bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Tool Surface Properties Generated by Directed Energy Deposition and Subsequent Ball Burnishing
Authors: Komodromos Anna , Grodotzki Joshua , Kolpak Felix , Tekkaya A. Erman 
Published: October 2023

Abstract
By directed energy deposition (DED), a flexible design of cooling channels in forming tools, e.g., hot stamping, with a variety of sizes and a high positioning flexibility compared to machining processes is possible. The subsequent ball burnishing of the tool surfaces, in combination with a variation of the DED process parameters, enables control of the tool surface properties and friction behavior. Parameters such as the ball-burnishing pressure or the path overlapping in the DED process are investigated to quantify their effects on roughness, hardness, friction, residual stresses, and heat transfer coefficient of generic tool surfaces. The friction coefficient at elevated temperatures depends strongly on the surface roughness of the tool steel surfaces generated by DED and ball burnishing. The latter process improves the surface integrity: the roughness peaks are leveled by up to 75%, and the hardness and the residual stresses are enhanced by up to 20% and 70%, respectively. However, the roughness of the tool surfaces is determined mainly by the path overlapping of the welded beads in the DED process. Despite the higher surface roughness, the heat transfer coefficient is in the range of conventionally manufactured tool surfaces of up to 2700 W/m2K for contact pressures up to 40 MPa. First hot stamping experiments demonstrate that the tools manufactured by the novel process combination are able to manufacture 22MnB5 hat profiles with an increased and more homogeneous hardness, as well as more homogeneous thickness distribution, compared to conventionally manufactured tools.
Design and Analysis of Bionic Continuum Robot With Helical Winding Grasping Function
Authors: Jiang Xiong , Li Shouzhong , Ma Chong , Kuang Xinyu , Zhang Wenlong , Zhao Hongzhe 
Published: October 2023

Abstract
In the field of grasping application, continuum robots are characterized by flexible grasping and high adaptability. Based on research on the physiological structure and winding method of seahorses, a continuum robot with a helical winding grasping function is presented in this paper. The continuum robot is driven by cables and uses a new flexural pivot with large deformation as a rotation joint. Firstly, based on the Serret–Frenet frame of the spatial cylindrical helix, the helical winding continuum robot is modeled and solved. The change rules of parameters such as the rotation angle of the joint and the helix parameters under the helical winding method are derived. Then, the compliance matrix of the joint is solved using the structural matrix method, and a stiffness model is established to analyze the relationship between the load and deformation of the continuum robot. The kinematics model of the continuum robot is established by using the modified Denavit–Hartenberg parameter method. The static model of the continuum robot is solved by vector analysis under the condition of considering gravity, and the relationship between the length change of cables and joint curvature is obtained. Finally, the stiffness model and static model of the continuum robot are verified by simulations and experiments. The test results show that within a certain radial range, the continuum robot has the function of helical winding and grasping for objects. Compared to the previous imitation seahorse tail robot, the helical winding structure not only provides a larger grasping area compared to in-plane form but also achieves a better bionic effect.
Seneca Valley virus 3C
pro
antagonizes type I interferon response by targeting STAT1-STAT2-IRF9 and KPNA1 signals
Authors: Song Jiangwei , Guo Yitong , Wang Dan , Quan Rong , Wang Jing , Liu Jue 
Published: October 2023

ABSTRACT

The Seneca Valley virus (SVV) is an emerging pathogen that causes vesicular disease in pigs, posing a threat to the pork industry. The type I interferon (IFN) signaling pathway is the major defense mechanism of host innate immune responses, and SVV has developed numerous strategies to antagonize the IFN signaling and promote viral replication. However, the molecular mechanisms by which SVV affects IFN signaling components have not been fully elucidated. Here, we revealed that SVV proteinase (3C
pro
) inhibited IFN-α signaling by degrading signal transducer and activator of transcription (STAT) 1, STAT2, and interferon regulatory factor 9 (IRF9) through its protease activity, which is dependent on the caspase pathway. 3C
pro
was further found to cleave STAT2 at glutamine 758 (Q758) within the transactivation domain, and the cleaved STAT2 products attenuated its ability to activate IFN-stimulated responsive element activity and induce the production of IFN-stimulated genes. Additionally, 3C
pro
impaired the nuclear import and formation of the IFN-stimulated gene factor 3 complex. 3C
pro
also induced karyopherin 1 degradation to block STAT1/STAT2 nuclear localization. Collectively, SVV 3C
pro
is capable of subverting the type I IFN response by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which uncovers a novel mechanism exploited by SVV to evade host type I IFN response for efficient replication.

