bluuebunny/crossref_metadata_2025 huggingface dataset:
Two New Species and One New Genus of Glass Sponges (Hexactinellida: Euplectellidae and Euretidae), From a Transect on a Seamount in the Northwestern Pacific Ocean
Authors: Shen Chengcheng , Cheng Hong , Zhang Dongsheng , Wang Chunsheng
Published: May 2022

Hexactinellid sponges often form structural habitats for other organisms and thus support high biodiversity. Two representative morphotypes of hexactinellid sponges were sampled by a remotely operated vehicle along a transect (depths of 2377–2758 m) on the Ko-Hakucho Guyot in the northwestern Pacific Ocean, both new to science. One new species,Flavovirens hemiglobusgen. et sp. nov., which is pedunculate and bears the main choanosomal spicules of diactins, is clearly attributed to the euplectellid subfamily Bolosominae. Its set of microscleres present (namely, predominating oxyhexasters and discasters, and rare discohexasters and staurodiscs) characterizes it as a new genus. The other new species,Chonelasma tyloscopulatumsp. nov., which is funnel in form without dichotomous branching tubes or lateral oscula and has firm body walls supported by a three-layered dictyonal framework, is clearly attributed to the euretid genusChonelasma(subfamily Chonelasmatinae). Its presence of surface pentactins, two types of scopules, and both oxy- and disco-tipped hexasters or hemihexasters as common microscleres, characterizes it as a new species. The placements are also supported by molecular phylogenetic evidence from nuclear 18S rDNA and 28S rDNA, and mitochondrial 16S rDNA and cytochrome c oxidase subunit I (COI) gene. More sampling efforts should be conducted to improve the understanding of the biodiversity of deep-sea seamount sponges.
Informed Consent in Clinical Studies Involving Human Participants: Ethical Insights of Medical Researchers in Germany and Poland
Authors: Timmermann Cristian , Orzechowski Marcin , Kosenko Oxana , Woniak Katarzyna , Steger Florian
Published: May 2022

Background

The internationalization of clinical studies requires a shared understanding of the fundamental ethical values guiding clinical studies. It is important that these values are not only embraced at the legal level but also adopted by clinicians themselves during clinical studies.

Objective

Our goal is to provide an insight on how clinicians in Germany and Poland perceive and identify the different ethical issues regarding informed consent in clinical studies.

Methods

To gain an understanding of how clinicians view clinical studies in the countries they work in, we carried out semi-structured problem-centered interviews per telephone in Poland (n = 6) and Germany (n = 6). Our interviewees concentrated on three main topics: an appraisal of the normative framework, challenges in the information process and the protection of all participants in clinical studies.

Results

Clinicians generally supported the normative framework, even though they considered it quite complex. In the two study countries, a widely noted dilemma in the information process was whether to overburden participants with extensive information or risking leaving out important facts. Clinicians were ready to exclude larger population groups from participating in clinical studies when the information process could not be carried out with standard procedures or when their inclusion was ethically sensitive.

Conclusion

Clinicians need to gain a better understanding of the consequences of excluding larger population groups form participating in clinical studies. They should seek assistance in improving the information process for the inclusion of underrepresented groups in clinical studies.
Complete Genome Sequence of Weissella cibaria NH9449 and Comprehensive Comparative-Genomic Analysis: Genomic Diversity and Versatility Trait Revealed
Authors: Surachat Komwit , Kantachote Duangporn , Wonglapsuwan Monwadee , Chukamnerd Arnon , Deachamag Panchalika , Mittraparp-arthorn Pimonsri , Jeenkeawpiam Kongpop
Published: May 2022

