bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental and analytical investigations of the removal of spatters by various process gases during the powder bed fusion of metals using a laser beam
Authors: Baehr Siegfried , Klecker Tobias , Pielmeier Sebastian , Ammann Thomas , Zaeh Michael F. 
Published: August 2023

AbstractThe powder bed fusion of metals using a laser beam (PBF-LB/M) is increasingly being utilized in industrial applications. This is due to several advantages over conventional manufacturing processes when it comes to the fabrication of complex part designs. However, the process still poses various challenges that have to be overcome. One of these challenges is the formation of a significant amount of spatters and fumes. These could attenuate the laser beam or decrease the powder reusability. To lower their negative impact on the process and the mechanical properties of the parts, a process gas flow is used in PBF-LB/M to remove these by-products from the processing zone. This study was, therefore, dedicated to investigating the potential of various gases on the removal of spatters. The focus was placed on argon, helium, and their mixtures. After theoretical considerations determining the range of applicable gas flow velocities, the experimental results unveiled the real spread of spatters over the powder bed and their characteristics. Whilst the removal of spatters was found to be worse for an argon–helium gas mixture at comparable gas flow velocities, increasing the velocity turned out to be a proper measure to enhance the removal for low-density gases. At this flow condition, the use of the argon–helium gas mixture led to a similar removal of spatters and the creation of a lower spatter mass in total (reduced to 40%) compared to argon.
Falsch-positive – falsch-negative Befunde – Stellenwert der PSMA-PET/CT beim Staging von Patienten mit Prostatakarzinom
Authors: Lenart Sebastian , Maurer Tobias 
Published: August 2023

ZusammenfassungDie PSMA-Positronenemissionstomographie (PET) findet seit über 10 Jahren Anwendung im Staging von Prostatakrebspatienten und stellt die Bildgebung mit der höchsten Sensitivität in der Ausbreitungsdiagnostik dar. Zahlreiche Studien aber zeigten, dass das prostataspezifische Membranantigen (PSMA) nicht nur auf Prostata- und Prostatakrebszellen vorkommt, sondern Anreicherungen des Tracers auch in anderen Organen, unabhängig vom Prostatakarzinom, stattfinden. Dies kann zu falsch-positiven Befunden führen, mit Beeinflussung der Therapieplanung. Aber auch falsch-negative Befunde können Therapieplanveränderungen bedeuten. Während die PSMA-PET/CT in der Primärdiagnostik (noch) einen eingeschränkten Stellenwert hat, ist sie in der Rezidivdiagnostik das bildgebende Verfahren der ersten Wahl.
Milk coagulation properties are moderately heritable in dairy cows: a meta-analysis using the random-effects model
Authors: Ghavi Hossein-Zadeh Navid 
Published: August 2023

AbstractThis study aimed to conduct a meta-analysis using the random-effects model to merge published genetic parameter estimates for milk coagulation properties (MCP: comprising rennet coagulation time (RCT), curd-firming time (k20), curd firmness 30 min after rennet addition (a30), titrable acidity (TA) and milk acidity or pH) in dairy cows. Overall, 80 heritability estimates and 157 genetic correlations from 23 papers published between 1999 and 2020 were used. The heritability estimates for RCT, a30, k20, TA, and pH were 0.273, 0.303, 0.278, 0.189 and 0.276, respectively. The genetic correlation estimates between RCT-a30, RCT-pH, and RCT-TA were 0.842, 0.549 and −0.565, respectively. Genetic correlation estimates between RCT and production traits were generally low and ranged from −0.142 (between RCT and casein content) to 0.094 (between RCT and somatic cell score). Moderate and significant genetic correlations were observed between a30-pH (−0.396) and a30-TA (0.662). Also, the genetic correlation estimates between a30 and production traits were low to moderate and varied from −0.165 (between a30 and milk yield) to 0.481 (between a30 and casein content). Genetic correlation estimates between pH and production traits were low and varied from −0.190 (between pH and milk protein percentage) to 0.254 (between pH and somatic cell score). The results of this meta-analysis indicated the existence of additive genetic variation for MCP that could be used in genetic selection programs for dairy cows. Because of the moderate heritability of MCP and small genetic correlations with production traits, it could be possible to improve MCP with negligible correlated effects on production traits.
The role of a mobile hearing application in secondary care ENT (HAppENT)
Authors: Thompson G , Abdelhamid A , Khudan A , Dobbs S , Suleman M T , Salem O M , Khwaja S 
Published: August 2023

