bluuebunny/crossref_metadata_2025 huggingface dataset:
State of the Art in Power Supply of Electrical Discharge Machining, Electrochemical Machining and their Variants
Authors: Zhao Ruming , Dong Hang , Zhou Jianping , Li Ruixiang , Chen Changke , You Pengfei
Published: March 2023

Power supply is the indispensable component for stable non-traditional machining based on electric power, such as electrical discharge machining (EDM), electrochemical machining (ECM), EDM-ECM combined machining, and EDM-ECM hybrid machining. The properties of power supply have significant effects on the machining performance, including efficiency, accuracy, and surface quality. This paper reviews the research progress and technical application in power supply of EDM, ECM, EDM-ECM combined machining, and EDM-ECM hybrid machining. The circuit principle, performance index, process effect of power supply are systematically analyzed. Moreover, the applications are summarized, and the future development are prospected.
Research and Realization of Hierarchical Information Interaction in Multi-load Regulation System
Authors: Zhang Liuliu , He Minyi , Xie Wei , He Zhen , Tan Zhijun
Published: March 2023

In the context of advancing the integration of power source network load storage and multi-energy complementary development, it is necessary to optimize the integration of power source, grid side, and load side resources to build a new power system with a high degree of integration of source network load and storage. The article analyzes the adjustable load distribution. In the scenario of multi-layer collaborative control, access methods are divided around load resource types and response characteristics, and an information interaction technology oriented to multiple load adjustments is proposed to achieve flexible and friendly interaction with various load aggregator systems. At present, research results have been obtained in the project. In practical applications, the flexible and friendly interaction of adjustable load resources enhances the flexible adjustment capability of the power grid and expands the space of adjustable load resources.
Jiles-Atherton Iron Core Hysteresis Model Parameter Identification with Enhanced Artificial Bee Colony Algorithm
Authors: Tang Hao , Chen Xuxuan , Yu Yuchen , Lei Yuanyuan
Published: March 2023

An enhanced artificial bee colony algorithm is proposed for the problems of insufficient accuracy and slow convergence of existing algorithms in J-A model parameter recognition, which introduces the Boltzmann selection strategy in the process of bee colony selection of nectar sources to dynamically adjust the convergence pressure of the algorithm. To enhance the overall optimization performance, at the same time, a global factor is added to the search formula to enhance the optimization capability of a single bee. Finally, a reverse learning strategy is used in the search process of the scout bee to enhance the quality of the solution in the later iteration to speed up the algorithm convergence. The identification and comparison experiments are carried out in combination with the simulation data and the measured data of silicon steel sheets. The results show that the identification results using the enhanced algorithm have better accuracy and faster convergence speed.
The Application of GaN/ZnO Heterojunction in Water Splitting
Authors: Liu Kai , Chen Zhizhong , Zhao Lixia , Su Kang , Xi Xin , Li Tuo , Wang Changhong
Published: March 2023

Different morphology of ZnO were deposited on GaN substrate using magnetron sputtering method by changing deposition conditions. The ZnO and GaN can form II-type heterojunction due to its higher conduction and lower valence band compared to GaN. The electric field generated by space charge region can separate the photo generated carriers more promptly. In the photocatalytic test, the best performance of GaN/ZnO photoanode with fine crystal quality is about 1.39 times compared to planar GaN. Our research paves a new way for the application of GaN in water splitting performance.
Thermal Calculation and Analysis of 9FA Type Gas Turbine Basic Conditions
Authors: Li Jiahu , Ma Chi , Wu Shaohua , Li Jiaxing
Published: March 2023

This paper takes GE’s PG9351FA gas turbine as the research object. From the perspective of energy conservation and mass balance, the compressor, the combustion chamber and the turbine are modeled separately, and then the models are coupled. Key parameters such as fuel, air and gas properties, unit fuel volume, cooling air volume, cooling air volume of the first stage vanes, equivalent turbine front temperature, and compressor efficiency are obtained through the model. The research results meet the engineering error requirements and have certain reference significance for the thermal design of gas turbines.
Transformer Fault Synthetic Diagnosis Method Based on Fusion of Multi-Neural Networks and Evidence Theory in Cloud Computing
Authors: Liu Rongsheng , Cui Shuguang , Lin Anping , Liao Yong
Published: March 2023

As the core equipment of power system, the failure of transformer will result in paralysis of the whole system. Therefore, timely diagnosis of transformer fault types is the most important task to ensure the stable operation of power system. Through the cloud computing method, the neural network is combined with the advantages of evidence theory, by comparing the chromatographic data of the transformer and the electrical test data. A comprehensive diagnosis method of transformer fault based on the fusion of multi neural network and evidence theory based on cloud computing is proposed. The fault diagnosis performance of the transformer is measured by the inspection of the fault transformer. The results show that compared with the traditional single data comparison, this method can improve the reliability and accuracy of diagnosis by comparing many kinds of data.
Design of Equipment Fault Diagnosis System Based on Audio Analysis Technology
Authors: Zhou Xinyu
Published: March 2023

