bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of self-regulated learning in a novel MOOC platform
Authors: Onah Daniel F. O. , Pang Elaine L. L. , Sinclair Jane E.
Published: December 2022

Despite the proliferation of massive open online courses (MOOCs) and the impressive levels of enrolment they attract, many participants do not complete these courses. High drop-out has been identified as one of the major problems with existing MOOC formats. Our work addresses two factors relating to non-completion. Firstly, MOOCs require a high degree of self-regulated learning (SRL) skills but most do not adequately develop such skills, thus making them inaccessible in practice to many. Related to this is the inflexibility and passivity of many current MOOC formats, preventing individuals from setting their own learning objectives and directing their own learning. This paper presents preliminary findings from an investigation into MOOC learners’ SRL skills and the relationship to how participants learn. Following a design science methodology, we have developed a novel MOOC platform to support learner choice and to assist participants in defining learning goals and developing individual study paths. This paper describes the architecture of the system and presents findings from a pilot MOOC developed on the platform. Our results indicate that there is a high demand for more flexible, self-directed learning but that MOOC learners exhibit deficiencies in specific SRL skills including help seeking and task strategies. The contextualised nature of SRL skills means that even learners with a strong background of formal education may not deploy the best strategies for MOOC learning. This work is of significance to MOOC development in general as it highlights the need for targeted strategies to encourage SRL in MOOC platforms and innovation.
Increases in External Sensory Observing Cross-Sectionally Mediate the Repair of Positive Affect Following Mindfulness-Based Cognitive Therapy in Individuals with Residual Depression Symptoms
Authors: Dunn Barnaby D. , Wiedemann Hanna , Kock Merle , Peeters Frenk , Wichers Marieke , Hayes Rachel , Kuyken Willem , Geschwind Nicole
Published: December 2022

Objectives

Mindfulness-Based Cognitive Therapy for Depression (MBCT-D) has been shown to be effective at repairing positive affect deficits in depressed individuals, but the mechanism of action underpinning these changes has not been empirically examined. To address this issue, secondary analyses of two randomised controlled trials in individuals with residual depression were conducted.

Method

Study 1 was a cross-sectional mediation analysis of a trial reporting superior effects of MBCT-D to a waitlist control in bolstering momentary positive affect in individuals with residual depression symptoms (n = 130). Study 2 replicated this analysis in the subset of individuals with residual depression symptoms (n = 117) from a second, larger trial comparing MBCT-D to maintenance antidepressants (M-ADM) to prevent depressive relapse that also included a positive affect outcome.

Results

In Study 1, an increase in external sensory observing uniquely mediated the superiority of MBCT-D over the control in repairing momentary positive affect. Replicating these findings, in Study 2, MBCT-D was superior to M-ADM at repairing positive affect and this was cross-sectionally mediated by changes in external sensory observing.

Conclusions

These findings suggest that one way in which MBCT-D enhances positive affect in individuals with residual depression may be by training the capacity to attend to external sensory experience.
A resimulation framework for event loss tables based on clustering
Authors: Funke Benedikt , Roering Harmen
Published: December 2022

Catastrophe loss modeling has enormous relevance for various insurance companies due to the huge loss potential. In practice, geophysical-meteorological models are widely used to model these risks. These models are based on the simulation of meteorological and physical parameters that cause natural events and evaluate the corresponding effects on the insured exposure of a certain company. Due to their complexity, these models are often operated by external providers—at least seen from the perspective of a variety of insurance companies. The outputs of these models can be made available, for example, in the form of event loss tables, which contain different statistical characteristics of the simulated events and their caused losses relative to the exposure. The integration of these outputs into the internal risk model framework is fundamental for a consistent treatment of risks within the companies. The main subject of this work is the formulation of a performant resimulation algorithm of given event loss tables, which can be used for this integration task. The newly stated algorithm is based on cluster analysis techniques and represents a time-efficient way to perform sensitivities and scenario analyses.
Effective removal of hexavalent chromium from water by sustainable nano-scaled waste avocado seeds: adsorption isotherm, thermodynamics, kinetics, and error function
Authors: Mahmoud Mohamed E. , El-Said Ghada F. , Ibrahim Ghada A. A. , Elnashar Almaza A. S.
Published: December 2022

