bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrovascular Accidents Related to Snakebites in the Amazon—Two Case Reports
Authors: Sachett Jacqueline de Almeida Gonçalves , Mota da Silva Ageane , Dantas Alba Waldilene Coelho Batista , Dantas Theobaldo Rebouças , Colombini Mônica , Moura da Silva Ana Maria , Monteiro Wuelton Marcelo , Bernarde Paulo Sérgio
Published: August 2020

The objective of this case series was to describe 2 patients presenting with subarachnoid hemorrhage with hydrocephalus and hemoventricle after a snakebite caused by presumed Bothrops ssp. Both cases occurred in the municipality of Guajará (Amazonas state), Western Brazilian Amazon. Both cases featured delay in administration of serum therapy, which may have contributed to the emergence of complications such as stroke. Patient 1 was admitted to hospital 16 h after the snakebite occurred. Before receiving antivenom, testing showed the patient as having unclottable blood. She developed hemorrhagic stroke (a subarachnoid hemorrhage with hydrocephalus and hemoventricle). On the seventh day, she was discharged from hospital. Patient 2 arrived at the hospital 3 d after the snakebite occurred and presented with unclottable blood. He had a stroke (right frontoparietal hemorrhage, intraparenchymal hemorrhage already open to the ventricle) and died on the eighth day after the snakebite. Delay in seeking health care after snake envenomation can result in worse outcome.
Visitor Incidents in Western Australian Protected Areas, 2011–2017
Authors: Gstaettner Anna Maria
Published: August 2020

Introduction

Protected areas in Western Australia are a significant resource base for nature-based tourism and recreation. Visitor incidents are of special interest to managers of these areas because of concerns regarding public safety. The ongoing monitoring and analysis of visitor incidents plays a major role in reducing incident occurrence.

Methods

Incident data recorded by the Parks and Wildlife Service from July 2011 to June 2017 were analyzed for an overview of trends and patterns of incident occurrence. For parks with the highest incident frequency, the level of risk experienced by visitors, combining incident probability and severity, was determined.

Results

A total of 459 visitor incidents were recorded, 77±11 per year. Minor incidents accounted for 48% of incidents, 43% were major, and 8% were fatal. Trip/Slip incidents were most frequent. Fatalities were mostly falls from a height or water-related incidents. Karijini National Park (highest number of incidents) and Ningaloo (highest number of fatalities) were identified as priority areas for managing visitor risk. The greatest individual visitor risk values were calculated for Mitchell River and Karijini national parks.

Conclusions

Recreational injuries are of great concern to the Parks and Wildlife Service in Western Australia. Quantifying and categorizing visitor incidents helps in understanding the trends and patterns of incident occurrence in protected areas, and priority areas for targeted visitor risk management intervention can be identified.
Outcomes from an infectious disease physician-guided evaluation of hospitalized persons under investigation for coronavirus disease 2019 (COVID-19) at a large US academic medical center
Authors: Dugdale Caitlin M. , Turbett Sarah E. , McCluskey Suzanne M. , Zachary Kimon C. , Shenoy Erica S. , Ciaranello Andrea L. , Walensky Rochelle P. , Rosenberg Eric S. , Anahtar Melis N. , Hooper David C. , Hyle Emily P.
Published: August 2020

We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.
Misvaluation and Corporate Inventiveness
Authors: Dong Ming , Hirshleifer David , Teoh Siew Hong
Published: August 2020

We test how market overvaluation affects corporate innovation. Estimated stock overvaluation is strongly associated with measures of innovative inventiveness (novelty, originality, and scope), as well as research and development (R&D) and innovative output (patent and citation counts). Misvaluation affects R&D more via a nonequity channel than via equity issuance. The sensitivity of innovative inventiveness to misvaluation increases with share turnover and overvaluation. The frequency of exceptionally high innovative inputs/outputs increases with overvaluation. This evidence suggests that market overvaluation may generate social value by increasing innovative output and encouraging firms to engage in “moon shots.”
Prolonged intra-operative thermal exposure in endoscopic ear surgery: is it really safe?
Authors: Das A , Mitra S , Agarwal P , Sengupta A
Published: August 2020

Objective

The aim of this study was to assess change in temperature, audiometric outcomes and post-operative complications following exposure to different light sources during endoscopic ear surgery.

Method

A total of 64 patients diagnosed with chronic otitis media with central perforation and pure conductive hearing loss underwent endoscopic type 1 tympanoplasty. The patients were randomised into two groups based on the light source used: xenon or light-emitting diode. Temperature was measured using a K type thermocouple at the promontory and round window niche. Mean temperature change with respect to operating time, mean audiometric change, incidence of vomiting in the first 24 hours, vertigo and tinnitus at the end of the first week were observed.

Results

Mean temperature change showed a statistically significant difference with increasing length of operating time with the xenon light source and when the two light sources were compared for a particular time interval. Mean audiometric change showed statistically significant deterioration at higher frequencies (4, 6 and 8 kHz) with the xenon light source but only at 8 kHz for the light emitting diode source. When the mean audiometric change was compared between light sources for a particular frequency, statistical significance was found at 4, 6 and 8 kHz. Post-operative complications were vomiting, vertigo and tinnitus (p-values of 0.042, 0.099 and 0.147, respectively, between two groups).

