bluuebunny/crossref_metadata_2025 huggingface dataset:
Discerning the role of polymyxin B nonapeptide in restoring the antibacterial activity of azithromycin against antibiotic-resistant Escherichia coli
Authors: Al-Marzooq Farah , Ghazawi Akela , Tariq Saeed , Daoud Lana , Collyns Timothy
Published: September 2022

Antimicrobial resistance is a global public health threat. Antibiotic development pipeline has few new drugs; therefore, using antibiotic adjuvants has been envisioned as a successful method to preserve existing medications to fight multidrug-resistant (MDR) pathogens. In this study, we investigated the synergistic effect of a polymyxin derivative known as polymyxin B nonapeptide (PMBN) with azithromycin (AZT). A total of 54 Escherichia coli strains were first characterized for macrolide resistance genes, and susceptibility to different antibiotics, including AZT. A subset of 24 strains was then selected for synergy testing by the checkerboard assay. PMBN was able to re-sensitize the bacteria to AZT, even in strains with high minimum inhibitory concentrations (MIC: 32 to ≥128 μg/ml) for AZT, and in strains resistant to the last resort drugs such as colistin and meropenem. The fractional inhibitory concentration index was lower than 0.5, demonstrating that PMBN and AZT combinations had a synergistic effect. The combinations worked efficiently in strains carrying mphA gene encoding macrolide phosphotransferase which can cause macrolide inactivation. However, the combinations were inactive in strains having an additional ermB gene encoding macrolide methylase which causes ribosomal drug target alteration. Killing kinetics study showed a significant reduction of bacterial growth after 6 h of treatment with complete killing achieved after 24 h. Transmission electron microscopy showed morphological alterations in the bacteria treated with PMBN alone or in combination with AZT, with evidence of damage to the outer membrane. These results suggested that PMBN acted by increasing the permeability of bacterial outer membrane to AZT, which was also evident using a fluorometric assay. Using multiple antimicrobial agents could therefore be a promising strategy in the eradication of MDR bacteria. PMBN is a good candidate for use with other antibiotics to potentiate their activity, but further studies are required in vivo. This will significantly contribute to resolving antimicrobial resistance crisis.
Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
Authors: Huang Shan , Thomsson Kristina A. , Jin Chunsheng , Ryberg Henrik , Das Nabangshu , Struglics André , Rolfson Ola , Björkman Lena I. , Eisler Thomas , Schmidt Tannin A. , Jay Gregory D. , Krawetz Roman , Karlsson Niclas G.
Published: September 2022

The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation.
Observing protein dynamics during DNA-lesion bypass by the replisome
Authors: Wilkinson Elise M. , Spenkelink Lisanne M. , van Oijen Antoine M.
Published: September 2022

Faithful DNA replication is essential for all life. A multi-protein complex called the replisome contains all the enzymatic activities required to facilitate DNA replication, including unwinding parental DNA and synthesizing two identical daughter molecules. Faithful DNA replication can be challenged by both intrinsic and extrinsic factors, which can result in roadblocks to replication, causing incomplete replication, genomic instability, and an increased mutational load. This increased mutational load can ultimately lead to a number of diseases, a notable example being cancer. A key example of a roadblock to replication is chemical modifications in the DNA caused by exposure to ultraviolet light. Protein dynamics are thought to play a crucial role to the molecular pathways that occur in the presence of such DNA lesions, including potential damage bypass. Therefore, many assays have been developed to study these dynamics. In this review, we discuss three methods that can be used to study protein dynamics during replisome–lesion encounters in replication reactions reconstituted from purified proteins. Specifically, we focus on ensemble biochemical assays, single-molecule fluorescence, and cryo-electron microscopy. We discuss two key model DNA replication systems, derived from Escherichia coli and Saccharomyces cerevisiae. The main methods of choice to study replication over the last decades have involved biochemical assays that rely on ensemble averaging. While these assays do not provide a direct readout of protein dynamics, they can often be inferred. More recently, single-molecule techniques including single-molecule fluorescence microscopy have been used to visualize replisomes encountering lesions in real time. In these experiments, individual proteins can be fluorescently labeled in order to observe the dynamics of specific proteins during DNA replication. Finally, cryo-electron microscopy can provide detailed structures of individual replisome components, which allows functional data to be interpreted in a structural context. While classic cryo-electron microscopy approaches provide static information, recent developments such as time-resolved cryo-electron microscopy help to bridge the gap between static structures and dynamic single-molecule techniques by visualizing sequential steps in biochemical pathways. In combination, these techniques will be capable of visualizing DNA replication and lesion encounter dynamics in real time, whilst observing the structural changes that facilitate these dynamics.
Case report: Traumatic median neuropathy in the distal forearm after massage therapy
Authors: Suh Mi Rim , Song Jun Hyeong , Park Yongbum , Lee Seok Hyeon , Ahn Jaeki
Published: September 2022

