bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral Consequences of Velocity Commands: Brownian Processes in Human Motor Tasks
Authors: Tessari Federico , Hermus James , Sugimoto-Dimitrova Rika , Hogan Neville
Published: December 2023

The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce “random walks”, also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity.
Pregnancy in myasthenia gravis: A retrospective analysis of maternal and neonatal outcome from a large tertiary care center in Germany
Authors: Draxler Jakob , Meisel Andreas , Stascheit Frauke , Stein Maike , Gerischer Lea , Mergenthaler Philipp , Herdick Meret , Doksani Paolo , Lehnerer Sophie , Verlohren Stefan , Hoffmann Sarah
Published: December 2023

Purpose: Myasthenia gravis (MG) is a rare, potentially life-threatening autoimmune disease with fluctuating muscle weakness frequently affecting women of childbearing age. MG can affect maternal as well as neonatal outcome with risk of worsening of myasthenic symptoms in the mothers and risk of transient neonatal myasthenia gravis (TNMG) and arthrogryposis multiplex congenita (AMC) or fetal acetylcholine receptor antibody-associated disorders (FARAD) in the neonates.
Methods: Retrospective analysis of maternal and neonatal outcome in a cohort of pregnant MG patients treated at a tertiary care center in Germany.
Results: Overall, 66 pregnancies were analysed. During 40 (63%) pregnancies, women experienced a worsening of myasthenic symptoms, of whom 10 patients (15.7%) needed acute therapy with IVIg or plasma exchange. There was no case of myasthenic crisis. Rate of caesarian section was comparable to the overall C-section rate at our centre (38% vs. 40%). However, there was a slightly higher rate for operative vaginal delivery (15% vs. 10%) as potential indicator for fatiguing striated musculature in MG patients during the expulsion stage. Rate of TNMG as well as AMC was 3% (two cases each).
Conclusions: Maternal and neonatal outcome in our cohort was favorable with a low rate of myasthenic exacerbations requiring acute therapies and a low rate of TNMG and AMC/FARAD. Our data might help neurologists and obstetricians to advice MG patients with desire to have children.
Comparison of cooking emissions mitigation between automated and manually operated air quality interventions in one-bedroom apartments
Authors: Pantelic Jovan , Tang Mengjia , Byun Kunjun , Knobloch Yaakov , Son Young Joo
Published: December 2023

We implemented a crossover study design exposing 15 participants to two indoor air quality conditions in the Well Living Lab. The first condition, the Standard Control Condition, resembled the ventilation and air supply of a typical home in the USA with a manually operated stove hood. The second condition, Advanced Control, had an automated: (i) stove hood, (ii) two portable air cleaners (PAC), and (iii) bathroom exhaust. The PM2.5 sensors were placed in the kitchen, living room, bedroom, and bathroom. Once the sensor detected a PM2.5 level of 15 µg/m3 or higher, an air quality intervention (stove hood, PAC or bathroom exhaust) in that space was activated and turned off when the corresponding PM2.5 sensor had three consecutive readings below 6 µg/m3. Advanced Control in the overall apartment reduced PM2.5 concentration by 40% compared to the Standard Control. In the kitchen, the PM2.5 concentration difference between Advanced and Standard Control was ~ 20%. This can be attributed to using the stove hood manually in 66.5% of cooking PM2.5 emission events for 323.6 h compared to 88 h stove hood used in automated mode alongside 61.9 h and 33.7 h of PAC use in living room and bedroom, respectively.
Heteromorphic ZZ/ZW sex chromosomes sharing gene content with mammalian XX/XY are conserved in Madagascan chameleons of the genus Furcifer
Authors: Rovatsos Michail , Mazzoleni Sofia , Augstenová Barbora , Altmanová Marie , Velenský Petr , Glaw Frank , Sanchez Antonio , Kratochvíl Lukáš
Published: December 2023

