bluuebunny/crossref_metadata_2025_split huggingface dataset:
The serum metabolomic profile of a distinct, inflammatory subtype of acute psychosis
Authors: Lennox Belinda , Xiong Wenzheng , Waters Patrick , Coles Alasdair , Jones Peter B. , Yeo Tianrong , May Jeanne Tan May , Yeeles Ksenija , Anthony Daniel , Probert Fay 
Published: September 2022

AbstractA range of studies suggest that a proportion of psychosis may have an autoimmune basis, but this has not translated through into clinical practice—there is no biochemical test able to accurately identify psychosis resulting from an underlying inflammatory cause. Such a test would be an important step towards identifying who might require different treatments and have the potential to improve outcomes for patients. To identify novel subgroups within patients with acute psychosis we measured the serum nuclear magnetic resonance (NMR) metabolite profiles of 75 patients who had identified antibodies (anti-glycine receptor [GlyR], voltage-gated potassium channel [VGKC], Contactin-associated protein-like 2 [CASPR2], leucine-rich glioma inactivated 1 [LGI1], N-methyl-D-aspartate receptor [NMDAR] antibody) and 70 antibody negative patients matched for age, gender, and ethnicity. Clinical symptoms were assessed using the positive and negative syndrome scale (PANSS). Unsupervised principal component analysis identified two distinct biochemical signatures within the cohort. Orthogonal partial least squared discriminatory analysis revealed that the serum metabolomes of NMDAR, LGI1, and CASPR2 antibody psychosis patients were indistinct from the antibody negative control group while VGKC and GlyR antibody patients had significantly decreased lipoprotein fatty acids and increased amino acid concentrations. Furthermore, these patients had more severe presentation with higher PANSS scores than either the antibody negative controls or the NMDAR, LGI1, and CASPR2 antibody groups. These results suggest that a proportion of patients with acute psychosis have a distinct clinical and biochemical phenotype that may indicate an inflammatory subtype.
High-throughput design of functional-engineered MXene transistors with low-resistive contacts
Authors: Guha Sirsha , Kabiraj Arnab , Mahapatra Santanu 
Published: September 2022

AbstractTwo-dimensional material-based transistors are being extensively investigated for CMOS (complementary metal oxide semiconductor) technology extension; nevertheless, downscaling appears to be challenging owing to high metal-semiconductor contact resistance. Here, we propose a functional group-engineered monolayer transistor architecture that takes advantage of MXenes’ natural material chemistry to offer low-resistive contacts. We design an automated, high-throughput computational pipeline that first performs hybrid density functional theory-based calculations to find 16 sets of complementary transistor configurations by screening more than 23,000 materials from an MXene database and then conducts self-consistent quantum transport calculations to simulate their current-voltage characteristics for channel lengths ranging from 10 nm to 3 nm. Performance of these devices has been found to meet the requirements of the international roadmap for devices and systems (IRDS) for several benchmark metrics (on current, power dissipation, delay, and subthreshold swing). The proposed balanced-mode, functional-engineered MXene transistors may lead to a realistic solution for the sub-decananometer technology scaling by enabling doping-free intrinsically low contact resistance.
Antibody targeting of E3 ubiquitin ligases for receptor degradation
Authors: Marei Hadir , Tsai Wen-Ting K. , Kee Yee-Seir , Ruiz Karen , He Jieyan , Cox Chris , Sun Tao , Penikalapati Sai , Dwivedi Pankaj , Choi Meena , Kan David , Saenz-Lopez Pablo , Dorighi Kristel , Zhang Pamela , Kschonsak Yvonne T. , Kljavin Noelyn , Amin Dhara , Kim Ingrid , Mancini Andrew G. , Nguyen Thao , Wang Chunling , Janezic Eric , Doan Alexander , Mai Elaine , Xi Hongkang , Gu Chen , Heinlein Melanie , Biehs Brian , Wu Jia , Lehoux Isabelle , Harris Seth , Comps-Agrar Laetitia , Seshasayee Dhaya , de Sauvage Frederic J. , Grimmer Matthew , Li Jing , Agard Nicholas J. , de Sousa e Melo Felipe 
Published: September 2022

