. However, the molecular mechanisms underlying NPC growth and metastasis are poorly understood.

Methods

LHX2 expression was examined in NPC cell lines and NPC tissues using quantitative reverse transcription-polymerase chain reaction, western blotting and Immunohistochemistry assay. NPC cells overexpressing or silencing LHX2 were used to perform CCK-8 assay, colony-formation assay, EdU assay, wound-healing and invasion assays in vitro. Xenograft tumour models and lung metastasis models were involved for the in vivo assays. The Gene Set Enrichment Analysis (GSEA), ELISA assay, western blot, chromatin immunoprecipitation (ChIP) assay and Luciferase reporter assay were applied for the downstream target mechanism investigation.

Results

LIM-homeodomain transcription factor 2 (LHX2) was upregulated in NPC tissues and cell lines. Elevated LHX2 was closely associated with poor survival in NPC patients. Ectopic LHX2 overexpression dramatically promoted the growth, migration and invasion of NPC cells both in vitro and in vivo. Mechanistically, LHX2 transcriptionally increased the fibroblast growth factor 1 (FGF1) expression, which in turn activated the phosphorylation of STAT3 (signal transducer and activator of transcription 3), ERK1/2 (extracellular regulated protein kinases 1/2) and AKT signalling pathways in an autocrine and paracrine manner, thereby promoting the growth and metastasis of NPC. Inhibition of FGF1 with siRNA or FGFR inhibitor blocked LHX2-induced nasopharyngeal carcinoma cell growth, migration and invasion.

Conclusions

Our study identifies the LHX2-FGF1-FGFR axis plays a key role in NPC progression and provides a potential target for NPC therapy.
Transepithelial photorefractive keratectomy: a prospective randomized comparative study between the two-step and the single-step techniques
Authors: Abdel-Radi Mahmoud , Shehata Mohamed , Mostafa Magdi Mohammad , Aly Mohamed Omar M.
Published: July 2022

Objectives

To assess and compare the six-month outcome of the two-step transepithelial phototherapeutic keratectomy- photorefractive keratectomy (PTK-PRK) and the single-step transepithelial PRK for myopia and myopic astigmatism.

Methods

A prospective randomized study. The study enrolled 100 eyes of 50 patients with mild to moderate myopia or myopic astigmatism stratified into two groups, PTK-PRK (n = 50 eyes) and single step PRK (n = 50 eyes). Primary outcome measures were visual acuity and manifest refraction. Secondary outcome measures were epithelial healing duration, post-PRK pain scores and 3-month postoperative haze grading.

Results

Preoperative characteristics were similar in both groups (p value > 0.05). The mean uncorrected distance visual acuity (UDVA) at 1 week, 1 month, 3 and 6 months was significantly better in the single-step PRK group than in the two-step PTK-PRK group (p < 0.001). The mean manifest sphere, cylinder and spherical equivalent showed a significant difference at all follow up visits in favour of the single-step PRK (p value < 0.001). Epithelial healing duration was faster in single-step PRK (p value < 0.001). Pain scores were significantly lower following single-step PRK at 8 h, 1 day, 3 days (p value < 0.001) but were similar at the 7th day. Haze scores showed no statistical difference between the two groups at 3-month follow-up.

Conclusion

The two transepithelial PRK techniques were effective in correcting mild to moderate myopia and myopic astigmatism. However, Single-step transepithelial PRK achieved faster visual recovery, better refractive outcome and shorter epithelial healing time with less post-PRK pain.