In the aspect of state monitoring of hydropower unit, the main technical means is to collect and monitor the data on site by deploying various sensors and cameras in the unit and its affiliated units, relying on computer monitoring system and unit state monitoring system. However, it is difficult to intuitively feel the audio characteristics of the unit when it is running. Therefore, an equipment fault diagnosis system based on audio analysis technology is proposed, which makes use of audio analysis technology to analyze and process the on-site sound online, and provides a new auxiliary monitoring means for the equipment running status. Furthermore, the effectiveness of the system is verified by the operation of a power plant.
Heat Dissipation Performance Research of Power Lithium Battery Based on High Thermal Conductivity Graphite Film
Authors: Jin Biao , Fei Qiang , Lin Ruizhe , Zou Wuyuan
Published: March 2023

Heat will be generated inside the power lithium-ion battery during operation, if heat dissipation is not carried out in time, its temperature will rise continuously, causing thermal safety accidents once the temperature exceeds its normal work temperature range. In addition, the uniformity of the battery temperature will affect its performance, life, and even safety. Therefore, research on the heat dissipation performance of lithium battery can effectively improve its safety characteristics and working performance. To improve the temperature uniformity of single battery, different high thermal conductivity graphite films are used as the thermal conductivity enhanced scheme, the heat production and heat generation rate model of single battery was established, and its temperature simulation model was built by Ansys software to simulate heat dissipation performance. The results show that the high thermal conductivity graphite film can significantly enhance the battery heat dissipation performance, and its thickness, specific heat capacity and density have important effects on its performance.
Study on the Applicable Height of Self-lifting (Self-supporting) Crossing Equipment Frame
Authors: Li Wenjie , Tang Yongcun , Ma Yong , Sun Lijiang , Meng Fanhao
Published: March 2023

Crossing frames with different heights can bear different external loads, which leads to the limitation of their application occasions. In order to explore the applicable occasions of self-lifting (self-supporting) crossing frame and guide the construction company to choose the height of crossing frame that meets the requirements, the parametric finite element model of crossing frame was established in this paper according to the preliminary design scheme of crossing frame. By analyzing the load combination of the crossing frame under different working conditions and taking the strength and stiffness of the frame as constraints, the applicable height of the crossing frame under working conditions, non-working conditions with stay wires and non-working conditions without stay wires was calculated respectively. The calculation results show that, the frame body without stay wires in non-working condition has more stringent requirements on the use of span frame body than the other two conditions. Therefore, the applicable height value of the frame body in the form of non-working condition without stay wires is taken as the standard value for design and use.
Influence of the position relationship between gas–liquid interface and laser focus on plasma evolution characteristics in jet LIBS technology
Authors: XUE Yuanyuan , SUI Mingda , LIU Runze , WANG Yiping , GUO Jinjia , TIAN Ye , LI Jiamin , LIU Meijie , ZHONG Shilei , XUE Gongyi
Published: March 2023

In order to understand the characteristics of breakdown process, plasma evolution and spectral emission in liquid jets laser-induced breakdown spectroscopy methods under the influence of the position variation between laser focus and gas–liquid interface, this work takes the plasma generated by laser-induced liquid jets as the object of study and discusses the changes in the spatial and temporal evolution characteristics and spectral radiation of the plasma when the position parameters between the laser focal point and the gas–liquid interface are different. The initial breakdown position is always between the front interface and the focus when the laser focus moves along the vertical direction of the interface, forming a phenomenon like ‘interface effect’. The relationship between laser pulse energy and breakdown probability exhibits a law similar to a ‘hysteresis curve’ in the study of breakdown threshold. In this work, plasma with smaller size, rounder shape, stronger radiation, higher temperature, and higher density can be produced when the focus position is in the liquid column 0.2 mm away from the front interface. Simultaneously, the spectral signal intensity and signal-to-back ratio of the characteristic peaks of target elements in water reach maximum values, and the spectral signal becomes more stable (relative standard deviation value reaches 2%). The Ca element’s ion radiation at 393.366 nm and atomic radiation at 422.673 nm are studied using narrow-band filtering imaging and time-space resolution spectroscopy. The findings demonstrate that the laws of ion and atomic radiation are not perfectly consistent in space and time.
Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration
Authors: Saha Suvrajit , Town Jason P. , Weiner Orion D.
Published: March 2023

mTORC2 is an evolutionarily conserved regulator of membrane homeostasis and cellular polarity. Here we probe the logic of mechanosensitive activation of mTORC2 and how mTORC2 pathways independently regulate the leading and trailing edge polarity programs to mediate front-back coordination during neutrophil migration.
TGF-β1 induced activations of Smad2 and miRNAs inhibit SF-1- and LRH-1-dependent CYP19 expression in rat Leydig cells
Authors: Ma Binfang , Qiao Huilian , Guo Ying , Wei Jinhua , Yang Qianqian , Feng Xiao , Li Zhen
Published: March 2023