Conclusion

Light emitting diodes are associated with less significant middle-ear temperature rises and audiometric changes at higher frequencies when compared to xenon light sources. Hence, xenon should be replaced with cooler light sources.
Livestock ownership and anaemia in Sub-Saharan African households
Authors: Acharya Yubraj , Yang Di , Jones Andrew D
Published: August 2020

Objective:

To determine the association between livestock ownership and Hb concentration of women of child-bearing age (WCBA) and preschool-aged children in Sub-Saharan Africa (SSA).

Design:

A prospective analysis of publicly available cross-sectional data, using linear and logistic regressions controlling for potential confounders.

Setting:

Twenty-eight countries in SSA.

Participants:

162 305 WCBA and 118 607 children aged 6–59 months.

Results:

More than half of WCBA (62·5 %) and children (58 %) belonged to households that owned livestock. The average altitude-adjusted blood Hb concentration for WCBA and children was 12.23 and 10·24 g/dL, respectively. In adjusted models, higher number of livestock owned was associated with lower Hb concentration for children but not for WCBA. The magnitude of the association for children was small, with one additional unit of livestock owned reducing Hb concentration by 0·001 g/dL. Higher numbers of cattle, cows and bulls, sheep, and goats were associated with lower Hb concentration for both groups. The number of certain categories of livestock owned was associated with the consumption of relevant foods by children. There was no association between the consumption of animal-source foods and Hb concentration or between livestock ownership and diarrhoeal diseases or fever among children.

Conclusions:

Livestock ownership in SSA had a net negative association with the Hb concentration of children and no association with that of WCBA. The results highlight the need for research aimed at clarifying the mechanisms linking livestock ownership and nutritional status, and identifying entry points for leveraging livestock ownership to improve the health of women and children in SSA.
Contact inequality: first contact will likely be with an older civilization
Authors: Kipping David , Frank Adam , Scharf Caleb
Published: August 2020

First contact with another civilization, or simply another intelligence of some kind, will likely be quite different depending on whether that intelligence is more or less advanced than ourselves. If we assume that the lifetime distribution of intelligences follows an approximately exponential distribution, one might naively assume that the pile-up of short-lived entities dominates any detection or contact scenario. However, it is argued here that the probability of contact is proportional to the age of said intelligence (or possibly stronger), which introduces a selection effect. We demonstrate that detected intelligences will have a mean age twice that of the underlying (detected + undetected) population, using the exponential model. We find that our first contact will most likely be with an older intelligence, provided that the maximum allowed mean lifetime of the intelligence population, τmax, is ≥ e times larger than our own. Older intelligences may be rare but they disproportionately contribute to first contacts, introducing what we call a ‘contact inequality’, analogous to wealth inequality. This reasoning formalizes intuitional arguments and highlights that first contact would likely be one-sided, with ramifications for how we approach SETI.
A practical support vector regression algorithm and kernel function for attritional general insurance loss estimation
Authors: Kwasa Shadrack , Jones Daniel
Published: August 2020

The aim of the paper is to derive a simple, implementable machine learning method for general insurance losses. An algorithm for learning a general insurance loss triangle is developed and justified. An argument is made for applying support vector regression (SVR) to this learning task (in order to facilitate transparency of the learning method as compared to more “black-box” methods such as deep neural networks), and SVR methodology derived is specifically applied to this learning task. A further argument for preserving the statistical features of the loss data in the SVR machine is made. A bespoke kernel function that preserves the statistical features of the loss data is derived from first principles and called the exponential dispersion family (EDF) kernel. Features of the EDF kernel are explored, and the kernel is applied to an insurance loss estimation exercise for homogeneous risk of three different insurers. Results of the cumulative losses and ultimate losses predicted by the EDF kernel are compared to losses predicted by the radial basis function kernel and the chain-ladder method. A backtest of the developed method is performed. A discussion of the results and their implications follows.
Marine Sediment Characterized by Ocean‐Bottom Fiber‐Optic Seismology
Authors: Spica Zack J. , Nishida Kiwamu , Akuhara Takeshi , Pétrélis François , Shinohara Masanao , Yamada Tomoaki
Published: August 2020

The Sanriku ocean‐bottom seismometer system uses an optical fiber cable to guarantee real‐time observations at the seafloor. A dark fiber connected to a Distributed Acoustic Sensing (DAS) interrogator converted the cable in an array of 19,000 seismic sensors. We use these measurements to constrain the velocity structure under a section of the cable. Our analysis relies on 24 hr of ambient seismic field recordings. We obtain a high‐resolution 2‐D shear‐wave velocity profile by inverting multimode dispersion curves extracted from frequency‐wave number analysis. We also produce a reflection image from autocorrelations of ambient seismic field, highlighting strong impedance contrasts at the interface between the sedimentary layers and the basement. In addition, earthquake wavefield analysis and modeling help to further constrain the sediment properties under the cable. Our results show for the first time that ocean‐bottom DAS can produce detailed images of the subsurface, opening new opportunities for cost‐effective ocean‐bottom imaging in the future.
Spatial and Temporal Development of Incipient Dunes
Authors: Gadal C. , Narteau C. , Ewing R. C. , Gunn A. , Jerolmack D. , Andreotti B. , Claudin P.
Published: August 2020

