bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a shift to regional and organic diets reduce greenhouse gas emissions from the food system? A case study from Qatar
Authors: Vicente-Vicente José Luis , Piorr Annette 
Published: January 2021

AbstractBackgroundQatar is one of the countries with the highest carbon (C) footprints per capita in the world with an increasing population and food demand. Furthermore, the international blockade by some countries that is affecting Qatar—which has been traditionally a highly-dependent country on food imports—since 2017 has led the authorities to take the decision of increasing food self-sufficiency. In this study we have assessed the effect on greenhouse gas (GHG) emissions of shifting diets from conventional to organic products and from import-based diets to more regionalized diets for the first time in a Gulf country.ResultsWe found that considering the production system, the majority of the emissions come from the animal products, but the differences between conventional and organic diets are very small (738 and 722 kg CO2-eq capita−1 year−1, of total emissions, respectively). Conversely, total emissions from plant-based products consumption might be around one order of magnitude smaller, but the differences in the emissions between the organic and conventional systems were higher than those estimated for animal products, leading to a decrease in 44 kg CO2-eq capita−1 year−1when changing from 100% conventional to 50% of organic consumption of plant-based products. Regarding the shift to regionalized diets, we found that packaging has a small influence on the total amount of GHG emissions, whereas emissions from transportation would be reduced in around 450 kg CO2capita−1 year−1when reducing imports from 100 to 50%.ConclusionsHowever, these results must be read carefully. Due to the extreme adverse pedoclimatic conditions of the country, commercial organic regional livestock would not be possible without emitting very high GHG emissions and just only some traditional livestock species may be farmed in a climate-friendly way. On the other hand, organic and regional low-CO2emission systems of plant-based products would be possible by implementing innovations in irrigation or other innovations whose GHG emissions must be further studied in the future. Therefore, we conclude that shifting towards more plant-based organic regional consumption by using climate-friendly irrigation is a suitable solution to both increasing self-sufficiency and reducing C footprint. We encourage national authorities to including these outcomes into their environmental and food security policies.
Psychological processes in the experience of hereditary angioedema in adult patients: an observational study
Authors: Savarese Livia , Bova Maria , Maiello Assunta , Petraroli Angelica , Mormile Ilaria , Cancian Mauro , Senter Riccardo , Zanichelli Andrea , Spadaro Giuseppe , Freda Maria Francesca 
Published: January 2021

Abstract
Background
Hereditary angioedema associated to C1 inhibitor deficiency (C1-INH-HAE) is a pathological condition characterized by episodes of subcutaneous swelling and it is frequently associated with discomfort and social impairment of the patients, due to the anxiety experienced for an unpreventable manifestation of an attack during daily life. In children increased level of stress and alexithymia have been associated to C1-INH-HAE, and the latter correlated also with the severity of the disease. We hypothesized that the involvement of psychological issues may impact on the severity of C1-INH-HAE in adult patients as well, interfering with their ability to engage with the management of the disease.

Methods
28 adult patients with C1-INH-HAE were evaluated for clinical (C1-INH-HAE Severity Score) and psychological factors (alexithymia, emotion regulation, stress, patient health engagement, general severity index) by means of validated questionnaires.

Results
Mean age (standard deviation [SD]) was 45 (11) years and time from diagnosis was 20 (12) years. The mean C1-INH-HAE severity score was 6.4. Alexithymia was absent in 22 (78%) patients. Moderate and high stress levels were present in 17 (61%) and 4 (14%) patients, respectively. Moderate-high discomfort was experienced by 9 (36%) patients and a discomfort beyond the clinical attention threshold was shown by 3 (12%) patients. Stress correlated with patient health engagement and with psychological discomfort.

Conclusions
In C1-INH-HAE, patients health engagement and moderate-high psychological discomfort are linked with stress but not with the severity of the disease or alexithymia. A better patient health engagement may be a target for psychological intervention in clinics to ameliorate the stress perceived by C1-INH-HAE patients.
Effect of a peer‐led intervention combining mental health promotion with coping‐strategy‐based workshops on mental health awareness, help‐seeking behavior, and wellbeing among university students in Hong Kong
Authors: Ahorsu Daniel Kwasi , Sánchez Vidaña Dalinda Isabel , Lipardo Donald , Shah Parth Bharat , Cruz González Pablo , Shende Sachin , Gurung Shilpa , Venkatesan Harun , Duongthipthewa Anchalee , Ansari Talha Qasim , Schoeb Veronika 
Published: January 2021

Abstract
Background
The psychological well-being of university students is an important factor in successfully coping with the demands of academic life. This study aimed to assess the impact of a peer-led intervention of mental health promotion combined with coping-strategy-based group workshops on mental health awareness and help-seeking behavior among university students in Hong Kong.

