bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidental pulmonary embolism in patients with cancer: prevalence, underdiagnosis and evaluation of an AI algorithm for automatic detection of pulmonary embolism
Authors: Wiklund Peder , Medson Koshiar , Elf Johan
Published: August 2022

Objectives

To assess the prevalence of reported and unreported incidental pulmonary embolism (iPE) in patients with cancer, and to evaluate an artificial intelligence (AI) algorithm for automatic detection of iPE.

Methods

Retrospective cohort study on patients with cancer with an elective CT study including the chest between 2018-07-01 and 2019-06-30. All study reports and images were reviewed to identify reported and unreported iPE and were processed by the AI algorithm.

Results

One thousand sixty-nine patients (1892 studies) were included. Per study, iPE was present in 75 studies (4.0%), of which 16 (21.3%) were reported. Unreported iPE had a significantly lower number of involved vessels compared to reported iPE, with a median of 2 (interquartile range, IQR, 1–4) versus 5 (IQR 3–9.75), p < 0.001. There were no significant differences in age, cancer type, or attenuation of the main pulmonary artery. The AI algorithm correctly identified 68 of 75 iPE, with 3 false positives (sensitivity 90.7%, specificity 99.8%, PPV 95.6%, NPV 99.6%). False negatives occurred in cases with 1–3 involved vessels. Of the unreported iPE, 32/59 (54.2%) were proximal to the subsegmental arteries.

Conclusion

In patients with cancer, the prevalence of iPE was 4.0%, of which only 21% were reported. Greater than 50% of unreported iPE were proximal to the subsegmental arteries. The AI algorithm had a very high sensitivity and specificity with only three false positives, with the potential to increase the detection rate of iPE.

Key Points

• In a retrospective single-center study on patients with cancer, unreported iPE were common, with the majority lying proximal to the subsegmental arteries.

• The evaluated AI algorithm had a very high sensitivity and specificity, so has the potential to increase the detection rate of iPE.
Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes
Authors: Piona Claudia , Costantini Silvia , Zusi Chiara , Cozzini Tiziano , Pedrotti Emilio , Marigliano Marco , Fornari Elena , Maguolo Alice , Morandi Anita , Maffeis Claudio
Published: August 2022

Background

Early ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs.

Aims

To determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D.

Methods

A total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype–phenotype association analysis were performed.

Results

The C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and − 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and − 0.286, respectively).

Conclusions

These results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.
Factors associated with re-admission in the year after acute postpartum psychiatric treatment
Authors: Taylor Billie Lever , Sweeney Angela , Potts Laura C. , Trevillion Kylee , Howard Louise M.
Published: August 2022

Purpose

To examine factors associated with being re-admitted in the year after discharge from acute postpartum psychiatric treatment.

Methods

Secondary data analysis of information collected from mothers who were admitted to acute psychiatric services in the year after childbirth between 2013 and 2017. We carried out univariable analyses and multivariable hierarchical logistic regression to examine risk factors for women’s re-admission to acute psychiatric care (inpatient or community crisis care) in the year following discharge.

Results

Sixty-seven (24.1%) of 278 women were re-admitted in the year after discharge from acute care; the median number of days to re-admission was 86 (IQR 35–214), and women who were re-admitted accessed a median of two further acute services (IQR 1–3). In adjusted analyses, reporting a history of childhood trauma (aOR 1.02; 95% CI 1.00- 1.03, p = 0.036), a higher level of difficulties in the mother–infant bond (aOR 1.03; 95% CI 1.01–1.06, p = 0.009) and younger age (aOR 0.95; 95% CI 0.90–1.00, p = 0.066) were associated with re-admission.

Conclusion

This study confirms that the role of childhood adverse experiences on mental health is relevant for outcomes in women experiencing acute postpartum psychiatric episodes. Ongoing parent–infant bonding difficulties are also independently associated with re-admission. Perinatal mental health services therefore need to offer evidence-based interventions to address histories of trauma and to support parent–infant bonding to optimise mental health in women following discharge from acute psychiatric services. However, further research is needed to explore what other factors, not measured in our study, are also influential to re-admission.
Development of metal oxide incorporated Al-Zn-Sn sacrificial anodes processed by stir casting and heat treatment
Authors: Elsayed Abdelrahman , Nofal Adel , Attia Galal
Published: August 2022

Aluminum sacrificial anodes are currently the first choice for cathodic protection in numerous applications. The galvanic performance of aluminum-based sacrificial anodes is considerably enhanced by addition of certain alloying elements called activators. Recent researches proved that incorporation of specific metal oxides like MnO2, CeO2, RuO2, and IrO2 into the aluminum matrix could enhance the galvanic efficiency of aluminum anodes; however, the mechanism by which metal oxides improve galvanic properties of aluminum is still subject to discussion. The present work investigates the effect of incorporating commercially available low-cost manganese dioxide concentrate into Al-5Zn-0.1Sn sacrificial anodes in different volume fractions. It also studies the influence of heat treatment on anode’s galvanic performance by performing solution treatment at 3 different temperatures (250 °C, 400 °C, 550 °C). The electrochemical testing results proved an increase in efficiency of anodes incorporated with metal oxides and solution treated at 550 °C. The SEM imaging and EDX elemental mapping declared that the presence of SiO2 particles in the anode matrix which might cause effective and uniform corrosion of Al anodes and decreased non-coulombic losses.