Chameleons are well-known lizards with unique morphology and physiology, but their sex determination has remained poorly studied. Madagascan chameleons of the genus Furcifer have cytogenetically distinct Z and W sex chromosomes and occasionally Z1Z1Z2Z2/Z1Z2W multiple neo-sex chromosomes. To identify the gene content of their sex chromosomes, we microdissected and sequenced the sex chromosomes of F. cf. oustaleti (ZZ/ZW) and F. pardalis (Z1Z1Z2Z2/Z1Z2W). In addition, we sequenced the genomes of a male and a female of F. lateralis (ZZ/ZW) and F. pardalis and performed a comparative coverage analysis between the sexes. Despite the notable heteromorphy and distinctiveness in heterochromatin content, the Z and W sex chromosomes share approximately 90% of their gene content. This finding demonstrates poor correlation of the degree of differentiation of sex chromosomes at the cytogenetic and sequence level. The test of homology based on the comparison of gene copy number variation revealed that female heterogamety with differentiated sex chromosomes remained stable in the genus Furcifer for at least 20 million years. These chameleons co-opted for the role of sex chromosomes the same genomic region as viviparous mammals, lacertids and geckos of the genus Paroedura, which makes these groups excellent model for studies of convergent and divergent evolution of sex chromosomes.
Transcriptome analysis reveals a new insights toward molecular mechanisms of Methylmalonic acidemia in hepatocytes
Authors: Zhang Zhilei , Wang Xin , Wang Yanyun , Li Yahong , Yang Peiying , Sun Yun , tao jiang
Published: December 2023

Background: The overabundance of methylmalonic acid due to the mutation of methylmalonyl-CoA mutase in the mitochondria contributes to hepatocyte damage, impacting various functions, especially energy metabolism. Our study focuses on analyzing transcriptomic alterations induced by methylmalonic acid to elucidate novel mechanisms through which the deficiency of methylmalonyl-CoA mutase causes cellular damage.
Results: In this study, we observed that excessive accumulated methylmalonic acid inhibited endoplasmic reticulum (ER)-phagy by downregulating the expression of the ER-phagy receptor FAM134B. This inhibition coincided with an increase in extracellular Ca2+ influx, which aimed to counterbalance the insufficient Ca2+ levels within the overloaded ER. In addition, methylmalonic acid accumulation in hepatocytes triggered ER stress, initiating unfolded protein response via IRE1α-XBP1 pathway. This response aimed to eliminate misfolded proteins and restore ER homeostasis. Moreover, ER stress and increased Ca2+ levels in the cytoplasm activated autophagy, facilitating the degradation misfolded proteins and the affected organelles. The persistent presence of methylmalonic acid hindered mitophagy by inducing the expression of BCL2L1, leading to the accumulation of dysfunctional mitochondria in hepatocytes, thereby exacerbating cellular damage.
Conclusions: Our study delves into the impact of methylmalonic acid on hepatocyte functions, shedding light on the interplay between ER-phagy, ER stress, disturbances in Ca2+ flow and mitophagy. By examining these intricate mechanisms, our research unveils promising, previously unexplored therapeutic targets for methylmalonic acidemia.
Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1
Authors: Giannakopoulos Theodoros , Richter Manfred , Kostin Sawa , Krizanic Florian , Sasko Benjamin , Ritter Oliver , Pagonas Nikolaos , Kostin Sawa
Published: December 2023

Background and aim. The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation.
Methods. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n=7), inflammatory (MYO, n=6) and ischemic (ICM, n=7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot.
Results. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A 5-fold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased 2-fold in DCM and MYO, and more than 3-fold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively 3-fold increased in all groups of patients.
Conclusions: This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.
Cryptanalysis of efficient multiparty quantum secret sharing based on a novel structure and single qubits
Authors: Cai Xiao-Qiu , Liu Zi-Fan , Li Shuang , Wang Tian-Yin
Published: December 2023

Quantum secret sharing is a basic quantum cryptographic primitive, which has a lot of applications in information security and privacy preservation. An efficient multiparty quantum secret sharing protocol [EPJ Quantum Technology 2023 10: 29] based on a novel structure and single qubits was reported recently. In this paper, we give a cryptanalysis of this protocol and show that it cannot satisfy the security requirement for secret sharing because an unauthorized set of agents can gain access to some information on the dealer's secret by a special collusion attack. Furthermore, we put forward an effective way to deal with the security problem.
An open-source controller to build a dynamic light intensity setup
Authors: Caracciolo Ludovico , Philippi John , Theeuwen Tom P.J.M. , Amerongen Herbert van , Harbinson Jeremy
Published: December 2023

Background
The development and physiology of plants are influenced by light intensity and its changes. Despite the significance of this phenomenon, there is a lack of understanding regarding the processes light regulates. This lack of understanding is partly due to the complexity of plant's responses, but also due to the limited availability of light setups capable of producing specific light patterns.
Results
While unraveling the complexities of plant responses will require further studies, this research proposes a simple method to implement dynamic light setups. In this study, we introduce two distinct electronic circuits that are cost-effective and enable the control of dimmable power supply.
Conclusion
This method enables the generation of intricate light patterns and rapid intensity fluctuations, providing a means to investigate how plants respond and develop when exposed to dynamic light conditions.
Tumor marker index based on CYFRA21-1 and NSE is an important screening index for early-stage esophageal squamous cell carcinoma high-risk groups
Authors: Guo Meng , Li Yarui , Lu Guifang , He Shuixiang , Ren Mudan
Published: December 2023

