bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of extracellular vesicle-mediated immune evasion in melanoma
Authors: Dieterich Lothar C.
Published: August 2022

Melanoma-derived extracellular vesicles (EVs) have been found to promote tumor growth and progression, and to predict patient responsiveness to immunotherapy. Consequently, EVs have been implicated in tumor immune evasion, and multiple studies reported immune-regulatory activities of melanoma EVs in vitro and in vivo. This review highlights mechanistic insights in EV-mediated regulation of various immune cell types, including effects on inflammatory, apoptotic, stress-sensing and immune checkpoint pathways as well as antigen-dependent responses. Additionally, current challenges in the field are discussed that need to be overcome to determine the clinical relevance of these various mechanisms and to develop corresponding therapeutic approaches to promote tumor immunity and immunotherapy responsiveness in melanoma patients in the future.
The striking mimics between COVID-19 and malaria: A review
Authors: Konozy Emadeldin Hassan E. , Osman Makarim El-fadil M. , Ghartey-Kwansah George , Abushama Hind Mohamed
Published: August 2022

Objectives

COVID-19 is a transmissible illness triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its onset in late 2019 in Wuhan city of China, it continues to spread universally, leading to an ongoing pandemic that shattered all efforts to restrain it. On the other hand, in Africa, the COVID-19 infection may be influenced by malaria coinfection. Hence, in this review article, we aimed to give a comprehensive account of the similarities between COVID-19 and malaria in terms of symptoms, clinical, immunological, and molecular perspectives.

Methodology

In this article, we reviewed over 50 research papers to highlight the multilayered similarities between COVID-19 and malaria infections that might influence the ontology of COVID-19.

Results

Despite the poor health and fragile medical system of many sub-Saharan African countries, they persisted with a statistically significantly low number of COVID-19 cases. This was attributed to many factors such as the young population age, the warm weather, the lack of proper diagnosis, previous infection with malaria, the use of antimalarial drugs, etc. Additionally, population genetics appears to play a significant role in shaping the COVID-19 dynamics. This is evident as recent genomic screening analyses of the angiotensin-converting enzyme 2 (ACE2) and malaria-associated-variants identified 6 candidate genes that might play a role in malaria and COVID-19 incidence and severity. Moreover, the clinical and pathological resemblances between the two diseases have made considerable confusion in the diagnosis and thereafter curb the disease in Africa. Therefore, possible similarities between the diseases in regards to the clinical, pathological, immunological, and genetical ascription were discussed.

Conclusion

Understanding the dynamics of COVID-19 infection in Sub-Saharan Africa and how it is shaped by another endemic disease like malaria can provide insights into how to tailor a successful diagnostic, intervention, and control plans that lower both disease morbidity and mortality.
Enhancement of liver mitochondrial complex I and energy metabolism induced by enteritis: The key role of gut microbiota derived endotoxins
Authors: Fu Lele , Liu Haokun , Chen Wen , Hooft Jamie Marie , Øverland Margareth , Cai Wanjie , Han Dong , Zhu Xiaoming , Yang Yunxia , Jin Junyan , Xie Shouqi
Published: August 2022

Inflammation is an energy-intensive process and the liver is a key organ in energy regulation. Since the intestine and liver exchange nutrients and metabolites, enteritis can affect the liver. To investigate the correlation between enteritis and liver metabolism, we developed an intestinal inflammation model with concentration-dependent 2,4,6-trinitrobenzene sulfonic acid (TNBS) in gibel carp (Carassius gibelio). The results showed the dysregulation of intestinal tight junction, increased permeability of the gut barrier, and apoptosis of epithelial cells during the development of enteritis. The liver metabolome was analyzed by LC-MS and the live respiration was determined using Oxygraph-2k. The results showed that glycolysis, the TCA cycle and pyrimidine metabolism were affected by intestinal inflammation. In particular, the activity of hepatic mitochondrial respiratory chain complex I was significantly increased. Structure and abundance changes of gut microbiota were analyzed by 16S rRNA sequencing analysis. Pathogenic bacteria in the intestine, as well as plasma LPS, increased significantly. Using a liver cell line, we verified that the dysfunctional metabolism of the liver is related to the dislocation of LPS. All results imply the existence of a connection between enteritis and liver metabolism in gibel carp, and the gut microbiome plays a critical role in this process.
Akt isoforms in the immune system
Authors: Guerau-de-Arellano Mireia , Piedra-Quintero Zayda L. , Tsichlis Philip N.
Published: August 2022

Akt is a PI3K-activated serine-threonine kinase that exists in three distinct isoforms. Akt’s expression in most immune cells, either at baseline or upon activation, reflects its importance in the immune system. While Akt is most highly expressed in innate immune cells, it plays crucial roles in both innate and adaptive immune cell development and/or effector functions. In this review, we explore what’s known about the role of Akt in innate and adaptive immune cells. Wherever possible, we discuss the overlapping and distinct role of the three Akt isoforms, namely Akt1, Akt2, and Akt3, in immune cells.
The removal of atmospheric aerosols in a heavy industrial coastal city in China with frequent rainfall
Authors: Zhou Xin , Li Zhiyang , Chen Chunqing , Luo Huijie , Zhu Qingmei , Zeng Zhen , Lao Qibin
Published: August 2022