Lactic acid bacteria (LAB) in the genus Weissella spp. contain traits in their genome that confer versatility. In particular, Weissella cibaria encodes several beneficial genes that are useful in biotechnological applications. The complete genome of W. cibaria NH9449 was sequenced and an in silico comparative analysis was performed to gain insight into the genomic diversity among members of the genus Weissella. A total of 219 Weissella genomes were used in a bioinformatics analysis of pan-genomes, phylogenetics, self-defense mechanisms, virulence factors, antimicrobial resistance, and carbohydrate-active enzymes. These investigations showed that the strain NH9449 encodes several restriction-modification-related genes and a CRISPR-Cas region in its genome. The identification of carbohydrate-active enzyme-encoding genes indicated that this strain could be beneficial in biotechnological applications. The comparative genomic analysis reveals the very high genomic diversity in this genus, and some marked differences in genetic variation and genes among Weissella species. The calculated average amino acid identity (AAI) and phylogenetic analysis of core and accessory genes shows the possible existence of three new species in this genus. These new genomic insights into Weissella species and their biological functions could be useful in the food industry and other applications.
Incomplete Concordance Between Host Phylogeny and Gut Microbial Community in Tibetan Wetland Birds
Authors: Bo Tingbei , Song Gang , Tang Shiyu , Zhang Mengru , Ma Zhiwei , Lv Hongrui , Wu Yun , Zhang Dezhi , Yang Le , Wang Dehua , Lei Fumin
Published: May 2022

Gut microbial communities of animals play key roles in host evolution, while the relationship between gut microbiota and host evolution in Tibetan birds remains unknown. Herein, we sequenced the gut microbiota of 67 wild birds of seven species dwelling in the Tibetan wetlands. We found an obvious species-specific structure of gut microbiota among these plateau birds whose habitats were overlapped. Different from plateau mammals, there was no strict synergy between the hierarchical tree of gut microbial community and species phylogeny. In brown-headed gulls (Larus brunnicephalus) as an example, the structure of gut microbiota differed in different habitats, and the relative abundance of bacteria, such as Lactobacillus, Streptococcus, Paracoccus, Lachnospiraceae, and Vibrio, significantly correlated with altitude. Finally, we found various pathogenic bacteria in the birds of these plateau wetlands, and the interspecific differences were related to their diet and living environments.
Harnessing the Potential of Bacillus altitudinis MT422188 for Copper Bioremediation
Authors: Khan Maryam , Kamran Muhammad , Kadi Roqayah H. , Hassan Mohamed M. , Elhakem Abeer , Sakit ALHaithloul Haifa Abdulaziz , Soliman Mona H. , Mumtaz Muhammad Zahid , Ashraf Muhammad , Shamim Saba
Published: May 2022

The contamination of heavy metals is a cause of environmental concern across the globe, as their increasing levels can pose a significant risk to our natural ecosystems and public health. The present study was aimed to evaluate the ability of a copper (Cu)-resistant bacterium, characterized as Bacillus altitudinis MT422188, to remove Cu from contaminated industrial wastewater. Optimum growth was observed at 37°C, pH 7, and 1 mm phosphate, respectively. Effective concentration 50 (EC50), minimum inhibitory concentration (MIC), and cross-heavy metal resistance pattern were observed at 5.56 mm, 20 mm, and Ni > Zn > Cr > Pb > Ag > Hg, respectively. Biosorption of Cu by live and dead bacterial cells in its presence and inhibitors 1 and 2 (DNP and DCCD) was suggestive of an ATP-independent efflux system. B. altitudinis MT422188 was also able to remove 73 mg/l and 82 mg/l of Cu at 4th and 8th day intervals from wastewater, respectively. The presence of Cu resulted in increased GR (0.004 ± 0.002 Ug−1FW), SOD (0.160 ± 0.005 Ug−1FW), and POX (0.061 ± 0.004 Ug−1FW) activity. Positive motility (swimming, swarming, twitching) and chemotactic behavior demonstrated Cu as a chemoattractant for the cells. Metallothionein (MT) expression in the presence of Cu was also observed by SDS-PAGE. Adsorption isotherm and pseudo-kinetic-order studies suggested Cu biosorption to follow Freundlich isotherm as well as second-order kinetic model, respectively. Thermodynamic parameters such as Gibbs free energy (∆G°), change in enthalpy (∆H° = 10.431 kJ/mol), and entropy (∆S° = 0.0006 kJ/mol/K) depicted the biosorption process to a feasible, endothermic reaction. Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy-Dispersive X-Ray Spectroscopy (EDX) analyses revealed the physiochemical and morphological changes in the bacterial cell after biosorption, indicating interaction of Cu ions with its functional groups. Therefore, these features suggest the potentially effective role of B. altitudinis MT422188 in Cu bioremediation.
Neural Plasticity Induced by Hearing Aid Use
Authors: Karawani Hanin , Jenkins Kimberly , Anderson Samira
Published: May 2022

