bluuebunny/crossref_metadata_2025 huggingface dataset:
Online interprofessional education materials through a community learning program during the COVID 19 pandemic in Chile
Authors: Torres Sandra Oyarzo , Barrios Mónica Espinoza
Published: March 2022

This article aims to share the online collaborative experience of interprofessional teamwork among healthcare undergraduate students based on community learning during the coronavirus disease 2019 (COVID-19) pandemic in Chile. This experience took place in 48 different communities in Chile from November 10, 2020 to January 12, 2021. It was a way of responding to the health education needs of the community when the entire Chilean population was in confinement. Students managed to adapt to the COVID-19 pandemic despite the challenges, including internet connectivity problems and the limited time available to do the work. The educational programs and videos shared in this article will be helpful for other interprofessional health educators to implement the same kind of program.
Immeasurability loss? An analysis of the impacts of accountability measures on counselling within VET
Authors: Rosenblad Niklas , Schaffar Birgit , Löfström Erika
Published: March 2022

Comparative measures of learning outcomes and professional actions are set out to indicate accountability of VET. Individualisation and fragmentation of education emphasise counselling of students as support for their learning. The purpose of the article is to identify how counsellor and teacher practitioners perceive opportunities and challenges in merging their pedagogical and fundamental conventions of their work with structures and frameworks of accountability constituting their practice. Theoretically the study is influenced by socio-cultural perspectives. The analysis follows an abductive approach, reporting on the results from ethnographic observations of guidance counselling (N=29) within VET and subsequent interviews (N=12). We ask how the tension between the immeasurable and measurable contextualises within counselling, and how counselling is construed by counsellors and teachers. The results suggest adherence to quality measures in VET exchanged processes of human interactions and agreements with assumptions of outcomes. The effort of reaching the measures led to failure in achieving the purpose of what the targets are meant to underscore, portraying a disillusion of control. Accountability addressed a critical point concerning responsibility and evoked professional ethical dilemmas for the practitioners. Certain categorised actions of counselling processes were made externally visible by documentation but depleted counselling as learning processes inwards.
Remediation of Lead-Contaminated Water by Red Yeast and Different Types of Phosphate
Authors: Tian Da , Cheng Xiaohui , Wang Liyan , Hu Jun , Zhou Ningning , Xia Jingjing , Xu Meiyue , Zhang Liangliang , Gao Hongjian , Ye Xinxin , Zhang Chaochun
Published: March 2022

Rhodotorulamucilaginosa (Rho) can secrete large amounts of extracellular polymeric substances (EPS) to resist lead (Pb) toxicity. Phosphate is an effective material for the remediation of Pb. This study explored the Pb remediation by the combination of Rho and different types of phosphate in water. To do so, four phosphates, namely, ferric phosphate (FePO4, Fe-P), aluminum phosphate (AlPO4, Al-P), calcium phosphate [Ca3(PO4)2, Ca-P], and phosphogypsum (PG) were employed along with Rho. Compared with Rho application, the addition of phosphate significantly promoted the secretion of EPS by Rho (21–25 vs 16 mg). The formed EPS-Pb contributes to the Pb immobilization in the combination of Rho and phosphate. After 6 days of incubation, Rho + phosphate treatments immobilized over 98% of Pb cations, which is significantly higher than Rho treatment (94%). Of all Rho + phosphate treatments, Ca-P and PG-amended Rho had higher secretion of EPS, resulting in higher Pb removal. Nevertheless, PG had the highest efficiency for Pb removal compared with other phosphates, which reached 99.9% after 6 days of incubation. Likewise, new Pb minerals, such as pyromorphite and lead sulfate, only appeared in Rho + PG treatment. Altogether, this study concludes on the combined application of Rho and phosphate as an efficient approach to promote Pb remediation, particularly using PG waste.
Feasibility of Specular Reflection Imaging for Extraction of Neck Vessel Pressure Waveforms
Authors: Saiko Gennadi , Burton Timothy , Douplik Alexandre
Published: March 2022

Cardiovascular disease (CVD) is a leading cause of death worldwide and was responsible for 31% of all deaths in 2015. Changes in fluid pressures within the vessels of the circulatory system reflect the mechanical function of the heart. The jugular venous (JV) pulse waveform is an important clinical sign for assessing cardiac function. However, technology able to aid evaluation and interpretation are currently lacking. The goal of the current study was to develop a remote monitoring tool that aid clinicians in robust measurements of JV pulse waveforms. To address this need, we have developed a novel imaging modality, Specular Reflection Vascular Imaging (SRVI). The technology uses specular reflection for visualization of skin displacements caused by pressure pulsations in blood vessels. SRVI has been tested on 10 healthy volunteers. 10-seconds videos of the neck illuminated with a diffuse light source were captured at 250 fps. SRVI was able to identify and discriminate skin displacements caused by carotid artery and jugular vein pulsations to extract both carotid artery and jugular vein waveforms, making them easier to be visualized and interpreted. The method provided a 6-fold improvement in signal strength over a comparator remote PPG dataset. The current pilot study is a proof-of-concept demonstration of the potential of Specular Reflection Vascular Imaging for extraction of JV pulse waveforms.
Mitochondrial Population in Mouse Eosinophils: Ultrastructural Dynamics in Cell Differentiation and Inflammatory Diseases
Authors: Bonjour Kennedy , Palazzi Cinthia , Silva Thiago P. , Malta Kássia K. , Neves Vitor H. , Oliveira-Barros Eliane G. , Neves Igor , Kersten Victor A. , Fortuna Bruno T. , Samarasinghe Amali E. , Weller Peter F. , Bandeira-Melo Christianne , Melo Rossana C. N.
Published: March 2022