Graphical abstract
Comment on the applicability of the Gurvich rule for estimation of pore volume in microporous zeolites
Authors: Farmahini Amir H. , Limbada Khalid , Sarkisov Lev
Published: August 2022

This comment seeks to establish a relation between two definitions of the pore volume of a microporous crystalline material. According to the first definition based on the Gurvich rule, the volume of the pores can be estimated from the saturated amount of vapour adsorbed, using the bulk liquid density of adsorbate as the conversion factor. The second definition is based on a purely geometric consideration of the porous space. With argon as the adsorbate and all-silica zeolite structures from the International Zeolite Association (IZA) database as the model adsorbents, we generate adsorption data using Grand Canonical Monte Carlo simulations and structural characteristics of the materials from the Poreblazer PB4.0 software. Under confinement in zeolitic pores, adsorbed argon forms structures very different from the liquid-like configurations. However, the pore volumes of these materials obtained from the Gurvich may deviate positively or negatively from the reference geometric value. Considering simply the geometric features of the materials, such as the pore volume itself or the pore size distribution, it proved to be difficult to anticipate how the volume from the Gurvich rule would deviate from the geometric volume for a particular structure. Overall, volume from the Gurvich rule agrees with the geometric volume within 25% error for 82% of the structures from the IZA database. As an additional outcome of this study, we provide a comprehensive database of textural characteristics and simulated argon adsorption data for all-silica zeolites, which can be used as reference values for the assessment of the quality of the microporous samples of all-silica zeolites in future experimental studies.
From inexact optimization to learning via gradient concentration
Authors: Stankewitz Bernhard , Mücke Nicole , Rosasco Lorenzo
Published: August 2022

Optimization in machine learning typically deals with the minimization of empirical objectives defined by training data. The ultimate goal of learning, however, is to minimize the error on future data (test error), for which the training data provides only partial information. In this view, the optimization problems that are practically feasible are based on inexact quantities that are stochastic in nature. In this paper, we show how probabilistic results, specifically gradient concentration, can be combined with results from inexact optimization to derive sharp test error guarantees. By considering unconstrained objectives, we highlight the implicit regularization properties of optimization for learning.
Convergence of GHGs emissions in the long-run: aerosol precursors, reactive gases and aerosols—a nonlinear panel approach
Authors: Romero-Ávila Diego , Omay Tolga
Published: August 2022

Anthropogenic emissions of reactive gases, aerosols and aerosol precursor compounds are responsible for the ozone hole, global warming and climate change, which have altered ecosystems and worsened human health. Environmental authorities worldwide have responded to these climate challenges through the 2030 Agenda for Sustainable Development. In this context, it is key to ascertain empirically whether emission levels are converging among the countries forming the industrialized world. In doing so, we focus on 23 industrialized countries using a novel dataset with ten series of annual estimates of anthropogenic emissions that include aerosols, aerosol precursor and reactive compounds, and carbon dioxide over the 1820–2018 period. We apply four state-of-the-art panel unit root tests that allow for several forms of time-dependent and state-dependent nonlinearity. Our evidence supports stochastic convergence following a linear process for carbon dioxide, whereas the adjustment is nonlinear for black carbon, carbon monoxide, methane, non-methane volatile organic compounds, nitrous oxide, nitrogen oxides and sulfur dioxide. In contrast, ammonia and organic carbon emissions appear to diverge. As for deterministic convergence, carbon dioxide converges linearly, while black carbon, carbon monoxide, nitrogen oxides, non-methane volatile organic compounds and sulfur dioxide adjust nonlinearly. Our results carry important policy implications concerning the achievement of SDG13 of the global 2030 Agenda for Sustainable Development, which appears to be feasible for the converging compounds.
Effect of the BMPR-II-SMAD3/MRTF pathway on proliferation and migration of ASMCs and the mechanism in asthma
Authors: Gu Wenbo , Lei Jiahui , Zhu He , Xiao Yali , Zhang Zhenping , Zhao Limin
Published: August 2022

Background

A variety of smooth muscle-specific genes and proteins, including SMAD3, BMPR-II, and MRTF, are involved in airway remodeling in asthma. As a receptor of bone morphogenetic protein (BMP) signaling, BMPR-II has important roles in airway remodeling in asthma. However, the underlying mechanism of BMPR-II in airway smooth muscle cells (ASMCs) in asthma remains incomplete.

