bluuebunny/crossref_metadata_2025 huggingface dataset:
Triads in Lean Management: Analyzing Buyer–Supplier-Supplier and Buyer–Supplier-Supplier’s Supplier Relationships for Zero-Defect Manufacturing
Authors: Kovalevskaya Daria , Pedersen Ann-Charlott , Holmen Elsebeth , Kaloudis Aristidis , Ringen Geir
Published: December 2022

Many studies on buyer–supplier-supplier triads demonstrate the value of the interactions between three business actors instead of two for identifying triadic collaboration strategies that can lead firms to improve their performance. However, there is little research to date that has explored which specific lean improvements the various types of buyer–supplier-supplier triads lead to. This paper fills this gap. We study an automotive supplier manufacturing company (the buyer) and its seven types of buyer–supplier-supplier triads emerging from the buyers’ attempt to implement zero-defect manufacturing (ZDM) in the production process of a crash management system. The case study shows how a buyer manages their first-tier suppliers through three types of closed buyer–supplier-supplier triads, where all three actors collaborate to work for the common goal of ZDM. The case also shows four additional types of open triads, where the buyer relies on the first-tier supplier to manage the second-tier supplier without directly interacting with the latter. The paper discusses what types of triads in the case study seem to be associated with the buyers’ efforts to achieve the following lean sub-goals of ZDM: full automation, production line flexibility, product flexibility, low cost, low defect rate, short cycle time, and minimum quality control. Finally, we also analyze the role of geographic proximity between the actors in open and closed buyer–supplier-supplier ZDM triads.
Subjectivity and Non-Objectifying Awareness
Authors: O’Conaill Donnchadh
Published: December 2022

We are each aware of our own experiences as they occur, but in this inner awareness our experiences do not seem to be presented to us as objects in the way that they typically are when we reflect on them. A number of philosophers, principally in the phenomenological tradition, have characterised this in terms of inner awareness being a non-objectifying mode of awareness. This claim has faced persistent objections that the notion of non-objectifying awareness is obscure or merely negatively characterised. In this paper I shall outline a positive conception of a non-objectifying mode of awareness, feature-encountering awareness. I shall apply this conception to our awareness of our experiences, characterising it as an awareness of instantiations of phenomenal properties in a temporal dimension. Inner awareness thus characterised clearly differs from standard modes of objectifying awareness.
Thanks to reviewers and editorial office
Authors: Maggio Lauren A. , Driessen Erik W.
Published: December 2022

None
Large improvement of mental health during in outpatient short-term group psychotherapy treatment—a naturalistic pre-/post-observational study
Authors: Riedl David , Labek Karin , Gstrein Ines , Rothmund Maria-Sophie , Sperner-Unterweger Barbara , Kantner-Rumplmair Wilhelm
Published: December 2022

Background

Group psychotherapy is an effective treatment for patients with mental health issues. This study aims to evaluate data on the effectiveness of a cost-free short-term outpatient group psychotherapy project for patients with mixed mental health issues in Tyrol, Austria.

Methods

In this naturalistic observational study, outpatients taking part in the psychotherapeutic group treatment between spring 2018 and spring 2020 were included. Patients completed the patient health questionnaire (PHQ-D), an item of the working ability index (WAI) and single items on symptom burden, treatment expectation and perceived benefit before the first (T0) and/or last group session (T1). Mean changes were investigated using repeated measure analyses of variance (rANOVA).

Results

A total of 98 patients were included in the study. Statistically significant improvements with medium to large effect sizes were observed for depression (η2 = 0.22, p < 0.001), somatization (η2 = 0.10, p = 0.008), anxiety (η2 = 0.18, p < 0.001), and subjective working ability (η2 = 0.22, p < 0.001). Neither age (p = 0.85), sex (p = 0.34), baseline symptoms (p = 0.29–0.77), nor previous experience with individual (p = 0.15) or group psychotherapy (p = 0.29) were associated with treatment outcome. However, treatment expectation at baseline was significantly associated with the patients’ perception of the treatment benefit (r = 0.39, p < 0.001).

Conclusion

Our study highlights the benefit of outpatient short-term group psychotherapy for individuals with mental health issues. Group psychotherapy should be offered free of charge to individuals with mental health issues by social health providers.
Ultralow Interfacial Thermal Resistance of Graphene Thermal Interface Materials with Surface Metal Liquefaction
Authors: Dai Wen , Ren Xing-Jie , Yan Qingwei , Wang Shengding , Yang Mingyang , Lv Le , Ying Junfeng , Chen Lu , Tao Peidi , Sun Liwen , Xue Chen , Yu Jinhong , Song Chengyi , Nishimura Kazuhito , Jiang Nan , Lin Cheng-Te
Published: December 2022

