bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge mapping and research trends of IL-33 from 2004 to 2022: a bibliometric analysis
Authors: Jin Jingyi , Wan Yantong , Shu Qiang , Liu Jinghua , Lai Dengming
Published: April 2023

Background

IL-33 has been studied widely but its comprehensive and systematic bibliometric analysis is yet available. The present study is to summarize the research progress of IL-33 through bibliometric analysis.

Methods

The publications related to IL-33 were identified and selected from the Web of Science Core Collection (WoSCC) database on 7 December 2022. The downloaded data was analyzed with bibliometric package in R software. CiteSpace and VOSviewer were used to conduct IL-33 bibliometric and knowledge mapping analysis.

Results

From 1 January 2004 to 7 December 2022, 4711 articles on IL-33 research published in 1009 academic journals by 24652 authors in 483 institutions from 89 countries were identified. The number of articles had grown steadily over this period. The United States of America(USA) and China are the major contributors in the field of research while University of Tokyo and University of Glasgow are the most active institutions. The most prolific journal is Frontiers in Immunology, while the Journal of Immunity is the top 1 co-cited journal. Andrew N. J. Mckenzie published the most significant number of articles and Jochen Schmitz was co-cited most. The major fields of these publications are immunology, cell biology, and biochemistry & molecular biology. After analysis, the high-frequency keywords of IL-33 research related to molecular biology (sST2, IL-1), immunological effects (type 2 immunity, Th2 cells), and diseases (asthma, cancer, cardiovascular diseases). Among these, the involvement of IL-33 in the regulation of type 2 inflammation has strong research potential and is a current research hotspot.

Conclusion

The present study quantifies and identifies the current research status and trends of IL-33 using bibliometric and knowledge mapping analysis. This study may offer the direction of IL-33-related research for scholars.
Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler’s virus
Authors: Kim Byung S.
Published: April 2023

Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced demyelinating disease. Various cytokines are produced via TLRs, and MDA-5 signals linked with NF-κB activation following TMEV infection. In turn, these signals further amplify TMEV replication and the persistence of virus-infected cells. The signals further elevate cytokine production, promoting the development of Th17 responses and preventing cellular apoptosis, which enables viral persistence. Excessive levels of cytokines, particularly IL-6 and IL-1β, facilitate the generation of pathogenic Th17 immune responses to viral antigens and autoantigens, leading to TMEV-induced demyelinating disease. These cytokines, together with TLR2 may prematurely generate functionally deficient CD25-FoxP3+ CD4+ T cells, which are subsequently converted to Th17 cells. Furthermore, IL-6 and IL-17 synergistically inhibit the apoptosis of virus-infected cells and the cytolytic function of CD8+ T lymphocytes, prolonging the survival of virus-infected cells. The inhibition of apoptosis leads to the persistent activation of NF-κB and TLRs, which continuously provides an environment of excessive cytokines and consequently promotes autoimmune responses. Persistent or repeated infections of other viruses such as COVID-19 may result in similar continuous TLR activation and cytokine production, leading to autoimmune diseases.
A new acid isolated from V. negundo L. inhibits NLRP3 inflammasome activation and protects against inflammatory diseases
Authors: Di Qianqian , Zhao Xibao , Lin Jing , Li Xunwei , Li Xiaoli , Tang Haimei , Zhang Ruihan , Xiao Weilie , Chen Weilin
Published: April 2023

The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.
Development and validation of early death risk score model for emergency status prediction in very severe aplastic anemia
Authors: Liu Xu , Yang Wenrui , Zhang Li , Jing Liping , Ye Lei , Zhou Kang , Li Yuan , Li Jianping , Fan Huihui , Yang Yang , Xiong Youzhen , Zhao Xin , Zhang Fengkui
Published: April 2023

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation cohort results were consistent with those of the training cohort. The area under the receiver operating characteristic curve for the model was 0.835 (0.734,0.936) in the training cohort and 0.862 (0.730,0.994) in the validation cohort. The calibration plots showed high agreement, and decision curve analysis showed good benefit in clinical applications. The VSAA Early Death Risk Score Model can help with early identification of emergency VSAA and optimize treatment strategies. Emergency VSAA with high risk is associated with high early death rate, and alternative donor hematopoietic stem cell transplantation could be a better treatment than IST even without HLA-matching.
CO1 barcodes resolve an asymmetric biphyletic clade for Diabrotica undecimpunctata subspecies and provide nucleotide variants for differentiation from related lineages using real-time PCR
Authors: Tembrock Luke R. , Wilson Christina R. , Zink Frida A. , Timm Alicia E. , Gilligan Todd M. , Konstantinov Alexander S. , Tishechkin Alexey K.
Published: April 2023

