bluuebunny/crossref_metadata_2025_split huggingface dataset:
SDG 8 and the food–energy–water nexus: a two-country dynamic computable general equilibrium CGE model
Authors: Schlör Holger , Schubert Stefanie A. 
Published: October 2022

AbstractBackgroundIn the twenty-first century, the success story of the Post-World-War-II World has been called into question by climate change and other challenges. De-growth or zero economic growth are discussed as possible solutions for mitigating climate change. The traditional economic growth model is increasingly challenged by the demand for sustained economic growth expressed in United Nations Sustainable Development Goal 8 “sustained economic growth” (UN-SDG 8) and supported by the European Green Deal. The aim of this paper is to contribute to the general understanding of characteristics, effects and challenges of new economic growth ideas as well as their interlinkages with the food–energy–water (FEW) nexus.MethodsTo address these challenges, a stylized dynamic General Equilibrium Model (GEM) was developed, which consists of two countries: an emerging, developing European country A and a developed European country B. Country A is assumed to grow, while country B shrinks. The model is based on artificial data sets. This approach was chosen to prevent the blurring of counterfactual comparison by country-specific effects of economic turbulences such as the Lehman crash or the economic break-in during the Covid-19 pandemic.ResultsThe gross output of the emerging European country increases, whereas the output of the developed European country decreases according to the different growth strategies. The analysis reveals that a constantly widening gap between the emerging and the developed country is created. It can further be shown how this influences the relevant economic indicators (CO2emissions, household budget, trade balance, utility and social welfare).ConclusionsThe analysis of the two-country stylized GE model makes distortions visible: insignificant gaps in the values and development of analyzed economic indicators become prevalent. The welfare gap affects the core of the traditional socio-economic system, because the development of the utility of the households is central for the stability of political processes. A sufficiency and subsistence sector may be an option to even out the welfare losses from the de-growth strategy of the traditional economic system to avoid that the de-growth gaps are perceived by the community as welfare losses which can endanger the realization of UN-SDG 8.
Attitudes and training related to substance use in pediatric emergency departments
Authors: Hoch Ariel M. , Schoenberger Samantha F. , Boyle Tehnaz P. , Hadland Scott E. , Gai Mam Jarra , Bagley Sarah M. 
Published: October 2022

Abstract
Background
In recent years, pediatric emergency departments (PED) have seen an increase in presentations related to substance use among their adolescent patient population. We aimed to examine pediatric emergency medicine (PEM) physicians’ knowledge, attitudes, and beliefs on caring for adolescents with substance use.

Methods
We conducted a cross-sectional online survey of PEM physicians through the American Academy of Pediatrics Pediatric Emergency Medicine Collaborative Research Committee (PEM-CRC) listserv. The 41-item survey contained the following domains: demographics, current protocols and education for managing adolescent substance use, and attitudes about treatment of substance use. We calculated descriptive statistics for each variable within the domains.

Results
Of 177 respondents (38.2% response rate), 55.4% were female, 45.2% aged ≥ 50 years, 78% worked in a children’s hospital, and 50.8% had > 15 years clinical practice. Overall, 77.8% reported caring for adolescents with a chief complaint related to non-opioid substance use and 26.0% opioid use at least once a month. Most (80.9%) reported feeling comfortable treating major medical complications of substance use, while less than half were comfortable treating withdrawal symptoms. 73% said that they were not interested in prescribing buprenorphine.