Developing advanced thermal interface materials (TIMs) to bridge heat-generating chip and heat sink for constructing an efficient heat transfer interface is the key technology to solve the thermal management issue of high-power semiconductor devices. Based on the ultra-high basal-plane thermal conductivity, graphene is an ideal candidate for preparing high-performance TIMs, preferably to form a vertically aligned structure so that the basal-plane of graphene is consistent with the heat transfer direction of TIM. However, the actual interfacial heat transfer efficiency of currently reported vertically aligned graphene TIMs is far from satisfactory. In addition to the fact that the thermal conductivity of the vertically aligned TIMs can be further improved, another critical factor is the limited actual contact area leading to relatively high contact thermal resistance (20–30 K mm2 W−1) of the “solid–solid” mating interface formed by the vertical graphene and the rough chip/heat sink. To solve this common problem faced by vertically aligned graphene, in this work, we combined mechanical orientation and surface modification strategy to construct a three-tiered TIM composed of mainly vertically aligned graphene in the middle and micrometer-thick liquid metal as a cap layer on upper and lower surfaces. Based on rational graphene orientation regulation in the middle tier, the resultant graphene-based TIM exhibited an ultra-high thermal conductivity of 176 W m−1 K−1. Additionally, we demonstrated that the liquid metal cap layer in contact with the chip/heat sink forms a “liquid–solid” mating interface, significantly increasing the effective heat transfer area and giving a low contact thermal conductivity of 4–6 K mm2 W−1 under packaging conditions. This finding provides valuable guidance for the design of high-performance TIMs based on two-dimensional materials and improves the possibility of their practical application in electronic thermal management.
The impact on air quality of PM10 emissions from the bus fleet of Buenos Aires City
Authors: Accorinti Jesica , Allende David , Puliafito Salvador E.
Published: December 2022

Automobile transport in megacities poses serious problems in the area of sustainability and environmental security. In the City of Buenos Aires (CABA) it represents 37% of GHG emissions and is an important source of pollutants dangerous to human health. As such, it is an energy consumption sector targeted for the implementation of methods that allow for sustainable urban transport. At the same time, very few previous studies about transport vehicle emissions have utilized the PM10 as an indicator of environmental contamination, considering that the negative impact of this environmental contaminant on human health is widely studied. An emission model linked to an atmospheric dispersion model, statistically validated, were used to study different scenarios of emissions generated by diesel buses. It was observed that in a scenario of zero bus emissions (E0), PM10 immission (air concentrations) concentration in CABA is reduced by half. When studying the energy transition from diesel buses to electric energy, while the rest of the vehicle fleet was maintained at the expense of fossil fuels, the local immission concentration of PM10 in CABA was of the same magnitude of that which was obtained when simulating the (E0) scenario of only private vehicle fleet. This study is relevant in the evaluation of public policy on vehicle emission mitigation that seeks to reduce health risks from poor air quality and to develop a more progressively sustainable city.

Article Highlights

Transition energy exclusively for buses could reduce PM10 immission values of CABA by 50%.

Thermal energy needed to the energy transition does not significant impact the PM10 immission values on the local air quality.

Electric buses could reduce the maximum PM10 immission value by half.
Three dimensional BC/rGA aerogel: preparation, characterization, and adsorption of Cr(VI)
Authors: Che Naiju , Liu Na , Li Yinhui , Li Chao , Liu Yanli , Li Chengliang
Published: December 2022

Graphene-based composite aerogel doped with other low-cost materials can reduce the cost and promote the use in water treatment. This work prepared ball-milled biochar/reduced graphene oxide aerogel (BC/rGA) using GO and low-cost ball-milled biochar (BC) in a certain proportion with the freeze-thawing technique and sol–gel method, and applied BC/rGA on the Cr(VI) removal from aquatic environments. The characterization results showed that aerogel had a honeycomb briquette three-dimension (3D) and mesoporous structure with interconnected pores, and proved the preparation progress of aerogel in principle. Compared with GO, rGA and BC/rGA had better adsorption performance with 3D structure and well-developed pores, and BC/rGA with the mixture ratio of BC and GO of 1:4 was more appropriate. The adsorption kinetics data of rGA and BC/rGA(1:4) were fitting well with the pseudo-second-order model (R2 > 0.951), and the isotherm adsorption results were fitting the Langmuir model well (R2 > 0.974). The results demonstrated that the adsorption process was monolayer and endothermic adsorption involving chemisorption. Additionally, the adsorption capacities of rGA and BC/rGA(1:4) at solution pH 2 were 3.71 and 3.89 times greater than those at solution pH 8, respectively. High background ion strength and low temperature slightly inhibited the adsorption of Cr(VI) by both rGA and BC/rGA(1:4). The adsorption mechanisms of Cr(VI) on rGA and BC/rGA(1:4) were electrostatic interaction, reduction and ion exchange. The use of BC/rGA could reduce the cost and promote the green reuse of agricultural waste. Overall, BC/rGA could be used as a promising green adsorbent alternative for the feasible treatment of heavy metal contaminated water.