AbstractMost current therapies that target plasma membrane receptors function by antagonizing ligand binding or enzymatic activities. However, typical mammalian proteins comprise multiple domains that execute discrete but coordinated activities. Thus, inhibition of one domain often incompletely suppresses the function of a protein. Indeed, targeted protein degradation technologies, including proteolysis-targeting chimeras1 (PROTACs), have highlighted clinically important advantages of target degradation over inhibition2. However, the generation of heterobifunctional compounds binding to two targets with high affinity is complex, particularly when oral bioavailability is required3. Here we describe the development of proteolysis-targeting antibodies (PROTABs) that tether cell-surface E3 ubiquitin ligases to transmembrane proteins, resulting in target degradation both in vitro and in vivo. Focusing on zinc- and ring finger 3 (ZNRF3), a Wnt-responsive ligase, we show that this approach can enable colorectal cancer-specific degradation. Notably, by examining a matrix of additional cell-surface E3 ubiquitin ligases and transmembrane receptors, we demonstrate that this technology is amendable for ‘on-demand’ degradation. Furthermore, we offer insights on the ground rules governing target degradation by engineering optimized antibody formats. In summary, this work describes a strategy for the rapid development of potent, bioavailable and tissue-selective degraders of cell-surface proteins.
Structural basis for directional chitin biosynthesis
Authors: Chen Wei , Cao Peng , Liu Yuansheng , Yu Ailing , Wang Dong , Chen Lei , Sundarraj Rajamanikandan , Yuchi Zhiguang , Gong Yong , Merzendorfer Hans , Yang Qing 
Published: September 2022

AbstractChitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting ofN-acetylglucosamine (GlcNAc) units1. The key reactions of chitin biosynthesis are catalysed by chitin synthase2–4, a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to a growing chitin chain. However, the precise mechanism of this process has yet to be elucidated. Here we report five cryo-electron microscopy structures of a chitin synthase from the devastating soybean root rot pathogenic oomycetePhytophthora sojae(PsChs1). They represent the apo, GlcNAc-bound, nascent chitin oligomer-bound, UDP-bound (post-synthesis) and chitin synthase inhibitor nikkomycin Z-bound states of the enzyme, providing detailed views into the multiple steps of chitin biosynthesis and its competitive inhibition. The structures reveal the chitin synthesis reaction chamber that has the substrate-binding site, the catalytic centre and the entrance to the polymer-translocating channel that allows the product polymer to be discharged. This arrangement reflects consecutive key events in chitin biosynthesis from UDP-GlcNAc binding and polymer elongation to the release of the product. We identified a swinging loop within the chitin-translocating channel, which acts as a ‘gate lock’ that prevents the substrate from leaving while directing the product polymer into the translocating channel for discharge to the extracellular side of the cell membrane. This work reveals the directional multistep mechanism of chitin biosynthesis and provides a structural basis for inhibition of chitin synthesis.
The Anglo-Saxon migration and the formation of the early English gene pool
Authors: Gretzinger Joscha , Sayer Duncan , Justeau Pierre , Altena Eveline , Pala Maria , Dulias Katharina , Edwards Ceiridwen J. , Jodoin Susanne , Lacher Laura , Sabin Susanna , Vågene Åshild J. , Haak Wolfgang , Ebenesersdóttir S. Sunna , Moore Kristjan H. S. , Radzeviciute Rita , Schmidt Kara , Brace Selina , Bager Martina Abenhus , Patterson Nick , Papac Luka , Broomandkhoshbacht Nasreen , Callan Kimberly , Harney Éadaoin , Iliev Lora , Lawson Ann Marie , Michel Megan , Stewardson Kristin , Zalzala Fatma , Rohland Nadin , Kappelhoff-Beckmann Stefanie , Both Frank , Winger Daniel , Neumann Daniel , Saalow Lars , Krabath Stefan , Beckett Sophie , Van Twest Melanie , Faulkner Neil , Read Chris , Barton Tabatha , Caruth Joanna , Hines John , Krause-Kyora Ben , Warnke Ursula , Schuenemann Verena J. , Barnes Ian , Dahlström Hanna , Clausen Jane Jark , Richardson Andrew , Popescu Elizabeth , Dodwell Natasha , Ladd Stuart , Phillips Tom , Mortimer Richard , Sayer Faye , Swales Diana , Stewart Allison , Powlesland Dominic , Kenyon Robert , Ladle Lilian , Peek Christina , Grefen-Peters Silke , Ponce Paola , Daniels Robin , Spall Cecily , Woolcock Jennifer , Jones Andy M. , Roberts Amy V. , Symmons Robert , Rawden Anooshka C. , Cooper Alan , Bos Kirsten I. , Booth Tom , Schroeder Hannes , Thomas Mark G. , Helgason Agnar , Richards Martin B. , Reich David , Krause Johannes , Schiffels Stephan 
Published: September 2022