AbstractObjectiveSudden hearing loss is a common presentation to ENT. In the authors’ practice, patients often wait many weeks for formal hearing testing. This study aimed to assess whether a tablet-based hearing test, hearTest, could aid clinical decision-making within secondary care ENT.MethodThis was a multi-centre, prospective, non-randomised study to assess the feasibility, usability and accuracy of hearTest.ResultsIn the sample, hearTest was shown to be an acceptable method of testing for hearing loss by both patients and clinicians. The 0.5–4 kHz range had an average clinical agreement rate of 95.1 per cent when compared with formal pure tone audiometry, deeming it an accurate test to diagnose hearing loss.ConclusionThe authors propose that hearTest can be used within ENT as a clinical decision support tool when manual audiometry is not immediately available. Within the authors’ practice, hearTest is used to aid diagnosis and management of sudden sensorineural hearing loss.
Shang dynasty's “nine generations chaos” and the reign of Wu Ding: towards a unilineal line of transmission of royal power
Authors: Boileau Gilles 
Published: August 2023

AbstractThis article explores the political crisis before Wu Ding. The accession of king Wu Ding to the throne was not a given but the result of a political move by his father Xiao Yi. It must be seen as one of the consequences of an earlier political crisis named the “nine generations chaos” by Sima Qian, during which an attempt to share royal power between two royal lines finally collapsed and led to a move by Pan Geng to a new capital. This new city has recently been discovered north of the Huai river. The political crisis of the time led Shang kings to try to implement a unilineal system of succession. Other steps, ritual in particular, were involved after the reign of the king Zu Jia, one of the reigning sons of Wu Ding, in order to ensure the primacy of the unilineal system of royal succession.
Understanding household healthcare expenditure can promote health policy reform
Authors: Best Rohan , Tuncay Berna 
Published: August 2023

AbstractStudies of health care expenditure often exclude explanatory variables measuring wealth, despite the intuitive importance and policy relevance. We use the Household, Income and Labour Dynamics in Australia Survey to assess impacts of income and wealth on health expenditure. We investigate four different dependent variables related to health expenditure and use three main methodological approaches. These approaches include a first difference model and introduction of a lagged dependent variable into a cross-sectional context. The key findings include that wealth tends to be more important than income in identifying variation in health expenditure. This applies for health variables which are not directly linked to means testing, such as spending on health practitioners and for being unable to afford required medical treatment. In contrast, the paper includes no evidence of different impacts of income and wealth on spending on medicines, prescriptions or pharmaceuticals. The results motivate two novel policy innovations. One is the introduction of an asset test for determining rebate eligibility for private health insurance. The second is greater focus on asset testing, rather than income tests, for a wide range of general welfare payments that can be used for health expenditure. Australia's world-leading use of means testing can provide a test case for many countries.
Circulating tumor cell-derived preclinical models: current status and future perspectives
Authors: Kahounová Zuzana , Pícková Markéta , Drápela Stanislav , Bouchal Jan , Szczyrbová Eva , Navrátil Jiří , Souček Karel 
Published: August 2023

AbstractDespite the advancements made in the diagnosis and treatment of cancer, the stages associated with metastasis remain largely incurable and represent the primary cause of cancer-related deaths. The dissemination of cancer is facilitated by circulating tumor cells (CTCs), which originate from the primary tumor or metastatic sites and enter the bloodstream, subsequently spreading to distant parts of the body. CTCs have garnered significant attention in research due to their accessibility in peripheral blood, despite their low abundance. They are being extensively studied to gain a deeper understanding of the mechanisms underlying cancer dissemination and to identify effective therapeutic strategies for advanced stages of the disease. Therefore, substantial efforts have been directed towards establishing and characterizing relevant experimental models derived from CTCs, aiming to provide relevant tools for research. In this review, we provide an overview of recent progress in the establishment of preclinical CTC-derived models, such as CTC-derived xenografts (CDX) and cell cultures, which show promise for the study of CTCs. We discuss the advantages and limitations of these models and conclude by summarizing the potential future use of CTCs and CTC-derived models in cancer treatment decisions and their utility as precision medicine tools.
Impaired renal autoregulation and pressure-natriuresis: any role in the development of heart failure in normotensive and angiotensin II-dependent hypertensive rats?
Authors: Honetschlägerová Zuzana , Sadowski Janusz , Kompanowska-Jezierska Elzbieta , Maxová Hana , Táborský Miloš , Kujal Petr , Červenka Luděk 
Published: August 2023