Method
A mixed-method concurrent design was used for this study. Quantitative data, based on one-group pretest-posttest design, were collected using Mental Health Knowledge Schedule Questionnaire to assess mental health awareness, and Attitude Towards Seeking Professional Help Questionnaire-Short Form to examine help-seeking behavior of university students from The Hong Kong Polytechnic University. Qualitative data were collected from written post-activity reflections and focus group discussions which were thematically analyzed.

Results
A total of 62 university students (mean age: 23.2 ± 5.1 years) were included in this study. Mental health awareness was significantly improved (p = 0.015, 95% Confidence Interval of − 2.670, − 0.297) after program implementation. Help-seeking behavior mean score increased from pretest to posttest, however, no significant difference was observed (p = 0.188, 95% CI = − 1.775, 0.355). Qualitative analysis revealed that the program helped participants learn about coping strategies to help themselves and others with mental health challenges.

Conclusions
The peer-led intervention provided a positive impact through increased mental health awareness and knowledge of coping strategies on self-help and helping others among university students. Further study could focus on the impact of the program when applied regularly throughout the entire academic year.
Patient-friendly integrated first trimester screening by NIPT and fetal anomaly scan
Authors: Srebniak Malgorzata Ilona , Knapen Maarten F. C. M. , Joosten Marieke , Diderich Karin E. M. , Galjaard Sander , Van Opstal Diane 
Published: January 2021

AbstractMany major structural fetal anomalies can be diagnosed by first trimester fetal anomaly scan. NIPT can accurately detect aneuploidies and large chromosomal aberrations in cfDNA in maternal blood plasma. This study shows how a patient-friendly first trimester screening for both chromosomal and structural fetal anomalies in only two outpatient visits can be provided. Genotype-first approach assures not only the earliest diagnosis of trisomy 21 (the most prevalent chromosome aberration), but also completion of the screening at 12–14 weeks. To ensure proper management and avoid unnecessary anxiety abnormal NIPT different from trisomy 21, 18 and 13 should be referred for genetic counseling.
Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells
Authors: Park So Jung , Bae Ji-Eun , Jo Doo Sin , Kim Joon Bum , Park Na Yeon , Fang Jianguo , Jung Yong-Keun , Jo Dong Gyu , Cho Dong-Hyung 
Published: January 2021

AbstractAs a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimer’s disease (AD) is still largely unknown. Dynamin‐related protein 1 (Drp1) is an essential regulator for mitochondria fission. Among various posttranslational modifications, O-GlcNAcylation plays a role as a sensor for nutrient and oxidative stress. In this study, we identified that Drp1 is regulated by O-GlcNAcylation in AD models. Treatment of Aβ as well as PugNAc resulted in mitochondrial fragmentation in neuronal cells. Moreover, we found that AD mice brain exhibits an upregulated Drp1 O-GlcNAcylation. However, depletion of OGT inhibited Drp1 O-GlcNAcylation in Aβ-treated cells. In addition, overexpression of O-GlcNAc defective Drp1 mutant (T585A and T586A) decreased Drp1 O-GlcNAcylation and Aβ-induced mitochondria fragmentation. Taken together, these finding suggest that Aβ regulates mitochondrial fission by increasing O-GlcNAcylation of Drp1.
Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy
Authors: Wang Bin , Zhao Qin , Zhang Yuyu , Liu Zijing , Zheng Zhuangzhuang , Liu Shiyu , Meng Lingbin , Xin Ying , Jiang Xin 
Published: January 2021

AbstractWith the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with cancer still do not benefit from this revolutionary therapy. Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology. Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact of hypoxia within the TME, in terms of key immune cell populations, and the contribution to immune suppression are discussed. In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy.
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Authors: Qian Weikun , Chen Ke , Qin Tao , Xiao Ying , Li Jie , Yue Yangyang , Zhou Cancan , Ma Jiguang , Duan Wanxing , Lei Jianjun , Han Liang , Li Li , Shen Xin , Wu Zheng , Ma Qingyong , Wang Zheng 
Published: January 2021

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.

Methods
The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR).

Results
In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.