Conclusions
Among this national sample of PEM physicians, 3 of 4 physicians managed substance-related visits monthly, but 52% lacked comfort in managing withdrawal symptoms and 73.1% were not interested in prescribing buprenorphine. Almost all PEM physician identified substance use-related education is important but lacked access to faculty expertise or educational content. Expanded access to education and training for PEM physicians related to substance use is needed.
Utilization of Basaltic Quarry Dust as a Partial Replacement of Cement for Hollow Concrete Block Production
Authors: Mitikie Bahiru Bewket , Alemu Yohannis Lemma , Reda Shumet Getahun 
Published: October 2022

AbstractThis research was conducted to examine the potential of basaltic crusher dust as a partial replacement for Portland Pozzolana cement in hollow concrete block (HCB) production. Quarry dust is one of the waste materials abundantly available and pozzolanic material in the quarry industry. In doing so, physical tests of cement pastes and hollow concrete blocks of different classes, i.e., A, B, and C, were produced by partially replacing the cement content with 10%, 20%, 30%, and 40% by weight of basaltic crusher dust using vibrating block molding machine. The units without basaltic crusher dust (0%) serve as a control variable. The cement pastes were examined for consistency and setting time, and the blocks produced were tested to determine their compressive strength, water absorption rate, and density. Furthermore, the possible cost advantages of using basaltic crusher dust as a partial replacement of cement in the hollow concrete block were analyzed. The result indicates that the experimental HCB of classes A and C surpassed the required standard of compressive strength, water absorption, and density specified by the Ethiopian standard ES 596:2001; whereas, the compressive strength of class B fails at 40% cement replacement. It was concluded that hollow concrete blocks of classes A and C with up to 40% replacement and class B with up to 30% replacement can be used for load-bearing walls and save the e cost of hollow concrete blocks with comparable properties.
The long way to innovation adoption: insights from precision agriculture
Authors: Masi Margherita , De Rosa Marcello , Vecchio Yari , Bartoli Luca , Adinolfi Felice 
Published: October 2022

AbstractThe adoption of innovations may boost the transition to sustainable agricultural models. Among these innovations, precision farming offers a fundamental contribution to sustainable soil management and the improvement in product quality. The work is set against this background and aims to analyse the rate of introducing precision farming tools and the variables that prevent/facilitate this adoption. Although adoption rates in Italy remain relatively low, it is vital to underline the obstacles that limit the broader use of precision agricultural technologies inside farms. To this end, the literature has highlighted various elements of complexity (farm characteristics, socio-economic and psychological), which can hinder or generate perceived complexity and significantly reduce the potential for technology adoption. In this context emerges the increasing importance of public and private activities related to knowledge transfer. The paper focuses on agricultural knowledge and innovation systems, which are also relevant in light of the recent proposal for the new regulation on rural development. The awareness–knowledge–adoption–product (AKAP) sequence was used to reveal the gap between the potential and actual adoption of innovation on Italian farms to comprehend the adoption process and identify relevant barriers and the role knowledge systems played. Empirical findings show that AKIS has a critical mediating function in promoting innovation uptake. Strengthening knowledge systems, acting on the different phases of the AKAP sequence, could allow a greater understanding of precision agriculture techniques and bottlenecks to adoption.
Dexmedetomidine alleviates inflammatory response and oxidative stress injury of vascular smooth muscle cell via α2AR/GSK-3β/MKP-1/NRF2 axis in intracranial aneurysm
Authors: Zhang Ze , Mu Xiue , Zhou Xiaohui 
Published: October 2022