Mitochondria are multifunctional organelles of which ultrastructure is tightly linked to cell physiology. Accumulating evidence shows that mitochondrial remodeling has an impact on immune responses, but our current understanding of the mitochondrial architecture, interactions, and morphological changes in immune cells, mainly in eosinophils, is still poorly known. Here, we applied transmission electron microscopy (TEM), single-cell imaging analysis, and electron tomography, a technique that provides three-dimensional (3D) views at high resolution, to investigate mitochondrial dynamics in mouse eosinophils developing in cultures as well as in the context of inflammatory diseases characterized by recruitment and activation of these cells (mouse models of asthma, H1N1 influenza A virus (IAV) infection, and schistosomiasis mansoni). First, quantitative analyses showed that the mitochondrial area decrease 70% during eosinophil development (from undifferentiated precursor cells to mature eosinophils). Mitophagy, a consistent process revealed by TEM in immature but not in mature eosinophils, is likely operating in mitochondrial clearance during eosinophilopoiesis. Events of mitochondria interaction (inter-organelle membrane contacts) were also detected and quantitated within developing eosinophils and included mitochondria-endoplasmic reticulum, mitochondria-mitochondria, and mitochondria-secretory granules, all of them significantly higher in numbers in immature compared to mature cells. Moreover, single-mitochondrion analyses revealed that as the eosinophil matures, mitochondria cristae significantly increase in number and reshape to lamellar morphology. Eosinophils did not change (asthma) or reduced (IAV and Schistosoma infections) their mitochondrial mass in response to inflammatory diseases. However, asthma and schistosomiasis, but not IAV infection, induced amplification of both cristae numbers and volume in individual mitochondria. Mitochondrial cristae remodeling occurred in all inflammatory conditions with the proportions of mitochondria containing only lamellar or tubular, or mixed cristae (an ultrastructural aspect seen just in tissue eosinophils) depending on the tissue/disease microenvironment. The ability of mitochondria to interact with granules, mainly mobilized ones, was remarkably captured by TEM in eosinophils participating in all inflammatory diseases. Altogether, we demonstrate that the processes of eosinophilopoiesis and inflammation-induced activation interfere with the mitochondrial dynamics within mouse eosinophils leading to cristae remodeling and inter-organelle contacts. The understanding of how mitochondrial dynamics contribute to eosinophil immune functions is an open interesting field to be explored.
Single-Cell Multiomics Techniques: From Conception to Applications
Authors: Dimitriu Maria A. , Lazar-Contes Irina , Roszkowski Martin , Mansuy Isabelle M.
Published: March 2022

Recent advances in methods for single-cell analyses and barcoding strategies have led to considerable progress in research. The development of multiplexed assays offers the possibility to conduct parallel analyses of multiple factors and processes for comprehensive characterization of cellular and molecular states in health and disease. These technologies have expanded extremely rapidly in the past years and constantly evolve and provide better specificity, precision and resolution. This review summarizes recent progress in single-cell multiomics approaches, and focuses, in particular, on the most innovative techniques that integrate genome, epigenome and transcriptome profiling. It describes the methodologies, discusses their advantages and limitations, and explains how they have been applied to studies on cell heterogeneity and differentiation, and epigenetic reprogramming.
SARS-CoV-2 Mutations and COVID-19 Clinical Outcome: Mutation Global Frequency Dynamics and Structural Modulation Hold the Key
Authors: Maurya Ranjeet , Mishra Pallavi , Swaminathan Aparna , Ravi Varsha , Saifi Sheeba , Kanakan Akshay , Mehta Priyanka , Devi Priti , Praveen Shaista , Budhiraja Sandeep , Tarai Bansidhar , Sharma Shimpa , Khyalappa Rajesh J. , Joshi Meghnad G. , Pandey Rajesh
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an enormous burden on the healthcare system worldwide as a consequence of its new emerging variants of concern (VOCs) since late 2019. Elucidating viral genome characteristics and its influence on disease severity and clinical outcome has been one of the crucial aspects toward pandemic management. Genomic surveillance holds the key to identify the spectrum of mutations vis-à-vis disease outcome. Here, in our study, we performed a comprehensive analysis of the mutation distribution among the coronavirus disease 2019 (COVID-19) recovered and mortality patients. In addition to the clinical data analysis, the significant mutations within the two groups were analyzed for their global presence in an effort to understand the temporal dynamics of the mutations globally in comparison with our cohort. Interestingly, we found that all the mutations within the recovered patients showed significantly low global presence, indicating the possibility of regional pool of mutations and the absence of preferential selection by the virus during the course of the pandemic. In addition, we found the mutation S194L to have the most significant occurrence in the mortality group, suggesting its role toward a severe disease progression. Also, we discovered three mutations within the mortality patients with a high cohort and global distribution, which later became a part of variants of interest (VOIs)/VOCs, suggesting its significant role in enhancing viral characteristics. To understand the possible mechanism, we performed molecular dynamics (MD) simulations of nucleocapsid mutations, S194L and S194*, from the mortality and recovered patients, respectively, to examine its impacts on protein structure and stability. Importantly, we observed the mutation S194* within the recovered to be comparatively unstable, hence showing a low global frequency, as we observed. Thus, our study provides integrative insights about the clinical features, mutations significantly associated with the two different clinical outcomes, its global presence, and its possible effects at the structural level to understand the role of mutations in driving the COVID-19 pandemic.
Development of Klebsiella pneumoniae Capsule Polysaccharide-Conjugated Vaccine Candidates Using Phage Depolymerases
Authors: Lin Tzu-Lung , Yang Feng-Ling , Ren Chien-Tai , Pan Yi-Jiun , Liao Kuo-Shiang , Tu I-Fan , Chang Yu-Pei , Cheng Yang-Yu , Wu Chung-Yi , Wu Shih-Hsiung , Wang Jin-Town
Published: March 2022