Diabrotica undecimpunctata is a multivoltine polyphagous beetle species that has long been documented as a significant agricultural pest throughout its native range in North America. This beetle can vector bacterial and viral plant pathogens that result in major losses to crops such as cucumber and soybean. Many countries outside the Americas treat D. undecimpunctata as a species of quarantine importance, while in the USA only the subspecies D. u. duodecimnotata is subject to quarantine, to prevent introduction from Mexico. Identification of D. undecimpunctata on the basis of morphology alone can be complicated given the use of conflicting characters in the description of some subspecific taxa. To better understand relationships among D. undecimpunctata subspecies and other related species, we sequenced mitochondrial cytochrome oxidase 1 (CO1) and nuclear internal transcribed spacer 2 (ITS2) DNA from individuals in different subspecific taxa and across different parts of the species range using museum samples and interceptions. When our data were combined with publicly available Diabrotica data, no pattern of divergence consistent with the currently recognized subspecific designations was found. In addition, we compared phylogenetic patterns in CO1 data from the congener D. virgifera to demonstrate the utility of mitochondrial data in resolving subspecies. From the CO1 data, a diagnostic real-time PCR assay was developed that could successfully identify all haplotypes within the large D. undecimpunctata clade for use in surveys and identification at ports of entry. These findings underscore the need to resolve molecular and morphological datasets into cogent, lineage-based groupings. Such efforts will provide an evolutionary context for the study of agriculturally important attributes of Diabrotica such as host preferences, xenobiotic metabolism, and natural and anthropogenic patterns of dispersal.
Decreased feeding rates of the copepod Acartia tonsa when exposed to playback harbor traffic noise
Authors: Kühn Saskia , King Franziska , Heubel Katja
Published: April 2023

Introduction

Copepods present the largest and most diverse group of zooplankton and their feeding behavior can affect top-down and bottom-up processes. Thus, how efficient feeding is executed determines the abundance of copepods’ prey and their predators and, with that, carbon transfer and storage in ecosystems. The rise of anthropogenic underwater noise from shipping, oil exploration and exploitation, wind farm construction and operation, and more, is increasingly changing the marine acoustic environment. This acoustic pollution can have detrimental effects on biological life. Studies on this topic increasingly indicate that anthropogenic underwater noise adversely affects primary producers, marine mammals, fish, and invertebrates. However, little data exist on the effects of anthropogenic underwater noise on the feeding behavior of zooplankton.

Methods

Here, we investigated the ingestion and clearance rates of the copepodAcartia tonsaon a motile phytoplankton as a function of prey density under ambient aquarium sound conditions and, when exposed to playback, harbor traffic noise.

Results

We measured significantly decreased ingestion rates and clearance rates ofA. tonsawhen exposed to harbor noise compared to ambient conditions. The negative impact of noise on the ingestion rates was found at all given phytoplankton cell densities between 1k to 10k cells ml−1. Clearance rates were fitted to the Rogers random predator equation which revealed significantly decreased capture rates on phytoplankton under the exposure of harbor noise while handling times remained the same in both sound treatments.

Discussion

Our results call for follow-up studies to focus on noise driven community-effects in field experiments to confirm laboratory results and to predict the outcome of a changing world with multiple stressors. Further, the underlying mechanism on how noise affects the feeding behavior of copepods is still unknown. Noise may distract copepods or mask hydromechanical cues of the prey. Noise may also adversely affect copepod physiology or morphology that would lead to changes in the feeding behavior. All potential mechanisms need to be investigated rigorously in future experiments.
Seasonal variations of siliceous microplankton fluxes and radiolarian assemblages linked to environmental conditions in Prydz Bay polynya, Eastern Antarctica
Authors: Zhang Haifeng , Wang Rujian , Han Zhengbing , Sun Yongming , Fan Gaojing , Zhao Jun , Hu Ji , Ren Jian , Pan Jianming
Published: April 2023

