bluuebunny/crossref_metadata_2025 huggingface dataset:
UBE2C promotes malignancy of cutaneous squamous cell carcinoma
Authors: Luo Ruiting , Bai Ruimin , Guo Jiaqi , Xian Ningyi , Zheng Yan
Published: November 2023

Background

Our study aimed to study the involvement of ubiquitin‐conjugating enzyme E2C (UBE2C) in cutaneous squamous cell carcinoma (cSCC). As the second most common malignancy with a rising incidence, understanding the molecular mechanisms driving cSCC is crucial for improved diagnosis and treatment.

Methods

We combined multiple datasets of cSCC in Gene Expression Omnibus (GEO) repository to investigate its expression and diagnostic value. We collected patient specimens and performed immunohistochemistry to examine its expression in patients and its correlation with tumor histological grade. Moreover, we compared UBE2C expression between cSCC cells and primary human epidermal keratinocytes. Subsequently, we explored the effects of UBE2C inhibition on tumor cell proliferation, migration and apoptosis through CCK8, wound healing, Transwell, and flow cytometry assay.

Results

The integrated analysis revealed an upregulation of UBE2C level in cSCC. Immunohistochemistry demonstrated high UBE2C expression was associated with poorer tumor histological grade. Cell experiments further supported the crucial role of UBE2C in promoting the malignant behavior of cSCC cells.

Conclusion

Our findings indicate UBE2C is up‐regulated in cSCC and contributes to its malignant behavior. These results suggest UBE2C has the potential to serve as both a cSCC biomarker and a therapeutic target.
Xenoreactive antibodies in α‐granules of human platelets bind pig liver endothelial cells
Authors: Burlak Christopher , Wang Zheng Yu , Martens Greg , Estrada Jose , Reyes Luz , Novara Gennuso Victor Manuel , Vianna Rodrigo , Tector Matt , Tector Alfred Joseph
Published: November 2023

Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α‐granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α‐granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α‐granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.
Experimental Investigation of the Effect of Bleed on the Aerodynamics of a Low-Pressure Compressor Stage in a Turbofan Engine
Authors: Spanelis Apostolos , Denman Paul A. , Mariah Ian , Walker A. Duncan
Published: November 2023

The compression system in modern turbofan engines is split into stages linked by transition ducts. Downstream of the low-pressure system, a handling bleed is often required and, in conjunction with structural vanes, can introduce component interactions, which compromise aerodynamic performance. In this paper, a fully annular, low-speed test facility incorporating a 1½ stage axial compressor is used to examine the flow in the last stage of a low-pressure compressor and the downstream transition duct. The transition duct incorporated load-bearing struts, including a so-called king strut with twice the thickness of the regular struts. The bleed utilized a 360-deg annular slot located on the casing immediately downstream of the low-pressure rotor and upstream of the outlet guide vane. The results showed that both the regular and king strut caused a similar flow distortion in the vane row but overall imposed a negligible effect on overall performance. The addition of bleed had a larger effect, generating an increasing outboard bias at the rotor exit as the bleed flow migrated toward the offtake. At the design operating point, the outlet guide vanes were relatively insensitive to this until the highest bleed rate (18%) where evidence of stall was observed. At a lower operating point, a modification to the rotor swirl caused additional incidence onto the vanes, resulting in an earlier onset of the stall; a full stall was observed above 10% bleed. Increasing bleed caused a gradual increase in duct loss up to stall when losses increased rapidly.
Determination of Load Collective for Sizing of a Hydraulic Drive Network System Considering Simultaneity Between Actuator Loads
Authors: van Binsbergen-Galán Mikkel , Schmidt Lasse
Published: November 2023

Designing and sizing the drive system for a multi-actuator machine controlled by a human driver, the drive system requirements are difficult to define. In this case it may be most sensible to size the drive system based on measurements from an existing and similar machine in the same size class, but possibly with a different drive topology. However, this poses two main challenges. First, the measurements likely contain dynamics from interactions with the surroundings. Secondly, the measured motion is influenced by the drive characteristics of the test machine as well as imperfect driver control by the human driver.

This paper proposes a method for determination of a load collective for design and sizing of an electro-hydraulic variablespeed drive network (VDN), seeking to account for the aforementioned effects by modifying measurements to create design load cycles constituting a load collective, while obtaining equal maximum actuator forces and speeds. The method is applied for the case of a knuckle boom crane, showcasing a significant impact on drive system size. This demonstrates the significance of properly defining a load collective when designing and sizing drive network systems.
Efficiency of a Digital Displacement Pump Operating With Partial Strokes
Authors: Dumnov Daniil , Lagarde Jérémie
Published: November 2023