P450 aromatase, encoded by the Cyp19 gene, catalyzes the synthesis of estrogen, which is crucial for mammalian germ cell differentiation. We have previously shown that transforming growth factor beta 1 (TGF-β1) attenuated the accumulation of steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1) and eventually reduced the transcription of Cyp19 in rat Leydig cells (LCs). Here, we report that TGF-β1 treatment-induced phosphorylation of Smad2 and decreased the expression levels of SF-1 and LRH-1 by elevating the expression levels of microRNA-21-3p and microRNA-339-5p in vivo and in vitro. Furthermore, both TGF-β1 treatment and over-expression of Smad2 inhibited the SF-1 or LRH-1-regulated promoter activity of the Cyp19 gene, and p-Smad2 physically interacted with SF-1 and LRH-1. Our findings collectively suggest that TGF-β1 may inhibit the expression of CYP19 in LCs mainly through two ways. On the one hand, TGF-β1 acts through Smad2 to repress the accumulation of SF-1 and LRH-1 at post-transcriptional level by upregulating specific microRNAs. On the other hand, TGF-β1 inhibits the transcriptional activity of Cyp19 through the interaction of p-Smad2 with SF-1/LRH-1.
Surgical interhospital transfer mortality: national analysis
Authors: Murshed Ishraq , Gupta Aashray K , Camilos Angelique N , Sabab Ahad , Bacchi Stephen , Kovoor Joshua G , Chan Justin C Y , Maddern Guy J
Published: March 2023

Background

Interhospital transfers of surgical patients are an independent risk factor for mortality. The Australian and New Zealand Audit of Surgical Mortality (ANZASM) aims to improve surgical care through assessment of all cases of surgical mortality. This study aimed to describe common clinical management issues that contributed to interhospital transfer patient mortality.

Methods

Data for all surgical patient mortality in Australia (except New South Wales) that underwent interhospital transfer between 1 January 2010 and 31 December 2019 were extracted from ANZASM. The surgeons’ reports and assessors’ evaluations were examined to identify clinical management issues. Thematic analysis was performed to develop pertinent themes and subthemes.

Results

Some 8679 patients were identified over the 10-year period. Of these, 2171 (25.0 per cent) had 3259 clinical management issues identified. Prominent themes were operative design (n = 466, 14.3 per cent), decision to operate (n = 425, 13.0 per cent), medical conditions (n = 344, 10.6 per cent), diagnosis (n = 326, 10 per cent), transfer (n = 293, 10.0 per cent), intraoperative issues (n = 278, 8.5 per cent), inadequate assessment (n = 238, 7.3 per cent), communication (n = 224, 6.9 per cent), delay in recognizing complications (n = 180, 5.5 per cent), coagulopathy (n = 151, 4.6 per cent), insufficient monitoring (n = 127, 3.9 per cent), infection (n = 107, 3.3 per cent), and hospital resources (n = 100, 3.1 per cent). Assessors considered 58.4 per cent of clinical management issues (n = 1903) probably or definitely preventable.

Conclusion

This study identified 13 themes of potentially avoidable management issues present in surgical mortality following interhospital transfers. Quality-improvement initiatives targeting these areas may improve surgical patient outcomes.
Impaired dopamine release in Parkinson’s disease
Authors: Cramb Kaitlyn M L , Beccano-Kelly Dayne , Cragg Stephanie J , Wade-Martins Richard
Published: March 2023

Parkinson’s disease is the second most common neurodegenerative disease and yet the early pathophysiological events of the condition and sequences of dysfunction remain unclear. The loss of dopaminergic neurons and reduced levels of striatal dopamine are descriptions used interchangeably as underlying the motor deficits in Parkinson’s disease. However, decades of research suggest that dopamine release deficits in Parkinson’s disease do not occur only after cell death, but that there is dysfunction or dysregulation of axonal dopamine release before cell loss. Here we review the evidence for dopamine release deficits prior to neurodegeneration in Parkinson’s disease, drawn from a large and emerging range of Parkinson’s disease models, and the mechanisms by which these release deficits occur. The evidence indicates that impaired dopamine release can result from disruption to a diverse range of Parkinson’s disease-associated genetic and molecular disturbances, and can be considered as a potential pathophysiological hallmark of Parkinson’s disease.
Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis
Authors: Lin Jianfeng , Zhou Jiawei , Xu Yan
Published: March 2023

Multiple sclerosis is a complex autoimmune disease, and several therapies for multiple sclerosis have been developed and widely used. However, existing medications for multiple sclerosis were far from satisfactory due to their failure to suppress relapses and alleviate disease progression. Novel drug targets for multiple sclerosis prevention are still needed.

We performed Mendelian randomization to explore potential drug targets for multiple sclerosis using summary statistics from the International Multiple Sclerosis Genetics Consortium (nCase = 47 429, nControl = 68 374) and further replicated in UK Biobank (nCase = 1356, nControl = 395 209) and FinnGen cohorts (nCase = 1326, nControl = 359 815). Genetic instruments for 734 plasma and 154 CSF proteins were obtained from recently published genome-wide association studies. The reverse causality detection using bidirectional Mendelian randomization analysis and Steiger filtering, Bayesian co-localization, and phenotype scanning that searched previously reported genetic variant–trait associations were implemented to consolidate the Mendelian randomization findings further. In addition, the protein–protein interaction network was performed to reveal potential associations among proteins and/or present multiple sclerosis medications.