Siliceous microplankton is an effective proxy for connecting modern and past marine environments; however, radiolarians have been understudied in Prydz Bay, Eastern Antarctica. This study investigated the changes in the siliceous microbiota fluxes and radiolarian assemblages captured in a 1-year time-series sediment trap (February 2014 to February 2015, ~490 m water depth) in the polynya of Prydz Bay. The results exhibited the strong seasonality in the radiolarian assemblages and the fluxes of radiolarians, diatoms, silicoflagellates and sponge spicules, with low numbers in winter and high numbers in summer. Seasonal variations in the sea ice and plankton community were critical in these patterns. The total radiolarian flux (TRF) displayed three peaks with higher flux than the annual average TRF over the year, all of which occurred in summer. These TRF peaks were mainly driven by seasonal fluctuations of sea ice, primary productivity, grazing pressure caused by phytophagous zooplankton and resuspension of small radiolarians in the surface sediments induced by modified Circumpolar Deep Water (mCDW) intrusion onto the shelf. There were also two notable low-TRF stages, mainly related to full sea-ice coverage and high grazing pressure. Two dominant assemblages were recognized by means of Q-factor analysis. Dominant assemblage one was composed of three small-sized taxa,Antarctissasp.,Phormacantha hystrixandPlectacantha oikiskos, which could be used as a proxy for primary productivity in the Marginal Ice Zone (MIZ) in Prydz Bay. Dominant assemblage two was composed ofAntarctissa strelkoviandAntarctissa denticulata, withA. strelkovidominating. The high flux and high relative abundance ofA. strelkovimarked the extension of Ice Shelf Water (ISW) to the shelf area in Prydz Bay. These findings will provide new insights and reliable proxies for modern and paleoceanographic research in the Southern Ocean.
Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit
Authors: Nogueira Matheus Carvalho Alves , Nobre Vandack , Pires Magda Carvalho , Ramos Lucas Emanuel Ferreira , Ribeiro Yara Cristina Neves Marques Barbosa , Aguiar Rubia Laura Oliveira , Vigil Flavia Maria Borges , Gomes Virginia Mara Reis , Santos Camila de Oliveira , Miranda Davi Mesquita , Durães Pamela Andrea Alves , Costa Josiane Moreira da , Schwarzbold Alexandre Vargas , Gomes Angélica Gomides dos Reis , Pessoa Bruno Porto , Matos Carolina Cunha , Cimini Christiane Corrêa Rodrigues , Carvalho Cíntia Alcântara de , Ponce Daniela , Manenti Euler Roberto Fernandes , Cenci Evelin Paola de Almeida , Anschau Fernando , Costa Flávia Carvalho Cardoso , Nascimento Francine Janaina Magalhães , Bartolazzi Frederico , Grizende Genna Maira Santos , Vianna Heloisa Reniers , Nepomuceno Jomar Cristeli , Ruschel Karen Brasil , Zandoná Liege Barella , Castro Luís César de , Souza Maíra Dias , Carneiro Marcelo , Bicalho Maria Aparecida Camargos , Vilaça Mariana do Nascimento , Bonardi Naiara Patrícia Fagundes , Oliveira Neimy Ramos de , Lutkmeier Raquel , Francisco Saionara Cristina , Araújo Silvia Ferreira , Delfino-Pereira Polianna , Marcolino Milena Soriano
Published: April 2023

Objectives

To assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score).

Materials and methods

Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality.

Results

ABC2-SPH had an area under the curve of 0.716 (95% CI 0.693–0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score.

Conclusion

ABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients.
A new multidimensional group intervention for cognitive and psychosocial functioning for older adults: Background, content, and process evaluation
Authors: Chadjikyprianou Andreas , Constantinidou Fofi
Published: April 2023

Introduction

An essential element of quality aging is the maintenance of cognitive and psychosocial functioning. The principal objective of the present paper was to present the theoretical framework, content and process evaluation of a newly developed multi-dimensional group intervention designed to strengthen/improve areas of cognitive and psychosocial functioning in adults over 65.

Methods

The intervention implements multiple methodologies aiming to facilitate contextual integration of learned concepts and strategies derived from clinical psychology and rehabilitation. It moves seamlessly on the cognition–emotion axes and consists of five active ingredients selected to address challenges associated with aging: Memory Compensatory Strategies, Problem-Solving, Emotion Regulation, Mindfulness, and Locus of Control. Thirty participants joined the intervention group aged 65–75  years (M = 69.03; SD = 3.04). All 30 participants who were included in the intervention group completed the program.

Results

Results from the Participant Satisfaction Scale indicate that the program was perceived very positively by participants, who also reported implementing their newly learned strategies in activities of daily life. Furthermore, there was high correlation between internal locus of control and the learned strategies.

Discussion

The outcomes of this analysis indicate that the intervention is feasible and well tolerated by our target group. This multidimensional intervention may offer a valuable contribution to public health care and dementia prevention for older adults.

Clinical Trial Registration

[https://clinicaltrials.gov/ct2/results?cond=NCT01481246], identifier [NCT01481246].
The role of replication-induced chromosomal copy numbers in spatio-temporal gene regulation and evolutionary chromosome plasticity
Authors: Teufel Marc , Henkel Werner , Sobetzko Patrick
Published: April 2023