Median nerve damage caused by trauma is rare, especially after the massage therapy. There have been no reports of median neuropathy in the distal forearm following massage therapy. A 61-year-old man developed paresthesia and numbness in the right hand after two sessions of massage therapy. Electrophysiologic studies, ultrasound, and magnetic resonance imaging were used to localize and confirm the median nerve lesion in the distal forearm. Ultrasound-guided perineural steroid injection and oral pregabalin were administered. At the 1-month follow-up, more than 80% of the sensory symptoms had resolved, and the results of the sensory nerve conduction study and ultrasound showed improvement. Although massage-induced mononeuropathy is uncommon, massage therapy should be performed carefully to avoid complications.
Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice
Authors: Jia Yuxiang , Tang Lele , Yao Yu , Zhuo Limin , Qu Dongxiao , Chen Xingxing , Ji Yonghua , Tao Jie , Zhu Yudan
Published: September 2022

Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities.
Infra-Low Frequency Neurofeedback rapidly ameliorates schizophrenia symptoms: A case report of the first session
Authors: Nestoros Joannis N. , Vallianatou Nionia G.
Published: September 2022

A 38-year-old army officer started therapy in 2020 with a four-year history of auditory hallucinations and delusions of reference, persecution and grandeur, symptoms that were resistant to traditional antipsychotic medications. He follows an integrative psychotherapy program that aims to reduce his anxiety, continues his antipsychotic medications, and has Infra-Low Frequency Neurofeedback. After his initial assessment he had a 40 min session of Infra-Low Frequency Neurofeedback before any other kind of intervention. Before and immediately after the session he completed the SCL-90 scale and the Visual Analog Scale covering 20 aspects of his psychological and physical state as well as his schizophrenic symptoms. This first Neurofeedback session had dramatic effects on his psychotic symptoms, levels of anxiety and psychosomatic condition, before his first psychotherapy session and/or any changes in his antipsychotic medication. The above results have great importance due to the severity and chronicity of schizophrenia. Informed consent was obtained from the participant for the publication of this case report (including all data and images).
Communication in non-communicable diseases (NCDs) and role of immunomodulatory nutraceuticals in their management
Authors: Kumar Abhiram , Sakhare Kalyani , Bhattacharya Dwaipayan , Chattopadhyay Raktim , Parikh Purvish , Narayan Kumar P. , Mukherjee Anubhab
Published: September 2022

Conveyance of pathogens between organisms causes communicable diseases. On the other hand, a non-communicable disease (NCD) was always thought to have no causative transmissible infective agents. Today, this clear distinction is increasingly getting blurred and NCDs are found to be associated with some transmissible components. The human microbiota carries a congregation of microbes, the majority and the most widely studied being bacteria in the gut. The adult human gut harbors ginormous inhabitant microbes, and the microbiome accommodates 150-fold more genes than the host genome. Microbial communities share a mutually beneficial relationship with the host, especially with respect to host physiology including digestion, immune responses, and metabolism. This review delineates the connection between environmental factors such as infections leading to gut dysbiosis and NCDs and explores the evidence regarding possible causal link between them. We also discuss the evidence regarding the value of appropriate therapeutic immunomodulatory nutritional interventions to reduce the development of such diseases. We behold such immunomodulatory effects have the potential to influence in various NCDs and restore homeostasis. We believe that the beginning of the era of microbiota-oriented personalized treatment modalities is not far away.
Minimal residual disease in EGFR-mutant non-small-cell lung cancer
Authors: Bain Nathan T. , Wang Yang , Arulananda Surein
Published: September 2022