Graphical Abstract
The role of post-transcriptional modifications during development
Authors: Hamar Renáta , Varga Máté
Published: December 2022

While the existence of post-transcriptional modifications of RNA nucleotides has been known for decades, in most RNA species the exact positions of these modifications and their physiological function have been elusive until recently. Technological advances, such as high-throughput next-generation sequencing (NGS) methods and nanopore-based mapping technologies, have made it possible to map the position of these modifications with single nucleotide accuracy, and genetic screens have uncovered the “writer”, “reader” and “eraser” proteins that help to install, interpret and remove such modifications, respectively. These discoveries led to intensive research programmes with the aim of uncovering the roles of these modifications during diverse biological processes. In this review, we assess novel discoveries related to the role of post-transcriptional modifications during animal development, highlighting how these discoveries can affect multiple aspects of development from fertilization to differentiation in many species.
Efficient Path and Action Planning Method for Multi-Agent Pickup and Delivery Tasks under Environmental Constraints
Authors: Yamauchi Tomoki , Miyashita Yuki , Sugawara Toshiharu
Published: December 2022

We propose a method called path and action planning with orientation (PAPO) that efficiently generates collision-free paths to satisfy environmental constraints, such as restricted path width and node size, for the multi-agent pickup and delivery in non-uniform environment (N-MAPD) problem. The MAPD problem, wherein multiple agents repeatedly pick up and carry materials without collisions, has attracted considerable attention; however, conventional MAPD algorithms assume a specially designed environment and thus use simple, uniform models with few environmental constraints. Such conventional algorithms cannot be applied to realistic applications where agents need to move in more complex and restricted environments. For example, the actions and orientations of agents are strictly restricted by the sizes of agents and carrying materials and the width of the passages at a construction site and a disaster area. In our N-MAPD formulation, which is an extension of the MAPD problem to apply to non-uniform environments with constraints, PAPO considers not only the path to the destination but also the agents’ direction, orientation, and timing of rotation. It is costly to consider all these factors, especially when the number of nodes is large. Our method can efficiently generate acceptable plans by exploring the search space via path planning, action planning, and conflict resolution in a phased manner. We experimentally evaluated the performance of PAPO by comparing it with our previous method, which is the preliminary version of PAPO, the baseline method in a centralized approach, and fundamental meta-heuristic algorithms. Finally, we demonstrate that PAPO can efficiently generate sub-optimal paths for N-MAPD instances.
Does number of rods matter? 4-, 5-, and 6-rods across a lumbar pedicle subtraction osteotomy: a finite element analysis
Authors: Shekouhi Niloufar , Vosoughi Ardalan S. , Goel Vijay K. , Theologis Alekos A.
Published: December 2022

Purpose

To assess biomechanics of a lumbar PSO stabilized with different multi-rod constructs (4-, 5-, 6-rods) using satellite and accessory rods.

Methods

A validated spinopelvic finite element model with a L3 PSO was used to evaluate the following constructs: 2 primary rods T10-pelvis (“Control”), two satellite rods (4-rod), two satellite rods + one accessory rod (5-rod), or two satellite rods + two accessory rods (6-rod). Data recorded included: ROM T10-S1 and L2-L4, von Mises stresses on primary, satellite, and accessory rods, factor of safety yield stress, and force across the PSO surfaces. Percent differences relative to Control were calculated.

Results

Compared to Control, 4-rods increased PSO flexion and extension. Lower PSO ROMs were observed for 5- and 6-rods compared to 4-rods. However, 4-rod (348.6 N) and 5-rod (343.2 N) showed higher PSO forces than 2-rods (336 N) and 6-rods had lower PSO forces (324.2 N). 5- and 6-rods led to the lowest rod von Mises stresses across the PSO. 6-rod had the maximum factor of safety on the primary rods.

Conclusions

In this finite element analysis, 4-rods reduced stresses on primary rods across a lumbar PSO. Although increased rigidity afforded by 5- and 6-rods decreased rod stresses, it resulted in less load transfer to the anterior vertebral column (particularly for 6-rod), which may not be favorable for the healing of the anterior column. A balance between the construct’s rigidity and anterior load sharing is essential.
An empirical analysis of the relationship between nature of science and critical thinking through science definitions and thinking skills
Authors: Manassero-Mas María Antonia , Vázquez-Alonso Ángel
Published: December 2022

Critical thinking (CRT) skills transversally pervade education and nature of science (NOS) knowledge is a key component of science literacy. Some science education researchers advocate that CRT skills and NOS knowledge have a mutual impact and relationship. However, few research studies have undertaken the empirical confirmation of this relationship and most fail to match the two terms of the relationship adequately. This paper aims to test the relationship by applying correlation, regression and ANOVA procedures to the students’ answers to two tests that measure thinking skills and science definitions. The results partly confirm the hypothesised relationship, which displays some complex features: on the one hand, the relationship is positive and significant for the NOS variables that express adequate ideas about science. However, it is non-significant when the NOS variables depict misinformed ideas about science. Furthermore, the comparison of the two student cohorts reveals that two years of science instruction do not seem to contribute to advancing students’ NOS conceptions. Finally, some interpretations and consequences of these results for scientific literacy, teaching NOS (paying attention both to informed and misinformed ideas), for connecting NOS with general epistemic knowledge, and assessing CRT skills are discussed.
Lessons for science and technology policy? Probing the Linkedin network of an RDI organisation
Authors: Sachini Evi , Sioumalas-⁠ Christodoulou Konstantinos , Bouras Nikias , Karampekios Nikolaos
Published: December 2022