For a coherent response to environmental changes, bacterial evolution has formed a complex transcriptional regulatory system comprising classical DNA binding proteins sigma factors and modulation of DNA topology. In this study, we investigate replication-induced gene copy numbers - a regulatory concept that is unlike the others not based on modulation of promoter activity but on replication dynamics. We show that a large fraction of genes are predominantly affected by transient copy numbers and identify cellular functions and central pathways governed by this mechanism in Escherichia coli. Furthermore, we show quantitatively that the previously observed spatio-temporal expression pattern between different growth phases mainly emerges from transient chromosomal copy numbers. We extend the analysis to the plant pathogen Dickeya dadantii and the biotechnologically relevant organism Vibrio natriegens. The analysis reveals a connection between growth phase dependent gene expression and evolutionary gene migration in these species. A further extension to the bacterial kingdom indicates that chromosome evolution is governed by growth rate related transient copy numbers.
Alleviation of DSS-induced colitis in mice by a new-isolated Lactobacillus acidophilus C4
Authors: Liu Qianqian , Jian Wenwen , Wang Lu , Yang Shenglin , Niu Yutian , Xie ShuaiJing , Hayer Kim , Chen Kun , Zhang Yi , Guo Yanan , Tu Zeng
Published: April 2023

Introduction

Probiotic is adjuvant therapy for traditional drug treatment of ulcerative colitis (UC). In the present study, Lactobacillus acidophilus C4 with high acid and bile salt resistance has been isolated and screened, and the beneficial effect of L. acidophilus C4 on Dextran Sulfate Sodium (DSS)-induced colitis in mice has been evaluated. Our data showed that oral administration of L. acidophilus C4 remarkably alleviated colitis symptoms in mice and minimized colon tissue damage.

Methods

To elucidate the underlying mechanism, we have investigated the levels of inflammatory cytokines and intestinal tight junction (TJ) related proteins (occludin and ZO-1) in colon tissue, as well as the intestinal microbiota and short-chain fatty acids (SCFAs) in feces.

Results

Compared to the DSS group, the inflammatory cytokines IL-1β, IL-6, and TNF-α in L. acidophilus C4 group were reduced, while the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were found to be elevated. In addition, proteins linked to TJ were elevated after L. acidophilus C4 intervention. Further study revealed that L. acidophilus C4 reversed the decrease in intestinal microbiota diversity caused by colitis and promoted the levels of SCFAs.

Discussion

This study demonstrate that L. acidophilus C4 effectively alleviated DSS-induced colitis in mice by repairing the mucosal barrier and maintaining the intestinal microecological balance. L. acidophilus C4 could be of great potential for colitis therapy.
Hybridization alters the gut microbial and metabolic profile concurrent with modifying intestinal functions in Tunchang pigs
Authors: He Jiayi , Zhang Yunchao , Li Hui , Xie Yanshe , Huang Guiqing , Peng Chen , Zhao Pengju , Wang Zhengguang
Published: April 2023

Introduction

Hybridization has been widely used among Chinese wild boars to improve their growth performance and maintain meat quality. Most studies have focused on the genetic basis for such variation. However, the differences in the gut environment between hybrid and purebred boars, which can have significant impacts on their health and productivity, have been poorly understood.

Methods

In the current study, metagenomics was used to detect the gut microbial diversity and composition in hybrid Batun (BT, Berkshire × Tunchang) pigs and purebred Tunchang (TC) pigs. Additionally, untargeted metabolomic analysis was used to detect differences in gut metabolic pathways. Furthermore, multiple molecular experiments were conducted to demonstrate differences in intestinal functions.

Results

As a result of hybridization in TC pigs, a microbial change was observed, especially in Prevotella and Lactobacillus. Significant differences were found in gut metabolites, including fatty acyls, steroids, and steroid derivatives. Furthermore, the function of the intestinal barrier was decreased by hybridization, while the function of nutrient metabolism was increased.

Discussion

Evidences were shown that hybridization changed the gut microbiome, gut metabolome, and intestinal functions of TC pigs. These findings supported our hypothesis that hybridization altered the gut microbial composition, thereby modifying the intestinal functions, even the host phenotypes. Overall, our study highlights the importance of considering the gut microbiome as a key factor in the evaluation of animal health and productivity, particularly in the context of genetic selection and breeding programs.
The rearrangement of actin cytoskeleton in mossy fiber synapses in a model of experimental febrile seizures
Authors: Yang Nuo , Chen Yin-Bo , Zhang Yan-Feng
Published: April 2023

Background

Experimental complex febrile seizures induce a persistent hippocampal hyperexcitability and an enhanced seizure susceptibility in adulthood. The rearrangement of filamentous actin (F-actin) enhances the excitability of hippocampus and contributes to epileptogenesis in epileptic models. However, the remodeling of F-actin after prolonged febrile seizures is to be determined.

Methods

Prolonged experimental febrile seizures were induced by hyperthermia on P10 and P14 rat pups. Changes of actin cytoskeleton in hippocampal subregions were examined at P60 and the neuronal cells and pre- /postsynaptic components were labeled.

Results

F-actin was increased significantly in the stratum lucidum of CA3 region in both HT + 10D and HT + 14D groups and further comparison between the two groups showed no significant difference. The abundance of ZNT3, the presynaptic marker of mossy fiber (MF)-CA3 synapses, increased significantly whereas the postsynaptic marker PSD95 did not change significantly. Overlapping area of F-actin and ZNT3 showed a significant increase in both HT+ groups. The results of cell counts showed no significant increase or decrease in the number of neurons in each area of hippocampus.