Conclusion
Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
YAP and endothelin-1 signaling: an emerging alliance in cancer
Authors: Tocci Piera , Blandino Giovanni , Bagnato Anna 
Published: January 2021

AbstractThe rational making the G protein-coupled receptors (GPCR) the centerpiece of targeted therapies is fueled by the awareness that GPCR-initiated signaling acts as pivotal driver of the early stages of progression in a broad landscape of human malignancies. The endothelin-1 (ET-1) receptors (ET-1R), known as ETA receptor (ETAR) and ETB receptor (ETBR) that belong to the GPCR superfamily, affect both cancer initiation and progression in a variety of cancer types. By the cross-talking with multiple signaling pathways mainly through the scaffold protein β-arrestin1 (β-arr1), ET-1R axis cooperates with an array of molecular determinants, including transcription factors and co-factors, strongly affecting tumor cell fate and behavior. In this scenario, recent findings shed light on the interplay between ET-1 and the Hippo pathway. In ETAR highly expressing tumors ET-1 axis induces the de-phosphorylation and nuclear accumulation of the Hippo pathway downstream effectors, the paralogous transcriptional cofactors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). Recent evidence have discovered that ET-1R/β-arr1 axis instigates a transcriptional interplay involving YAP and mutant p53 proteins, which share a common gene signature and cooperate in a oncogenic signaling network. Mechanistically, YAP and mutp53 are enrolled in nuclear complexes that turn on a highly selective YAP/mutp53-dependent transcriptional response. Notably, ET-1R blockade by the FDA approved dual ET-1 receptor antagonist macitentan interferes with ET-1R/YAP/mutp53 signaling interplay, through the simultaneous suppression of YAP and mutp53 functions, hampering metastasis and therapy resistance. Based on these evidences, we aim to review the recent findings linking the GPCR signaling, as for ET-1R, to YAP/TAZ signaling, underlining the clinical relevance of the blockade of such signaling network in the tumor and microenvironmental contexts. In particular, we debate the clinical implications regarding the use of dual ET-1R antagonists to blunt gain of function activity of mutant p53 proteins and thereby considering them as a potential therapeutic option for mutant p53 cancers. The identification of ET-1R/β-arr1-intertwined and bi-directional signaling pathways as targetable vulnerabilities, may open new therapeutic approaches able to disable the ET-1R-orchestrated YAP/mutp53 signaling network in both tumor and stromal cells and concurrently sensitizes to high-efficacy combined therapeutics.
Heterogeneous constitutional mismatch repair deficiency with MSH6 missense mutation clinically benefits from pembrolizumab and regorafenib combination therapy: a case report and literature review
Authors: Xie Tong , Feng Qin , Li Zhongwu , Lu Ming , Li Jian , Lizaso Analyn , Xiang Jianxing , Zhang Lu , Shen Lin , Peng Zhi 
Published: January 2021

Abstract
Background
Germline DNA mismatch repair (MMR) gene aberrations are associated with colorectal cancer (CRC) predisposition and high tumor mutation burden (TMB-H), with increased likelihood of favorable response to immune checkpoint inhibitors (ICIs).

Case presentation
We present a 32-year old male patient diagnosed with constitutional MMR deficiency (CMMRD) CRC whose MMR immunohistochemistry (IHC) revealed inconsistent results from two tumor blocks. Targeted sequencing of two tumor specimens used in MMR-IHC and plasma-derived circulating tumor DNA consistently revealed the detection of bi-allelic germline MSH6 c.3226C > T (p.R1076C) mutation, TMB-H as well as the genetic heterogeneity of the tumor samples. Unexpectedly, both blocks were microsatellite stable (MSS) after PCR confirmation. Interestingly, the patient failed to show response to ICI monotherapy or dual therapy, but clinically benefitted from combined therapy of ICI pembrolizumab plus multi-kinase inhibitor regorafenib.

Conclusion
Our case reported a CMMRD patient with heterogeneous MMR results who showed complicated response to ICIs, highlighting the importance of accurate diagnosis using targeted sequencing with multiple specimens to reveal the possible mechanism of response to ICI in patients with CMMRD.
Integration of human cell lines gene expression and chemical properties of drugs for Drug Induced Liver Injury prediction
Authors: Lesiński Wojciech , Mnich Krzysztof , Golińska Agnieszka Kitlas , Rudnicki Witold R. 
Published: January 2021

Abstract
Motivation
Drug-induced liver injury (DILI) is one of the primary problems in drug development. Early prediction of DILI can bring a significant reduction in the cost of clinical trials. In this work we examined whether occurrence of DILI can be predicted using gene expression profile in cancer cell lines and chemical properties of drugs.