Objective: The purpose of this study was to evaluate a novel tumor marker index (TMI) based on cytokeratin-19 fragments (CYFRA21-1) and neuron-specific enolase(NSE) in early-stage esophageal squamous cell carcinoma (ESCC) screening.
Methods: This study retrospectively included a total of 192 individuals who received gastroscopy or treatment between the period of October 2021 and October 2022. TMI was defined as the geometric mean of the normalized values of serum CYFRA21-1 and NSE concentration. Binary logistic regression analysis model was used to determine the independent risk factors for early-stage ESCC. Furthermore, a risk prediction model including TMI and epidemiological factors was developed.
Results: According to the receiver operating characteristic curve, the cut-off value of TMI was 0.681, and participants were grouped into high and low TMI cohorts. Univariate and multivariate analyses showed that TMI was an independent risk factor for early-stage ESCC (p = 0.027). Moreover, according to the logistic regression, the model indicated excellent predictive performance in assessing individuals' risk of early-stage ESCC via TMI and epidemiological factors.
Conclusion: The study indicated that TMI based on CYFRA21-1 and NSE can be used as a novel indicator for screening high-risk population of early-stage ESCC.
A novel gammapartitivirus from the Penicillium oxalicum RCEF7482
Authors: Huang Bo , Sun Jing , Wang Ping , Lu Hanwen , Yang Guogen
Published: December 2023

Penicillium oxalicum, an essential biocontrol fungus in China, has been a subject of extensive study due to its role in combating various pathogenic fungi. Despite the prevalence of mycoviruses with double-stranded (ds) RNA genomes in filamentous fungi, no instances of mycovirus infection have been reported in P. oxalicum. In this investigation, we present the identification and characterization of a novel dsRNA virus isolated from P. oxalicum, designated as "Penicillium oxalicum partitivirus 1" (PoPV1). The genome of PoPV1 consists of two dsRNA segments, dsRNA1 (1,770 bp) and dsRNA2 (1,584 bp), each hosting a single open reading frame (ORF): ORF1 and ORF2. Comparative analysis revealed that PoPV1's RdRp and CP sequences share the highest identity (89.18% and 73.97%, respectively) with Penicillium aurantiogriseum partitivirus 1 (PaPV1). Motif analysis based on RdRp amino acid sequences places PoPV1 in the genus Gammapartitivirus within the familyPartitiviridae, with a distinctive motif VI (R/KV/ILGDD). Phylogenetic analysis further establishes PoPV1's close relationship with PaPV1, forming a unique clade within gammapartitiviruses. Consequently, we propose that Penicillium oxalicum partitivirus 1 represents a novel species in the genus Gammapartitivirus, marking the first reported case of dsRNA in P. oxalicum.
Study Protocol for the Development and Validation of a People Perceived Quality of Health Systems Scale Based on the People's Voice Survey
Authors: li Chunping , Wang Xiaohui , Zhong Dongmei , Zhong Lexin , Yang Ting , Cai Yiyuan , He Wenjun , Luo Meng , Zhao Hongmei , Lv Sensen , Huang Wanqing , Zhang Lanping , Li Jiaqi , Xie Yunyun , Zhao Qing , Liu Siyuan , Chen Xiaoshan , Xu Dong(Roman)
Published: December 2023

