bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances in date palm genomics: A comprehensive review
Authors: Rahman Hifzur , Vikram Prashant , Hammami Zied , Singh Rakesh Kumar
Published: September 2022

As one of the oldest fruit trees of the Arabian peninsula, other Middle-Eastern countries, and also North Africa, the date palm (Phoenix dactyliferaL.), is highly significant for the economy of the region. Listed as part of UNESCO’s Intangible Cultural Heritage of Humanity, the date palm is believed to be the first tree cultivated by human beings, and was probably first harvested for its fruit nearly 7,000 years ago. Initial research efforts in date palm genetics focused on understanding the genetic diversity of date palm germplasm collections and its phylogenetic history, both important prerequisites for plant improvement. Despite various efforts, the center of origin of the date palm is still unclear, although genomic studies suggest two probable domestication events: one in the Middle East and the other in North Africa, with two separate gene pools. The current review covers studies related to omics analyses that have sought to decipher the present genetic diversity of the date palm. With advances and cost reductions in sequencing technologies, rapid progress has been made in the past few years in date palm genomics research. Along with organellar genomes, several reference genomes of the date palm are now available. In addition, several genotypes have been re-sequenced, either to detect single nucleotide polymorphisms (SNPs), or to study domestication and identification of key genes/loci associated with important agronomic traits, such as sex, fruit color, and sugar composition. These genomics research progress has paved the way to perform fast-track and precise germplasm improvement processes in date palm. In this study, we review the advances made in the genetics and genomics of the date palm so as to strategize targeted crop improvement plans for marginal areas of the Middle Eastern peninsula, North Africa, and other parts of the world.
A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL)
Authors: Tanaka Yuetsu , Tanaka Reiko , Imaizumi Naoki , Mizuguchi Mariko , Takahashi Yoshiaki , Hayashi Masaki , Miyagi Takashi , Uchihara Junnosuke , Ohshiro Kazuiku , Masuzaki Hiroaki , Fukushima Takuya
Published: September 2022

Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.
A comprehensive review of BBV152 vaccine development, effectiveness, safety, challenges, and prospects
Authors: Dotiwala Farokh , Upadhyay Arun K.
Published: September 2022

The world has responded to the COVID-19 pandemic with unprecedented speed and vigor in the mass vaccination campaigns, targeted to reduce COVID-19 severity and mortality, reduce the pressure on the healthcare system, re-open society, and reduction in disease mortality and morbidity. Here we review the preclinical and clinical development of BBV152, a whole virus inactivated vaccine and an important tool in the fight to control this pandemic. BBV152, formulated with a TLR7/8 agonist adjuvant generates a Th1-biased immune response that induces high neutralization efficacy against different SARS-CoV-2 variants of concern and robust long-term memory B- and T-cell responses. With seroconversion rates as high as 98.3% in vaccinated individuals, BBV152 shows 77.8% and 93.4% protection from symptomatic COVID-19 disease and severe symptomatic COVID-19 disease respectively. Studies in pediatric populations show superior immunogenicity (geometric mean titer ratio of 1.76 compared to an adult) with a seroconversion rate of >95%. The reactogenicity and safety profiles were comparable across all pediatric age groups between 2-18 yrs. as in adults. Like most approved vaccines, the BBV152 booster given 6 months after full vaccination, reverses a waning immunity, restores the neutralization efficacy, and shows synergy in a heterologous prime-boost study with about 3-fold or 300% increase in neutralization titers against multiple SARS-CoV-2 variants of concern. Based on the interim Phase III data, BBV152 received full authorization for adults and emergency use authorization for children from ages 6 to 18 years in India. It is also licensed for emergency use in 14 countries globally. Over 313 million vaccine doses have already been administered in India alone by April 18th, 2022.
Human differentiated eosinophils release IL-13 in response to IL-33 stimulation
Authors: Uchida Amiko M. , Ro Gabrielle , Qiang Li , Peterson Kathryn A. , Round June , Dougan Michael , Dougan Stephanie K.
Published: September 2022

Objective

Eosinophils are hallmarks in allergic type 2 inflammation and are known to release cytotoxic granule proteins that contribute to inflammation. Eosinophils develop in the bone marrow from hematopoietic stem cells and once mature, have a limited lifespan in culture, making them difficult to studyex vivo. IL-33 has increasingly been shown as a key regulator of type 2 inflammationviasignaling through its receptor, ST2. The present study was conducted to detail a method of eosinophil differentiation from hematopoietic stem cells and determine the response to IL-33.

Methods

CD34+ and CD14+ cells were isolated from donor apheresis cones and differentiated into eosinophils or macrophage controls, respectively. Morphologic, transcriptional and protein analyses were performed to validate this method of eosinophil differentiation. The effect of IL-33 on differentiated eosinophils was assessed using qPCR, immunofluorescence, and multiplex cytokine array.