Conclusion

F-actin was significantly up-regulated in the stratum lucidum of CA3, corresponding to the increase of the presynaptic marker of MF-CA3 synapses after prolonged febrile seizures, which may enhance the excitatory output from the dentate gyrus to CA3 and contribute to the hippocampal hyperexcitability.
Clinical features of patients with MOG-IgG associated disorders and analysis of the relationship between fibrinogen-to-albumin ratio and the severity at disease onset
Authors: Li Yue , Wang Sai , Liu Panpan , Ma Jinxiu , Liu Xinjing , Yuan Jing
Published: April 2023

Objective

The study aimed to investigate the differences in clinical features between pediatric and adult patients with first-episode MOG-IgG associated disorders (MOGAD) and evaluate the relationship between the fibrinogen-to-albumin ratio (FAR) and the severity of neurological deficits at disease onset.

Methods

We retrospectively collected and analyzed biochemical test results, imaging characteristics, clinical manifestations, expanded disability status scale (EDSS) score, and FAR. The Spearman correlation analysis and logistic regression models were used to examine the association between FAR and severity. Receiver operating characteristic (ROC) curve analysis was to analyze the predictive ability of FAR for the severity of neurological deficits.

Results

Fever (50.0%), headache (36.1%), and blurred vision (27.8%) were the most common clinical manifestations in the pediatric group (<18 years old). However, in the adult group (≥18 years old), the most common symptoms were blurred vision (45.7%), paralysis (37.0%), and paresthesia (32.6%). Fever was more common in the pediatric group, while paresthesia was more common in the adult patients, with all differences statistically significant (P < 0.05). The most frequent clinical phenotype in the pediatric group was acute disseminated encephalomyelitis (ADEM; 41.7%), whereas optic neuritis (ON; 32.6%) and transverse myelitis (TM; 26.1%) were more common in the adult group. The differences in clinical phenotype between the two groups were statistically significant (P < 0.05). In both pediatric and adult patients, cortical/subcortical and brainstem lesions were the most common lesions on cranial magnetic resonance imaging (MRI), whereas, for spinal MRI, cervical and thoracic spinal cord lesions were the most commonly observed. According to binary logistic regression analysis, FAR was an independent risk factor for the severity of neurological deficits (odds ratio = 1.717; 95% confidence interval = 1.191–2.477; P = 0.004). FAR (r = 0.359, P = 0.001) was positively correlated with the initial EDSS score. The area under the ROC curve was 0.749.

Conclusion

The current study found age-dependent phenotypes in MOGAD patients as ADEM was more commonly observed in patients < 18 years old, while ON and TM were more frequently found in patients ≥18 years old. A high FAR level was an independent indicator for more severe neurological deficits at disease onset in patients with a first episode of MOGAD.
Perspective: Vagal nerve stimulation in the treatment of new-onset refractory status epilepticus
Authors: Mantoan Ritter Laura , Selway Richard
Published: April 2023

Introduction

Resistance to drug therapy is a major hurdle in new-onset refractory status epilepticus (NORSE) treatment and there is urgent need to develop new treatment approaches. Non-drug approaches such as neuromodulation offer significant benefits and should be investigated as new adjunct treatment modalities. An important unanswered question is whether desynchronizing networks by vagal nerve stimulation (VNS) may improve seizure control in NORSE patients.

Main text

We present a summary of published NORSE cases treated with VNS and our own data, discuss possible mechanisms of action, review VNS implantation timing, stimulation setting titration protocols and outcomes. Further, we propose avenues for future research.

Discussion

We advocate for consideration of VNS for NORSE both in early and late stages of the presentation and hypothesize a possible additional benefit from implantation in the acute phase of the disease. This should be pursued in the context of a clinical trial, harmonizing inclusion criteria, accuracy of documentation and treatment protocols. A study planned within our UK-wide NORSE-UK network will answer the question if VNS may confer benefits in aborting unremitting status epilepticus, modulate ictogenesis and reduce long-term chronic seizure burden.
Identification of resting-state networks using dynamic brain perfusion SPECT imaging: A fSPECT case report
Authors: Doyen Matthieu , Hossu Gabriela , Heyer Sébastien , Zaragori Timothée , Imbert Laetitia , Verger Antoine
Published: April 2023

