bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue macrophages contribute to the zebrafish neoangiogenesis by vascular mimicry
Authors: Senk Anita , Fazzari Jennifer , Djonov Valentin
Published: August 2023

Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally the amount of macrophages is significantly reduced by about 60%. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.
Preferences and perspectives of MS nurses and patients with multiple sclerosis regarding the new RebiSmart® 3.0 autoinjector versus other assistive devices
Authors: Colten Sridevi , Cantogno Elisabetta Verdun , Jack Dominic
Published: August 2023

Background
RebiSmart® is an electromechanical multidose autoinjector developed for administering subcutaneous interferon β-1a in patients with multiple sclerosis (pwMS). This online survey aimed to understand MS nurses’ and pwMS preferences and perceptions regarding the features of an upgraded version of the RebiSmart device (RebiSmart 3.0) compared to other assistive devices used for multiple sclerosis (MS) therapy.
Patients and methods:
Eligible MS nurses and pwMS from Germany, Italy, and the United Kingdom completed a double-blind, 30-minute online self-administered questionnaire, including a 10-minute video describing the features of RebiSmart 3.0 and its use in administering interferon β-1a.
Results
In total, 102 participants (MS nurses, n = 52; patients, n = 50) completed the survey. Overall, 70% respondents found the RebiSmart 3.0 device “very”/“extremely” appealing, 53% were “very”/“extremely” interested in learning more, and 71% stated they would be “very”/“extremely” comfortable using (pwMS) or educating (MS nurses) on it. Respondents ranked customizable injection process (including injection speed, hold time, depth and rotation guide), self-injection process, and hidden needle as the most important self-assistive device features. RebiSmart 3.0 was rated higher than other self-injecting devices on all tested features. After reviewing the video, 52% respondents had no questions, 67% nurses recommended providing more information on the customizable injection process feature of RebiSmart 3.0 to patients, and 88% nurses considered patient demonstration materials to be the most helpful type of information for them when initiating and educating pwMS on self-assistive devices.
Conclusions
The overall reactions of MS nurses and pwMS to the RebiSmart 3.0 device features were positive. The incremental advances over previous versions of the device as well as in comparison with other currently available assistive devices were welcomed. The MS nurses identified key needs for patient education on the use of the device and the suitable approaches (training videos and educational leaflets) to support MS nurses and pwMS.
Coupled Landslide Analyses Through Dynamic Susceptibility and Forecastable Hazard Analysis
Authors: Francis Daniel , Bryson L. Sebastian
Published: August 2023

Landslides, specifically those triggered through an increase of soil moisture after a rainfall event, pose severe threats to surrounding infrastructure. Potential landslide occurrences are monitored through identification of areas susceptible to occurrence, through susceptibility analyses, or areas likely to experience a landslide at a given time, through hazard analyses. Traditional landslide susceptibility systems are created as a function of static geomorphologic data. This is to say that, while spatially differing, susceptibility via this system does not change with time. Landslide hazard analyses consider dynamic data, such as that of precipitation, and provide warnings of when landslide occurrences are likely. However, these hazard analysis systems typically only provide warnings in near real time (i.e., over the next few days). Therefore, dynamic susceptibility (susceptibility that is seen to change with time rather than remain static) as well as the ability to forecast landslide hazard analyses beyond real time is desired. The study herein presents a novel workflow for the creation of dynamic landslide susceptibility and forecastable hazard analyses over a domain within Eastern Kentucky. Dynamic susceptibility was developed through inclusion of static geomorphic parameters and dynamic vegetation levels over sites of interest. These susceptibility data were used in the development of a logistic regression classification machine learning approach which yielded susceptibility classifications with an accuracy of 89%. Forecastable hazard analyses were developed as a function of forecasted soil moisture, assumed to be a controlling factor in landslide occurrence, over a site. Forecasting of soil moisture was conducted through development of a Long Short-Term Memory (LSTM) forecasting machine learning system. Forecasts of soil moisture were then assimilated into an infinite slope stability equation to provide forecasts of hazard analyses. These forecasted hazard analyses were investigated over known landslides with satisfactory results obtained. Therefore, this study presents a novel workflow for both dynamic and forecastable hazard analyses that will undoubtedly provide greater warning and preparation periods to those within landslide prone regions.
Transposon insertion in pmel17 rewired skin and muscle transcriptomes in Mozambique tilapia
Authors: Sun Fei , Wang Le , Yue Gen Hua
Published: August 2023

