bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policy mixes for sustainable development pathways: representation in integrated assessment models
Authors: Dombrowsky Ines , Iacobuţă Gabriela Ileana , Daioglou Vassilis , Keppler Dorothee , Soergel Bjoern , Weindl Isabelle , Kriegler Elmar 
Published: December 2024

Abstract
The Paris Agreement on climate change and the 2030 Agenda on Sustainable Development require unprecedented transformations to sustainability, while maximising synergies and minimising trade-offs between the two agendas. The policy studies and sustainability transition literatures suggest that addressing the complex policy interlinkages requires ambitious, coherent, comprehensive and credible policy mixes supported by synergistic combinations of governance modes. We investigate to which extent these assumptions are reflected in quantitative scenarios produced with integrated assessment models. As a case study, we assess a new set of target-seeking sustainable development pathway (SDP) scenarios. We scrutinise the modelling protocols and the scenario results to analyse the extent to which these modelled SDPs represent governance modes and policy instrument types and purposes, and assess the resulting policy mix characteristics. As such, we bridge the scenario modelling and policy mix literatures and provide an initial pathway appraisal. We find that the modelled SDPs use policy mixes to constrain negative side-effects of unmitigated climate measures to achieve several SDGs simultaneously. The policy mixes speak to several policy mix characteristics. However, they are only partially spelled so far and their credibility remains limited. This calls for additional policy-translation efforts.
Study on the rheological properties of nano-SiO2 composite modified basalt mineral fiber asphalt mortar
Authors: Gao Haiwei , Zheng Nanxiang , Zhang Xiang , Li Zhihui , Cong Zhuohong 
Published: December 2024

Abstract
To investigate the impact of mineral fiber modification and dosage on the rheological properties of fiber asphalt mastic, basalt fiber surface roughness was enhanced using nano-SiO2 solution. Fiber asphalt mastic was prepared with a filler-bitumen ratio of 1.6 and fiber dosages of 0%, 1.3%, 2.6%, 3.9%, and 5.2%. The taper entry test, dynamic shear rheology test, and bending beam rheology test were employed to analyze the variations in taper entry, shear strength, complex modulus (G*), phase angle (δ), rutting factor (G*/sinδ), modulus of strength (S), and rate of change of strength (m) of the fiber asphalt mastic. The results indicate that the optimal dosage of mineral fibers in fiber asphalt mastic is 2.6%. Nano-modified basalt fibers significantly enhance the anti-shear capacity of asphalt mastic. The high-temperature stability of fiber asphalt mastic improves with increasing fiber dosage, but the improvement becomes negligible beyond a 2.6% dosage. The interfacial bonding layer formed by asphalt on the fiber surface enhances the high-temperature performance and stress dissipation at low temperatures, thereby improving low-temperature cracking resistance.
Development of objective test functions for modeling and sensitivity analysis of the mechanical behaviour of aluminum-agro-marine waste composites
Authors: Barah Obinna Onyebuchi , Nnamchi Stephen Ndubuisi , Selvam Milon Dennison , Mundu Mustafah Muhamad , Abdulkarim Abubakar 
Published: December 2024

Abstract
Aluminum-based composites reinforced with agro-marine waste materials present an eco-friendly, cost-effective solution for industries needing lightweight and durable materials. This study develops and evaluates the mechanical properties of aluminum (AA6061) composites reinforced with plantain stem ash, eucalyptus wood ash, and periwinkle shell powder for potential aerospace, automotive, and marine applications. Composite samples were prepared according to ASTM standards for tensile, compressive, flexural, wear, and fatigue tests. Objective Test Functions (OTFs) were derived using physical modeling and sensitivity analysis to filter impactful variables. Testing was conducted using universal testing machines, and wear/friction tests followed ASTM G99 guidelines. The physical models showed strong correlations (adjusted R2: 0.9033–1.0000). Measured properties included tensile strength (1907.46–2000.05 Pa), compressive strength (30.33–215.14 Pa), flexural strength (412.72–556.42 N-m2), wear rate (55.01–63.27 m3/m), coefficient of friction (0.102), and fatigue cycle (13.81–27.63 cycles). Except for the coefficient of friction, all results were consistent with the developed OTFs, confirming the material’s structural integrity. The composites displayed favourable properties for use in aerospace, automotive, and marine industries, offering strength, lightweight characteristics, and corrosion resistance. The OTFs validated the material’s performance, making it a viable alternative to conventional materials. Consequently, aluminum-agro-marine waste composites demonstrate excellent mechanical properties, with high potential for industrial applications.
Wear behaviour of friction surfaced Al-Ni and Al-SiC coatings over mild steel
Authors: Sivalingam Vinodh , Thirumalaisamy Ramakrishnan , Ramasamy Padmanaban 
Published: December 2024