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an effective treatment for EGFR-mutant non-small-cell lung cancer (NSCLC), however most patients invariably relapse after a period of minimal residual disease (MRD). This mini-review explores the mechanistic pathways leading to tumour dormancy, cellular senescence and epigenetic changes involving YAP/TEAD activation. We describe the various approaches of utilising TKIs in combination with agents to intensify initial depth of response, enhance apoptosis and target senescence-like dormancy. This mini-review will also highlight the potential novel therapies under development targeting MRD to improve outcomes for patients with EGFR-mutant NSCLC.
DIRAS3, GPR171 and RAC2 were identified as the key molecular patterns associated with brain metastasis of breast cancer
Authors: Dai Ji , Chen Qi , Li Guoqing , Chen Mengze , Sun Haohang , Yan Meidi
Published: September 2022

Objective

Brain metastasis is a primary cause of morbidity and mortality in breast cancer patients. Therefore, elucidation and understanding of the underlying mechanisms are essential for the development of new therapeutic strategies.

Methods

Differential gene analysis was performed for those with and without distant metastasis in The Cancer Genome Atlas (TCGA) database and those with and without recurrence in the brain in the dataset GSE12276. The differentially expressed genes procured from the two databases were intersected to obtain the intersecting genes associated with brain metastasis. Thereafter, the intersecting genes were subjected to LASSO model construction to screen for prognostic genes. The expression of the obtained genes in metastatic breast cancer was observed, and survival analysis was performed. Finally, GSEA analysis of the obtained genes was performed, and the relationship between them and immune cells was explored.

Results

A total of 335 differential genes for the occurrence of distant metastases were obtained based on the TCGA database. A total of 1070 differential genes for recurrence to the brain were obtained based on the dataset GSE12276. The Venn diagram showed 24 intersecting genes associated with brain metastasis. The LASSO prognostic model contained a total of five genes (GBP2, GPR171, DIRAS3, RAC2, and CACNA1D). Expression difference analysis showed that GBP2, GPR171, DIRAS3, and RAC2 were significantly down-regulated in expression in metastatic breast cancer compared with primary breast cancer tumors. Only GPR171, DIRAS3, and RAC2 were strongly correlated with the overall survival of breast cancer patients. Their correlation analysis with immune cells showed that the correlation coefficient between the expression levels of DIRAS3 and immune cells was low, and the expression levels of GPR171 and RAC2 were more closely correlated with B cells and macrophages.

Conclusions

The expression of DIRAS3, GPR171 and RAC2, genes associated with brain metastasis, was reduced in metastatic breast cancer, and GPR171 was found to promote brain metastasis of breast cancer cells by inducing B cells and thereby.
Aquaporins: New players in breast cancer progression and treatment response
Authors: Charlestin Verodia , Fulkerson Daniel , Arias Matus Carlos E. , Walker Zachary T. , Carthy Kevin , Littlepage Laurie E.
Published: September 2022

Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patient’s response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment.
A review study of fetal circulatory models to develop a digital twin of a fetus in a perinatal life support system
Authors: van Willigen Bettine G. , van der Hout-van der Jagt M. Beatrijs , Huberts Wouter , van de Vosse Frans N.
Published: September 2022

Background

Preterm birth is the main cause of neonatal deaths with increasing mortality and morbidity rates with decreasing GA at time of birth. Currently, premature infants are treated in neonatal intensive care units to support further development. However, the organs of, especially, extremely premature infants (born before 28 weeks of GA) are not mature enough to function optimally outside the womb. This is seen as the main cause of the high morbidity and mortality rates in this group. A liquid-filled incubator, a so-called PLS system, could potentially improve these numbers for extremely premature infants, since this system is designed to mimic the environment of the natural womb. To support the development and implementation of such a complex system and to interpret vital signals of the fetus during a PLS system operation, a digital twin is proposed. This mathematical model is connected with a manikin representing the digital and physical twin of the real-life PLS system. Before developing a digital twin of a fetus in a PLS system, its functional and technical requirements are defined and existing mathematical models are evaluated.

Method and results

This review summarizes existing 0D and 1D fetal circulatory models that potentially could be (partly) adopted for integration in a digital twin of a fetus in a PLS system based on predefined requirements. The 0D models typically describe hemodynamics and/or oxygen transport during specific events, such as the transition from fetus to neonate. Furthermore, these models can be used to find hemodynamic differences between healthy and pathological physiological states. Rather than giving a global description of an entire cardiovascular system, some studies focus on specific organs or vessels. In order to analyze pressure and flow wave profiles in the cardiovascular system, transmission line or 1D models are used. As for now, these models do not include oxygen transport.