Klebsiella pneumoniae is an important pathogen associated with nosocomial infection and has developed increasing resistance to antibiotics such as extended-spectrum β-lactams and carbapenem. In recent years, K. pneumoniae isolates have emerged as a major cause of global community-acquired infections such as pneumonia and pyogenic liver abscess. Although serotypes K1 and K2 have been identified as the predominant capsular types associated with invasive infections, no K. pneumoniae vaccine is commercially available, probably due to immunogenicity loss in the traditional depolymerization method to obtain capsule polysaccharide (CPS) for the preparation of conjugated vaccine. In this study, we successfully retained immunogenicity by using K1 (K1-ORF34) and K2 (K2-ORF16) CPS depolymerases that were identified from phages to cleave K1 and K2 CPSs into intact structural units of oligosaccharides with intact modifications. The obtained K1 and K2 oligosaccharides were separately conjugated with CRM197 carrier protein to generate CPS-conjugated vaccines. Immunization experiments of mice showed both K1 and K2 CPS-conjugated vaccines induced anti-CPS antibodies with 128-fold and 64-fold increases of bactericidal activities, respectively, compare to mice without vaccinations. Challenge tests indicated that K1 or K2 CPS-conjugated vaccine and divalent vaccine (a mixture of K1 and K2 CPS-conjugated vaccines) protected mice from subsequent infection of K. pneumoniae by the respective capsular type. Thus, we demonstrated K1 and K2 CPS-conjugated vaccines prepared by CPS depolymerases is a promising candidate for developing vaccines against human K. pneumoniae infections.
Why Does Piscirickettsia salmonis Break the Immunological Paradigm in Farmed Salmon? Biological Context to Understand the Relative Control of Piscirickettsiosis
Authors: Rozas-Serri Marco
Published: March 2022

Piscirickettsiosis (SRS) has been the most important infectious disease in Chilean salmon farming since the 1980s. It was one of the first to be described, and to date, it continues to be the main infectious cause of mortality. How can we better understand the epidemiological situation of SRS? The catch-all answer is that the Chilean salmon farming industry must fight year after year against a multifactorial disease, and apparently only the environment in Chile seems to favor the presence and persistence ofPiscirickettsia salmonis. This is a fastidious, facultative intracellular bacterium that replicates in the host’s own immune cells and antigen-presenting cells and evades the adaptive cell-mediated immune response, which is why the existing vaccines are not effective in controlling it. Therefore, the Chilean salmon farming industry uses a lot of antibiotics—to control SRS—because otherwise, fish health and welfare would be significantly impaired, and a significantly higher volume of biomass would be lost per year. How can the ever-present risk of negative consequences of antibiotic use in salmon farming be balanced with the productive and economic viability of an animal production industry, as well as with the care of the aquatic environment and public health and with the sustainability of the industry? The answer that is easy, but no less true, is that we must know the enemy and how it interacts with its host. Much knowledge has been generated using this line of inquiry, however it remains insufficient. Considering the state-of-the-art summarized in this review, it can be stated that, from the point of view of fish immunology and vaccinology, we are quite far from reaching an effective and long-term solution for the control of SRS. For this reason, the aim of this critical review is to comprehensively discuss the current knowledge on the interaction between the bacteria and the host to promote the generation of more and better measures for the prevention and control of SRS.
Dengue and Dengue Virus in Guangdong, China, 1978–2017: Epidemiology, Seroprevalence, Evolution, and Policies
Authors: Cui Fengfu , He Feiwu , Huang Xiaorong , Tian Lina , Li Saiqiang , Liang Chumin , Zeng Lilian , Lin Huifang , Su Juan , Liu Liping , Zhao Wei , Sun Limei , Lin Lifeng , Sun Jiufeng
Published: March 2022

Background

Guangdong is a hyperepidemic area of dengue, which has over 0.72 million cumulative cases within the last four decades, accounting for more than 90% of cases in China. The local epidemic of dengue in Guangdong is suspected to be triggered by imported cases and results in consequent seasonal transmission. However, the comprehensive epidemiological characteristics of dengue in Guangdong are still unclear.