Age-related hearing loss is one of the most prevalent health conditions in older adults. Although hearing aid technology has advanced dramatically, a large percentage of older adults do not use hearing aids. This untreated hearing loss may accelerate declines in cognitive and neural function and dramatically affect the quality of life. Our previous findings have shown that the use of hearing aids improves cortical and cognitive function and offsets subcortical physiological decline. The current study tested the time course of neural adaptation to hearing aids over the course of 6 months and aimed to determine whether early measures of cortical processing predict the capacity for neural plasticity. Seventeen (9 females) older adults (mean age = 75 years) with age-related hearing loss with no history of hearing aid use were fit with bilateral hearing aids and tested in six testing sessions. Neural changes were observed as early as 2 weeks following the initial fitting of hearing aids. Increases in N1 amplitudes were observed as early as 2 weeks following the hearing aid fitting, whereas changes in P2 amplitudes were not observed until 12 weeks of hearing aid use. The findings suggest that increased audibility through hearing aids may facilitate rapid increases in cortical detection, but a longer time period of exposure to amplified sound may be required to integrate features of the signal and form auditory object representations. The results also showed a relationship between neural responses in earlier sessions and the change predicted after 6 months of the use of hearing aids. This study demonstrates rapid cortical adaptation to increased auditory input. Knowledge of the time course of neural adaptation may aid audiologists in counseling their patients, especially those who are struggling to adjust to amplification. A future comparison of a control group with no use of hearing aids that undergoes the same testing sessions as the study’s group will validate these findings.
Astrocyte Reprogramming in Stroke: Opportunities and Challenges
Authors: Peng Zhouzhou , Lu Hui , Yang Qingwu , Xie Qi
Published: May 2022

Stroke is a major cause of morbidity and mortality worldwide. In the early stages of stroke, irreversible damage to neurons leads to high mortality and disability rates in patients. However, there are still no effective prevention and treatment measures for the resulting massive neuronal death in clinical practice. Astrocyte reprogramming has recently attracted much attention as an avenue for increasing neurons in mice after cerebral ischemia. However, the field of astrocyte reprogramming has recently been mired in controversy due to reports questioning whether newborn neurons are derived from astrocyte transformation. To better understand the process and controversies of astrocyte reprogramming, this review introduces the method of astrocyte reprogramming and its application in stroke. By targeting key transcription factors or microRNAs, astrocytes in the mouse brain could be reprogrammed into functional neurons. Additionally, we summarize some of the current controversies over the lack of cell lineage tracing and single-cell sequencing experiments to provide evidence of gene expression profile changes throughout the process of astrocyte reprogramming. Finally, we present recent advances in cell lineage tracing and single-cell sequencing, suggesting that it is possible to characterize the entire process of astrocyte reprogramming by combining these techniques.
Sex Differences in the Association Between Poor Sleep Quality and Alcohol-Related Problems Among Heavy Drinkers With Insomnia
Authors: Verlinden Justin J. , Moloney Mairead E. , Whitehurst Lauren N. , Weafer Jessica
Published: May 2022

Background

Alcohol Use Disorder (AUD) and insomnia are highly comorbid; at least 40% of individuals with AUD suffer from insomnia. Women are more likely to report insomnia than men and have seen a concerning rise in rates of AUD in recent years. As such, the association between AUD and insomnia could be particularly pronounced in women. However, currently little is known regarding sex differences in this association. Here we examined the degree to which relationships between alcohol use and sleep quality differ between women and men.

Methods

Heavy drinking women (n = 66) and men (n = 45) completed the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Alcohol Use Disorders Identification Test (AUDIT) to assess alcohol use and alcohol-related problems. Hierarchical regression analyses were conducted to determine sex differences in the association between poor sleep quality and alcohol-related problems.

Results

After controlling for age, global subjective stress, and depression, sex significantly moderated the positive association between poor sleep quality and alcohol-related problems. Further analyses of the simple slopes for each sex revealed that poorer sleep quality (i.e., higher scores on the PSQI) were associated with greater alcohol-related problems (i.e., higher scores on the AUDIT) in women, but not in men.

