bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of neutrophils excels the therapeutic potential of Mycobacterium indicus pranii and heat‐induced promastigotes against antimony‐resistant Leishmania donovani infection
Authors: Roy Kamalika , Ghosh Sanhita , Karan Mintu , Karmakar Suman , Nath Supriya , Das Bedanta , Paul Sharmistha , Mandal Pritam , Ray Monalisa , Das Mousumi , Mukherjee Soumyadip , Dey Somaditya , Pal Chiranjib 
Published: January 2024

AbstractRepurposing drugs and adjuvants is an attractive choice of present therapy that reduces the substantial costs, chances of failure, and systemic toxicity. Mycobacterium indicus pranii was originally developed as a leprosy vaccine but later has been found effective against Leishmania donovani infection. To extend our earlier study, here we reported the immunotherapeutic modulation of the splenic and circulatory neutrophils in favour of hosts as neutrophils actually serve as the pro‐parasitic portable shelter to extend the Leishmania infection specifically during the early entry into the hosts' circulation. We targeted to disrupt this early pro‐parasitic incidence by the therapeutic combination of M. indicus pranii and heat‐induced promastigotes against antimony‐resistant L. donovani infection. The combination therapy induced the functional expansion of CD11b+Ly6CintLy6Ghi neutrophils both in the post‐infected spleen, and also in the circulation of post‐treated animals followed by the immediate Leishmania infection. More importantly, the enhanced expression of MHC‐II, phagocytic uptake of the parasites by the circulatory neutrophils as well as the oxidative burst were induced that limited the chances of the very early establishment of the infection. The enhanced expression of pro‐inflammatory cytokines, like IL‐1α and TNF‐α indicated resistance to the parasite‐mediated takeover of the neutrophils, as these cytokines are critical for the activation of T cell‐mediated immunity and host‐protective responses. Additionally, the induction of essential transcription factors and cytokines for early granulocytic lineage commitment suggests that the strategy not only contributed to the peripheral activation of the neutrophils but also promoted granulopoiesis in the bone marrow.
COVID‐19 in organ donors: An organ procurement organization perspective
Authors: Mezochow Alyssa K. , Anesi Judith , West Sharon , Hasz Richard , Edwards John , Blumberg Emily A. 
Published: January 2024

AbstractBackgroundThe COVID‐19 pandemic presented a significant challenge for Organ Procurement Organizations (OPOs) with the use of SARS‐CoV‐2 positive donors varying widely. This study used detailed single OPO data to determine the success of using SARS‐CoV‐2 positive donors.MethodsWe performed a retrospective cohort study including all SARS‐CoV‐2 positive donors referred to the Gift of Life OPO from January 1, 2021, to June 30, 2023. Descriptive analyses were performed to characterize referral and organ utilization.ResultsThere were 861 organ referrals with 1 positive SARS‐Cov‐2 test: 282 were ruled out with telephone evaluation, 431 referrals were ruled out with onsite evaluation (“evaluated nondonors”) and 148 became donors. For donors who had both nasopharyngeal and lower respiratory testing completed, there was notable result discordance observed. Median cycle threshold (Ct) values were similar between donors and evaluated nondonors with no change in median donor Ct values over the study period. Transplanted organs from COVID‐positive donors included 27 hearts, 88 livers, 5 pancreata, and 107 kidneys; no lung donation occurred. The proportion of COVID‐positive donors significantly increased over the study period.ConclusionThis large volume donor referral study demonstrates increasing COVID‐19 referrals progressing to donation over time, supporting the increased use of these donors for nonlung transplantation.
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Characterization of Flex-Fuel Prechamber Enabled Mixing-Controlled Combustion With Gasoline/Ethanol Blends at High Load
Authors: Zeman Jared , Dempsey Adam 
Published: January 2024