Digital Displacement® pumps use solenoid operated on/off valves to control the pressurization of each individual cylinder on a stroke-by-stroke basis. The overall pump displacement is commonly varied by changing the proportion of cylinders which are not pressurized to those delivering their maximum volume. This strategy leads to high efficiency but can increase pulsation in the downstream hydraulic system. As an alternative, the timing of the valve actuation can be adjusted so that cylinders are only pressurized for a portion of their stroke. This paper presents measurements of overall power loss and efficiency of a 96cc/rev pump at a variety of speeds and pressures with variation of the cylinder stroke size from 10–100%. The efficiency of the pump decreases as cylinder stroke is reduced, but the change is relatively small, with efficiencies over 86% measured in all conditions above 100 bar and 50% stroke. The measured data is used to develop and validate a loss model for the Digital Displacement pump when operating using partial cylinder strokes. By combining this loss model with operating data from a 16-tonne excavator, the impact of different cylinder operating strategies on energy savings in an off-road system is evaluated. For the excavator performing digging, grading and travel it is predicted that changing from a full-stroke to a partial-stroke operating strategy has the effect of reducing the average pump efficiency by less than 2% in all duty cycles.
Projection Method for Hydraulic Piston Motor Torque Control
Authors: Darnet Justin , Bideaux Éric , Trégouët Jean-François
Published: November 2023

Hydraulic systems are mostly known for their high-power density and their ability to precisely modulate the ratio of the power transmission between a prime mover and other actuators. This power modulation is generally achieved by controlling the displacement of the pump/motors implemented in the hydraulic system. Several component architectures and/or control strategies have been developed in this sense, as described in [1]. However, for hydrostatic transmissions, beyond the displacement control, a precise and efficient torque control of hydraulic motors is often preferable in order to optimize the driveability and/or the energy consumption. This constitutes a major technological problem, which could be addressed step-by-step by simplifying the architecture of the hydraulic motor studied and dividing the control in elementary bricks.

The paper presents an application of this early torque control strategy to a three-piston hydraulic motor. A simplified model of such a motor leads to a state-space representation, which is then transformed using specific change of variables that enable a direct torque control. Both torque and internal dynamics are then splitted in two different submodels that facilitate the motor torque control. Simulation results illustrate the potential of this approach before concluding.
External Gear Pump Performance With Graphene Hydraulic Fluid
Authors: Chiavola Ornella , Palmieri Fulvio , Liscio Andrea , Ligi Simone
Published: November 2023

The literature reports that the addition of nanoparticles to hydraulic fluids significantly improves their fundamental properties such as viscosity index, lubricity, and anti-wear performance. Among the others, graphene-based nanomaterials are a potential candidate for hydraulic nanofluids due to their atomic thickness, high thermal conductivity, high thermal stability, and ecological nature.

Based on the research reported so far at tribological level, it is interesting to assess whether, and to what extent, the properties of nanofluids have an impact on hydraulic components performance. Accordingly, the article is devoted to highlight the effects of graphene based nanofluid on pump performance. Two formulations of graphene hydraulic fluid are prepared with the same standard mineral oil and graphene particles.

Pump performance is expressed in terms of volumetric efficiency and torque efficiency, measured in a wide range of pump speed and load pressure. The pump efficiency has been previously benchmarked with the standard hydraulic fluid. Then, for each formulation, experimental tests have been compared to the reference case, allowing quantitative performance comparison. The results have been lumped through loss coefficients, providing new data for modeling activities and for research and development in the field of hydraulic nanofluids.
Disturbance Observer-Based Nonlinear Motion Control of the Parallel Platform for Wave Compensation
Authors: Wang Tianzhu , Wei Jianhua , Zhang Qiang , Fang Jinhui
Published: November 2023

Offshore installations, such as marine transportation and shipboard cranes, are highly vulnerable to sea conditions, resulting in reduced efficiency and economic losses. To reduce the impact of waves on offshore equipment operations, this paper presents a nonlinear controller for a parallel compensation platform to isolate the load motion from the ship motion. The parallel platform is equipped with multiple hydraulic actuators so that this platform can obtain the advantages of the hydraulic system such as large-power density and large output power. Considering the complication of the platform dynamics model under non-inertia and the nonlinear characteristics of the hydraulic system, this paper proposes a nonlinear cascade controller based on inverse kinematic model, which contains a disturbance observer and a sliding model surface. The disturbance observer accounts for the complicated non-inertial forces and other nonlinearities. In addition, the outer inverse kinematic model tracking loop uses sliding mode surface to guarantee the tracking transient performance, with desired hydraulic driving force as control output. The inner force control loop is designed through the backstepping method. Finally, Lyapunov-based analysis demonstrates the stability of the closed-loop system, and simulation results verify the effectiveness of the compensation performance in the proposed scheme.
Smooth Particle Hydrodynamic As a Computational Model for the Design and Analysis of Hydraulic Components
Authors: Durango Marvin , Garcia-Bravo Jose
Published: November 2023