Methods

The epidemiology, seroprevalence, molecular evolution of dengue virus, and the development of policies and strategies on the prevention and control of dengue were analyzed in Guangdong, China from 1978 to 2017.

Findings

Seasonal transmission of dengue virus in Guangdong, China was mainly sustained from July to October of each year. August to September was the highest risk period of local dengue outbreaks. Most of the dengue cases in Guangdong were young and middle-aged adults. Five hundred and three fatal cases were recorded, which declined within the last two decades (n = 10). The serological test of healthy donors' serum samples showed a positive rate of 5.77%. Dengue virus 1–4 (DENV 1–4) was detected in Guangdong from 1978 to 2017. DENV 1 was the dominant serotype of dengue outbreaks from 1978 to 2017, with an increasing tendency of DENV 2 since 2010. Local outbreaks of DENV 3 were rare. DENV 4 was only encountered in imported cases in Guangdong, China. The imported cases were the main source of outbreaks of DENV 1–2. Early detection, management of dengue cases, and precise vector control were the key strategies for local dengue prevention and control in Guangdong, China.

Interpretation

Dengue has not become an endemic arboviral disease in Guangdong, China. Early detection, case management, and implementation of precise control strategies are key findings for preventing local dengue transmission, which may serve for countries still struggling to combat imported dengue in the west pacific areas.
Mitochondrial Transcription of Entomopathogenic Fungi Reveals Evolutionary Aspects of Mitogenomes
Authors: Varassas Stylianos P. , Kouvelis Vassili N.
Published: March 2022

Entomopathogenic fungi and more specifically genera Beauveria and Metarhizium have been exploited for the biological control of pests. Genome analyses are important to understand better their mode of action and thus, improve their efficacy against their hosts. Until now, the sequences of their mitochondrial genomes were studied, but not at the level of transcription. Except of yeasts and Neurospora crassa, whose mt gene transcription is well described, in all other Ascomycota, i.e., Pezizomycotina, related information is extremely scarce. In this work, mt transcription and key enzymes of this function were studied. RT-PCR experiments and Northern hybridizations reveal the transcriptional map of the mt genomes of B. bassiana and M. brunneum species. The mt genes are transcribed in six main transcripts and undergo post-transcriptional modifications to create single gene transcripts. Promoters were determined in both mt genomes with a comparative in silico analysis, including all known information from other fungal mt genomes. The promoter consensus sequence is 5′-ATAGTTATTAT-3′ which is in accordance with the definition of the polycistronic transcripts determined with the experiments described above. Moreover, 5′-RACE experiments in the case of premature polycistronic transcript nad1-nad4-atp8-atp6 revealed the 5′ end of the RNA transcript immediately after the in silico determined promoter, as also found in other fungal species. Since several conserved elements were retrieved from these analyses compared to the already known data from yeasts and N. crassa, the phylogenetic analyses of mt RNA polymerase (Rpo41) and its transcriptional factor (Mtf1) were performed in order to define their evolution. As expected, it was found that fungal Rpo41 originate from the respective polymerase of T7/T3 phages, while the ancestor of Mtf1 is of alpha-proteobacterial origin. Therefore, this study presents insights about the fidelity of the mt single-subunit phage-like RNA polymerase during transcription, since the correct identification of mt promoters from Rpo41 requires an ortholog to bacterial sigma factor, i.e., Mtf1. Thus, a previously proposed hypothesis of a phage infected alpha-proteobacterium as the endosymbiotic progenitor of mitochondrion is confirmed in this study and further upgraded by the co-evolution of the bacterial (Mtf1) and viral (Rpo41) originated components in one functional unit.
Weaning Time Affects the Archaeal Community Structure and Functional Potential in Pigs
Authors: Deng Feilong , Peng Yunjuan , Zhang Zhihao , Howe Samantha , Wu Zhuosui , Dou Jieying , Li Yuling , Wei Xiaoyuan , Wang Xiaofan , Liang Yong , Zhao Jiangchao , Li Ying
Published: March 2022

