bluuebunny/crossref_metadata_2025_split huggingface dataset:
The practices and beliefs of dental professionals regarding the management of patients taking anticoagulant and antiplatelet drugs
Authors: Kelly Niamh , Beaton Laura , Knights Jennifer , Stirling Douglas , West Michele , Young Linda 
Published: January 2023

Abstract
Aim
This study aimed to inform the implementation of the updated Scottish Dental Clinical Effectiveness Programme (SDCEP) guidance, ‘Management of Dental Patients taking Anticoagulant or Antiplatelet Drugs’, and to determine training needs by investigating dental professionals’ current practice and beliefs regarding management of patients taking these medications.

Methods
Dental professionals were recruited via the NHS Education for Scotland Portal. The online questionnaire collected demographic information, data on current practice and information about beliefs regarding behaviours related to the management of patients on anticoagulant or antiplatelet medication. Quantitative data were analysed using SPSS and subjected to frequency calculations, t-tests, one-way ANOVA and linear regression. Qualitative data were collected via free text boxes and analysed using thematic analysis.

Results
One hundred and fifty-seven participants responded to the questionnaire. The majority of respondents stated they were aware of the guidance and always based their practice on it. The majority of respondents always assessed the patient’s individual bleeding risk prior to dental procedures. Most respondents felt that they did not know how to appropriately manage patients taking low doses of low molecular weight heparins (LMWH), and only 38% of respondents always followed SDCEP guidance about direct oral anticoagulants (DOAC) medication and procedures with a low associated risk of bleeding.

Discussion
This study demonstrates a need for further educational support surrounding LMWHs and management of patients on DOAC medication. Time and remuneration represent barriers to guidance implementation in primary care.

Conclusion
There is good awareness and adherence to the guidance in primary care settings, however training needs were identified to support implementation.
Verteporfin reverses progestin resistance through YAP/TAZ-PI3K-Akt pathway in endometrial carcinoma
Authors: Wei Lina , Ma Xiaohong , Hou Yixin , Zhao Tianyi , Sun Rui , Qiu Chunping , Liu Yao , Qiu Ziyi , Liu Zhiming , Jiang Jie 
Published: January 2023

AbstractProgestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.
Transcriptomic analyses of patient peripheral blood with hemoglobin depletion reveal glioblastoma biomarkers
Authors: Qi Dan , Geng Yiqun , Cardenas Jacob , Gu Jinghua , Yi S. Stephen , Huang Jason H. , Fonkem Ekokobe , Wu Erxi 
Published: January 2023

AbstractPeripheral blood is gaining prominence as a noninvasive alternative to tissue biopsy to develop biomarkers for glioblastoma (GBM); however, widely utilized blood-based biomarkers in clinical settings have not yet been identified due to the lack of a robust detection approach. Here, we describe the application of globin reduction in RNA sequencing of whole blood (i.e., WBGR) and perform transcriptomic analysis to identify GBM-associated transcriptomic changes. By using WBGR, we improved the detection sensitivity of informatic reads and identified differential gene expression in GBM blood. By analyzing tumor tissues, we identified transcriptomic traits of GBM blood. Further functional enrichment analyses retained the most changed genes in GBM. Subsequent validation elicited a 10-gene panel covering mRNA, long noncoding RNA, and microRNA (i.e., GBM-Dx panel) that has translational potential to aid in the early detection or clinical management of GBM. Here, we report an integrated approach, WBGR, with comprehensive analytic capacity for blood-based marker identification.
Soft wearable flexible bioelectronics integrated with an ankle-foot exoskeleton for estimation of metabolic costs and physical effort
Authors: Kim Jihoon , Kantharaju Prakyath , Yi Hoon , Jacobson Michael , Jeong Hyungkeun , Kim Hojoong , Lee Jinwoo , Matthews Jared , Zavanelli Nathan , Kim Hyeonseok , Jeong Heejin , Kim Myunghee , Yeo Woon-Hong 
Published: January 2023