Rapid urbanization and heavy industrialization generally result in serious aerosol pollution. Contrary to this conventional wisdom, Zhanjiang, one industrial city in the southernmost point of the Chinese mainland, is not accompanied by aerosol pollution and its air quality index always ranks high compared to other cities in China. To investigate this contradiction, 72-hour total suspended particles (TSPs) and water-soluble inorganic ions (WSIIs; including Mg2+, Ca2+, K+, Na+, NH4+, Cl-, NO3-, and SO42-) were collected in Zhanjiang, China, from November 2018 to November 2019. The relative humidity (RH) was higher than 80% throughout the whole year in Zhanjiang. However, the TSPs and WSIIs were not correlated with RH, indicating that RH can increase the particle size, but this had a minor impact on the dry deposition rate. The larger particles induced by RH were easily captured by wet precipitation, leading to a seasonal pattern with higher TSP and WSII mass concentrations during the dry and cool season and lower values during the hot and rainy season. This seasonal pattern and high aerosol acidity indicate that TSPs, WSIIs, and acidic gaseous precursors from the local sources were preferentially scavenged by the abundant rainfall and high precipitation frequency. Principal component analysis (PCA) results suggest that relatively clean marine emissions and secondary aerosols were the most important sources of TSPs and WSIIs. Our results indicate that the inconsistency between the heavy industrial activities and excellent air quality in Zhanjiang may be related to the high precipitation frequency (63%) and the marine dilution effect (27%).
Revealing underlying mechanisms affecting electrokinetic remediation of an artificially Cu- and Pb-contaminated loess using the external regulatory system with adsorbent
Authors: Hu Wenle , Cheng Wen-Chieh , Wen Shaojie , Kang Nongbo
Published: August 2022

Considering extensive metallurgical mining activities in the northwest of China, handling Cu- and Pb-rich wastewater is a challenging task. Inappropriate handling of the Cu- and Pb-rich wastewater can lead to accumulation of Cu and Pb in the surrounding environment, thereby posing a serious threat to human health. Electrokinetic (EK) technology is an increasingly popular alternative to traditional approaches for contaminated soil remediation owing to its high effectiveness and low risk of secondary pollution. This study first proposed an external regulatory system with the adsorbent (ERSA) and investigated the effect of electrode type, ERSA, and cation exchange membrane (CEM) on the EK remediation of an artificially Cu- and Pb-contaminated loess. An EK reactor incorporating ERSA was applied to the EK experiments to circulate the electrolyte, not only making pH surrounding the cathode lower, but also preventing the formation of precipitation. The electrokinetic geosynthetics electrode released H+ and OH− faster and promoted their migration toward the specimen. However, because of the faster precipitation near the cathode, the boost in the remediation efficiency was hindered. Furthermore, considering the ERSA use, a decrease in soil pH near the cathode reduced the precipitation, thereby enhancing the EK remediation efficiency. In contrast, the use of CEM lowered the soil pH, increased the soil electrical conductivity (EC) and electric current, and aggravated the electroosmotic flow. The Cu remediation efficiency using the modified EK reactor was largely lifted to 85.52%, while the Pb remediation efficiency increased to 75.51%. These results shed light on an enhancement on the EK remediation efficiency and the potential of applying the modified EK reactor to remedy Cu- and Pb-rich water bodies.
Biocontrol potential of Bacillus velezensis EM-1 associated with suppressive rhizosphere soil microbes against tobacco bacterial wilt
Authors: Sui Xiaona , Han Xiaobin , Cao Jianmin , Li Yiqiang , Yuan Yuan , Gou Jianyu , Zheng Yanfen , Meng Chen , Zhang Chengsheng
Published: August 2022

Tobacco bacterial wilt caused by Ralstonia solanacearum is one of the most devastating diseases. Microbial keystone taxa were proposed as promising targets in plant disease control. In this study, we obtained an antagonistic Bacillus isolate EM-1 from bacterial wilt-suppressive soil, and it was considered rhizosphere-resident bacteria based on high (100%) 16S rRNA gene similarity to sequences derived from high-throughput amplicon sequencing. According to 16S rRNA gene sequencing and MLSA, strain EM-1 was identified as Bacillus velezensis. This strain could inhibit the growth of R. solanacearum, reduce the colonization of R. solanacearum in tobacco roots, and decrease the incidence of bacterial wilt disease. In addition, strain EM-1 also showed a strong inhibitory effect on other phytopathogens, such as Alternaria alternata and Phytophthora nicotianae, indicating a wide antagonistic spectrum. The antimicrobial ability of EM-1 can be attributed to its volatile, lipopeptide and polyketide metabolites. Iturin A (C14, C15, and C16) was the main lipopeptide, and macrolactin A and macrolactin W were the main polyketides in the fermentation broth of EM-1, while heptanone and its derivatives were dominant among the volatile organic compounds. Among them, heptanones and macrolactins, but not iturins, might be the main potential antibacterial substances. Complete genome sequencing was performed, and the biosynthetic gene clusters responsible for iturin A and macrolactin were identified. Moreover, strain EM-1 can also induce plant resistance by increasing the activity of CAT and PPO in tobacco. These results indicated that EM-1 can serve as a biocontrol Bacillus strain for tobacco bacterial wilt control. This study provides a better insight into the strategy of exploring biocontrol agent based on rhizosphere microbiome.
Open pangenome of Lactococcus lactis generated by a combination of metagenome-assembled genomes and isolate genomes
Authors: Zhai Yiting , Wei Chaochun
Published: August 2022