Conclusion

This study shows that none of the models identified in literature meet all the requirements relevant for a digital twin of a fetus in a PLS system. Nevertheless, it does show the potential to develop this digital twin by integrating (parts) of models into a single model.
Automated identification of innocent Still's murmur using a convolutional neural network
Authors: Shekhar Raj , Vanama Ganesh , John Titus , Issac James , Arjoune Youness , Doroshow Robin W.
Published: September 2022

Background

Still's murmur is the most prevalent innocent heart murmur of childhood. Auscultation is the primary clinical tool to identify this murmur as innocent. Whereas pediatric cardiologists routinely perform this task, primary care providers are less successful in distinguishing Still's murmur from the murmurs of true heart disease. This results in a large number of children with a Still's murmur being referred to pediatric cardiologists.

Objectives

To develop a computer algorithm that can aid primary care providers to identify the innocent Still's murmur at the point of care, to substantially decrease over-referral.

Methods

The study included Still's murmurs, pathological murmurs, other innocent murmurs, and normal (i.e., non-murmur) heart sounds of 1,473 pediatric patients recorded using a commercial electronic stethoscope. The recordings with accompanying clinical diagnoses provided by a pediatric cardiologist were used to train and test the convolutional neural network-based algorithm.

Results

A comparative analysis showed that the algorithm using only the murmur sounds recorded at the lower left sternal border achieved the highest accuracy. The developed algorithm identified Still's murmur with 90.0% sensitivity and 98.3% specificity for the default decision threshold. The area under the receiver operating characteristic curve was 0.943.

Conclusions

Still's murmur can be identified with high accuracy with the algorithm we developed. Using this approach, the algorithm could help to reduce the rate of unnecessary pediatric cardiologist referrals and use of echocardiography for a common benign finding.
Breaking barriers in establishing simulation in India–A collaborative approach by pediatric simulation training and research society (PediSTARS)
Authors: Jamalpuri Vijayanand , Gunda Ranjit Kumar , Ramachandra Geethanjali , Thyagarajan Sujatha , Shetty Rakshay , Seethamraju Rajasri R. , Nadkarni Vinay M. , Shepherd Michael
Published: September 2022

Simulation based training (SBT) plays a pivotal role in quality improvement and patient safety. Simulation is not only for training health care professionals but also an excellent tool for systems and facility changes which will potentially improve patient safety and ultimately outcomes. SBT is already established both as a training modality, and as a quality improvement tool in high income countries. It’s use in low and middle-income countries (LMIC), including India, however, is sporadic and variable because of multiple barriers. The barriers for establishment of simulation are lack of knowledge about benefits of simulation, psychological resistance, cost, and lack of trained faculty. PediSTARS (Pediatric Simulation Training and Research Society), a simulation society was founded in August 2013 to spread the simulation across India and thus improve the quality and safety of health care using SBT. In this article we discuss various barriers for healthcare simulation in India and also our attempts to overcome some of these barriers by collaborative practice.
Case report: Leukemia cutis as the first manifestation of chronic neutrophilic leukemia in a 6-year-old girl
Authors: Zhou Ya Bin , Yao Jia Feng , Xu Zi Gang , Wu Rui Hui
Published: September 2022

Chronic neutrophilic leukemia (CNL) is a rare BCR-ABL negative myeloproliferative neoplasm that usually affects older adults with a poor prognosis. Leukemia cutis is an extramedullary manifestation of leukemia and may be misdiagnosed by dermatologists. Here, we describe a case of CNL in a 6-year-old Chinese girl with leukemia cutis as the first manifestation. Her skin rashes failed to attract the attention of dermatologists in early stages. The diagnosis was confirmed by peripheral smear, bone marrow studies, genomic analysis and skin biopsy.
Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis
Authors: Yang Longfei , Zhang Yuwei , Wang Yang , Jiang Peng , Liu Fengping , Feng Ninghan
Published: September 2022

Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.
Study on the stability of particle packing structure based on cells
Authors: Hua Yunsong , Xin Yujiao , Dai Hongyang , Yang Hui , Chi Zhipeng , Li Ran
Published: September 2022