In this paper, we seek to examine the network of the Greek National Documentation Centre (EKT) as formed by its LinkedIn followers. By applying specific data collection and processing techniques, we explore the network of all the individuals that follow EKT’s LinkedIn page. Significant manual and automatic approaches have been implemented with regard to data extraction, data curation and data homogenization. The aim is to identify the network’s advancement over time, the institutions involved and the countries. The timeframe of the study spans from when the relevant LinkedIn page was constructed in 2015 to 2020. Findings indicate that there is a steady increase in the number of new followers, peaking in 2020. On an international scale, the evolution of the network of followers is imprinted and distributed in worldwide maps. In total, 68 countries have followed EKT over the examined time period. Also, in terms of followers’ institutional sector the Business Sector (BES) stands out (46.5%). Higher Education (HES) and Government Sector (GOV) are associated with 26.4 and 22.2% of the followers, respectively. Lastly, this paper provides a first institutional and country-level mapping of who constitutes the organisation’s interlocutors in the national and global RDI ecosystem.
HOTAIR gene polymorphisms and risk of glioma in Chinese children
Authors: Lin Lei , Chen Yong-Ping , Liao Yuxiang , Yuan Li , Huang Xiao-Kai , Ruan Ji-Chen , Li Meng , Lin Hui-Ran , Miao Lei
Published: December 2022

Purpose

Glioma is the most common malignant brain tumor in children. Hox transcription antisense intergenic RNA (HOTAIR) has been shown to promote cancers. However, the role of genetic variation of HOTAIR gene on glioma susceptibility has not been fully elucidated. We aimed to evaluate whether HOTAIR gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to glioma.

Methods

The trial included a total of 171 glioma patients and 228 non-glioma controls from Chinese children. Genotyping of HOTAIR gene was evaluated by TaqMan. The strength of the association between HOTAIR gene polymorphism (rs920778 A > G, rs4759314 A > G, rs1899663 C > A) and glioma susceptibility was assessed using odds ratios and 95% confidence intervals. Stratified analysis was further conducted.

Results

Of the three SNPs analyzed, the rs920778 variant and the rs1899663 variant were associated with increased glioma susceptibility. In addition, the combination of two risk genotypes (OR = 1.63, P = 0.028) and one to three risk genotypes (OR = 1.58, P = 0.027) showed a significantly higher increase in glioma susceptibility than zero risk genotypes. These two SNPs (rs920778 A > G, rs1899663 C > A) were significantly associated with increased glioma susceptibility in certain subgroups in stratified analysis. Similar results were found in stratified analyses for one to three risk genotypes compared with zero risk genotypes. Splice quantitative trait loci (sQTLs) indicated rs920778 A > G and rs1899663 C > A are associated with splicing events in certain genes (HOTAIR, HOXC5, HOXC10, HOXC6, and HOXC4).

Conclusion

Overall, our results suggest that some HOTAIR SNPs are associated with increased glioma susceptibility.
An Introduction to Infinite-Dimensional Differential Geometry
Authors: Schmeding Alexander
Published: December 2022

Introducing foundational concepts in infinite-dimensional differential geometry beyond Banach manifolds, this text is based on Bastiani calculus. It focuses on two main areas of infinite-dimensional geometry: infinite-dimensional Lie groups and weak Riemannian geometry, exploring their connections to manifolds of (smooth) mappings. Topics covered include diffeomorphism groups, loop groups and Riemannian metrics for shape analysis. Numerous examples highlight both surprising connections between finite- and infinite-dimensional geometry, and challenges occurring solely in infinite dimensions. The geometric techniques developed are then showcased in modern applications of geometry such as geometric hydrodynamics, higher geometry in the guise of Lie groupoids, and rough path theory. With plentiful exercises, some with solutions, and worked examples, this will be indispensable for graduate students and researchers working at the intersection of functional analysis, non-linear differential equations and differential geometry. This title is also available as Open Access on Cambridge Core.
Evolution and Christianity
Authors: Ruse Michael
Published: December 2022

This Element discusses the relationship between Christianity and evolutionary theory, with special emphasis on Darwinian evolutionary theory (Darwinism). The Creationists argue that the two are incompatible and it is religion that is the truth and Darwinism the falsity. The New Atheists argue that the two are incompatible and it is religion that is the falsity and Darwinism the truth. Through a careful examination of both Darwinian theory and Christianity, it is shown that both extremes are mistaken. It is accepted that there are difficult issues to be solved, for example the problem of evil - which some think is exacerbated by Darwinism - and the necessarily appearance of Homo sapiens - which is problematic if evolutionary theory does not guarantee progress and the evolution of humans as the apotheosis. It is argued that there are ways forward, and Christianity and evolutionary thinking can be shown compatible.
Physics of Wave Turbulence
Authors: Galtier Sébastien
Published: December 2022

A century ago, Lewis Fry Richardson introduced the concept of energy cascades in turbulence. Since this conceptual breakthrough, turbulence has been studied in diverse systems and our knowledge has increased considerably through theoretical, numerical, experimental and observational advances. Eddy turbulence and wave turbulence are the two regimes we can find in nature. So far, most attention has been devoted to the former regime, eddy turbulence, which is often observed in water. However, physicists are often interested in systems for which wave turbulence is relevant. This textbook deals with wave turbulence and systems composed of a sea of weak waves interacting non-linearly. After a general introduction which includes a brief history of the field, the theory of wave turbulence is introduced rigorously for surface waves. The theory is then applied to examples in hydrodynamics, plasma physics, astrophysics and cosmology, giving the reader a modern and interdisciplinary view of the subject.
Rethinking ‘Jurisdiction’ in International Human Rights Law in Rescue Operations at Sea in the Light of AS and Others v Italy and AS and Others v Malta: A New Right to be Rescued at Sea?
Authors: Dimitrova Silvia
Published: December 2022