Lactococcus lactis (L. lactis) is a well isolated and cultured lactic acid bacterium, but if utilizing the isolate genomes alone, the genome-based analysis of this taxon would be incomplete, because there are still uncultured strains in some ecological niches. In this study, we recovered 93 high-quality metagenome-assembled genomes (MAGs) of L. lactis from food and human gut metagenomes with a culture-independent method. We then constructed a unified genome catalog of L. lactis by integrating these MAGs with 70 publicly available isolated genomes. Having this comprehensive resource, we assessed the genomic diversity and phylogenetic relationships to further explore the genetic and functional properties of L. lactis. An open pangenome of L. lactis was generated using our genome catalog, consisting of 13,066 genes in total, from which 5,448 genes were not identified in the isolate genomes. The core genome-based phylogenetic analysis showed that L. lactis strains we collected were separated into two main subclades corresponding to two subspecies, with some uncultured phylogenetic lineages discovered. The species disparity was also indicated in PCA analysis based on accessory genes of our pangenome. These various analyzes shed further light on unexpectedly high diversity within the taxon at both genome and gene levels and gave clues about its population structure and evolution. Lactococcus lactis has a long history of safe use in food fermentations and is considered as one of the important probiotic microorganisms. Obtaining the complete genetic information of L. lactis is important to the food and health industry. However, it can naturally inhabit many environments other than dairy products, including drain water and human gut samples. Here we presented an open pan-genome of L. lactis constructed from 163 high-quality genomes obtained from various environments, including MAGs recovered from environmental metagenomes and isolate genomes. This study expanded the genetic information of L. lactis about one third, including more than 5,000 novel genes found in uncultured strains. This more complete gene repertoire of L. lactis is crucial to further understanding the genetic and functional properties. These properties may be harnessed to impart additional value to dairy fermentation or other industries.
Network pharmacology identify intersection genes of quercetin and Alzheimer’s disease as potential therapeutic targets
Authors: Wei Caihui , Li Shu , Zhu Yu , Chen Wenzhi , Li Cheng , Xu Renshi
Published: August 2022

Background

Currently, there are no efficient therapies for Alzheimer’s disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients’ frontal cortex, current study aims to identify the potential mechanisms of quercetin’s pharmacological targets.

Materials and methods

The pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.

Results

In the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.

Conclusion

The role of quercetin in AD appears to be multifaceted, and it can affect patients’ frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.
Association between physical exercise, executive function, and cerebellar cortex: A cross-sectional study among the elderly in Chinese communities
Authors: Li Wei , Li Yong , Chen Yaopian , Yue Ling , Xiao Shifu
Published: August 2022

Background

Previous studies have confirmed that physical exercise may be beneficial for brain health, but there is little data on this among older Chinese.

Objective

The purpose of this study was to explore the relationship between physical exercise and cognitive impairment, and to explore the possible mechanism by which physical exercise prevents cognitive decline.

Materials and methods

192 older adults with dementia, 610 older adults with mild cognitive impairment (MCI), and 2,218 healthy older adults were included in the study. Through standardized questionnaires, we obtained their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension and diabetes) and physical exercise information (such as whether they did physical exercise and the frequency of physical exercise, etc.). The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, while the Wechsler block diagram was used to assess their executive function. Moreover, 164 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included hippocampus, gray matter, and cerebellar cortex.

Results

By using stepwise multiple logistics regression analysis, we found that physical exercise was associated with both MCI (p = 0.001*, OR = 0.689, 95%CI: 0.553–0.859) and dementia (p < 0.001*, OR = 0.501, 95%CI: 0.354–0.709), independent of gender, age, education, and other factors. The results of ROC curve showed that the area under the curve of physical exercise in predicting MCI and dementia was 0.551 (p < 0.001*, 95%CI: 0.525–0.577) and 0.628 (p = 0.001*, 95%CI: 0.585–0.671), respectively. The results of partial correlation analysis showed that physical exercise was associated with left cerebellar cortex (r = 0.163, p = 0.023), right cerebellar cortex (r = 0.175, p = 0.015) and Wechsler block diagram score (r = 0.235, p = 0.011). Moreover, the results of linear regression analysis mediation model showed that physical exercise may affect Wechsler block diagram score through influencing the thickness of right cerebellum cortex, and the latter may play a partial mediation effect (indirect B = 0.001, p = 0.045).