Abstract
The friction surfacing (FS) method offers solid-state deposition of both identical and distinct coatings while avoiding a number of the issues that encompass the traditional fusion coating process. This study investigates FS for depositing aluminium based metal matrix composites (MMCs) onto AISI1018 mild steel substrates. The Al-2Si-15SiC and Al7075-15Ni MMC consumables used for the FS process were fabricated via stir casting. The FS process, optimized at 1200 rpm for Al-SiC and 1500 rpm for Al-Ni, resulted in refined microstructures and enhanced properties. Scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDAX) of the coating reveals surface with equiaxed and fine grains. The development of Al3Ni intermetallic compounds at the coating’s interface strengthens the bond by allowing the substrate and coating material to diffuse into each other. An excellent bonding strength of 147 MPa and 142 MPa is observed for the Al7075-15Ni and Al-2Si-15SiC coating deposits, respectively. In comparison to MMC consumable rods, the FS composite coating delivers 80%–85% reduction in grain size and enhances hardness. Vickers microhardness tests showed substantial hardness increases, with Al-Ni coatings reaching 183 HV. Wear tests indicated that Al-Ni coatings outperformed Al-SiC coatings and the steel substrate, exhibiting lower wear rates and friction coefficients. This research underscores FS’s effectiveness in improving the properties of aluminium MMC coatings on mild steel, with Al-Ni coatings showing exceptional wear resistance and bond strength for industrial applications.
Modelling long-term greenhouse gas mitigation pathways for Mongolia
Authors: Namkhainyam Tsolmon , Ovgor Bavuudorj , Jargal Dorjpurev , Malley Christopher S 
Published: December 2024

Abstract
Mongolia’s faces substantial challenges to reduce its Greenhouse Gas (GHG) emissions due to reliance on coal to meet electricity, heat and other energy demand and large livestock emissions. Despite this, Mongolia has committed to reduce GHG emissions by 22.7% in 2030 compared to a baseline scenario. Greenhouse gas mitigation assessments for Mongolia have focussed on actions to achieve emission reductions by 2030, but not on the potential for further reductions over the longer-term. This study addresses this gap through the development of long-term (2050) GHG emission pathways for Mongolia. These pathways aim to inform what level of GHG reduction targets Mongolia could commit to for the period after its current target expires. Greenhouse gas emissions are quantified for historic years (2010–2019) for all major GHG emitting sectors, and projected to 2050 based on the population and economic forecasts. Finally, mitigation scenarios modelling implementation of 49 specific mitigation measures are developed, to quantify their emission reduction potential. Without mitigation, GHG emissions were estimated to increase by 67% and 139% in 2030 and 2050, respectively, compared to 2019 levels (39 million tonnes CO2-eq emissions). Implementation of the 49 mitigation measures could reduce GHG emissions by 40% in 2050 compared to the baseline. Therefore, post-2030, Mongolia could increase its climate change mitigation ambition. Renewable Electricity generation, and energy efficiency were the measures that could achieve the majority of these additional emission reductions. However, there remains a substantial gap between the emission reduction potential of technically feasible measures currently being considered in Mongolia’s climate change mitigation planning, and full decarbonisation.
Stakeholder perspectives on fostering the water-energy-food nexus in Jordan: lessons beyond agricultural water management
Authors: Chemura Abel , Al-Smadi Walaa , Abkar Ali , Sawwan Jamal , Alananbeh Azzam , Farhan Ibrahim , Ghnaimat Amina , Alkhatatbeh Hamad Adel , Al Daraien Reem , Al-Qudah Tamara , Hassouneh Kholoud , Naimat Maram Al , Hamdi Luma , Abu Hammour Wafaa , Handam Ahmed , Hamdan Mutaz M , Daoud Hussein , Issa Ala Bani , Al-Salaymeh Bilal , Hammour Rashed Abu , Awamleh Ali , Alnimri Nataly , Alzyoud Samia , Ellsäßer Florian J , Dou Yue , Nelson Andrew , Al-Salaymeh Ahmed , Darvishzadeh Roshanak 
Published: December 2024