Background
Current research underscores the necessity of assessing the quality of health systems from the people's perspective. The Lancet Global Health Commission has proposed a High-Quality Health System (HQHS) framework, which covers system foundations, care quality, user experience, outcomes, and confidence. The commission has also developed an English version of the People's Voice Survey (PVS) based on the HQHS framework. Lanzhou University has created a Chinese version of PVS. However, the PVS, being a survey, poses challenges in quantifying outcomes. Additionally, its considerable length can limit its usefulness and validity in application.
Methods
The development and validation of the scale will undergo the following six phases: (1) constructing an initial version of the scale item pool and dimensions based on the existing People's Voice Survey; (2) employing an improved Delphi consultation method to assess the comprehensiveness of the scale items and dimensions in measuring the intended concepts, followed by conducting content validity evaluation; (3) conducting cognitive interviews to explore participants' understanding and difficulties with the items, collecting information to subsequently refine the scale, and enhance face validity; (4) conducting a pilot test to optimize the survey process before the formal validation test; and (5) employing a validation test to assess the scale's test-retest reliability, internal consistency, content validity, face validity, construct validity (including structural validity and hypothesis testing), language and length, following the recommendations of health measurement tool selection guidelines.
Discussion
This study aims to develop the "People Perceived Quality of Health Systems Scale (PEQSYS)" based on the HQHS and PVS. The PEQSYS will adhere to the rigorous scale development process proposed by COSMIN and PAPERS, among other standards, and aim to possess robust psychometric properties.The anticipated result is a scale possessing essential attributes, including robust psychometric properties, repeatability, quantifiability, and comparability. These characteristics will facilitate a swift and quantitative evaluation of perceived health system quality, ensuring the scale's applicability in diverse contexts.
Comparative Transcriptomic Analysis of two Asian Medicinal and Aromatic Species of Salvia subg. Perovskia – a Contribution Towards Molecular Background of Abietane-type Diterpenoid Biosynthesis
Authors: Bielecka Monika , Stafiniak Marta , Pencakowski Bartosz , Ślusarczyk Sylwester , Jastrzębski Jan Paweł , Paukszto Łukasz , Łaczmański Łukasz , Gharibi Shima , Matkowski Adam
Published: December 2023

Tanshinones, are a group of diterpenoid red pigments present in Danshen – an important herbal drug of Traditional Chinese Medicine which is a dried root of Salvia miltiorrhiza Bunge. Some of the tanshinones are sought after as pharmacologically active natural products. To date, the biosynthetic pathway of tanshinones has been only partially elucidated. These compounds are also present in some of the other Salvia species, i.a. from subgenus Perovskia, such as S. abrotanoides (Kar.) Sytsma and S. yangii B.T. Drew. Despite of the close genetic relationship between these species, significant qualitative differences in their diterpenoid profile have been discovered. In this work, we have used the Liquid Chromatography–Mass Spectrometry analysis to follow the content of diterpenoids during the vegetation season, which confirmed our previous observations of a diverse diterpenoid profile. As metabolic differences are reflected in different transcript profile of a species or tissues, we used metabolomics-guided transcriptomic approach to select candidate genes, which expression possibly led to observed chemical differences. Using an RNA-sequencing technology we have sequenced and de novo assembled transcriptomes of leaves and roots of S. abrotanoides and S. yangii. As a result, 134,443 transcripts were annotated by UniProt and 56,693 of them were assigned as Viridiplantae. In order to seek for differences, the differential expression analysis was performed, which revealed that 463, 362, 922 and 835 genes indicated changes in expression in four comparisons. GO enrichment analysis and KEGG functional analysis of selected DEGs were performed. The homology and expression of two gene families, associated with downstream steps of tanshinone and carnosic acid biosynthesis were studied, namely: cytochromes P-450 and 2-oxoglutarate-dependend dioxygenases. Additionally, BLAST analysis revealed existence of 39 different transcripts related to abietane diterpenoid biosynthesis in transcriptomes of S. abrotanoides and S. yangii. We have used quantitative real-time RT-PCR analysis of selected candidate genes, to follow their expression levels over the vegetative season. A hypothesis of an existence of a multifunctional CYP76AH89 in transcriptomes of S. abrotanoides and S. yangii is discussed and potential roles of other CYP450 homologs are speculated. By using the comparative transcriptomic approach, we have generated a dataset of candidate genes which provides a valuable resource for further elucidation of tanshinone biosynthesis. In a long run, our investigation may lead to optimization of diterpenoid profile in S. abrotanoides and S. yangii, which may become an alternative source of tanshinones for further research on their bioactivity and pharmacological therapy.
FLT3-ITD-Specific PROTAC: Enhanced Safety and Increased Synergy with Venetoclax in Acute Myeloid Leukemia
Authors: Tan Yuxin , Xin Lilan , Wang Qian , Xu Rong , Tong Xiqin , Chen Guopeng , Ma Linlu , Yang Fuwei , Jiang Hongqiang , Zhang Nan , Wu Jinxian , Li Xinqi , Guo Xinyi , Wang Chao , Zhou Haibing , Zhou Fuling
Published: December 2023