In January 2021 the Human Rights Committee determined that Italy and Malta had both failed to protect the right to life of more than 200 migrants who perished in a shipwreck in 2013. The Committee tackled for the first time the question of extraterritorial application of the International Covenant on Civil and Political Rights to persons in distress at sea. While finding the decision against Malta to be inadmissible, the Committee engaged in a significant analysis of the concept of jurisdiction in both decisions. This article analyses how the decisions interpret the concept of ‘jurisdiction’ and juxtaposes this analysis against the approaches taken in other international legal regimes. The article then theorises on the impact of these two decisions in helping to crystallise a new ‘right to be rescued at sea’.
CBT treatment delivery formats for panic disorder: a systematic review and network meta-analysis of randomised controlled trials
Authors: Papola Davide , Ostuzzi Giovanni , Tedeschi Federico , Gastaldon Chiara , Purgato Marianna , Del Giovane Cinzia , Pompoli Alessandro , Pauley Darin , Karyotaki Eirini , Sijbrandij Marit , Furukawa Toshi A. , Cuijpers Pim , Barbui Corrado
Published: December 2022

Several in-person and remote delivery formats of cognitive-behavioural therapy (CBT) for panic disorder are available, but up-to-date and comprehensive evidence on their comparative efficacy and acceptability is lacking. Our aim was to evaluate the comparative efficacy and acceptability of all CBT delivery formats to treat panic disorder. To answer our question we performed a systematic review and network meta-analysis of randomised controlled trials. We searched MEDLINE, Embase, PsycINFO, and CENTRAL, from inception to 1st January 2022. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO. We found a total of 74 trials with 6699 participants. Evidence suggests that face-to-face group [standardised mean differences (s.m.d.) −0.47, 95% confidence interval (CI) −0.87 to −0.07; CINeMA = moderate], face-to-face individual (s.m.d. −0.43, 95% CI −0.70 to −0.15; CINeMA = Moderate), and guided self-help (SMD −0.42, 95% CI −0.77 to −0.07; CINeMA = low), are superior to treatment as usual in terms of efficacy, whilst unguided self-help is not (SMD −0.21, 95% CI −0.58 to −0.16; CINeMA = low). In terms of acceptability (i.e. all-cause discontinuation from the trial) CBT delivery formats did not differ significantly from each other. Our findings are clear in that there are no efficacy differences between CBT delivered as guided self-help, or in the face-to-face individual or group format in the treatment of panic disorder. No CBT delivery format provided high confidence in the evidence at the CINeMA evaluation.
Global Three‐Dimensional Draping of Magnetic Field Lines in Earth’s Magnetosheath From In‐Situ Spacecraft Measurements
Authors: Michotte de Welle B. , Aunai N. , Nguyen G. , Lavraud B. , Génot V. , Jeandet A. , Smets R.
Published: December 2022

Magnetic field draping occurs when the magnetic field lines frozen in a plasma flow wrap around a body or plasma environment. The draping of the interplanetary magnetic field (IMF) around the Earth’s magnetosphere has been confirmed in the early days of space exploration. However, its global and three‐dimensional structure is known from modeling only, mostly numerical. Here, this structure in the dayside of the Earth’s magnetosheath is determined as a function of the upstream IMF orientation purely from in‐situ spacecraft observations. We show the draping structure can be organized in three regimes depending on how radial the upstream IMF is. Quantitative analysis demonstrates how the draping pattern results from the magnetic field being frozen in the magnetosheath flow, deflected around the magnetopause. The role of the flow is emphasized by a comparison of the draping structure to that predicted to a magnetostatic draping.
Composition and Evolution of Continental Crust at Orogenic Belts: Constraints From a 3‐D Crustal Model of Southeast China
Authors: Sun Yao , Gao Ruohan , Li Zhiwei , Wang Andong , Han Ran , Xi Yufei , Liu Jingao
Published: December 2022

The chemical composition of continental crust is fundamental and crucial to understanding its origin and evolution. Orogenic belts make up about 30% of the global continental crust, yet their chemical compositions are still poorly constrained. In this study, we report an overall estimate for the continental crust composition of a collisional orogenic belt terrane: the Southeast China. The estimate is obtained through a 3‐D crustal model combining a lithology proportion model and probability density function models for element concentrations of various lithologies. Based on our model, the Southeast China crust is amongst one of the most evolved continental crust composition estimates (71.0% SiO2 content for the upper crust and 64.7% SiO2 for the bulk crust). A strong correlation between SiO2 and the chemical index of alteration (CIA) of different composition models for upper continental crust (UCC) indicates that chemical weathering is a controlling factor for the development of a felsic UCC. In contrast, weak correlations of SiO2 with Ninorm (15.9*Ni/Al2O3) and CIA suggest that igneous differentiation and chemical weathering act together to modify the composition of the bulk continental crust. Orogenic belt terranes like the Southeast China can develop a highly evolved crustal composition, especially for the upper crust, due to extensive intracrustal reworking and differentiation, enhanced chemical weathering, and potential subsequent delamination and removal of thickened crust root. Therefore, an overall estimation of the average composition of continental crust should take into account the more evolved composition of orogenic belts.
Iron Reduction Controls Carbon Mineralization in Aquaculture Shrimp Pond Sediments in Subtropical Estuaries
Authors: Tan Ji , Luo Min , Tan Fengfeng , Lichtfouse Eric , Zhang Changwei , Chen Xin , Huang Jiafang , Tan Yang , Xiao Leilei
Published: December 2022