AbstractVascular smooth muscle cell (VSMC) phenotypic modulation regulates the initiation and progression of intracranial aneurysm (IA). Dexmedetomidine (DEX) is suggested to play neuroprotective roles in patients with craniocerebral injury. Therefore, we investigated the biological functions of DEX and its mechanisms against IA formation and progression in the current study. The rat primary VSMCs were isolated from Sprague–Dawley rats. IA and superficial temporal artery (STA) tissue samples were obtained from patients with IA. Flow cytometry was conducted to identify the characteristics of isolated VSMCs. Hydrogen peroxide (H2O2) was used to mimic IA-like conditions in vitro. Cell viability was detected using CCK-8 assays. Wound healing and Transwell assays were performed to detect cell motility. ROS production was determined by immunofluorescence using DCFH-DA probes. Western blotting and RT-qPCR were carried out to measure gene expression levels. Inflammation responses were determined by measuring inflammatory cytokines. Immunohistochemistry staining was conducted to measure α2-adrenergic receptor levels in tissue samples. DEX alleviated the H2O2-induced cytotoxicity, attenuated the promoting effects of H2O2on cell malignancy, and protected VSMCs against H2O2-induced oxidative damage and inflammation response. DEX regulated the GSK-3β/MKP-1/NRF2 pathway via the α2AR. DEX alleviates the inflammatory responses and oxidative damage of VSMCs by regulating the GSK-3β/MKP-1/NRF2 pathway via the α2AR in IA.
Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma
Authors: Joshkon Ahmad , Tabouret Emeline , Traboulsi Wael , Bachelier Richard , Simoncini Stéphanie , Roffino Sandrine , Jiguet-Jiglaire Carine , Badran Bassam , Guillet Benjamin , Foucault-Bertaud Alexandrine , Leroyer Aurelie S. , Dignat-George Françoise , Chinot Olivier , Fayyad-Kazan Hussein , Bardin Nathalie , Blot-Chabaud Marcel 
Published: October 2022

Abstract
Rationale
Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma.

Methods
The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice.

Results
We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone.

Conclusion
We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma.
High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy
Authors: Pai Balagopal , Tome-Garcia Jessica , Cheng Wan Sze , Nudelman German , Beaumont Kristin G. , Ghatan Saadi , Panov Fedor , Caballero Elodia , Sarpong Kwadwo , Marcuse Lara , Yoo Jiyeoun , Jiang Yan , Schaefer Anne , Akbarian Schahram , Sebra Robert , Pinto Dalila , Zaslavsky Elena , Tsankova Nadejda M. 
Published: October 2022

AbstractThe pathophysiology of epilepsy underlies a complex network dysfunction between neurons and glia, the molecular cell type-specific contributions of which remain poorly defined in the human disease. In this study, we validated a method that simultaneously isolates neuronal (NEUN +), astrocyte (PAX6 + NEUN–), and oligodendroglial progenitor (OPC) (OLIG2 + NEUN–) enriched nuclei populations from non-diseased, fresh-frozen human neocortex and then applied it to characterize the distinct transcriptomes of such populations isolated from electrode-mapped temporal lobe epilepsy (TLE) surgical samples. Nuclear RNA-seq confirmed cell type specificity and informed both common and distinct pathways associated with TLE in astrocytes, OPCs, and neurons. Compared to postmortem control, the transcriptome of epilepsy astrocytes showed downregulation of mature astrocyte functions and upregulation of development-related genes. To gain further insight into glial heterogeneity in TLE, we performed single cell transcriptomics (scRNA-seq) on four additional human TLE samples. Analysis of the integrated TLE dataset uncovered a prominent subpopulation of glia that express a hybrid signature of both reactive astrocyte and OPC markers, including many cells with a mixed GFAP + OLIG2 + phenotype. A further integrated analysis of this TLE scRNA-seq dataset and a previously published normal human temporal lobe scRNA-seq dataset confirmed the unique presence of hybrid glia only in TLE. Pseudotime analysis revealed cell transition trajectories stemming from this hybrid population towards both OPCs and reactive astrocytes. Immunofluorescence studies in human TLE samples confirmed the rare presence of GFAP + OLIG2 + glia, including some cells with proliferative activity, and functional analysis of cells isolated directly from these samples disclosed abnormal neurosphere formation in vitro. Overall, cell type-specific isolation of glia from surgical epilepsy samples combined with transcriptomic analyses uncovered abnormal glial subpopulations with de-differentiated phenotype, motivating further studies into the dysfunctional role of reactive glia in temporal lobe epilepsy.
Reversal of cancer gene expression identifies repurposed drugs for diffuse intrinsic pontine glioma
Authors: Zhao Guisheng , Newbury Patrick , Ishi Yukitomo , Chekalin Eugene , Zeng Billy , Glicksberg Benjamin S. , Wen Anita , Paithankar Shreya , Sasaki Takahiro , Suri Amreena , Nazarian Javad , Pacold Michael E. , Brat Daniel J. , Nicolaides Theodore , Chen Bin , Hashizume Rintaro 
Published: October 2022