Abstract
This numerical study focuses on the characterization of prechamber-enabled mixing-controlled combustion (PC-MCC) at ∼18 bar brake mean effective pressure (BMEP) and 2200 rpm with 10% by volume ethanol-gasoline blend (E10) and pure ethanol (E100). Computational fluid dynamic (CFD) simulations of a stock and prechamber retrofitted single-cylinder Caterpillar C9.3B are carried out using CONVERGE. Prechamber equivalence ratio at spark timing, prechamber spark timing advance, and main chamber injection strategy are assessed with respect to their impact on ignition assistance performance and emissions characteristics relative to a diesel baseline at the same boundary conditions. Simulation results indicate that PC-MCC is flex-fuel capable and operates well for both E10 and E100 at the operating conditions considered. The results demonstrate that the use of a pilot-main injection strategy enables spark timing in the prechamber to be advanced and thus reduces spark plug firing pressure while maintaining robust ignition assistance. Results also indicate that the rich prechamber operation is favored for improved ignition assistance capabilities. The findings of this work suggest that a heavy-duty vehicle using a PC-MCC engine can utilize any blend of gasoline and ethanol, up to including pure ethanol, with no major sacrifices in performance relative to the diesel engine.
Complete Kinematics/Dynamics Modeling and Performance Analysis of a Novel SCARA Parallel Manipulator Based on Screw Theory
Authors: Liang Dong , Mao Yi , Song Yimin , Chang Boyan , Sun Tao 
Published: January 2024

Abstract
In this paper, a novel Selective Compliance Assembly Robot Arm (SCARA) high-speed parallel manipulator that can realize three-translation and one-rotation motion is proposed, and an accurate dynamic modeling methodology is investigated. The mechanism is composed of four limbs with a double parallelogram structure and a single moving platform. The high bearing capacity and high dynamic response of the novel mechanism make it a viable alternative choice for this kind of automation equipment. The degree-of-freedom (DOF) of the mechanism is analyzed by the screw theory. At the same time, the velocity mapping model of the mechanism is established by the twist screw and the actuated Jacobian matrix. Then, the acceleration mapping model of the mechanism, including the generalized kinematic pairs, is established by reduced acceleration state, the modified Lie screw, and the acceleration Hessian matrix. On this basis, the complete dynamic model with a compact form of the mechanism is deduced by the combination of screw theory and virtual work principle, and the correctness of the developed model is verified by multibody simulation software. Finally, considering the inertial characteristics of the mechanism, the dynamic performance distribution in the reachable workspace of the mechanism is analyzed by the Joint-Reflected Inertia (JRI) index and Coefficient of Variation of joint-space Inertia (CVI) index, and some areas are selected as the task workspace using the above index to guarantee good dynamic performance.
Design, Modeling, and Control of a Compact and Reconfigurable Variable Stiffness Actuator Using Disc Spring
Authors: Ji Chen , Zhang Zhongqiang , Cheng Guanggui , Kong Minxiu , Li Ruifeng 
Published: January 2024

Abstract
This paper proposes a compact and reconfigurable variable stiffness actuator (VSA) using disc spring which is named as SDS-VSA (symmetrical disc spring variable stiffness actuator). To enhance the actuator’s torque density, symmetric compression springs are integrated into the cam-roller-spring mechanism, and a disc spring combination design is employed instead of conventional springs. The disc spring configuration is tailored to achieve a broader stiffness range within a limited size, aligned with stiffness and dimensional requirements. Subsequently, the dynamics of the cam-roller-spring mechanism are derived. To tackle the challenge of strong coupling dynamics, a decoupled modeling method by introducing mismatched and matched disturbances is proposed. A back-stepping tracking controller and proportional-derivative (PD) controller with feedforward are proposed to track the link-side and stiffness motor-side trajectories, respectively. Tracking experiments under significant stiffness alteration are conduced to verify the performance of the prototype SDS-VSA.
Identification of a novel growth-associated promoter for biphasic expression of heterogenous proteins in
Pichia pastoris
Authors: Shen Qi , Cui Jie , Wang Yang , Hu Zhong-Ce , Xue Ya-Ping , Zheng Yu-Guo 
Published: January 2024