Conclusion

These results suggest that in heavy drinkers with insomnia, poor sleep is more strongly associated with drinking problems in women than in men. Future research is needed to investigate potential mechanisms underlying this relationship. Specifically, it will be important to determine whether sleep problems in heavy drinking women are a cause or consequence, or both, of heavy drinking.
Sequential Prefrontal and Temporoparietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Tinnitus With and Without Comorbid Depression: A Case Series and Systematic Review
Authors: Marder Katharine G. , Cho Janice , Chincanchan Ruth , Wilson Andrew C. , Corlier Juliana , Krantz David E. , Ginder Nathaniel D. , Lee Jonathan C. , Wilke Scott A. , Tadayonnejad Reza , Levitt Jennifer , Ishiyama Akira , Leuchter Michael K. , Leuchter Andrew F.
Published: May 2022

Background

Tinnitus distress is related to both the loudness and intrusiveness of the tinnitus percept. Treatment approaches targeting both attentional/limbic and auditory systems may better alleviate tinnitus distress than approaches targeting the auditory system alone.

Materials and Methods

Ten subjects with chronic tinnitus received sequential rTMS treatment involving: 1) excitatory stimulation administered to the left dorsolateral prefrontal cortex (DLPFC) or inhibitory stimulation administered to the right DLPFC, followed by 2) inhibitory stimulation administered to primary auditory cortex (Heschel's gyrus or HG). A systematic literature review was performed to evaluate the existing literature on sequential repetitive Transcranial Magnetic Stimulation (rTMS) treatment approaches for tinnitus. Results of the case series are interpreted in the context of tinnitus neurobiology and the extant literature.

Results

Subjects experienced a significant decrease (average 21.7%) in symptoms on the Tinnitus Functional Index (TFI). Those with tinnitus alone experienced a greater mean symptom reduction than those with comorbid MDD (27.7 vs. 17.0%, respectively). Adverse effects were transient and minor. Literature review confirmed that sequential approaches had some advantages compared to single site rTMS; in general, the addition of 1 Hz treatment at DLPFC was superior to single site rTMS in the short term (1–12 weeks), while the addition of 20 Hz treatment at DLPFC appeared superior in the long term (90–180 days).

Conclusions

Sequential rTMS approaches for the treatment of tinnitus—particularly those administering low-frequency treatment at left DLPFC—merit further investigation.
Immune-Mediated Mechanisms of COVID-19 Neuropathology
Authors: Dunai Cordelia , Collie Ceryce , Michael Benedict D.
Published: May 2022

Although SARS-CoV-2 causes a respiratory viral infection, there is a large incidence of neurological complications occurring in COVID-19 patients. These range from headaches and loss of smell to encephalitis and strokes. Little is known about the likely diverse mechanisms causing these pathologies and there is a dire need to understand how to prevent and treat them. This review explores recent research from the perspective of investigating how the immune system could play a role in neurological complications, including cytokines, blood biomarkers, immune cells, and autoantibodies. We also discuss lessons learnt from animal models. Overall, we highlight two key points that have emerged from increasing evidence: (1) SARS-CoV-2 does not invade the brain in the majority of cases and so the associated neurological complications might arise from indirect effects, such as immune activation (2) although the immune system plays a critical role in controlling the virus, its dysregulation can cause pathology.
Machine Learning Classifiers to Evaluate Data From Gait Analysis With Depth Cameras in Patients With Parkinson’s Disease
Authors: Muñoz-Ospina Beatriz , Alvarez-Garcia Daniela , Clavijo-Moran Hugo Juan Camilo , Valderrama-Chaparro Jaime Andrés , García-Peña Melisa , Herrán Carlos Alfonso , Urcuqui Christian Camilo , Navarro-Cadavid Andrés , Orozco Jorge
Published: May 2022

Introduction

The assessments of the motor symptoms in Parkinson’s disease (PD) are usually limited to clinical rating scales (MDS UPDRS III), and it depends on the clinician’s experience. This study aims to propose a machine learning technique algorithm using the variables from upper and lower limbs, to classify people with PD from healthy people, using data from a portable low-cost device (RGB-D camera). And can be used to support the diagnosis and follow-up of patients in developing countries and remote areas.

Methods

We used Kinect®eMotion system to capture the spatiotemporal gait data from 30 patients with PD and 30 healthy age-matched controls in three walking trials. First, a correlation matrix was made using the variables of upper and lower limbs. After this, we applied a backward feature selection model using R and Python to determine the most relevant variables. Three further analyses were done using variables selected from backward feature selection model (Dataset A), movement disorders specialist (Dataset B), and all the variables from the dataset (Dataset C). We ran seven machine learning models for each model. Dataset was divided 80% for algorithm training and 20% for evaluation. Finally, a causal inference model (CIM) using the DoWhy library was performed on Dataset B due to its accuracy and simplicity.