AbstractThe history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6.
Crosswalks among stewardship maturity assessment approaches promoting trustworthy FAIR data and repositories
Authors: Peng Ge , Gross Wendy S. , Edmunds Rorie 
Published: September 2022

AbstractVarious maturity assessment approaches have been developed to help research data repositories effectively manage their holdings at both the organizational and dataset levels. Repositories can use these approaches as self-assessment tools—potentially leading to formal certification—to benchmark the maturity of their data holdings, highlight gaps in their practices, and improve their sustainability. Understanding the differences among these assessment approaches can provide beneficial information on stewardship best practices for supporting FAIR data managed by Trustworthy Data Repositories. However, it is a daunting task due to diversity in the perspectives of the approaches and the potential for subjective interpretation of individual criteria. In this article, we outline the commonalities and distinctions of three established assessment approaches: i) CoreTrustSeal Trustworthy Data Repositories Requirements, ii) Data Stewardship Maturity Matrix, and iii) FAIR Guiding Principles. Strong correlations are found in data discovery, accessibility, interoperability, and usability due to overlapping requirements in digital object management. The study also reveals that the complexity of the approaches can lead to a large variety of inferred crosswalks among them.
Diagnostic features and management options for duodenal neuroendocrine neoplasms: a retrospective, multi-centre study
Authors: Mandair Dalvinder , Kamieniarz Lukasz , Pizanias Michail , Weickert Martin O. , Narayan Akshay , O’Mahony Luke Furtado , Caplin Martyn , Ramage John , Prachalias Andreas , Srirajaskanthan Rajaventhan , Toumpanakis Christos 
Published: September 2022

AbstractDuodenal neuroendocrine neoplasms (dNENs) are rare neoplasms but their incidence is on the rise. They are classified into 5 sub-types but there remains much heterogeneity in behaviour in particular of non-functioning dNENs. To retrospectively analyse outcomes for all types of dNENs, and highlight prognostic factors associated with worse outcome. 102 (57 m/45f.) patients were identified with mean age at diagnosis 62 (range 32–87) years. The majority were non-functioning tumours 87/102 and median size was 10 mm (range 0.9–130 mm). 83 patients had Stage I or II disease, of which 17 underwent endoscopic resection with R1 rate of 45% and complication rate 12%. 36 patients were kept under endoscopic surveillance. There were 11 deaths of which 4 were disease related. Age and Ki67 > 20% were associated with worse OS in all dNENs. In non-functioning dNENs Ki67 > 3% was a predictor of lymph nodes metastases with OR 18.2 (2.54–13) (p < 0.005) in univariate analyses and liver metastases with OR 6.79 (1.56–29.5) (p < 0.05) in the multivariate analysis. Lesions 11–20 mm in size had OR 11.1 (1.16–106) compared to lesions < 11 mm for the prediction of lymph node metastases in the multivariate analysis (p < 0.05). ROC analysis of size of non-functioning dNENs to predict LN metastases found < 15 mm had an AUROC of 0.9 (0.81–0.99) with a sensitivity of 85% and specificity of 88%. dNENs are increasing in incidence, however low grade and smaller lesions have an indolent course and the role of endoscopic resection and active surveillance needs to be reviewed.
Association of TSHR gene single nucleotide intronic polymorphism with the risk of hypothyroid and hyperthyroid disorders in Yazd province
Authors: Naghibi Fahime Sadat , Miresmaeili Seyed Mohsen , Javid Amaneh 
Published: September 2022