Connectivity studies with nuclear medicine systems are scarce in literature. They mainly employ PET imaging and group level analyses due to the low temporal resolution of PET and especially SPECT imaging. Our current study analyses connectivity at an individual level using dynamic SPECT imaging, which has been enabled by the improved temporal resolution performances provided by the 360°CZT cameras. We present the case of an 80-year-old man referred for brain perfusion SPECT imaging for cognitive disorders for whom a dynamic SPECT acquisition was performed utilizing a 360°CZT camera (temporal sampling of 15 frames × 3 s, 10 frames × 15 s, 14 frames × 30 s), followed by a conventional static acquisition of 15 m. Functional SPECT connectivity (fSPECT) was assessed through a seed correlation analysis and 5 well-known resting-state networks were identified: the executive, the default mode, the sensory motor, the salience, and the visual networks. This case report supports the feasibility of fSPECT imaging to identify well known resting-state networks, thanks to the novel properties of a 360°CZT camera, and opens the way to the development of more dedicated functional connectivity studies using brain perfusion SPECT imaging.
Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy
Authors: Sahara Naruhiko , Yanai Rin
Published: April 2023

Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheimer’s disease. For tau-targeting therapy, experimental models recapitulating human tau pathologies are indispensable. However, there are limited numbers of animal models that display intracellular filamentous tau aggregations. At present, several lines of P301L/S mutant tau-expressing transgenic mice successfully developed neurofibrillary pathology in the central nervous system, while most non-mutant tau-expressing transgenic mice rarely developed tau pathology. Importantly, recent studies have revealed that transgenes disrupt the coding sequence of endogenous genes, resulting in deletions and/or structural variations at the insertion site. Although any impact on the pathogenesis of tauopathy is unknown, gene disruptions may affect age-related neurodegeneration including tangle formation and brain atrophy. Moreover, some mouse lines show strain-dependent pathological features. These limitations (FTDP-17 mutations, insertion/deletion mutations, and genetic background) are a major hindrance to the establishment of a precise disease model of tauopathy. In this review, we noticed both the utility and the pitfalls of current P301L/S mutant tau-expressing transgenic mice, and we propose future strategies of mouse modeling to replicate human tauopathies.
Evaluation of a low-resource soy protein production method and its products
Authors: Gulkirpik Ece , Donnelly Annette , Nowakunda Kephas , Liu Keshun , Andrade Laborde Juan E.
Published: April 2023

Introduction

One key approach to achieve zero hunger in Sub-Saharan Africa (SSA) is to develop sustainable, affordable, and green technologies to process nutritious food products from locally available sources. Soybeans are an inexpensive source of high-quality protein that may help reduce undernutrition, but it is underutilized for human consumption. This research evaluated the feasibility of a low-cost method developed initially at the United States Department of Agriculture to produce soy protein concentrate (SPC) from mechanically pressed soy cake and thus create a more valuable ingredient to improve protein intake in SSA.

Methods

The method was initially tested in the bench scale to assess process parameters. Raw ingredients comprised defatted soy flour (DSF), defatted toasted soy flour (DTSF), low-fat soy flour 1 (LFSF1; 8% oil), and LFSF2 (13% oil). Flours were mixed with water (1:10 w/v) at two temperatures (22 or 60°C) for two durations (30 or 60 min). After centrifugation, supernatants were decanted, and pellets were dried at 60°C for 2.5 h. Larger batches (350 g) of LFSF1 were used to examine the scalability of this method. At this level, protein, oil, crude fiber, ash, and phytic acid contents were measured. Thiobarbituric acid reactive substances (TBARS), hexanal concentration and peroxide value were measured in SPC and oil to evaluate oxidative status. Amino acid profiles, in vitro protein digestibility, and protein digestibility corrected amino acid score (PDCAAS) were determined to assess protein quality.

Results

Bench scale results showed accumulation of protein (1.5-fold higher) and reduction of oxidative markers and phytic acid to almost half their initial values. Similarly, the large-scale production trials showed high batch-to-batch replicability and 1.3-fold protein increase from initial material (48%). The SPC also showed reductions in peroxide value (53%), TBARS (75%), and hexanal (32%) from the starting material. SPC’s in vitro protein digestibility was higher than the starting material.

Conclusion

The proposed low-resource method results in an SPC with improved nutritional quality, higher oxidative stability, and lower antinutrient content, which enhances its use in food-to-food fortification for human consumption and is thus amenable to address protein quantity and quality gaps among vulnerable populations in SSA.
Culturally-tailored cookbook for promoting positive dietary change among hypertensive Filipino Americans: a pilot study
Authors: Sijangga Madelyn O. , Pack David V. , Yokota Nicole O. , Vien Morgan H. , Dryland Alexander D. G. , Ivey Susan L.
Published: April 2023

Introduction

Among all Asian American subgroups, Filipino-Americans have consistently been shown to have the highest rates of hypertension, raising risks of heart attack and stroke. Despite this alarming fact, little has been done to investigate culturally-sensitive interventions to control hypertension rates in this vulnerable population. To address the lack of culturally-relevant lifestyle options for blood pressure management currently available to the Filipino community, this exploratory pilot study used a design thinking approach informed by culinary medicine to develop a culturally-tailored, heart-healthy, and low sodium recipe cookbook for Filipino Americans with hypertension and evaluate its feasibility as a hypertension intervention.