In the current investigation, an efficient low-cost nano-scaled material was prepared from waste avocado seeds (NASs) and employed as a sustainable nanosorbent for removal of hexavalent chromium ions. The adsorption and surface characteristics with respect to the availability of functional groups, basic component elements, and structural properties of NASs were achieved by different techniques. Analysis of NASs referred to the presence of carbon and oxygen contents providing 97.21%. The NASs particles were homogenously identified and ranged between 18.68 and 19.05 nm. The impact of various affecting adsorption parameters on hexavalent chromium ions removal was elaborated and optimized at pH 2.0, NASs dose 10 mg, contact time 30 min, and temperature 25 °C by the batch adsorption assay. Fifteen linear and nonlinear modeling tests were applied to evaluate the adsorption isotherms and arranged in the following fitting order: Tempkin < BET < Dubinin-Radushkevich < Generalized < Halsey ˂ Flory–Huggins < Freundlich < Harkins–Jura ˂ Langmuir for linear formulas and Weber-van Vliet < Langmuir < Generalized < Radke–Prausnitz (II) < Radke–Prausnitz (III) < Fritz-Schlunder IV < Baudu < Multilayer < Fritz-Schlunder V < Toth for nonlinear formulas with 2 to 5 parameters. Linear and nonlinear pseudo-second-order models, intraparticle diffusion, and Elovich models were also scrutinized, and both pore diffusion and film were similarly involved in the rate-limiting step. The values of ΔS° (0.21 kJ/mol), ΔH° (− 41.02 kJ/mol) and ΔG° (− 28.30 to − 19.97 kJ/mol) at high concentration of hexavalent chromium (50 mg L−1) and a temperature range of 20–60 °C reflected the disordering, spontaneously exothermic adsorption process. The activation energy (Ea) was also confirmed to include the diffusion process at the activation energy in the rate-limiting step. The potential application of NASs in hexavalent chromium removal from wastewater, seawater, and tap water as real aqueous matrices referred to excellent percentage removal values in the range from 98.44 to 98.86%. Based on the outlined results, one can deduce that excellent performance and efficiency for removal of high hexavalent chromium concentration at high temperature, low nanosorbent mass, and low pH from different aqueous matrices were accomplished by the evaluated NAS nanosorbent. Accordingly, the investigated NAS nanosorbent is recommended to apply in high stress industrial and wastewater treatment plants.
Multi-feature contrastive learning for unpaired image-to-image translation
Authors: Gou Yao , Li Min , Song Yu , He Yujie , Wang Litao
Published: December 2022

Unpaired image-to-image translation for the generation field has made much progress recently. However, these methods suffer from mode collapse because of the overfitting of the discriminator. To this end, we propose a straightforward method to construct a contrastive loss using the feature information of the discriminator output layer, which is named multi-feature contrastive learning (MCL). Our proposed method enhances the performance of the discriminator and solves the problem of model collapse by further leveraging contrastive learning. We perform extensive experiments on several open challenge datasets. Our method achieves state-of-the-art results compared with current methods. Finally, a series of ablation studies proved that our approach has better stability. In addition, our proposed method is also practical for single image translation tasks. Code is available at https://github.com/gouayao/MCL.
A hybrid differential evolution algorithm for a location-inventory problem in a closed-loop supply chain with product recovery
Authors: Guo Hao , Liu Gang , Zhang Ying , Zhang Chunnan , Xiong Chuanhui , Li Wenli
Published: December 2022

Product recovery is an important business because of its great economic, social, and environmental benefits in practice. In this paper, a location-inventory problem (LIP) in a closed-loop supply chain (CLSC) is investigated to optimize facility location and inventory control decisions by considering product recovery. The objective is to optimize facility location and inventory control decisions to minimize the total cost of business operations in a closed-loop supply chain system. We formulate this problem as a mixed-integer nonlinear programming model and design a modified hybrid differential evolution algorithm (MHDE) to solve it efficiently. Finally, numerical results are presented to validate the performance of the new algorithm. The results show that MHDE is more efficient and effective than Lingo and other algorithms for the research problem under study. Managerial insights are also derived for business managers to improve their supply chain performance.
Analysis of Hamming and Hausdorff 3D distance measures for complex pythagorean fuzzy sets and their applications in pattern recognition and medical diagnosis
Authors: Wu Dong-Lun , Zhu Zhiyi , Ullah Kifayat , Liu Lantian , Wu Xinxing , Zhang Xu
Published: December 2022

Similarity measures are very effective and meaningful tool used for evaluating the closeness between any two attributes which are very important and valuable to manage awkward and complex information in real-life problems. Therefore, for better handing of fuzzy information in real life, Ullah et al. (Complex Intell Syst 6(1): 15–27, 2020) recently introduced the concept of complex Pythagorean fuzzy set (CPyFS) and also described valuable and dominant measures, called various types of distance measures (DisMs) based on CPyFSs. The theory of CPyFS is the essential modification of Pythagorean fuzzy set to handle awkward and complicated in real-life problems. Keeping the advantages of the CPyFS, in this paper, we first construct an example to illustrate that a DisM proposed by Ullah et al. does not satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Then, combining the 3D Hamming distance with the Hausdorff distance, we propose a new DisM for CPyFSs, which is proved to satisfy the axiomatic definition of complex Pythagorean fuzzy DisM. Moreover, similarly to some DisMs for intuitionistic fuzzy sets, we present some other new complex Pythagorean fuzzy DisMs. Finally, we apply our proposed DisMs to a building material recognition problem and a medical diagnosis problem to illustrate the effectiveness of our DisMs. Finally, we aim to compare the proposed work with some existing measures is to enhance the worth of the derived measures.
Resonance algorithm: an intuitive algorithm to find all shortest paths between two nodes
Authors: Liu Yu , Lin Qiguang , Hong Binbin , Peng Yunru , Hjerpe Daniel , Liu Xiaofeng
Published: December 2022