The macroscopic mechanical property and the stability of granular mechanics system are determined by packing structure. Cells play a fundamental role in granular statistical mechanics and thus cells were utilized in this paper to research the packing structure of disk particles and gear particles in a two-dimensional cubic container. The probability distribution of cell order satisfies the exponential function distribution and is independent of intergranular friction, the size of system and vibration. Furthermore, it is observed that friction and system size are the key factors affecting the stability of particle packing structure. Significantly, the relationship between volume fraction and packing structure of disk particles is established under vibration. The experimental results reveal the characteristics of ordered packing structure of disordered particle system in mesoscale and provide data reference for perfecting the theory of particle mechanics.
Non-invasive estimation of QLV from the standard 12-lead ECG in patients with left bundle branch block
Authors: Melgaard Jacob , van Dam Peter M. , Sommer Anders , Fruelund Patricia , Nielsen Jens Cosedis , Riahi Sam , Graff Claus
Published: September 2022

Background: Cardiac resynchronization therapy (CRT) is a treatment for patients with heart failure and electrical dyssynchrony, i.e., left bundle branch block (LBBB) ECG pattern. CRT resynchronizes ventricular contraction with a right ventricle (RV) and a left ventricle (LV) pacemaker lead. Positioning the LV lead in the latest electrically activated region (measured from Q wave onset in the ECG to LV sensing by the left pacemaker electrode [QLV]) is associated with favorable outcome. However, optimal LV lead placement is limited by coronary venous anatomy and the inability to measure QLV non-invasively before implantation. We propose a novel non-invasive method for estimating QLV in sinus-rhythm from the standard 12-lead ECG.

Methods: We obtained 12-lead ECG, LV electrograms and LV lead position in a standard LV 17-segment model from procedural recordings from 135 standard CRT recipients. QLV duration was measured post-operatively. Using a generic heart geometry and corresponding forward model for ECG computation, the electrical activation pattern of the heart was fitted to best match the 12-lead ECG in an iterative optimization procedure. This procedure initialized six activation sites associated with the His-Purkinje system. The initial timing of each site was based on the directions of the vectorcardiogram (VCG). Timing and position of the sites were then changed iteratively to improve the match between simulated and measured ECG. Noninvasive estimation of QLV was done by calculating the time difference between Q-onset on the computed ECG and the activation time corresponding to centroidal epicardial activation time of the segment where the LV electrode is positioned. The estimated QLV was compared to the measured QLV. Further, the distance between the actual LV position and the estimated LV position was computed from the generic ventricular model.

Results: On average there was no difference between QLV measured from procedural recordings and non-invasive estimation of QLV (ΔQLV=−3.0±22.5 ms, p=0.12). Median distance between actual LV pacing site and the estimated pacing site was 18.6 mm (IQR 17.3 mm).

Conclusion: Using the standard 12-lead ECG and a generic heart model it is possible to accurately estimate QLV. This method may potentially be used to support patient selection, optimize implant procedures, and to simulate optimal stimulation parameters prior to pacemaker implantation.
Canadian aging and inactivity study: Spaceflight-inspired exercises during head-down tilt bedrest blunted reductions in muscle-pump but not cardiac baroreflex in older persons
Authors: Sadeghian Farshid , Divsalar Donya Naz , Fadil Rabie , Tavakolian Kouhyar , Blaber Andrew P.
Published: September 2022