Methods

Wistar rats were intraperitoneally injected with ovalbumin antigen suspension and aluminium hydroxide and, stimulated with ovalbumin nebulized inhalation to constructed asthma model. Primary ASMCs were isolated with collagenase I and identified by testing the α-SMA expression. Quantitative polymerase chain reaction (qPCR) and western blot assay were employed to detect the gene expression. CCK8, Transwell and Fluo-4 A assays were introduced to measure the cell viability, migration and intracellular Ca2+. Co-Immunoprecipitation (Co-IP) assay was applied to test the interaction among proteins.

Results

First, we observed significant increases in BMPR-II in asthmatic rat model and ASMCs at both the mRNA and protein levels. Second, we observed that silencing of siBMPR-II inhibited proliferation, migratory capacity and intracellular Ca2+ concentration in ASMCs. Furthermore, our study demonstrated that siBMPR-II inhibited the Smad3 expression and overexpression promoted the bioactivity of ASMCs. In addition, this study showed that p-Smad3 could interacted with MRTF and siMRTF inhibits the bioactivity of ASMCs. Finally, our results revealed BMPR-II-SMAD3/MRTF pathway affected the bioactivity of ASMCs.

Conclusions

This study indicates that the BMPR-II-SMAD3/MRTF signaling pathway is involved in the process of ASMCs remodeling, providing novel avenues for the identification of new therapeutic modalities.
A deep learning approach for parkinson’s disease severity assessment
Authors: Aşuroğlu Tunç , Oğul Hasan
Published: August 2022

Purpose

Parkinson’s Disease comes on top among neurodegenerative diseases affecting 10 million worldwide. To detect Parkinson’s Disease in a prior state, gait analysis is an effective choice. However, monitoring of Parkinson’s Disease using gait analysis is time consuming and exhaustive for patients and physicians. To assess severity of symptoms, a rating scale called Unified Parkinson's Disease Rating Scale is used. It determines mild and severe cases. Today, Parkinson’s Disease severity assessment is made in gait laboratories and by manual examination. These are time consuming and it is costly for health institutions to build and maintain laboratories. By using low-cost wearables and an effective model, aforementioned problems can be solved.

Methods

We provide a computerized solution for quantifiable assessment of Parkinson’s Disease symptoms severity. By using wearable sensors, our framework can predict exact symptom values to assess Parkinson’s Disease severity. We propose a deep learning approach that utilizes Ground Reaction Force sensors. From sensor signals, features are extracted and fed to a hybrid deep learning model. This model is the combination of Convolutional Neural Networks and Locally Weighted Random Forest.

Results

Proposed framework achieved 0.897, 3.009, 4.556 in terms of Correlation Coefficient, Mean Absolute Error and Root Mean Square Error, respectively. Proposed framework outperformed other machine and deep learning models. We also evaluated classification performance for disease detection. We outperformed most of the previous studies, achieving 99.5% accuracy, 98.7% sensitivity and 99.1% specificity.

Conclusion

This is the first study to use a deep learning regression approach to predict exact symptom value of Parkinson’s Disease patients. Results show that this approach can be effectively employed as a disease severity assessment tool using wearable sensors.
Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice—a fifteen-year journey at a tertiary referral centre
Authors: Casadei Riccardo , Ricci Claudio , Ingaldi Carlo , Alberici Laura , De Raffele Emilio , Barcia Bianca , Mosconi Cristina , Diegoli Margherita , Di Marco Mariacristina , Brandi Giovanni , Zagari Rocco Maurizio , Pagano Nico , Eusebi Leonardo Henry , Serra Carla , Migliori Marina , Guido Alessandra , Santini Donatella , Rosini Francesca , Malvi Deborah , Minni Francesco
Published: August 2022

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006–2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006–2010); period B (2011–2015) and period C (2016–2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P < 0.001) showed significant differences. Computed tomography scans (P < 0.001), endoscopic ultrasound (P < 0.001), fine needle aspiration, fine needle biopsy (P < 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P < 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P < 0.001). The MDTB evaluation increased significantly (P < 0.001). Up-front surgery and exploratory laparotomy decreased (P < 0.001), neoadjuvant treatment increased (P < 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential.
Effect of wet Hydrogen Sulfide on Carbon Steels Degradation in Refinery Based on Case Study
Authors: Orlikowski Juliusz , Jazdzewska Agata , Uygur Ilyas , Gospos Radoslaw , Olczak Tomasz , Darowicki Kazimierz
Published: August 2022