In zones of loose sand, wind‐blown sand dunes emerge due the linear instability of a flat sedimentary bed. This instability has been studied in experiments and numerical models but rarely in the field, due to the large time and length scales involved. We examine dune formation at the upwind margin of the White Sands Dune Field in New Mexico (USA), using 4 years of lidar topographic data to follow the spatial and temporal development of incipient dunes. Data quantify dune wavelength, growth rate, and propagation velocity and also the characteristic length scale associated with the growth process. We show that all these measurements are in quantitative agreement with predictions from linear stability analysis. This validation makes it possible to use the theory to reliably interpret dune‐pattern characteristics and provide quantitative constraints on associated wind regimes and sediment properties, where direct local measurements are not available or feasible.
Estimation of the Electron Density From Spacecraft Potential During High‐Frequency Electric Field Fluctuations
Authors: Roberts O. W. , Nakamura R. , Torkar K. , Graham D. B. , Gershman D. J. , Holmes J. C. , Varsani A. , Escoubet C. P. , Vörös Z. , Wellenzohn S. , Khotyaintsev Y. , Ergun R. E. , Giles B. L.
Published: August 2020

Spacecraft potential has often been used to infer electron density with much higher time resolution than is typically possible with plasma instruments. However, recently, two studies by Torkar et al. (2017, https://doi.org/10.1002/2017JA024724) and Graham, Vaivads, Khotyaintsev, Eriksson, et al. (2018, https://doi.org/10.1029/2018JA025874) have shown that external electric fields can also have an effect on the spacecraft potential by enhancing photoelectron escape from the surface. Consequently, should the electron density derived from the spacecraft potential be used during an event with a large electric field, the estimation would be contaminated and the user would see the effects of the electric field rather than density perturbations. The goal of this paper is to propose a method to remove the electric field effects to allow the density derived from spacecraft potential to be used even during large‐amplitude wave events such as Langmuir waves or upper hybrid waves.
Are Sporadic Plasma Layers at 90 km in the Mars Ionosphere Produced by Solar Energetic Particle Events
Authors: Withers Paul
Published: August 2020

Layers of dayside ionospheric plasma have been sporadically observed on Mars at 90 km altitude. Several causes for these layers have been proposed. Here we test the hypothesis that solar energetic particle (SEP) events produce these layers. Several independent lines of evidence show that SEP events do increase plasma densities at low altitudes. We compare the occurrence of low‐altitude plasma layers to a proxy for the flux of solar energetic particles at Mars. For the ionospheric layers, we use 71 instances of low‐altitude plasma layers found in 5,600 electron density profiles acquired by Mars Global Surveyor. For the proxy for solar energetic particle flux, we use the flux recorded in the highest energy channel of the Mars Global Surveyor Electron Reflectometer. We find that these low‐altitude plasma layers are not significantly more likely to occur during SEP events.
Decoupled Spatial Distribution of PAHs Degraders Determined by Taxonomic 16S rRNA and Degrading Genes Across Chinese Forest Soils
Authors: Jiang Longfei , Song Mengke , Luo Chunling , Zhang Dayi , Sun Yingtao , Li Jun , Ostle Nicholas J. , Zhang Gan
Published: August 2020

Knowing the structure and distribution of microbial communities and the underlying mechanisms shaping microbial geographic patterns is crucial for soil ecology and biogeochemical cycles of elements. Studies have explored the diversity, composition, and distribution of whole microbial communities based on taxonomic (16S rRNA) genes in many habitats. However, it is unclear whether the active microbes characterized by other genetic elements are driven by the same environmental variables and follow similar distribution patterns owing to technical limits on identifying the active functional genes in complex communities. Here, we employed ubiquitous phenanthrene as a model compound and applied DNA‐stable isotope probing to investigate the active phenanthrene degraders by 16S rRNA genes and phenanthrene‐degrading genes in forest soils. The effects of environmental variables and geographic distance on the diversity and composition of both genetic elements were examined. The diversity and similarity of whole microbial communities was closely linked with the total phenanthrene‐degrading genes. However, the abundance and diversity of the active phenanthrene‐degrading genes mismatched those of the active 16S rRNA genes, suggesting their distinct responses to environment variables and geographic distance. Geographic distance had a strong effect on the active phenanthrene‐degrading community identified by taxonomic genes but not the active phenanthrene‐degrading genes. Dispersal and mutation might explain the decoupled biogeographic patterns between the active taxonomic 16S rRNA and phenanthrene‐degrading genes. This study provides new insights into the different driving forces for the active functional microbes characterized by various genetic elements, implying the diverse evolutionary mechanisms between functional genetic elements and 16S rRNA genes.
Methane and Primary Productivity in Lakes: Divergence of Temporal and Spatial Relationships
Authors: Bertolet B. L. , Olson C. R. , Szydlowski D. K. , Solomon C. T. , Jones S. E.
Published: August 2020