Methods

Our team developed a cookbook using participatory methods and design thinking, utilizing input from five Filipino culinary experts and a Registered Dietitian. The cookbook incorporates traditional Filipino recipes, excerpts from community members’ interviews, and nutrient analyses. Twenty Filipinx-identifying individuals* who self-reported physician-diagnosed hypertension were recruited from Filipino community-based organizations, enrolled into this study, provided with the cookbook, and asked to cook at least one recipe. Pre- and post-intervention surveys were conducted and centered around behavior change and features of the cookbook.

Results

This study provided evidence for the cookbook’s acceptability and feasibility, with participants’ open-ended responses revealing that the recipes, nutrition labels, illustrations, and cultural aspects of the cookbook increased motivation to achieve dietary change, including reducing sodium in their diet to improve their blood pressure. Participant responses also indicated positive behavior change as a result of using the cookbook, with participants reporting increased likelihood of adopting recommended actions to lower their BP after utilizing the cookbook (x¯ = 80.83%), compared to before (x¯ = 63.75%, p < 0.008), according to Hypertension Self-Care Management scaled scores.

Discussion

In conclusion, the results of this pilot study demonstrated acceptability of this unique cookbook and provide preliminary findings consistent with increased motivation in participants to make dietary changes and improve personal health, drawing attention to the importance of considering future culturally-tailored health interventions. Next steps should include a robust, randomized controlled trial design comparing measured blood pressure outcomes of an intervention vs. control group. *Filipinx is an inclusive term representing the gender identities of all participants in our study.
Lead detoxification of edible fungi Auricularia auricula and Pleurotus ostreatus: the purification of the chelation substances and their effects on rats
Authors: Zhang Weiwei , Zheng Xiaojie , Chen Xiangdong , Jiang Xuezhen , Wang Hexiang , Zhang Guoqing
Published: April 2023

Lead is a global pollutant that causes widespread concern. When a lead enters the body, it is distributed throughout the body and accumulates in the brain, bone, and soft tissues such as the kidney, liver, and spleen. Chelators used for lead poisoning therapy all have side effects to some extent and other drawbacks including high cost. Exploration and utilization of natural antidotes become necessary. To date, few substances originating from edible fungi that are capable of adsorbing lead have been reported. In this study, we found that two commonly eaten mushrooms Auricularia auricula and Pleurotus ostreatus exhibited lead adsorption capacity. A. auricula active substance (AAAS) and P. ostreatus active substance (POAS) were purified by hot-water extraction, ethanol precipitation from its fruiting bodies followed by ion exchange chromatography, ultrafiltration, and gel filtration chromatography, respectively. AAAS was 3.6 kDa, while POAS was 4.9 kDa. They were both constituted of polysaccharides and peptides. The peptide sequences obtained by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) proved that they were rich in amino acids with side chain groups such as hydroxyl, carboxyl, carbonyl, sulfhydryl, and amidogen. Two rat models were established, but only a chronic lead-induced poisoning model was employed to determine the detoxification of AAAS/POAS and their fruiting body powder. For rats receiving continuous lead treatment, either AAAS or POAS could reduce the lead levels in the blood. They also promoted the elimination of the burden of lead in the spleen and kidney. The fruiting bodies were also proved to have lead detoxification effects. This is the first study to identify new functions of A. auricula and P. ostreatus in reducing lead toxicity and to provide dietary strategies for the treatment of lead toxicity.
Protocol for a randomized controlled trial evaluating the effect of Hibiscus syriacus L. flower extract on sleep quality
Authors: Choi Yujin , Park Yu Hwa , Yang Changsop , Kim Do Hoon , Lee Kye Wan , Lee Mi Young
Published: April 2023

Introduction

Hibiscus syriacus L. flower (HSF) is a food ingredient commonly used for tea, and previous animal studies have reported its sleep-promoting effect. This study aims to test the potential of HSF extract as functional food that improves sleep in humans.

Methods and analysis

Eighty participants with sleep disturbances who meet the inclusion/exclusion criteria will be enrolled in this study. Since the effect of HSF extract on sleep is considered to be that of a functional food rather than a medicine, participants with severe insomnia will be excluded from the study. The enrolled participants will be randomly assigned to the HSF extract or placebo groups in a 1:1 ratio. The HSF extract and placebo capsules will look identical, and participants, investigators, and outcome assessors will be blinded to the allocation. Four capsules of HSF extract or placebo will be orally administered 30–60 min before bedtime for 4 weeks. The primary outcome of this study will be the change in the Pittsburgh Sleep Quality Index (PSQI) global score from the baseline after 4 weeks. The subjective and objective changes in the participants’ sleep will be evaluated using the Insomnia Severity Index (ISI), Epworth Sleep Scale (ESS), sleep diary, and polysomnography (PSG). The occurrence of adverse events will be closely monitored.