Clinical trials registry

(Clinical Trials.gov Identifier): NCT04710082.
A quantum dot crossbar with sublinear scaling of interconnects at cryogenic temperature
Authors: Bavdaz P. L. , Eenink H. G. J. , van Staveren J. , Lodari M. , Almudever C. G. , Clarke J. S. , Sebasatiano F. , Veldhorst M. , Scappucci G.
Published: July 2022

We demonstrate a 36 × 36 gate electrode crossbar that supports 648 narrow-channel field effect transistors (FET) for gate-defined quantum dots, with a quadratic increase in quantum dot count upon a linear increase in control lines. The crossbar is fabricated on an industrial 28Si-MOS stack and shows 100% FET yield at cryogenic temperature. We observe a decreasing threshold voltage for wider channel devices and obtain a normal distribution of pinch-off voltages for nominally identical tunnel barriers probed over 1296 gate crossings. Macroscopically across the crossbar, we measure an average pinch-off of 1.17 V with a standard deviation of 46.8 mV, while local differences within each unit cell indicate a standard deviation of 23.1 mV. These disorder potential landscape variations translate to 1.2 and 0.6 times the measured quantum dot charging energy, respectively. Such metrics provide means for material and device optimization and serve as guidelines in the design of large-scale architectures for fault-tolerant semiconductor-based quantum computing.
Strong control of effective radiative forcing by the spatial pattern of absorbing aerosol
Authors: Williams Andrew I. L. , Stier Philip , Dagan Guy , Watson-Parris Duncan
Published: July 2022

Over the coming decades, it is expected that the spatial pattern of anthropogenic aerosol will change dramatically and the global aerosol composition will become relatively more absorbing. Yet, the climatic impact of this evolving spatial pattern of absorbing aerosol has received relatively little attention, in particular its impact on global-mean effective radiative forcing. Here, using model experiments, we show that the effective radiative forcing from absorbing aerosol varies strongly depending on their location, driven by rapid adjustments of clouds and circulation. Our experiments generate positive effective radiative forcing in response to aerosol absorption throughout the midlatitudes and most of the tropical regions, and a strong ‘hot spot’ of negative effective radiative forcing in response to aerosol absorption over the tropical Western Pacific. Further, these diverse responses can be robustly attributed to changes in atmospheric dynamics and highlight the importance of this ‘aerosol pattern effect’ for transient forcing from regional biomass-burning aerosol.
Origin and function of activated fibroblast states during zebrafish heart regeneration
Authors: Hu Bo , Lelek Sara , Spanjaard Bastiaan , El-Sammak Hadil , Simões Mariana Guedes , Mintcheva Janita , Aliee Hananeh , Schäfer Ronny , Meyer Alexander M. , Theis Fabian , Stainier Didier Y. R. , Panáková Daniela , Junker Jan Philipp
Published: July 2022

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.
Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)
Authors: Zhang Ziyang , Guiley Keelan Z. , Shokat Kevan M.
Published: July 2022

Drugs that directly impede the function of driver oncogenes offer exceptional efficacy and a therapeutic window. The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point. KRAS is the most frequently mutated proto-oncogene in human cancer, yet despite success targeting the G12C allele, targeted therapy for other hotspot mutants of KRAS has not been described. Here we report the discovery of small molecules that covalently target a G12S somatic mutation in K-Ras and suppress its oncogenic signaling. We show that these molecules are active in cells expressing K-Ras(G12S) but spare the wild-type protein. Our results provide a path to targeting a second somatic mutation in the oncogene KRAS by overcoming the weak nucleophilicity of an acquired serine residue. The chemistry we describe may serve as a basis for the selective targeting of other unactivated serines.
Glimmers of hope in large carnivore recoveries
Authors: Ingeman Kurt E. , Zhao Lily Z. , Wolf Christopher , Williams David R. , Ritger Amelia L. , Ripple William J. , Kopecky Kai L. , Dillon Erin M. , DiFiore Bartholomew P. , Curtis Joseph S. , Csik Samantha R. , Bui An , Stier Adrian C.
Published: July 2022