Results

CD34 differentiated eosinophils appear morphologically similar by H&E and express eosinophil peroxidase (EPX) protein as well as the conventional eosinophil transcriptsEPX,CLC, andMBP. In addition, differentiated eosinophils expressed both isoforms of the IL-33 receptor,ST2Land sST2throughout the differentiation process. Transcript levels of both IL-33 receptors were up-regulated by treatment with IL-33 at earlier timepoints in the differentiation. These cells also expressedIL-4andIL-13mRNA which were up-regulated by IL-33 as well. Notably,IL-13expression was significantly higher with IL-33 treatment compared to media control at every timepoint measured. IL-33 significantly increased cellular secretion of IL-13 protein at most timepoints throughout differentiation. IL-8, LIF, CCL1, CCL5, CCL7, and CCL8 were also significantly secreted after IL-33 stimulation.

Conclusions

Our findings suggest that CD34 differentiated eosinophils are morphologically and phenotypically similar to peripheral eosinophils. The release of specific cytokines in direct response to IL-33 may contribute to the pathogenesis of type 2 inflammation and facilitates new avenues for studying eosinophils as effector cellsin vitro.
The immune system as a system of relations
Authors: Daëron Marc
Published: September 2022

Progress in neuroimmunology established that the nervous and the immune systems are two functionally related physiological systems. Unique sensory and immune receptors enable them to control interactions of the organism with the inner and the outer worlds. Both systems undergo an experience-driven selection process during their ontogeny. They share the same mediators/neurotransmitters and use synapses for intercellular communication. They keep a memory of previous experiences. Immune cells can affect nervous cells, nervous cells can affect immune cells, and they regulate each other. I however argue that the two systems differ by three major points: 1) Unlike the nervous system, the immune system has a loose anatomical structure, in which molecular and cellular events mostly occur at random; 2) The immune system can respond tomolecules oftheliving worldwhereas the nervous system can respond tophenomena of the physical world; 3) Responses of the immune system act both on the organism and on the stimulus that triggered the response, whereas responses of the nervous system act on the organism only. The nervous and the immune systems therefore appear as two complementarysystems of relationsthat closely work together, and whose reactivities are well-suited to deal with physical and biological stimuli, respectively. Its ability both to adapt the organism to the living world and to adapt the living world to the organism endows the immune system with powerful adaptive properties that enable the organism to live in peace with itself and with other living beings, whether pathogens or commensals.
Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis
Authors: Wang He , Li Sihan , Liu Tingting , Chen Jun , Dang Jun
Published: September 2022

Background

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer. Nevertheless, efficacy and safety for this new strategy have not been clearly demonstrated.

Patients and methods

PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible trials until June 30, 2022. The primary outcome of interest was pathological complete response (pCR). The random-effect model was used for statistical analysis.

Results

Twenty-seven trials with 809 patients were identified. The estimated rates of pCR for nICRT and nICT were comparable (32.7%, 95% CI: 20.3%-45.1% vs 26.3%, 95% CI: 19.8%-32.8%; P = 0.37). As for safety, surgical resection rate, R0 resection rate, surgical delay rate, and surgical mortality rate were similar between nICRT and nICT, while more grade ≥3 treatment-related adverse events were observed for nICRT (52.6%, 95% CI: 30.7%-74.5% vs 19.9%, 95% CI: 8.8%-31.0%; P = 0.01). In subgroup analysis, nICRT achieved higher pCR rate compared to nICT (56.2%, 95% CI: 41.0%-71.3% vs 27.2%, 95% CI: 20.2%-34.1%; P < 0.001) for squamous cell carcinoma (SCC) but adenocarcinoma. In patients receiving nICT, PD-L1 expression CPS ≥1 showed higher pCR rate compared to CPS <1 (51.3%, 95% CI: 41.4%-61.2% vs 26.6%, 95% CI: 8.6%-44.5%; P = 0.02); regimen of paclitaxel plus carboplatin/cisplatin (PC/TP) and 3-4 cycles of nICT did not lead to an significantly improved pCR rate compared to other chemotherapy regimens and 2 cycles of nICT, respectively, despite without increased toxicity.

Conclusion

Both nICT and nICRT achieved promising pCR rates with acceptable tolerability, and nICRT was likely to have more antitumor efficacy compared to nICT for patients with SCC. PD-L1 status seemed to be predictive of pCR in patients receiving nICT; pCR rate did not appear to be greatly affected by CT regimen and increasing cycles of nICT.
Accuracy of point-of-care Panbio™ SARS-CoV-2 antigen-detection test in a socioeconomically vulnerable population in Brazil
Authors: Gontijo Carolina Carvalho , Brito Raíssa Nogueira de , Teixeira Ana Izabel Passarella , Romero Gustavo Adolfo Sierra , Pedrette Priscilla , Ramalho Walter Massa , Noronha Elza , Haddad Rodrigo , Araújo Wildo Navegantes de
Published: September 2022

Background

Development and validation of point-of-care (POC) diagnostic tests with high accuracy is critical for underrepresented populations, allowing for wider access to diagnosis. Here, we evaluate the performance of the Panbio™ antigen-rapid test device (Ag-RTD) for SARS-CoV-2, our index test, having RT-qPCR as the reference standard.