The pmel17 gene plays a crucial role in melanin pigmentation. Our previous studies showed that in Mozambique tilapia, a transposon inserted into the 3’ untranslated region (3′ UTR) of pmel17 resulted in the silencing of pmel17and led to the loss of melanin pigments (golden mutant phenotype). Additionally, the transposon insertion caused reduced growth performance and increased locomotion. In this study, to investigate the mechanisms underlying these phenotypic changes, we sequenced transcriptomes of the skin and muscle samples collected from wildtype and mutant tilapias. A total of 51 and 141 differentially expressed genes (DEGs) were identified in the skin and muscle transcriptomes, respectively. DEGs in the skin were primarily down-regulated in golden genotypes and associated with neural crest development and melanin pigmentation pathways. Besides these DEGs involved in the classic melanin pigmentation pathway of vertebrates, 14 DEGs were also observed to be related to melanogenesis. In muscle transcriptomes, there was an enrichment of GO terms associated with growth factors and cellular lipid catabolic processes. Specifically, DEGs related to growth factor binding exhibited a down-regulation, while those related to lipid metabolism showed an up-regulation in mutant genotypes. These findings agree with observed phenotypic changes. Furthermore, several DEGs associated with muscle function and mobility were up-regulated. Our study sheds light on how a single mutation in a gene can modulate multiple phenotypes by rewiring gene regulation networks. The research also provides valuable insights into the complex genetic mechanisms underlying the regulation of diverse phenotypic traits by a single gene.
Utility of the Spinal Instability Score in Patients with Spinal Metastases and the Impact on Clinical Outcome
Authors: Bonk Maximilian-Niklas , Sommer Björn , Wolfert Christina , Hackanson Bjoern , Stemmer Bastian , Kahl Klaus-Henning , Stueben Georg , Trepel Martin , Maerkl Bruno , Shiban Ehab , Krauss Philipp
Published: August 2023

Objective
Spinal metastases may cause spinal instability. The Spinal Instability Neoplastic Score (SINS) was developed to assess spinal neoplastic-related instability. Aim of this study was to determine the utility of SINS in predicting progression of a pathologic fracture due to spinal metastases.
Methods
A retrospective analysis of patients with a pathologic fracture due to a spinal metastases between January 2018 and December 2018 was performed. We selected patients with a minimum follow-up of 12 months and analysed them according to the SINS criteria. The primary endpoint was the progression of vertebral body fracture following radiotherapy.
Results
332 Patients were identified. Median age was 68 SD +/- 10,3. 38% were Female. Median follow-up was 26 months (range 12–29). 30, 283 and 19 Patients presented with low (0–6), moderate (7–12) and high (13–18) SINS, respectively. Fracture progression following radiotherapy was seen in 9 (30%), 84 (30%) and 8 (42%) in cases with low, moderate, or high SINS (P = 0.522), respectively. During follow-up, 25% of patients with low SINS showed a progression to moderate SINS without neurological deficits. In the originally moderate group, 17% had progression with neurological deficits needing surgery. None had functional recovery postoperatively. 83% of the progression cases in the moderate group did not develop neurological deficits and 4 underwent surgery for pain management. 63% of all progressions in the high group developed neurological deficits, however none of them recover postoperatively (P < 0.001).
Conclusion
SINS is a very useful tool for assess stability of a pathologic fracture due to spinal metastases after radiotherapy for spinal metastases. Moderate or high SINS are associated with a high risk of fracture progression as well as risk for neurological deterioration, therefore surgical instrumentation in these groups may be advised prior to radiotherapy.
Association of Skin Autofluorescence with Blood Glucose Levels in Children with Type 1 Diabetes Mellitus
Authors: Deng Tinghan , Wu Jingping , Cheng Hongbin
Published: August 2023

Background
People with diabetes mellitus are particularly vulnerable to chronic glycation of proteins and tissue damage caused by the buildup of advanced glycation end products (AGEs). A non-invasive optical technique called skin autofluorescence (SAF) can be used to detect the accumulation of AGEs in the skin. There is a significant association between elevated SAF and diabetes and it predicts the development of complications associated with diabetes. This study evaluated the correlation between SAF and both status and development and also SAF's possible clinical utility as a tool for detecting type 1 diabetes mellitus (T1DM) and its complications in children.
Methods
A systematic search was conducted across the following databases: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Control Trials, Science Direct, Scopus, and Web of Science. We used a random effects model for FOX analysis to examined the link between AGEs detected through SAF levels and T1DM in children. The SAF values of children with and without T1DM were compared. Analysis of 95% confidence interval correlation coefficients based on DerSimonian and Laird methods was performed for application of SAF measurements as a noninvasive alternative to T1DM diagnosis and complications.
Results
Three case-control studies and one retrospective cohort study were included in the systematic review and meta-analysis. The AGE Reader® (DiagnOptics Technologies, Groningen, The Netherlands) was used to evaluate the SAF of all included studies. The results showed that there was statistically significant heterogeneity among the four studies (I2 = 82.00% P < 0.05). The random effect model showed that higher SAF levels were positively correlated with T1DM in children [0.20 (0.16, 0.25)], which indicated that in the four studies, the SAF value of T1DM children was higher than that of non-type 1 diabetic children.
Conclusion
Our findings suggest that measuring SAF levels may serve as a non-invasive marker for T1DM in children and its associated complications. Nevertheless, to obtain more robust conclusions and support specific data on T1DM complications, further research with a larger population and a longer follow-up duration is necessary.
Evaluation of Rock Burst Tendency in Western Hubei Based on BP Neural Network
Authors: Chai Xiuwei , Sheng Yiming , Zhang Long , Nie Zheng , Zhang Dianji
Published: August 2023

