bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentials and limits of mechanical plastic recycling
Authors: Klotz Magdalena , Haupt Melanie , Hellweg Stefanie 
Published: May 2023

AbstractPlastics consumption continues to steeply increase worldwide, while resultant waste is currently mostly landfilled, discarded to the environment, or incinerated. This significantly contributes to global warming and causes negative health and ecosystem effects. Increasing the circularity of plastics can reduce these impacts. This study investigated to which extent plastics' circularity can be increased by mechanical recycling. For this purpose, future scenarios involving increased waste collection, improved product design, and improved waste sorting were assessed. The system studied consists of 11 plastic types in 69 product groups consumed and arising as waste in Switzerland. By means of a material flow analysis, the amounts of consumption, waste, and secondary material utilizable in product manufacturing were quantified for the year 2040. For the waste not mechanically recycled, treatment situations mainly involving energy recovery in waste‐to‐energy plants and cement kilns were modeled. A life cycle assessment of the complete plastic material flow system was conducted. We found that the mechanical recycling rate calculated based on the utilizable secondary material can be increased to up to 31%. This can lower the plastic carbon footprint by one quarter (1.3% of today's total Swiss carbon footprint) compared to no recycling. Important barriers to a further increase of the recycling rate were inaccessibility, the large diversity of plastic grades, and contamination. The remaining impact at maximum recycling is mainly caused by polyurethanes, polypropylene, and polystyrene production. In conclusion, the potential of mechanical plastic recycling is limited, but it can, as one of several measures, contribute to combating climate change.
Insomnia nosology: a systematic review and critical appraisal of historical diagnostic categories and current phenotypes
Authors: Nyhuis Casandra C. , Fernandez‐Mendoza Julio 
Published: May 2023

SummaryInsomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)‐III‐R first distinguished between ‘primary’ and ‘secondary’ insomnia. Prior International Classification of Sleep Disorders (ICSD) nosology ‘split’ diagnostic phenotypes to address insomnia's heterogeneity and the DSM nosology ‘lumped’ them into primary insomnia, while both systems assumed causality for insomnia secondary to health conditions. In this systematic review, we discuss the historical phenotypes in prior insomnia nosology, present findings for currently proposed insomnia phenotypes based on more robust approaches, and critically appraise the most relevant ones. Electronic databases PsychINFO, PubMED, Web of Science, and references of eligible articles, were accessed to find diagnostic manuals, literature on insomnia phenotypes, including systematic reviews or meta‐analysis, and assessments of the reliability or validity of insomnia diagnoses, identifying 184 articles. The data show that previous insomnia diagnoses lacked reliability and validity, leading current DSM‐5‐TR and ICSD‐3 nosology to ‘lump’ phenotypes into a single diagnosis comorbid with health conditions. However, at least two new, robust insomnia phenotyping approaches were identified. One approach is multidimensional‐multimethod and provides evidence for self‐reported insomnia with objective short versus normal sleep duration linked to clinically relevant outcomes, while the other is multidimensional and provides evidence for two to five clusters (phenotypes) based on self‐reported trait, state, and/or life‐history data. Some approaches still need replication to better support whether their findings identify true phenotypes or simply different patterns of symptomatology. Regardless, these phenotyping efforts aim at improving insomnia nosology both as a classification system and as a mechanism to guide treatment.
Critical literacy: an approach to child rights education in Uganda and Canada
Authors: Jones Shelley , Manion Kathleen 
Published: May 2023

AbstractFor children to know how to fully participate in and most effectively lead the world they will inherit, they must learn how to critically engage with it and be knowledgeable about foundational rights and instruments that support such engagement. Together, critical literacy, which encourages the examination and interrogation of the underlying assumptions of dominant narratives and ‘legitimate’ knowledge, and children's rights education, which involves children in learning how to express their ideas and fully participate in society (as appropriate to their age and ability), offer a powerful approach—theoretical and pedagogical—to engage children in active engagement of the world, especially with respect to the promotion of social justice. However, the layers of complexity and risks associated with deep consideration of challenging topics require expert guidance and compassionate role modelling from teachers of young children. Our paper considers the intersections between critical literacy and global child rights with reference to a study conducted with young school children in Canada and Uganda to discuss how teachers can support meaningful learning experiences in the classroom that can promote children's agency and social justice commitments.
Medium‐Run Impacts of Iron‐Fortified School Lunch on Anaemia, Cognition, and Learning Outcomes in India*
Authors: von Grafenstein Liza , Kumar Abhijeet , Kumar Santosh , Vollmer Sebastian 
Published: April 2023