Archaea are considered a “keystone” of the gut microbiome and are linked with the host’s energy harvest and health. Although a few studies have investigated the gut archaea in pigs, especially piglets, little is known about the effects of weaning on archaeal structure and function. In this study, we explored the effects of weaning on the longitudinal changes of archaeal composition, diversity, and functional potential in pigs overtime by re-analyzing a recently published metagenomic dataset that included 176 fecal samples collected from commercial pigs on days 7, 14, 21, 28, 35, 70, and 140 after birth. Overall, the richness and diversity of archaeal species showed an increasing trend, and weaning significantly affected the richness of archaeal species. Methanobrevibacter A smithii significantly decreased and was replaced by Methanobrevibacter A sp900769095 within 2 weeks after weaning. For the functional potential, the richness of KEGG KOs increased over time. LEfSe analysis identified 18 KOs, including for example, ko04623 (cytosolic DNA-sensing pathway), ko00500 (starch and sucrose metabolism), and so on, significantly enriched in the weaning pigs, suggesting the involvement of archaea in the piglets’ adaptation to the new diet after weaning. Correlation analysis based on Random Forest regression and Pearson correlation showed that archaeal species richness was significantly associated with pig bodyweight on both days 70 and 140. Methanobrevibacter A sp900769095 (R = 0.405, p = 0.040) and Methanobrevibacter A smithii (R = 0.535, p = 0.004) were positively linked with pigs’ bodyweight on days 70 and 140, respectively. Our results revealed the dynamic changes of archaeal diversity and functions and demonstrated the effects of weaning on the gut archaea of pigs, suggesting archaea might play essential roles in swine nutrition, metabolism, and growth performance, especially during the critical weaning process.
Functional Connectivity Hypointensity of Middle Cingulate Gyrus and Thalamus in Age-Related Macular Degeneration Patients: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Xiao Ang , Li Hai-Jun , Li Qiu-Yu , Liang Rong-Bin , Shu Hui-Ye , Ge Qian-Min , Liao Xu-Lin , Pan Yi-Cong , Wu Jie-Li , Su Ting , Zhang Li-Juan , Zhou Qiong , Shao Yi
Published: March 2022

Objective

Age-related macular degeneration (AMD) causes visual damage and blindness globally. The purpose of this study was to investigate changes in functional connectivity (FC) in AMD patients using resting-state functional magnetic resonance imaging (rs-fMRI).

Subjects and Methods

A total of 23 patients (12 male, 11 female) with AMD were enrolled to the AMD patients group (AMDs), and 17 healthy age-, sex-, and education-matched controls (9 male, 8 female) to the healthy controls group (HCs). All participants underwent rs-fMRI and mean FC values were compared between the two groups.

Results

Significantly higher FC values were found in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), inferior parietal lobule (IPL), rectal gyrus (RTG), and superior parietal lobule (SPL) in AMDs compared with HCs. Conversely, FC values in the cerebellum posterior lobe (CPL), middle cingulate gyrus (MCG), medulla (MDL), cerebellum anterior lobe (CAL), and thalamus (TLM) were significantly lower in AMDs than in HCs.

Conclusion

This study demonstrated FC abnormalities in many specific cerebral regions in AMD patients, and may provide new insights for exploration of potential pathophysiological mechanism of AMD-induced functional cerebral changes.
First Study in Men Evaluating a Surgical Robotic Tool Providing Autonomous Inner Ear Access for Cochlear Implantation
Authors: Topsakal Vedat , Heuninck Emilie , Matulic Marco , Tekin Ahmet M. , Mertens Griet , Van Rompaey Vincent , Galeazzi Pablo , Zoka-Assadi Masoud , van de Heyning Paul
Published: March 2022

Image-guided and robot-assisted surgeries have found their applications in skullbase surgery. Technological improvements in terms of accuracy also opened new opportunities for robotically-assisted cochlear implantation surgery (RACIS). The HEARO® robotic system is an otological next-generation surgical robot to assist the surgeon. It first provides software-defined spatial boundaries for orientation and reference information to anatomical structures during otological and neurosurgical procedures. Second, it executes a preplanned drill trajectory through the temporal bone. Here, we report how safe the HEARO procedure can provide an autonomous minimally invasive inner ear access and the efficiency of this access to subsequently insert the electrode array during cochlear implantation. In 22 out of 25 included patients, the surgeon was able to complete the HEARO® procedure. The dedicated planning software (OTOPLAN®) allowed the surgeon to reconstruct a three-dimensional representation of all the relevant anatomical structures, designate the target on the cochlea, i.e., the round window, and plan the safest trajectory to reach it. This trajectory accommodated the safety distance to the critical structures while minimizing the insertion angles. A minimal distance of 0.4 and 0.3 mm was planned to facial nerve and chorda tympani, respectively. Intraoperative cone-beam CT supported safe passage for the 22 HEARO® procedures. The intraoperative accuracy analysis reported the following mean errors: 0.182 mm to target, 0.117 mm to facial nerve, and 0.107 mm to chorda tympani. This study demonstrates that microsurgical robotic technology can be used in different anatomical variations, even including a case of inner ear anomalies, with the geometrically correct keyhole to access to the inner ear. Future perspectives in RACIS may focus on improving intraoperative imaging, automated segmentation and trajectory, robotic insertion with controlled speed, and haptic feedback. This study [Experimental Antwerp robotic research otological surgery (EAR2OS) and Antwerp Robotic cochlear implantation (25 refers to 25 cases) (ARCI25)] was registered at clinicalTrials.gov under identifier NCT03746613 and NCT04102215.

Clinical Trial Registration

https://www.clinicaltrials.gov, Identifier: NCT04102215.
Prediction of Vagal Nerve Stimulation Efficacy in Drug-Resistant Epilepsy (PRECISE): Prospective Study for Pre-implantation Prediction/Study Design
Authors: Dolezalova Irena , Koritakova Eva , Souckova Lenka , Chrastina Jan , Chladek Jan , Stepanova Radka , Brazdil Milan
Published: March 2022

Background

Vagal nerve stimulation (VNS) can be indicated in patients with drug-resistant epilepsy, who are not eligible for resective epilepsy surgery. In VNS therapy, the responder rate (i.e., percentage of subjects experiencing ≥50% seizure reduction) is ~50%. At the moment, there is no widely-accepted possibility to predict VNS efficacy in a particular patient based on pre-implantation data, which can lead to unnecessary surgery and improper allocation of financial resources. The principal aim of PRediction of vagal nerve stimulation EfficaCy In drug-reSistant Epilepsy (PRECISE) study is to verify the predictability of VNS efficacy by analysis of pre-implantation routine electroencephalogram (EEG).