Abstract
The water–energy–food (WEF) nexus is an integrated conceptual tool for achieving sustainable development especially for countries facing limitations in one or more of its three pillars. The approach relies on bringing different stakeholders from the water, food and energy sectors together to collaboratively plan and adopt a holistic approach to resources management. This enables them to address sector-specific issues and develop a comprehensive understanding of the connected sectors leading to better outcomes. However, WEF nexus implementation is currently in its infancy in many countries and stakeholders are in the process of learning how to effectively communicate and collaborate with each other. In this paper, we report the state of the WEF nexus in Jordan, a dry country grappling with water, energy and food production challenges in a changing climate. Stakeholders from line ministries, academics, private sector players and non-state actors were brought together to discuss the status of the WEF nexus and identify challenges that need to be overcome for full realization of the WEF nexus as an operational framework for integrated development at country level. Stakeholders identified 7 cardinal lessons in the process of WEF nexus implementation in Jordan. These are that (i) data/information sharing is vital (ii) WEF nexus requires funding, (iii) collaborations among actors is key, (iv) inclusivity in planning is necessary, (v) clear responsibilities and boundaries among stakeholders are needed, (vi) sustainability and cohesion are a must and (vii) building trust among and within organizations is a primary ingredient for success. A deeper understanding of the interrelated dynamics of these challenges is required to foster the WEF nexus in Jordan as the issues are grave but not insurmountable. It is therefore suggested that deliberate efforts are needed from a technical and policy angle to ensure full operationalization of the WEF nexus approach in Jordan and elsewhere.
The SLE‐associated TREX1‐P212fs mutation disrupts ER association leading to type I interferonopathy
Authors: Xu Shan , Xiao Nanyang , Du Hekang , Zhou Xueyuan , Huang Miaohui , Feng Sisi , Hu Shun , Zhang Xiaoxiong , Zhang Sitong , Cui Dongya , Zhang Sheng , Chen Qi 
Published: December 2024

AbstractThe TREX1 gene encodes a highly efficient DNA exonuclease that plays an important role in maintaining DNA homeostasis in the cytoplasm. TREX1 mutations lead to a spectrum of type I interferonopathies that are characterized by systemic inflammation, high blood levels of autoantibodies, and spontaneously activated immunity. The TREX1‐P212fs mutation is thought to be linked to systemic lupus erythematosus (SLE). Here, we analyzed the functions of 20 TREX1 mutants and found that the TREX1‐P212fs mutant was able to reduce DNA enzyme activity and missed endoplasmic reticulum localization. Mouse‐derived in situ Trex1 models of transcoding mutations have not been reported. We successfully constructed Trex1‐P212fs mice by CRISPR‐Cas9 technology. Trex1P212fs/P212fs mice exhibit systemic inflammation, lymphocytosis, vasculitis, and kidney disease. The excessive autoantibody production was also present in these mice. We further demonstrated that TREX1 (1–212) protein lost its interaction with RPN1, the subunit that makes up the oligosaccharyl transferase (OST) complex. These data suggest an important role of TREX1‐C‐terminal association with the endoplasmic reticulum in inducing immune activation and the Trex1‐P212fs model may provide theoretical support for a better understanding of SLE treatment and defense.
Chloroquine‐induced proinsulin misfolding in the endoplasmic reticulum underlies the attenuation of mature insulin synthesis
Authors: Xu Jialu , Zhu Ruimin , Chen Yiyu , Li Xin , Chen Xuequn , Liu Ming , Huang Yumeng 
Published: December 2024