Material degradation caused by wet hydrogen sulfide (Wet H2S) is one of the major issues in refineries. Carbon steel is the main construction material used in refineries and is subjected not only to thickness loss but the hydrogen is the major concern. H2S leads to high atomic hydrogen penetration in steel which causes degradation in the form of blistering and/or cracking (HIC/SOHIC) and stress cracking in the area of welds and heat affected zones. Mechanism is unusually dangerous due to high difficulty of threat assessment, which is mostly based on ultrasonic measurements or calculations based on the API standards. This research is based on evaluation of the real threat of wet H2S degradation based on examination of construction materials after 41 years of exploitation in refinery. The comparison of the theoretical calculation based on API standards and experience of the degradation of the real objects was characterized. Laboratory measurements include mechanical tests involving the elongation in the function of tensile stress and deformation, with analysis of material hardness and gas chromatography analysis. The results are complemented by studies of the chemical composition of the streams and analytical studies of the hydrogen content in the material obtained by the gas chromatography method. The tests showed compliance of the standard analysis of the corrosion risk with the laboratory tests performed on the real samples. Research leads to indication of the destructive methods which can be used on the materials obtained during scheduled material replacements or installation modernizations.
Estimation of the Complexity of a Finite Mixture Distribution: From Well- to Less Known Methods
Authors: Balabdaoui Fadoua , Kolar Andrei , Kulagina Yulia , Müller Lilian
Published: August 2022

Mixture models occur in numerous settings including random and fixed effects models, clustering, deconvolution, empirical Bayes problems and many others. They are often used to model data originating from a heterogeneous population, consisting of several homogeneous subpopulations, and the problem of finding a good estimator for the number of components in the mixture arises naturally. Estimation of the order of a finite mixture model is a hard statistical task, and multiple techniques have been suggested for solving it. We will concentrate on several methods that have not gained much popularity yet deserve the attention of practitioners. These can be categorized into three groups: tools built upon the determinant of the Hankel matrix of moments of the mixing distribution, minimum distance estimators, likelihood ratio tests. We will address theoretical pillars underlying each of the methods, provide some useful modifications for enhancing their performance and present the results of the comparative numerical study that has been conducted under various scenarios. According to the results, none of the methods proves to be a “magic pill”. The results uncover limitations of the techniques and provide practical hints for choosing the best-suited tool under specific conditions.
Feasibility, impact, and priority of key strategies to enhance diverse and inclusive training programs in clinical and translational research: A mixed methods study
Authors: Campbell Jennifer A. , Walker Rebekah J. , Dawson Aprill Z. , Ozieh Mukoso N. , Schmidt Susanne , Shay L. Aubree , Williams Joni S. , Phillips Shane A. , Egede Leonard E.
Published: August 2022

Background:

Enhancing diversity in the scientific workforce is a long-standing issue. This study uses mixed methods to understand the feasibility, impact, and priority of six key strategies to promote diverse and inclusive training and contextualize the six key strategies across Clinical and Translational Science Awards (CTSAs) Program Institutions.

Methods:

Four breakout sessions were held at the NCATS 2020 CTSA Program annual meeting focused on diversity, equity, and inclusion (DEI) efforts. This paper focuses on the breakout session for Enhancing DEI in Translational Science Training Programs. Data were analyzed using a mixed methods convergent approach. The quantitative strand includes the online polling results. The qualitative strand includes the breakout session and the chat box in response to the training presentation.

Results:

Across feasibility, impact, and priority questions, prioritizing representation ranked number 1. Building partnerships ranked number 2 in feasibility and priority, while making it personal ranked number 2 for impact. Across each strategy, rankings supported the qualitative data findings in feasibility through shared experiences, impact in the ability to increase DEI, and priority rankings in comparison to the other strategies. No divergence was found across quantitative and qualitative data findings.

Conclusion:

Findings provide robust support for prioritizing representation as a number one strategy to focus on in training programs. Specifically, this strategy can be operationalized through integration of community representation, diversity advocates, and adopting a holistic approach to recruiting a diverse cadre of scholars into translational science training programs at the national level across CTSAs.
The moments of the time of ruin in Sparre Andersen risk models
Authors: Dickson David C.M.
Published: August 2022

We derive formulae for the moments of the time of ruin in both ordinary and modified Sparre Andersen risk models without specifying either the inter-claim time distribution or the individual claim amount distribution. We illustrate the application of our results in the special case of exponentially distributed claims, as well as for the following ordinary models: the classical risk model, phase-type(2) risk models, and the Erlang(
$\mathscr{n}$
) risk model. We also show how the key quantities for modified models can be found.
Toxic “Forever Chemicals” Accumulate Above the Water Table
Authors: Fritts Rachel
Published: August 2022

PFAS pose a public health risk, but there are major gaps in our knowledge of how these chemicals move through the ground.
Hippocampal circuit dysfunction in psychosis
Authors: Knight Samuel , McCutcheon Robert , Dwir Daniella , Grace Anthony A. , O’Daly Owen , McGuire Philip , Modinos Gemma
Published: August 2022