As part of the first Canadian aging and inactivity study (CAIS) we assessed the efficacy of space-based exercise countermeasures for maintenance of cardiac and muscle-pump baroreflex in older persons during bedrest. An initiative of the Canadian Space Agency, Canadian Institutes of Health Research and the Canadian Frailty Network, CAIS involved 14 days of 6-degree head-down tilt bedrest (HDBR) with (Exercise) or without (Control) combined upper and lower body strength, aerobic, and high-intensity interval training exercise countermeasures. Twenty healthy men and women aged 55 to 65, randomly divided into control and exercise groups (male control (MC, n = 5), male exercise (ME, n = 5), female control (FC, n = 6), female exercise (FE, n = 4)) (age: 58.7 ± 0.5 years, height: 1.67 ± 0.02 m, body mass: 70.2 ± 3.2 kg; mean ± SEM), completed the study. Cardiac and muscle-pump baroreflex activity were assessed with supine-to-stand tests. Wavelet transform coherence was used to characterise cardiac and muscle-pump baroreflex fraction time active (FTA) and gain values, and convergent cross-mapping was used to investigate causal directionality between blood pressure (BP) and heart rate, as well as BP and lower leg muscle electromyography (EMG). Seven of the twenty participants were unable to stand for 6 minutes after HDBR, with six of those being female. Our findings showed that 2 weeks of bedrest impaired skeletal muscle’s ability to return blood to the venous circulation differently across various sexes and intervention groups. Comparing values after bed rest with before bed rest values, there was a significant increase in heart rates (∆ of +25%; +17% in MC to +33% in FC; p < 0.0001), beat-to-beat EMG decreased (∆ of −43%; −25% in ME to −58% in MC; p < 0.02), while BP change was dependent on sex and intervention groups. Unlike their male counterparts, in terms of muscle-pump baroreflex, female participants had considerably decreased FTA after HDBR (p < 0.01). All groups except female control demonstrated parallel decreases in cardiac active gain and causality, while the FC demonstrated an increase in cardiac causality despite a similar decline in cardiac active gain. Results showed that the proposed exercises may alleviate muscle-pump baroreflex declines but could not influence the cardiac baroreflex decline from 14 days of inactivity in older adults.
Early enzyme replacement therapy prevents dental and craniofacial abnormalities in a mouse model of mucopolysaccharidosis type VI
Authors: Nagpal Rohit , Georgi Gina , Knauth Sarah , Schmid-Herrmann Carmen , Muschol Nicole , Braulke Thomas , Kahl-Nieke Bärbel , Amling Michael , Schinke Thorsten , Koehne Till , Petersen Julian
Published: September 2022

Mucopolysaccharidosis VI (MPS VI) is a hereditary lysosomal storage disease caused by the absence of the enzyme arylsulfatase B (ARSB). Craniofacial defects are common in MPS VI patients and manifest as abnormalities of the facial bones, teeth, and temporomandibular joints. Although enzyme replacement therapy (ERT) is the treatment of choice for MPS VI, the effects on the craniofacial and dental structures are still poorly understood. In this study, we used an Arsb-deficient mouse model (Arsbm/m) that mimics MPS VI to investigate the effects of ERT on dental and craniofacial structures and compared these results with clinical and radiological observations from three MPS VI patients. Using micro-computed tomography, we found that the craniofacial phenotype of the Arsbm/m mice was characterized by bone exostoses at the insertion points of the masseter muscles and an overall increased volume of the jaw bone. An early start of ERT (at 4 weeks of age for 20 weeks) resulted in a moderate improvement of these jaw anomalies, while a late start of ERT (at 12 weeks of age for 12 weeks) showed no effect on the craniofacial skeleton. While teeth typically developed in Arsbm/m mice, we observed a pronounced loss of tooth-bearing alveolar bone. This alveolar bone loss, which has not been described before in MPS VI, was also observed in one of the MPS VI patients. Interestingly, only an early start of ERT led to a complete normalization of the alveolar bone in Arsbm/m mice. The temporomandibular joints in Arsbm/m mice were deformed and had a porous articular surface. Histological analysis revealed a loss of physiological cartilage layering, which was also reflected in an altered proteoglycan content in the cartilage of Arsbm/m mice. These abnormalities could only be partially corrected by an early start of ERT. In conclusion, our results show that an early start of ERT in Arsbm/m mice achieves the best therapeutic effects for tooth, bone, and temporomandibular joint development. As the MPS VI mouse model in this study resembles the clinical findings in MPS VI patients, our results suggest enzyme replacement therapy should be started as early as possible.
Metabolomic and transcriptomic analyses reveal a MYB gene, CsAN1, involved in anthocyanins accumulation separation in F1 between ‘Zijuan’ (Camellia sinensis var. assamica) and ‘Fudingdabaicha’ (C. sinensis var. sinensis) tea plants
Authors: Huang Feiyi , Duan Jihua , Lei Yu , Kang Yankai , Luo Yi , Chen Yingyu , Ding Ding , Li Saijun
Published: September 2022