AbstractThe aim of the present study was to assess the autoregulatory capacity of renal blood flow (RBF) and of the pressure-natriuresis characteristics in the early phase of heart failure (HF) in rats, normotensive and with angiotensin II (ANG II)-dependent hypertension. Ren-2 transgenic rats (TGR) were employed as a model of ANG II-dependent hypertension. HF was induced by creating the aorto-caval fistula (ACF). One week after ACF creation or sham-operation, the animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. In ACF TGR the basal mean arterial pressure, RBF, urine flow (UF), and absolute sodium excretion (UNaV) were all significantly lower tha n in sham-operated TGR. In the latter, reductions in renal arterial pressure (RAP) significantly decreased RBF whereas in ACF TGR they did not change. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former. Our data show that compared with sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and improved slope of the pressure-natriuresis relationship. Thus, even though in the very early HF stage renal dysfunction was demonstrable, in the HF model of ANG II-dependent hypertensive rat such dysfunction and the subsequent HF decompensation cannot be simply ascribed to impaired renal autoregulation and pressure-natriuresis relationship.
Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells
Authors: Rattigan Kevin M. , Brabcova Zuzana , Sarnello Daniele , Zarou Martha M. , Roy Kiron , Kwan Ryan , de Beauchamp Lucie , Dawson Amy , Ianniciello Angela , Khalaf Ahmed , Kalkman Eric R. , Scott Mary T. , Dunn Karen , Sumpton David , Michie Alison M. , Copland Mhairi , Tardito Saverio , Gottlieb Eyal , Vignir Helgason G. 
Published: August 2023

AbstractDeregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.
A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination
Authors: Luo Shih-Chi , Yeh Min-Chi , Lien Yu-Hsiang , Yeh Hsin-Yi , Siao Huei-Lun , Tu I-Ping , Chi Peter , Ho Meng-Chiao 
Published: August 2023

AbstractATP-dependent RAD51 recombinases play an essential role in eukaryotic homologous recombination by catalyzing a four-step process: 1) formation of a RAD51 single-filament assembly on ssDNA in the presence of ATP, 2) complementary DNA strand-exchange, 3) ATP hydrolysis transforming the RAD51 filament into an ADP-bound disassembly-competent state, and 4) RAD51 disassembly to provide access for DNA repairing enzymes. Of these steps, filament dynamics between the ATP- and ADP-bound states, and the RAD51 disassembly mechanism, are poorly understood due to the lack of near-atomic-resolution information of the ADP-bound RAD51–DNA filament structure. We report the cryo-EM structure of ADP-bound RAD51–DNA filaments at 3.1 Å resolution, revealing a unique RAD51 double-filament that wraps around ssDNA. Structural analysis, supported by ATP-chase and time-resolved cryo-EM experiments, reveals a collapsing mechanism involving two four-protomer movements along ssDNA for mechanical transition between RAD51 single- and double-filament without RAD51 dissociation. This mechanism enables elastic change of RAD51 filament length during structural transitions between ATP- and ADP-states.
Molecular rearrangement of bicyclic peroxy radicals is a key route to aerosol from aromatics
Authors: Iyer Siddharth , Kumar Avinash , Savolainen Anni , Barua Shawon , Daub Christopher , Pichelstorfer Lukas , Roldin Pontus , Garmash Olga , Seal Prasenjit , Kurtén Theo , Rissanen Matti 
Published: August 2023

AbstractThe oxidation of aromatics contributes significantly to the formation of atmospheric aerosol. Using toluene as an example, we demonstrate the existence of a molecular rearrangement channel in the oxidation mechanism. Based on both flow reactor experiments and quantum chemical calculations, we show that the bicyclic peroxy radicals (BPRs) formed in OH-initiated aromatic oxidation are much less stable than previously thought, and in the case of the toluene derived ipso-BPRs, lead to aerosol-forming low-volatility products with up to 9 oxygen atoms on sub-second timescales. Similar results are predicted for ipso-BPRs formed from many other aromatic compounds. This reaction class is likely a key route for atmospheric aerosol formation, and including the molecular rearrangement of BPRs may be vital for accurate chemical modeling of the atmosphere.
Machine learning the microscopic form of nematic order in twisted double-bilayer graphene
Authors: Sobral João Augusto , Obernauer Stefan , Turkel Simon , Pasupathy Abhay N. , Scheurer Mathias S. 
Published: August 2023