In the face of an accelerating extinction crisis, scientists must draw insights from successful conservation interventions to uncover promising strategies for reversing broader declines. Here, we synthesize cases of recovery from a list of 362 species of large carnivores, ecologically important species that function as terminal consumers in many ecological contexts. Large carnivores represent critical conservation targets that have experienced historical declines as a result of direct exploitation and habitat loss. We examine taxonomic and geographic variation in current extinction risk and recovery indices, identify conservation actions associated with positive outcomes, and reveal anthropogenic threats linked to ongoing declines. We find that fewer than 10% of global large carnivore populations are increasing, and only 12 species (3.3%) have experienced genuine improvement in extinction risk, mostly limited to recoveries among marine mammals. Recovery is associated with species legislation enacted at national and international levels, and with management of direct exploitation. Conversely, ongoing declines are robustly linked to threats that include habitat modification and human conflict. Applying lessons from cases of large carnivore recovery will be crucial for restoring intact ecosystems and maintaining the services they provide to humans.
Analytical method validation for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products by RP-HPLC
Authors: Analakkattillam Sandhyarani , Langsi Victor K. , Hanrahan John P. , Moore Eric
Published: July 2022

A simple quantitative reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products. The RP-HPLC method was developed and optimized for the mobile phase composition, flow rate, column selection and detector wavelength. An isocratic elution of samples were performed on SOLAS 100 Å C18 150 mm × 4.6 mm, 5 μm column with a mobile phase containing 75/25 acetonitrile/water v/v, with a flow rate of 1.5 mL/min by using an ultraviolet–visible (UV/Vis) detector operating at 214 nm. The RP-HPLC method was validated to meet regulatory requirements which covers specificity, accuracy, range, linearity, precision, system suitability and robustness. The validated assay test method was applied successfully to quantify cannabidiol and tetrahydrocannabinol in commercial hemp oil infused products such as tablets, soft gel capsules, plant extract oils, oral drops, tincture, and beverage enhancers. All the test results were found acceptable as per ICH guidelines, and this confirmed the feasibility of this method for its intended use in regular quality control and assay of cannabidiol and tetrahydrocannabinol in hemp oil infused products.
Enhanced osteogenic differentiation of stem cells by 3D printed PCL scaffolds coated with collagen and hydroxyapatite
Authors: Ebrahimi Zahra , Irani Shiva , Ardeshirylajimi Abdolreza , Seyedjafari Ehsan
Published: July 2022

Bone tissue engineering uses various methods and materials to find suitable scaffolds that regenerate lost bone due to disease or injury. Poly(ε-caprolactone) (PCL) can be used in 3D printing for producing biodegradable scaffolds by fused deposition modeling (FDM). However, the hydrophobic surfaces of PCL and its non-osteogenic nature reduces adhesion and cell bioactivity at the time of implantation. This work aims to enhance bone formation, osteogenic differentiation, and in vitro biocompatibility via PCL scaffolds modification with Hydroxyapatite (HA) and Collagen type I (COL). This study evaluated the osteosupportive capacity, biological behavior, and physicochemical properties of 3D-printed PCL, PCL/HA, PCL/COL, and PCL/HA/COL scaffolds. Biocompatibility and cells proliferation were investigated by seeding human adipose tissue-derived mesenchymal stem cells (hADSCs) onto the scaffolds, which were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and 6-diamidino-2-phenylindole (DAPI) staining. In addition, the bone differentiation potential of the hADSCs was assessed using calcium deposition, alkaline phosphatase (ALP) activity, and bone-related protein and genes. Although all constructed scaffolds support hADSCs proliferation and differentiation, the results showed that scaffold coating with HA and COL can boost these capacities in a synergistic manner. According to the findings, the tricomponent 3D-printed scaffold can be considered as a promising choice for bone tissue regeneration and rebuilding.
Forecast of a future leveling of the incidence trends of female breast cancer in Taiwan: an age-period-cohort analysis
Authors: Chen Yi-Chu , Su Shih-Yung , Jhuang Jing-Rong , Chiang Chun-Ju , Yang Ya-Wen , Wu Chao-Chun , Lin Li-Ju , Lee Wen-Chung
Published: July 2022