In lakes, the production and emission of methane (CH4) have been linked to lake trophic status. However, few studies have quantified the temporal response of lake CH4 dynamics to primary productivity at the ecosystem scale or considered how the response may vary across lakes. Here, we investigate relationships between lake CH4 dynamics and ecosystem primary productivity across both space and time using data from five lakes in northern Wisconsin, USA. From 2014 to 2019, we estimated hypolimnetic CH4 storage rates for each lake using timeseries of hypolimnetic CH4 concentration through the summer season. Across all lakes and years, hypolimnetic CH4 storage ranged from <0.001 to 7.6 mmol CH4 m−2 d−1 and was positively related to the mean summer rate of gross primary productivity (GPP). However, within‐lake temporal responses to GPP diverged from the spatial relationship, and GPP was not a significant predictor of interannual variability in CH4 storage at the lake scale. Using these data, we consider how and why temporal responses may differ from spatial patterns and demonstrate how extrapolating cross‐lake relationships for prediction at the lake scale may substantially overestimate the rate of change of CH4 dynamics in response to lake primary productivity. We conclude that future predictions of lake‐mediated climate feedbacks in response to a shifting distribution of trophic status should incorporate both varying lake responses and the temporal scale of change.
EEG microstates as biomarker for psychosis in ultra-high-risk patients
Authors: de Bock Renate , Mackintosh Amatya J. , Maier Franziska , Borgwardt Stefan , Riecher-Rössler Anita , Andreou Christina
Published: August 2020

Resting-state EEG microstates are brief (50–100 ms) periods, in which the spatial configuration of scalp global field power remains quasi-stable before rapidly shifting to another configuration. Changes in microstate parameters have been described in patients with psychotic disorders. These changes have also been observed in individuals with a clinical or genetic high risk, suggesting potential usefulness of EEG microstates as a biomarker for psychotic disorders. The present study aimed to investigate the potential of EEG microstates as biomarkers for psychotic disorders and future transition to psychosis in patients at ultra-high-risk (UHR). We used 19-channel clinical EEG recordings and orthogonal contrasts to compare temporal parameters of four normative microstate classes (A–D) between patients with first-episode psychosis (FEP; n = 29), UHR patients with (UHR-T; n = 20) and without (UHR-NT; n = 34) later transition to psychosis, and healthy controls (HC; n = 25). Microstate A was increased in patients (FEP & UHR-T & UHR-NT) compared to HC, suggesting an unspecific state biomarker of general psychopathology. Microstate B displayed a decrease in FEP compared to both UHR patient groups, and thus may represent a state biomarker specific to psychotic illness progression. Microstate D was significantly decreased in UHR-T compared to UHR-NT, suggesting its potential as a selective biomarker of future transition in UHR patients.
Germline HOXB13 G84E mutation carriers and risk to twenty common types of cancer: results from the UK Biobank
Authors: Wei Jun , Shi Zhuqing , Na Rong , Wang Chi-Hsiung , Resurreccion W. Kyle , Zheng S. Lilly , Hulick Peter J. , Cooney Kathleen A. , Helfand Brian T. , Isaacs William B. , Xu Jianfeng
Published: August 2020

Germline HOXB13 G84E mutation has been consistently associated with prostate cancer (PCa) risk, but its association with other cancers is controversial. We systematically tested its association with the 20 most common cancer types in subjects from the UK Biobank. The G84E mutation was found in 1,545 (0.34%) of 460,224 participants of European ancestry. While mutation status did not associate with cancer risk in females, it was significantly associated with increased risk in males; odds ratio (OR) (95% confidence interval) for overall cancer diagnosis was 2.19 (1.89–2.52), P = 2.5E-19. The association remained after excluding PCa; OR = 1.4 (1.16–1.68), P = 0.003, suggesting association with other cancers. Indeed, suggestive novel associations were found for two other cancer types; rectosigmoid cancer, OR = 2.25 (1.05–4.15), P = 0.05 and non-melanoma skin cancer (NMSC), OR = 1.40 (1.12–1.74), P = 0.01. For NMSC, the association was found only in basal cell carcinoma, OR = 1.37 (1.07–1.74), P = 0.03. These findings have potential clinical utility for genetic counselling regarding HOXB13.
Antisense oligonucleotides targeting lncRNA AC104041.1 induces antitumor activity through Wnt2B/β-catenin pathway in head and neck squamous cell carcinomas
Authors: Li Mengwei , Ding Xu , Zhang Yinan , Li Xin , Zhou Haoze , Yang Li , Li Yilin , Yang Peiwei , Zhang Xiaomin , Hu Jialiang , Nice Edouard , Wu Heming , Xu Hanmei
Published: August 2020