The aim of this work is to study the flow variables of a hydraulic component, a spool valve. Numerical simulations are implemented to analyze the behavior of the component, the method utilized here is called Smooth Particle hydrodynamic (SPH), which uses a Lagrangian approach. The traditional approach for this kind of analysis is CFD, this technique relies on the discretization of the Navier-Stokes equation in an Eulerian form, despite its accuracy it becomes unaffordable in terms of computational power, being the main reason SPH is selected over CFD. The computational model predicts forces and pressure at the same level as its counterpart, CFD. The simulation is conducted in DualSPhysics, open-source software for fluid modeling. Moreover, this study includes implementing the moving spool, which brings other difficulties when using CFD. However, there are other challenges to face during the set-up state of the model while imposing boundary conditions. The inlet/outlet conditions for SPH resort to particles not accounted as part of the computational domain, meaning the simulator stops tracking once the particles reach one of the boundaries. This study explains in detail how to set this condition correctly for inner flow in a control volume. The computational model developed in this study successfully described the physical phenomenon occurring in the spool valve. the typical jet velocity accruing between the shoulder and the closing spool is described by the SPH model. The latter fact is an indicator that this model spots the conversion of momentum and satisfies the continuity equitation.
Digital Displacement Motoring Characteristics of Dynamic Energy Recovery and Hydraulic Transformation
Authors: Pavlis Vojtech , McMillan Colin , Nørgård Christian , Caldwell Niall James
Published: November 2023

The Digital Displacement® Pump (DDP) is a highly innovative hydraulic variable displacement radial piston pump, driven by a central crankshaft, wherein each cylinder can be independently controlled. With each crank rotation a given cylinder may idle, operate a full pumping stroke or operate a partial stroke. The Digital Displacement® Pump/Motor (DDPM) technology is expected to improve component and system efficiency as well as enable recovery of useful energy which would otherwise be lost. The machine’s unique capabilities include direct hydraulic transformation, allowing for pressure amplification or reduction on the machine pump service, with the pumping cylinders purely driven by the motoring ones.

This paper presents the efficiency results of a newly developed Digital Displacement machine, which comprises 30 radially arranged DD modules with a total displacement of 300cc/rev. Test demonstrator data shows overall pumping and motoring efficiency above 94.5% for most of the datapoints (at 100% displacement fraction) within the main working operation envelope for excavators, i.e. 150–250 bar and 1400–1800 rpm. The machine also allows for dynamic energy recovery, with a peak efficiency of 93.5% achieved from the hydraulic input power to the DDP150D to the mechanical shaft power of the prime mover. The paper concludes that the machine’s capabilities make it a promising solution for hydraulic transformation, with a peak efficiency of above 90% as a hydraulic transformer achieved for both pressure amplification and reduction at the pump service.
Hydraulic Drive Trains in Wind Turbines for Rapidly Changing Strong Winds
Authors: Manhartsgruber Bernhard
Published: November 2023

Wind energy is among the most important technologies for reducing our carbon footprint in the atmosphere. An analysis of the wind energy market over the last years shows a favor for wind turbine technology with a rather low nominal speed resulting in a frequent down-regulation or limitation of the harvested wind power by the commonly used pitch control mechanism. Two reasons for this development can be named. Firstly, it is economically infeasible to size the electric generator for a very high peak power that will not show up very often during operation. Secondly, setting the target towards rather low nominal wind speeds results in a situation where the wind power plants can operate very steadily, especially in situations with rather stable wind conditions like offshore plants. Hydraulic drive trains for wind turbines have been researched in the past mainly with the goal of getting rid of the expensive mechanical transmissions between wind rotor and generator, most remarkably by the Artemis company in Edinburgh, Scotland. Also hybrid technologies with hydropneumatic accumulators for buffering energy have already been presented, e.g. by the group around Prof. Kim Stelson at the University of Minnesota. This paper deals with the situation of a wind rotor without pitch control, i.e. with fixed blades, and a rotor speed floating free with the wind speed. A system of differently sized hydraulic pumps is used in a digital fluid power manner to feed the harvested energy into a high pressure accumulator. This accumulator powers a variable displacement hydraulic motor driving a synchronous generator at grid frequency. Basic concepts and a simulation study are presented in order to get insight into the potentials of this technology. A first prototype is under construction in cooperation with a wind energy startup company.
Towards Energy-Efficient Semi-Autonomous Operation of Hydraulic Mobile Cranes
Authors: Zhidchenko Victor , Komarov Timofei , Handroos Heikki
Published: November 2023

This paper describes a method for an automatic control of hydraulic mobile crane movement that decreases required energy and allows avoiding obstacles. The method was originally developed for mobile log cranes and provides automatic transportation of the grappled logs to the desired position. The trajectory is calculated taking into account hydraulic energy needed for the movement. The method can also be applied to other machines, such as loader cranes. An input to the method is the positions of the endpoints and a map of the working space that defines the obstacles. To calculate an energy-efficient trajectory, the method uses a modified version of the A* search algorithm. The method includes two steps. First, a set of simulation experiments must be performed with a multi-physics model of the crane. The model should describe mechanical and hydraulic parts of the system and provide the value of hydraulic energy spent in each experiment. The first step represents a learning phase of the algorithm and must be executed once. A set of energy efficiency matrices is generated at this phase, which is used in the second step of the method to calculate a heuristic for the modified A* algorithm. The first step requires several hours of calculations depending on the model complexity and available computational resources. The second step can be executed faster than in a second, which makes it suitable for the real-time operation of the machine. To move the crane by the generated energy-efficient trajectory, a control algorithm was developed by combining feed-forward and PID control.