The shortest path problem (SPP) is a classic problem and appears in a wide range of applications. Although a variety of algorithms already exist, new advances are still being made, mainly tuned for particular scenarios to have better performances. As a result, they become more and more technically complex and sophisticated. In this paper, we developed an intuitive and nature-inspired algorithm to compute all possible shortest paths between two nodes in a graph: Resonance Algorithm (RA). It can handle any undirected, directed, or mixed graphs, irrespective of loops, unweighted or positively weighted edges, and can be implemented in a fully decentralized manner. Although the original motivation for RA is not the speed per se, in certain scenarios (when sophisticated matrix operations can be employed, and when the map is very large and all possible shortest paths are demanded), it out-competes Dijkstra’s algorithm, which suggests that in those scenarios, RA could also be practically useful.
Can financial stress be anticipated and explained? Uncovering the hidden pattern using EEMD-LSTM, EEMD-prophet, and XAI methodologies
Authors: Ghosh Indranil , Dragan Pamucar
Published: December 2022

Global financial stress is a critical variable that reflects the ongoing state of several key macroeconomic indicators and financial markets. Predictive analytics of financial stress, nevertheless, has seen very little focus in literature as of now. Futuristic movements of stress in markets can be anticipated if the same can be predicted with a satisfactory level of precision. The current research resorts to two granular hybrid predictive frameworks to discover the inherent pattern of financial stress across several critical variables and geography. The predictive structure utilizes the Ensemble Empirical Mode Decomposition (EEMD) for granular time series decomposition. The Long Short-Term Memory Network (LSTM) and Facebook’s Prophet algorithms are invoked on top of the decomposed components to scrupulously investigate the predictability of final stress variables regulated by the Office of Financial Research (OFR). A rigorous feature screening using the Boruta methodology has been utilized too. The findings of predictive exercises reveal that financial stress across assets and continents can be predicted accurately in short and long-run horizons even at the time of steep financial distress during the COVID-19 pandemic. The frameworks appear to be statistically significant at the expense of model interpretation. To resolve the issue, dedicated Explainable Artificial Intelligence (XAI) methods have been used to interpret the same. The immediate past information of financial stress indicators largely explains patterns in the long run, while short-run fluctuations can be tracked by closely monitoring several technical indicators.
Mitigation of laser plasma parametric instabilities with broadband lasers
Authors: Zhao Yao , Weng Su-Ming , Ma Hang-Hang , Bai Xiao-Jun , Sheng Zheng-Ming
Published: December 2022

Laser plasma instabilities (LPIs) cause laser energy loss, asymmetric and insufficient compression, and target preheating, thus are assumed to be among the major concerns of inertial confinement fusion research. Mitigation of LPIs can enhance the laser–target coupling efficiency and optimize the target compression dynamics, which is critical for the realization of robust and high-efficiency fusion ignition. Broadband lasers with polychromatic components or random phases have been investigated for decades as an effective alternative to mitigate LPIs. Here, we present a brief overview on the progress of broadband LPIs, including the models of broadband lasers, the involved physics, the conditions for effective suppression of LPIs, and some schemes to produce broadband lasers.
Kinetic Alfven wave (KAW) eigenmode in magnetosphere magnetic reconnection
Authors: Dai Lei , Wang Chi
Published: December 2022

One prominent signature of collisionless magnetic reconnection in the magnetosphere is the Hall effect. In the ion-scale region of reconnection, ions cannot follow the magnetic field line whereas electrons are still magnetized. The difference in the motions of electrons and ions leads to charge separation, the resulting transverse Hall electric field, the field-aligned streaming of electrons to preserve charge neutrality, and the corresponding Hall magnetic field. Such physics has long been invoked in the discovery of kinetic Alfven waves (KAW) when the perpendicular wavelength becomes comparable to the ion scale. In this review, we present recent progresses in theoretical modeling, numerical simulations and in situ observations that analyze Hall effects in terms of KAW eigenmode. This review will also cover analysis of the impact of KAW eigenmode on the ion acceleration and energy conversion in reconnection. We emphasize that the KAW perspective can provide a unified description of various phenomena in magnetic reconnection, including Hall magnetic fields, Hall electric fields, the field-aligned current, the electric field parallel to B, the non-gyrotropy velocity distribution of ions, and a close connection between Hall fields and a fast reconnection rate ($$\sim$$
∼
0.1). The quantitative description of these aspects is necessary for a Petschek-type model in the era of collisionless reconnection.
RETRACTED ARTICLE: Immersive animation scene design in animation language under virtual reality
Authors: Xu Chao
Published: December 2022