AbstractModern scanning probe techniques, such as scanning tunneling microscopy, provide access to a large amount of data encoding the underlying physics of quantum matter. In this work, we show how convolutional neural networks can be used to learn effective theoretical models from scanning tunneling microscopy data on correlated moiré superlattices. Moiré systems are particularly well suited for this task as their increased lattice constant provides access to intra-unit-cell physics, while their tunability allows for the collection of high-dimensional data sets from a single sample. Using electronic nematic order in twisted double-bilayer graphene as an example, we show that incorporating correlations between the local density of states at different energies allows convolutional neural networks not only to learn the microscopic nematic order parameter, but also to distinguish it from heterostrain. These results demonstrate that neural networks are a powerful method for investigating the microscopic details of correlated phenomena in moiré systems and beyond.
One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids
Authors: Geurts Maarten H. , Gandhi Shashank , Boretto Matteo G. , Akkerman Ninouk , Derks Lucca L. M. , van Son Gijs , Celotti Martina , Harshuk-Shabso Sarina , Peci Flavia , Begthel Harry , Hendriks Delilah , Schürmann Paul , Andersson-Rolf Amanda , Chuva de Sousa Lopes Susana M. , van Es Johan H. , van Boxtel Ruben , Clevers Hans 
Published: August 2023

AbstractOptimization of CRISPR/Cas9-mediated genome engineering has resulted in base editors that hold promise for mutation repair and disease modeling. Here, we demonstrate the application of base editors for the generation of complex tumor models in human ASC-derived organoids. First we show efficacy of cytosine and adenine base editors in modelingCTNNB1hot-spot mutations in hepatocyte organoids. Next, we use C > T base editors to insert nonsense mutations inPTENin endometrial organoids and demonstrate tumorigenicity even in the heterozygous state. Moreover, drug sensitivity assays on organoids harboring eitherPTENorPTENandPIK3CAmutations reveal the mechanism underlying the initial stages of endometrial tumorigenesis. To further increase the scope of base editing we combine SpCas9 and SaCas9 for simultaneous C > T and A > G editing at individual target sites. Finally, we show that base editor multiplexing allow modeling of colorectal tumorigenesis in a single step by simultaneously transfecting sgRNAs targeting five cancer genes.
Ligand recognition and G protein coupling of the human itch receptor MRGPRX1
Authors: Guo Lulu , Zhang Yumu , Fang Guoxing , Tie Lu , Zhuang Yuming , Xue Chenyang , Liu Qi , Zhang Minghui , Zhu Kongkai , You Chongzhao , Xu Peiyu , Yuan Qingning , Zhang Chao , Liu Lei , Rong Naikang , Peng Shengxuan , Liu Yuan , Wang Chuanzheng , Luo Xin , Lv Zongyao , Kang Dongwei , Yu Xiao , Zhang Cheng , Jiang Yi , Dong Xinzhong , Zhou Jiuyao , Liu Zhongmin , Yang Fan , Eric Xu H. , Sun Jin-Peng 
Published: August 2023

AbstractMRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal “RF/RY” motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the G6.48XP6.50F6.51G6.52X(2)F/W6.55 motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.
Machine learning force fields for molecular liquids: Ethylene Carbonate/Ethyl Methyl Carbonate binary solvent
Authors: Magdău Ioan-Bogdan , Arismendi-Arrieta Daniel J. , Smith Holly E. , Grey Clare P. , Hermansson Kersti , Csányi Gábor 
Published: August 2023

AbstractHighly accurate ab initio molecular dynamics (MD) methods are the gold standard for studying molecular mechanisms in the condensed phase, however, they are too expensive to capture many key properties that converge slowly with respect to simulation length and time scales. Machine learning (ML) approaches which reach the accuracy of ab initio simulation, and which are, at the same time, sufficiently affordable hold the key to bridging this gap. In this work we present a robust ML potential for the EC:EMC binary solvent, a key component of liquid electrolytes in rechargeable Li-ion batteries. We identify the necessary ingredients needed to successfully model this liquid mixture of organic molecules. In particular, we address the challenge posed by the separation of scale between intra- and inter-molecular interactions, which is a general issue in all condensed phase molecular systems.
Cardiovascular disease behavioural risk factors in rural interventions: cross-sectional study
Authors: Akinosun Adewale Samuel , Kamya Sylvia , Watt Jonathan , Johnston William , Leslie Stephen J. , Grindle Mark 
Published: August 2023

AbstractThis study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99–69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population’s socio-economic outcomes rather than to regional rurality or urbanity.