Expanding worldwide aquaculture has greatly increased greenhouse gas emissions; however, the underlying microbial mechanisms are poorly understood. In particular, the role of ferric iron [Fe(III)] (hydro)oxides in carbon mineralization in aquaculture pond sediments remains unclear. Here, we studied the rates of microbial Fe(III) reduction, sulfate reduction, methanogenesis, and carbon mineralization in aquaculture shrimp (Litopenaeus vannamei) ponds of various salinities before, during, and after shrimp farming in subtropical estuaries in southeast China. Sediment samples (0–10 cm) were collected to investigate the content of iron species, characteristics of organic matter, and abundance of Geobacter, a proxy of iron reducers. Overall, Fe(III) reduction (46.1% ± 19.1%) dominated carbon mineralization, followed by sulfate reduction (39.6% ± 16.8%) and methanogenesis (1.5% ± 1.1%). Microbial Fe(III) reduction contributed more to carbon mineralization during farming than before and after farming. This enhancement in Fe(III) reduction is attributed to a significant increase in Fe(III) content during farming. Additionally, the contributions of microbial Fe(III) reduction to carbon mineralization were lower in the high‐salinity ponds than in the low‐salinity ponds due to the suppression of sulfate reduction, abiotic Fe(III) reduction by sulfides, and lower oxidation‐reduction potential. Our findings demonstrate that microbial Fe(III) reduction plays a significant role in carbon mineralization in aquaculture pond sediments. Future carbon flux prediction models of aquaculture pond systems should fully integrate microbial Fe(III) reduction.
Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy
Authors: Meng Yang , Qiu Lei , Zeng Xinyi , Hu Xiaoyan , Zhang Yaguang , Wan Xiaowen , Mao Xiaobing , Wu Jian , Xu Yongfeng , Xiong Qunli , Chen Zhixin , Zhang Bo , Han Junhong
Published: December 2022

Chemoresistance has long been the bottleneck of ovarian cancer (OC) prognosis. It has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC, but the underlying mechanisms remain equivocal. Here, we demonstrate a new mechanism where CRL4CUL4A/DDB1 manipulates OC cell chemoresistance by regulating mitochondrial dynamics and mitophagy. CRL4CUL4A/DDB1 depletion enhanced mitochondrial fission by upregulating AMPKαThr172 and MFFSer172/Ser146 phosphorylation, which in turn recruited DRP1 to mitochondria. CRL4CUL4A/DDB1 loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented mitochondria. Importantly, CRL4CUL4A/DDB1 loss inhibited OC cell proliferation, whereas inhibiting autophagy partially reversed this disruption. Our findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission, mitophagy, and OC chemoresistance. Disruption of CRL4CUL4A/DDB1 and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC.
Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value
Authors: Berg Hege F. , Engerud Hilde , Myrvold Madeleine , Lien Hilde E. , Hjelmeland Marta Espevold , Halle Mari K. , Woie Kathrine , Hoivik Erling A. , Haldorsen Ingfrid S. , Vintermyr Olav , Trovik Jone , Krakstad Camilla
Published: December 2022

Background

The endometrial cancer mismatch repair (MMR) deficient subgroup is defined by loss of MSH6, MSH2, PMS2 or MLH1. We compare MMR status in paired preoperative and operative samples and investigate the prognostic impact of differential MMR protein expression levels.

Methods

Tumour lesions from 1058 endometrial cancer patients were immunohistochemically stained for MSH6, MSH2, PMS2 and MLH1. MMR protein expression was evaluated as loss or intact to determine MMR status, or by staining index to evaluate the prognostic potential of differential expression. Gene expression data from a local (n = 235) and the TCGA (n = 524) endometrial cancer cohorts was used for validation.

Results

We identified a substantial agreement in MMR status between paired curettage and hysterectomy samples. Individual high expression of all four MMR markers associated with non-endometrioid subtype, and high MSH6 or MSH2 strongly associated with several aggressive disease characteristics including high tumour grade and FIGO stage, and for MSH6, with lymph node metastasis. In multivariate Cox analysis, MSH6 remained an independent prognostic marker, also within the endometrioid low-grade subgroup (P < 0.001).

Conclusion

We demonstrate that in addition to determine MMR status, MMR protein expression levels, particularly MSH6, may add prognostic information in endometrial cancer.
All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex
Authors: Wang Lu , Zhang Qi , Ye Li , Ye Xingnong , Yang Wenli , Zhang Hua , Zhou Xinping , Ren Yanling , Ma Liya , Zhang Xiang , Mei Chen , Xu Gaixiang , Li Kongfei , Luo Yingwan , Jiang Lingxu , Lin Peipei , Zhu Shuanghong , Lang Wei , Wang Yuxia , Shen Chuying , Han Yueyuan , Liu Xiaozhen , Yang Haiyang , Lu Chenxi , Sun Jie , Jin Jie , Tong Hongyan
Published: December 2022

Background

Decitabine (DAC) is used as the first-line therapy in patients with higher-risk myelodysplastic syndromes (HR-MDS) and elderly acute myeloid leukaemia (AML) patients unsuitable for intensive chemotherapy. However, the clinical outcomes of patients treated with DAC as a monotherapy are far from satisfactory. Adding all-trans retinoic acid (ATRA) to DAC reportedly benefitted MDS and elderly AML patients. However, the underlying mechanisms remain unclear and need further explorations from laboratory experiments.