Methods
We used gene expression profiles from 13 human cell lines, as well as molecular properties of drugs to build Machine Learning models of DILI. To this end, we have used a robust cross-validated protocol based on feature selection and Random Forest algorithm. In this protocol we first identify the most informative variables and then use them to build predictive models. The models are first built using data from single cell lines, and chemical properties. Then they are integrated using Super Learner method with several underlying methods for integration. The entire modelling process is performed using nested cross-validation.

Results
We have obtained weakly predictive ML models when using either molecular descriptors, or some individual cell lines (AUC ∈(0.55−0.61)). Models obtained with the Super Learner approach have a significantly improved accuracy (AUC=0.73), which allows to divide substances in two categories: low-risk and high-risk.
Why call it developmental bias when it is just development?
Authors: Salazar-Ciudad Isaac 
Published: January 2021

AbstractThe concept of developmental constraints has been central to understand the role of development in morphological evolution. Developmental constraints are classically defined as biases imposed by development on the distribution of morphological variation.This opinion article argues that the concepts of developmental constraints and developmental biases do not accurately represent the role of development in evolution. The concept of developmental constraints was coined to oppose the view that natural selection is all-capable and to highlight the importance of development for understanding evolution. In the modern synthesis, natural selection was seen as the main factor determining the direction of morphological evolution. For that to be the case, morphological variation needs to be isotropic (i.e. equally possible in all directions). The proponents of the developmental constraint concept argued that development makes that some morphological variation is more likely than other (i.e. variation is not isotropic), and that, thus, development constraints evolution by precluding natural selection from being all-capable.This article adds to the idea that development is not compatible with the isotropic expectation by arguing that, in fact, it could not be otherwise: there is no actual reason to expect that development could lead to isotropic morphological variation. It is then argued that, since the isotropic expectation is untenable, the role of development in evolution should not be understood as a departure from such an expectation. The role of development in evolution should be described in an exclusively positive way, as the process determining which directions of morphological variation are possible, instead of negatively, as a process precluding the existence of morphological variation we have no actual reason to expect.This article discusses that this change of perspective is not a mere question of semantics: it leads to a different interpretation of the studies on developmental constraints and to a different research program in evolution and development. This program does not ask whether development constrains evolution. Instead it asks questions such as, for example, how different types of development lead to different types of morphological variation and, together with natural selection, determine the directions in which different lineages evolve.
Geographical distribution of Gyrodactylus salaris Malmberg, 1957 (Monogenea, Gyrodactylidae)
Authors: Paladini Giuseppe , Shinn Andrew P. , Taylor Nicholas G. H. , Bron James E. , Hansen Haakon 
Published: January 2021

Abstract
Background
Gyrodactylus salaris Malmberg, 1957 is an OIE (Office International des Epizooties)-listed parasitic pathogen and had until the current study been reported from 19 countries across Europe, although many of these records require confirmation. The last comprehensive evaluation regarding the distribution of G. salaris, however, was made in 2007, although some of the states identified as being G. salaris-positive were ascribed this status based on misidentifications, on partial data resulting from either morphological or molecular tests, or from records that have not been revisited since their early reporting. It is thus important to go through the reports on G. salaris to obtain a status for each country.

Methods
To provide a revised update of the G. salaris distribution, a literature review was necessary. This literature, however, was not always readily accessible and, in certain cases, the article only made superficial reference to the parasite without providing details or data to support the identification. In most cases, the original specimens were not deposited in a national collection. Additional Gyrodactylus material for the current study was obtained from selected salmonid populations with the aim to contribute to current understanding regarding the distribution of G. salaris. Additional parasite material collected for this study was processed following standard procedures for species identification in Gyrodactylus [1].

Results
From the work conducted in the current study, G. salaris is reported from a further three regions in Italy, alongside three other species, and appears to occur extensively throughout central Italy without causing significant mortalities to its rainbow trout, Oncorhynchus mykiss (Walbaum), host. The analysis of archive material from G. salaris-positive farms would suggest that G. salaris has been in this country since at least 2000. Material obtained from rainbow trout from Finland and Germany are confirmed as G. salaris, supporting existing data for these countries. No specimens of G. salaris, however, were found in the additional Gyrodactylus material obtained from rainbow trout reared in Portugal and Spain. A morphologically similar species, Gyrodactylus teuchis Lautraite, Blanc, Thiery, Daniel et Vigneulle, 1999, however, was found.

Conclusions
Following the present review, Gyrodactylus salaris is reported from 23 out of 50 recognised states throughout Europe; only records from 14 of these states have been confirmed by either morphology and/or by an appropriate molecular test and are considered valid, while only nine of these records have been confirmed by a combination of both methods.

Graphical Abstract