AbstractThe present study was carried out, for the first time, to evaluate the association of rs2268458 polymorphism, biochemical and environmental factors on hypothyroid and hyperthyroid disorders in thyroid patients and healthy individuals in Yazd province, Iran. In this study, blood samples were collected from a total of 100 cases, including 60 hypothyroid, 20 hyperthyroid and 20 normal individuals. DNA was extracted from blood samples and the rs2268458 single nucleotide intronic polymorphism was evaluated using Restriction Fragment Length Polymorphism PCR (RFLP-PCR). The results have shown that 59 individuals were homozygote (TT), 40 cases were heterozygote (TC) and one homozygote (CC) case. Of 59 TT homozygote cases, 25 cases were hypothyroid females and 7 hypothyroid male patients. While, heterozygote TC group consisted of 20 hypothyroid females and 7 hypothyroid male cases. Furthermore, only 1 (CC) homozygote male hypothyroid patient was observed in this study. The hyperthyroid population consisted of 7 (TT) homozygote hyperthyroid female cases, 8 (TC) heterozygote hyperthyroid female cases, 3 (TT) homozygote hyperthyroid male cases and 2 (TC) heterozygote hyperthyroid male cases. According to our study, heterozygote cases (TC) showed less severe symptoms, while homozygote cases (TT) showed no serious symptoms and the (CC) homozygote case showed severe thyroid abnormalities. So, it can be concluded that the TSHR-related rs2268458 polymorphism is associated with hypothyroidism and hyperthyroidism in the male and female populations of Yazd Province, Iran and C allele can be a risk factor for some physio-biochemical and hormonal imbalance in the thyroid disorder patients.
Association between irregular daily routine and risk of incident stroke and coronary heart disease in a large Japanese population
Authors: Yoshizaki Takahiro , Ishihara Junko , Kotemori Ayaka , Kokubo Yoshihiro , Saito Isao , Yatsuya Hiroshi , Yamagishi Kazumasa , Sawada Norie , Iwasaki Motoki , Iso Hiroyasu , Tsugane Shoichiro ,   The JPHC Study Group
Published: September 2022

AbstractCircadian misalignments have been linked to adverse cardiometabolic outcomes. However, the association between irregular daily routine and the risk of cardiovascular disease (CVD) remains unknown. We examined this association in a prospective study in Japan. The study included 78,115 Japanese participants aged 45–74 years. The self-reported daily routine was evaluated using the question, ‘Is your daily routine or activity schedule regular?’ The response (yes/no) was obtained as a binary variable. Cox proportional hazard regression analysis was used to estimate the hazard ratios and 95% confidence intervals for the association between an irregular daily routine and CVD incidence risk. Among the participants, 23.7% reported an irregular daily routine. During the mean follow-up period of 13.3 years, we observed 4641 CVD events. An irregular daily routine was significantly associated with increased risks of CVD and total stroke in women, but not in men. This positive association between an irregular daily routine and the risk of CVD was weak in the high vegetable and fruit consuming population. An irregular daily routine is positively associated with the risk of incident CVD, especially in women. These associations may be weak in populations that consume a diet rich in vegetables and fruits.
Effect of surgical mask on fMRI signals during task and rest
Authors: Klugah-Brown Benjamin , Yu Yue , Hu Peng , Agoalikum Elijah , Liu Congcong , Liu Xiqin , Yang Xi , Zeng Yixu , Zhou Xinqi , Yu Xin , Rypma Bart , Michael Andrew M. , Li Xiaobo , Becker Benjamin , Biswal Bharat 
Published: September 2022