The study aims to explore a new form of immersive animation scene design and improve the application effect of virtual reality (VR) in immersive animation scene design. First, the research status of VR and the related concepts of animation scene design are analyzed, and the basic characteristics of visual effects in immersive VR animation scenes are summarized. Second, three elements to create immersion in a VR animation scene are color, light and shadow, and digital information technology. Finally, the application of VR technology to an animation scene design is analyzed, the problem of vertigo caused by VR animation scenes is deeply discussed, the vertigo test process in an immersive VR scene is proposed, and an experiment is designed to verify it. The results show that in the design of an immersive VR scene, the relative moving speed of the forward straight line should be maintained less than 6.5 times of the audience’s perceived speed, and the optimal relative moving speed of the scene should be maintained below 5 times of the audience’s perceived speed when they moving backward. In the design of a rotating animation scene, the long-term high-speed rotation should be avoided. If there must be a rotating scene, the rotation speed should be as low as 50°/s. The research provides some guidance for the application of VR to immersive animation scene design.

This study discusses immersive animation scene design from dizziness prospective. It is novel.

This study introduces relative motion perception illusion and use displacement velocity and relative displacement to analyze VR vertigo.

Len motion is divided into forward and reverse linear, horizontal and vertical rotation and camera center rotation to study vertigo source.

The dizziness evaluation model is designed and combined with the virtual indoor scene developed to achieve a visual immersion experience.
Effects of ultrasonic waves on seedling growth, biochemical constituents, genetic stability of fenugreek (Trigonella foenum-graecum) under salinity stress
Authors: El-Sattar Amira Mohamed Abd , Tawfik Eman
Published: December 2022

Fenugreek is a globally important legume that is widely cultivated for its therapeutic benefits in most parts of the world. Seeds on the other hand have a poor germination and growth rate when exposed to salinity. The effect of ultrasonic exposure period on germination and early seedling behaviors of fenugreek seeds under salt stress was investigated in a laboratory experiment. During germination and early seedling stages, all tests were conducted at 40 kHz in a water bath ultrasonic device with two durations (10 and 20 min) under salinity stress using different concentrations of NaCl (0, 1000, 3000, and 5000 mg/l). The results revealed a substantial decrease in germination percentage, all growth criteria, with increasing NaCl concentration and a significant increase in biomass produced by the Fenugreek (total soluble protein, total soluble carbohydrate, and proline), all of which are thought to be mechanisms for salinity resistance. Ultrasonication of fenugreek seeds for 10 and 20 min has a significant impact on seed germination, early seedling development and biochemical constituents under normal and stress conditions. The genetic stability of fenugreek DNA content was affected by these different treatments. This variation was estimated by RAPD-PCR molecular marker, and resulted in a total polymorphism percentage of 49.72% from all the primers. All these different treatments caused variation in the physiological responses and DNA content. This variation enhanced with more ultrasonic and salt treatments. Hence, these stresses can be used for enhancing the variable metabolic processes in fenugreek plant and stimulate its medicinal properties.
A highly sensitive pre-column derivatization method for fluorescence detection of tobramycin using 2-naphthalenesulfonyl chloride as a derivatizing agent
Authors: Mabrouk Mokhtar M. , Soliman Suzan M. , El-Agizy Heba M. , Mansour Fotouh R.
Published: December 2022

A new, simple, rapid and highly sensitive high performance liquid chromatographic method was developed for the determination of tobramycin (TOB) in ophthalmic solutions. The developed method was based on derivatizing this non-chromophoric drug with 2-naphthalenesulfonyl chloride (NSCl), at 80 ºC for 40 min, and measuring the fluorescent product. Elution from the column was isocratic, using a mobile phase consisting of acetonitrile –1% phosphoric acid in water, (90:10, v/v), with a flow rate of 2 mL/min, at 40 ºC. Determination was developed using fluorescence detection at an excitation wavelength of 300 nm and an emission wavelength of 380 nm. The chromatographic separation was achieved on Knauer-Eurospher 100–5 C18 silica column (300 mm × 4 mm i.d, 5 μm). Different approaches were used to optimize the conditions of the method and to reach the maximum yield. The linear regression data for the calibration plot showed acceptable correlation coefficient (r2 = 0.9998) at the concentration ranges of 2.5–1000 ng/mL for TOB. The method was successfully validated according to the guidelines of the International Council on Harmonization, and was found suitable for pharmaceutical applications. The method was new, simple and precise for analysis of TOB and applicable for routine analysis in quality control laboratories.
Periodic Dynamics of a Class of Non-autonomous Contact Hamiltonian Systems
Authors: Li Zhanyong , Tang Yaozong , Sha Bier A. Mina , Ye Jianguo
Published: December 2022

In this paper, we investigate the existence, number and stability of periodic orbits for the following contact Hamiltonian system $$H(p,q,s,t)=\frac{p^{2}}{2m}+G(t,q,m)-mdq+cs(c>0)$$