AbstractUsing a phase‐in research design, we provide experimental evidence on the impacts of early versus late initiation of iron fortification in school lunch programmes on children's health and cognitive outcomes in India. We find higher haemoglobin levels and a lower likelihood of anaemia in the early treatment group that experienced 4 years of treatment, compared to the late treatment group that was exposed to one and a half years of treatment. Despite significant health gains, we do not find evidence for treatment effects on cognitive and educational outcomes. Heterogeneity analyses show evidence of gendered effects – the anaemia reduction is lower among females relative to males.
Efficient methods for multiple types of precise gene‐editing in Chlamydomonas
Authors: Chen Hui , Yang Qing‐Lin , Xu Jia‐Xi , Deng Xuan , Zhang Yun‐Jie , Liu Ting , Rots Marianne G. , Xu Guo‐Liang , Huang Kai‐Yao 
Published: April 2023

SUMMARYPrecise gene‐editing using CRISPR/Cas9 technology remains a long‐standing challenge, especially for genes with low expression and no selectable phenotypes in Chlamydomonas reinhardtii, a classic model for photosynthesis and cilia research. Here, we developed a multi‐type and precise genetic manipulation method in which a DNA break was generated by Cas9 nuclease and the repair was mediated using a homologous DNA template. The efficacy of this method was demonstrated for several types of gene editing, including inactivation of two low‐expression genes (CrTET1 and CrKU80), the introduction of a FLAG‐HA epitope tag into VIPP1, IFT46, CrTET1 and CrKU80 genes, and placing a YFP tag into VIPP1 and IFT46 for live‐cell imaging. We also successfully performed a single amino acid substitution for the FLA3, FLA10 and FTSY genes, and documented the attainment of the anticipated phenotypes. Lastly, we demonstrated that precise fragment deletion from the 3′‐UTR of MAA7 and VIPP1 resulted in a stable knock‐down effect. Overall, our study has established efficient methods for multiple types of precise gene editing in Chlamydomonas, enabling substitution, insertion and deletion at the base resolution, thus improving the potential of this alga in both basic research and industrial applications.
NATURE MAKES AN ASCENT FROM THE LOWER TO THE HIGHER: GREGORY OF NYSSA ON HUMAN DISTINCTIVENESS
Authors: Behr John 
Published: May 2023

AbstractThis essay explores the way in which early Christian writers held an eschatological understanding of what it is to be human, something that is to be attained, through the transformation of death and resurrection, and something that requires our assent. In this context, the article offers a new reading of the late fourth‐century work entitled On the Human Image of God (otherwise known in English as On the Making of Man) by Gregory of Nyssa. It argues that Gregory structured his text in parallel to the three parts of Timaeus’ speech in Plato's dialogue. The resulting picture sees creation as a dynamic ascent from the lower forms of life to the higher, a growth which is recapitulated in the life‐span of each human being, and also the growth of the human race into the totality of human beings that together constitute the human being in the image of God, the body of Christ.
Haematopinus suis Infestation in Pig Farms in Busogo Sector, Rwanda
Authors: Niyonsenga E. , Twizerimana J. , Mwabonimana M. F. 
Published: May 2023

Haematopinus suis(H. suis) is a common ectoparasite of pigs and is economically important worldwide. H. suis is responsible for anemia and poor feed conversion rate that lead to poor growth in pig husbandry. This study assessed the prevalence and risk factors of H. suis in pigs through a cross-sectional survey in Busogo sector of Musanze district. Fifty-five (55) pigs, representing 10% of 555 pigs from 20 farms, were examined physically for the presence of H. suis, and a total number of 559 H. suis were collected from them in Busogo sector of Musanze district. Data were analyzed using the Statistical Package for the Social Sciences (SPSS). Results showed that out of 55 pigs, a total number of 35 pigs (63.6%), were found infested with H. suis in Busogo sector of Musanze district. The infestation by H. suis was associated with the farming system, animal breeds, animal’s category, sex, pig hygiene, and piggery hygiene. Results showed a high (