AbstractActivities and physical effort have been commonly estimated using a metabolic rate through indirect calorimetry to capture breath information. The physical effort represents the work hardness used to optimize wearable robotic systems. Thus, personalization and rapid optimization of the effort are critical. Although respirometry is the gold standard for estimating metabolic costs, this method requires a heavy, bulky, and rigid system, limiting the system’s field deployability. Here, this paper reports a soft, flexible bioelectronic system that integrates a wearable ankle-foot exoskeleton, used to estimate metabolic costs and physical effort, demonstrating the potential for real-time wearable robot adjustments based on biofeedback. Data from a set of activities, including walking, running, and squatting with the biopatch and exoskeleton, determines the relationship between metabolic costs and heart rate variability root mean square of successive differences (HRV-RMSSD) (R = −0.758). Collectively, the exoskeleton-integrated wearable system shows potential to develop a field-deployable exoskeleton platform that can measure wireless real-time physiological signals.
Excessive daytime sleepiness in a model of Parkinson’s disease improved by low-frequency stimulation of the pedunculopontine nucleus
Authors: Davin Aurélie , Chabardès Stéphan , Devergnas Annaelle , Benstaali Caroline , Gutekunst Claire-Anne N. , David Olivier , Torres-Martinez Napoléon , Piallat Brigitte 
Published: January 2023

AbstractPatients with Parkinson’s disease often complain of excessive daytime sleepiness which negatively impacts their quality of life. The pedunculopontine nucleus, proposed as a target for deep brain stimulation to improve freezing of gait in Parkinson’s disease, is also known to play a key role in the arousal system. Thus, the putative control of excessive daytime sleepiness by pedunculopontine nucleus area stimulation merits exploration for treating Parkinson’s disease patients. To this end, two adult nonhuman primates (macaca fascicularis) received a deep brain stimulation electrode implanted into the pedunculopontine nucleus area along with a polysomnographic equipment. Stimulation at low frequencies and high frequencies was studied, in healthy and then MPTP-treated nonhuman primates. Here, we observed that MPTP-treated nonhuman primates suffered from excessive daytime sleepiness and that low-frequency stimulation of the pedunculopontine nucleus area was effective in reducing daytime sleepiness. Indeed, low-frequency stimulation of the pedunculopontine nucleus area induced a significant increase in sleep onset latency, longer continuous periods of wakefulness and thus, a partially restored daytime wake architecture. These findings may contribute to the development of new therapeutic strategies in patients suffering from excessive daytime sleepiness.
Attosecond field emission
Authors: Kim H. Y. , Garg M. , Mandal S. , Seiffert L. , Fennel T. , Goulielmakis E. 
Published: January 2023

AbstractField emission of electrons underlies great advances in science and technology, ranging from signal processing at ever higher frequencies1 to imaging of the atomic-scale structure of matter2 with picometre resolution. The advancing of electron microscopy techniques to enable the complete visualization of matter on the native spatial (picometre) and temporal (attosecond) scales of electron dynamics calls for techniques that can confine and examine the field emission on sub-femtosecond time intervals. Intense laser pulses have paved the way to this end3,4 by demonstrating femtosecond confinement5,6 and sub-optical cycle control7,8 of the optical field emission9 from nanostructured metals. Yet the measurement of attosecond electron pulses has remained elusive. We used intense, sub-cycle light transients to induce optical field emission of electron pulses from tungsten nanotips and a weak replica of the same transient to directly investigate the emission dynamics in real time. Access to the temporal properties of the electron pulses rescattering off the tip surface, including the duration τ = (53 as ± 5 as) and chirp, and the direct exploration of nanoscale near fields open new prospects for research and applications at the interface of attosecond physics and nano-optics.
Annelid functional genomics reveal the origins of bilaterian life cycles
Authors: Martín-Zamora Francisco M. , Liang Yan , Guynes Kero , Carrillo-Baltodano Allan M. , Davies Billie E. , Donnellan Rory D. , Tan Yongkai , Moggioli Giacomo , Seudre Océane , Tran Martin , Mortimer Kate , Luscombe Nicholas M. , Hejnol Andreas , Marlétaz Ferdinand , Martín-Durán José M. 
Published: January 2023

AbstractIndirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2–11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called ‘head larvae’ of other bilaterians13–17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins.
Insulin-regulated serine and lipid metabolism drive peripheral neuropathy
Authors: Handzlik Michal K. , Gengatharan Jivani M. , Frizzi Katie E. , McGregor Grace H. , Martino Cameron , Rahman Gibraan , Gonzalez Antonio , Moreno Ana M. , Green Courtney R. , Guernsey Lucie S. , Lin Terry , Tseng Patrick , Ideguchi Yoichiro , Fallon Regis J. , Chaix Amandine , Panda Satchidananda , Mali Prashant , Wallace Martina , Knight Rob , Gantner Marin L. , Calcutt Nigel A. , Metallo Christian M. 
Published: January 2023

AbstractDiabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3–7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8–10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10–14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.
Triassic stem caecilian supports dissorophoid origin of living amphibians
Authors: Kligman Ben T. , Gee Bryan M. , Marsh Adam D. , Nesbitt Sterling J. , Smith Matthew E. , Parker William G. , Stocker Michelle R. 
Published: January 2023

AbstractLiving amphibians (Lissamphibia) include frogs and salamanders (Batrachia) and the limbless worm-like caecilians (Gymnophiona). The estimated Palaeozoic era gymnophionan–batrachian molecular divergence1 suggests a major gap in the record of crown lissamphibians prior to their earliest fossil occurrences in the Triassic period2–6. Recent studies find a monophyletic Batrachia within dissorophoid temnospondyls7–10, but the absence of pre-Jurassic period caecilian fossils11,12 has made their relationships to batrachians and affinities to Palaeozoic tetrapods controversial1,8,13,14. Here we report the geologically oldest stem caecilian—a crown lissamphibian from the Late Triassic epoch of Arizona, USA—extending the caecilian record by around 35 million years. These fossils illuminate the tempo and mode of early caecilian morphological and functional evolution, demonstrating a delayed acquisition of musculoskeletal features associated with fossoriality in living caecilians, including the dual jaw closure mechanism15,16, reduced orbits17 and the tentacular organ18. The provenance of these fossils suggests a Pangaean equatorial origin for caecilians, implying that living caecilian biogeography reflects conserved aspects of caecilian function and physiology19, in combination with vicariance patterns driven by plate tectonics20. These fossils reveal a combination of features that is unique to caecilians alongside features that are shared with batrachian and dissorophoid temnospondyls, providing new and compelling evidence supporting a single origin of living amphibians within dissorophoid temnospondyls.
Structure of the lysosomal mTORC1–TFEB–Rag–Ragulator megacomplex
Authors: Cui Zhicheng , Napolitano Gennaro , de Araujo Mariana E. G. , Esposito Alessandra , Monfregola Jlenia , Huber Lukas A. , Ballabio Andrea , Hurley James H. 
Published: January 2023

AbstractThe transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy1. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)2–5is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN6,7. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the ‘megacomplex’. Two full Rag–Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag–Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag–Ragulator complex (non-canonical) docks onto the first through a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB with a RagCGDP-dependent aspartate clamp in the cleft between the Rag G domains. In cellulo mutation of the clamp drives TFEB constitutively into the nucleus while having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.
Fine-resolution global maps of root biomass carbon colonized by arbuscular and ectomycorrhizal fungi
Authors: Barceló Milagros , van Bodegom Peter M. , Soudzilovskaia Nadejda A. 
Published: January 2023

AbstractDespite the recognized importance of mycorrhizal associations in ecosystem functioning, the actual abundance patterns of mycorrhizal fungi belowground are still unknown. This information is key for better quantification of mycorrhizal impacts on ecosystem processes and for incorporating mycorrhizal pathways into global biogeochemical models. Here we present the first high-resolution maps of fine root stocks colonized by arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) fungi (MgC ha−1). The maps were assembled by combining multiple open-source databases holding information on root biomass carbon, the proportion of AM and EcM tree biomass, plot-level relative abundance of plant species and intensity of AM and EcM root colonization. We calculated root-associated AM and EcM abundance in 881 spatial units, defined as the combination of ecoregions and land cover types across six continents. The highest AM abundances are observed in the (sub-)tropics, while the highest EcM abundances occur in the taiga regions. These maps serve as a basis for future research where continuous spatial estimates of root mycorrhizal stocks are needed.
Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis
Authors: Deng Hui , Jiang Jing , Zhang Sisi , Wu Lijuan , Zhang Qinglian , Sun Wenkui 
Published: January 2023

AbstractRheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease that may lead to joint damage, deformity, and disability, if not treated effectively. Hedyotis diffusa Willd (HDW) and its main components have been widely used to treat a variety of tumors and inflammatory diseases. The present study utilized a network pharmacology approach, microarray data analysis and molecular docking to predict the key active ingredients and mechanisms of HDW against RA. Eleven active ingredients in HDW and 180 potential anti-RA targets were identified. The ingredients-targets-RA network showed that stigmasterol, beta-sitosterol, quercetin, kaempferol, and 2-methoxy-3-methyl-9,10-anthraquinone were key components for RA treatment. KEGG pathway results revealed that the 180 potential targets were inflammatory-related pathways with predominant enrichment of the AGE-RAGE, TNF, IL17, and PI3K-Akt signaling pathways. Screened through the PPI network and with Cytoscape software, RELA, TNF, IL6, TP53, MAPK1, AKT1, IL10, and ESR1 were identified as the hub targets in the HDW for RA treatment. Molecular docking was used to identify the binding of 5 key components and the 8 related-RA hub targets. Moreover, the results of network pharmacology were verified by vitro experiments. HDW inhibits cell proliferation in MH7A cells in a dose and time-dependent manner. RT-qPCR and WB results suggest that HDW may affect hub targets through PI3K/AKT signaling pathway, thereby exerting anti-RA effect. This study provides evidence for a clinical effect of HDW on RA and a research basis for further investigation into the active ingredients and mechanisms of HDW against RA.
Direct cell extraction of membrane proteins for structure–function analysis
Authors: Drulyte Ieva , Gutgsell Aspen Rene , Lloris-Garcerá Pilar , Liss Michael , Geschwindner Stefan , Radjainia Mazdak , Frauenfeld Jens , Löving Robin 
Published: January 2023

AbstractMembrane proteins are the largest group of therapeutic targets in a variety of disease areas and yet, they remain particularly difficult to investigate. We have developed a novel one-step approach for the incorporation of membrane proteins directly from cells into lipid Salipro nanoparticles. Here, with the pannexin1 channel as a case study, we demonstrate the applicability of this method for structure–function analysis using SPR and cryo-EM.
Comparison of blood gas parameters, ions, and glucose concentration in polish Holstein-Friesian Dairy cows at different milk production levels
Authors: Pawliński Bartosz , Gołębiewski Marcin , Trela Michał , Witkowska-Piłaszewicz Olga 
Published: January 2023

AbstractGenetic selection for increased milk yield has been a key driver of dairy intensification. The modern dairy cow produces much higher amounts of milk than the cattle of several years ago, and this may have an influence on hematologic values at different stages of lactation and on cows with different levels of milk production. The purpose of the study was to investigate the variations in blood parameters such as Ht, tHb, sO2, FO2Hb, FCOHb, FMetHb, FHHb, pH, pCO2, pO2, standard HCO3−, actual HCO3−, BE, BE ecf, ctCO2, BO2, p50, and ctO2in cows at different milk production levels. In addition, ions such as Na+, K+ , Ca++, Ca++ (7.4), and Cl−, and AnGap and glucose were examined. Our findings indicated that differences in the examined blood parameters between low and high-production dairy cattle do exist. The most apparent differences were connected with blood pH (p < 0.01), oxygen metabolism (Ht, tHb, sO2, FO2Hb;p < 0.01), and glucose utilization (p < 0.01) The results confirm that the parameters connected with blood oxygen metabolism and glucose metabolism increase significantly in high-production animals. In conclusion, reference values should be considered in light of the lactation stage and level of milk production, because these might influence how changes should be interpreted. The main limitation of the study is the delay to analysis. However, the blood was properly stored (4C), thus changes were delayed. Anyway, it is very hard in the field practice to perform it within 5 min after the blood collection and according to studies it has low impact on clinical outcomes.