The paper presents the simulation results obtained with a real-time model of a log truck created using commercial software. The results demonstrate the median value of energy savings of 5 percent compared to the shortest path for the work task of loading and unloading the truck using common endpoint positions of logs. Validation of the method with a real device is planned for future research.
Polar lake microbiomes have distinct evolutionary histories
Authors: Tytgat Bjorn , Verleyen Elie , Sweetlove Maxime , Van den Berge Koen , Pinseel Eveline , Hodgson Dominic A. , Chown Steven L. , Sabbe Koen , Wilmotte Annick , Willems Anne ,   The Polar Lake Sampling Consortium, Vyverman Wim
Published: November 2023

Toward the poles, life on land is increasingly dominated by microorganisms, yet the evolutionary origin of polar microbiomes remains poorly understood. Here, we use metabarcoding of Arctic, sub-Antarctic, and Antarctic lacustrine benthic microbial communities to test the hypothesis that high-latitude microbiomes are recruited from a globally dispersing species pool through environmental selection. We demonstrate that taxonomic overlap between the regions is limited within most phyla, even at higher-order taxonomic levels, with unique deep-branching phylogenetic clades being present in each region. We show that local and regional taxon richness and net diversification rate of regionally restricted taxa differ substantially between polar regions in both microeukaryotic and bacterial biota. This suggests that long-term evolutionary divergence resulting from low interhemispheric dispersal and diversification in isolation has been a prominent process shaping present-day polar lake microbiomes. Our findings illuminate the distinctive biogeography of polar lake ecosystems and underscore that conservation efforts should include their unique microbiota.
DOT1L is a barrier to histone acetylation during reprogramming to pluripotency
Authors: Wille Coral K. , Zhang Xiaoya , Haws Spencer A. , Denu John M. , Sridharan Rupa
Published: November 2023

Embryonic stem cells (ESCs) have transcriptionally permissive chromatin enriched for gene activation–associated histone modifications. A striking exception is DOT1L-mediated H3K79 dimethylation (H3K79me2) that is considered a positive regulator of transcription. We find that ESCs are depleted for H3K79me2 at shared locations of enrichment with somatic cells, which are highly and ubiquitously expressed housekeeping genes, and have lower RNA polymerase II (RNAPII) at the transcription start site (TSS) despite greater nascent transcription. Inhibiting DOT1L increases the efficiency of reprogramming of somatic to induced pluripotent stem cells, enables an ESC-like RNAPII pattern at the TSS, and functionally compensates for enforced RNAPII pausing. DOT1L inhibition increases H3K27 methylation and RNAPII elongation–enhancing histone acetylation without changing the expression of the causal histone-modifying enzymes. Only the maintenance of elevated histone acetylation is essential for enhanced reprogramming and occurs at loci that are depleted for H3K79me2. Thus, DOT1L inhibition promotes the hyperacetylation and hypertranscription pluripotent properties.
The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer
Authors: Ikram Sabeen , Rege Apurv , Negesse Maraki Y. , Casanova Alexandre G. , Reynoird Nicolas , Green Erin M.
Published: November 2023

Aberrant activation of Ras/Raf/mitogen-activated protein kinase (MAPK) signaling is frequently linked to metastatic prostate cancer (PCa); therefore, the characterization of modulators of this pathway is critical for defining therapeutic vulnerabilities for metastatic PCa. The lysine methyltransferase SET and MYND domain 3 (SMYD3) methylates MAPK kinase kinase 2 (MAP3K2) in some cancers, causing enhanced activation of MAPK signaling. In PCa, SMYD3 is frequently overexpressed and associated with disease severity; however, its molecular function in promoting tumorigenesis has not been defined. We demonstrate that SMYD3 critically regulates tumor-associated phenotypes via its methyltransferase activity in PCa cells and mouse xenograft models. SMYD3-dependent methylation of MAP3K2 promotes epithelial-mesenchymal transition associated behaviors by altering the abundance of the intermediate filament vimentin. Furthermore, activation of the SMYD3-MAP3K2 signaling axis supports a positive feedback loop continually promoting high levels of SMYD3. Our data provide insight into signaling pathways involved in metastatic PCa and enhance understanding of mechanistic functions for SMYD3 to reveal potential therapeutic opportunities for PCa.
Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1
Authors: Wattenberg Max M. , Coho Heather , Herrera Veronica M. , Graham Kathleen , Stone Meredith L. , Xue Yuqing , Chang Renee B. , Cassella Christopher , Liu Mingen , Choi-Bose Shaanti , Thomas Stacy K. , Choi Hana , Li Yan , Markowitz Kelly , Melendez Lauren , Gianonne Michael , Bose Nandita , Beatty Gregory L.
Published: November 2023