Despite strong evidence of the neurodevelopmental origins of psychosis, current pharmacological treatment is not usually initiated until after a clinical diagnosis is made, and is focussed on antagonising striatal dopamine receptors. These drugs are only partially effective, have serious side effects, fail to alleviate the negative and cognitive symptoms of the disorder, and are not useful as a preventive treatment. In recent years, attention has turned to upstream brain regions that regulate striatal dopamine function, such as the hippocampus. This review draws together these recent data to discuss why the hippocampus may be especially vulnerable in the pathophysiology of psychosis. First, we describe the neurodevelopmental trajectory of the hippocampus and its susceptibility to dysfunction, exploring this region’s proneness to structural and functional imbalances, metabolic pressures, and oxidative stress. We then examine mechanisms of hippocampal dysfunction in psychosis and in individuals at high-risk for psychosis and discuss how and when hippocampal abnormalities may be targeted in these groups. We conclude with future directions for prospective studies to unlock the discovery of novel therapeutic strategies targeting hippocampal circuit imbalances to prevent or delay the onset of psychosis.
LncRNA HEPFAL accelerates ferroptosis in hepatocellular carcinoma by regulating SLC7A11 ubiquitination
Authors: Zhang Baofu , Bao Wenming , Zhang Sina , Chen Bo , Zhou Xiang , Zhao Jungang , Shi Zhehao , Zhang Tan , Chen Ziyan , Wang Luhui , Zheng Xiangtao , Chen Gang , Wang Yi
Published: August 2022

Ferroptosis is a new type of cell death that has been recognized in recent years and is different from apoptosis, autophagy, and necrosis. It is mainly due to cellular iron homeostasis and lipid peroxidation of iron metabolism caused by large accumulation. There is a close correlation between ferroptosis and hepatocellular carcinoma (HCC). This study shows that the expression of the long noncoding RNA HEPFAL was reduced in HCC tissues. We found that lncRNA HEPFAL can promote ferroptosis by reducing the expression of solute carrier family 7 member 11 (SLC7A11) and increasing the levels of lipid reactive oxygen species (ROS) and iron (two surrogate markers of ferroptosis). In addition, we found that lncRNA HEPFAL increases the sensitivity of erastin-induced ferroptosis, which may be related to mTORC1, and lncRNA HEPFAL can promote the ubiquitination of SLC7A11 and reduce the stability of the SLC7A11 protein, resulting in decreased expression. Understanding these mechanisms indicates that lncRNAs related to ferroptosis are essential for the occurrence and treatment of HCC.
Self-cycled photo-Fenton-like system based on an artificial leaf with a solar-to-H2O2 conversion efficiency of 1.46%
Authors: Dong Chaoran , Yang Yilong , Hu Xuemin , Cho Yoonjun , Jang Gyuyong , Ao Yanhui , Wang Luyang , Shen Jinyou , Park Jong Hyeok , Zhang Kan
Published: August 2022

Millions of families around the world remain vulnerable to water scarcity and have no access to drinking water. Advanced oxidation processes (AOPs) are an effective way towards water purification with qualified reactive oxygen species (ROSs) while are impeded by the high-cost and tedious process in either input of consumable reagent, production of ROSs, and the pre-treatment of supporting electrolyte. Herein, we couple solar light-assisted H2O2 production from water and photo-Fenton-like reactions into a self-cyclable system by using an artificial leaf, achieving an unassisted H2O2 production rate of 0.77 μmol/(min·cm2) under 1 Sun AM 1.5 illumination. Furthermore, a large (70 cm2) artificial leaf was used for an unassisted solar-driven bicarbonate-activated hydrogen peroxide (BAP) system with recycled catalysts for real-time wastewater purification with requirements for only water, oxygen and sunlight. This demonstration highlights the feasibility and scalability of photoelectrochemical technology for decentralized environmental governance applications from laboratory benchtops to industry.
Convergence in phosphorus constraints to photosynthesis in forests around the world
Authors: Ellsworth David S. , Crous Kristine Y. , De Kauwe Martin G. , Verryckt Lore T. , Goll Daniel , Zaehle Sönke , Bloomfield Keith J. , Ciais Philippe , Cernusak Lucas A. , Domingues Tomas F. , Dusenge Mirindi Eric , Garcia Sabrina , Guerrieri Rossella , Ishida F. Yoko , Janssens Ivan A. , Kenzo Tanaka , Ichie Tomoaki , Medlyn Belinda E. , Meir Patrick , Norby Richard J. , Reich Peter B. , Rowland Lucy , Santiago Louis S. , Sun Yan , Uddling Johan , Walker Anthony P. , Weerasinghe K. W. Lasantha K. , van de Weg Martine J. , Zhang Yun-Bing , Zhang Jiao-Lin , Wright Ian J.
Published: August 2022

Tropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.
In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions
Authors: Nicolas Clara T. , VanLith Caitlin J. , Hickey Raymond D. , Du Zeji , Hillin Lori G. , Guthman Rebekah M. , Cao William J. , Haugo Benjamin , Lillegard Annika , Roy Diya , Bhagwate Aditya , O’Brien Daniel , Kocher Jean-Pierre , Kaiser Robert A. , Russell Stephen J. , Lillegard Joseph B.
Published: August 2022

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)−1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy is well tolerated and provides stable long-term expression of FAH in pigs with HT1. Genomic integration displays a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach.
Current Siberian heating is unprecedented during the past seven millennia
Authors: Hantemirov Rashit M. , Corona Christophe , Guillet Sébastien , Shiyatov Stepan G. , Stoffel Markus , Osborn Timothy J. , Melvin Thomas M. , Gorlanova Ludmila A. , Kukarskih Vladimir V. , Surkov Alexander Y. , von Arx Georg , Fonti Patrick
Published: August 2022

The Arctic is warming faster than any other region on Earth. Putting this rapid warming into perspective is challenging because instrumental records are often short or incomplete in polar regions and precisely-dated temperature proxies with high temporal resolution are largely lacking. Here, we provide this long-term perspective by reconstructing past summer temperature variability at Yamal Peninsula – a hotspot of recent warming – over the past 7638 years using annually resolved tree-ring records. We demonstrate that the recent anthropogenic warming interrupted a multi-millennial cooling trend. We find the industrial-era warming to be unprecedented in rate and to have elevated the summer temperature to levels above those reconstructed for the past seven millennia (in both 30-year mean and the frequency of extreme summers). This is undoubtedly of concern for the natural and human systems that are being impacted by climatic changes that lie outside the envelope of natural climatic variations for this region.
Towards critical white ice conditions in lakes under global warming
Authors: Weyhenmeyer Gesa A. , Obertegger Ulrike , Rudebeck Hugo , Jakobsson Ellinor , Jansen Joachim , Zdorovennova Galina , Bansal Sheel , Block Benjamin D. , Carey Cayelan C. , Doubek Jonathan P. , Dugan Hilary , Erina Oxana , Fedorova Irina , Fischer Janet M. , Grinberga Laura , Grossart Hans-Peter , Kangur Külli , Knoll Lesley B. , Laas Alo , Lepori Fabio , Meier Jacob , Palshin Nikolai , Peternell Mark , Pulkkanen Merja , Rusak James A. , Sharma Sapna , Wain Danielle , Zdorovennov Roman
Published: August 2022

The quality of lake ice is of uppermost importance for ice safety and under-ice ecology, but its temporal and spatial variability is largely unknown. Here we conducted a coordinated lake ice quality sampling campaign across the Northern Hemisphere during one of the warmest winters since 1880 and show that lake ice during 2020/2021 commonly consisted of unstable white ice, at times contributing up to 100% to the total ice thickness. We observed that white ice increased over the winter season, becoming thickest and constituting the largest proportion of the ice layer towards the end of the ice cover season when fatal winter drownings occur most often and light limits the growth and reproduction of primary producers. We attribute the dominance of white ice before ice-off to air temperatures varying around the freezing point, a condition which occurs more frequently during warmer winters. Thus, under continued global warming, the prevalence of white ice is likely to substantially increase during the critical period before ice-off, for which we adjusted commonly used equations for human ice safety and light transmittance through ice.
Specificity of TGF-β1 signal designated by LRRC33 and integrin αVβ8
Authors: Duan Zelin , Lin Xuezhen , Wang Lixia , Zhen Qiuxin , Jiang Yuefeng , Chen Chuxin , Yang Jing , Lee Chia-Hsueh , Qin Yan , Li Ying , Zhao Bo , Wang Jianchuan , Zhang Zhe
Published: August 2022

Myeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αVβ8 activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin αVβ8/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin αVβ8 and L-TGF-β1, which shows higher avidity and more efficient L-TGF-β1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit β8 determines its exquisite affinity to L-TGF-β1. Together, our findings provide important insights into the specificity of TGF-β1 signaling achieved by LRRC33 and integrin αVβ8.
CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis
Authors: Guo Yuegui , Zhu Zhehui , Huang Zhenyu , Cui Long , Yu Wei , Hong Wanjin , Zhou Zhaocai , Du Peng , Liu Chen-Ying
Published: August 2022