Conclusion

Physical exercise might be a protective factor for mild cognitive impairment and dementia among the Chinese elderly, and there might be an association among physical exercise, executive function, and the thickness of the cerebellar cortex.
Structural and functional organization of the midline and intralaminar nuclei of the thalamus
Authors: Vertes Robert P. , Linley Stephanie B. , Rojas Amanda K. P.
Published: August 2022

The midline and intralaminar nuclei of the thalamus form a major part of the “limbic thalamus;” that is, thalamic structures anatomically and functionally linked with the limbic forebrain. The midline nuclei consist of the paraventricular (PV) and paratenial nuclei, dorsally and the rhomboid and nucleus reuniens (RE), ventrally. The rostral intralaminar nuclei (ILt) consist of the central medial (CM), paracentral (PC) and central lateral (CL) nuclei. We presently concentrate on RE, PV, CM and CL nuclei of the thalamus. The nucleus reuniens receives a diverse array of input from limbic-related sites, and predominantly projects to the hippocampus and to “limbic” cortices. The RE participates in various cognitive functions including spatial working memory, executive functions (attention, behavioral flexibility) and affect/fear behavior. The PV receives significant limbic-related afferents, particularly the hypothalamus, and mainly distributes to “affective” structures of the forebrain including the bed nucleus of stria terminalis, nucleus accumbens and the amygdala. Accordingly, PV serves a critical role in “motivated behaviors” such as arousal, feeding/consummatory behavior and drug addiction. The rostral ILt receives both limbic and sensorimotor-related input and distributes widely over limbic and motor regions of the frontal cortex—and throughout the dorsal striatum. The intralaminar thalamus is critical for maintaining consciousness and directly participates in various sensorimotor functions (visuospatial or reaction time tasks) and cognitive tasks involving striatal-cortical interactions. As discussed herein, while each of the midline and intralaminar nuclei are anatomically and functionally distinct, they collectively serve a vital role in several affective, cognitive and executive behaviors – as major components of a brainstem-diencephalic-thalamocortical circuitry.
Combining backpropagation with Equilibrium Propagation to improve an Actor-Critic reinforcement learning framework
Authors: Kubo Yoshimasa , Chalmers Eric , Luczak Artur
Published: August 2022

Backpropagation (BP) has been used to train neural networks for many years, allowing them to solve a wide variety of tasks like image classification, speech recognition, and reinforcement learning tasks. But the biological plausibility of BP as a mechanism of neural learning has been questioned. Equilibrium Propagation (EP) has been proposed as a more biologically plausible alternative and achieves comparable accuracy on the CIFAR-10 image classification task. This study proposes the first EP-based reinforcement learning architecture: an Actor-Critic architecture with the actor network trained by EP. We show that this model can solve the basic control tasks often used as benchmarks for BP-based models. Interestingly, our trained model demonstrates more consistent high-reward behavior than a comparable model trained exclusively by BP.
A simplicial analysis of the fMRI data from human brain dynamics under functional cognitive tasks
Authors: Bishal Rabindev , Cherodath Sarika , Singh Nandini Chatterjee , Gupte Neelima
Published: August 2022

The topological analysis of fMRI time series data has recently been used to characterize the identification of patterns of brain activity seen during specific tasks carried out under experimentally controlled conditions. This study uses the methods of algebraic topology to characterize time series networks constructed from fMRI data measured for adult and children populations carrying out differentiated reading tasks. Our pilot study shows that our methods turn out to be capable of identifying distinct differences between the activity of adult and children populations carrying out identical reading tasks. We also see differences between activity patterns seen when subjects recognize word and nonword patterns. The results generalize across different populations, different languages and different active and inactive brain regions.
Fewer neurocognitive deficits and less brain atrophy by third ventricle measurement in PLWH treated with modern ART: A prospective analysis
Authors: Kaddu-Mulindwa Dominic , Heit Matthias , Wagenpfeil Gudrun , Bewarder Moritz , Fassbender Klaus , Behnke Stefanie , Yilmaz Umut , Fousse Mathias
Published: August 2022

Background

Despite antiretroviral therapy, cognitive dysfunction seems to remain a major issue for people living with human immunodeficiency virus (PLWH). Previous studies showed a correlation between the width of the third ventricle (WTV) and neurocognitive disorders in PLWH.

Patients and methods

We investigated prevalence and correlation of neuropsychological disorders using WTV as a brain atrophy marker examined by transcranial sonography and MRI in PLWH and healthy age- and gender-matched controls. We used Becks Depression Inventory (BDI) for depression screening, the questionnaires Fatigue Severity Scale (FSS) for fatigue and Short-Form-36 (SF36) for quality of life (QoL) evaluation and Consortium to establish a registry for Alzheimer's disease (CERAD-PLUS) as neuropsychological test battery.