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40. In mouse models of checkpoint inhibitor–resistant pancreatic cancer, coactivation of Dectin-1, via systemic β-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Antitumor activity was dependent on cDC1s and T cells but did not require classical T cell–mediated cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell–mediated IFN-γ signaling, which converged with Dectin-1 activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be invoked by coactivation of complementary myeloid signaling pathways.
Time to rethink academic publishing: the peer reviewer crisis
Authors: Tropini Carolina , Finlay B. Brett , Nichter Mark , Melby Melissa K. , Metcalf Jessica L. , Dominguez-Bello Maria Gloria , Zhao Liping , McFall-Ngai Margaret J. , Geva-Zatorsky Naama , Amato Katherine R. , Undurraga Eduardo A. , Poinar Hendrik N. , Gilbert Jack A.
Published: November 2023

There is concern that the time taken to publish academic papers in microbiological science has significantly increased in recent years. While the data do not specifically support this, evidence suggests that editors are having to invite more and more reviewers to identify those willing to perform peer review.
Characterization and genome sequence of
Microbacterium foliorum
phage Morrigan, of cluster EA6 with siphovirus morphology
Authors: Guerrero Jennifer A. , Maldonado Nery , Mbajiofor Emmanuella O. , Ramirez Lisette , Valencia Mary Jo , Healy Creehan D. , Garza Alejandro A. , Mizell Samantha A. , Jackson Brianna N. , Vargas Ayala Mayra
Published: November 2023

Bacteriophage Morrigan, which was isolated from soil using
Microbacterium foliorum
NRRL B-24224, is lytic with siphovirus morphology. Morrigan’s 40,509-bp genome has a GC content of 62.8% and 66 putative protein-coding genes, of which 31 could be assigned putative functions. Based on gene content similarity to actinobacteriophages, Morrigan is assigned to subcluster EA6.
p97/VCP targets
Toxoplasma gondii
vacuoles for parasite restriction in interferon-stimulated human cells
Authors: Clough Barbara , Fisch Daniel , Mize Todd H. , Encheva Vesela , Snijders Ambrosius , Frickel Eva-Maria
Published: November 2023

Infection with the parasite
Toxoplasma gondii
leads to production of interferon gamma (IFNγ) that stimulates cells to upregulate defense proteins targeting the parasite for cell intrinsic elimination or growth restriction. Various host defense mechanisms operate at the parasitophorous vacuole (PV) in different human cell types leading to PV disruption, acidification, or membrane envelopment. Ubiquitin and p62 are players in all human host control mechanisms of
Toxoplasma
, but other unifying proteins have not been identified. Here, we show that p97/valosin-containing protein (VCP), as well as its associated proteins ANKRD13A and UBXD1 control
Toxoplasma
infection while recruited to the PV in IFNγ-stimulated endothelial cells. Convergent deposition of ANKRD13A, p97/VCP, and UBXD1 onto the same vacuole is dependent on vacuolar ubiquitination and observed within 2 h post-infection. ANKRD13A, p97/VCP, and UBXD1 all drive the acidification mechanism of the vacuole, which is the IFNγ-dependent control pathway of
Toxoplasma
in endothelial cells. We assessed p97/VCP in
Toxoplasma
control in various human cells and demonstrate that p97/VCP is a universal IFNγ-dependent host restriction factor targeting the
Toxoplasma
PV in epithelial (HeLa) and endothelial cells (human umbilical vein endothelial cells), fibroblasts (human foreskin fibroblast), and macrophages (THP1).

IMPORTANCE

Toxoplasma gondii
(Tg) is a ubiquitous parasitic pathogen, infecting about one-third of the global population. Tg is controlled in immunocompetent people by mechanisms that are not fully understood. Tg infection drives the production of the inflammatory cytokine interferon gamma (IFNγ), which upregulates intracellular anti-pathogen defense pathways. In this study, we describe host proteins p97/VCP, UBXD1, and ANKRD13A that control Tg at the parasitophorous vacuole (PV) in IFNγ-stimulated endothelial cells. p97/VCP is an ATPase that interacts with a network of cofactors and is active in a wide range of ubiquitin-dependent cellular processes. We demonstrate that PV ubiquitination is a pre-requisite for recruitment of these host defense proteins, and their deposition directs Tg PVs to acidification in endothelial cells. We show that p97/VCP universally targets PVs in human cells and restricts Tg in different human cell types. Overall, these findings reveal new players of intracellular host defense of a vacuolated pathogen.
The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections
Authors: Driedger Matt , Daneman Nick , Brown Kevin , Gold Wayne L. , Jorgensen Sarah C.J. , Maxwell Colleen , Schwartz Kevin L. , Morris Andrew M. , Thiruchelvam Deva , Langford Bradley , Leung Elizabeth , MacFadden Derek
Published: November 2023