AbstractDiffuse intrinsic pontine glioma (DIPG) is an aggressive incurable brainstem tumor that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. This study aimed to identify potential therapeutic agents using a computational pipeline to perform an in silico screen for novel drugs. We then tested the identified drugs against a panel of patient-derived DIPG cell lines. Using a systematic computational approach with publicly available databases of gene signature in DIPG patients and cancer cell lines treated with a library of clinically available drugs, we identified drug hits with the ability to reverse a DIPG gene signature to one that matches normal tissue background. The biological and molecular effects of drug treatment was analyzed by cell viability assay and RNA sequence. In vivo DIPG mouse model survival studies were also conducted. As a result, two of three identified drugs showed potency against the DIPG cell lines Triptolide and mycophenolate mofetil (MMF) demonstrated significant inhibition of cell viability in DIPG cell lines. Guanosine rescued reduced cell viability induced by MMF. In vivo, MMF treatment significantly inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, we identified clinically available drugs with the ability to reverse DIPG gene signatures and anti-DIPG activity in vitro and in vivo. This novel approach can repurpose drugs and significantly decrease the cost and time normally required in drug discovery.
Qualitative and quantitative three-dimensional evaluation of maxillary basal and dentoalveolar dimensions in patients with and without maxillary impacted canines
Authors: Sharhan Hasan M. , Almashraqi Abeer A. , Al-fakeh Hanan , Alhashimi Najah , Abdulghani Ehab A. , Chen Wenyuanfeng , Al-Sosowa Abeer A. , Cao BaoCheng , Alhammadi Maged S. 
Published: October 2022

Abstract
Background
This study aimed to three-dimensionally evaluate the qualitative and quantitative maxillary basal, dentoalveolar, and dental dimensions in patients with unilateral or bilateral maxillary impacted canines relative to their normal peers.

Materials and methods
This is a retrospective comparative study. Cone-beam computed tomography images of one hundred and fifty adult patients were divided into three equal groups: unilateral, bilateral, and control groups. Each had 50 patients that were three-dimensionally analysed. The quantitative measurements involved three basal (molar basal width, premolar basal width, and arch depth), seven dentoalveolar (molar alveolar width, premolar alveolar width, inter-molar width, inter-premolar width, inter-canine width, arch length, and arch perimeter), and two dental (canine length and width) measurements. The qualitative measurements included four bone density areas (buccal, lingual, mesial, and distal) around the maxillary impacted canines.

Result
Differences between the three groups were statistically different for the quantitative measurements involving the two basal variables (molar basal width and premolar basal width) and all measured dentoalveolar variables; these were smaller in the unilateral and bilateral groups compared with the control group (p < 0.001). Unilateral and bilateral impacted canine groups showed significantly wider and shorter canines than the control group (p < 0.001). The qualitative measurements (the four bone density areas) around unilateral and bilateral impacted canine groups showed significantly greater density than the control group (p < 0.001). There was no significant qualitative or quantitative difference between the unilateral and bilateral impacted canines. The three groups had no significant variations in terms of arch depth.