H

(
p
,
q
,
s
,
t
)

=

p
2

2
m

+
G

(
t
,
q
,
m
)

-
m
d
q
+
c
s

(
c
>
0
)

. At the same time, unbounded conditions of each solution are also given. The contact Hamiltonian system actually represents a kind of physical phenomenon with non-conservation of energy, but the contact Hamiltonian system studied in this paper represents a one-dimensional damped oscillator system with constant variable sign damping coefficient under certain conditions. Therefore, it is of great physical significance to study the periodic dynamic properties of such system.
Fast Three‐Dimensional Search Algorithm to Improve the Carrier Tracking Performance During the Entry, Descent, and Landing (EDL) Phase of Mars Probes
Authors: Deng Tao , Ma Maoli , Liu Qinghui
Published: December 2022

Carrier tracking for highly dynamic and extremely weak signals is challenging, including during the entry, descent, and landing phase of Mars rovers and the soft landing of lunar probes. In this study, a novel frequency detector is designed based on the frequency maximum likelihood estimator, and a frequency‐locked loop algorithm is constructed. The frequency‐locked loop is suitable for tracking Doppler shifts with large first and second derivatives. Compared with the Jet Propulsion Laboratory frequency maximum likelihood estimator, the computation time is significantly reduced. The simulation results illustrate the effectiveness of the proposed algorithm. This method provides a good method for Doppler frequency measurement in deep space exploration, especially when tracking highly dynamic and extremely weak signals.
Carbonates in the Critical Zone
Authors: Covington M. D. , Martin J. B. , Toran L. E. , Macalady J. L. , Sekhon N. , Sullivan P. L. , García Á. A. , Heffernan J. B. , Graham W. D.
Published: December 2022

Earth's Critical Zone (CZ), the near‐surface layer where rock is weathered and landscapes co‐evolve with life, is profoundly influenced by the type of underlying bedrock. Previous studies employing the CZ framework have focused primarily on landscapes dominated by silicate rocks. However, carbonate rocks crop out on approximately 15% of Earth's ice‐free continental surface and provide important water resources and ecosystem services to ∼1.2 billion people. Unlike silicates, carbonate minerals weather congruently and have high solubilities and rapid dissolution kinetics, enabling the development of large, interconnected pore spaces and preferential flow paths that restructure the CZ. Here we review the state of knowledge of the carbonate CZ, exploring parameters that produce contrasts in the CZ in different carbonate settings and identifying important open questions about carbonate CZ processes. We introduce the concept of a carbonate‐silicate CZ spectrum and examine whether current conceptual models of the CZ, such as the conveyor model, can be applied to carbonate landscapes. We argue that, to advance beyond site‐specific understanding and develop a more general conceptual framework for the role of carbonates in the CZ, we need integrative studies spanning both the carbonate‐silicate spectrum and a range of carbonate settings.
2021 February Texas Ice Storm Induced Spring GPP Reduction Compensated by the Higher Precipitation
Authors: Yang Linqing , Liu Meng
Published: December 2022

Climate extremes are more frequent and affect the carbon cycle. On 10–20 February, an exceptional winter storm in Texas brought severe ecological and economic effects. However, its impacts on vegetation activities and the carbon cycle are unclear. This study evaluated the early 2021 ice storm effects on spring phenology and the carbon cycle. The results showed that the ice storm led to a significant later vegetation spring phenology and a reduction of 42.32 Tg C in gross primary production (GPP) and a reduction of 34. 47 Tg C net ecosystem production (NEP) in spring. In the 2021 spring, Texas became a carbon source from the carbon sink. More precipitation in late spring and summer precipitation recharged the rootzone soil moisture, which enhanced summer vegetation GPP and NEP and compensated for the effects of the ice storm on spring carbon uptake. The summer GPP enhancement offset all the spring GPP reduction, and thus GPP was increased by 4.97% during 2021. 91.47% of the spring NEP reduction was compensated by summer NEP enhancement due to higher root zone soil moisture. Due to the NEP enhancement during autumn, NEP did not decrease as well and increased by 10.88% during 2021. This observation‐based research highlights the seasonal compensation effects on the interactions between extreme climate events and the biosphere.
A Subjective Bayesian Framework for Synthesizing Deep Uncertainties in Climate Risk Management
Authors: Doss‐Gollin James , Keller Klaus
Published: December 2022