Methods

This phase III validation study was conducted concomitantly with a primary health care center routine tending to a low-income Brazilian population. Eligibility criteria were residing at Cidade Estrutural and presenting flu-like/respiratory symptoms for 3-10 days.

Results

Among the 505 participants, 45.15% (228/505) tested positive for RT-qPCR and 54.85% (277/505) for the Ag-RTD. Overall sensitivity was 76.32% (CI95% 70.39-81.37) and specificity was 98.92% (96.02-99.82).

Conclusions

Our results show that the Panbio™ Ag-RTD does not meet the minimum performance requirements established by the World Health Organization (≥ 80% sensitivity and ≥ 97% specificity compared to a reference test in suspected COVID-19 cases). Thus, we do not recommend the implementation of Panbio™Ag-RTD as a single diagnostic tool in underrepresented and disadvantaged populations. Finally, we discuss a possible setting for the use of Panbio™Ag-RTD under combined sensitivity.
Symbiont starvation affects the stability of the coral–Symbiodiniaceae symbiosis
Authors: Martinez Stephane , Grover Renaud , Ferrier-Pagès Christine
Published: September 2022

Coral bleaching, the breakdown of the coral-Symbiodiniaceae association has been identified as a major cause of coral reef decline worldwide. When symbiont functions are compromised, corals receive fewer photosynthetic products from their symbionts and suffer significant starvation along with changes in nutrient cycling. Not all coral species are equally susceptible to bleaching, but despite intensive research, our understanding of the causes for coral bleaching remains incomplete. Here, we investigated nutrient exchange between host and symbionts of two coral- Symbiodiniaceae associations that are differentially susceptible to bleaching when maintained under heterotrophy in the dark. We followed the fate of heterotrophic nutrients using bulk isotope and compound-specific (amino acid) isotope analyses. We showed that symbiont starvation is a major cause of symbiotic breakdown in the dark. WhileOculina patagonicatransferred almost all heterotrophically-acquired amino acids within two weeks in the dark to its symbionts and did not bleach,Turbinaria reniformis, transferred only 2 amino acids to its symbionts after 4 weeks in the dark, and experienced significant bleaching. These results pave the way for future studies on the role of nutrition in coral stress response and the importance of maintaining a healthy symbiont population to avoid coral bleaching.
Circadian dysregulation induces alterations of visceral sensitivity and the gut microbiota in Light/Dark phase shift mice
Authors: Hu Lilin , Li Gangping , Shu Yanyun , Hou Xiaohua , Yang Ling , Jin Yu
Published: September 2022

Background

It is well-established that several features of modern lifestyles, such as shift work, jet lag, and using electronics at night, disturb normal circadian rhythm and increase the risk of suffering from functional gastrointestinal disease. Although substantial evidence demonstrates that shift work is closely correlated with the symptoms of visceral hypersensitivity, few basic studies have revealed the mechanism of visceral hypersensitivity induced by circadian rhythm disturbance, especially light/dark phase shifts. Our study explored the mechanism underlying visceral hypersensitivity caused by light/dark phase shift in mice.

Methods

A 6-h delay light/dark phase shift mice model was constructed. Visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR) score induced by colorectal distention (CRD) in vivo and contraction of colonic muscle strips induced by acetylcholine ex vivo. Intestinal permeability was evaluated by transepithelial resistance (TEER) and FD4 permeability. The expression of tight junction proteins was detected by western blotting and immunofluorescence staining. The gut microbiota was examined by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) was performed to confirm the relationship between the light/dark phase shift, gut microbiota, and visceral hypersensitivity.

Results

We found that light/dark phase shift increased visceral sensitivity and disrupted intestinal barrier function, caused low-grade intestinal inflammation. Moreover, we found decreased microbial species richness and diversity and a shift in microbial community with a decreased proportion of Firmicutes and an elevated abundance of Proteobacteria at the phylum level. Besides, after the light/dark phase shift, the microflora was significantly enriched in biosynthesizing tryptophan, steroid hormone, secondary metabolites, lipids, and lipopolysaccharides. Mice that underwent FMT from the light/dark phase shift mice model exhibited higher visceral hypersensitivity and worse barrier function. Dysbiosis induced by light/dark phase shift can be transmitted to the mice pretreated with antibiotics by FMT not only at the aspect of microbiota composition but also at the level of bacterial function.

Conclusion

Circadian rhythm disturbance induced by the light/dark phase shift produces visceral hypersensitivity similar to the pathophysiology of IBS through modulating the gut microbiota, which may disrupt intestinal barrier function or induce a low-degree gut inflammation.
Microbial containment device: A platform for comprehensive analysis of microbial metabolism without sample preparation
Authors: Mohammadi Mehdi , Bishop Stephanie L. , Aburashed Raied , Luqman Saad , Groves Ryan A. , Bihan Dominique G. , Rydzak Thomas , Lewis Ian A.
Published: September 2022