Methods

PRECISE is designed as a prospective multicentric study in which patients indicated to VNS therapy will be recruited. Patients will be classified as predicted responders vs. predicted non-responders using pre-implantation EEG analyses. After the first and second year of the study, the real-life outcome (responder vs. non-responder) will be determined. The real-life outcome and predicted outcome will be compared in terms of accuracy, specificity, and sensitivity. In the meantime, the patients will be managed according to the best clinical practice to obtain the best therapeutic response. The primary endpoint will be the accuracy of the statistical model for prediction of response to VNS therapy in terms of responders and non-responders. The secondary endpoint will be the quantification of differences in EEG power spectra (Relative Mean Power, %) between real-life responders and real-life non-responders to VNS therapy in drug-resistant epilepsy and the sensitivity and specificity of the model.

Discussion

PRECISE relies on the results of our previous work, through which we developed a statistical classifier for VNS response (responders vs. non-responders) based on differences in EEG power spectra dynamics (Pre-X-Stim).

Trial Registration

www.ClinicalTrials.gov, identifier: NCT04935567.
Downregulation of m6A Methyltransferase in the Hippocampus of Tyrobp–/– Mice and Implications for Learning and Memory Deficits
Authors: Lv Zhanyun , Xu Tongxiao , Li Ran , Zheng Dejie , Li Yanxin , Li Wei , Yang Yan , Hao Yanlei
Published: March 2022

Loss-of-function mutations in the gene that encodes TYRO protein kinase-binding protein (TYROBP) cause Nasu-Hakola disease, a heritable disease resembling Alzheimer’s disease (AD). Methylation of N6 methyl-adenosine (m6A) in mRNA plays essential roles in learning and memory. Aberrant m6A methylation has been detected in AD patients and animal models. In the present study, Tyrobp–/– mice showed learning and memory deficits in the Morris water maze, which worsened with age. Tyrobp–/– mice also showed elevated levels of total tau, Ser202/Thr205-phosphorylated tau and amyloid β in the hippocampus and cerebrocortex, which worsened with aging. The m6A methyltransferase components METTL3, METTL14, and WTAP were downregulated in Tyrobp–/– mice, while expression of demethylases that remove the m6A modification (e.g., FTO and ALKBH5) were unaltered. Methylated RNA immunoprecipitation sequencing identified 498 m6A peaks that were upregulated in Tyrobp–/– mice, and 312 m6A peaks that were downregulated. Bioinformatic analysis suggested that most of these m6A peaks occur in sequences near stop codons and 3′-untranslated regions. These findings suggest an association between m6A RNA methylation and pathological TYROBP deficiency.
The Shaping of AMPA Receptor Surface Distribution by Neuronal Activity
Authors: Chater Thomas Edward , Goda Yukiko
Published: March 2022

Neurotransmission is critically dependent on the number, position, and composition of receptor proteins on the postsynaptic neuron. Of these, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are responsible for the majority of postsynaptic depolarization at excitatory mammalian synapses following glutamate release. AMPARs are continually trafficked to and from the cell surface, and once at the surface, AMPARs laterally diffuse in and out of synaptic domains. Moreover, the subcellular distribution of AMPARs is shaped by patterns of activity, as classically demonstrated by the synaptic insertion or removal of AMPARs following the induction of long-term potentiation (LTP) and long-term depression (LTD), respectively. Crucially, there are many subtleties in the regulation of AMPARs, and exactly how local and global synaptic activity drives the trafficking and retention of synaptic AMPARs of different subtypes continues to attract attention. Here we will review how activity can have differential effects on AMPAR distribution and trafficking along with its subunit composition and phosphorylation state, and we highlight some of the controversies and remaining questions. As the AMPAR field is extensive, to say the least, this review will focus primarily on cellular and molecular studies in the hippocampus. We apologise to authors whose work could not be cited directly owing to space limitations.
Development and Validation of a Novel Survival Model for Cutaneous Melanoma Based on Necroptosis-Related Genes
Authors: Niu Zehao , Wang Xin , Xu Yujian , Li Yan , Gong Xiaojing , Zeng Quan , Zhang Biao , Xi Jiafei , Pei Xuetao , Yue Wen , Han Yan
Published: March 2022

Background

Necroptosis is crucial for organismal development and pathogenesis. To date, the role of necroptosis in skin cutaneous melanoma (SKCM) is yet unveiled. In addition, the part of melanin pigmentation was largely neglected in the bioinformatic analysis. In this study, we aimed to construct a novel prognostic model based on necroptosis-related genes and analysis the pigmentation phenotype of patients to provide clinically actionable information for SKCM patients.