Rock burst tendency evaluation is the basis of rock burst risk assessment in underground engineering. In order to realize the accurate evaluation of rock burst tendency in western Hubei, the four parameters of rock burst strength, uniaxial compressive strength of rock σc, the ratio of uniaxial compressive strength to tensile strength σc/σt, rock mass integrity coefficient Kv, the ratio of tangential stress to uniaxial compressive strength σθ/σc were selected as the evaluation index of rock burst tendency in western Hubei.In order to realize the measurement of the above indexes, the location and phenomenon of the rock burst in western Hubei are summarized, and the rock burst is sampled. Then, through the combination of the field and indoor tests, the measurement of the rock burst tendency evaluation index in western Hubei is completed. Finally, based on the Matlab toolbox, round and rank functions are used to generate random training samples and construct the BP neural network model, and the model was tested. The prediction results show that the rock explosion mainly occurs in dolomite and phosphorus rock, and the evaluation results are consistent with the actual situation. The model is practical and relatively easy to calculate, which reduces the deviation caused by individual influencing factors and is easy to popularize in practice.
Simulating Timeshifting for Long-Running Large Language Models
Authors: Jagannadharao Akshaya , Beckage Nicole , Nafus Dawn , Chamberlin Scott
Published: August 2023

Language models play a vital role in various natural language processing tasks, but their training can be computationally intensive and lead to significant carbon emissions. In this study, we explore the effectiveness of timeshifting strategies to mitigate the environmental impact of long-running language models (LLMs). We develop a simulation tool that estimates carbon emissions for LLMs, enabling developers to make informed decisions before running their workloads. By leveraging historical carbon intensity data from WattTime, we investigate the potential benefits and limitations of time-shifting in different locations, considering diverse energy profiles. Our findings demonstrate that time-shifting can substantially reduce emissions for certain workloads, but it is highly dependent on the region's carbon intensity and energy mix. We present insights into the trade-offs between emissions reduction and workload runtime, acknowledging the need for further advancements in carbon-aware computing practices. Our research contributes to the growing field of sustainable computing and encourages developers to adopt environmentally conscious strategies in language model training.
Origin and spatial population structure of Malagasy native chickens based on mitochondrial DNA
Authors: Yonezawa Takahiro , Mannen Hideyuki , Honma Kaho , Matsunaga Megumi , Rakotondraparany Felix , Ratsoavina Fanomezana Mihaja , Wu Jiaqi , Nishibori Masahide , Yamamoto Yoshio
Published: August 2023

Since Malagasy human culture became established in a multi-layered way by genetic admixture of Austronesian (Indonesia), Bantu (East Africa) and West Asian populations, the Malagasy native livestock should also have originated from these regions. While recent genetic studies revealed that Malagasy native dogs and goats were propagated from Africa, the origin of Malagasy native chickens is still controversial. Here, we conducted a phylogeographic analysis of the native chickens, focusing on the historical relationships among the Indian Ocean rim countries and based on mitochondrial D-loop sequences. Although previous work suggested that the rare Haplogroup D occurs with high frequencies in Island Southeast Asia–Pacific, East Africa and Madagascar, the major mitochondrial lineage in Malagasy populations is actually not Haplogroup D but the Sub-haplogroup C2, which is also observed in East Africa, North Africa, India and West Asia. We demonstrate that the Malagasy native chickens were propagated directly from West Asia (including India and North Africa), and not via East Africa. Furthermore, they display clear genetic differentiation within Madagascar, separated into the Highland and Lowland regions as seen in the human genomic landscape on this island. Our findings provide new insights for better understanding the intercommunion of material/non-material cultures within and around Madagascar.
Design a new unsymmetrical Schiff base chiral Co-complex containing ionic liquid groups as a reusable green catalyst in the epoxidation of alkenes
Authors: mohammadian reza , Sandaroos Reza , Allahresani Ali
Published: August 2023

A chiral magnetic catalyst, L-Co (II) - γ-Fe2O3, was prepared by complexing a chiral Schiff base ligand containing an ionic liquid to cobalt chloride and then stabilizing the complex on γ-Fe2O3 nanoparticles. The catalyst and ligand were characterized using HNMR, CNMR, CHN, EDX, SEM, UV-Vis, ICP, TGA, VSM, FT-IR, and XRD analyses. Excellent catalytic activity and enantioselectivity were observed in the green epoxidation of alkenes in the presence of TBHP and EtOAc solvent. The catalyst with magnetic separation capability was recovered with a slight decrease in conversion and yield of epoxidation after five runs.
Fluid Intake, Fiber Consumption and Physical Activity Related to Constipation among Elderly, Which One Is More Important? A cross sectional study from Iran
Authors: safarnaveh Maryam , ghanbari Mahin , Mahmoodi Zohreh , Salehi leili
Published: August 2023