Discussion

The results of this trial will provide data on the efficacy and safety of HSF extract in enhancing sleep quality. Based on the results, the potential of HSF extract as a functional food that improves sleep in humans will be evaluated, and the findings of the trial will be submitted to the Korean Ministry of Food and Drug Safety for consideration as a new functional ingredient that may help to improve sleep quality.

Clinical trial registration

: Clinical Research Information Service: KCT0007314; Registered 19 May 2022, https://cris.nih.go.kr/cris/search/detailSearch.do/21497.
Advanced diffuse hepatic angiosarcoma treated successfully with TACE and targeted immunotherapy: A case report
Authors: Lin Yucheng , Chen Zheng , Yang Jianchuan , Lin Ying , Chen Sheng , Xie Ying , Wu Songsong
Published: April 2023

Primary hepatic angiosarcoma (PHA), a rare soft tissue tumor, accounts for only 2% of all liver malignancies. Pathologically challenging, PHA is difficult to be distinguished from other malignancies with ultrasound, Computed Tomography (CT), or Magnetic Resonance Imaging (MRI). Due to late diagnosis and resistance against traditional chemotherapy and/or radiotherapy, only 3% of PHA patients can survive up to two years after diagnosis. To our best knowledge, this case report presents the first case of an advanced diffuse PHA with ruptured hemorrhage that has been effectively treated with TACE and Anlotinib plus Camrelizumab. So far, the patient has received 10 cycles of treatment and is faring well. Latest MRI results show that the tumor has shrunk by 56% and can be assessed as a partial response (PR). This case report includes our experience in treating such a advanced malignancy, and we hope that larger studies on advanced PHA can better quantify the potential benefit.
Operative management of immune checkpoint colitis following in-transit melanoma: Case report
Authors: Childers Betzaira G. , Donovan Eileen , Lo Winifred M. , Janowak Lauren M. , Sussman Jeffrey , Janowak Christopher F.
Published: April 2023

Immune checkpoint inhibitors are increasingly used as powerful anti-neoplastic therapies in the setting of melanoma. Colitis is a known complication of immune checkpoint inhibitors that if often medically managed. We present a patient with stage IV melanoma with demonstrated in-transit disease undergoing immune checkpoint inhibitor therapy. The patient subsequently developed recalcitrant severe colitis that necessitated operative intervention and bowel resection. The association of immune check point inhibitors and immune related adverse effects are discussed as well as treatments of advanced colitis, including the possibility of surgical management in the setting of severe colitis with complications.
Potential of Novel Methyl Jasmonate Analogs as Anticancer Agents to Metabolically Target HK-2 Activity in Glioblastoma Cells
Authors: Uludağ Damla , Bay Sadık , Sucu Bilgesu Onur , Şavluğ İpek Özgecan , Mohr Thomas , Güzel Mustafa , Karakaş Nihal
Published: April 2023

Change in the energy metabolism of cancer cells, which display significant differences compared to normal cells, is a rising phenomenon in developing new therapeutic approaches against cancers. One of the metabolic enzymes, hexokinase-II (HK-II) is involved in glycolysis, and inhibiting the HK-II activity may be a potential metabolic target for cancer therapy as most of the drugs in clinical use act on DNA damage. Methyl jasmonate (MJ) is one of the compounds blocking HK-II activity in cancer cells. In a previous study, we showed that the novel MJ analogs inhibit HK-II activity through VDAC detachment from the mitochondria. In this study, to evaluate the potential of targeting HK-2 activity, through patient cohort analysis, we first determined HK-2 expression levels and prognostic significance in highly lethal glioblastoma (GBM) brain tumor. We then examined the in vitro therapeutic effects of the novel analogs in the GBM cells. Here, we report that, among all, compound-10 (C-10) showed significant in vitro therapeutic efficacy as compared to MJ which is in use for preclinical and clinical studies. Afterward, we analyzed cell death triggered by C-10 in two different GBM cell lines. We found that C-10 treatment increased the apoptotic/necrotic cells and autophagy in GBM cells. The newly developed analog, C-10, was found to be lethal against GBM by the activation of cell death authorities, mostly in a necrotic and autophagic fashion at the early stages of the treatment. Considering that possibly decreased intracellular ATP levels by C-10 mediated inhibition of HK-2 activity and disabled VDAC interaction, a more detailed analysis of HK-2 inhibition–mediated cell death can provide a deep understanding of the mechanism of action on the oncosis/necroptosis axis. These findings provide an option to design clinically relevant and effective novel HK-II inhibitors and suggest novel MJ analogs to further study them as potential anticancer agents against GBM.