Methods

We downloaded the SKCM data from the TCGA and GEO databases in this study and identified the differently expressed and prognostic necroptosis-related genes. Patients’ pigmentation phenotype was evaluated by the GSVA method. Then, using Lasso and Cox regression analysis, a novel prognostic model was constructed based on the intersected genes. The risk score was calculated and the patients were divided into two groups. The survival differences between the two groups were compared using Kaplan-Meier analysis. The ROC analysis was performed and the area under curves was calculated to evaluate the prediction performances of the model. Then, the GO, KEGG and GSEA analyses were performed to elucidate the underlying mechanisms. Differences in the tumor microenvironment, patients’ response to immune checkpoint inhibitors (ICIs) and pigmentation phenotype were analyzed. In order to validate the mRNA expression levels of the selected genes, quantitative real-time PCR (qRT-PCR) was performed.

Results

Altogether, a novel prognostic model based on four genes (BOK, CD14, CYLD and FASLG) was constructed, and patients were classified into high and low-risk groups based on the median risk score. Low-risk group patients showed better survival status. The model showed high accuracy in the training and the validation cohort. Pathway and functional enrichment analysis indicated that immune-related pathways were differently activated in the two groups. In addition, immune cells infiltration patterns and sensitivity of ICIs showed a significant difference between patients from two risk groups. The pigmentation score was positively related to the risk score in pigmentation phenotype analysis.

Conclusion

In conclusion, this study established a novel prognostic model based on necroptosis-related genes and revealed the possible connections between necroptosis and melanin pigmentation. It is expected to provide a reference for clinical treatment.
Exploring Mental Health and Academic Outcomes of Children Receiving Non-manualized, Transdiagnostic, Task-Shifted Mental Health Care From Their Teachers in a Low-and-Middle Income Country
Authors: Vanderburg Juliana L. , Dukpa Choden , Rauniyar Abhishek K. , Giri Priscilla , Bhattarai Surekha , Thapa Arpana , Gaynes Bradley N. , Hampanda Karen , Lamb Molly M. , Matergia Michael , Cruz Christina M.
Published: March 2022

A majority of children worldwide who face mental health difficulties, especially in low-and-middle income countries, remain undiagnosed and untreated. This deficit roots in part from a lack of trained professionals qualified to provide care. Task-shifting the provision of treatment to teachers, individuals with consistent access to children, can reduce the care gap. The current study investigated whether the implementation of a pilot trial of Tealeaf-Mansik Swastha (Teachers Leading the Frontlines—Mental Health; “Tealeaf”) was associated with improvements in child mental health and academic outcomes. Tealeaf is a transdiagnostic, non-manualized, task-shifting intervention in which teachers identify students in need of mental health care and then provide task-shifted care for them using an emerging, novel therapy modality, “education as mental health therapy” (Ed-MH). Pre-post standardized quantitative measures focused on child mental health status and academics. The measures were completed by multiple raters and compared to determine whether changes occurred. Results indicated that primary teacher raters observed significant improvements in child mental health symptoms overall, while secondary teacher raters and caregivers noted improvement for certain diagnostic categories. Caregivers observed on average a decreased impact of their children's mental health symptoms on their children's lives. Academically, math scores significantly improved while reading trended toward significance. Preliminary evidence overall supports the viability of Tealeaf and Ed-MH for positively impacting child mental health and academics. Future directions include the implementation of a formalized, randomized-controlled trial to strengthen preliminary outcomes.
Host Resistance to Bacterial Infection Varies Over Time, but Is Not Affected by a Previous Exposure to the Same Pathogen
Authors: Acuña Hidalgo Beatriz , Armitage Sophie A. O.
Published: March 2022

Immune priming describes the phenomenon whereby after a primary pathogen exposure, a host more effectively fights a lethal secondary exposure (challenge) to the same pathogen. Conflicting evidence exists for immune priming in invertebrates, potentially due to heterogeneity across studies in the pathogen species tested, the antigen preparation for the primary exposure, and the phenotypic trait used to test for priming. To explore these factors, we injectedDrosophila melanogasterwith one of two bacterial species,Lactococcus lactisorProvidencia burhodogranariea, which had either been heat-killed or inactivated with formaldehyde, or we injected a 1:1 mixture of the two inactivation methods. Survival and resistance (the inverse of bacterial load) were assessed after a live bacterial challenge. In contrast to our predictions, none of the primary exposure treatments provided a survival benefit after challenge compared to the controls. Resistance in the acute phase, i.e., 1 day post-challenge, separated into a lower- and higher-load group, however, neither group varied according to the primary exposure. In the chronic phase, i.e., 7 days post-challenge, resistance did not separate into two groups, and it was also unaffected by the primary exposure. Our multi-angled study supports the view that immune priming may require specific circumstances to occur, rather than it being a ubiquitous aspect of insect immunity.
Strengths Use for Tasks and Relationships in Organizations: Development and Validation of a Strengths Use Scale
Authors: Hai Shenyang , Park In-Jo
Published: March 2022