The COVID-19 pandemic has likely influenced the epidemiology of bacterial infections through wide-ranging changes to clinical practices and infection control and prevention interventions. We sought to determine how the detection and incidence of bloodstream infections (BSIs) have been influenced by the pandemic. We performed a retrospective analysis of blood culture data in the province of Ontario, Canada, from 1 January 2017 to 31 December 2020. Outcomes included a weekly incidence of blood culture tests, BSIs, and contaminant results. Results were stratified by hospital, community, and long-term care (LTC) settings. An interrupted time series analysis using segmented regression models was used to determine changes in outcome incidence/prevalence during the pre- and peri-pandemic periods. Of the 14,083,853 individuals included, 129,329 (0.92%) developed a bloodstream infection. The blood culture ordering rate increased during the pandemic in the hospital setting only [Incidence rate ratio (IRR) 1.09, 95% confidence interval (CI) 1.01–1.19]. There was a decline in the incidence of community-acquired (IRR 0.95, 95% CI 0.91–0.99) and LTC-acquired (IRR 0.85, 95% CI 0.76–0.94) BSIs. Hospital-acquired BSIs were unchanged. The proportion of blood culture contaminants increased in the community (7% increase,
P
< 0.01) and LTC settings (14% increase,
P
< 0.05). There was decreased incidence of community-acquired
Streptococcus pneumoniae
(IRR 0.43, 95% CI 0.33–0.57) and
Staphylococcus aureus
(IRR 0.91, 95% CI 0.84–0.99) bacteremia. Pandemic-related changes in the performance of blood cultures and the epidemiology of BSIs have implications for current and future pandemic antimicrobial use, healthcare resource allocation, and hospital and laboratory policies.

IMPORTANCE

Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.
A SEVA-based, CRISPR-Cas3-assisted genome engineering approach for
Pseudomonas
with efficient vector curing
Authors: Lammens Eveline-Marie , Volke Daniel Christophe , Schroven Kaat , Voet Marleen , Kerremans Alison , Lavigne Rob , Hendrix Hanne
Published: November 2023

The development of CRISPR-Cas-based engineering technologies has revolutionized the microbial biotechnology field. Over the years, the Class II Type II CRISPR-Cas9 system has become the gold standard for genome editing in many bacterial hosts. However, the Cas9 system does not allow efficient genomic integration in
Pseudomonas putida
, an emerging Synthetic Biology host, without the assistance of lambda-Red recombineering. In this work, we utilize the alternative Class I Type I-C CRISPR-Cas3 system from
Pseudomonas aeruginosa
as a highly efficient genome editing tool for
P. putida
and
P. aeruginosa
. This system consists of two vectors, one encoding the Cas genes, CRISPR array and targeting spacer, and a second Standard European Vector Architecture vector, containing the homologous repair template. Both vectors are Golden Gate compatible for rapid cloning and are available with multiple antibiotic markers, for application in various Gram-negative hosts and different designs. By employing this Cas3 system, we successfully integrated an 820-bp cassette in the genome of
P. putida
and performed several genomic deletions in
P. aeruginosa
within a week, with an efficiency of >83% for both hosts. Moreover, by introducing a universal self-targeting spacer, the Cas3 system rapidly cures all helper vectors, including itself, from the host strain in a matter of days. As such, this system constitutes a valuable engineering tool for
Pseudomonas
, to complement the existing range of Cas9-based editing methods, and facilitates genomic engineering efforts of this important genus.

IMPORTANCE

The CRISPR-Cas3 editing system as presented here facilitates the creation of genomic alterations in
Pseudomonas putida
and
Pseudomonas aeruginosa
in a straightforward manner. By providing the Cas3 system as a vector set with Golden Gate compatibility and different antibiotic markers, as well as by employing the established Standard European Vector Architecture (SEVA) vector set to provide the homology repair template, this system is flexible and can readily be ported to a multitude of Gram-negative hosts. Besides genome editing, the Cas3 system can also be used as an effective and universal tool for vector curing. This is achieved by introducing a spacer that targets the origin-of-transfer, present on the majority of established (SEVA) vectors. Based on this, the Cas3 system efficiently removes up to three vectors in only a few days. As such, this curing approach may also benefit other genomic engineering methods or remove naturally occurring plasmids from bacteria.
Pulmonary nocardiosis following nodular bronchiectaticMycobacterium aviumcomplex pulmonary disease in an immunocompetent patient
Authors: Ito Yasuhiro , Miwa Seiich , Shirai Masahiro
Published: November 2023