ABSTRACT

Pichia pastoris
(
P. pastoris
) is one of the most popular cell factories for expressing exogenous proteins and producing useful chemicals. The alcohol oxidase 1 promoter (P
AOX1
) is the most commonly used strong promoter in
P. pastoris
and has the characteristic of biphasic expression. However, the inducer for P
AOX1
, methanol, has toxicity and poses risks in industrial settings. In the present study, analyzing transcriptomic data of cells collected at different stages of growth found that the formate dehydrogenase (FDH) gene ranked 4960th in relative expression among 5032 genes during the early logarithmic growth phase but rose to the 10th and 1st during the middle and late logarithmic growth phases, respectively, displaying a strict biphasic expression characteristic. The unique transcriptional regulatory profile of the FDH gene prompted us to investigate the properties of its promoter (P
FDH800
). Under single-copy conditions, when a green fluorescent protein variant was used as the expression target, the P
FDH800
achieved 119% and 69% of the activity of the glyceraldehyde-3-phosphate dehydrogenase promoter and P
AOX1
, respectively. After increasing the copy number of the expression cassette in the strain to approximately four copies, the expression level of GFPuv driven by P
FDH800
increased to approximately 2.5 times that of the strain containing GFPuv driven by a single copy of P
AOX1
. Our P
FDH800
-based expression system exhibited precise biphasic expression, ease of construction, minimal impact on normal cellular metabolism, and high strength. Therefore, it has the potential to serve as a new expression system to replace the P
AOX1
promoter.

IMPORTANCE

The alcohol oxidase 1 promoter (PAOX1) expression system has the characteristics of biphasic expression and high expression levels, making it the most widely used promoter in the yeast
Pichia pastoris
. However, PAOX1 requires methanol induction, which can be toxic and poses a fire hazard in large quantities. Our research has found that the activity of PFDH800 is closely related to the growth state of cells and can achieve biphasic expression without the need for an inducer. Compared to other reported non-methanol-induced biphasic expression systems, the system based on the PFDH800 offers several advantages, including high expression levels, simple construction, minimal impact on cellular metabolism, no need for an inducer, and the ability to fine-tune expression.
Two sirtuin proteins, Hst3 and Hst4, modulate asexual development, stress tolerance, and virulence by affecting global gene expression in
Beauveria bassiana
Authors: Cai Qing , Tian Li , Xie Jia-Tao , Jiang Dao-Hong 
Published: January 2024

ABSTRACT

Beauveria bassiana
is a widely used entomopathogenic fungus in insect biological control applications. In this study, we investigated the role of two sirtuin homologs, BbHst3 and BbHst4, in the biological activities and pathogenicity of
B. bassiana
. Our results showed that deletion of
BbHst3
and/or
BbHst4
led to impaired sporulation, reduced (~50%) conidial production, and decreased tolerance to various stresses, including osmotic, oxidative, and cell wall-disturbing agents. Moreover, BbHst4 plays dominant roles in histone H3-K56 acetylation and DNA damage response, while BbHst3 is more responsible for maintaining cell wall integrity. Transcriptomic analyses revealed significant changes (>1,500 differentially expressed genes) in gene expression patterns in the mutant strains, particularly in genes related to secondary metabolism, detoxification, and transporters. Furthermore, the Δ
BbHst3
, Δ
BbHst4
, and Δ
BbHst3
Δ
BbHst4
strains exhibited reduced virulence in insect bioassays, with decreased (~20%) abilities to kill insect hosts through topical application and intra-hemocoel injection. These findings highlight the crucial role of BbHst3 and BbHst4 in sporulation, DNA damage repair, cell wall integrity, and fungal infection in
B. bassiana
. Our study provides new insights into the regulatory mechanisms underlying the biological activities and pathogenicity of
B. bassiana
and emphasizes the potential of targeting sirtuins for improving the efficacy of fungal biocontrol agents.

IMPORTANCE

Sirtuins, as a class of histone deacetylases, have been shown to play important roles in various cellular processes in fungi, including asexual development, stress response, and pathogenicity. By investigating the functions of BbHst3 and BbHst4, we have uncovered their critical contributions to important phenotypes in
Beauveria bassiana
. Deletion of these sirtuin homologs led to reduced conidial yield, increased sensitivity to osmotic and oxidative stresses, impaired DNA damage repair processes, and decreased fungal virulence. Transcriptomic analyses showed differential expression of numerous genes involved in secondary metabolism, detoxification, transporters, and virulence-related factors, potentially uncovering new targets for manipulation and optimization of fungal biocontrol agents. Our study also emphasizes the significance of sirtuins as key regulators in fungal biology and highlights their potential as promising targets for the development of novel antifungal strategies.
Optimization of the STARlet workflow for semi-automatic SARS-CoV-2 screening of swabs and deep respiratory materials using the RealAccurate Quadruplex SARS-CoV-2 PCR kit and Allplex SARS-CoV-2 PCR kit
Authors: Flipse Jacky , Tromp Angelino T. , Thijssen Danique , van Xanten-Jans-Beken Nicole , Pauwelsen Roy , van der Veer Harmen J. , Schlaghecke Juliëtte M. , Swanink Caroline M. A. 
Published: January 2024

ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic triggered the implementation of large-scale screenings in the health care and in the general population. Consequently, medical laboratories have to apply lean laboratory management to design workflows that are able to process large batches within short turnaround times while maintaining flexibility to use different SARS-CoV-2 reverse transcription polymerase chain reactions (RT-PCRs) and to be able to process a variety of clinical samples. We validated two SARS-CoV-2 PCR assays on the STARlet workflow: Allplex SARS-CoV-2 PCR kit and RealAccurate Quadruplex SARS-CoV-2 PCR kit. Furthermore, we optimized and validated the STARlet workflow for semi-automatic screening for SARS-CoV-2 in upper respiratory swabs and deep respiratory materials (sputa, bronchoalveolar lavage, and aspirate). Strikingly, guanidine-containing lysis buffers allow for easy processing and can enhance sensitivity of SARS-COV-2 screening since sampling in these buffers may preserve viral transcripts as evident by the higher copy numbers of the SARS-CoV-2 N gene. Moreover, using the principles of lean laboratory management, several bottlenecks that are typical for medical laboratories were addressed. We show that lean laboratory management resulted in significant reduction of the turnaround times of the SARS-CoV-2 PCR in our laboratory. This report thus describes a useful framework for laboratories to implement similar semi-automated workflows.

IMPORTANCE
The SARS-CoV-2 pandemic triggered the implementation of large-scale screenings in the health care and in the general population. Consequently, medical laboratories had to adapt and evolve workflows that are able to process large batches within short turnaround times while maintaining flexibility to use different assays and to be able to process a variety of clinical samples. We describe how the need for increased outputs and greater flexibility was addressed with respect to clinical samples and assays (Allplex SARS-CoV-2 PCR and RealAccurate Quadruplex SARS-CoV-2 PCR). Strikingly, we found that upper respiratory swabs collected in guanidine-containing lysis buffers both improved the ease of processing as well as enhanced the sensitivity of the SARS-CoV-2 screening. This report thus describes a useful framework for laboratories to implement and optimize similar semi-automated workflows.
Interaction of the Exoplanet Hat–P–11b with Stellar Wind
Authors: Belenkaya E. S. 
Published: January 2024

Abstract
We discuss possible existence of a magnetodisk around the exoplanet HAT–P–11b. We used available observations to determine properties of the exoplanet and the stellar wind passing by it and obtained a rough estimate of the size of the planet’s magnetosphere. Comparing our estimate to published results of computations in a 3D electromagnetic relativistic and collisionless particle-in-cell model of the magnetosphere, we found a discrepancy in the magnetosphere size estimated using these two techniques. A possible interpretation of the discrepancy is suggested.
Scale-Invariant Mode in Collisionless Spherical Stellar Systems
Authors: Polyachenko E. V. , Shukhman I. G. 
Published: January 2024

Abstract
An analytical solution for the perturbed equations, applicable to all ergodic models of collisionless spherical stellar systems with a single length parameter, has been derived. This solution corresponds to variations in this parameter, i.e., the expansion or contraction of the sphere while conserving total mass. During this process, the system maintains an equilibrium state. The simplicity of the solution allows for the explicit expression of the distribution function, potential, and density across all orders of perturbation theory. This, in turn, aids in clarifying the concept of perturbation energy, which, being of second order in amplitude, cannot be calculated using linear theory. It is demonstrated that the correct expression for perturbation energy, accounting for second-order perturbations, does not align with the well-known expression for perturbation energy via a quadratic form, derived from first-order perturbations within linear theory. However, both these energies are integrals of motion and differ only by a constant. The derived solution can be utilized to verify the correctness of codes and the precision of calculations in the numerical study of collisionless stellar models.
Are menstrual disturbances associated with an energy availability threshold? A critical review of the evidence
Authors: Salamunes Ana Carla C. , Williams Nancy I. , De Souza Mary Jane 
Published: January 2024

Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a threshold of energy availability (EA) of 30 kcal/kg lean body mass (LBM)/day. This paper is a critical review of the evidence regarding the theory that disruptions to the reproductive axis and menstrual disturbances occur below the proposed threshold. Short-term laboratory studies demonstrated that 4–5 days of an EA below 30 kcal/kg LBM/day, induced with or without exercise, decreased serum triiodothyronine and LH pulse frequency, and increased LH pulse amplitude in sedentary, regularly menstruating women. Fewer studies have investigated downstream ovarian effects after long-term exposure to low EA. The Sargent Camp Study was the first randomized trial that induced luteal phase defects, delayed menses, and anovulation by causing weight loss (−4 ± 0.3 kg) with an abrupt increase in exercise volume for two menstrual cycles. The BioEnergetics Study was a randomized controlled trial that induced varying levels of energy deficits by manipulating energy intake and expenditure for three menstrual cycles. LH pulse frequency and triiodothyronine decreased, and 57% of women developed luteal phase defects, anovulation, and/or oligomenorrhea. An EA below 30 kcal/kg fat free mass/day increased the chance of experiencing a menstrual disturbance by 50%. However, menstrual disturbances were observed above and below that EA threshold, and changes in LH pulse frequency predicted only luteal phase defects, not oligomenorrhea or anovulation. The proposed EA threshold is not a cut-off below which menstrual disturbances occur, but represents an increased risk of experiencing menstrual disturbances.
Averaging generalized scalar field cosmologies IV: locally rotationally symmetric Bianchi V model
Authors: Millano Alfredo D. , Leon Genly 
Published: January 2024

AbstractThis research focuses on scalar field cosmologies with a generalized harmonic potential. Our attention is centred on the anisotropic LRS Bianchi I and III metrics, Bianchi V metrics, and their isotropic limits. We provide a comprehensive overview of the first two metrics classes and offer new findings for Bianchi V metrics. We show that the Hubble parameter is a time-dependent perturbation parameter that controls the magnitude of the error between full-system and time-averaged solutions as it decreases, such that those complete and time-averaged systems have the same asymptotic behaviour. Therefore, oscillations entering the system can be controlled and smoothed out, simplifying the problem.
Abstract A031: ZEB2 induced EMT drives therapy resistance by activating nucleotide excision repair I gene ERCC1 And ERCC4 n colorectal cancer
Authors: Saihati Hajir Al 
Published: January 2024

Abstract
Resistance to adjuvant chemotherapy is a major clinical problem in the treatment of colorectal cancer (CRC). The aim of this study was to elucidate the role of an epithelial to mesenchymal transition (EMT)-inducing protein, ZEB2, in chemoresistance of CRC, and to uncover the underlying mechanism. We performed IHC for ZEB2 and association analyses with clinical outcomes on primary CRC and matched CRC liver metastases in compliance with observational biomarker study guidelines. ZEB2 expression in primary tumors was an independent prognostic marker of reduced overall survival and disease-free survival in patients who received adjuvant FOLFOX chemotherapy. ZEB2 expression was retained in 96% of liver metastases. The ZEB2-dependent EMT transcriptional program activated nucleotide excision repair (NER) pathway largely via upregulation of the ERCC1 gene and other components in NER pathway, leading to enhanced viability of CRC cells upon oxaliplatin treatment. ERCC1-overexpressing CRC cells did not respond to oxaliplatin in vivo, as assessed using a murine orthotopic model in a randomized and blinded preclinical study. Our findings show that ZEB2 is a biomarker of tumor response to chemotherapy and risk of recurrence in CRC patients. We propose that the ZEB2-ERCC1 axis is a key determinant of chemoresistance in CRC.
Citation Format: Hajir Al Saihati. ZEB2 induced EMT drives therapy resistance by activating nucleotide excision repair I gene ERCC1 And ERCC4 n colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A031.