‘Zijuan’ (Camellia sinensisvar.assamica), a somatic mutant with purple foliage and stem selected from the Yunnan Daye cultivar, has been well developed owing to abnormal pattern of anthocyanin accumulation. However, the genetic basis for the specific accumulation of phloem glycosides is not clear. Tea plants are self-incompatible, so parents with large differences in foliage color were used for crosses to investigate the genetic mechanism of anthocyanins. In this study, ‘Zijuan’ and green foliage cultivar ‘Fudingdabaicha’ (C. sinensisvar.sinensis) were used as female and male parents, respectively, to generated F1 hybrid progenies with various anthocyanin contents. In order to decipher the genetic rules of anthocyanins accumulation, we performed widely targeted metabolic and transcriptomic profiling. The results showed that cyanidin-3-O-galactoside, delphinidin-3-O-galactoside and petunidin-3-O-galactoside were the major types of anthocyanins and factors directly led to the color variation between parents and F1 plants. Transcriptomic analyses suggested the significant up-regulation of anthocyanidin synthase gene (CsANS1) andCsAN1, a MYB family gene positively regulated the expression ofCsANS1, in anthocyanin-rich tea plants. Furthermore, the deletion mutation ofCsAN1was found by cloning and alignment in anthocyanin-lacking cultivars. Taken together, the function deficiency ofCsAN1is predominantly responsible for the inability of anthocyanins accumulation, and this trait is heritable in progenies through hybridization. The present study elucidated the molecular basis of leaf purple trait formation in ‘zijuan’ and ‘Fudingdabaicha’ and their F1 plants, which helps to elucidate the genetic mechanism of leaf anthocyanin accumulation regulation in tea plants, and the results provide a research reference for the selection and breeding of high anthocyanin type tea varieties.
Combined effects of Bacillus sp. M6 strain and Sedum alfredii on rhizosphere community and bioremediation of cadmium polluted soils
Authors: Abid Abbas Ali , Zhang Gengmiao , He Dan , Wang Huanhe , Batool Itrat , Di Hongjie , Zhang Qichun
Published: September 2022

Concerns regarding inevitable soil translocation and bioaccumulation of cadmium (Cd) in plants have been escalating in concomitance with the posed phytotoxicity and threat to human health. Exhibiting a Cd tolerance, Bacillus sp. M6 strain has been reported as a soil amendment owing to its capability of reducing metal bioavailability in soils. The present study investigated the rhizospheric bacterial community of the Cd hyperaccumulator Sedum alfredii using 16S rRNA gene sequencing. Additionally, the Cd removal efficiency of strain Bacillus sp. M6 was enhanced by supplementing with biochar (C), glutamic acid (G), and rhamnolipid (R) to promote the phytoremediation effect of hyperaccumulator S. alfredii. To the best of our knowledge, this is the first time the amendments such as C, G, and R together with the plant-microbe system S. alfredii-Bacillus sp. M6 has been used for Cd bioremediation. The results showed that soil CaCl2 and DTPA (Diethylenetriamine penta-acetic acid) extractable Cd increased by 52.77 and 95.08%, respectively, in all M6 treatments compared to unamended control (CK). Sedum alfredii with Bacillus sp. M6 supplemented with biochar and rhamnolipid displayed a higher phytoremediation effect, and the removal capability of soil Cd (II) reached up to 16.47%. Moreover, remediation of Cd polluted soil by Bacillus sp. M6 also had an impact on the soil microbiome, including ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), and cadmium transporting ATPase (cadA) genes. Quantitative PCR analysis confirmed the Bacillus sp. M6 strain increased the abundance of AOB and cadA in both low Cd (LC) and high Cd (HC) soils compared to AOA gene abundance. Besides, the abundance of Proteobacteria and Actinobacteria was found to be highest in both soils representing high tolerance capacity against Cd. While Firmicutes ranked third, indicating that the additionof strain could not make it the most dominant species. The results suggested the presence of the hyperaccumulator S. alfredii and Cd tolerant strain Bacillus sp. M6 supplemented with biochar, and rhamnolipid, play a unique and essential role in the remediation process and reducing the bioavailability of Cd.
An analysis of the trickle-down effect of supervisor knowledge hiding on subordinate knowledge hiding based on displaced aggression theory
Authors: Tang Yanzhao , Zhu Hong-Ming , Du Xingcheng
Published: September 2022