Metabolomics is a mainstream strategy for investigating microbial metabolism. One emerging application of metabolomics is the systematic quantification of metabolic boundary fluxes – the rates at which metabolites flow into and out of cultured cells. Metabolic boundary fluxes can capture complex metabolic phenotypes in a rapid assay, allow computational models to be built that predict the behavior of cultured organisms, and are an emerging strategy for clinical diagnostics. One advantage of quantifying metabolic boundary fluxes rather than intracellular metabolite levels is that it requires minimal sample processing. Whereas traditional intracellular analyses require a multi-step process involving extraction, centrifugation, and solvent exchange, boundary fluxes can be measured by simply analyzing the soluble components of the culture medium. To further simplify boundary flux analyses, we developed a custom 96-well sampling system—the Microbial Containment Device (MCD)—that allows water-soluble metabolites to diffuse from a microbial culture well into a bacteria-free analytical well via a semi-permeable membrane. The MCD was designed to be compatible with the autosamplers present in commercial liquid chromatography-mass spectrometry systems, allowing metabolic fluxes to be analyzed with minimal sample handling. Herein, we describe the design, evaluation, and performance testing of the MCD relative to traditional culture methods. We illustrate the utility of this platform, by quantifying the unique boundary fluxes of four bacterial species and demonstrate antibiotic-induced perturbations in their metabolic activity. We propose the use of the MCD for enabling single-step metabolomics sample preparation for microbial identification, antimicrobial susceptibility testing, and other metabolic boundary flux applications where traditional sample preparation methods are impractical.
Association between kinking of the cervical carotid or vertebral artery and ischemic stroke/TIA
Authors: Wang Junjie , Lu Jun , Qi Peng , Li Chunwei , Yang Ximeng , Chen Kunpeng , Wang Daming
Published: September 2022

Introduction

Kinking of the cervical carotid or vertebral artery is a common structural abnormality in patients with cerebrovascular disease. However, there is no consensus about the relationship between kinking and ischemic stroke/TIA. We aim to determine the effect of arterial kinking on ischemic stroke/TIA.

Methods

A retrospective study was performed on patients who underwent cerebral angiography with DSA between January 2014 and December 2018. Demographic information and comorbidities were recorded. Each anatomical circulation system was defined as an observation unit. Kinking and stenosis of each circulation unit were recorded. Ischemia stroke or TIA within 6 months and its location were assessed as an outcome. Logistic regression with a generalized estimating equation approach was used for the analysis.

Results

A total of 1,062 patients (mean age 57.9 ± 14.5 years, 740 males and 322 females) were included in the study. Of the patients, 369 (35%) had kinking and 771 (73%) had ischemic stroke/TIA. There were 110 left anterior, 90 right anterior, and 308 posterior circulation units, among which 343 had mild, 160 had moderate, and 243 had severe kinking. Multivariate regression analysis showed that ischemic stroke/TIA was associated with severe kinking (OR 1.39, 95% CI 1.03–1.88, P = 0.03). Posterior circulation was more vulnerable to acute ischemia than left anterior and right anterior circulation (OR 3.58, 95% CI 2.81–4.56, P < 0.0001).

Conclusion

Severe kinking of the cervical carotid or vertebral artery may be associated with a higher risk of ischemic stroke/TIA, especially when the kinking is located in the posterior circulation.
Identification of magnetic resonance imaging features for the prediction of unrecognized atrial fibrillation in acute ischemic stroke
Authors: Chen Chao-Hui , Lee Meng , Weng Hsu-Huei , Lee Jiann-Der , Yang Jen-Tsung , Tsai Yuan-Hsiung , Huang Yen-Chu
Published: September 2022

Background and purpose

The early identification of cardioembolic stroke is critical for the early initiation of anticoagulant treatment. However, it can be challenging to identify the major cardiac source, particularly since the predominant source, paroxysmal atrial fibrillation (AF), may not be present at the time of stroke. In this study, we aimed to evaluate imaging predictors for unrecognized AF in patients with acute ischemic stroke.

Methods

We performed a cross-sectional analysis of data and magnetic resonance imaging (MRI) scans from two prospective cohorts of patients who underwent serial 12-lead electrocardiography and 24-h Holter monitoring to detect unrecognized AF. The imaging patterns in diffusion-weighted imaging and imaging characteristics were assessed and classified. A logistic regression model was used to identify predictive factors for newly detected AF in patients with acute ischemic stroke.

Results

A total of 734 patients were recruited for analysis, with a median age of 72 (interquartile range: 65–79) years and a median National Institutes of Health Stroke Scale score of 4 (interquartile range: 2–6). Of these patients, 64 (8.7%) had newly detected AF during the follow-up period. Stepwise multivariate logistic regression revealed that age ≥75 years [adjusted odds ratio (aOR) 5.66, 95% confidence interval (CI) 2.98–10.75], receiving recombinant tissue plasminogen activator treatment (aOR 4.36, 95% CI 1.65–11.54), congestive heart failure (aOR 6.73, 95% CI 1.85–24.48), early hemorrhage in MRI (aOR 3.62, 95% CI 1.52–8.61), single cortical infarct (aOR 6.49, 95% CI 2.35–17.92), and territorial infarcts (aOR 3.54, 95% CI 1.06–11.75) were associated with newly detected AF. The C-statistic of the prediction model for newly detected AF was 0.764.