P

< 0.05) prevalence in pigs reared in the intensive system (91.4%), whereas large whites were the most affected breed (60%). The prevalence of H. suis varied significantly (

P

< 0.05) among sexes, and females were the most affected (60%). Results related to pig hygiene revealed that all farmers were practicing washing skin three times per week, whereas only 60.0% of them were removing the bedding in their piggery. The study concluded that H. suis is present and remains a problem in the study area. Therefore, the study recommends to create farmer’s awareness on the disease in pigs and its impact through training. Researchers should continue further studies on H. suis prevention with appropriate pig husbandry and management practices and the efficacy of acaricides used.
Abstract A017: Deciphering the role of integrated stress response (ISR) in the developmental stages of mutant KRAS lung cancer
Authors: Diao Shiqi , Ghaddar Nour , Zou Jia Yi , Wang Shuo , Koromilas Antonis E. 
Published: May 2023

Abstract
Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) constitutes 80% of all lung malignancies with 15-25% attributed to mutations in the KRAS gene. KRAS mutations expose cells to stress-inducing conditions, e.g., genotoxic, proteotoxic and metabolic stress, which disrupt normal proliferation and tissue homeostasis. Successful proliferation of tumors is dependent on stress-adaptive pathways, which promote growth and contribute to resistance to chemotherapeutic drugs. Thus, inhibition of the adaptation process is considered a suitable anti-tumor approach for the treatment of KRAS cancers including lung cancer. An important mechanism of adaptation to stress involves the phosphorylation of the translation initiation factor eIF2α at serine 52 (p-eIF2α). Increased p-eIF2α is the nodal point of the integrated stress response (ISR), a master regulator of translational and transcriptional reprogramming that determines survival and adaptation to stress. We demonstrated the tumorigenic function of p-eIF2α in a mouse model of mutant KRAS cancer (Nature Communications 2021). We delineate the role of the ISR in lineage diversity and tumor heterogeneity during KRAS LUAD progression by single-cell RNA sequencing (sc-RNA seq). As such, the ISR was found to drive high stemness and epithelial to mesenchymal transition (EMT) programs in KRAS LUAD cells. The ISR also employs a high-plasticity cell-state mechanism for successful lung tumor progression and evolution. The involvement of the ISR in the mentioned processes further emphasizes its role as master regulator of pro-tumorigenic pathways and highlights the therapeutic potential of ISR inhibitors as novel targets in KRAS lung cancer. Our recent findings demonstrate that increased p-eIF2α stimulates the activity of the gene trans-activator proteins YAP and TAZ in mutant KRAS lung tumors. Genetic approaches identify a stimulatory effect of p-eIF2 on the expression of YAP/TAZ-dependent genes with roles in proliferation and epithelial to mesenchymal transition (EMT) including genes of WNT signaling pathway. We provide strong evidence that stimulation of YAP/TAZ activity by p-eIF2α occurs, at least partially, through the upregulation of the transcription factor ATF4 in tumor cells. Our findings demonstrate that p-eIF2α is a focal point of different tumorigenic pathways, intimately implicated in mutant KRAS-mediated transformation and tumor resistance to mutant KRAS inactivation.
Citation Format: Shiqi Diao, Nour Ghaddar, Jia Yi Zou, Shuo Wang, Antonis E. Koromilas. Deciphering the role of integrated stress response (ISR) in the developmental stages of mutant KRAS lung cancer [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr A017.
Abstract A027: Defining the role of PER1 and circadian rhythm dysregulation in KRAS/LKB1-mutant lung adenocarcinoma
Authors: Parker Rebecca E. , Koo Junghui , Dwivedi Bhakti , Marcus Adam I. , Gilbert-Ross Melissa 
Published: May 2023