Individual character strengths have been increasingly valued, as they facilitate social functioning, well-being, and performance. However, little is known about how individuals use their strengths for important but distinct goals including task accomplishment and relationship maintenance in organizations. The purpose of this study is to develop and validate a Strengths Use Scale that can be used to measure the use of strengths for tasks and relationships in the workplace. For this purpose, we used the exploratory mixed-method design and conducted a series of studies. In Study 1, we conducted an exploratory factor analysis to ensure the construct validity of the Strengths Use Scale on a sample of 187 employees. We found that the scale comprises two dimensions: strengths use for tasks and strengths use for relationships. In Study 2a, we verified the two-factor structure of the Strengths Use Scale using the confirmatory factor analysis on a separate sample of 213 employees. The results of Study 2b demonstrated that the scale has good measurement invariance across gender and age groups, on the sample of 205 employees. Moreover, strengths use for tasks and strengths use for relationships positively correlated with well-being and work engagement and negatively correlated with turnover intention, supporting the criterion-related validity of the scale. In Study 3, a test–retest reliability analysis with a sample of 94 employees indicated that the scale has high reliability. Theoretical and practical implications of the findings are discussed.
Assessing Groundwater Dynamics and Hydrological Processes in the Sand River Deposits of the Limpopo River, Mozambique
Authors: Saveca Paulo Sérgio Lourenço , Abi Attoumane , Stigter Tibor Yvan , Lukas Eelco , Fourie Francois
Published: March 2022

Drought and water scarcity constrain the socioeconomic development of many (semi-)arid regions of Southern Africa. Moreover, due to the increase of water withdrawals upstream, the Limpopo River is no longer perennial in Mozambique. Fortunately, its river bed can store significant amounts of freshwater, because of the occurrence of thick and often coarse sand deposits formed through pronounced dryland weathering, erosion, and sedimentation in the river channel. Such so-called “sand rivers” exist in many parts of semi-arid Africa and have varying configurations and hydrological conditions. The current research aims to comparatively assess the Limpopo sand river aquifer in terms of recharge and discharge dynamics, storage potential, and interactions with the surface water flow, as a function of its specific hydrological conditions: its large size, location downstream of a dam releasing permanent ecological flow, and its relatively undeveloped state. For this purpose field investigations were carried out at two sites, involving groundwater level measurements, 2D geoelectrical surveying, water chemical and stable isotope analysis, and sediment classification. These investigations reveal the occurrence of medium to coarse sands with thicknesses that can reach 10–15 m, dropping to 2–5 m in the main river channel, underlain by less permeable clays and silts. Analysis of the river level shows that large parts of the sand river are flooded almost every year, providing optimal conditions for recurring and rapid recharge of the system (confirmed by infiltration tests) through two mechanisms: direct infiltration of surface runoff and lateral flow toward non-flooded areas of the river valley, also confirmed by the chemical and isotope study. During the dry season, groundwater provides base flow to the river and the average water level drop in the sand river system is about 1.8 m. The connectivity with the river margins is limited, due to the clayey nature of the river bank sediment, but local paleochannels can result in a continuation of sand layers. Hydrological processes controlling the water quality are evapoconcentration, mixing of discharging groundwater with the perennial surface water flow, and to a minor extent mineral dissolution, with the groundwater being of Ca-HCO3 type. The combination of the large size, high permeability, and frequent flooding of the sand river deposits provides optimal conditions for groundwater abstraction, requiring additional assessment of the impact on riparian vegetation and downstream users.
Double-Docking Technique, an Optimized Process for Intrathoracic Esophagogastrostomy in Robot-Assisted Ivor Lewis Esophagectomy
Authors: Wang Fuqiang , Zhang Hanlu , Qiu Guanghao , Wang Zihao , Li Zhiyang , Wang Yun
Published: March 2022

Background

Though robotic Ivor Lewis esophagectomy has been increasingly applied, intrathoracic esophagogastrostomy is still a technical barrier. In this retrospective study, we introduced a double-docking technique for intrathoracic esophagogastrostomy to optimize surgical exposure and facilitate intrathoracic anastomosis. Moreover, we compared the clinical outcomes between the double-docking technique and anastomosis with a single-docking procedure in robotic Ivor Lewis esophagectomy.

Methods

From March 2017 to September 2020, the clinical data of 68 patients who underwent robotic Ivor Lewis esophagectomy were reviewed, including 23 patients who underwent the double-docking technique (double-docking group) and 45 patients who underwent single-docking robotic esophagectomy (single-docking group). All patients were diagnosed with esophageal cancer or gastro-esophageal junction by biopsy before surgery. The technical details of the double-docking technique are described in this article.

Results

There was no difference in the patient demographics data between the two groups. The median surgical time in the double-docking group was slightly shorter than in the classic group without statistical difference (380 vs. 395 min, p = 0.368). In the double-docking group, the median blood loss was 90 mL, the median number of lymph nodes harvested was 17, and the R0 resection rates were 100% (23/23). There were no differences in the surgical outcomes between the two groups.

Conclusions

Based on our experience, the double-docking technique provides good surgical exposure when fashioning anastomosis, and such a technique does not increase the surgical time. Therefore, we believe that the double-docking technique is a safe and effective method for intrathoracic esophagogastrostomy while providing good exposure and ensuring the convenience and reliability of intrathoracic anastomosis.