Methods

We used MDS and AML cell lines and primary cells to evaluate the combined effects of DAC and ATRA as well as the underlying mechanisms. We used the MOLM-13-luciferase murine xenograft model to verify the enhanced cytotoxic effect of the drug combination.

Results

The combination treatment reduced the viability of MDS/AML cells in vitro, delayed leukaemia progress, and extended survival in murine xenograft models compared to non- and mono-drug treated models. DAC application as a single agent induced Nrf2 activation and downstream antioxidative response, and restrained reactive oxygen species (ROS) generation, thus leading to DAC resistance. The addition of ATRA blocked Nrf2 activation by activating the RARα-Nrf2 complex, leading to ROS accumulation and ROS-dependent cytotoxicity.

Conclusions

These results demonstrate that combining DAC and ATRA has potential for the clinical treatment of HR-MDS/AML and merits further exploration.
Cancer-derived exosomal miR-197-3p confers angiogenesis via targeting TIMP2/3 in lung adenocarcinoma metastasis
Authors: Chang Rui-Min , Fu Yao , Zeng Jun , Zhu Xiao-Yan , Gao Yang
Published: December 2022

Cancer-derived exosomal miRNAs are implicated in tumorigenesis and development of lung adenocarcinoma (LUAD). The objective of this study is to unravel the biological function of exosomal miR-197-3p in LUAD metastasis. qRT-PCR showed that elevated miR-197-3p in LUAD tissues was positively correlated with LUAD metastasis. CCK-8, tube formation, transwell and wound healing assays revealed that exosomal miR-197-3p from LUAD cells promoted the proliferation, angiogenesis and migration of HUVECs in vitro. LUAD cells-derived exosomal miR-197-3p also facilitated tumor growth and angiogenesis in LUAD cells-derived tumor xenograft model. TIMP2 and TIMP3 were identified as target genes of miR-197-3p in HUVECs by bioinformatics analysis and luciferase reporter assay. Functional studies illustrated that exosomal miR-197-3p promoted angiogenesis and migration via targeting TIMP2 and TIMP3 in HUVECs. In vivo data further supported that exosomal miR-197-3p promoted lung metastasis via TIMP2/3-mediated angiogenesis. In conclusion, LUAD cells-derived exosomal miR-197-3p conferred angiogenesis via targeting TIMP2/3 in LUAD metastasis.
Lysosomal cathepsins act in concert with Gasdermin-D during NAIP/NLRC4-dependent IL-1β secretion
Authors: Branco Laura Migliari , Amaral Marcelo Pires , Boekhoff Henning , de Lima Ana Beatriz Figueiredo , Farias Ingrid Sancho , Lage Silvia Lucena , Pereira Gustavo José Silva , Franklin Bernardo Simões , Bortoluci Karina Ramalho
Published: December 2022

The NAIP/NLRC4 inflammasome is classically associated with the detection of bacterial invasion to the cytosol. However, recent studies have demonstrated that NAIP/NLRC4 is also activated in non-bacterial infections, and in sterile inflammation. Moreover, in addition to the well-established model for the detection of bacterial proteins by NAIP proteins, the participation of other cytosolic pathways in the regulation of NAIP/NLRC4-mediated responses has been reported in distinct contexts. Using pharmacological inhibition and genetic deletion, we demonstrate here that cathepsins, well known for their involvement in NLRP3 activation, also regulate NAIP/NLRC4 responses to cytosolic flagellin in murine and human macrophages. In contrast to that observed for NLRP3 agonists, cathepsins inhibition did not reduce ASC speck formation or caspase-1 maturation in response to flagellin, ruling out their participation in the effector phase of NAIP/NLRC4 activation. Moreover, cathepsins had no impact on NF-κB-mediated priming of pro-IL-1β, thus suggesting these proteases act downstream of the NAIP/NLRC4 inflammasome activation. IL-1β levels secreted in response to flagellin were reduced in the absence of either cathepsins or Gasdermin-D (GSDMD), a molecule involved in the induction of pyroptosis and cytokines release. Notably, IL-1β secretion was abrogated in the absence of both GSDMD and cathepsins, demonstrating their non-redundant roles for the optimal IL-1β release in response to cytosolic flagellin. Given the central role of NAIP/NLRC4 inflammasomes in controlling infection and, also, induction of inflammatory pathologies, many efforts have been made to uncover novel molecules involved in their regulation. Thus, our findings bring together a relevant contribution by describing the role of cathepsins as players in the NAIP/NLRC4-mediated responses.
A dimensionless framework for predicting submarine fan morphology
Authors: Wahab Abdul , Hoyal David C. , Shringarpure Mrugesh , Straub Kyle M.
Published: December 2022