At Bonferroni significance (P < 5.63 × 10−5), Mendelian randomization analysis revealed six protein–multiple sclerosis pairs. In plasma, per standard deviation increase in FCRL3, TYMP and AHSG had a protective effect. Odds ratios for the proteins above were 0.83 (95% CI, 0.79–0.89), 0.59 (95% CI, 0.48–0.71) and 0.88 (95% CI, 0.83–0.94), respectively. In CSF, per 10-fold increase in MMEL1 (OR, 5.03; 95% CI, 3.42–7.41) increased the risk of multiple sclerosis, while SLAMF7 (OR, 0.42; 95% CI, 0.29–0.60) and CD5L (OR, 0.30; 95%CI, 0.18–0.52) decreased the risk. None of the six proteins had reverse causality. Bayesian co-localization suggested that FCRL3 [coloc.abf-posterior probability of hypothesis 4 (PPH4) = 0.889], TYMP (coloc.susie-PPH4 = 0.896), AHSG (coloc.abf-PPH4 = 0.957, coloc.susie-PPH4 = 0.973), MMEL1 (coloc.abf-PPH4 = 0.930) and SLAMF7 (coloc.abf-PPH4 = 0.947) shared the same variant with multiple sclerosis. FCRL3, TYMP and SLAMF7 interacted with target proteins of current multiple sclerosis medications. MMEL1 was replicated in both UK Biobank and FinnGen cohorts.

Our integrative analysis suggested that genetically determined levels of circulating FCRL3, TYMP, AHSG, CSF MMEL1 and SLAMF7 had causal effects on multiple sclerosis risk. These findings suggested those five proteins might be promising drug targets for multiple sclerosis and warrant further clinical investigation, especially FCRL3 and SLAMF7.
Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment
Authors: Liu Fang , Liang Chen , Li Zhengchang , Zhao Sen , Yuan Haiming , Yao Ruen , Qin Zailong , Shangguan Shaofang , Zhang Shujie , Zou Li-Ping , Chen Qian , Gao Zhijie , Wen Suiwen , Peng Jing , Yin Fei , Chen Fei , Qiu Xiaoxia , Luo Jingsi , Xie Yingjun , Lu Dian , Zhang Yu , Xie Hua , Li Guozhuang , Zhang Terry Jianguo , Luan Pengfei , Wang Hongying , Cui Xiaodai , Huang Hailiang , Liu Ruize , Sun Xiaofang , Chen Chao , Wu Nan , Wang Jian , Liu Chunyu , Shen Yiping , Gusella James F , Chen Xiaoli
Published: March 2023

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes.

Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers.
Positive Impact of [18F]FDG-PET/CT on Mortality in Patients With Staphylococcus aureus Bacteremia Explained by Immortal Time Bias
Authors: van der Vaart Thomas W , Prins Jan M , van Werkhoven Cornelis H , ten Doesschate Thijs , Soetekouw Robin , van Twillert Gitte , Veenstra Jan , Herpers Bjorn L , Rozemeijer Wouter , Jansen Rogier R , Bonten Marc J M , van der Meer Jan T M
Published: March 2023

Background

Several studies have suggested that in patients with Staphylococcus aureus bacteremia (SAB) [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) improves outcome. However, these studies often ignored possible immortal time bias.

Methods

Prospective multicenter cohort study in 2 university and 5 non-university hospitals, including all patients with SAB. [18F]FDG-PET/CT was performed on clinical indication as part of usual care. Primary outcome was 90-day all-cause mortality. Effect of [18F]FDG-PET/CT was modeled with a Cox proportional hazards model using [18F]FDG-PET/CT as a time-varying variable and corrected for confounders for mortality (age, Charlson score, positive follow-up cultures, septic shock, and endocarditis). Secondary outcome was 90-day infection-related mortality (assessed by adjudication committee) using the same analysis. In a subgroup-analysis, we determined the effect of [18F]FDG-PET/CT in patients with high risk of metastatic infection.

Results

Of 476 patients, 178 (37%) underwent [18F]FDG-PET/CT. Day-90 all-cause mortality was 31% (147 patients), and infection-related mortality was 17% (83 patients). The confounder adjusted hazard ratio (aHR) for all-cause mortality was 0.50 (95% confidence interval [CI]: .34–.74) in patients that underwent [18F]FDG-PET/CT. Adjustment for immortal time bias changed the aHR to 1.00 (95% CI .68–1.48). Likewise, after correction for immortal time bias, [18F]FDG-PET/CT had no effect on infection-related mortality (cause specific aHR 1.30 [95% CI .77–2.21]), on all-cause mortality in patients with high-risk SAB (aHR 1.07 (95% CI .63–1.83) or on infection-related mortality in high-risk SAB (aHR for 1.24 [95% CI .67–2.28]).