A woman in her 70s with a history of nodular bronchiectaticMycobacterium aviumcomplex pulmonary disease (MAC-PD) presented with an exacerbated productive cough and worsening findings on chest imaging. Although repeated sputum culture tests were negative for acid-fast bacilli and only revealed normal respiratory flora, a bronchoscopy identifiedNocardiasp. Consequently, she was diagnosed with pulmonary nocardiosis and was successfully treated with levofloxacin. It is known that pulmonary nocardiosis can manifest in immunocompetent individuals with bronchiectasis. For cases of refractory nodular bronchiectatic MAC-PD, it is vital to consider bronchoscopy to identify potential co-infections, such asNocardia.
Keloidal atypical fibroxanthoma of the scalp
Authors: McClelland Kathryn , Brady Aidan , Reid Paula , Houghton Joe
Published: November 2023

Atypical fibroxanthoma (AFX) is a rare low-grade sarcoma that occurs mainly in the elderly and may recur locally. There are multiple variants including keloidal AFX (KAF). KAF is characterised by a proliferation of atypical spindled and epithelioid cells admixed with bizarre pleomorphic cells. These cells intersect among broad bands of keloidal collagen. AFX is a diagnosis of exclusion so a broad panel of immunohistochemical staining should be applied to rule out other differentials (squamous cell carcinoma (SCC), melanoma, leiomyosarcoma, etc). There is added difficulty with the diagnosis of KAF as it may mimic multiple keloidal lesions, including exuberant scarring, as in this case. p53 immunohistochemistry staining can be useful in highlighting the presence of tumour cells. Additionally, next generation sequencing can detect genetic mutations identified in clonal proliferations consistent with tumour formation. KAF is easily overlooked and it should be included in the differential diagnosis for keloidal lesions showing even mild atypia.
A Global Health Reciprocal Innovation grant programme: 5-year review with lessons learnt
Authors: Ruhl Laura J , Kiplagat Jepchirchir , O'Brien Rishika , Wools-Kaloustian Kara , Scanlon Michael , Plater David , Thomas Melissa R , Pastakia Sonak , Gopal-Srivastava Rashmi , Morales-Soto Nydia , Nyandiko Winstone , Vreeman Rachel C , Litzelman Debra K , Laktabai Jeremiah
Published: November 2023

Unilateral approaches to global health innovations can be transformed into cocreative, uniquely collaborative relationships between low-income and middle-income countries (LMICs) and high-income countries (HIC), constituted as ‘reciprocal innovation’ (RI). Since 2018, the Indiana Clinical and Translational Sciences Institute (CTSI) and Indiana University (IU) Center for Global Health Equity have led a grants programme sculpted from the core elements of RI, a concept informed by a 30-year partnership started between IU (Indiana) and Moi University (Kenya), which leverages knowledge sharing, transformational learning and translational innovations to address shared health challenges. In this paper, we describe the evolution and implementation of an RI grants programme, as well as the challenges faced. We aim to share the successes of our RI engagement and encourage further funding opportunities to promote innovations grounded in the RI core elements. From the complex series of challenges encountered, three major lessons have been learnt: dedicating extensive time and resources to bring different settings together; establishing local linkages across investigators; and addressing longstanding inequities in global health research. We describe our efforts to address these challenges through educational materials and an online library of resources for RI projects. Using perspectives from RI investigators funded by this programme, we offer future directions resulting from our 5-year experience in applying this RI-focused approach. As the understanding and implementation of RI grow, global health investigators can share resources, knowledge and innovations that have the potential to significantly change the face of collaborative international research and address long-standing health inequities across diverse settings.
Impact of time of culture specimen collection on the recovery ofNeisseria gonorrhoeaeafter a positive nucleic acid amplification test
Authors: Nadal-Barón Patricia , Trejo-Zahinos Jesús , García Jorge Nestor , Salmerón Paula , Sulleiro Elena , Arando Maider , Descalzo Vicente , Álvarez-Lopez Patricia , El Ouazzani Rachid , López Luis , Zarzuela Francesc , Ruiz Edurne , Llinas Montserrat , Blanco-Grau Albert , Curran Adrian , Larrosa María Nieves , Pumarola Tomàs , Hoyos-Mallecot Yannick
Published: November 2023

Objectives

Culture ofNeisseria gonorrhoeaeremains essential for antimicrobial resistance (AMR) surveillance. We evaluated the effect of time of specimen collection on culture yield following a positive nucleic acid amplification test (NAAT).

Methods

We retrospectively assessedN. gonorrhoeaeculture yield among asymptomatic individuals (largely men who have sex with men) who attended for sexual health screening and had a positive NAAT. Participants underwent either same-day testing and notification (Drassanes Exprés) or standard screening with deferred testing.