Dysregulation of Hippo pathway leads to hyperactivation of YAP-TEAD transcriptional complex in various cancers, including colorectal cancer (CRC). In this study, we observed that HHEX (Hematopoietically expressed homeobox) may enhance transcription activity of the YAP-TEAD complex. HHEX associates with and stabilizes the YAP-TEAD complex on the regulatory genomic loci to coregulate the expression of a group of YAP/TEAD target genes. Also, HHEX may indirectly regulate these target genes by controlling YAP/TAZ expression. Importantly, HHEX is required for the pro-tumorigenic effects of YAP during CRC progression. In response to serum stimulation, CK2 (Casein Kinase 2) phosphorylates HHEX and enhances its interaction with TEAD4. A CK2 inhibitor CX-4945 diminishes the interaction between HHEX and TEAD4, leading to decreased expression of YAP/TEAD target genes. CX-4945 synergizes the antitumor activity of YAP-TEAD inhibitors verteporfin and Super-TDU. Elevated expression of HHEX is correlated with hyperactivation of YAP/TEAD and associated with poor prognosis of CRC patients. Overall, our study identifies HHEX as a positive modulator of YAP/TEAD to promote colorectal tumorigenesis, providing a new therapeutic strategy for targeting YAP/TEAD in CRC.
Catalytic ozone decomposition and adsorptive VOCs removal in bimetallic metal-organic frameworks
Authors: Dong Chen , Yang Jia-Jia , Xie Lin-Hua , Cui Ganglong , Fang Wei-Hai , Li Jian-Rong
Published: August 2022

Atmospheric ozone has long been a threat to human health, however, rational design of high-performance O3-decomposition catalysts remains challenging. Herein, we demonstrate the great potential of a series of isomorphous bimetallic MOFs denoted as PCN-250(Fe2M) (M = Co2+, Ni2+, Mn2+) in catalytic O3 decomposition. Particularly, PCN-250(Fe2Co) showed 100% O3 removal efficiency for a continuous air flow containing 1 ppm O3 over a wide humidity range (0 ‒ 80% RH) at room temperature. Mechanism studies suggested that the high catalytic performance originated from the introduction of open Co(II) sites as well as its porous structure. Additionally, at low pressures around 10 Pa, PCN-250(Fe2Co) exhibited high adsorption capacities (89 ‒ 241 mg g−1) for most VOCs, which are not only a class of hazardous air pollutants but also the precursor of O3. This work opens up a new avenue to develop advanced air purification materials for O3 and VOCs removal in one.
Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein
Authors: Ulamec Sabine M. , Maya-Martinez Roberto , Byrd Emily J. , Dewison Katherine M. , Xu Yong , Willis Leon F. , Sobott Frank , Heath George R. , van Oosten Hawle Patricija , Buchman Vladimir L. , Radford Sheena E. , Brockwell David J.
Published: August 2022

Alpha-synuclein (αSyn) is a protein involved in neurodegenerative disorders including Parkinson’s disease. Amyloid formation of αSyn can be modulated by the ‘P1 region’ (residues 36-42). Here, mutational studies of P1 reveal that Y39A and S42A extend the lag-phase of αSyn amyloid formation in vitro and rescue amyloid-associated cytotoxicity in C. elegans. Additionally, L38I αSyn forms amyloid fibrils more rapidly than WT, L38A has no effect, but L38M does not form amyloid fibrils in vitro and protects from proteotoxicity. Swapping the sequence of the two residues that differ in the P1 region of the paralogue γSyn to those of αSyn did not enhance fibril formation for γSyn. Peptide binding experiments using NMR showed that P1 synergises with residues in the NAC and C-terminal regions to initiate aggregation. The remarkable specificity of the interactions that control αSyn amyloid formation, identifies this region as a potential target for therapeutics, despite their weak and transient nature.
Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Authors: Arostegui Martin , Scott R. Wilder , Böse Kerstin , Underhill T. Michael
Published: August 2022

Tissue development and regeneration rely on the cooperation of multiple mesenchymal progenitor (MP) subpopulations. We recently identified Hic1 as a marker of quiescent MPs in multiple adult tissues. Here, we describe the embryonic origin of appendicular Hic1+ MPs and demonstrate that they arise in the hypaxial somite, and migrate into the developing limb at embryonic day 11.5, well after limb bud initiation. Time-resolved single-cell-omics analyses coupled with lineage tracing reveal that Hic1+ cells generate a unique MP hierarchy, that includes both recently identified adult universal fibroblast populations (Dpt+, Pi16+ and Dpt+Col15a1+) and more specialised mesenchymal derivatives such as, peri and endoneurial cells, pericytes, bone marrow stromal cells, myotenocytes, tenocytes, fascia-resident fibroblasts, with limited contributions to chondrocytes and osteocytes within the skeletal elements. MPs endure within these compartments, continue to express Hic1 and represent a critical reservoir to support post-natal growth and regeneration.
Arctic sea-ice loss is projected to lead to more frequent strong El Niño events
Authors: Liu Jiping , Song Mirong , Zhu Zhu , Horton Radley M. , Hu Yongyun , Xie Shang-Ping
Published: August 2022