Results

The Random Forest model is the most accurate for all three variable Datasets (Dataset A: 81.8%; Dataset B: 83.6%; Dataset C: 84.5%) followed by the support vector machine. The CIM shows a relation between leg variables and the arms swing asymmetry (ASA) and a proportional relationship between ASA and the diagnosis of PD with a robust estimator (1,537).

Conclusions

Machine learning techniques based on objective measures using portable low-cost devices (Kinect®eMotion) are useful and accurate to classify patients with Parkinson’s disease. This method can be used to evaluate patients remotely and help clinicians make decisions regarding follow-up and treatment.
MicroRNA Alterations in Chronic Traumatic Encephalopathy and Amyotrophic Lateral Sclerosis
Authors: Alvia Marcela , Aytan Nurgul , Spencer Keith R. , Foster Zachariah W. , Rauf Nazifa Abdul , Guilderson Latease , Robey Ian , Averill James G. , Walker Sean E. , Alvarez Victor E. , Huber Bertrand R. , Mathais Rebecca , Cormier Kerry A. , Nicks Raymond , Pothast Morgan , Labadorf Adam , Agus Filisia , Alosco Michael L. , Mez Jesse , Kowall Neil W. , McKee Ann C. , Brady Christopher B. , Stein Thor D.
Published: May 2022

Repetitive head impacts (RHI) and traumatic brain injuries are risk factors for the neurodegenerative diseases chronic traumatic encephalopathy (CTE) and amyotrophic lateral sclerosis (ALS). ALS and CTE are distinct disorders, yet in some instances, share pathology, affect similar brain regions, and occur together. The pathways involved and biomarkers for diagnosis of both diseases are largely unknown. MicroRNAs (miRNAs) involved in gene regulation may be altered in neurodegeneration and be useful as stable biomarkers. Thus, we set out to determine associations between miRNA levels and disease state within the prefrontal cortex in a group of brain donors with CTE, ALS, CTE + ALS and controls. Of 47 miRNAs previously implicated in neurological disease and tested here, 28 (60%) were significantly different between pathology groups. Of these, 21 (75%) were upregulated in both ALS and CTE, including miRNAs involved in inflammatory, apoptotic, and cell growth/differentiation pathways. The most significant change occurred in miR-10b, which was significantly increased in ALS, but not CTE or CTE + ALS. Overall, we found patterns of miRNA expression that are common and unique to CTE and ALS and that suggest shared and distinct mechanisms of pathogenesis.
A Role for Gene-Environment Interactions in Autism Spectrum Disorder Is Supported by Variants in Genes Regulating the Effects of Exposure to Xenobiotics
Authors: Santos João Xavier , Rasga Célia , Marques Ana Rita , Martiniano Hugo , Asif Muhammad , Vilela Joana , Oliveira Guiomar , Sousa Lisete , Nunes Ana , Vicente Astrid M.
Published: May 2022