Observations of active turbidity currents at field scale offers a limited scope which challenges the development of theory that links flow dynamics to the morphology of submarine fans. Here we offer a framework for predicting submarine fan morphologies by simplifying critical environmental forcings such as regional slopes and properties of sediments, through densimetric Froude (ratio of inertial to gravitational forces) and Rouse numbers (ratio of settling velocity of sediments to shear velocity) of turbidity currents. We leverage a depth-average process-based numerical model to simulate an array of submarine fans and measure rugosity as a proxy for their morphological complexity. We show a systematic increase in rugosity by either increasing the densimetric Froude number or decreasing the Rouse number of turbidity currents. These trends reflect gradients in the dynamics of channel migration on the fan surface and help discriminate submarine fans that effectively sequester organic carbon rich mud in deep ocean strata.
Low Pt loading for high-performance fuel cell electrodes enabled by hydrogen-bonding microporous polymer binders
Authors: Tang Hongying , Geng Kang , Aili David , Ju Qing , Pan Ji , Chao Ge , Yin Xi , Guo Xiang , Li Qingfeng , Li Nanwen
Published: December 2022

A key challenge for fuel cells based on phosphoric acid doped polybenzimidazole membranes is the high Pt loading, which is required due to the low electrode performance owing to the poor mass transport and severe Pt poisoning via acid absorption on the Pt surface. Herein, these issues are well addressed by design and synthesis of effective catalyst binders based on polymers of intrinsic microporosity (PIMs) with strong hydrogen-bonding functionalities which improve phosphoric acid binding energy, and thus preferably uphold phosphoric acid in the vicinity of Pt catalyst particles to mitigate the adsorption of phosphoric acid on the Pt surface. With combination of the highly mass transport microporosity, strong hydrogen-bonds and high phosphoric acid binding energy, the tetrazole functionalized PIM binder enables an H2-O2 cell to reach a high Pt-mass specific peak power density of 3.8 W mgPt−1 at 160 °C with a low Pt loading of only 0.15 mgPt cm−2.
Slow growing behavior in African trypanosomes during adipose tissue colonization
Authors: Trindade Sandra , De Niz Mariana , Costa-Sequeira Mariana , Bizarra-Rebelo Tiago , Bento Fábio , Dejung Mario , Narciso Marta Valido , López-Escobar Lara , Ferreira João , Butter Falk , Bringaud Frédéric , Gjini Erida , Figueiredo Luisa M.
Published: December 2022

When Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure.
Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases
Authors: Nishida Yuya , Yanagisawa Sachiko , Morita Rikuri , Shigematsu Hideki , Shinzawa-Itoh Kyoko , Yuki Hitomi , Ogasawara Satoshi , Shimuta Ken , Iwamoto Takashi , Nakabayashi Chisa , Matsumura Waka , Kato Hisakazu , Gopalasingam Chai , Nagao Takemasa , Qaqorh Tasneem , Takahashi Yusuke , Yamazaki Satoru , Kamiya Katsumasa , Harada Ryuhei , Mizuno Nobuhiro , Takahashi Hideyuki , Akeda Yukihiro , Ohnishi Makoto , Ishii Yoshikazu , Kumasaka Takashi , Murata Takeshi , Muramoto Kazumasa , Tosha Takehiko , Shiro Yoshitsugu , Honma Teruki , Shigeta Yasuteru , Kubo Minoru , Takashima Seiji , Shintani Yasunori
Published: December 2022

Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.
A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma
Authors: Xia Lingfang , Zhou Qi , Gao Yunong , Hu Wenjing , Lou Ge , Sun Hong , Zhu Jianqing , Shu Jin , Zhou Xianfeng , Sun Rong , Wu Xiaohua
Published: December 2022

This phase 2 study assesses the efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (anti-angiogenic agent) in women with pretreated recurrent or metastatic cervical cancer (ClinicalTrials.gov NCT03827837). Patients with histologically or cytologically confirmed cervical squamous cell carcinoma experiencing relapse or progression during or after 1–2 lines of systemic therapy for recurrent or metastatic disease are enrolled. Eligible patients receive camrelizumab 200 mg intravenously on day 1 of each 3-week cycle plus famitinib 20 mg orally once daily. The primary endpoint is the objective response rate. Secondary endpoints are duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. The trial has met pre-specified endpoint. Thirty-three patients are enrolled; median follow-up lasts for 13.6 months (interquartile range: 10.0–23.6). Objective responses are observed in 13 (39.4%, 95% confidence interval [CI]: 22.9–57.9) patients; the 12-month duration of response rate is 74.1% (95% CI: 39.1–90.9). Median progression-free survival is 10.3 months (95% CI: 3.5–not reached) and the 12-month overall survival rate is 77.7% (95% CI: 58.9–88.7). All patients experience treatment-related adverse events; grade ≥3 events occur in 26 (78.8%) patients. Treatment-related serious adverse events and deaths are observed in 9 (27.3%) and 2 (6.1%) patients, respectively. Camrelizumab plus famitinib shows promising antitumor activity with a manageable and tolerable safety profile in patients with pretreated recurrent or metastatic cervical squamous cell carcinoma. This combination may represent a treatment option for this population.