The harm of horizontal knowledge hiding behavior (colleague–colleague) to individuals and organizations has been discussed and confirmed by many studies. The negative consequences of top-down (supervisor–subordinate) knowledge hiding have now emerged as a new focus of research. This study aims to enrich the understanding of the consequences of supervisor knowledge hiding by exploring its trickle-down effect and mechanism. Based on the displaced aggression theory in psychology, this paper analyses and examines the cognitive psychological process and mechanism informing employee knowledge hiding from colleagues when faced with their supervisor’s malicious knowledge hiding behavior. Using a three-stage time-lag questionnaire survey strategy, we collect 233 valid samples of full-time employees from representative provinces and cities in China, covering multiple industries. The following findings are observed: (1) Supervisor knowledge hiding from subordinates (SKHS) positively affects subordinate knowledge hiding from colleagues (SKHC); (2) Revenge motivation plays a mediating role; (3) Traditionality weakens the influence of supervisor knowledge hiding on a subordinates’ revenge motivation. This study confirms the trickle-down effects of supervisor knowledge hiding behavior, extends research on the consequences of top-down knowledge hiding and its mechanism and provides new insights for organizational practice.
Burnout status of healthcare workers in the world during the peak period of the COVID-19 pandemic
Authors: Ulfa Maria , Azuma Momoyo , Steiner Andrea
Published: September 2022

During the COVID-19 pandemic, healthcare workers have a high workload and have been exposed to various psychosocial stressors. This study aimed to evaluate health workers during the COVID-19 pandemic in the world. The method used in this research is qualitative with a literature review approach. The data sources in this study were taken from the Scopus database using the keywords “health workers,” “burnout,” AND “coronavirus” from the time range of 2020 to April 25, 2022. From the determination of the time range, 150 documents emerged. This study revealed that the Pearson correlation between total burnout scale scores on healthcare workers, professionals, exhaustion, mental, stress, personal, depression, symptoms, emergency, system, job, and impact indicated that overall burnout scores were associated with depression and anxiety. Stress symptoms had correlation values ranging from 0.84 to 0.73. Job burnout had a significant relationship with exhaustion at 0.89; depression r = 0.73), impacting a score of 0.66. At the same time, the fulfillment of professional and interpersonal disengagement showed a Pearson correlation between the total burnout scale scores on health workers, professionals, exhaustion, mental, stress, personal, depression, symptoms, emergency, system, job, and impact. Overall, the participants in health care workers worldwide experienced high levels of psychological distress. We also found that health workers dealing with COVID-19 pandemic patients were more likely to experience depression, stress, and burnout than health staff who were not personally involved in medical work. Furthermore, this study will be a follow-up study using the Work Ability Index (WAI) to measure work ability and work satisfaction.
Opportunities, challenges, and contextual supports to promote enacting maturing during adolescence
Authors: Ballard Parissa J. , Hoyt Lindsay Till , Johnson Jasmine
Published: September 2022

Conceptions of adolescent “storm and stress” may be tied to a developmental mismatch that exists between young people’s need for meaningful roles and autonomy – which we refer to as a need for enacting maturity – and the lack of such opportunities in most adolescents’ contexts. First, we summarize our previous work on enacting maturity, including a review of the key components, links to wellbeing, and the nuances and limitations of this construct. Next, we extend this work by considering how the ecological contexts (e.g., family, school, community) young people are embedded in and their various intersecting social positions and identities (e.g., race/ethnicity, gender, immigrant origin) influence their experiences with enacting maturity. In this section, we pose several key questions for developmental scientists around: (a) identifying a young person’s desire for, and phenomenological processing of, their adult-like roles, (b) understanding how complex and unequal responses to physical maturation shape opportunities for enacting maturity, and (c) attending to disparities in curricular and extracurricular pathways to leadership, responsibility, and autonomy. Finally, we discuss spaces with high potential to support enacting maturity, including both specially designed programs (e.g., youth participatory action research, leadership programs) as well as routine, everyday opportunities (e.g., interactions with teachers, training for companies that employ youth). We offer two levers for supporting enacting maturity across both types of spaces: adult allies and responsive organizations. Looking to exemplary programs, innovative leaders, social media, and case studies, we re-imagine how adults and organizations can promote young people enacting maturing in ways that are safe, worthwhile, and equitable.
A narrative inquiry into the agency of an EFL teacher in Western China
Authors: Gu Haibo , Liang Yulian , Wang Qian
Published: September 2022

Despite the increasing interest in teacher agency in the field of language teacher psychology, little attention has been paid to how language teachers enact their agency in an under-resourced environment. To address the research gap, this narrative study explored how a secondary English as a foreign language teacher in Western China enacted his agency for professional development and identified its sources. The findings revealed that this teacher enacted his agency through passionate exploration of adaptive teaching and continuous investment in autonomous learning. His agency was attributed to the interplay of his past experiences, long-term goals, teaching beliefs, and the challenging working environment. Consequently, implications for teacher agency research and practice are discussed.