Heritability estimates support the contribution of genetics and the environment to the etiology of Autism Spectrum Disorder (ASD), but a role for gene-environment interactions is insufficiently explored. Genes involved in detoxification pathways and physiological permeability barriers (e.g., blood-brain barrier, placenta and respiratory airways), which regulate the effects of exposure to xenobiotics during early stages of neurodevelopment when the immature brain is extremely vulnerable, may be particularly relevant in this context. Our objective was to identify genes involved in the regulation of xenobiotic detoxification or the function of physiological barriers (the XenoReg genes) presenting predicted damaging variants in subjects with ASD, and to understand their interaction patterns with ubiquitous xenobiotics previously implicated in this disorder. We defined a panel of 519 XenoReg genes through literature review and database queries. Large ASD datasets were inspected for in silico predicted damaging Single Nucleotide Variants (SNVs) (N = 2,674 subjects) or Copy Number Variants (CNVs) (N = 3,570 subjects) in XenoReg genes. We queried the Comparative Toxicogenomics Database (CTD) to identify interaction pairs between XenoReg genes and xenobiotics. The interrogation of ASD datasets for variants in the XenoReg gene panel identified 77 genes with high evidence for a role in ASD, according to pre-specified prioritization criteria. These include 47 genes encoding detoxification enzymes and 30 genes encoding proteins involved in physiological barrier function, among which 15 are previous reported candidates for ASD. The CTD query revealed 397 gene-environment interaction pairs between these XenoReg genes and 80% (48/60) of the analyzed xenobiotics. The top interacting genes and xenobiotics were, respectively, CYP1A2, ABCB1, ABCG2, GSTM1, and CYP2D6 and benzo-(a)-pyrene, valproic acid, bisphenol A, particulate matter, methylmercury, and perfluorinated compounds. Individuals carrying predicted damaging variants in high evidence XenoReg genes are likely to have less efficient detoxification systems or impaired physiological barriers. They can therefore be particularly susceptible to early life exposure to ubiquitous xenobiotics, which elicit neuropathological mechanisms in the immature brain, such as epigenetic changes, oxidative stress, neuroinflammation, hypoxic damage, and endocrine disruption. As exposure to environmental factors may be mitigated for individuals with risk variants, this work provides new perspectives to personalized prevention and health management policies for ASD.
Analysis of Microcirculation Changes in the Macular Area and Para-Optic Disk Region After Implantable Collamer Lens Implantation in Patients With High Myopia
Authors: Xu Yingnan , Yang Weihua , Long Tan , Shang Weihong , Xu Xiangzhong , Wang Jinfan , Yao Jin , Li Keran
Published: May 2022

Myopia has become an important public health problem to be solved urgently. Posterior chamber phakic implantable Collamer lens (ICL) implantation is one of the latest and safest products for myopia correction worldwide. This prospective cross-sectional case series aimed to observe changes in the macular retinal thickness, retinal nerve fiber layer (RNFL) thickness of para-optic disk region, and blood flow density after posterior ICL implantation in patients with high myopia using optical coherence tomography angiography (OCTA). A total of 67 eyes of 67 patients with high myopia, who underwent ICL implantation at The Affiliated Eye Hospital of Nanjing Medical University from January 2020 and December 2020, were included. The spherical equivalent (SE) of the operative eyes was >−6.00 D. The changes in vision, intraocular pressure (IOP), SE, and vault were observed pre-operatively, and follow-up were performed 1 week, 1 month, and 3 months. OCTA was used to observe the changes in the CRT, retinal thickness of paracentral fovea, FAZ, superficial and deep retinal blood flow density in the macular area, RNFL thickness of para-optic disk region, and blood flow density before and after ICL implantation. The uncorrected distance visual acuity (UDVA) and best corrected distance visual acuity (CDVA) of the patients post-operation were significantly improved (P < 0.001). The IOP increased in comparison with other time points at 1 week post-operation (P < 0.05). There were no significant changes in CRT post-operation. The retinal thickness in the upper, lower, nasal, and temporal quadrants of the paracentral fovea increased significantly at 1 month and 3 months post-operation (P < 0.05). The FAZ area at all postoperative time points were decreased (P < 0.001). At 3 months post-operation, the blood flow density of the superficial and deep retinal layers in the upper, lower, and nasal macular area were significantly reduced (P < 0.05). At 1 month post-operation, the RNFL thickness in the temporal para-optic disk region and blood flow density were significantly reduced (P = 0.001 and P < 0.05, respectively). ICL implantation for highly myopic eyes led to an increase of the retinal thickness in the upper, lower, nasal, and temporal regions of the paracentral fovea; reduction of RNFL thickness in the temporal area of para-optic disk; decrease in FAZ area; and decrease in the blood flow density of some deep and superficial retinal layers as well as that of the temporal para-optic disk region.
Periodontitis Salivary Microbiota Aggravates Ischemic Stroke Through IL-17A
Authors: Chen Yan-Lin , Bai Lan , Dilimulati Dilirebati , Shao Shuai , Qiu Che , Liu Ting , Xu Shuo , Bai Xue-Bing , Du Lin-Juan , Zhou Lu-Jun , Lin Wen-Zhen , Meng Xiao-Qian , Jin Yi-Chao , Liu Yan , Zhang Xiao-Hua , Duan Sheng-Zhong , Jia Feng
Published: May 2022