Results

Among 10 423 screened individuals, 809 (7.7%) tested positive forN. gonorrhoeae. A total of 995 different anatomical sites of infection culture was performed in 583 of 995 (58.6%) of anatomical sites (Drassanes Exprés 278 of 347, 80.1%; standard screening 305 of 648, 47.1%; p<0.001). Recovery was highest when culture specimens were collected within 3–7 days of screening with only a slight drop in recovery when the interval extended to 7 days . Recovery from pharynx was 38 of 149 (25.5%) within 3 days, 19 of 81 (23.4%) after 4–7 days (p=0.7245), 11 of 102 (10.7%) after 8–14 days (p<0.0036) and 1 of 22 (4.5%) with longer delays (p=0.00287). Recovery from rectum was 49 of 75 (65.3%) within 3 days, 28 of 45 (62.2%) after 4–7 days (p=0.7318), 41 of 69 (59.4%) after 8–14 days (p=0.4651) and 6 of 18 (33.3%) with longer delays (p=0.0131). Median culture specimen collection time was 1 day within Drassanes Exprés vs 8 days within standard screening. Consequently, the overall culture yield was slightly higher within Drassanes Exprés (102/278, 36.6% vs 99/305, 32.5%; p=0.2934).

Conclusion

Reducing the interval between screening and collection of culture specimens increasedN. gonorrhoeaerecovery in extragenital samples. Implementing a same-day testing and notification programme increased collection of culture samples and culture yield in our setting, which may help AMR surveillance.
Nitric oxide and potassium channels but not opioid and cannabinoid receptors mediate tramadol-induced peripheral antinociception in rat model of paw pressure withdrawal
Authors: Soares-Santos Raquel R. , Machado Daniel P. , Romero Thiago L. , Duarte Igor D.G.
Published: November 2023

Tramadol, an analgesic classified as an “atypical opioid”, exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 µg/paw); AM251 (80 µg/paw) and AM630 (100 µg/paw) as the selective antagonists for types 1 and 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 µg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ, and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol's effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol's antinociception effect. Notably, glibenclamide blocked tramadol's antinociception in a dose-dependent manner. These findings suggest that tramadol's peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.
Enhancing optical properties and wettability of colorless polyimide films by direct fluorination
Authors: Liu Yaqiang , Gao Jingxia , Chen Qingqing
Published: November 2023

Colorless polyimide (CPI) films were modified by direct fluorination. The effects of fluorination duration on the chemical structure and surface physical morphology of CPI films were investigated in detail. The results show that direct fluorination induces significant changes in the surface composition and structure, leading to an enhancement in the F/C and O/C ratios. Fluoridation also resulted in increased surface microcracking. In comparison to the original CPI films, the fluorinated CPI films showed good thermal stability and higher glass transition temperatures ([Formula: see text]), and higher optical transmittance (about 93.0%) in the ultraviolet–visible light region. Moreover, the fluorinated surfaces exhibit a high hydrophily and lipophilicity, and consequently a very high surface energy, according to contact angle measurements.
Numerical computation of Gerber–Shiu function for insurance surplus process with additional investment
Authors: Punaluek Sutipon , Imamura Yuri
Published: November 2023

This paper studies the Gerber–Shiu function for the insurance surplus process with additional investment under the Bachelier model. The Gerber–Shiu function allows us to study the moments of the time of ruin, which is the first time that the surplus is negative. First, we use the martingale theory in deriving the integro-differential equation of the Gerber–Shiu function. Then, we give the exact solution of the ruin probability in case the amount of claims follows the exponential distribution. Under a general distribution case, we propose a numerical method of the Gerber–Shiu function using the finite differential method based on the integro-differential equation. Then, numeric illustrations are provided to study the effect of the parameters on the Gerber–Shiu function.
Machine Learning and Natural Language Processing Algorithms in the Remote Mobile Medical Diagnosis System of Internet Hospitals
Authors: Huang Yong , Zhang Lu
Published: November 2023

In order to alleviate the contradiction between supply and demand of professional pharmacists, integrate medical resources, and ensure the safety of patients’ medication, the telemedicine diagnosis system has played a great role. Today, in this “Internet +” era, all walks of life have begun to integrate with Internet technology. The purpose of this article was to discuss the practical utility of machine learning and natural language processing algorithms in the remote mobile medical diagnosis system of Internet hospitals, for which this article conducted in-depth discussion. This article first introduced the basic concepts, development, and characteristics of machine learning and natural language processing algorithms in detail, and carefully studied and analyzed the development and culture of traditional offline medical diagnosis models. Based on machine learning and natural language processing algorithms, a remote mobile medical diagnosis is designed. By combining with the medical diagnosis system of traditional hospitals, a new type of remote mobile medical diagnosis system for Internet hospitals was designed and developed, and the combination of traditional medical industry and Internet technology was deeply studied. According to each functional requirement, the image module, heart rate measurement module, and user setting module are designed, respectively. Compared to traditional medical diagnosis systems, the accuracy of the remote mobile medical diagnosis system based on machine learning applied in Internet hospital diagnosis in this article reached 80% or even higher. At the same time, it was found through experiments that when the evolution number was 3, the maximum fit value and average fit value were the same, both of which were 0.6. This indicates that the system can accommodate more than 10,000 people at the same time, and patients can receive good treatment plans, with a very broad application prospect