Arctic sea ice has decreased substantially and is projected to reach a seasonally ice-free state in the coming decades. Little is known about whether dwindling Arctic sea ice is capable of influencing the occurrence of strong El Niño, a prominent mode of climate variability with global impacts. Based on time slice coupled model experiments, here we show that no significant change in the occurrence of strong El Niño is found in response to moderate Arctic sea-ice loss that is consistent with satellite observations to date. However, as the ice loss continues and the Arctic becomes seasonally ice-free, the frequency of strong El Niño events increases by more than one third, as defined by gradient-based indices that remove mean tropical Pacific warming induced by the seasonally ice-free Arctic. By comparing our time slice experiments with greenhouse warming experiments, we conclude that at least 37–48% of the increase of strong El Niño near the end of the 21st century is associated specifically with Arctic sea-ice loss. Further separation of Arctic sea-ice loss and greenhouse gas forcing only experiments implies that the seasonally ice-free Arctic might play a key role in driving significantly more frequent strong El Niño events.
Thiol-Yne click chemistry of acetylene-enabled macrocyclization
Authors: Lü Shiwei , Wang Zipeng , Zhu Shifa
Published: August 2022

Macrocycles have fascinated scientists for over half a century due to their aesthetically appealing structures and broad utilities in chemical, material, and biological research. However, the efficient preparation of macrocycles remains an ongoing research challenge in organic synthesis because of the high entropic penalty involved in the ring-closing process. Herein we report a photocatalyzed thiol-yne click reaction to forge diverse sulfur-containing macrocycles (up to 35-membered ring) and linear C2-linked 1,2-(S-S/S-P/S-N) functionalized molecules, starting from the simplest alkyne, acetylene. Preliminary mechanistic experiments support a visible light-mediated radical-polar crossover dihydrothiolation process. This operationally straightforward reaction is also amenable to the synthesis of organometallic complexes, bis-sulfoxide ligand and a pleuromutilin antibiotic drug Tiamulin, which provides a practical route to synthesize highly valued compounds from the feedstock acetylene gas.
Co-assembled perylene/graphene oxide photosensitive heterobilayer for efficient neuromorphics
Authors: Zhang He-Shan , Dong Xue-Mei , Zhang Zi-Cheng , Zhang Ze-Pu , Ban Chao-Yi , Zhou Zhe , Song Cheng , Yan Shi-Qi , Xin Qian , Liu Ju-Qing , Li Yin-Xiang , Huang Wei
Published: August 2022

Neuromorphic electronics, which use artificial photosensitive synapses, can emulate biological nervous systems with in-memory sensing and computing abilities. Benefiting from multiple intra/interactions and strong light-matter coupling, two-dimensional heterostructures are promising synaptic materials for photonic synapses. Two primary strategies, including chemical vapor deposition and physical stacking, have been developed for layered heterostructures, but large-scale growth control over wet-chemical synthesis with comprehensive efficiency remains elusive. Here we demonstrate an interfacial coassembly heterobilayer films from perylene and graphene oxide (GO) precursors, which are spontaneously formed at the interface, with uniform bilayer structure of single-crystal perylene and well-stacked GO over centimeters in size. The planar heterostructure device exhibits an ultrahigh specific detectivity of 3.1 × 1013 Jones and ultralow energy consumption of 10−9 W as well as broadband photoperception from 365 to 1550 nm. Moreover, the device shows outstanding photonic synaptic behaviors with a paired-pulse facilitation (PPF) index of 214% in neuroplasticity, the heterosynapse array has the capability of information reinforcement learning and recognition.
Oligodendrocyte differentiation alters tRNA modifications and codon optimality-mediated mRNA decay
Authors: Martin Sophie , Allan Kevin C. , Pinkard Otis , Sweet Thomas , Tesar Paul J. , Coller Jeff
Published: August 2022

Oligodendrocytes are specialized cells that confer neuronal myelination in the central nervous system. Leukodystrophies associated with oligodendrocyte deficits and hypomyelination are known to result when a number of tRNA metabolism genes are mutated. Thus, for unknown reasons, oligodendrocytes may be hypersensitive to perturbations in tRNA biology. In this study, we survey the tRNA transcriptome in the murine oligodendrocyte cell lineage and find that specific tRNAs are hypomodified in oligodendrocytes within or near the anticodon compared to oligodendrocyte progenitor cells (OPCs). This hypomodified state may be the result of differential expression of key modification enzymes during oligodendrocyte differentiation. Moreover, we observe a concomitant relationship between tRNA hypomodification and tRNA decoding potential; observing oligodendrocyte specific alterations in codon optimality-mediated mRNA decay and ribosome transit. Our results reveal that oligodendrocytes naturally maintain a delicate, hypersensitized tRNA/mRNA axis. We suggest this axis is a potential mediator of pathology in leukodystrophies and white matter disease when further insult to tRNA metabolism is introduced.