IMPORTANCE

Type I interferon (IFN) signaling plays a principal role in host innate immune responses against invading viruses. Viruses have evolved diverse mechanisms that target the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway to modulate IFN response negatively. Seneca Valley virus (SVV), an emerging porcine picornavirus, has received great interest recently because it poses a great threat to the global pork industry. However, the molecular mechanism by which SVV evades host innate immunity remains incompletely clear. Our results revealed that SVV proteinase (3C
pro
) antagonizes IFN signaling by degrading STAT1, STAT2, and IRF9, and cleaving STAT2 to escape host immunity. SVV 3C
pro
also degrades karyopherin 1 to block IFN-stimulated gene factor 3 nuclear translocation. Our results reveal a novel molecular mechanism by which SVV 3C
pro
antagonizes the type I IFN response pathway by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which has important implications for our understanding of SVV-evaded host innate immune responses.
Stability of magistral phage preparations before therapeutic application in patients with chronic rhinosinusitis, sepsis, pulmonary, and musculoskeletal infections
Authors: Uyttebroek Saartje , Bessems Laura , Metsemakers Willem-Jan , Debaveye Yves , Van Gerven Laura , Dupont Lieven , Depypere Melissa , Wagemans Jeroen , Lavigne Rob , Merabishvili Maya , Pirnay Jean-Paul , Devolder David , Spriet Isabel , Onsea Jolien 
Published: October 2023

ABSTRACT

Bacteriophages have (re)gained popularity as an adjunct antibacterial therapy. On top of the self-amplifying character of phages, their titer can be influenced by several factors which could lead to reduced titers after preparation and storage. The stability of phage preparations, used for the treatment of chronic rhinosinusitis (CRS), sepsis, pulmonary, and musculoskeletal infections, was investigated.
Staphylococcus aureus
phage ISP and
Pseudomonas aeruginosa
phages PNM, 14-1 and PT07 were evaluated. These phages were magistrally prepared by diluting active pharmaceutical products and storing them in different polypropylene/polycarbonate syringes at 4°C. Titers were monitored for 7–21 days using the double-agar overlay method. For 7 days, titers remained stable. Afterwards, the phage titer reduced for all phages with an average reduction of 0.78 log (
P
< 0.0001) plaque-forming units (PFUs)/mL after 14 days and 1 log PFU/mL after 21 days (
P
< 0.0001). PT07 titers dropped below the predefined threshold after 2 days in polycarbonate syringes. In addition, the stability after irrigation using a nasal douche (CRS) and infusion through a catheter (sepsis) was assessed. No changes were observed after using these devices with a mean change in titer of −0.07 log PFU/mL (
P
= 0.9062) and −0.03 log PFU/mL (
P
= 0.7350), respectively. In conclusion, a decreased titer after storage of a phage solution can lead to administration of subtherapeutic concentrations. In our experiments, we demonstrated that liquid phage solutions can be stored in syringes at 4°C for 5–7 days. PT07 appeared to be less stable, especially in polycarbonate syringes. Irrigation using a nasal douche or infusion through a catheter does not impact phage titer.

IMPORTANCE
As antimicrobial resistance becomes more prevalent, the application of (bacterio)phage therapy as an alternative treatment for difficult-to-treat infections is (re)gaining popularity. Over the past decade, numerous promising case reports and series have been published demonstrating the therapeutic potential of phage therapy. However, important questions remain regarding the optimal treatment protocol and, unlike for medicinal products, there are currently no predefined quality standards for the stability of phage preparations. Phage titers can be influenced by several factors which could lead to reduced titers after preparation and storage and, ultimately, subtherapeutic applications. Determining the stability of different phages in different recipients according to the route of administration is therefore one of the first important steps in establishing a standardized protocol for phage therapy.
Proteomic analysis of anti-MRSA activity of caerin 1.1/1.9 in a murine skin infection model and their
in vitro
anti-biofilm effects against
Acinetobacter baumannii
Authors: Zhang Pingping , Tang Shuxian , Fu Quanlan , Luo Yuandong , Li Junjie , Chen Zhu , Li Hejie , Ni Guoying , Wang Tianfang , Chen Guoqiang , Liu Xiaosong 
Published: October 2023