Conclusion

Initial MRI at the time of stroke may be useful to predict which patients have cardioembolic stroke caused by unrecognized AF. Further studies are warranted to verify these findings and their application to high-risk patients.
Case report: Corneal endothelial degeneration and optic atrophy in dentatorubral-pallidoluysian atrophy quantified by specular micrography and optical coherence tomography
Authors: Takizawa Shunya , Mitamura Hiroto , Ohnuki Yuko , Kawai Kenji , Ohnuki Yoichi , Nagata Eiichiro , Takahashi Wakoh
Published: September 2022

Introduction

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with various neurological manifestations. Corneal endothelial degeneration and optic atrophy have been reported separately; however, there are no reports of corneal endothelial degeneration with optic atrophy.

Cases

Herein, we present four related patients with DRPLA: two patients (69-year-old woman and 80-year-old man) who exhibited both corneal endothelial degeneration and optic atrophy and another two (49- and 51-year-old women, respectively) who exhibited only corneal endothelial degeneration. We quantified the reduction in corneal endothelial cell density (ECD) and hexagonality using specular microscopy and thinning of the circumpapillary retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT).

Conclusion

This is the first report of DRPLA accompanied by corneal endothelial degeneration and/or optic atrophy, which were both quantified based on the corneal ECD and the circumpapillary RNFL thickness using specular micrography and OCT, respectively. The pathophysiological mechanism is unclear; however, the involvement of the nuclear receptor TLX interacting with atrophin-1 may be implicated in ophthalmic manifestations of DRPLA. Therefore, we recommend performing specular micrography and/or OCT when patients with DRPLA experience visual disturbances.
Investigating the contribution of cytoarchitecture to diffusion MRI measures in gray matter using histology
Authors: Baxi Madhura , Cetin-Karayumak Suheyla , Papadimitriou George , Makris Nikos , van der Kouwe Andre , Jenkins Bruce , Moore Tara L. , Rosene Douglas L. , Kubicki Marek , Rathi Yogesh
Published: September 2022

Postmortem studies are currently considered a gold standard for investigating brain structure at the cellular level. To investigate cellular changes in the context of human development, aging, or disease treatment, non-invasive in-vivo imaging methods such as diffusion MRI (dMRI) are needed. However, dMRI measures are only indirect measures and require validation in gray matter (GM) in the context of their sensitivity to the underlying cytoarchitecture, which has been lacking. Therefore, in this study we conducted direct comparisons between in-vivo dMRI measures and histology acquired from the same four rhesus monkeys. Average and heterogeneity of fractional anisotropy and trace from diffusion tensor imaging and mean squared displacement (MSD) and return-to-origin-probability from biexponential model were calculated in nine cytoarchitectonically different GM regions using dMRI data. DMRI measures were compared with corresponding histology measures of regional average and heterogeneity in cell area density. Results show that both average and heterogeneity in trace and MSD measures are sensitive to the underlying cytoarchitecture (cell area density) and capture different aspects of cell composition and organization. Trace and MSD thus would prove valuable as non-invasive imaging biomarkers in future studies investigating GM cytoarchitectural changes related to development and aging as well as abnormal cellular pathologies in clinical studies.
Volumetric optoacoustic neurobehavioral tracking of epileptic seizures in freely-swimming zebrafish larvae
Authors: Özsoy Çağla , Hotz Adriana L. , Rieser Nicolas N. , Chen Zhenyue , Deán-Ben Xosé Luís , Neuhauss Stephan C. F. , Razansky Daniel
Published: September 2022

Fast three-dimensional imaging of freely-swimming zebrafish is essential to understand the link between neuronal activity and behavioral changes during epileptic seizures. Studying the complex spatiotemporal patterns of neuronal activity at the whole-brain or -body level typically requires physical restraint, thus hindering the observation of unperturbed behavior. Here we report on real-time volumetric optoacoustic imaging of aberrant circular swimming activity and calcium transients in freely behaving zebrafish larvae, continuously covering their motion across an entire three-dimensional region. The high spatiotemporal resolution of the technique enables capturing ictal-like epileptic seizure events and quantifying their propagation speed, independently validated with simultaneous widefield fluorescence recordings. The work sets the stage for discerning functional interconnections between zebrafish behavior and neuronal activity for studying fundamental mechanisms of epilepsy and in vivo validation of treatment strategies.
Evaluation of the efficacy of transcatheter arterial embolization combined with apatinib on rabbit VX2 liver tumors by intravoxel incoherent motion diffusion-weighted MR imaging
Authors: Chen Can , Liu Xiao , Deng Lingling , Liao Yunjie , Liu Sheng , Hu Pengzhi , Liang Qi
Published: September 2022

Background and purpose

It is crucial to evaluate the efficacy, recurrence, and metastasis of liver tumors after clinical treatment. This study aimed to investigate the value of Introvoxel Incoherent Motion (IVIM) imaging in the evaluation of rabbit VX2 liver tumors treated with Transcatheter Arterial Embolization (TAE) combined with apatinib.