Projections of nonstationary climate risks can vary considerably from one source to another, posing considerable communication and decision‐analytical challenges. One such challenge is how to present trade‐offs under deep uncertainty in a salient and interpretable manner. Some common approaches include analyzing a small subset of projections or treating all considered projections as equally likely. These approaches can underestimate risks, hide deep uncertainties, and are mostly silent on which assumptions drive decision‐relevant outcomes. Here we introduce and demonstrate a transparent Bayesian framework for synthesizing deep uncertainties to inform climate risk management. The first step of this workflow is to generate an ensemble of simulations representing possible futures and analyze them through standard exploratory modeling techniques. Next, a small set of probability distributions representing subjective beliefs about the likelihood of possible futures is used to weight the scenarios. Finally, these weights are used to compute and characterize trade‐offs, conduct robustness checks, and reveal implicit assumptions. We demonstrate the framework through a didactic case study analyzing how high to elevate a house to manage coastal flood risks.
Projection of Hourly Extreme Precipitation Using the WRF Model Over Eastern China
Authors: Tang Jianping , Lu Yun , Wang Shuguang , Guo Ziyue , Lu Yutong , Fang Juan
Published: December 2022

The Weather Research and Forecasting (WRF) model was applied to simulate the current and future climates over eastern China at a convection‐permitting resolution (∼4 km). A continuous 10‐year (1998–2007) simulation was performed for the historical climate, and three pseudo‐global warming (PGW) experiments driven by climate perturbations during 2070–2099 were conducted under the RCP2.6, RCP4.5, and RCP8.5 scenarios. After validation against reanalysis and observational data, the historical simulation was found capable of reasonably reproducing the characteristics of mean precipitation, extreme hourly precipitation, and large‐scale circulation. The PGW experiments projected an increase in precipitation intensity over most regions, especially North China under the RCP8.5 scenario (up to 30%). However, the precipitation frequency was projected to decrease, especially over the Yangtze River Basin in summer. A wetting (drying) trend was observed over North China (South China) in summer (winter), due to the increase (decrease) in precipitation intensity (frequency). The intensity and frequency of extreme events were projected to increase over most areas of eastern China, and the increase was the most dramatic under the RCP8.5 scenario, indicating a greater flood risk under stronger global warming. The relationship between extreme precipitation and temperature (EP–T) displayed a hook‐shape structure in both the present and future climates. The extreme precipitation intensity increased with temperature at a super Clausius–Clapeyron (C–C) scaling rate (>7%/K) until reaching a peak at temperatures of around 25–29°C, and then decreased at higher temperatures. The decreases were mainly attributed to moisture limitation at high temperatures. In the future, the EP–T relationship is expected to change mostly following the C–C law, with greater precipitation peaks under scenarios with higher carbon emissions, indicating that warmer climates contribute to further enhancement of extreme precipitation.
Mixed heavy metal stress induces global iron starvation response
Authors: Goff Jennifer L , Chen Yan , Thorgersen Michael P , Hoang Linh T , Poole Farris L , Szink Elizabeth G , Siuzdak Gary , Petzold Christopher J , Adams Michael W W
Published: December 2022

Multiple heavy metal contamination is an increasingly common global problem. Heavy metals have the potential to disrupt microbially mediated biogeochemical cycling. However, systems-level studies on the effects of combinations of heavy metals on bacteria are lacking. For this study, we focused on the Oak Ridge Reservation (ORR; Oak Ridge, TN, USA) subsurface which is contaminated with several heavy metals and high concentrations of nitrate. Using a native Bacillus cereus isolate that represents a dominant species at this site, we assessed the combined impact of eight metal contaminants, all at site-relevant concentrations, on cell processes through an integrated multi-omics approach that included discovery proteomics, targeted metabolomics, and targeted gene-expression profiling. The combination of eight metals impacted cell physiology in a manner that could not have been predicted from summing phenotypic responses to the individual metals. Exposure to the metal mixture elicited a global iron starvation response not observed during individual metal exposures. This disruption of iron homeostasis resulted in decreased activity of the iron-cofactor-containing nitrate and nitrite reductases, both of which are important in biological nitrate removal at the site. We propose that the combinatorial effects of simultaneous exposure to multiple heavy metals is an underappreciated yet significant form of cell stress in the environment with the potential to disrupt global nutrient cycles and to impede bioremediation efforts at mixed waste sites. Our work underscores the need to shift from single- to multi-metal studies for assessing and predicting the impacts of complex contaminants on microbial systems.
Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre
Authors: Scheiter Alexander , Hierl Frederik , Lüke Florian , Keil Felix , Heudobler Daniel , Einhell Sabine , Klier-Richter Margit , Konstandin Nikola P. , Weber Florian , Scheiter Andrea , Kandulski Arne , Schlosser Sophie , Cosma Lidia-Sabina , Tews Hauke , Weiss Andreas R. R. , Grube Matthias , Bumes Elisabeth , Hau Peter , Proescholdt Martin , Steger Felix , Troeger Anja , Haferkamp Sebastian , Reibenspies Lucas E. , Schnabel Marco J. , Schulz Christian , Drexler Konstantin , Hatzipanagiotou Maria E. , Seitz Stephan , Klinkhammer-Schalke Monika , Unberath Philipp , Calvisi Diego F. , Pukrop Tobias , Dietmaier Wolfgang , Evert Matthias , Utpatel Kirsten
Published: December 2022

Background

Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021.