Background
Patients with acute myeloid leukemia (AML) carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis, high risk of relapse, and short overall survival. While some FLT3 small molecule inhibitors have been used clinically, challenges such as short efficacy, poor specificity, and resistance persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher targeting capability, and the minimal amount of PROTAC can rapidly degrade proteins. This technology may address issues of poor specificity or resistance seen with small molecule inhibitors.
Methods
Gilteritinib was used as the ligand for the target protein FLT3-ITD, and different E3 ligase ligands were connected to synthesize several series of PROTAC targeting FLT3-ITD.
Results
Through in vitro and in vivo screening and structural optimization, PROTAC Z29 linked to VHL E3 ligase ligand, the optimal lead compound, was obtained. Kinase screening showed that the synthesized PROTAC Z29 exhibited better specificity and targeting ability than existing small molecule inhibitors. In vitro, Z29 significantly inhibited the proliferation of FLT3-ITD+ MOLM13 and MV-4-11 cells and induced FLT3 protein degradation through the proteasome pathway at the nanomolar level. In vivo, Z29 significantly inhibited tumor growth rate at a dose of 30 mg/kg in subcutaneous xenograft mice while maintaining the stable body weight of mice. Compared to Gilteritinib, Z29, when used in combination with Venetoclax, demonstrated a higher synergy score in MOLM13 and MV-4-11 cells. We also verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model, which may be due to the minimal expression of VHL ligase in platelets. The combination of Z29 and Venetoclax showed better anti-tumor effects and lower platelet toxicity and hepatic toxicity.
Conclusion
PROTAC technology can enhance drug targeting specificity. The rapid degradation ability and higher targeting specificity of FLT3-ITD PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy. These findings establish a solid foundation for FLT3-ITD-PROTAC as an effective strategy for the treatment of patients with FLT3-ITD mutation.
A green approach for metoclopramide quantification in pharmaceutical products. New HPLC and spectrophotometric methods
Authors: DEMİR İbrahim , Bulduk İbrahim , DARWISH Ibrahim A. , ENGİNAR Hüseyin
Published: December 2023

Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min− 1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 minutes. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. The developed methods are proposed as excellent environmental and operator-friendly alternatives for the quantification of metoclopramide in pharmaceutical formulations.
Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: A pragmatic, randomised, double blind, placebo- controlled trial
Authors: Huet Olivier , Gargadennec Thomas , Oilleau Jean-Ferréol , Rozec Bertrand , Nesseler Nicolas , Bouglé Adrien , Kerforne Thomas , Lasocki Sigismond , Eljezi Vedat , Dessertaine Géraldine , Amour Julien , Chapalain Xavier
Published: December 2023

Background
After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality in ICU. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery.
Methods
Randomized, pragmatic, multicentre, double blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8PM to 8AM and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery.
Results
A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 26, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. In as-treated population, sleep quality assessed by numerical scale was significantly higher in the patients receiving dexmedetomidine (5.7 vs. 5; p = 0.01), as was the evaluation with the Leeds sleep evaluation questionnaire (-4.0 vs. -7.3; p = 0.02).
Conclusion
In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium.
Trial registration:
This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018)
The Complex Role of Immune Cells in Age-Related Eye Disease: Which? How?
Authors: Tan Xin , Sun Huixin , Chen Shirong
Published: December 2023

Background With the study of the eye as a specialized immune region, there is increasing evidence of the important role of immune cells for eye function. There is also an important association between immune cells and age-related eye disease (AED), but this association remains difficult to identify due to limitations of previous studies.Methods We overcame the limitations of previous studies by a novel approach (Mendelian Randomization) to investigate the effects of all 731 immune cells on common AEDs. The three approaches were used to jointly screen for trustworthy results, and then heterogeneity and horizontal pleiotropy tests were used to ensure the reliability of the results. Finally, inverse analysis was used to look for possible inverse effects. Finally, reverse MR analysis is used to look for possible reverse effects.Results Four, five, and six immune cell types have been found to be associated with cataract, glaucoma, and age-related macular degeneration separately, and the associations are both protective and risk factors. Heterogeneity analyses indicated the presence of heterogeneity, so we appropriately moderated the screening method, which combined with the results of horizontal pleiotropy together ensured the stability of the results. Reverse MR analysis did not find a reverse effect and avoided confounding due to reverse causation.Conclusion Our results uncovered associations between several classes of immune cells and common AEDs, with future potential as markers for diagnosis and treatment.
Oxidation process of 1,4-dihydropyridine, 1,4-dihydropyrimidine and pyrrolo-1,4-dihydropyrimidine: quantum chemical study
Authors: Shyshkina Mariia O. , Desenko Serhiy M.
Published: December 2023