Results

52 PLWH (47 males) and 28 non-infected controls (23 males) with a median age of 52 years (24–78 years) and 51 years (22–79) were analyzed. WTV correlated significantly with age (p < 0.01) but showed no significantly difference in PLWH (median = 3.4 mm) compared to healthy controls (median = 2.8 mm) (p = 0.085). PLWH had both significantly higher BDI-Scores (p = 0.005) and FSS-Scores (p = 0.012). Controls reported higher QoL (SF-36) with significant differences in most items. However, the overall cognitive performance (CERAD total score) showed no significant difference. The WTV of all subjects correlated with neurocognitive performance measured as CERAD total score (p = 0.009) and trail making tests A (p < 0.001) and B (p = 0.018). There was no correlation between the scores of BDI, FSS, SF-36, and CERAD-PLUS items and WTV.

Conclusion

WTV is considered as a predictor of cognitive deficits in neurodegenerative diseases. Nevertheless, we found no significant difference in WTV or overall cognitive performance between PLWH and controls. PLWH suffer more often from depression and fatigue and report reduced QoL when compared to healthy controls.
Hashimoto's encephalopathy with cerebellar ataxia as the main symptom: A case report and literature review
Authors: Wei Chunxiao , Shen Yanxin , Zhai Weijie , Shang Tianling , Wang Zicheng , Wang Yongchun , Li Mingxi , Zhao Yang , Sun Li
Published: August 2022

Hashimoto's encephalopathy (HE), also known as steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), has a variety of clinical manifestations, with various neuropsychiatric characteristics, including tremors, transient aphasia, seizures, altered consciousness, myoclonus, cognitive impairment, and psychiatric manifestations. The hallmark presenting feature is a non-specific encephalopathy characterized by alteration of mental status and consciousness ranging from confusion to coma and impaired cognitive function, while those with cerebellar ataxia as the main manifestation is rare. We reported a case of Hashimoto's encephalopathy with cerebellar ataxia as the main manifestation, elevated anti-thyroid antibodies (anti-TPO/TG), and normal thyroid function. The symptoms of cerebellar ataxia improved after steroid treatment. Meanwhile, we reviewed the clinical features of 20 representative cases of HE with cerebellar ataxia as the core symptoms. In conclusion, based on our case findings and literature review, the diagnosis of HE should be suspected in cases of encephalopathy without an obvious cause, to quickly start an effective treatment.
PE augmented mindfulness: A neurocognitive framework for research and future healthcare
Authors: Sars David
Published: August 2022

Various well-controlled studies have suggested that practitioners in mindfulness can be prone to patient drop-out (e.g., due to chronic stress, pathology, cognitive reactivity), despite researchers having identified the underlying mechanisms that link mindfulness to mental health. In this article, a framework for physical exercise (PE) augmented mindfulness is proposed, which posits that consistently practiced PE before meditation can support (early-stage) mindfulness. Neurocognitive research shows PE (aerobic exercises or yoga) and mindfulness to impact similar pathways of stress regulation that involve cognitive control and stress regulation, thereby supporting the proposed synergistic potential of PE augmented mindfulness. Research focused on the psychophysiological impact of PE, showed its practice to promote short-term neurocognitive changes that can promote both cognitive control and the attainment of mindful awareness (MA). In order to chart dose responses required for protocol development, further research will be presented. Together these findings are discussed in light of future research on this multidisciplinary topic, protocol development, mindful walking, and further application in healthcare and beyond.
Dynamic changes of amplitude of low-frequency in systemic lupus erythematosus patients with cognitive impairment
Authors: Yang Yifan , Zhao Ruotong , Zhang Fengrui , Bai Ru , Li Shu , Cui Ruomei , Liu Shuang , Xu Jian
Published: August 2022

Background

Cognitive dysfunction (CI) is frequently reported in patients with systemic lupus erythematosus (SLE), but the identification and assessment of SLE-related CI remain challenging. Previous studies have focused on changes in static brain activity, and no studies have investigated the characteristics of dynamic brain activity in SLE patients with CI.

Objects

We calculated the dynamic amplitude of low-frequency fluctuation (dALFF) by combining the ALFF with a sliding window method to assess the temporal variability of brain functional activity in SLE patients with and without CI.

Methods

Thirty-eight SLE with CI, thirty-eight SLE without CI, and thirty-eight healthy controls (HCs) were recruited. By comparing static ALFF (sALFF) and dALFF among the three groups, changes in brain activity intensity and its temporal variability were assessed in patients with SLE with or without CI. Spearman correlation coefficients were calculated between the brain function indicator and Mini-mental State Examination (MMSE) scores of SLE with CI.

Results

Subjects among the three groups exhibited significant sALFF differences in the right parahippocampal gyrus, left caudate nucleus, right putamen, and left cuneus. Compared to the SLE without CI, the right parahippocampal gyrus exhibited higher sALFF in the SLE with CI group. Compared to the HCs, the left caudate nucleus exhibited increased sALFF in the SLE with CI group. Participants in the three groups exhibited significant dALFF variability in the right parahippocampal gyrus, right lingual gyrus, and bilateral inferior occipital gyrus. Compared to the HCs, the right lingual gyrus exhibited reduced dALFF in the SLE without CI group. Compared to the HCs, the right parahippocampal gyrus exhibited increased dALFF, left calcarine fissure, and the surrounding cortex exhibited reduced dALFF in the SLE with CI group. There was no significant correlation between the MMSE score, sALFF, and dALFF in the SLE with CI group.