Breast cancer is the most common cancer among women in Taiwan. The age-standardized incidence rate has doubled in just 20 years, causing considerable concern to health professionals and the general public. This study used an ensemble of age-period-cohort models to estimate breast cancer incidence trends in Taiwan from 1997 to 2016 and project trends up to 2035. The (truncated) world standard population (World Health Organization 2000) proportions (age groups: 25–29, 30–34, …, 80–84, and older than 85 years) were used to calculate age-standardized incidence rates. The age-standardized incidence rate from 1997 (60.33/100,000 population) to 2016 (128.20/100,000 population) increased rapidly. The projection is that the increase in the age-standardized incidence will subsequently slow and exhibit a plateau in 2031 (151.32/100,000 population). From 2026 to 2035, the age-specific incidence rates for women older than 55 years old (postmenopausal breast cancer) are projected to increase with larger percentage increments for older women. A future leveling of female breast cancer incidence trends in Taiwan is anticipated. The majority of the patients with breast cancer in the future will be women aged 55 years and older. Education on lifestyle recommendations and mammography screening is required to reduce the burden of breast cancer. The results should have implications for other countries which are also confronted with the same public health problem of rapidly increasing breast cancer incidences.
Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development
Authors: Moulis Manon , Runser Steve Vincent Maurice , Glorieux Laura , Dauguet Nicolas , Vanderaa Christophe , Gatto Laurent , Tyteca Donatienne , Henriet Patrick , Spagnoli Francesca M. , Iber Dagmar , Pierreux Christophe E.
Published: July 2022

Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.
Decision effect of a deep-learning model to assist a head computed tomography order for pediatric traumatic brain injury
Authors: Heo Sejin , Ha Juhyung , Jung Weon , Yoo Suyoung , Song Yeejun , Kim Taerim , Cha Won Chul
Published: July 2022

The study aims to measure the effectiveness of an AI-based traumatic intracranial hemorrhage prediction model in the decisions of emergency physicians regarding ordering head computed tomography (CT) scans. We developed a deep-learning model for predicting traumatic intracranial hemorrhages (DEEPTICH) using a national trauma registry with 1.8 million cases. For simulation, 24 cases were selected from previous emergency department cases. For each case, physicians made decisions on ordering a head CT twice: initially without the DEEPTICH assistance, and subsequently with the DEEPTICH assistance. Of the 528 responses from 22 participants, 201 initial decisions were different from the DEEPTICH recommendations. Of these 201 initial decisions, 94 were changed after DEEPTICH assistance (46.8%). For the cases in which CT was initially not ordered, 71.4% of the decisions were changed (p < 0.001), and for the cases in which CT was initially ordered, 37.2% (p < 0.001) of the decisions were changed after DEEPTICH assistance. When using DEEPTICH, 46 (11.6%) unnecessary CTs were avoided (p < 0.001) and 10 (11.4%) traumatic intracranial hemorrhages (ICHs) that would have been otherwise missed were found (p = 0.039). We found that emergency physicians were likely to accept AI based on how they perceived its safety.
Eolian erosion of polygons in the Atacama Desert as a proxy for hyper-arid environments on Earth and beyond
Authors: Sager Christof , Airo Alessandro , Arens Felix L. , Schulze-Makuch Dirk
Published: July 2022