Conclusions

After adjustment for immortal time bias [18F]FDG-PET/CT was not associated with day-90 all-cause or infection-related mortality in patients with SAB.
Exploring the learning curve in minimally invasive esophagectomy: a systematic review
Authors: Chan Kai Siang , Oo Aung Myint
Published: March 2023

Minimally invasive esophagectomy (MIE) has been shown to be superior to open esophagectomy with reduced morbidity, mortality, and comparable lymph node (LN) harvest. However, MIE is technically challenging. This study aims to perform a pooled analysis on the number of cases required to surmount the learning curve (LC), i.e. NLC in MIE. PubMed, Embase, Scopus, and the Cochrane Library were systematically searched for articles from inception to June 2022. Inclusion criteria were articles that reported LC in video-assisted MIE (VAMIE) and/or robot-assisted MIE (RAMIE). Poisson means (95% confidence interval [CI]) was used to determine NLC. Negative binomial regression was used for comparative analysis. There were 41 articles with 45 data sets (n = 7755 patients). The majority of tumors were located in the lower esophagus or gastroesophageal junction (66.7%, n = 3962/5939). The majority of data sets on VAMIE (n = 16/26, 61.5%) used arbitrary analysis, while the majority of data sets (n = 14/19, 73.7%) on RAMIE used cumulative sum control chart analysis. The most common outcomes reported were overall operating time (n = 30/45) and anastomotic leak (n = 28/45). Twenty-four data sets (53.3%) reported on LN harvest. The overall NLC was 34.6 (95% CI: 30.4–39.2), 68.5 (95% CI: 64.9–72.4), 27.5 (95% CI: 24.3–30.9), and 35.9 (95% CI: 32.1–40.2) for hybrid VAMIE, total VAMIE, hybrid RAMIE, and total RAMIE, respectively. NLC was significantly lower for total RAMIE compared to total VAMIE (incidence rate ratio: 0.52, P = 0.032). Studies reporting NLC in MIE are heterogeneous. Further studies should clearly define prior surgical experiences and assess long-term oncological outcomes using non-arbitrary analysis.
Is there a peer status gradient in mortality? Findings from a Swedish cohort born in 1953 and followed to age 67
Authors: Almquist Ylva B , Östberg Viveca , Modin Bitte
Published: March 2023

Background

Similar to having a less advantaged socioeconomic position, children in lower peer status positions typically experience a situation characterized by less power, influence and command over resources, followed by worse health outcomes. The aim of this study was to examine whether peer status position is further associated with increased risks for premature all-cause mortality.

Methods

Data were drawn from a 1953 cohort born in Stockholm, Sweden. Peer status positions were established through survey data on peer nominations within the school class at age 13, whereas national registers were used to identify all-cause mortality across ages 14–67. Differences in hazard rates and median survival time, according to peer status position, were estimated with Cox regression and Laplace regression, respectively.

Results

Although differences in hazard rates were not large, they were consistent and clear, also after taking childhood socioeconomic status into account. Regarding median survival time, the number of years lost increased gradually as peer status decreased, with a difference of almost 6 years when comparing individuals in the lowest and highest positions.

Conclusions

Children’s positions in the peer status hierarchy play a role for their chances of health and survival, pointing to the relevance of addressing opportunities for positive peer interaction and mitigating any adverse consequences that may stem from negative experiences within the peer context.
Does genetic testing offer utility as a supplement to traditional family health history intake for inherited disease risk?
Authors: May Thomas , Smith Crystal L , Kelley Whitley , East Kelly , Orlando Lori , Cochran Meagan , Colletto Sierra , Moss Irene , Nakano-Okuno Mariko , Korf Bruce , Limdi Nita
Published: March 2023

Content

This study examines the potential utility of genetic testing as a supplement to family health history to screen for increased risk of inherited disease. Medical conditions are often misreported or misunderstood, especially those related to different forms of cardiac disease (arrhythmias vs. structural heart disease vs. coronary artery disease), female organ cancers (uterine vs. ovarian vs. cervical), and type of cancer (differentiating primary cancer from metastases to other organs). While these nuances appear subtle, they can dramatically alter medical management. For example, different types of cardiac failure (structural, arrhythmia, and coronary artery disease) have inherited forms that are managed with vastly different approaches.

Methods

Using a dataset of over 6,200 individuals who underwent genetic screening, we compared the ability of genetic testing and traditional family health history to identify increased risk of inherited disease. A further, in-depth qualitative study of individuals for whom risk identified through each method was discordant, explored whether this discordance could be addressed through changes in family health history intake.

Findings

Of 90 individuals for whom genetic testing indicated significant increased risk for inherited disease, two-thirds (66%) had no corroborating family health history. Specifically, we identify cardiomyopathy, arrhythmia, and malignant hyperthermia as conditions for which discordance between genetic testing and traditional family health history was greatest, and familial hypercholesterolaemia, Lynch syndrome, and hereditary breast and ovarian cancer as conditions for which greater concordance existed.