Long non-coding RNAs (lncRNAs) contribute to the initiation and progression of various tumors, including head and neck squamous carcinoma (HNSCC), which is a common malignancy with high morbidity and low survival rate. However, the mechanism of lncRNAs in HNSCC tumorigenesis remains largely unexplored. In this work, we identified a novel lncRNA AC104041.1 which is highly upregulated and correlated with poor survival in HNSCC patients. Moreover, AC104041.1 overexpression significantly promoted tumor growth and metastasis of HNSCC in vitro and in vivo. Mechanistically, AC104041.1 mainly located in the cytoplasm and could function as ceRNA (competing endogenous RNA) for miR-6817-3p, thereby stabilized Wnt2B, and consequently inducing β-catenin nuclear translocation and activation. Moreover, we demonstrate that salinomycin, which as a highly effective antibiotic in the elimination of cancer stem cells through the Wnt/β-catenin signaling, could enhance the inhibition of tumor growth by antisense oligonucleotides (ASO) targeting AC104041.1 in HNSCC cells and PDXs (patient-derived xenograft) model. Thus, our data provide preclinical evidence to support a novel strategy of ASOs targeting AC104041.1 in combination with salinomycin and may as a beneficial treatment approach for HNSCC.
Propofol-induced MiR-20b expression initiates endogenous cellular signal changes mitigating hypoxia/re-oxygenation-induced endothelial autophagy in vitro
Authors: Lu Yue , Wang Sijie , Cai Shuyun , Gu Xiaoxia , Wang Jingjing , Yang Yue , Hu Zhe , Zhang Xihe , Ye Yongcai , Shen Siman , Joshi Kiran , Ma Daqing , Zhang Liangqing
Published: August 2020

Certain miRNAs can attenuate hypoxia/re-oxygenation-induced autophagic cell death reported in our previous studies, but how these miRNAs regulate the autophagy-related cellular signaling pathway in preventing cell death is largely unknown. In the current study, the autophagy-related miRNAs of hsa-miR-20b were investigated in an in vitro model of hypoxia/re-oxygenation-induced endothelial autophagic cell death. Of these, miR-20b was found to be the most important miRNA which targeted on the key autophagy kinase ULK1 and inhibited hypoxia/re-oxygenation injury-induced autophagy by decreasing both autophagosomes and LC3I to II transition rate and P62 degradation. These processes were reversed by the transfection of an miR-20b inhibitor. Re-expression of ULK1 restores miR-20b-inhibited autophagy. Propofol, a commonly used anesthetic, promoted miR-20b and METTL3 expression and attenuated endothelial autophagic cell death. The inhibited endogenous expression of miR-20b or silenced METTL3 diminished the protective effect of propofol and accentuated autophagy. Additionally, METTL3 knockdown significantly inhibited miR-20b expression but up-regulated pri-miR-20b expression. Together, our data shows that propofol protects against endothelial autophagic cell death induced by hypoxia/re-oxygenation injury, associated with activation of METTL3/miR-20b/ULK1 cellular signaling.
LncRNA SNAI3-AS1 promotes PEG10-mediated proliferation and metastasis via decoying of miR-27a-3p and miR-34a-5p in hepatocellular carcinoma
Authors: Li Yarui , Guo Dan , Lu Guifang , Mohiuddin Chowdhury Abu Taiub Mohammed , Zhang Dan , Ren Mudan , Chen Yifei , Wang Ruhua , He Shuixiang
Published: August 2020

During recent years, long noncoding RNAs (lncRNAs) have received focal attention due to their important function in cancer regulation. Though the relation between lncRNA SNAI3-AS1 and the development of hepatocellular carcinoma (HCC) has been described in our previous study, the role and the exact mechanism of SNAI3-AS1 are still unclear. In this study, qRT-PCR analysis revealed that the expression of SNAI3-AS1 was elevated and was correlated with the levels of PEG10 in HCC tissues. Through functional experiments, we determined that knockdown of SNAI3-AS1 and PEG10 inhibited the proliferation and metastasis, whereas overexpression of SNAI3-AS1 and PEG10 promoted the proliferation and metastasis of HCC cells. In addition, rescue experiments confirmed that upregulation of PEG10 partially restored cell function inhibition induced by SNAI3-AS1 knockdown. Therefore, we hypothesized that PEG10 may be regulated by SNAI3-AS1, which in turn mediates the malignant biological processes of HCC cells regulated by PEG10. Further bioinformatics analysis and mechanistic experiments showed that SNAI3-AS1 functions as a competing endogenous RNA (ceRNA) to activate PEG10 by acting as a sponge for miR-27-3p and miR-34a-5p. In summary, our study revealed that SNAI3-AS1 is a tumor regulator of PEG10 in the progression of HCC, and may contribute to the improvement of HCC diagnosis and therapy.
PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury
Authors: Yu Fei , Zhang Weijie , Yan Chenxi , Yan Dan , Zhou Meng , Chen Junzhao , Zhao Xiangteng , Zhu Aoxue , Zhou Jie , Liu Huiqing , Sun Hao , Fu Yao
Published: August 2020

Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits corneal endothelial defects. However, the effects of PAX6 protein involved in corneal endothelial wound process are still unknown. Here, we found the upregulated protein levels of PAX6 in human corneal endothelial monolayer after injury; the expression of PAX6 also increased in murine and rat corneal endothelium injury models. Enforced PAX6 expression could alleviate the damages to CECs via regulating permeability by prompting cellular tight junction. In addition, SUMOylation mainly happened on both K53 and K89 residues of 48-kD PAX6 (the longest and main isoform expressed in cornea), and de-SUMOylation promoted the stability of PAX6 protein in vitro. In CECs of SENP1+/−mice, increased SUMOylation levels leading to instability and low expression of PAX6, delayed the repair of CECs after injury. Furthermore, overexpression of PAX6 accelerated the rate of corneal endothelial repair of SENP1+/−mice. Our findings indicate that SENP1-mediated de-SUMOylation improving the stability of PAX6, amplifies the protective effects of PAX6 on corneal endothelial injuries, highlighting potentials of PAX6 and/or SUMOylation to be used as a treatment target for corneal endothelial disorders.
Correction: LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway
Authors: Wang Tianfu , Hao Zhiyu , Liu Changcheng , Yuan Lebin , Li Li , Yin Menghong , Li Qing , Qi Zhiming , Wang Zi
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Correction: Intestinal vitamin D receptor knockout protects from oxazolone-induced colitis
Authors: Shi Yongyan , Liu Ziyun , Cui Xuewei , Zhao Qun , Liu Tianjing
Published: August 2020

The original version of this Article contained an error in the author affiliations. The affiliation of Tianjing Liu with Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China was inadvertently omitted. This has now been corrected in both the PDF and HTML versions.
Correction: Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways
Authors: Duan Chenyang , Kuang Lei , Xiang Xinming , Zhang Jie , Zhu Yu , Wu Yue , Yan Qingguang , Liu Liangming , Li Tao
Published: August 2020

The original version of this Article omitted the following from the Acknowledgements: “This work was supported by the National Natural Science foundation of China (No. 81700429) and the Key Program of the National Natural Science Foundation of China (No. 81730059).” This has now been corrected in both the PDF and HTML versions of the Article.
Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate
Authors: Pandey Akhilesh , Stawiski Eric W. , Durinck Steffen , Gowda Harsha , Goldstein Leonard D. , Barbhuiya Mustafa A. , Schröder Markus S. , Sreenivasamurthy Sreelakshmi K. , Kim Sun-Whe , Phalke Sameer , Suryamohan Kushal , Lee Kayla , Chakraborty Papia , Kode Vasumathi , Shi Xiaoshan , Chatterjee Aditi , Datta Keshava , Khan Aafaque A. , Subbannayya Tejaswini , Wang Jing , Chaudhuri Subhra , Gupta Sanjiv , Shrivastav Braj Raj , Jaiswal Bijay S. , Poojary Satish S. , Bhunia Shushruta , Garcia Patricia , Bizama Carolina , Rosa Lorena , Kwon Wooil , Kim Hongbeom , Han Youngmin , Yadav Thakur Deen , Ramprasad Vedam L. , Chaudhuri Amitabha , Modrusan Zora , Roa Juan Carlos , Tiwari Pramod Kumar , Jang Jin-Young , Seshagiri Somasekar
Published: August 2020

Gallbladder cancer (GBC) is an aggressive gastrointestinal malignancy with no approved targeted therapy. Here, we analyze exomes (n = 160), transcriptomes (n = 115), and low pass whole genomes (n = 146) from 167 gallbladder cancers (GBCs) from patients in Korea, India and Chile. In addition, we also sequence samples from 39 GBC high-risk patients and detect evidence of early cancer-related genomic lesions. Among the several significantly mutated genes not previously linked to GBC are ETS domain genes ELF3 and EHF, CTNNB1, APC, NSD1, KAT8, STK11 and NFE2L2. A majority of ELF3 alterations are frame-shift mutations that result in several cancer-specific neoantigens that activate T-cells indicating that they are cancer vaccine candidates. In addition, we identify recurrent alterations in KEAP1/NFE2L2 and WNT pathway in GBC. Taken together, these define multiple targetable therapeutic interventions opportunities for GBC treatment and management.
Gamma-ray flares from relativistic magnetic reconnection in the jet of the quasar 3C 279
Authors: Shukla A. , Mannheim K.
Published: August 2020

Spinning black holes in the centres of galaxies can release powerful magnetised jets. When the jets are observed at angles of less than a few degrees to the line-of-sight, they are called blazars, showing variable non-thermal emission across the electromagnetic spectrum from radio waves to gamma rays. It is commonly believed that shock waves are responsible for this dissipation of jet energy. Here we show that gamma-ray observations of the blazar 3C 279 with the space-borne telescope Fermi-LAT reveal a characteristic peak-in-peak variability pattern on time scales of minutes expected if the particle acceleration is instead due to relativistic magnetic reconnection. The absence of gamma-ray pair attenuation shows that particle acceleration takes place at a distance of ten thousand gravitational radii from the black hole where the fluid dynamical kink instability drives plasma turbulence.
Unique universal scaling in nanoindentation pop-ins
Authors: Sato Yuji , Shinzato Shuhei , Ohmura Takahito , Hatano Takahiro , Ogata Shigenobu
Published: August 2020