Conclusion

SLE patients with CI have abnormal brain activity intensity and stability. By analyzing the dynamics of intrinsic brain activity, it provides a new idea for evaluating SLE-related CI. However, more research and validation with multiple metrics are needed to determine the link between the severity of cognitive impairment (CI) and brain activity in patients with SLE.
Mind-body-medicine and comprehensive lifestyle-modification in patients with Crohn's disease—Feasibility of a randomized controlled trial under pandemic circumstances
Authors: Bauer Nina , Löffler Claudia , Öznur Özlem , Uecker Christine , Keil Thomas , Langhorst Jost
Published: August 2022

Introduction

Mind-body medicine (MBM) focuses on stress reduction and lifestyle changes. The primary objective of this pilot trial was to test study feasibility of a complex integrative MBM program for patients with Crohn's disease (CD), especially in rural regions, and under pandemic conditions.

Methods

Patients were stratified and randomized to the intervention group (IG) or the control group (CG). The intervention included a weekly 6-h session for 10 weeks. The CG (waiting list) received an initial 90-min workshop and started the intervention 9 months later. The primary outcome for study feasibility was recruitment and retention rates, as well as reasons for drop-out. The trial took place in Bamberg, Germany (September 2020 to December 2021).

Results

Totally 700 members of the German Crohn's and Colitis Organization—DCCV—were contacted. A total of 15% (102/700; 95% CI 12–17%) expressed interest to participate. Following screening, 41% (95% CI 32–50) were randomized to IG (n = 22) and CG (n = 20). The patients were on average (±standard deviation) 48 ± 13 years old, 67% were female, and have been suffering from CD for 20 ± 12 years. Patients traveled 71.5 ± 48.7 km (range: 9–227 km) to the intervention with no differences between IG and CG. At the 6-month follow-up, 36/42 (86%, 95% CI 74–95%) participants completed final assessment and 19/22 (86%, 95% CI 70–100%) the intervention. The most important reasons for non-responding were work-related (12/60; 20%) and for or drop-out pandemic-related anxiety (3/6). No patient and staff member became infected with SARS-CoV-2 during the study.

Conclusion

The feasibility of the MBM study was confirmed in terms of predefined recruitment and retention criteria, both despite difficult conditions (including the rural setting) and patients' fears associated with the pandemic. It was crucial to develop appropriate hygiene and safety concepts that enable chronically ill patients to participate in helpful group-based interventions even under pandemic conditions.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT05182645.
The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy
Authors: Bruera Sebastian , Suarez-Almazor Maria E.
Published: August 2022

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, abatacept, rituximab, and Janus kinase inhibitors (JAKi) on cancer-specific outcomes in the setting of immune checkpoint inhibitor use.
Molecular subtyping of CD5+ diffuse large B-cell lymphoma based on DNA-targeted sequencing and Lymph2Cx
Authors: Ma Dongshen , Ma Yuhan , Ma Yuanyuan , Liu Jia , Gu Ying , Liu Nian , Xiang Chenxi , Liu Hui , Sang Wei
Published: August 2022

Background

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) showed poor prognosis in the rituximab era, with limited research on its genetic characteristics and cell of origin (COO). We aimed to demonstrate the molecular characteristics of CD5+ DLBCL and to discover potential prognostic factors.

Methods

We included 24 cases of CD5+ DLBCL and 23 CD5-negative (CD5-) counterparts and collected their clinicopathological features. Targeted DNA sequencing of 475 lymphoma-related genes was performed, and all cases were assigned to distinct genetic subtypes using the LymphGen tool. The COO was determined by the Lymph2Cx assay. The Kaplan–Meier method and Cox proportional hazards model were applied to identify the possible prognostic factors.

Results

Compared with their CD5- counterparts, patients with CD5+ DLBCL tended to have a worse prognosis and a higher incidence of MYD88L265P and CD79B double mutation (MCD) subtype (54.17%, P = 0.005) and activated B cell-like (ABC) subtype (62.5%, P = 00017), as determined by next-generation sequencing and Lymph2Cx, respectively. Moreover, PIM1, MYD88, and KMT2D mutations were detected more frequently in CD5+ DLBCL cases (P < 0.05). According to multivariate analysis, MYC/BCL2 double expression and ABC subtype were correlated with unfavorable overall survival (OS). High mRNA expression of SERPINA9 and MME showed a significant correlation with a better OS, and high expression of MME showed a significant correlation with better progression-free survival in CD5+ DLBCL.