Conclusion

We conclude that genetic testing offers utility as a supplement to traditional family health history intake over certain conditions.
Give Me a Sign: Concrete Symbols Facilitate Orientation in Alzheimer’s Disease Dementia
Authors: Boedeker Sebastian , Driessen Martin , Schulz Philipp , Beblo Thomas , Kreisel Stefan , Toepper Max
Published: March 2023

Objectives

Persons with Alzheimer’s disease dementia (ADD) often show impaired orientation, particularly in unknown environments. Signs may offer an opportunity to compensate for these deficits and thus improve participation.

Methods

We assessed 30 persons with ADD and 36 healthy controls by using a sign comprehension paradigm (SCP) in a real-life environment. Nonparametric mixed model analyses of variance were used to analyze the effect of different symbols and additional scripture (coding condition) on SCP performance speed and accuracy.

Results

Analyses revealed a significant main effect of symbol design on SCP speed as well as an interaction effect of group × symbol, indicating a benefit of concrete, optimized signs for persons with ADD. Furthermore, analyses of SCP error rates revealed the main effects of group and coding condition as well as an interaction effect of group × coding. Persons with ADD made more errors than healthy controls, but SCP error rates decreased significantly in ADD in the double-coding condition.

Discussion

Our findings revealed an advantage of concrete double-coded symbols over conventional symbols and therefore strongly suggest the implementation of concrete double-coded signs to support older people living with ADD.
Co-designing a health promotion program for Australian Aboriginal and Torres Strait Islander girls: lessons learnt
Authors: English Madeleine , Canuto Karla , Schulenkorf Nico , Evans John , Curry Christina , Slater Cain , Caperchione Cristina M
Published: March 2023

Despite progression in the ethical and methodological conduct of Aboriginal and Torres Strait Islander health research, disparities still pervade, indicating limitations in knowledge translation. One identified gap is a lack of documented experiences detailing how ethical guidelines may be practically applied. This paper aims to (i) describe the research processes involved in co-designing a physical activity and psychosocial health program for Aboriginal and Torres Strait Islander girls and (ii) highlight learnings of the collaborative research journey. The Criteria for Strengthening Reporting of Health Research involving Indigenous Peoples (CONSIDER) statement was used to document participatory research activities undertaken with an Aboriginal community partner. Building upon the CONSIDER statement, Aboriginal (N = 3), Torres Strait Islander (N = 1) and non-Indigenous (N = 4) research team members engaged in critical reflection to identify lessons learnt. Researchers identified a tension between participatory research principles and the expectations of funding agencies and research institutions. Consequently, timelines must be flexible to foster meaningful community engagement and participatory processes. Additionally, researchers and community stakeholders are encouraged to embrace tensions that may associated with participatory research or the pressures Aboriginal and Torres Strait Islander researchers face from their community and organization. Furthermore, differences in professional (i.e. occupational) and cultural knowledge systems need to be acknowledged and accounted for within the early stages of a project to ensure informed decision-making. Identified lessons will assist relevant stakeholders in the development of future Aboriginal and Torres Strait Islander health programming, ensuring the most appropriate health solutions are devised with community.
Antibiotic-induced degradation of antitoxin enhances the transcription of acetyltransferase-type toxin-antitoxin operon
Authors: Li Peifei , Goh Ying-Xian , Ilic Bojana , Tai Cui , Deng Zixin , Chen Zhaoyan , Djordjevic Marko , Ou Hong-Yu
Published: March 2023

Background

Bacterial toxin-antitoxin (TA) modules respond to various stressful conditions. The Gcn5-related N-acetyltransferase-type toxin (GNAT) protein encoded by the GNAT-RHH TA locus is involved in the antibiotic tolerance of Klebsiella pneumoniae.

Objectives

To investigate the transcriptional mechanism of the GNAT-RHH operon kacAT under antibiotic stress.

Methods

The transcriptional level of the kacAT operon of K. pneumoniae was measured by quantitative real-time (qRT) PCR assay. The degradation of antitoxin KacA was examined by western blot and fluorescent protein. The ratio of [KacA]:[KacT] was calculated by the fluorescence intensity of KacA-eGFP and mCherry-KacT. Mathematical modelling predicted protein and transcript synthesis dynamics.

Results

A meropenem-induced increase in transcript levels of kacA and kacT resulted from the relief from transcriptional autoregulation of the kacAT operon. Meropenem induces the degradation of KacA through Lon protease, resulting in a reduction in the ratio of [KacA]:[KacT]. The decreased ratio causes the dissociation of the KacAT complex from its promoter region, which eliminates the repression of kacAT transcription. In addition, our dynamic model of kacAT expression regulation quantitatively reproduced the experimentally observed reduction of the [KacA]:[KacT] ratio and a large increase in kacAT transcript levels under the condition of strong promoter autorepression by the KacAT complex.