Derivatives of 1,4-dihydropyridine, 1,4-dihydropyrimidine and its azolo analogues possess a wide range of biological activity and are involved in cellular bioenergetics. Dihydrocycles can be oxidized up to corresponding aromatic ones due to two one-electron transfers. Mechanism of the oxidation process was modeled as a stepwise change of the 1,4-dihydropyridine, 1,4-dihydropyrimidine and pyrrolo-1,4-dihydropyrimidine using different levels of theory (Hartree-Fock, MP2, DFT), basis sets, and models of environment (vacuum approximation, PCM model describing a non-specific influence of polarizing environment, or PCM model with an explicit water molecule describing both non-specific and specific influence of neighboring molecules). It is shown that the potential of the first one-electron transfer I1 depends on the level of theory and the model of an environment used in calculations. The potential of the second one-electron transfer I2 depends only on the model of an environment. The analysis of their differences calculated using different approaches has revealed the dependence only from the level of theory. Since DFT methods provide the geometric characteristics of 1,4-dihydroheterocycles closest to the experimental data, it seems reasonable to use these relatively cheap calculations to study the oxidation process.
Anthropogenic influence on the skin microbiota of a syntropic anuran in the Atlantic rainforest in northeast Brazil
Authors: Santos Lara Costa , Santos Alcina Fonsêca , Souza Paula Mariana , Almeida Anna Carolina , Moura Geraldo Jorge
Published: December 2023

Environmental disturbances caused by anthropogenic activities include a loss of habitat and a restructuring of the ecological interactions of biodiversity. Species adapted to the urban ecosystem - synanthropic - can have their cryptic interactions with microorganisms altered. In the case of anurans, the skin bacterial microbiota plays a fundamental role in host protection. However, it is not known how the composition and diversity of the skin microbiota of Scinax x-signatus, a synanthropic anuran, behaves in different fragments. Therefore, this study aimed to compare the composition and diversity of the skin microbiota of Scinax x-signatus in two areas with different degrees of anthropisation in north-eastern Brazil. Eleven individuals of S. x-signatus had their skin microbiota sampled in a control area and an anthropised area of the Recife Botanical Garden (JBR). We reported 21 bacterial isolates that belong to 11 species and 3 families (Enterobacteriaceae, Bacillaceae and Moraxellaceae). Enterobacteria were more frequent, among which we report two species with pathogenic potential found on the skin of treefrogs from the anthropised area - Escherichia coli and Klebsiella pneumoniae. In the control area, Enterobacter hormaechei was an environmental indicator specie. The anthropised area was more diverse than the control area. With the exception of E. coli and K. pneumoniae, the species found have been previously reported as part of the cutaneous microbiota of anurans. The greater diversity of the anthropised area highlights the importance of anthropogenic changes in the emergence of transmission routes for pathogens with zoonotic potential to vertebrates, an indication of environmental quality.
Effects of Tai Chi practice on postural sway for older people during COVID-19 pandemic
Authors: Wang Di , Gao Ying , Liu Xiaoxia , Pain Matthew
Published: December 2023

Tai Chi has been promoted for older people to prevent falls and may be seen as a priority exercise during coronavirus (COVID-19) pandemic. The purpose of this study was to investigate the effects of Tai Chi practice on standing balance for older people in a nursing home. Thirty-eight older people recruited during COVID-19 extended restrictions, a Tai Chi group who were regularly performed Tai Chi during the periods (n = 18, more than five-year experience) and Control group (n = 20, no Tai Chi experience). Postural sway during standing balance was quantified under four different conditions:1) eyes open (EO); 2) eyes closed (EC); 3) eyes open and cross step with right leg forward (ER) and 4) with left leg forward (EL). Significantly less postural sway was observed in the Tai Chi group, particularly during EO and EL conditions. The findings of this study support the positive effects of Tai Chi practice on balance control. During COVID-19, although older people living in the nursing home limited their outdoor mobility, Tai Chi practice may maintain their physical function on a standing balance.
An Endogenous Promoter LpSUT2 Discovered in Duckweed: a Promising Transgenic Tool for Plants
Authors: Wei Cuicui , Hu Zhubin , Wang Songhu , Tan Xiao , Jin Yanling , Yi Zhuolin , He Kaize , Zhao Leyi , Chu Ziyue , Fang Yang , Chen Shuang , Liu Penghui , Zhao Hai
Published: December 2023

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35S promoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher priming activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg/L G418 and 6.18 times at 500 mg/L G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFP was weak, while the LpSUT2:eGFP only changed slightly. This is because under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This is a previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.
Powdered Activated Carbon (PAC)-Assisted Peroxymonosulfate Activation for Efficient Urea elimination in Ultrapure water Production from Reclaimed Water
Authors: Kim Chaelin , Yoo Heeji , Lee Gyubin , Hong Hye-Jin
Published: December 2023