Power laws are omnipresent and actively studied in many scientific fields, including plasticity of materials. Here, we report the power-law statistics in the second and subsequent pop-in magnitudes during load-controlled nanoindentation testing, whereas the first pop-in is characterized by Gaussian-like statistics with a well-defined average value. The transition from Gaussian-like to power-law is due to the change in the deformation mechanism from dislocation nucleation to dislocation network evolution in the sharp-indenter induced abruptly decaying stress and dislocation density fields. Based on nanoindentation testing on the (100) and (111) surfaces of body-centered cubic (BCC) iron and the (100) surface of face-centered cubic (FCC) copper, the scaling exponents of the power laws were determined to be 5.6, 3.9, and 6.4, respectively. These power-law exponents are much higher than those typically observed in micro-pillar plasticity (1.0–1.8), suggesting that the nanoindentation plasticity belongs to a different universality class than the micro-pillar plasticity.
End of Green Sahara amplified mid- to late Holocene megadroughts in mainland Southeast Asia
Authors: Griffiths Michael L. , Johnson Kathleen R. , Pausata Francesco S. R. , White Joyce C. , Henderson Gideon M. , Wood Christopher T. , Yang Hongying , Ersek Vasile , Conrad Cyler , Sekhon Natasha
Published: August 2020

Between 5 and 4 thousand years ago, crippling megadroughts led to the disruption of ancient civilizations across parts of Africa and Asia, yet the extent of these climate extremes in mainland Southeast Asia (MSEA) has never been defined. This is despite archeological evidence showing a shift in human settlement patterns across the region during this period. We report evidence from stalagmite climate records indicating a major decrease of monsoon rainfall in MSEA during the mid- to late Holocene, coincident with African monsoon failure during the end of the Green Sahara. Through a set of modeling experiments, we show that reduced vegetation and increased dust loads during the Green Sahara termination shifted the Walker circulation eastward and cooled the Indian Ocean, causing a reduction in monsoon rainfall in MSEA. Our results indicate that vegetation-dust climate feedbacks from Sahara drying may have been the catalyst for societal shifts in MSEA via ocean-atmospheric teleconnections.
Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates
Authors: Faure Louis , Wang Yiqiao , Kastriti Maria Eleni , Fontanet Paula , Cheung Kylie K. Y. , Petitpré Charles , Wu Haohao , Sun Lynn Linyu , Runge Karen , Croci Laura , Landy Mark A. , Lai Helen C. , Consalez Gian Giacomo , de Chevigny Antoine , Lallemend François , Adameyko Igor , Hadjab Saida
Published: August 2020

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.
T cell exhaustion and a failure in antigen presentation drive resistance to the graft-versus-leukemia effect
Authors: Zhou Meng , Sacirbegovic Faruk , Zhao Kai , Rosenberger Sarah , Shlomchik Warren D.
Published: August 2020

In hematopoietic cell transplants, alloreactive T cells mediate the graft-versus-leukemia (GVL) effect. However, leukemia relapse accounts for nearly half of deaths. Understanding GVL failure requires a system in which GVL-inducing T cells can be tracked. We used such a model wherein GVL is exclusively mediated by T cells that recognize the minor histocompatibility antigen H60. Here we report that GVL fails due to insufficient H60 presentation and T cell exhaustion. Leukemia-derived H60 is inefficiently cross-presented whereas direct T cell recognition of leukemia cells intensifies exhaustion. The anti-H60 response is augmented by H60-vaccination, an agonist αCD40 antibody (FGK45), and leukemia apoptosis. T cell exhaustion is marked by inhibitory molecule upregulation and the development of TOX+and CD39−TCF-1+cells. PD-1 blockade diminishes exhaustion and improves GVL, while blockade of Tim-3, TIGIT or LAG3 is ineffective. Of all interventions, FGK45 administration at the time of transplant is the most effective at improving memory and naïve T cell anti-H60 responses and GVL. Our studies define important causes of GVL failure and suggest strategies to overcome them.
High-temperature-resistant silicon-polymer hybrid modulator operating at up to 200 Gbit s−1 for energy-efficient datacentres and harsh-environment applications
Authors: Lu Guo-Wei , Hong Jianxun , Qiu Feng , Spring Andrew M. , Kashino Tsubasa , Oshima Juro , Ozawa Masa-aki , Nawata Hideyuki , Yokoyama Shiyoshi
Published: August 2020

To reduce the ever-increasing energy consumption in datacenters, one of the effective approaches is to increase the ambient temperature, thus lowering the energy consumed in the cooling systems. However, this entails more stringent requirements for the reliability and durability of the optoelectronic components. Herein, we fabricate and demonstrate silicon-polymer hybrid modulators which support ultra-fast single-lane data rates up to 200 gigabits per second, and meanwhile feature excellent reliability with an exceptional signal fidelity retained at extremely-high ambient temperatures up to 110 °C and even after long-term exposure to high temperatures. This is achieved by taking advantage of the high electro-optic (EO) activities (in-devicen3r33 = 1021 pm V−1), low dielectric constant, low propagation loss (α, 0.22 dB mm−1), and ultra-high glass transition temperature (Tg, 172 °C) of the developed side-chain EO polymers. The presented modulator simultaneously fulfils the requirements of bandwidth, EO efficiency, and thermal stability for EO modulators. It could provide ultra-fast and reliable interconnects for energy-hungry and harsh-environment applications such as datacentres, 5G/B5G, autonomous driving, and aviation systems, effectively addressing the energy consumption issue for the next-generation optical communication.
Molecular basis for DNA repair synthesis on short gaps by mycobacterial Primase-Polymerase C
Authors: Brissett Nigel C. , Zabrady Katerina , Płociński Przemysław , Bianchi Julie , Korycka-Machała Małgorzata , Brzostek Anna , Dziadek Jarosław , Doherty Aidan J.
Published: August 2020