Background: Chronic constipation is a common, self-reported, symptom-based disorder which can significantly impact an individual’s health-related quality of life [1]. Constipation affects the quality of life of a person with social problems and imposes many financial costs on the person The prevalence of constipation is estimated at 1 to 80% around the worldods: Inadequate fluid consumption is touted as a common culprit in constipation, and increasing fluid intake is a frequently recommended treatment. Evidence suggests, however, that increasing fluids is only of usefulness in individuals in a hypo hydrated state, and is of little utility in EU hydrated individuals".There is a strong association between obesity and constipation . Although obesity is also associated with constipation; it is not recognized as a causal factor of constipation. Another investigation indicated constipation and obesity have common risk factors. However, little is known about constipation in individuals with severe obesity and the associated factors The current study was conducted to investigate the effect of Water consumption, fiber intake, and PA on Constipation and which one is more critical by considering Mediating effect of BMIMethods:The study was a cross-sectional study performed on 400 older adults in 2019 referring to the comprehensive health service centers in Karaj, the capital of Alborz province,several instruments included demographic and antro pometric traits , PASE,fluid intakes, FFQ و WHO Qol, wexner cospitation were used to collect data.ُSPSS and lizrelsoftwares were used to analysize dataResults: Based on the final fitted model, PA is the most critical factor related to constipation compared to fluid intake and fiber consumption. The finding of the present study was in line with several studies.Based on the final fitted model, fiber consumption is the second most factor affecting constipation, and there is a negative association between constipation and fiber intake.Conclusions: As price is one of the barriers to fiber consumption in the elderly, the recommendation to do Physical activity such as walking to solve the problem of constipation is efficient and inexpensive advice for people with different socioeconomic statuses.
Novel fluorimetric procedure for estimation of Sumatriptan in its tablet formulation and in human plasma; Implementation to content symmetry testing
Authors: Alrofaidi Mohamed A. , Omar Mahmoud A. , Abdelmageed Osama H , Alahmadi Yaser M. , Eltoukhi Walid E.
Published: August 2023

A rapid, simple & specific fluorimetric method has been described for estimation of Sumatriptan succinate in its pharmaceutical preparation and in human plasma. The proposed procedure is based on the measurement of the fluorescence intensity of studied drug in sulphuric acid / methanol at 350 nm (λex286 nm). Straight correlation was obtained between the fluorescence intensity and concentrations studied over the concentration range 0.1 -2.0 µg/ml with correlation coefficient of 0.999. The detection and quantitation limits were 0.019 and 0.057 µg/ml, respectively. The suggested procedure was validated according to ICH and USP guidelines. It was applied successfully implemented to the estimation of STS in its tablet formulation and content uniformity testing. The suggested method was sensitive enough to allow the estimation of STS in human plasma.
Patient Engagement in Research Scale (PEIRS-22) - Danish translation, applicability, and user experience among cancer patients and caregivers
Authors: Christiansen Mille Guldager , Pappot Helle , Hamilton Clayon , Lund-Jacobsen Trine , Kristensen Anne Wilhøft , Nordentoft Sara , Høeg Beverley Lim , Bidstrup Pernille , Nielsen Iben Husted , Ulstrup Jane , Trip Anouk Kirsten , Jarden Mary , Piil Karin
Published: August 2023

Background
Patient and Public Involvement (PPI) in health research is gaining increased attention and acceptance worldwide. Reliable measurements are crucial to accurately assess, monitor, and evaluate patient involvement efforts in research. The Patient Engagement in Research Scale (PEIRS-22) measures meaningful patient and family caregiver engagement in research. This study focuses on three primary objectives: 1) translation of the PEIRS-22 from English to Danish, followed by linguistic validation and cultural adaptation; 2) assessing the applicability of the Danish PEIRS-22; and 3) focus group interviews to explore the user experiences of PPI.
Methods
A three-phase multi-method study was conducted. In phase one, the PEIRS-22 was translated, linguistically validated and culturally adapted to Danish. In phase two individuals from three distinct cancer patient advisory boards responded to the Danish version of PEIRS-22 to assess its applicability. Three focus group interviews were conducted in phase three, involving individuals from three patient cancer advisory boards.
Results
The translation process resulted in a Danish version of PEIRS-22, conceptually and culturally equivalent to the English version. Overall, among individuals of the three advisory boards (n=15) the applicability was found to be satisfactory, with no missing data and all items completed. The total PEIRS-22 score among the three advisory boards was 85.2 out of a possible 100, with higher scores indicating greater meaningful involvement. A nested sample of the three patient advisory boards (n=9) participated in focus group interviews. The analysis yielded four themes: 1) The Danish PEIRS-22 accurately captured the intended meaning and cultural nuances, 2) Internal motivation is a driver for involvement 3), Involvement brought a personal sense of empowerment and 4) Meaningful involvement collaborations are fostered by a trustful atmosphere.
Conclusions
The PEIRS-22 questionnaire has been translated, linguistically validated and culturally adapted into Danish. We propose that the PEIRS-22 is now ready for use in Danish populations. This study contributes to advancing patient-centered practices and fosters meaningful involvement and collaborations between patients and researchers in the field of cancer research in Denmark. Personal benefits of participating in PPI can vary, and we recommend using PEIRS-22 in conjunction with a qualitative approach to better explore perspectives on meaningful involvement.
Trial registration: The study was registered prospectively on October 22, 2022, by the Danish Data Protection Agency (jr. nr. P-2022-528)
Oxidative stress accompanies HIF1-dependent impairment of glucose metabolism in the hippocampus of adult rats survived prenatal severe hypoxia
Authors: Vetrovoy Oleg , Stratilov Viktor , Potapova Sofiya , Tyulkova Ekaterina
Published: August 2023