Abstract
KRAS and LKB1 are frequently co-mutated in lung adenocarcinoma and characterize a particularly aggressive, metastatic, and treatment-resistant subtype of this disease. We recently published that the outputs of biological rhythm pathways downstream of the AMPK kinase are altered in KRAS/LKB1-mutant tumors. In a live-cell phenotyping screen we used RNAseq to identify the circadian clock genes PER1 and PER2 as uniquely upregulated in partially transformed and invasive KRAS/LKB1-mutant human bronchial epithelial cells. We have analyzed expression of individual circadian clock genes in KRAS-mutant and KRAS/LKB1-mutant patient tumors and found that expression of the PER genes, particularly PER1, is increased in the KRAS/LKB1 subtype of lung adenocarcinoma. At the protein level, PER1 expression is increased in KRAS/LKB1-mutant HBECs as compared to KRAS-mutant cells. Addback of wild-type LKB1 in A549 cells, which are KRAS/LKB1-mutant, results in a decrease in PER1 protein levels, confirming that LKB1 has a role in controlling PER1 levels. Multiple phosphorylation events lead to PER1 nuclear translocation to control its role as a transcriptional repressor in the core clock. In circadian-synced HBECs, PER1 enters the nucleus in KRAS-mutant cells, but remains cytosolic in KRAS/LKB1-mutant cells. In circadian-synced A549 cells, we also observed a lack of nuclear PER1 localization. Addback of wild-type LKB1 restored nuclear localization of PER1, as did expression of kinase-dead LKB1, suggesting that LKB1’s regulation of PER1 localization is kinase-independent. Our current and future experiments aim to determine how clock-controlled gene expression may be altered in KRAS/LKB1-mutant cells, what the functional impact of altered PER1 expression and localization is on growth of KRAS/LKB1-mutant tumors, and whether pharmacological manipulation of LKB1-related signaling pathways can restore nuclear localization of PER1.
Citation Format: Rebecca E. Parker, Junghui Koo, Bhakti Dwivedi, Adam I. Marcus, Melissa Gilbert-Ross. Defining the role of PER1 and circadian rhythm dysregulation in KRAS/LKB1-mutant lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr A027.
Abstract A040: The SRG OncoRat supports growth of numerous RAS mutant cell lines, expanding pre-clinical RAS-inhibitor testing
Authors: Walton R. Grace , Begemann Diane , Dunn Cynthia , Steffey Valeria , Ross Abigail , Haque Razoanul , Noto Fallon K. 
Published: May 2023

Abstract
RAS family proteins are important drug targets in multiple cancers due to their central role in hypertrophic and pro-mitotic signaling. KRAS is a small GTPase that is activated in response to growth factors including HGF, TGFα, and EGF. KRAS then activates the MAP kinase (MAPK; RAF/MEK/ERK) signaling pathway, driving ERK translocation to the nucleus, and resulting in transcription of pro-mitotic and pro-growth genes. Additionally, KRAS contributes to PI3K/AKT/mTOR signaling, leading to transcriptional activation as well as hypertrophic protein synthesis via mTOR. We sought to validate several RAS mutant cell-derived tumor xenograft models in the SRG OncoRat. Cells were inoculated subcutaneously in the flank of SRG rats. To date, we have validated tumor growth using the HT-1080 fibrosarcoma NRAS mutant (Gln61Lys (c.181C&gt;A)) cell line. We have also validated a suite of KRAS mutant lines in the SRG OncoRat, including: A-549 lung adenocarcinoma (Gly12Ser (c.34G&gt;A)); NCI-H2122 NSCLC adenocarcinoma (Gly12Cys (c.34G&gt;T)); MIA PaCa-2 pancreatic ductal adenocarcinoma and H-358 NSCLC adenocarcinoma (Gly12Cys (c.34G&gt;T)); Capan-2 pancreatic ductal adenocarcinoma (Gly12Val (c.35G&gt;T)); NCI-H441 NSCLC papillary adenocarcinoma (Gly12Val (c.35G&gt;T)); NCI-H1734 NSCLC adenocarcinoma (Gly13Cys (c.37G&gt;T)); and MDA-MB-231 breast adenocarcinoma (Gly13Asp (c.38G&gt;A)). All cell lines showed robust and consistent tumor growth when injected subcutaneously into the SRG OncoRat. These models provide valuable tools for pre-clinical testing of RAS inhibition.
Citation Format: R. Grace Walton, Diane Begemann, Cynthia Dunn, Valeria Steffey, Abigail Ross, Razoanul Haque, Fallon K. Noto. The SRG OncoRat supports growth of numerous RAS mutant cell lines, expanding pre-clinical RAS-inhibitor testing [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr A040.
Abstract B020: Creating actionable neoantigens by design with KRAS(G12C) covalent inhibitors
Authors: Maso Lorenzo , Hattori Takamitsu , Araki Kiyomi , Koide Akiko , Rajak Epsa , Hayman James , Akkapeddi Padma , Bang Injin , Neel Benjamin G. , Koide Shohei 
Published: May 2023