Cells utilise specialized polymerases from the Primase-Polymerase (Prim-Pol) superfamily to maintain genome stability. Prim-Pol’s function in genome maintenance pathways including replication, repair and damage tolerance. Mycobacteria contain multiple Prim-Pols required for lesion repair, including Prim-PolC that performs short gap repair synthesis during excision repair. To understand the molecular basis of Prim-PolC’s gap recognition and synthesis activities, we elucidated crystal structures of pre- and post-catalytic complexes bound to gapped DNA substrates. These intermediates explain its binding preference for short gaps and reveal a distinctive modus operandi called Synthesis-dependent Template Displacement (STD). This mechanism enables Prim-PolC to couple primer extension with template base dislocation, ensuring that the unpaired templating bases in the gap are ushered into the active site in an ordered manner. Insights provided by these structures establishes the molecular basis of Prim-PolC’s gap recognition and extension activities, while also illuminating the mechanisms of primer extension utilised by closely related Prim-Pols.
Ecological uncertainty favours the diversification of host use in avian brood parasites
Authors: Antonson Nicholas D. , Rubenstein Dustin R. , Hauber Mark E. , Botero Carlos A.
Published: August 2020

Adaptive responses to ecological uncertainty may affect the dynamics of interspecific interactions and shape the course of evolution within symbioses. Obligate avian brood parasites provide a particularly tractable system for understanding how uncertainty, driven by environmental variability and symbiont phenology, influences the evolution of species interactions. Here, we use phylogenetically-informed analyses and a comprehensive dataset on the behaviour and geographic distribution of obligate avian brood parasites and their hosts to demonstrate that increasing uncertainty in thermoregulation and parental investment of parasitic young are positively associated with host richness and diversity. Our findings are consistent with the theoretical expectation that ecological risks and environmental unpredictability should favour the evolution of bet-hedging. Additionally, these highly consistent patterns highlight the important role that ecological uncertainty is likely to play in shaping the evolution of specialisation and generalism in complex interspecific relationships.
Transparent near-infrared perovskite light-emitting diodes
Authors: Xie Chenchao , Zhao Xiaofei , Ong Evon Woan Yuann , Tan Zhi-Kuang
Published: August 2020

Mobile and wearable devices are increasingly reliant on near-infrared (NIR) covert illumination for facial recognition, eye-tracking or motion and depth sensing functions. However, these small devices offer limited spatial real estate that is typically already occupied by their full-area electronic color displays. Here, we report a transparent perovskite light-emitting diode (LED) that could be overlaid across a color display to provide an efficient and high-intensity NIR illumination. Our transparent devices are constructed with an ITO/AZO/PEIE/FAPbI3/poly-TPD/MoO3/Al/ITO/Ag/ITO architecture, and offer a high average transmittance of more than 55% across the visible spectral region. In particular, our Al/ITO/Ag/ITO top transparent electrode was designed to offer a combination low sheet resistance and low plasma damage upon electrode deposition. The devices emit at 799 nm with a high total external quantum efficiency of 5.7% at a current density of 5.3 mA cm−2 and a high radiance of 1.5 W sr−1 m−2, and possess a large functional device area of 120 mm2. The efficient performance is ideal for battery-powered wearable devices, and could enable advanced security and sensing features on future smart-watches, phones, gaming consoles and augmented or virtual reality headsets.
Causal analysis of competing atomistic mechanisms in ferroelectric materials from high-resolution scanning transmission electron microscopy data
Authors: Ziatdinov Maxim , Nelson Christopher T. , Zhang Xiaohang , Vasudevan Rama K. , Eliseev Eugene , Morozovska Anna N. , Takeuchi Ichiro , Kalinin Sergei V.
Published: August 2020

Machine learning has emerged as a powerful tool for the analysis of mesoscopic and atomically resolved images and spectroscopy in electron and scanning probe microscopy, with the applications ranging from feature extraction to information compression and elucidation of relevant order parameters to inversion of imaging data to reconstruct structural models. However, the fundamental limitation of machine learning methods is their correlative nature, leading to extreme susceptibility to confounding factors. Here, we implement the workflow for causal analysis of structural scanning transmission electron microscopy (STEM) data and explore the interplay between physical and chemical effects in a ferroelectric perovskite across the ferroelectric–antiferroelectric phase transitions. The combinatorial library of the Sm-doped BiFeO3 is grown to cover the composition range from pure ferroelectric BFO to orthorhombic 20% Sm-doped BFO. Atomically resolved STEM images are acquired for selected compositions and are used to create a set of local compositional, structural, and polarization field descriptors. The information-geometric causal inference (IGCI) and additive noise model (ANM) analysis are used to establish the pairwise causal directions between the descriptors, ordering the data set in the causal direction. The causal chain for IGCI and ANM across the composition is compared and suggests the presence of common causal mechanisms across the composition series. Ultimately, we believe that the causal analysis of the multimodal data will allow exploring the causal links between multiple competing mechanisms that control the emergence of unique functionalities of morphotropic materials and ferroelectric relaxors.