Conclusion

The genetic profile of CD5+ DLBCL is characterized by PIM1, MYD88, and KMT2D mutations, with a higher incidence of MCD and ABC subtypes. MYC/BCL2 double expression, ABC subtype, and mRNA expression of SERPINA9 and MME are independently predictive of the prognosis of CD5+ DLBCL.
The Application of Pearls in Traditional Medicine of China and Their Chemical Constituents, Pharmacology, Toxicology, and Clinical Research
Authors: Song Yinglian , Chen Wanyue , Fu Ke , Wang Zhang
Published: August 2022

Although pearls are well known by most people, their medicinal value has not been popularized. This article collates the medicinal history of pearls over 2,000 years in China, including the application of pearls in the traditional medicine of China and their various preparations, as well as the progress of their chemical constituents, pharmacology, toxicology, and clinical research. Pearls from three different sources are used as medical materiel by 9 nationalities and 251 prescription preparations in China. In addition, pearls contain various inorganic constituents, such as calcium carbonate, trace elements, and water, and organic constituents, such as amino acids. In terms of pharmacology, pearls have many effects such as calming, improving cognitive ability, being anti-epileptic, promoting bone growth and regeneration, promoting the proliferation and migration of human microvascular endothelial cells, protecting the heart, anti-hemolysis, and anti-oxidation. In terms of toxicology, pearls are safe to take for a long time without exerting obvious adverse reactions. In terms of clinical application, pearls have been used to treat many diseases and conditions, such as convulsions, epilepsy, palpitations, eye diseases, ulcer diseases, skin diseases, or skin lesions. This article provides a reference for the application and research of pearls in the future.
Review of Urate-Lowering Therapeutics: From the Past to the Future
Authors: Jenkins Christopher , Hwang Jennifer H. , Kopp Jeffrey B. , Winkler Cheryl A. , Cho Sung Kweon
Published: August 2022

We reviewed all currently available ULT, as well as any medications in development using following databases: United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. We identified a total of 36 drugs, including 10 approved drugs, 17 in clinical testing phases, and 9 in preclinical developmental phases. The 26 drugs currently undergoing testing and development include 5 xanthine oxidase inhibitors, 14 uricosurics, 6 recombinant uricases, and one with multiple urate-lowering mechanisms of action. Herein, we reviewed the benefit and risk of each drug summarizing currently available drugs. New trials of uricosuric agents are underway to develop the new indication. New drugs are going on to improve the potency of recombinant uricase and to develop the new route administration of such as oral formulation. This review will provide valuable information on the properties, indications, and limitations of ULTs.
The add-on effects of Danhong injection among patients with ischemic stroke receiving Western medicines: A systematic review and meta-analysis
Authors: Ma Yu , Deng Ke , Liu Jiali , Ma Bin , Mei Fan , Hui Wen , Luo Xiaochao , Yao Minghong , Liu Yanmei , Qin Xuan , Zhou Xu , Zou Kang , Li Ling , Sun Xin
Published: August 2022

Background: Danhong injection is widely used for treating ischemic stroke in China. However, its effects on ischemic stroke patients when given along with Western medicines (i.e., the add-on effect) were not well-established.

Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases from inception to 20 July 2020 to identify randomized controlled trials (RCTs) that assessed the effects of Danhong injection as add-on therapy in patients with ischemic stroke. Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted the data. The outcomes were the National Institutes of Health Stroke Scale Score (NIHSS), Barthel index, activities of daily living (ADL), total cholesterol, and homocysteine (Hcy).

Results: Sixty-seven RCTs of 6594 patients with varying risk of bias were included. Compared with Western medicine alone, the addition of Danhong injection to Western medicine significantly lowered the NIHSS score (45 RCTs with 4565 patients; MD −4.21, 95% CI −4.96 to −3.46), total cholesterol (10 trials with 1019 patients; MD −1.14 mmol/L, 95% CI −1.57 to −0.72), and Hcy (four trials with 392 patients; MD −3.54 μmol/L, 95% CI −4.38 to −2.07). The addition of Danhong also increased the Barthel index (14 trials with 1270 patients; MD 8.71, 95% CI 3.68–13.74) and ADL (12 trials with 1114 patients; MD 14.48, 95% CI 9.04–19.92) scores. Subgroup analyses showed differential effects in the average cerebral blood flow rate by mean age of patients (<60 years: MD 0.74 cm/s, 95% CI 0.29–1.19; ≥60 years: MD 4.09 cm/s, 95% CI 2.02–6.16; interaction p = 0.002) and the NIHSS score by type of baseline Western medicines (interaction p < 0.00001).

Conclusion: The addition of Danhong injection to Western medicine may improve neurological function, self-care ability, and blood lipid level of ischemic stroke patients. However, given most included trials with unclear risk of bias, current evidence is not definitive, and more carefully designed and conducted trials are warranted to confirm our findings.

Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022298628].
BioSAXS–an emerging method to accelerate, enrich and de-risk antimicrobial drug development
Authors: Rumancev Christoph , Rosenhahn Axel , Hilpert Kai
Published: August 2022

Antimicrobial resistance is a worldwide threat to modern health care. Low-profit margin and high risk of cross-resistance resulted in a loss of interest in big pharma, contributing to the increasing threat. Strategies to address the problem are starting to emerge. Novel antimicrobial compounds with novel modes of action are especially valued because they have a lower risk of cross-resistance. Up to now determining the mode of action has been very time and resource consuming and will be performed once drug candidates were already progressed in preclinical development. BioSAXS is emerging as a new method to test up to thousands of compounds to classify them into groups based on ultra-structural changes that correlate to their modes of action. First experiments in E. coli (gram-negative) have demonstrated that using conventional and experimental antimicrobials a classification of compounds according to their mode of action was possible. Results were backed up by transmission electron microscopy. Further work showed that also gram-positive bacteria (Staphylococcus aureus) can be used and the effects of novel antimicrobial peptides on both types of bacteria were studied. Preliminary experiments also show that BioSAXS can be used to classify antifungal drugs, demonstrated on Candida albicans. In summary, BioSAXS can accelerate and enrich the discovery of antimicrobial compounds from screening projects with a novel mode of action and hence de-risk the development of urgently needed antimicrobial drugs.
Corporate social responsibility of pharmaceutical industry in Korea
Authors: Bae Green , Ahn Jeong-Hoon , Lim Kyung-Min , Bae SeungJin
Published: August 2022

Background: Global pharmaceutical companies in Korea argue that the development of innovative drugs should be recognized as a social contribution, yet it has been countered by various stakeholders. The need to distinguish between philanthropic activities and Corporate Social Responsibility (CSR) of pharmaceutical companies and reaching consensus in the Korean context has been raised. We sought to evaluate the CSR status of Korean pharmaceutical companies and collect the stakeholders’ opinions to define philanthropic activities and CSR related to pharmaceutical companies in Korea.

Methods: We conducted a literature review on the definition of CSR of pharmaceutical companies, and the CSR activities of the domestic pharmaceutical companies were compared with those of global pharmaceutical companies operating in Korea. The opinions of stakeholder groups (patient advocate groups, consumer organizations, and domestic/global pharmaceutical companies) were collected using focus group interviews (FGI) and written surveys.

Results: Literature review suggested that CSR is categorized as “must do” (economic and legal responsibilities), “ought to do” (ethical responsibilities), and “can do” (philanthropic responsibilities), whereas contributions beyond the economic, legal, or ethical responsibilities can be defined as “can do” (philanthropic responsibilities). Domestic pharmaceutical companies simply adopted systems for ethical and ESG (Environmental, Social, and Governance) management, which are at the “ought to do” level (ethical responsibility), whereas the headquarters of these global pharmaceutical companies established the CSR team and systematically reported on the CSR activity, including ESG management reports, which is at the “ought to do” level and further moving to the “can do” level, but the Korean branch rarely has CSR teams, and the CSR activities in Korea were also insufficient. At the FGI, the global pharmaceutical companies argued that CSR activities, such as innovative drug development, should be recognized as similar to philanthropic activities, yet stakeholders besides them suggested that those activities are “can do” rather than being philanthropic.

Discussion: We found that the pharmaceutical companies in Korea are attempting to achieve the “ought to do” level (ethical responsibilities) while complying with the “must do” level (legal and economic responsibilities) yet not philanthropic activities. A social consensus regarding the philanthropic responsibilities of pharmaceutical companies in Korea was not reached.
A randomized, double-blind, parallel control study to evaluate the biosimilarity of QL1209 with Perjeta® in healthy male subjects
Authors: Sun Yuanyuan , Yang Heng , Yang Xiaoyan , Yang Shuang , Guo Can , Chen Honghui , Cui Chang , Xiang Yuxia , Yang Guoping , Huang Jie
Published: August 2022

Purpose: This is the first study to compare the pharmacokinetics, safety and, immunogenicity of QL1209, a biosimilar of Perjeta®.

Methods: This study was a randomized, double-blind, parallel-controlled clinical trial evaluating the biosimilarity between QL1209 (specification: 420 mg:14 ml, single use via, manufacturer: Qilu Pharmaceutical Co., Ltd., batch number: 201808001KJL) and Perjeta® (specification: 420 mg: 14 ml, single use via, manufacturer: Roche Pharma AG, batch number: H0309H02). The trial period was 99 days (blood samples for PK were collected 99 days after infusion). Serum concentrations were determined using a validated assay. PK parameters were calculated using a non-compartmental model and analyzed statistically. Anti-drug antibody (ADA)-positive samples were further tested for the presence of neutralization antibody detection (NAb).

Results: A total of 137 healthy subjects were administrated. The subjects were randomized 1:1 to receive QL1209 or Perjeta® 420 mg intravenously. The geometric mean ratio (GMRs) for QL1209 versus Perjeta® are 104.14%, 104.09%, and 110.59% for Cmax, AUC0-t, and AUC0-∞, respectively, and their 90% confidence interval (CIs) all fell within the predefined bioequivalence margin 80.00–125%. The incidence of drug-related adverse events was 95.6% and 95.5% in the QL1209 and Perjeta® groups, respectively, also comparable between the two groups.

Conclusion: The results of this comparative clinical pharmacology study demonstrated the PK similarity of QL1209 (420 mg: 14 ml) and Perjeta® (420 mg: 14 ml) and there was no significant difference in safety and immunogenicity between QL1209 and Perjeta® manufactured by Roche Pharma AG.