ABSTRACT

Caerin 1 is a family of host defense peptides with antimicrobial properties originally isolated from the Australian tree frog. Both caerin 1.1 and caerin 1.9 have been demonstrated to inhibit infections caused by multiple antibiotic-resistant bacteria, both
in vitro
and
in vivo
. In this current study, we conducted a comparison of the minimum inhibitory concentrations of caerin 1.1 and caerin 1.9 (referred to as caerin 1.1/1.9) with commonly used antibiotics against various bacteria, including
Staphylococcus aureus
, Copper-Green
Pseudomonas aeruginosa
,
Acinetobacter baumannii
, and
Streptococcus haemolyticus
. Our findings reveal that caerin 1.1/1.9 not only prevent the formation of biofilms by
A. baumannii
but also exhibit a therapeutic effect on established biofilms. Furthermore, our study demonstrates that caerin 1.1/1.9 significantly inhibit the growth of methicillin-resistant
Staphylococcus aureus
(MRSA) strains in a murine skin infection model. A quantitative proteomic analysis conducted as part of our study indicates that caerin 1.1/1.9 primarily activate oxidative phosphorylation pathways, along with several pathways associated with tissue repair and growth. These findings were observed in comparison to untreated tissues that were infected with MRSA in mice. In summary, our research outcomes suggest that caerin 1.1/1.9 exhibit the potential to serve as promising drug candidates for treating complicated antibiotic-resistant bacterial infections in humans.

IMPORTANCE
Caerin 1.1 and caerin 1.9, natural antimicrobial peptides derived from tree frogs, have demonstrated the ability to inhibit the growth of antibiotic-resistant bacteria, comparable to certain widely used antibiotics. Additionally, these peptides exhibit the capacity to prevent or treat biofilms formed by bacteria in conjunction with bodily components. The mechanisms underlying their antibacterial effects were investigated through a mouse model of bacterial skin infection, utilizing proteomic analysis as a technological approach.
Association between self-reported alcohol consumption and diastolic dysfunction: a cross-sectional study
Authors: Daka Bledar , Bennet Louise , Råstam Lennart , Hellgren Margareta I , Li Ying , Magnusson Martin , Lindblad Ulf 
Published: October 2023

Background and objectivesWhile alcohol consumption is associated with common risk factors for diastolic dysfunction the independent impact of low levels of alcohol consumption on this condition in a community setting is still unclear.Thus, the aim of this study was to explore this association in a representative population sample employing optimal echocardiographic techniques.DesignCross-sectional observational study in community-based population.Settings, participants and methodsParticipants between 30 and 75 years of age were consecutively invited to a physical examination, interview, conventional echocardiography, including Tissue Velocity Imaging. Diastolic dysfunction was defined according to the European Society of Cardiology criteria, excluding subjects with ejection fraction <45%, self-reported history of heart failure or atrial fibrillation on ECG. Self-reported alcohol intake using a validated questionnaire was categorised asno intake, low and medium-highintake.ResultsIn total, 500 men and 538 women (mean age 55.4±13) were successfully examined. Diastolic dysfunction was identified in 16% (79/500) of the men and 13% (58/538) of the women. The multivariable adjusted model revealed a strong and independent association between alcohol intake and diastolic dysfunction. In fact, using no alcohol intake as reference, diastolic dysfunction was independently associated with alcohol consumption in a dose-dependent fashion;low consumption,OR 2.3 (95% CI 1.3 to 4.0) andmedium-high consumptionOR 3.1 (95% CI 1.6 to 6.2), respectively.ConclusionThere was a significant association between alcohol consumption and diastolic dysfunction starting already at low levels that was supported by a dose-dependent pattern. These results need confirmatory studies and are important in public health policies.
Effects of COVID-19 on malaria elimination initiatives in sub-Saharan Africa: a scoping review protocol
Authors: Nunu Wilfred Njabulo , Ndirangu James , Tsoka-Gwegweni Joyce 
Published: October 2023

IntroductionThe occurrence of the COVID-19 pandemic significantly impacted health systems, resulting in varied outcomes of different variables in terms of health. Due to the nature of the causative organism that is spread mainly in the air, the disease rapidly spread to numerous countries, leading to a series of mitigation measures being proposed and implemented, including but not limited to travel restrictions, decongesting and in some instances closure of workplaces and schools and banning of social gatherings. This could have negatively impacted implementing strategies meant to ensure the effective management of malaria, hoping to eliminate it in different countries in sub-Saharan Africa (SSA). This review seeks to explore the effect of the COVID-19 pandemic on malaria elimination initiatives in SSA.Methods and analysisAn exploratory scoping review will be conducted on literature (searched using keywords and a search strategy) sources published in English on Web of Science, Cochrane Library, PUBMED, Dimensions, ProQuest, Scopus and African Journals Online. These would then be imported to Rayyan Software for screening for possible inclusion. The JBI Guidelines on Reviews, Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist would guide the data collection, extraction and analysis from the accessed literature. Furthermore, charting, trends and developing themes would ensure the findings are presented comprehensively and yet understandable. The data collection and analysis process leading to the final submission of a review paper to a journal will be conducted from September 2023 to February 2024.Ethics and disseminationAn application for ethical approval was lodged with the Health Sciences Research Ethics Committee at the University of the Free State in Bloemfontein, South Africa. This ethics committee granted ethics clearance (ethics number: UFS-HSD2022/1754). Results will be communicated through peer-reviewed publications, presentations, conferences, workshops and other means and forums to reach the critical stakeholders.
Bayesian inference of transition matrices from incomplete graph data with a topological prior
Authors: Perri Vincenzo , Petrović Luka V. , Scholtes Ingo 
Published: October 2023