Conclusion
Maxillary unilateral and bilateral canine impactions are associated with reduced basal and dentoalveolar dimensions as well as wider and shorter maxillary canines compared to normal peers. The quality of bone around unilateral and bilateral impacted maxillary canines is higher than in non-impacted cases. Unilateral and bilateral canine impactions have quite similar qualitative and quantitative parameters.
Managing nirmatrelvir/ritonavir during COVID-19: pharmacists’ experiences from the Perak state of Malaysia
Authors: Chang Chee Tao , Ong Su Yin , Lim Xin Jie , Chew Lan Sim , Rajan Philip 
Published: October 2022

AbstractNovel therapeutic agents for SARS-CoV-2 have emerged over time, serving to reduce the severity of the disease, admission and mortality, especially among high-risk populations. Oral nirmatrelvir/ritonavir (Paxlovid®) was found to reduce the risk of disease progression. Pharmacists played multiple roles in handling the COVID-19 pandemic. This article highlights the roles of pharmacists in managing nirmatrelvir/ritonavir within the Malaysian context. Pharmacists were actively involved in Paxlovid® inventory management. To ensure the balance between supply and demand of new therapeutic drugs, pharmacists in health facilities constantly monitor the inventory levels of the medications. As Paxlovid® was initially reserved for a certain population who met the clinical eligibility criteria based on a scoring system, pharmacists were required to screen and exclude patients with non-indications or contraindications to the medication. During dispensing, pharmacists convey clear instructions on how to take the medications to ensure adherence and medication safety. The novel nature of the medications necessitates pharmacists to counsel patients regarding its indication, the mode of action, actions to take when missing a dose or overdose happens, side effects, storage and disposal methods, as well as mechanism of reporting adverse drug reactions. Pharmacists were required to follow-up all patients via phone call on Day 3 and Day 5 post-initiation, examining both adherence and adverse drug reactions associated with Paxlovid®. Pharmacists experienced multiple challenges in managing Paxlovid®, particularly due to increased workload, suboptimal follow-up response, stringent medication storage requirements, and adherence issues. Universal research and innovation initiatives were proposed to improve the delivery of novel therapeutic agents in the future health system.
The production of the first functional antibody mimetic in higher plants: the chloroplast makes the DARPin G3 for HER2 imaging in oncology
Authors: Ehsasatvatan Maryam , Kohnehrouz Bahram Baghban , Gholizadeh Ashraf , Ofoghi Hamideh , Shanehbandi Dariush 
Published: October 2022

Abstract
Background
Designed mimetic molecules are attractive tools in biopharmaceuticals and synthetic biology. They require mass and functional production for the assessment of upcoming challenges in the near future. The DARPin family is considered a mimetic pharmaceutical peptide group with high affinity binding to specific targets. DARPin G3 is designed to bind to the HER2 (human epidermal growth factor receptor 2) tyrosine kinase receptor. Overexpression of HER2 is common in some cancers, including breast cancer, and can be used as a prognostic and predictive tool for cancer. The chloroplasts are cost-effective alternatives, equal to, and sometimes better than, bacterial, yeast, or mammalian expression systems. This research examined the possibility of the production of the first antibody mimetic, DARPin G3, in tobacco chloroplasts for HER2 imaging in oncology.

Results
The chloroplast specific DARPin G3 expression cassette was constructed and transformed into N. tabacum chloroplasts. PCR and Southern blot analysis confirmed integration of transgenes as well as chloroplastic and cellular homoplasmy. The Western blot analysis and ELISA confirmed the production of DARPin G3 at the commercial scale and high dose with the rate of 20.2% in leaf TSP and 33.7% in chloroplast TSP. The functional analysis by ELISA confirmed the binding of IMAC purified chloroplast-made DARPin G3 to the extracellular domain of the HER2 receptor with highly effective picomolar affinities. The carcinoma cellular studies by flow cytometry and immunofluorescence microscopy confirmed the correct functioning by the specific binding of the chloroplast-made DARPin G3 to the HER2 receptor on the surface of HER2-positive cancer cell lines.

Conclusion
The efficient functional bioactive production of DARPin G3 in chloroplasts led us to introduce plant chloroplasts as the site of efficient production of the first antibody mimetic molecules. This report, as the first case of the cost-effective production of mimetic molecules, enables researchers in pharmaceuticals, synthetic biology, and bio-molecular engineering to develop tool boxes by producing new molecular substitutes for diverse purposes.