Methods and results

In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278).

Conclusion

The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly.
Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis
Authors: Guo Jiawei , Song Zihao , Yu Jie , Li Chengyi , Jin Chenchen , Duan Wei , Liu Xiu , Liu Yingying , Huang Shuai , Tuo Yonghua , Pei Fei , Jian Zhengyang , Zhou Pengyu , Zheng Shaoyi , Zou Zhaowei , Zhang Feng , Gong Quan , Liang Sijia
Published: December 2022

Ischemia/reperfusion (I/R)-induced liver injury with severe cell death is a major complication of liver transplantation. Transmembrane member 16A (TMEM16A), a component of hepatocyte Ca2+-activated chloride channel, has been implicated in a variety of liver diseases. However, its role in hepatic I/R injury remains unknown. Here, mice with hepatocyte-specific TMEM16A knockout or overexpression were generated to examine the effect of TMEM16A on hepatic I/R injury. TMEM16A expression increased in liver samples from patients and mice with I/R injury, which was correlated with liver damage progression. Hepatocyte-specific TMEM16A knockout alleviated I/R-induced liver damage in mice, ameliorating inflammation and ferroptotic cell death. However, mice with hepatic TMEM16A overexpression showed the opposite phenotype. In addition, TMEM16A ablation decreased inflammatory responses and ferroptosis in hepatocytes upon hypoxia/reoxygenation insult in vitro, whereas TMEM16A overexpression promoted the opposite effects. The ameliorating effects of TMEM16A knockout on hepatocyte inflammation and cell death were abolished by chemically induced ferroptosis, whereas chemical inhibition of ferroptosis reversed the potentiated role of TMEM16A in hepatocyte injury. Mechanistically, TMEM16A interacted with glutathione peroxidase 4 (GPX4) to induce its ubiquitination and degradation, thereby enhancing ferroptosis. Disruption of TMEM16A–GPX4 interaction abrogated the effects of TMEM16A on GPX4 ubiquitination, ferroptosis, and hepatic I/R injury. Our results demonstrate that TMEM16A exacerbates hepatic I/R injury by promoting GPX4-dependent ferroptosis. TMEM16A–GPX4 interaction and GPX4 ubiquitination are therefore indispensable for TMEM16A-regulated hepatic I/R injury, suggesting that blockades of TMEM16A–GPX4 interaction or TMEM16A inhibition in hepatocytes may represent promising therapeutic strategies for acute liver injury.
Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells
Authors: Occhigrossi Luca , D’Eletto Manuela , Vecchio Alessio , Piacentini Mauro , Rossin Federica
Published: December 2022

cGAS/STING axis is the major executor of cytosolic dsDNA sensing that leads to the production of type I interferon (IFNI) not only upon bacterial infection, but also in cancer cells, upon DNA damage. In fact, DNA damage caused by ionizing radiations and/or topoisomerase inhibitors leads to a release of free DNA into the cytosol, which activates the cGAS/STING pathway and the induction of IFNI expression. Doxorubicin-induced apoptotic cancer cells release damage-associated molecular patterns (DAMPs), including IFNI, which are able to stimulate the immune system. Our results indicate that Transglutaminase type 2 (TG2) is directly involved in the formation of a covalent cross-linked IRF3 (Interferon regulatory factor 3) dimers, thereby limiting the production of IFNI. Indeed, we demonstrated that upon doxorubicin treatment TG2 translocates into the nucleus of apoptotic melanoma cells interacting with IRF3 dimers. Interestingly, we show that both the knockdown of the enzyme as well as the inhibition of its transamidating activity lead to a decrease in the dimerization of IRF3 correlated with an increase in the IFNI mRNA levels. Taken together, these data demonstrate that TG2 negatively regulates the IRF3 pathway in human melanoma cells suggesting a so far unknown TG2-dependent mechanism by which cancer cells reduce the IFNI production after DNA damage to limit the immune system response.
Real world outcomes of photodynamic therapy for chronic central serous chorioretinopathy
Authors: Khandhadia Samir , Thulasidharan Suresh , Hoang Nguyen Thuy Vy , Ibrahim Sameh Alkhalili , Ouyang Yanling , Lotery Andrew
Published: December 2022

Objectives

We describe the real-world outcomes of photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR) in a single centre over nine years.

Methods

We carried out a retrospective analysis of patients with chronic CSCR who received half dose PDT in a single centre between 2011 and 2019. Visual acuity (VA) and retinal thickness (RT) was recorded between baseline visit and first recorded review visit.

Results

We included 125 eyes of 113 patients in this study. Mean age at treatment was 55.0 ± 12.1 years, with a higher male predominance (83 men, 30 women). Mean baseline VA was 0.40 ± 0.31 logMAR with a mean visual outcome gain post-PDT of 0.05 logMAR (p = 0.005). Mean baseline RT was 390 ± 82 microns with a mean reduction of RT post-PDT of 66 microns (p < 0.001). 17.6% of eyes were treated for recurrent CSCR.