AbstractMany network analysis and graph learning techniques are based on discrete- or continuous-time models of random walks. To apply these methods, it is necessary to infer transition matrices that formalize the underlying stochastic process in an observed graph. For weighted graphs, where weighted edges capture observations of repeated interactions between nodes, it is common to estimate the entries of such transition matrices based on the (relative) weights of edges. However in real-world settings we are often confronted with incomplete data, which turns the construction of the transition matrix based on a weighted graph into an inference problem. Moreover, we often have access to additional information, which capture topological constraints of the system, i.e. which edges in a weighted graph are (theoretically) possible and which are not. Examples include transportation networks, where we may have access to a small sample of passenger trajectories as well as the physical topology of connections, or a limited set of observed social interactions with additional information on the underlying social structure. Combining these two different sources of information to reliably infer transition matrices from incomplete data on repeated interactions is an important open challenge, with severe implications for the reliability of downstream network analysis tasks.Addressing this issue, we show that including knowledge on such topological constraints can considerably improve the inference of transition matrices, especially in situations where we only have a small number of observed interactions. To this end, we derive an analytically tractable Bayesian method that uses repeated interactions and a topological prior to perform data-efficient inference of transition matrices. We compare our approach against commonly used frequentist and Bayesian approaches both in synthetic data and in five real-world datasets, and we find that our method recovers the transition probabilities with higher accuracy. Furthermore, we demonstrate that the method is robust even in cases when the knowledge of the topological constraint is partial. Lastly, we show that this higher accuracy improves the results for downstream network analysis tasks like cluster detection and node ranking, which highlights the practical relevance of our method for interdisciplinary data-driven analyses of networked systems.
Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells
Authors: Hirai Soichi , Yamada Tadaaki , Katayama Yuki , Ishida Masaki , Kawachi Hayato , Matsui Yohei , Nakamura Ryota , Morimoto Kenji , Horinaka Mano , Sakai Toshiyuki , Sekido Yoshitaka , Tokuda Shinsaku , Takayama Koichi 
Published: October 2023

Abstract
Few treatment options exist for pleural mesothelioma (PM), which is a progressive malignant tumor. However, the efficacy of molecular-targeted monotherapy is limited, and further therapeutic strategies are warranted to treat PM. Recently, the cancer cell-cycle checkpoint inhibitors have attracted attention because they disrupt cell-cycle regulation. Here, we aimed to establish a novel combinational therapeutic strategy to inhibit the cell-cycle checkpoint kinase, ATR in PM cells. The siRNA screening assay showed that anexelekto (AXL) knockdown enhanced cell growth inhibition when exposed to ATR inhibitors, demonstrating the synergistic effects of the ATR and AXL combination in some PM cells. The AXL and ATR inhibitor combination increased cell apoptosis via the Bim protein and suppressed cell migration when compared with each monotherapy. The combined therapeutic targeting of AXL and ATR significantly delayed regrowth compared with monotherapy. Thus, optimal AXL and ATR inhibition may potentially improve the PM outcome.
Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma
Authors: Secrier Maria , McGrath Lara , Ng Felicia , Gulati Sakshi , Raymond Amelia , Nuttall Barrett R. B. , Berthe Julie , Jones Emma V. , Sidders Ben S. , Galon Jérôme , Barrett J. Carl , Angell Helen K. 
Published: October 2023

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumor microenvironment (TME) of 162 HNSCC primary tumors of diverse etiologic and spatial origin, through gene expression and IHC profiling of relevant immune proteins, T-cell receptor (TCR) repertoire analysis, and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (i) cytotoxic, (ii) plasma cell rich, (iii) dendritic cell rich, (iv) macrophage rich, and (v) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T-cell infiltration and immune checkpoint expression (e.g., PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history, and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents.

Significance:
Here we present our findings on the genomic and immune landscape of primary disease in a cohort of 162 patients with HNSCC, benefitting from detailed molecular and clinical characterization. By employing whole-exome sequencing and gene expression analysis of relevant immune markers, TCR profiling, and staining of relevant proteins involved in immune response, we highlight how distinct etiologies, cell intrinsic, and environmental factors combine to shape the landscape of HNSCC primary disease.