Many socially significant diseases are associated with disorders of prenatal development. Previously, we have shown the pathological role of hypoxia inducible factor HIF1 in post-hypoxic reoxygenation. This study aims to investigate the effect of prenatal severe hypoxia (PSH) on HIF1α protein expression as well as on HIF1-dependent activity of the pentose phosphate pathway (PPP) and anaerobic glycolysis in the hippocampus (HPC) of the offspring reached adulthood. We showed that PSH causes a stable increase in the content of HIF1α protein in the HPC which was accompanied by an increase in the efficacy of anaerobic glycolysis. This was testified by increased LDH activity and lactate concentration. At the same time, the amounts of G6PD, NADPH and also reduced glutathione decreased in the HPC of PSH rats, whereas the concentration of an oxidative stress marker, MDA, exceeded the control values. In a series of experiments using the model of emotional stress "learned helplessness" or the model of severe hypoxic stress, it was shown that in the HPC of control rats there was an increase in the amount of HIF1α in response to stress, which was also accompanied by more efficient anaerobic glycolysis and decreased efficacy of the PPP similar to the intact PSH rats. In the PSH rats, in turn, emotional stress resulted even in higher HIF1α levels without affecting glycolysis and PPP. Therefore, the increased content and activity of the transcription factor HIF1α in the HPC of adult rats exposed to prenatal hypoxia leads to the imbalance between glycolysis and the PPP which is accompanied by oxidative stress.
Dark diversity reinforces the importance of climate, soil and disturbance for Caatinga plant diversity
Authors: Araújo Magno Daniel Oliveira Gonçalves , Carvalho Carlos Eduardo , Pequeno Pedro Aurélio Costa Lima , Trindade Diego Pires Ferraz , Hughes Frederic , Araújo Francisca Soares , Partel Meelis , Sfair Julia Caram
Published: August 2023

Species richness is the most commonly used metric to quantify biodiversity. However, examining dark diversity, the group of absent species which can potentially inhabit a site, can provide insights about the factors influencing species assembly. In this study we aimed to understand how climate, soil, acute, and chronic disturbance factors affect not only observed diversity but also dark diversity, completeness (how large is the observed diversity compared to dark diversity) and species pool size (observed and dark diversity together) patterns of a Seasonally Dry Tropical Forest in Brazil. Along 144 0.4-ha plots for trees and 0.04-ha plots for shrubs, herbs, and lianas, we recorded 2148 stems from 232 native species. In general, rainfall was the major drive of plants diversity, whereas soil fertility, deforestation and chronic anthropogenic disturbance had a minor effect. Dark diversity, completeness, species pool and observed diversity respond differently to the different predictors, indicating the complex biodiversity relationship with environmental and disturbance factors. These results highlight the importance of using different metrics of species richness and considering different groups in plant communities’ studies.
Enhanced glycolysis-derived lactate promotes microglial activation in Parkinson's disease via histone lactylation
Authors: Qin Qixiong , Wang Danlei , Qu Yi , Li Jiangting , An Ke , Mao Zhijuan , Li Jingyi , Xiong Yongjie , Min Zhe , Xue Zheng
Published: August 2023

The metabolic switch from oxidative phosphorylation to glycolysis is a vital hallmark and prerequisite for microglia phenotype transition. Recently, histone lactylation was shown to promote macrophage homeostatic gene expression via transcriptional regulation. However, the role of histone lactylation in regulating microglia function in Parkinson’s disease (PD) remains unclear. Here, we show that glycolytic inhibitor 2-deoxy-D-glucose alleviatesmicrogliosis, neuroinflammation, and dopaminergic neuronal damage by reducing lactate accumulation. Notably, histone lactylation, especially H3K9la, is markedly increased in microglia within the substantia nigra of a mouse model of PD and lipopolysaccharide-stimulated primary microglia. Mechanistically, enhanced glycolysis-derived lactate induces H3K9la enrichment at the promoter of solute carrier family 7 member 11 (Slc7a11), promoting its transcription. Inhibition ofSLC7A11 by sulfasalazine mitigates microglia-mediated neuroinflammation and improves motor function in the mouse model PD mice. Moreover, lactate-induced histone lactylation is dependent on the p300/CBP. Collectively, ourfindings demonstrate that augmented glycolysis-derived lactate promotes microglial activation via histone lactylation and provide a novel therapeutic strategy for PD.
Association of mitral valve geometry at CT with secondary mitral regurgitation after transcatheter aortic valve replacement in patients with aortic regurgitation
Authors: Yin Minyan , Lu Yuntao , Chen Jinmiao , Yang Xue , Dong Lili , Wang Xiaolin , Wei Lai
Published: August 2023