Polygonal networks occur on various terrestrial and extraterrestrial surfaces holding valuable information on the pedological and climatological conditions under which they develop. However, unlike periglacial polygons that are commonly used as an environmental proxy, the information that polygons in the hyper-arid Atacama Desert can provide is little understood. To promote their use as a proxy, we investigated a polygonal network within an inactive channel that exhibits uncommonly diverse surface morphologies and mineral compositions, using geochemical and remote sensing techniques. Our findings show that the polygons belong to a continuous network of the same genetic origin. Their differences result from post-formational differential eolian erosion up to 50 cm depth, exposing indurated subsurface horizons rich in sulfate or nitrate and chloride. Their location in an ancient channel could lead to the misinterpretation of fluvial polygon erosion, however, we find no such signs but evidence for aqueous resurfacing of microtopography by fog and minimal rainwater infiltration. Our findings extend the use of polygons as proxies in the Atacama Desert, indicating saline soils and hyper-arid conditions. We conclude that this example of polygon erosion can guide future polygon research, especially regarding the use of erosional surfaces on Earth and beyond to gain valuable subsurface insights.
A simplified prediction model for end-stage kidney disease in patients with diabetes
Authors: Inoguchi Toyoshi , Okui Tasuku , Nojiri Chinatsu , Eto Erina , Hasuzawa Nao , Inoguchi Yukihiro , Ochi Kentaro , Takashi Yuichi , Hiyama Fujiyo , Nishida Daisuke , Umeda Fumio , Yamauchi Teruaki , Kawanami Daiji , Kobayashi Kunihisa , Nomura Masatoshi , Nakashima Naoki
Published: July 2022

This study aimed to develop a simplified model for predicting end-stage kidney disease (ESKD) in patients with diabetes. The cohort included 2549 individuals who were followed up at Kyushu University Hospital (Japan) between January 1, 2008 and December 31, 2018. The outcome was a composite of ESKD, defined as an eGFR < 15 mL min−1 [1.73 m]−2, dialysis, or renal transplantation. The mean follow-up was 5.6 $$\pm$$
±
3.7 years, and ESKD occurred in 176 (6.2%) individuals. Both a machine learning random forest model and a Cox proportional hazard model selected eGFR, proteinuria, hemoglobin A1c, serum albumin levels, and serum bilirubin levels in a descending order as the most important predictors among 20 baseline variables. A model using eGFR, proteinuria and hemoglobin A1c showed a relatively good performance in discrimination (C-statistic: 0.842) and calibration (Nam and D’Agostino $$\chi$$
χ
2 statistic: 22.4). Adding serum albumin and bilirubin levels to the model further improved it, and a model using 5 variables showed the best performance in the predictive ability (C-statistic: 0.895, $$\chi$$
χ
2 statistic: 7.7). The accuracy of this model was validated in an external cohort (n = 5153). This novel simplified prediction model may be clinically useful for predicting ESKD in patients with diabetes.
Microvalve array fabrication using selective PDMS (polydimethylsiloxane) bonding through Perfluorooctyl-trichlorosilane passivation for long-term space exploration
Authors: Estlack Zachary , Kim Jungkyu
Published: July 2022

To improve the versatility and robustness of microfluidic analytical devices for space exploration, a programmable microfluidic array (PMA) has been implemented to support a variety of missions. When designing a PMA, normally closed valves are advantageous to avoid cross contamination and leaking. However, a stable fabrication method is required to prevent these valves from sticking and bonding over time. This work presents how polydimethylsiloxane (PDMS) can be bonded selectively using chemical passivation to overcome PDMS sticking issue during long-term space exploration. First, on a PDMS stamp, the vaporized perfluorooctyl-trichlorosilane (PFTCS) are deposited under − 80 kPa and 150 °C conditions. The PFTCS was then transferred onto PDMS or glass substrates by controlling temperature and time and 15 min at 150 °C provides the optimal PFTCS transfer for selective bonding. With these characterized parameters, we successfully demonstrated the fabrication of PMA to support long-term space missions. To estimate the stability of the stamped PFTCS, a PMA has been tested regularly for three years and no stiction or performance alteration was observed. A flight test has been done with a Cessaroni L1395 rocket for high g-force and vibration test and there is no difference on PMA performance after exposure of launch and landing conditions. This work shows promise as a simple and robust technique that will expand the stability and capability of PMA for space exploration.
A phosphite-based screening platform for identification of enzymes favoring nonnatural cofactors
Authors: Liu Yuxue , Li Zhuoya , Guo Xiaojia , Wang Xueying , Zhao Zongbao K.
Published: July 2022