Conclusion

We found overall a mean improvement in VA and structural outcomes after PDT. In the absence of randomised clinical trials this study supports the use of half dose PDT for treatment of chronic CSCR.
Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease
Authors: Lekka Evangelia , Kokanovic Aleksandra , Mosole Simone , Civenni Gianluca , Schmidli Sandro , Laski Artur , Ghidini Alice , Iyer Pavithra , Berk Christian , Behera Alok , Catapano Carlo V. , Hall Jonathan
Published: December 2022

Lin28 RNA-binding proteins are stem-cell factors that play key roles in development. Lin28 suppresses the biogenesis of let-7 microRNAs and regulates mRNA translation. Notably, let-7 inhibits Lin28, establishing a double-negative feedback loop. The Lin28/let-7 axis resides at the interface of metabolic reprogramming and oncogenesis and is therefore a potential target for several diseases. In this study, we use compound-C1632, a drug-like Lin28 inhibitor, and show that the Lin28/let-7 axis regulates the balance between ketogenesis and lipogenesis in liver cells. Hence, Lin28 inhibition activates synthesis and secretion of ketone bodies whilst suppressing lipogenesis. This occurs at least partly via let-7-mediated inhibition of nuclear receptor co-repressor 1, which releases ketogenesis gene expression mediated by peroxisome proliferator-activated receptor-alpha. In this way, small-molecule Lin28 inhibition protects against lipid accumulation in multiple cellular and male mouse models of hepatic steatosis. Overall, this study highlights Lin28 inhibitors as candidates for the treatment of hepatic disorders of abnormal lipid deposition.
Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex
Authors: Wilson Madison N. , Thunemann Martin , Liu Xin , Lu Yichen , Puppo Francesca , Adams Jason W. , Kim Jeong-Hoon , Ramezani Mehrdad , Pizzo Donald P. , Djurovic Srdjan , Andreassen Ole A. , Mansour Abed AlFatah , Gage Fred H. , Muotri Alysson R. , Devor Anna , Kuzum Duygu
Published: December 2022

Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain.
Single planar photonic chip with tailored angular transmission for multiple-order analog spatial differentiator
Authors: Liu Yang , Huang Mingchuan , Chen Qiankun , Zhang Douguo
Published: December 2022

Analog spatial differentiation is used to realize edge-based enhancement, which plays an important role in data compression, microscopy, and computer vision applications. Here, a planar chip made from dielectric multilayers is proposed to operate as both first- and second-order spatial differentiator without any need to change the structural parameters. Third- and fourth-order differentiations that have never been realized before, are also experimentally demonstrated with this chip. A theoretical analysis is proposed to explain the experimental results, which furtherly reveals that more differentiations can be achieved. Taking advantages of its differentiation capability, when this chip is incorporated into conventional imaging systems as a substrate, it enhances the edges of features in optical amplitude and phase images, thus expanding the functions of standard microscopes. This planar chip offers the advantages of a thin form factor and a multifunctional wave-based analogue computing ability, which will bring opportunities in optical imaging and computing.
Ordovician–Silurian true polar wander as a mechanism for severe glaciation and mass extinction
Authors: Jing Xianqing , Yang Zhenyu , Mitchell Ross N. , Tong Yabo , Zhu Min , Wan Bo
Published: December 2022

The Ordovician–Silurian transition experienced severe, but enigmatic, glaciation, as well as a paradoxical combination of mass extinction and species origination. Here we report a large and fast true polar wander (TPW) event that occurred 450–440 million years ago based on palaeomagnetic data from South China and compiled reliable palaeopoles from all major continents. Collectively, a ~50˚ wholesale rotation with maximum continental speeds of ~55 cm yr−1 is demonstrated. Multiple isolated continents moving rapidly, synchronously, and unidirectionally is less consistent with and plausible for relative plate motions than TPW. Palaeogeographic reconstructions constrained by TPW controlling for palaeolongitude explain the timing and migration of glacial centers across Gondwana, as well as the protracted end-Ordovician mass extinction. The global quadrature pattern of latitude change during TPW further explains why the extinction was accompanied by elevated levels of origination as some continents migrated into or remained in the amenable tropics.
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Authors: Maher Allison K. , Burnham Katie L. , Jones Emma M. , Tan Michelle M. H. , Saputil Rocel C. , Baillon Laury , Selck Claudia , Giang Nicolas , Argüello Rafael , Pillay Clio , Thorley Emma , Short Charlotte-Eve , Quinlan Rachael , Barclay Wendy S. , Cooper Nichola , Taylor Graham P. , Davenport Emma E. , Dominguez-Villar Margarita
Published: December 2022

Although alterations in myeloid cells have been observed in COVID-19, the specific underlying mechanisms are not completely understood. Here, we examine the function of classical CD14+monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals. Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes. Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis. COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2. Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation. These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.