Purpose
To determine predictors of persistent moderate to severe secondary mitral regurgitation in patients with aortic regurgitation after transcatheter aortic valve replacement (TAVR) by mitral valve geometry assessment at CT.
Methods
This retrospective cohort study reviewed 242 consecutive patients with aortic regurgitation who underwent TAVR between May 2014 and February 2023. Patients with primary or less than moderate mitral regurgitation were excluded. Mitral annular dimensions (area, perimeter, anteroposterior, intercommissural, and trigone-to-trigone diameter), mitral valve tenting geometry (tenting area and tenting height), and papillary muscle displacement were systematically measured at CT. Mitral regurgitation improvement was assessed at 1 month after TAVR by echocardiography. Logistic regression was performed to explore the association of mitral valve geometry with mitral regurgitation improvement after TAVR.
Results
A total of 75 patients (mean age, 74 ± 7 years; 32.0% female) with moderate to severe secondary mitral regurgitation were included in the final analysis. Mitral regurgitation improved in 49 patients and remained unchanged in 26 patients. Mitral annular dimensions, including area, perimeter, anteroposterior, and intercommissural diameter, were associated with mitral regurgitation improvement. Mitral valve tenting area (MVTA) and tenting height were risk factors for sustained mitral regurgitation. In addition, QRS duration > 120ms and atrial fibrillation had an impact on the mitral regurgitation improvement. Mitral annular area (OR, 1.41; 95%CI: 1.05, 1.90; p = 0.02) and MVTA (OR, 7.24; 95%CI: 1.72, 30.44; p = 0.007) were independent predictors of persistent secondary mitral regurgitation after TAVR.
Conclusions
Mitral annular area and MVTA were independent predictors of persistent secondary mitral regurgitation after TAVR.
Increased ERCP-related adverse event from premature urgent ERCP following symptom onset in acute biliary pancreatitis with cholangitis
Authors: Lee See Young , Jang Sung Ill , Park Sang Ho , Do Min Young , Lee Dong Ki , Cho Jae Hee
Published: August 2023

Acute biliary pancreatitis (ABP) with cholangitis requires endoscopic retrograde cholangiopancreatography (ERCP) within 24 hours to resolve ductal obstruction. However, this recommendation is based on the timing of emergency room (ER) visits. We wanted to determine the optimal timing of ERCP for ABP based on the timing of symptom onset, not the timing of the ER visit. We retrospectively reviewed 162 patients with ABP with cholangitis who underwent urgent ERCP (within 24 hours of ER admission). Area under the receiver operating characteristic (ROC) curve (AUC) was analyzed to determine differences in complication rates according to time from symptom onset. A difference in ERCP-related adverse events (AEs) was identified, and Youden’s J statistic was used to determine a cutoff time from symptom onset (18 hours). We compared mortality and complications based on this cutoff. Based on time to symptom onset, significantly higher rates of aspiration pneumonia (odds ratio [OR]: 4.00, 95% confidence interval [CI]: 1.15–13.92, P = 0.021) and post-ERCP hypotension (OR: 11.9, 95% CI: 1.39–101.33, P = 0.005) were observed in the ≤ 18-hour group than in the > 18-hour group. The study found that patients who underwent ERCP within 18 hours of symptom onset is associated with an increased risk of ERCP-related AEs.
Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as a cross-species strategy to treat malaria
Authors: Creek Darren , Giannangelo Carlo , Challis Matthew , Siddiqui Ghizal , Edgar Rebecca , Malcolm Tess , Webb Chaille , Drinkwater Nyssa , Vinh Natalie , MacRaild Christopher , Counihan Natalie , Duffy Sandra , Wittlin Sergio , Devine Shane , Avery Vicky , de Koning-Ward Tania , Scammells Peter , McGowan Sheena
Published: August 2023

New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of Plasmodium M1 alanyl metalloaminopeptidase as an attractive drug target using the selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition of recombinant Plasmodium falciparum (PfA-M1) and Plasmodium vivax (Pv-M1) M1 metalloaminopeptidases, with selectivity over other Plasmodium and human aminopeptidases, and displayed excellent in vitro antimalarial activity with no significant host cytotoxicity. Orthogonal label-free chemoproteomic methods based on thermal stability and limited proteolysis of whole parasite lysates revealed that MIPS2673 solely targets PfA-M1 in parasites, with limited proteolysis also enabling estimation of the binding site on PfA-M1 to within ~5 Å of that determined by X-ray crystallography. Finally, functional investigation by untargeted metabolomics demonstrated that MIPS2673 inhibits the key role of PfA-M1 in haemoglobin digestion. Combined, our unbiased multi-omic target deconvolution strategies confirmed the on-target activity of MIPS2673, and validated selective inhibition of M1 alanyl metalloaminopeptidase as a promising multi-stage and cross-species antimalarial strategy.
Reliability-based mixed traffic equilibrium problem under endogenous market penetration of connected autonomous vehicles and uncertainty in supply
Authors: Qi Zhong , Lixin Miao
Published: August 2023