Urea is a problematic pollutant in reclaimed water for ultrapure water (UPW) production. The sulfate radical-based advanced oxidation process (SR-AOP) has been recognized as an effective method for urea degradation. However, conventional metal-based catalysts for peroxymonosulfate (PMS) activation are unsuitable for UPW production due to issues related to metal ion leaching. In this study, the use of powdered activated carbon (PAC) was investigated for the removal of urea from reclaimed water. The PAC exhibited a high degree of defects (ID/IG = 1.709) and various surface oxygen functional groups (C-OH, C = O, and C-O), which greatly enhanced its catalytic capability. The PAC significantly facilitated PMS activation in the PMS + PAC system, leading to the complete urea decomposition. The PMS + PAC system demonstrated excellent urea removal efficiency within a wide pH range, except for pH < 3. Among the various anions present, the CO32 − and PO43 − inhibited urea degradation, while the coexistence of Cl − promoted urea removal. Furthermore, the feasibility test was evaluated using actual reclaimed water. The quenching test revealed that SO4−·, ·OH, and O2−· played crucial roles in the degradation of urea in the PAC-assisted SR-AOP. The oxygen functional groups (C-OH and O-C = O) and defect sites of PAC clearly contributed to PMS activation.
Exosomes miR-24-3p Target S1PR1 to Promote Angiogenesis and Induce Tumor Metastasis in non-small cell lung cancer
Authors: Shen Lanxiao , Zhou Xiaobo , Peng Zheng , Ren Siyan , Meng Rui , Huang Wenduo , Yang Rongbo , Fang Ya , Pan Huanle , Cao Zhuo , Jin Xiance , Xie Congying
Published: December 2023

Background
Angiogenesis is critical to the growth and metastasis of malignant tumors. The aim of this study is to investigate the molecular mechanism of exosome miR-24-3p in angiogenesis and metastasis of non-small cell lung cancer (NSCLC).
Materials and methods
Plasma samples of 60 patients with confirmed NSCLC, 20 patients with benign lung disease, 20 healthy controls, and cancer and paracancerous tissues of 12 NSCLC patients were collected in authors’ hospital from June 2020 to December 2020 for the screening of reliable exocytotic microRNAs. Six cell lines were used to investigate the effect of exosome-derived miR-24-3p on vascular endothelial cells in tumors to clarify the pathways promoting tumor migration and proliferation. Animal experiments were conducted to further verify the function of miR-24-3p.
Results
The expression levels of miR-24-3p in plasma extracellular vesicles of NSCLC patients were significantly increased and correlated positively with disease stage. The miR-24-3p promoted angiogenesis and increased vascular permeability by inhibiting the expression of sphingosinel-phosphate receptor 1(S1PR1) in endothelial cells, indicating S1PR1 is a downstream target gene of miR-24-3p, which binds to the S1PR1 3’- UTR region.
Conclusions
Tumor-derived exosome miR-24-3p could enter vascular endothelial cells and promote angiogenesis and vascular permeability in NSCLC, which also enter the circulatory system to improve the pre-metastasis microenvironment in distant organs and ultimately promote the occurrence of tumor metastasis. miR-24-3p is a promising potential molecular biomarker and new drug therapeutic target for patients with NSCLC.
Noninvasive monitoring technologies to identify discomfort and distressing symptoms in persons with limited communication at the end of life: A scoping review
Authors: Xu Jingyuan , Smaling Hanneke JA , Schoones Jan W , Achterberg Wilco P , Steen Jenny T van der
Published: December 2023

Background
Discomfort and distressing symptoms are common at the end of life, while people in this stage are often no longer able to express themselves. Technologies may aid clinicians in detecting and treating these symptoms to improve end-of-life care. This review provides an overview of noninvasive monitoring technologies that may be applied to persons with limited communication at the end of life to identify discomfort or distressing symptoms.
Methods
A systematic search was performed in nine databases, and experts were consulted. Manuscripts were included if they were written in English, Dutch, German, French, Japanese or Chinese, if the monitoring technology measured discomfort or distressing symptoms, was noninvasive, could be continuously administered for 4 hours and was potentially applicable for bed-ridden people. The screening was performed by two researchers independently. Information about the technology, its clinimetrics (validity, reliability, sensitivity, specificity, responsiveness), acceptability, and feasibility were extracted.
Results
Of the 3,414 identified manuscripts, 229 met the eligibility criteria. A variety of monitoring technologies were identified, including actigraphy, brain activity monitoring, electrocardiography, electrodermal activity monitoring, surface electromyography, incontinence sensors, multimodal systems, and noncontact monitoring systems. The main symptoms monitored by these technologies were sleep, level of consciousness, risk of pressure ulcers, urinary incontinence, agitation, and pain. For the end-of-life phase, brain activity monitors could be helpful and acceptable to monitor the level of consciousness during palliative sedation. However, no manuscripts have reported on the clinimetrics, feasibility, and acceptability of the other technologies for the end-of-life phase.
Conclusions
Noninvasive monitoring technologies are available to measure common symptoms at the end of life. Future research should evaluate the quality of evidence provided by existing studies and investigate the feasibility, acceptability, and usefulness of these technologies in the end-of-life setting. Guidelines for studies on healthcare technologies should be better implemented and further developed.
Cervical Cancer Prevention in Iran: A policy Brief on Challenges and Evidence-Based Recommendations
Authors: Pirani Narges , Takian Amirhossein , Bagherzadeh Rafat , Jafari Mehdi
Published: December 2023