Methods

Twenty rabbit VX2 liver tumor models were established and randomly divided into either the experimental group (n=15) or the control group (n=5). The experimental group was treated with TAE combined with oral apatinib after successful tumor inoculation, while no treatment was administered following inoculation in the control group. IVIM sequence scan was performed in the experimental group before treatment, at 7 and 14 days after treatment. All rabbits were sacrificed after the last scan of the experimental group. Marginal tissues from the tumors of both groups were excised for immunohistochemical analysis to observe and compare the expression of microvessel density (MVD). The alterations of IVIM-related parameters of tumor tissues in the experimental group, including Apparent Diffusion Coefficient (ADC), True Diffusion Coefficient (D), Pseudodiffusion Coefficient (D*), and Perfusion Fraction (f) were compared at different periods, and the correlation between these parameters and MVD was analyzed.

Results

After treatment, ADC and D values significantly increased, whereas D* and f values both decreased, with statistically significant differences.(P<0.05). The average tumor MVD of the experimental group after TAE combined with apatinib ((33.750 ± 6.743) bars/high power field (HPF)) was significantly lower than that in the control group ((64.200 ± 10.164) bars/HPF)). Moreover, D and f were positively correlated with tumor MVD in the experimental group (r=0.741 for D and r=0.668 for f, P<0.05). However, there was no significant correlation between ADC and D* values of the experimental group and tumor MVD (r=0.252 for ADC and r=0.198 for D*, P>0.05).

Conclusion

IVIM imaging can be employed to evaluate the efficacy of TAE combined with apatinib in rabbit VX2 liver tumors. Alterations in D and f values were closely related to the MVD of liver tumor tissues.
Favorable outcome of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with nonmetastatic osteosarcoma and low-degree necrosis
Authors: Hong Kyung Taek , Park Hyun Jin , Kim Bo Kyung , An Hong Yul , Choi Jung Yoon , Cheon Jung-Eun , Park Sung-Hye , Kim Han-Soo , Kang Hyoung Jin
Published: September 2022

Background

A low-degree tumor necrosis after neoadjuvant chemotherapy is a poor prognostic factor for osteosarcoma (OSA). However, the role of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation in OSA remains controversial. We analyzed the treatment outcomes and prognostic factors of nonmetastatic OSA and compared the HDC and conventional chemotherapy (CC) outcomes of patients with <90% necrosis after neoadjuvant chemotherapy.

Methods

We retrospectively evaluated patients with OSA treated at the Seoul National University Children’s Hospital from 2000 to 2020. Totally, 113 patients with non-metastatic OSA at diagnosis were included. The majority were treated with cisplatin, doxorubicin, and methotrexate as neoadjuvant chemotherapy. This was continued when the postoperative necrosis rate was >90% (good response [GR]), whereas most cases with <90% (poor response [PR]) were changed to chemotherapy. The HDC regimen was composed of melphalan, etoposide, and carboplatin.

Results

The median age at diagnosis was 12.6 years (range, 5.0–20.3), and 61.9% of patients were men. The 5-year event-free survival (EFS) and overall survival (OS) rates were 75.8% and 91.5%, respectively. Among these, 59 and 44 patients were included in the GR and PR groups, respectively. The GR group had a better 5-year EFS rate than the PR group (82.4% vs. 67.3%, p=0.071). Age at diagnosis, sex, tumor site, type of neoadjuvant chemotherapy, and degree of tumor necrosis were not different between the PR-HDC (n=24) and PR-CC (n=20) groups. The 5-year EFS and OS rates in the PR-HDC (n=24) and PR-CC (n=20) groups were 78.6% and 53.6% (p=0.065) and 100% and 76.9% (p=0.024), respectively. In the Cox regression analysis, the PR-CC group (hazard ratio, 4.95; p=0.004) and age ≥12 years (hazard ratio, 2.68; p=0.024) were significant risk factors for 5-year EFS.

Conclusions

HDC showed favorable outcomes in patients with non-metastatic OSA and <90% necrosis after neoadjuvant chemotherapy.
Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents
Authors: Cásedas Guillermo , Moliner Cristina , Maggi Filippo , Mazzara Eugenia , López Víctor
Published: September 2022

Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide. In particular, the polar fraction of hemp including many phenolic compounds has been overlooked when compared with the more lipophilic fraction containing cannabinoids. Therefore, the aim of this study was to assess two extracts of industrial hemp (C. sativa) of different polarity (aqueous and hexane) by evaluating their antioxidant profile and their neuroprotective potential on pharmacological targets in the central nervous system (CNS). Several assays on in vitro antioxidant capacity (DPPH, superoxide radical, FRAP, ORAC), as well as inhibition of physiological enzymes such as acetylcholinesterase (AChE) and monoaminooxidase A (MAO-A) were carried out in order to find out how these extracts may be helpful to prevent neurodegenerative disorders. Neuro-2a cell line was selected to test the cytotoxic and neuroprotective potential of these extracts. Both extracts showed striking antioxidant capacity in the FRAP and ORAC assays, particularly the hexane extract, and interesting results for the DPPH and superoxide radical uptake assays, with the aqueous extract standing out especially in the latter. In enzyme inhibition assays, the aqueous extract showed AChE and MAO-A inhibitory activity, while the hexane extract only reached IC50 value for AChE inhibitory bioassay. Neuro-2a assays demonstrated that polyphenolic extract was not cytotoxic and exhibited cytoprotective properties against hydrogen peroxide and antioxidant response decreasing reactive oxygen species (ROS) production. These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.
Activation of uroepithelial 5-HT4R inhibits mechanosensory activity of murine bladder afferent nerves
Authors: Lu Yu , Li Jie , Dong Li , Luo Ping , Zhang Guohua , Rong Weifang
Published: September 2022