In this paper, we consider a novel reliability-based network equilibrium problem for mixed traffic flows of human-driven vehicles (HVs) and connected autonomous vehicles (CAVs) with endogenous CAV penetration rates and stochastic link capacity degradations. Travelers' perception errors on travel time and their risk-aversive behaviors on mode choice and path choice are incorporated in the model with a hierarchical choice structure. Due to the differences between HVs and CAVs, the perception errors and the safety margin reserved by risk-averse travelers are assumed to be related to the vehicle type. The path travel time distribution is derived by using the moment-matching method based on the assumption that link capacity follows lognormal distribution and link travel times are correlated. Then, the underlying problem is formulated as an equivalent variational inequality problem. A path-based algorithm embedded with the Monte Carlo simulation-based method is proposed to solve the model. Numerical experiments are conducted to illustrate the features of the model and the computational performance of the solution algorithm.
Cultural, Socioeconomic, and Demographic Factors Contributing to Child Mortality: Evidence from Sierra Leone Demographic and Health Survey 2019
Authors: Zahangir Mohammad Salim , Neyma Mahmuda Al , Tabassum Sawasan , Faruk Mohmmad Omar
Published: August 2023

Child mortality is the likelihood of a newborn dying before age five and is an essential issue in underdeveloped countries with limited healthcare facilities. Sierra Leone is one of the countries with the highest child mortality rate. This study examined the cultural, socioeconomic, and demographic factors associated with under-five deaths in Sierra Leone. Sierra Leone Demographic and Health Survey 2019 data were used in this study. A total of 4540 mothers aged 15–49 years with at least one child under five were included in the analysis. In the bivariate statistical analyses, Spearman’s and Kendal’s tau correlation, Mann-Whietney, and Kruskal Wallis H test have been performed to test the significance of the explanatory features and study variable. A range of statistical multivariate statistical discrete models has been performed in the multivariate analysis. The results revealed that the Zero-inflated Poisson regression model performed best compared to other discrete models to determine the factors influencing child mortality. The study showed that mental age and the mother’s education level significantly impact child mortality in Sierra Leone. In addition, the number of children of ever born and the mother’s working status significantly affect child mortality. Moreover, preceding birth intervals and geographical regions also substantially impact child death in Sierra Leone. The study results would help policymakers make the right interventions and reduce such mortality in Sierra Leone.
Ecological drivers of host-specificity among bat flies: the importance of season and presence of multi-species bat community inside roosts
Authors: SÁNDOR Attila D. , CORDUNEANU Alexandra , HORNOK Sándor , MIHALCA Andrei D. , PÉTER Áron
Published: August 2023

Bat flies are the most abundant ectoparasites of bats, showing remarkable morphological adaptations to the parasitic habit, while the relationship with their hosts is characterized by a high level of specificity. By collecting bat flies from live hosts, our intention was to elucidate the seasonal differences in bat fly occurrence and to describe factors regulating the level of incipient host specificity. Our results indicate that the prevalence and the intensity of infestation is increasing from spring to autumn for most host species, with significant differences among different fly species. Males showed higher infestation levels than females in autumn, suggesting a non-random host choice by flies, targeting the most active host sex. Bat-bat fly host specificity shows seasonal changes and host choice of bat flies are affected by the seasonal differences in hosts’ behavior and ecology, the intensity of infestation and the species composition of the local host community. By choosing a non-primary bat host may be an adaptive choice for bat flies in the host’s mating period, thus increasing their dispersive ability in a high activity phase of their hosts.
A Lego-like reconfigurable microfluidic stabilizer system with tunable fluidic RC constants
Authors: Zhuge Wuyang , Li Weihao , Wu Chunhui , Jiang Kyle , Ding Jun , Cheng Xing
Published: August 2023

In microfluidic systems, it is important to maintain flow stability to execute various functions such as chemical reaction, cells transportation, or liquid injection. Conventionally, the design and fabrication of a fluidic stabilizer rely on the soft lithography paradigm, which has inherent limitations in a number of ways, such as only capable of planar design and no reconfigurability. Additive manufacturing, also known as 3D printing, provides an alternative solution to these issues. In this work, we present a Lego-like microfluidic stabilizer system based on 3D printing, and demonstrate its capability to achieve twelve fluidic RC constants to tune transient behaviors of microfluidic systems. A simplified three-element circuit model is used to characterize the system and as a prediction model for system design. In order to evaluate the system’s effectiveness, droplet generation experiments are conducted and discussed. Results show that the microfluidic stabilizer system could significantly increase droplet diameter uniformity. This system provides a new venue for microfluidic stabilization with tunable RC constants, and its reconfigurable design could be utilized in a variety of applications requiring finetuning the fluid flow behaviors in microfluidic devices.
Constrained Query Optimization in Differentiated Feature Spaces
Authors: Wang Tian , Chen Cui , Chang Yubiao , Zhan Ding , Tian Chao , Tian Yunzhe , Chen Kang , Tong Endong , Niu Wenjia , Liu Jiqiang
Published: August 2023