Conclusions

Meropenem promotes the degradation of antitoxin by enhancing the expression of Lon protease. Degradation of antitoxin reduces the ratio of intracellular [antitoxin]:[toxin], leading to detachment of the TA complex from its promoter, and releasing repression of TA operon transcription. These results may provide an important insight into the transcriptional mechanism of GNAT-RHH TA modules under antibiotic stress.
Predicate counterparts of modal logics of provability: High undecidability and Kripke incompleteness
Authors: Rybakov Mikhail
Published: March 2023

In this paper, the predicate counterparts, defined both axiomatically and semantically by means of Kripke frames, of the modal propositional logics $\textbf {GL}$, $\textbf {Grz}$, $\textbf {wGrz}$ and their extensions are considered. It is proved that the set of semantical consequences on Kripke frames of every logic between $\textbf {QwGrz}$ and $\textbf {QGL.3}$ or between $\textbf {QwGrz}$ and $\textbf {QGrz.3}$ is $\Pi ^1_1$-hard even in languages with three (sometimes, two) individual variables, two (sometimes, one) unary predicate letters, and a single proposition letter. As a corollary, it is proved that infinite families of modal predicate axiomatic systems, based on the classical first-order logic and the modal propositional logics $\textbf {GL}$, $\textbf {Grz}$, $\textbf {wGrz}$ are not Kripke complete. Both $\Pi ^1_1$-hardness and Kripke incompleteness results of the paper do not depend on whether the logics contain the Barcan formula.
Provider Ownership and Indicators of Service Quality: Evidence from Swedish Residential Care Homes
Authors: Broms Rasmus , Dahlström Carl , Nistotskaya Marina
Published: March 2023

The provision of public services by for-profit and non-profit organizations is widespread in OECD countries, but the jury is still out on whether outsourcing has improved service quality. This article seeks to nuance existing debate by bringing to the fore variation in service quality between different types of non-public providers. Building on theories of dimensional publicness and incomplete contracts, we argue that different forms of non-public ownership are associated with varying intensity of incentives for profit maximization, ultimately affecting service quality. Using residential elder care homes in Sweden as our universe of cases, we leverage novel panel data for 2,639 facilities from 2012 to 2019, capturing the ownership type of the care home operators, against a set of indicators pertaining to inputs, processes, and outcomes. The results suggest that non-public providers with high-powered incentives to make profit, such as those owned by private equity firms and publicly traded companies, perform worse on most of the selected indicators compared to private limited liability companies and nonprofits. Our findings that the intensity of quality-shading incentives is not the same for all non-public providers have important implications for government contracting and contract management.
Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways
Authors: Gong Yuhang , Jiang Ting , Lu Fangying , Sun Jiacheng , Xu Wangjin , Qiu Jianxin , Zhang Weikang , Zheng Xiaohang , Yang Guangyong , Chu Binxiang , Ye Jiajing , Mi Shuang , Hong Zhenghua
Published: March 2023

Objectives

Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD.

Methods

An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc.

Key findings

Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model.

Conclusions

Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.
Urine Protein Immunofixation Electrophoresis: Free Light Chain Urine Immunofixation Electrophoresis Is More Sensitive than Conventional Assays for Detecting Monoclonal Light Chains and Could Serve as a Marker of Minimal Residual Disease
Authors: Singh Gurmukh , Arinze Nkechi , Manthei David M , Plapp Frederick V , Bollag Roni J
Published: March 2023

Background

Immunoglobulin monoclonal light chains (MLCs) in serum and urine are markers for monoclonal gammopathy and could serve as markers of minimal residual disease (MRD) in multiple myeloma (MM). Excretion of MLCs in urine is known to result in renal damage and shorter survival in patients with LC-predominant MM.

Methods

Retrospective review of urine immunofixation in 1738 specimens at 3 medical centers was conducted to assess the utility of urinalysis for diagnosis and monitoring of monoclonal gammopathy. We tested 228 stored urine specimens via the modified urine immunofixation method, using antisera to assay free LCs (FLCs).

Results

Our review of urine immunofixation results and medical records validated the theory that the only meaningful value-added finding was detection of monoclonal free light chains. Examination of 228 urine specimens using our novel method revealed 18.4% additional positive results. The rate of incremental findings for lambda LCs was nearly 3-fold higher than for kappa LCs.

Conclusions

The new method of urine immunofixation is significantly more sensitive and more efficient than the conventional method for detecting MLCs in urine. The new assay appears to be sensitive enough to prove that MLCs serve as a marker of MRD in MM.
Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run
Authors:   The LVK Collaboration
Published: March 2023

We describe a search for gravitational waves from compact binaries with at least one component with mass $0.2$–$1.0 \, \mathrm{M}_\odot$ and mass ratio q ≥ 0.1 in Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo data collected between 2019 November 1, 15:00 utc and 2020 March 27, 17:00 utc. No signals were detected. The most significant candidate has a false alarm rate of $0.2 \, \rm {yr}^{-1}$. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs $f_\mathrm{PBH} \gtrsim \, 0.6$ (at 90 per cent confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions, we are unable to rule out fPBH = 1. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound fDBH < 10−5 on the fraction of atomic dark matter collapsed into black holes.
UV-FIR SED modelling of AGNs in IR-luminous galaxies up to z ∼ 2.5: understanding the effects of torus models
Authors: Sokol Alyssa D , Yun M , Pope A , Kirkpatrick A , Cooke K
Published: March 2023