AbstractChloroquine (CQ), initially introduced for the clinical treatment of malaria, has subsequently been found to exhibit beneficial effects in combating diabetes mellitus. The anti‐hyperglycemic properties of chloroquine may be attributed to its anti‐inflammatory response and its ability to activate the insulin signaling pathway. However, both animal and clinical studies have yielded mixed results. Moreover, the impact of chloroquine on pancreatic β‐cells, the key player of glycemic control, was not known. To fill this knowledge gap, we investigated the effects of chloroquine on pancreatic β‐cell functions. Our findings revealed that while chloroquine did not alter proinsulin expression, it interfered with the conversion of proinsulin to insulin, resulting in reduced insulin levels. Using multiple independent approaches, we further showed that chloroquine disrupted proinsulin oxidative folding in the endoplasmic reticulum (ER) and impaired proinsulin trafficking from ER to Golgi, leading to ER stress and decreased insulin production. Notably, the elevated ER stress observed in chloroquine‐treated β‐cells was reversed upon knockout of insulin genes, indicating that chloroquine‐induced β‐cell ER stress primarily through the accumulation of misfolded proinsulin, rather than directly affecting ER homeostasis. Further investigation into the mechanisms underlying chloroquine‐induced proinsulin misfolding revealed that the accumulation of misfolded proinsulin was not caused by autophagy inhibition or the alkaline pH of chloroquine. Instead, it was primarily due to the disruption of the interaction between proinsulin and protein disulfide isomerase (PDI). Our findings unveiled new mechanisms of chloroquine treatment and raised important safety considerations regarding the use of chloroquine in diabetes treatment.
In the Eye of the Beholder: A Stakeholder Analysis of the Value of the “Promotion in Place” Competency-Based Time-Variable Graduate Medical Education Pilot
Authors: Balmer Dorene F. , Pusic Martin V. , Weinstein Debra F. , Co John Patrick T. , Goldhamer Mary Ellen J. 
Published: December 2024

Abstract

Purpose
Competency-based time-variable (CBTV) graduate medical education (GME) has been implemented in Canada, Europe, and the United States, yet its perceived value has not been explored. Promotion in Place (PIP) is a CBTV GME program in which residents graduating early advance to attending status with “sheltered independence” until the standard graduation date. This study describes perceived value of CBTV GME and PIP at Mass General Brigham by capturing diverse stakeholder perspectives.

Method
In this stakeholder analysis using semistructured interviews (June 2022–August 2023), 49 participants were invited (44 representative members and 5 external stakeholders) from 11 GME programs: PIP eligible residents, program directors (PDs), chairs, service chiefs, and external national medical education organization leaders. Authors’ understanding of value was informed by Harvey and Green’s conceptualization of quality in higher education as “fit for purpose,” “standards monitoring,” “transformation,” and “value for the money.” Deductive codes and inductive subcodes captured diverse perspectives of value.

Results
Of the 49 invited stakeholders, 34 (69%) were interviewed across 5 stakeholder groups. Nearly all groups cited aspects of PIP that are “fit for purpose” as evidence of value; PIP supported “workforce readiness” and provided “sheltered independence” as intended. External stakeholders, PDs, service chiefs, hospital leadership, and faculty cited value aligning with “standards monitoring” (e.g., PIP must maintain or improve patient and resident outcomes). Nearly all groups cited aspects of PIP aligning with “transformation” as evidence of value. PIP promoted “independent decision-making” and enhanced trainee confidence. Chairs cited aspects of PIP aligning with “value for the money” (e.g., “cost neutral” as optimal for sustainability and avoidance of “hidden costs” such as assessment burden).