Enzymes with dedicated cofactor preference are essential for advanced biocatalysis and biomanufacturing, especially when employing nonnatural nicotinamide cofactors in redox reactions. However, directed evolution of an enzyme to switch its cofactor preference is often hindered by the lack of efficient and affordable method for screening as the cofactor per se or the substrate can be prohibitively expensive. Here, we developed a growth-based selection platform to identify nonnatural cofactor-dependent oxidoreductase mutants. The growth of bacteria depended on the nicotinamide cytosine dinucleotide (NCD) mediated conversion of non-metabolizable phosphite into phosphate. The strain BW14329 lacking the ability to oxidize phosphite was suitable as host, and NCD-dependent phosphite dehydrogenase (Pdh*) is essential to the selection platform. Previously confirmed NCD synthetase with NCD synthesis capacity and NCD-dependent malic enzyme were successfully identified by using the platform. The feasibility of this strategy was successfully demonstrated using derived NCD-active malic enzyme as well as for the directed evolution of NCD synthetase in Escherichia coli. A phosphite-based screening platform was built for identification of enzymes favoring nonnatural cofactor NCD. In the future, once Pdh variants favoring other biomimetic or nonnatural cofactors are available this selection platform may be readily redesigned to attain new enzyme variants with anticipated cofactor preference, providing opportunities to further expand the chemical space of redox cofactors in chemical biology and synthetic biology.
Systematic characterization of the components and molecular mechanisms of Jinshui Huanxian granules using UPLC-Orbitrap Fusion MS integrated with network pharmacology
Authors: Yuan Jie , Zhao Di , Liu Xue-Fang , Tian Yan-Ge , Zhang Hao-Jie , Feng Su-Xiang , Li Jian-Sheng
Published: July 2022

Jinshui Huanxian granules (JSHX) is a clinical Chinese medicine formula used for treating pulmonary fibrosis (PF). However, the effective components and molecular mechanisms of JSHX are still unclear. In this study, a combination approach using ultra-high performance liquid chromatography-Orbitrap Fusion mass spectrometry (UPLC-Orbitrap Fusion MS) integrated with network pharmacology was followed to identify the components of JSHX and the underlying molecular mechanisms against PF. UPLC-Orbitrap Fusion MS was used to identify the components present in JSHX. On the basis of the identified components, we performed target prediction using the SwissTargetPrediction database, protein–protein interaction (PPI) analysis using STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using Metascape and constructed a component-target-pathway network using Cytoscape 3.7.2. Molecular docking technology was used to verify the affinity between the core components and targets. Finally, the pharmacological activities of three potentially bioactive components were validated in transforming growth factor β1 (TGF-β1)-induced A549 cell fibrosis model. As a result, we identified 266 components, including 56 flavonoids, 52 saponins, 31 alkaloids, 10 coumarins, 12 terpenoids and 105 other components. Of these, 90 validated components were predicted to act on 172 PF-related targets and they exhibited therapeutic effects against PF via regulation of cell migration, regulation of the mitogen-activated protein kinase (MAPK) cascade, reduction of oxidative stress, and anti-inflammatory activity. Molecular docking showed that the core components could spontaneously bind to receptor proteins with a strong binding force. In vitro, compared to model group, hesperetin, ruscogenin and liquiritin significantly inhibited the increase of α-smooth muscle actin (α-SMA) and fibronectin (FN) and the decrease of e-cadherin (E-cad) in TGF-β1-induced A549 cells. This study is the first to show, using UPLC-Orbitrap Fusion MS combined with network pharmacology and experimental validation, that JSHX might exert therapeutic actions against PF by suppressing the expression of key factors in PF. The findings provide a deeper understanding of the chemical profiling and pharmacological activities of JSHX and a reference for further scientific research and clinical use of JSHX in PF treatment.