UV-FIR spectral energy distribution (SED) modelling is an effective way to disentangle emission between star formation (SF) and active galactic nuclei (AGNs) in galaxies; however, this approach becomes uncertain for composite AGNs/SF galaxies that comprise 50–70 per cent of IR-samples. Cosmic X-ray background (XRB) models require a large fraction of obscured AGNs to reproduce the observed XRB peak, motivating reliable SED analyses in objects where the AGNs may be ‘buried’ in the galaxy and in the mid-IR to far-IR SED. In this paper, we study a 24 $\mu$m-selected (S24 > 100 $\mu$Jy) sample of 95 galaxies with $0~{{\ \rm per\ cent}} \lt f_{\mathrm{ MIR},\mathrm{ AGN}} \lt 100~{{\ \rm per\ cent}}$, 0.4 < z < 2.7, and 1011L⊙ < LIR < 1013L⊙. We test the performance of AGN models ranging in torus optical depth via SED fitting, comparing results with Spitzer mid-infrared spectroscopy and X-ray observations. The best-fitting torus optical depth can shed light on whether these galaxies host a luminous obscured AGN population. We find that permitting a broader AGN SED parameter space results in improved fit quality with higher optical depths, higher FIR AGN contributions, and higher LBol, impacting the bright end of the LBol luminosity function. Our results suggest there may be a population of dust-obscured composites that are bolometrically significant but have their AGNs mostly hidden in the mid-IR SED. If so, literature applications of SED fitting that often simplify AGN models or omit optically thick tori may largely underestimate AGN contribution from composite sources, as these sources are both numerous and have solutions sensitive to the assumed range of AGN models.
Study of central light distribution in nearby early-type galaxies hosting nuclear star clusters
Authors: Sruthi K , Ravikumar C D
Published: March 2023

We present analysis of 63 nearby (<44 Mpc) early-type galaxies hosting nuclear star clusters using the recently discovered parameter central intensity ratio (CIRI) determined from near-infrared (3.6 $\mu$m) observations with the Infrared Array Camera of Spitzer Space Telescope. The CIRI, when combined with filters involving age and B − K colour of host galaxies, helps identify two distinct classes of galaxies hosting nuclear star clusters. This is independently verified using Gaussian mixture model. CIR shows a positive trend with faint, low-mass, and blue galaxies in the sample, while the opposite is true for bright, high-mass, and red galaxies, albeit with large scatter. The variation of CIRI with central velocity dispersion, absolute B-band magnitude, dynamical mass, and stellar mass of host galaxies suggests that the mass of nuclear star clusters increases with that of host galaxies, for faint, low-mass, young, and blue galaxies in the sample. In bright, high-mass, old, and red galaxies, on the other hand, the evolution of nuclear star clusters appears complex, with no apparent trends. The analysis also reveals that redder galaxies (B − K > 3.76) are more likely to be dominated by the central black hole than the nuclear star clusters, while for bluer galaxies (B − K < 3.76) in the sample the situation is quite opposite.
The occurrence rate of giant planets orbiting low-mass stars withTESS
Authors: Bryant Edward M , Bayliss Daniel , Van Eylen Vincent
Published: March 2023

We present a systematic search for transiting giant planets ($0.6 \mbox{$R_{\rm J}$}\le \mbox{$R_{\rm P}$}\le 2.0 \mbox{$R_{\rm J}$}$) orbiting nearby low-mass stars ($\mbox{$M_{*}$}\le 0.71 \mbox{${\rm M}_{\odot }$}$). The formation of giant planets around low-mass stars is predicted to be rare by the core-accretion planet formation theory. We search 91 306 low-mass stars in the TESS 30 min cadence photometry detecting fifteen giant planet candidates, including seven new planet candidates which were not known planets or identified as TOIs prior to our search. Our candidates present an exciting opportunity to improve our knowledge of the giant planet population around the lowest mass stars. We perform planet injection-recovery simulations and find that our pipeline has a high detection efficiency across the majority of our targeted parameter space. We measure the occurrence rates of giant planets with host stars in different stellar mass ranges spanning our full sample. We find occurrence rates of 0.137 ± 0.097  per cent (0.088–0.26 M⊙), 0.108 ± 0.083 per cent (0.26–0.42 M⊙), and 0.29 ± 0.15 per cent (0.42–0.71 M⊙). For our full sample (0.088–0.71 M⊙), we find a giant planet occurrence rate of 0.194 ± 0.072 per cent. We have measured for the first time the occurrence rate for giant planets orbiting stars with $\mbox{$M_{*}$}\le 0.4\, \mbox{${\rm M}_{\odot }$}$ and we demonstrate this occurrence rate to be non-zero. This result contradicts currently accepted planet formation models and we discuss some possibilities for how these planets could have formed.