Serotonin (5-HT) is known to act via multiple 5-HT receptors at spinal and supraspinal levels to regulate micturition. However, the contribution of peripheral 5-HT and its receptors in bladder physiology and pathology is not very well understood, despite evidence showing expression of multiple 5-HT receptors in the bladder wall and 5-HT may activate bladder afferent nerves. The current study was designed to investigate the possible role of 5-HT4R in modulation of the sensitivity of bladder afferents to bladder filling. Immunofluorescent staining showed abundant 5-HT4R immunoreactivity largely confined to the uroepithelium in wild type (WT) but not 5-HT4R−/− mice. In the ex vivo bladder-pelvic nerve preparation, intravesical application of the 5-HT4R agonist RS67333 (1–30 μm) caused concentration-dependent decreases of the pelvic nerve response to bladder filling. Such effect was not observed in the presence of 5-HT4R antagonist GR125487 or in 5-HT4R−/− preparations. A cohort of 5-HT4R−/− and WT control mice were treated with intraperitoneal injections of cyclophosphamide (CYP) (75 mg/kg, three times at 2 days interval) to induce chronic cystitis. Void spot analysis showed that CYP-treated 5-HT4R−/− mice urinated more frequently than their CYP-treated WT counterparts. Concomitantly, bladder afferents of CYP-treated 5-HT4R−/− mice displayed exaggerated sensitivity to bladder filling in comparison with the CYP-treated WT controls. These data suggest that 5-HT4R expressed on uroepithelial cells plays an inhibitory role in mechanosensory transduction in the bladder. Loss of 5-HT4R-mediated inhibition may enhance bladder afferent sensitivity and exacerbate bladder overactivity in pathological conditions. We propose that 5-HT4R agonists might be exploited for the treatment of overactive and painful bladder symptoms.
First in vivo analysis of the regulatory protein CP12 of the model cyanobacterium Synechocystis PCC 6803: Biotechnological implications
Authors: Blanc-Garin Victoire , Veaudor Théo , Sétif Pierre , Gontero Brigitte , Lemaire Stéphane D. , Chauvat Franck , Cassier-Chauvat Corinne
Published: September 2022

We report the first in vivo analysis of a canonical CP12 regulatory protein, namely the unique CP12 of the model cyanobacterium Synechocystis PCC 6803, which has the advantage of being able to grow photoautotrophically, photomixotrophically, and photoheterotrophically. The data showed that CP12 is dispensable to cell growth under standard (continuous) light and light/dark cycle, whereas it is essential for the catabolism of exogenously added glucose that normally sustains cell growth in absence of photosynthesis. Furthermore, to be active in glucose catabolism, CP12 requires its three conserved features: its AWD_VEEL motif and its two pairs of cysteine residues. Also interestingly, CP12 was found to regulate the redox equilibrium of NADPH, an activity involving its AWD_VEEL motif and its C-ter cysteine residues, but not its N-ter cysteine residues. This finding is important because NADPH powers up the methylerythritol 4-phosphate (MEP) pathway that synthesizes the geranyl-diphosphate (GPP) and farnesyl-diphosphate (FPP) metabolites, which can be transformed into high-value terpenes by recombinant cyanobacteria producing plant terpene synthase enzymes. Therefore, we have introduced into the Δcp12 mutant and the wild-type (control) strain our replicative plasmids directing the production of the monoterpene limonene and the sesquiterpene bisabolene. The photosynthetic production of both bisabolene and limonene appeared to be increased (more than two-fold) in the Δcp12 mutant as compared to the WT strain. Furthermore, the level of bisabolene production was also higher to those previously reported for various strains of Synechocystis PCC 6803 growing under standard (non-optimized) photoautotrophic conditions. Hence, the presently described Δcp12 strain with a healthy photoautotrophic growth and an increased capability to produce terpenes, is an attractive cell chassis for further gene manipulations aiming at engineering cyanobacteria for high-level photoproduction of terpenes.
Generating distant analogies facilitates relational integration: Intermediary role of relational mindset and cognitive load
Authors: Du Xuesong , Sun Pei
Published: September 2022