Objective: Based on the International Agency for Research on Cancer (IARC), the prevalence and incidence of cervical cancer is increasing globally, especially in low and middle-income countries. Hence, developing a policy brief for meaningful formulation and successful implementation for prevention and control of cancer programs can guide policymakers.
Methods: This policy brief drew from a Ph.D. thesis on policy analysis of cervical cancer prevention in Iran. In this qualitative study, first a systematic review was conducted to compare the economic impact of combined strategies versus testing alone for cervical cancer screening worldwide. Next, a qualitative analysis of cervical cancer prevention and early detection was accomplished from July 2020 to September 2021, in Iran. Finally, to achieve the most important challenges, some solutions were recommended following the participants’ statements and review study.
Results: Compared with cytology-based screening tests or Visual Inspection with Acetic Acid, Human papillomavirus infection testing, alone or combined with other tests, has been reported as a cost-effective cervical cancer screening strategy worldwide, especially in high-income settings. In Iran, the low coverage of cervical cancer screening; inadequate knowledge, awareness and education on cervical cancer, and the economic problems of implementing new cervical cancer prevention strategies were all identified as the main challenges in Iran.
Conclusions: It is recommended to improve the purchasing power for vaccine procurement programs through coordinated action across global partners, i.e., Word Health Organization, Global Alliance for Vaccines and Immunization (Gavi), the Global Fund to Fight Aids, TB & Malaria, the Union for International Cancer Control, and the World Bank, in addition to collaboration with the private sector manufacturers of vaccines, diagnostics, and treatment equipment. Moreover, using educational models of health promotion can be helpful to increase public knowledge and awareness on cervical cancer prevention.
Human blood metabolites and calculus of kidney: A bidirectional Mendelian randomized analysis
Authors: ChenTianze Tianze , Zhu Rui , Zhao Xiaojun , Huang Yuhua , Qiu Feng , Pu Jinxian
Published: December 2023

Background Kidney stones affect people worldwide and place a burden on public healthcare systems. Understanding the underlying mechanism of its occurrence is helpful for its prevention. The analysis of serum metabolites may facilitate a more comprehensive comprehension of the underlying biological processes. Mendelian randomization (MR) can furnish valuable insights into the causality of associations.
Methods We applied a two-sample MR analysis to evaluate relationships between 1,091 metabolites and 309 metabolite ratios and kidney calculus. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of the exposure on the outcome, while The Cochran Q test statistic was utilized to quantify heterogeneity. The MR-PRESSO global test and MR-PRESSO outlier test were employed to calculate the horizontal pleiotropy and remove the outlying SNPs, respectively. Additionally, we conducted a "leave-one-out" sensitivity analysis to identify any potential impacts. We also performed reverse MR Analysis to determine the potential causal relationship between kidney stones and metabolites.
Results We identified 2 known (1 risk and 1 protective) and 1 unknown serum metabolites associated with kidney calculus. The results of the IVW analysis (Figure 2) elucidated that causal effects of the genetically predicted increased abundance of blood sugar levels (OR: 1.002, 95% CI: 1.001–1.003) at the genus level were associated with the higher risk of calculus of kidney, while the increased abundance of maltotriose levels (OR: 0.998, 95% CI: 0.997–0.999) and X-24947 levels (OR: 0.999, 95% CI: 0.998–0.999) at genus level were associated with the lower risk of calculus of kidney. The reverse MR suggests a causal relationship between the occurrence of kidney stones and blood sugar levels (OR = 7.77e+08, 95% CI = 12.956 – 4.66e+16, p = 0.025, IVW).
Conclusion Our study further validates the causal relationship between kidney stones and blood sugar levels, and identifies two other metabolites that act as protective factors for kidney stones, which may help prioritize metabolic features for kidney calculus mechanistic research and further evaluation of their potential role in risk assessment.