Abstract
Covalent inhibitors against KRAS(G12C) represent major breakthroughs in the effort to directly and selectively target oncogenic RAS mutants. However, similar to other targeted therapies, they lack durability. Immune therapy can be curative, and fragments of RAS containing a G12 mutation can be presented by the major histocompatibility complex (MHC) and thus could serve neoantigens. However, it is challenging to achieve selective targeting with minimal differences for RAS G12 mutations in the context of the large MHC molecule. To overcome these challenges and unify targeted and immune therapies, we have established a platform technology that exploits the large changes produced by the conjugation of a covalent inhibitor to create distinct neoantigens that selectively mark cancer cells. We performed proof-of-concept experiments using the FDA-approved covalent inhibitors sotorasib and osimertinib, and we developed “HapImmune” antibodies that bind to drug-peptide conjugate/MHC complexes but not to the free drugs. HapImmune-based bispecific T cell engager selectively and potently kills sotorasib-resistant lung cancer cells upon sotorasib treatment. Notably, it is effective against KRAS(G12C) mutant cells with different HLA supertypes, HLA-A*02, A*03 and A*11, suggesting loosening of MHC restriction. We have determined the structures of several HapImmune antibodies bound to drug-peptide conjugate/MHC complexes using cryo-electron microscopy, which revealed the molecular basis of their antigen recognition and will guide further improvement of their potency and specificity. Furthermore, we have developed additional antibodies to other KRAS(G12C) drugs and other targets, demonstrating the expansive scope of HapImmune approach that can potentially utilize the vast possible combinations of covalent inhibitors and oncoproteins.
Citation Format: Lorenzo Maso, Takamitsu Hattori, Kiyomi Araki, Akiko Koide, Epsa Rajak, James Hayman, Padma Akkapeddi, Injin Bang, Benjamin G. Neel, Shohei Koide. Creating actionable neoantigens by design with KRAS(G12C) covalent inhibitors [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B020.
Abstract B033: Wild-type RAS signaling is an essential therapeutic target in RAS-mutated cancers
Authors: Sealover Nancy , Finniff Bridget , Kortum Robert 
Published: May 2023

Abstract
Single-agent targeting of RAS-mutated cancers using RAF/MEK/ERK or PI3K/AKT pathway inhibitors is ineffective; blocking one pathway relieves negative feedback control of RTK signaling and hyperactivates parallel effector pathways. While combined MEK and PI3K inhibition is effective in preclinical models, toxicity of this combination prevents its clinical use. Alternative strategies for treating RAS-mutated cancers are essential. Therapeutics directly targeting mutated RAS proteins have the potential to spare normal cellular function thereby lessening overall toxicity. Unfortunately, direct RAS inhibition as a monotherapy does not fully block RAS effector signaling. RAS proteins show differential activation of RAF and PI3K pathways: KRAS potently activates RAF but poorly activates PI3K, whereas HRAS effectively activates PI3K but poorly activates RAF. Further, mutant RAS inhibition relieves negative feedback controls leading to rapid hyperactivation of RTK−WT RAS signaling. A more comprehensive understanding of the interplay between mutant RAS and RTK−WT RAS signaling is essential to developing rational therapeutic approaches to treat RAS-mutated cancers. We found that WT RAS enhanced mutant RAS-driven transformation by activating RAS effectors poorly engaged by mutated RAS. Further, inhibition of RAS effectors activated poorly by mutant RAS synergized with and limited resistance to mutant HRAS and KRAS inhibitors. The mutant HRAS inhibitor tipifarnib blocked PI3K signaling and synergized with MEK inhibitors in HRAS-mutated cancer cell lines; covalent KRASG12C inhibitors blocked MEK signaling and synergized with PI3K inhibitors in KRASG12C-mutated cell lines. Synergy between inhibitors of mutant RAS and RAS effectors was dependent on intact RTK/WT RAS signaling and was lost in both RASless or SOSless MEFs. These results should inform the design of clinical trials for patients with RAS-mutated cancers.
Citation Format: Nancy Sealover, Bridget Finniff, Robert Kortum. Wild-type RAS signaling is an essential therapeutic target in RAS-mutated cancers [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B033.