In recent years, with the increasing complexity of user demands, there is a growing need for hybrid multi-modal queries with both structured and unstructured constraints. A lot of constrained hybrid query methods were proposed to retrieval objects with similar features to the query while satisfying given structured attribute constraints. However, due to the overlook of attribution dimension differences and attribute ambiguity, these methods may exhibit reduced accuracy and limited robustness in a differentiated feature space. To address this problem, we propose an optimized constrained query method specifically for differentiated feature spaces. Firstly, interaction relationships between attributes are captured by Factorization Machines model. Then, a novel fusion distance metric is developed, incorporating both the Euclidean distance between feature vectors and semantic distance of the differentiated attributes. Furthermore, approximate matching is introduced to find the most suitable constraint conditions, finally achieving constrained query optimization in differentiated feature spaces. Experiments on four large-scale benchmark tests show the significant performance gains of our method in differentiated feature spaces. Our method is faster than the state-of-the-art hybrid query methods and achieves an average 98% recall@10 within one second under thousands of attribute constraints.
Ensemble Learning for Plant Leaf Disease Detection: A Novel Approach for Improved Classification Accuracy
Authors: Ganguly Abhisek , Tiwari Bhaskar , Reddy G. Pawan Kumar , Chauhan Manorama
Published: August 2023

Plant leaf diseases pose significant threats to agricultural productivity and food security. Accurate and timely detection of these diseases is crucial for effective disease management. This research paper proposes a novel approach for plant leaf disease detection using ensemble learning. Ensemble learning combines multiple base models to improve classification accuracy by leveraging their collective intelligence. The proposed ensemble model integrates Convolutional Neural Networks (CNN), ResNeXt, and InceptionV3 architectures, exploiting their diverse strengths in image classification tasks. Extensive experiments on a diverse dataset demonstrate that the ensemble model outperforms individual base models, achieving higher classification accuracy. Its ability to capture complementary features enhances generalization and robustness against variations in disease patterns and image quality. The ensemble model also offers benefits such as improved interpretability, model stability, and reduced overfitting risks. The proposed approach contributes to the advancement of automated plant disease diagnosis systems, enabling early detection and timely intervention to mitigate crop losses and ensure food security. By combining multiple models, the ensemble learning approach improves the accuracy and reliability of plant leaf disease detection, addressing a critical need in agricultural practices.
Summer Production of Lettuce, and Microclimate in High Tunnel and Open Field Plots in Kansas
Authors: Zhao Xin , Carey Edward E.
Published: August 2023

High tunnels have been shown to be a profitable season-extending production tool for many horticultural crops. Production of cool-season vegetables during the hot summer months represents a challenge to market growers in the midwestern United States. Two experiments were conducted to investigate the microclimate and production of eight leaf lettuce (Lactuca sativa) cultivars in high tunnels and open fields, using unshaded and shaded (39% white shadecloth) tunnels in Summer 2002 and 2003, respectively. Wind speed was consistently lower in high tunnels with the sidewalls and endwalls open. An unshaded high tunnel resulted in an increase of daily maximum and minimum air temperatures by ≈0.2 and 0.3 °C, respectively, in comparison with the open field. In contrast, daily maximum air temperature in a shaded high tunnel decreased by 0.4 °C, while the daily minimum air temperature was higher than that in the open field by 0.5 °C. Using high tunnels did not cause a marked change in relative humidity compared with the open field. When using shadecloth, the daily maximum soil temperature was lowered by ≈3.4 °C and the leaf surface temperature was reduced by 1.5 to 2.5 °C. The performance of lettuce during summer trials varied significantly among cultivars. Unshaded high tunnels generally led to more rapid bolting and increased bitterness of lettuce compared with the open field. Lettuce grown in high tunnels covered by shadecloth had a lower bolting rate, but decreased yield relative to the open field. Based on our results, summer lettuce production would not be recommended in high tunnels or open fields in northeastern Kansas, although the potential of shaded high tunnels deserves further studies. Reference crop evapotranspiration (ET0) was estimated from meteorological data on a daily basis using the FAO-56 method. The ET0 was lowest in the shaded high tunnel and was the highest in the open field. Relatively lower ET0 in high tunnels indicated a likely lower water requirement and therefore improved water use efficiency compared with the open field.
Germination and Seed Viability of Norway Maple Cultivars, Hybrids, and Species
Authors: Conklin Janine R. , Sellmer James C.
Published: August 2023

Norway maple (Acer platanoides), 15 cultivars, and two hybrids were assessed for 3 years to evaluate seed germination (e.g., growth chamber, open landscape, and forest) and viability in an initial attempt to understand their invasive potential. Differences in germination were observed among the cultivars over the study. Low to moderate germination was found in growth chambers (0%–35%). Lower germination was found at open landscape (0%–23%) and forest floor sites (0%–18%). Inconsistent viability was observed among cultivars across the seed lots. Viability testing with tetrazolium chloride under two protocols revealed that seed viability was higher than germination and that viability alone was not a good estimate of germination potential. Differences in the accuracy of viability testing procedures were also observed. Short-term germination and viability studies provide only limited information to characterize the possible invasiveness of cultivars.