Conclusions
Understanding perceptions of PIP and CBTV GME value is critical to engaging diverse stakeholders and extending CBTV GME to more programs and specialties. PIP’s transformative nature underscores the added value of CBTV GME.
Isorhynchophylline Inhibits Platelet Activation and Thrombus Formation
Authors: Liu Yun , Zhu Hui , Dai Yue , Zhang Jie , Li Yingying , Jiang Huimin , Sun Yueyue , Qiao Jianlin , Xu Xiaoqi 
Published: December 2024

Abstract:
Isorhynchophylline is a Chinese herbal medicine and has multiple effects such as anti-inflammatory and neuroprotective effects. Whether isorhynchophylline has antithrombotic property is unknown. This study aims to evaluate its role in platelet function. Human platelets were incubated with isorhynchophylline (0, 10, 20, and 40 μM) at 37°C for 1 hour to detect platelet aggregation and activation, receptors level, spreading, and calcium mobilization. In addition, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, adenosine triphosphate secretion, P-selectin expression, and αIIbβ3 activation induced by collagen-related peptide or thrombin without affecting surface level of receptors αIIbβ3, GPIbα, and glycoprotein VI. Meanwhile, isorhynchophylline-treated platelets showed reduced spreading. Moreover, isorhynchophylline reduced platelet calcium mobilization, phosphatidylserine exposure, and the phosphorylation of PLCγ2 and PKCα. Furthermore, administration of isorhynchophylline into mice impaired platelet hemostatic function and arterial/venous thrombosis without affecting coagulation. In conclusion, isorhynchophylline impairs platelet function and arterial/venous thrombosis, implying its potential to be a novel agent for treating thrombotic or cardiovascular diseases.
Modeling metabolic-associated steatohepatitis with human pluripotent stem cell-derived liver organoids
Authors: Wu Xiaoshan , Jiang Dacheng , Wang Yuchen , Li Xin , Liu Chenyu , Chen Yanhao , Sun Wei , He Ruikun , Yang Yi , Gu Xiaosong , Jiang Chunping , Ding Qiurong 
Published: December 2024

Background:
Metabolic-associated steatohepatitis (MASH) is one of the most prevalent liver diseases worldwide, with a global prevalence estimated between 3% and 5%, posing a significant health burden. Human liver organoids (HLOs) have previously been generated to model steatohepatitis, offering a potential cellular disease model for studying MASH. However, the current HLO model lacks detailed molecular characterizations and requires further improvement.

Methods:
HLOs derived from human pluripotent stem cells were treated with oleic acid and TGFβ to mimic the MASH progression. Treated HLOs were then analyzed using both bulk and single-cell RNA sequencing. Functional characterization was performed through staining with BODIPY, TMRM, CellROX, and Collagen I, as well as terminal deoxynucleotidyl transferase dUTP nick end labeling and ELISA assays. In addition, a test using the MASH HLO model to validate the hepatoprotective effects of several herb extracts was also conducted.

Results:
Both RNA-seq and single-cell RNA sequencing demonstrated a close resemblance of multiple molecular signatures and key intercellular communications in and between hepatocyte-like cells and stellate-like cells in the MASH HLO model, compared to human MASH. Furthermore, functional characterizations revealed progressive features of human MASH in the MASH HLO model, including severe steatosis, oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis. In addition, the Schisandra extracts have been demonstrated to have significant antioxidative, anti-inflammatory, and antifibrotic properties in the context of MASH.

Conclusions:
This study offers an improved HLO disease model of human MASH, which can be potentially applied to facilitate the understanding of the MASH pathogenesis and the discovery of effective treatments.
A 5-day course of repetitive transcranial magnetic stimulation before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency
Authors: Chowdhury Nahian S. , Taseen Khandoker J. , Chiang Alan KI. , Chang Wei-Ju , Millard Samantha K. , Seminowicz David A. , Schabrun Siobhan M. 
Published: December 2024

Abstract
Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine whether (1) 5 consecutive days of rTMS delivered prior to experimentally induced prolonged jaw pain has a prophylactic effect on future pain intensity and (2) whether these effects were accompanied by increases in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from day 0 to 4, 40 healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. Peak alpha frequency and CME were assessed on day 0 (before rTMS) and day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor in the right masseter muscle after the final rTMS session. From days 5 to 25, participants completed twice-daily electronic diaries including pain on chewing and yawning (primary outcomes), as well as pain during other activities (eg, talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Furthermore, active rTMS led to an increase in PAF. This is the first study to show that rTMS delivered prior to prolonged pain onset can protect against future pain. Our findings suggest that rTMS may hold promise as a prophylactic intervention for pain.