Relational integration is essential for learning, working, and living, as we must encode enormous volumes of information and extract their relations to construct knowledge about the environment. Recent research hints that generating distant analogies can temporarily facilitate learners’ state-based relational integration. This study aimed to investigate the internal mechanism underlying the facilitation effect and preliminarily confirm its application in education. First, we adopted the classical n-term premise integration task (Experiment 1a) and the Latin Square Task (Experiment 1b) to explore the robustness of the facilitation effect. Then we employed an emerging multidimensional relational reasoning task to further explore the internal mechanism underlying this facilitation effect (Experiment 2). Finally, we verified the practical role of the facilitation effect in learning the interaction concept in statistics (Experiment 3). The results showed that generating distant analogies did facilitate students’ relational integration performance, both in classical cognitive tasks and in a practical learning task, and a relational mindset and cognitive load play an intermediary role in the facilitation, supporting the cognitive load theory. The results suggest that generating distant analogies can be a useful warm-up activity to assist educators in promoting students’ relational integration.
Building a decoder of perceptual decisions from microsaccades and pupil size
Authors: Nakayama Ryohei , Bardin Jean-Baptiste , Koizumi Ai , Motoyoshi Isamu , Amano Kaoru
Published: September 2022

Many studies have reported neural correlates of visual awareness across several brain regions, including the sensory, parietal, and frontal areas. In most of these studies, participants were instructed to explicitly report their perceptual experience through a button press or verbal report. It is conceivable, however, that explicit reporting itself may trigger specific neural responses that can confound the direct examination of the neural correlates of visual awareness. This suggests the need to assess visual awareness without explicit reporting. One way to achieve this is to develop a technique to predict the visual awareness of participants based on their peripheral responses. Here, we used eye movements and pupil sizes to decode trial-by-trial changes in the awareness of a stimulus whose visibility was deteriorated due to adaptation-induced blindness (AIB). In the experiment, participants judged whether they perceived a target stimulus and rated the confidence they had in their perceptual judgment, while their eye movements and pupil sizes were recorded. We found that not only perceptual decision but also perceptual confidence can be separately decoded from the eye movement and pupil size. We discuss the potential of this technique with regard to assessing visual awareness in future neuroimaging experiments.
Engaging faith communities in public health messaging in response to COVID-19: Lessons learnt from the pandemic in Ituri, Democratic Republic of Congo
Authors: Baba Amuda , Grant Liz , Pearson Nigel , Wild-Wood Emma , Falisse Jean-Benoit , Way Yossa , Kangamina Sadiki
Published: September 2022

Purpose

To understand challenges faced by faith leaders in the Democratic Republic of Congo (DRC) in engaging with current public health strategies for the COVID-19 pandemic; to explain why long-standing collaborations between government, faith-based health services and leaders of faith communities had little impact; to identify novel approaches to develop effective messaging that resonates with local communities.

Methods

A qualitative participatory research design, using a workshop methodology was deployed to seek opinions of an invited group of faith leaders in the DRC provinces of Ituri and Nord-Kivu. A topic guide was developed from data gathered in prior qualitative interviews of faith leaders and members. Topics were addressed at a small workshop discussion. Emerging themes were identified.

Findings

Local faith leaders described how misinterpretation and misinformation about COVID-19 and public health measures led to public confusion. Leaders described a lack of capacity to do what was being asked by government authorities with COVID-19 measures. Leaders' knowledge of faith communities' concerns was not sought. Leaders regretted having no training to formulate health messages. Faith leaders wanted to co-create public health messages with health officials for more effective health messaging.

Conclusion

Public trust in faith leaders is crucial in health emergencies. The initial request by government authorities for faith leaders to deliver set health messages rather than co-develop and design messages appropriate for their congregations resulted in faith communities not understanding health messages. Delivering public health messages using language familiar to faith communities could help to ensure more effective public health communication and counter misinformation.
Non-occupational lead poisoning associated with traditional Chinese medicine: A case report
Authors: Ma Huan , Wu Li-meng , Zou Yu , Li Xiao-an
Published: September 2022

Introduction

Traditional Chinese medicine has a long history and is widely popular in China because of its safety and small side effects. In Chinese families, people believe that the combination of traditional Chinese and Western medicine is more effective, and in terms of conditioning and health care, they tend to rely on traditional Chinese medicine. However, the toxic and side effects of traditional Chinese medicine, especially heavy metal poisoning, should not be ignored.

Patient concerns

A case of non-occupational lead poisoning caused by long-term use of traditional Chinese medicine.

Diagnosis

A 21-year-old man with severe colic periumbilical pain was referred to our hospital. Through careful inquiry of his medical history, we found that he had been taking traditional Chinese medicine to treat facial acne in the past year. His test results showed anemia, liver damage, blood lead concentration of 1,268.4 μg/L, and bone marrow smear showed basophilic stippling erythrocyte. The patient was diagnosed with “lead poisoning.”

Interventions

The patient was given treatment with lead driving.

Outcomes

The patient recovered after treatment.

Conclusion

We found that lead poisoning in patients taking traditional Chinese medicine has been reported from time to time. Through consulting the data, we summarized the most common drugs leading to lead poisoning, and reviewed the pathogenesis and common clinical manifestations of lead poisoning. Because lead poisoning is easy to be misdiagnosed, we should ask more carefully about the past history and drug history of patients in order to make timely diagnosis and treatment.