AbstractWearing a face mask has become essential to contain the spread of COVID-19 and has become mandatory when collecting fMRI data at most research institutions. Here, we investigate the effects of wearing a surgical mask on fMRI data in n = 37 healthy participants. Activations during finger tapping, emotional face matching, working memory tasks, and rest were examined. Preliminary fMRI analyses show that despite the different mask states, resting-state signals and task activations were relatively similar. Resting-state functional connectivity showed negligible attenuation patterns in mask-on compared with mask-off. Task-based ROI analysis also demonstrated no significant difference between the two mask states under each contrast investigated. Notwithstanding the overall insignificant effects, these results indicate that wearing a face mask during fMRI has little to no significant effect on resting-state and task activations.
Identification of Δ-1-pyrroline-5-carboxylate derived biomarkers for hyperprolinemia type II
Authors: Merx Jona , van Outersterp Rianne E. , Engelke Udo F. H. , Hendriks Veronique , Wevers Ron A. , Huigen Marleen C. D. G. , Waterval Huub W. A. H. , Körver-Keularts Irene M. L. W. , Mecinović Jasmin , Rutjes Floris P. J. T. , Oomens Jos , Coene Karlien L. M. , Martens Jonathan , Boltje Thomas J. 
Published: September 2022

AbstractHyperprolinemia type II (HPII) is an inborn error of metabolism due to genetic variants in ALDH4A1, leading to a deficiency in Δ-1-pyrroline-5-carboxylate (P5C) dehydrogenase. This leads to an accumulation of toxic levels of P5C, an intermediate in proline catabolism. The accumulating P5C spontaneously reacts with, and inactivates, pyridoxal 5’-phosphate, a crucial cofactor for many enzymatic processes, which is thought to be the pathophysiological mechanism for HPII. Here, we describe the use of a combination of LC-QTOF untargeted metabolomics, NMR spectroscopy and infrared ion spectroscopy (IRIS) to identify and characterize biomarkers for HPII that result of the spontaneous reaction of P5C with malonic acid and acetoacetic acid. We show that these biomarkers can differentiate between HPI, caused by a deficiency of proline oxidase activity, and HPII. The elucidation of their molecular structures yields insights into the disease pathophysiology of HPII.
The conservation of human functional variants and their effects across livestock species
Authors: Zhao Rongrong , Talenti Andrea , Fang Lingzhao , Liu Shuli , Liu George , Chue Hong Neil P. , Tenesa Albert , Hassan Musa , Prendergast James G. D. 
Published: September 2022

AbstractDespite the clear potential of livestock models of human functional variants to provide important insights into the biological mechanisms driving human diseases and traits, their use to date has been limited. Generating such models via genome editing is costly and time consuming, and it is unclear which variants will have conserved effects across species. In this study we address these issues by studying naturally occurring livestock models of human functional variants. We show that orthologues of over 1.6 million human variants are already segregating in domesticated mammalian species, including several hundred previously directly linked to human traits and diseases. Models of variants linked to particular phenotypes, including metabolomic disorders and height, are preferentially shared across species, meaning studying the genetic basis of these phenotypes is particularly tractable in livestock. Using machine learning we demonstrate it is possible to identify human variants that are more likely to have an existing livestock orthologue, and, importantly, we show that the effects of functional variants are often conserved in livestock, acting on orthologous genes with the same direction of effect. Consequently, this work demonstrates the substantial potential of naturally occurring livestock carriers of orthologues of human functional variants to disentangle their functional impacts.
Cities leading hydrogen energy development: the pledges and strategies of 39 Chinese cities
Authors: Peng Yuan , Bai Xuemei 
Published: September 2022

AbstractHydrogen energy from renewables has the potential to address climate challenges, and technological advancements are vital for driving this energy transition. Globally, an increasing number of cities are actively adopting hydrogen strategies. The literature on the urban sustainability transition primarily focuses on policy innovations for technology adoption, while the role of cities in enabling technological innovation is underexplored. Here, we address this gap by analyzing 122 policy documents from 39 Chinese cities with hydrogen plans by using qualitative content analysis methods. The findings reveal myriad and critical roles of cities in fostering technological innovations in an emergent hydrogen economy via targeted policy support and investment in desired technologies. By moving ahead of the national government, these early movers play a critical role in creating early momentum and laying the foundation for future scale transition. Our findings also point to a clear need for these bottom-up initiatives to be better guided and channeled toward clean hydrogen development, as the lack of upper-level policy guidance can lead to diversified priorities and outcomes. Our findings call for renewed research and policy attention to the proactive role of cities in technological innovation and the sustainability transition and they stress the importance of engaging cities in hydrogen economy development nationally and internationally.