Although epidemiological studies suggest that periodontitis is tightly associated with ischemic stroke, its impact on ischemic stroke and the underlysing mechanisms are poorly understood. Recent studies have shown that alteration in gut microbiota composition influences the outcomes of ischemic stroke. In the state of periodontitis, many oral pathogenic bacteria in the saliva are swallowed and transmitted to the gut. However, the role of periodontitis microbiota in the pathogenesis and progression of ischemic stroke is unclear. Therefore, we hypothesized that the periodontitis salivary microbiota influences the gut immune system and aggravates ischemic stroke. Mice receiving gavage of periodontitis salivary microbiota showed significantly worse stroke outcomes. And these mice also manifested more severe neuroinflammation, with higher infiltration of inflammatory cells and expression of inflammatory cytokines in the ischemic brain. More accumulation of Th17 cells and IL-17+ γδ T cells were observed in the ileum. And in Kaede transgenic mice after photoconversion. Migration of CD4+ T cells and γδ T cells from the ileum to the brain was observed after ischemic stroke in photoconverted Kaede transgenic mice. Furthermore, the worse stroke outcome was abolished in the IL-17A knockout mice. These findings suggest that periodontitis salivary microbiota increased IL-17A-producing immune cells in the gut, likely promoted the migration of these cells from the gut to the brain, and subsequently provoked neuroinflammation after ischemic stroke. These findings have revealed the role of periodontitis in ischemic stroke through the gut and provided new insights into the worse outcome of ischemic stroke coexisting with periodontitis in clinical trials.
The Neuroimmune Interface and Chronic Pain Through the Lens of Production Animals
Authors: Johnston Charlotte H. , Whittaker Alexandra L. , Franklin Samantha H. , Hutchinson Mark R.
Published: May 2022

Communication between the central nervous system (CNS) and the immune system has gained much attention for its fundamental role in the development of chronic and pathological pain in humans and rodent models. Following peripheral nerve injury, neuroimmune signaling within the CNS plays an important role in the pathophysiological changes in pain sensitivity that lead to chronic pain. In production animals, routine husbandry procedures such as tail docking and castration, often involve some degree of inflammation and peripheral nerve injury and consequently may lead to chronic pain. Our understanding of chronic pain in animals is limited by the difficulty in measuring this pathological pain state. In light of this, we have reviewed the current understanding of chronic pain in production animals. We discuss our ability to measure pain and the implications this has on animal welfare and production outcomes. Further research into the neuroimmune interface in production animals will improve our fundamental understanding of chronic pain and better inform human clinical pain management and animal husbandry practices and interventions.
Aberrant Functional Network of Small-World in Sudden Sensorineural Hearing Loss With Tinnitus
Authors: Hua Jin-Chao , Xu Xiao-Min , Xu Zhen-Gui , Xu Jin-Jing , Hu Jing-Hua , Xue Yuan , Wu Yuanqing
Published: May 2022

Few researchers investigated the topological properties and relationships with cognitive deficits in sudden sensorineural hearing loss (SNHL) with tinnitus. To explore the topological characteristics of the brain connectome following SNHL from the global level and nodal level, we recruited 36 bilateral SNHL patients with tinnitus and 37 well-matched healthy controls. Every subject underwent pure tone audiometry tests, neuropsychological assessments, and MRI scanning. AAL atlas was employed to divide a brain into 90 cortical and subcortical regions of interest, then investigated the global and nodal properties of “small world” network in SNHL and control groups using a graph-theory analysis. The global characteristics include small worldness, cluster coefficient, characteristic path length, local efficiency, and global efficiency. Node properties include degree centrality, betweenness centrality, nodal efficiency, and nodal clustering coefficient. Interregional connectivity analysis was also computed among 90 nodes. We found that the SNHL group had significantly higher hearing thresholds and cognitive impairments, as well as disrupted internal connections among 90 nodes. SNHL group displayed lower AUC of cluster coefficient and path length lambda, but increased global efficiency. The opercular and triangular parts of the inferior frontal gyrus, rectus gyrus, parahippocampal gyrus, precuneus, and amygdala showed abnormal local features. Some of these connectome alterations were correlated with cognitive ability and the duration of SNHL. This study may prove potential imaging biomarkers and treatment targets for future studies.
Non-invasive Brain Stimulation for Central Neuropathic Pain
Authors: Yang Qi-Hao , Zhang Yong-Hui , Du Shu-Hao , Wang Yu-Chen , Fang Yu , Wang Xue-Qiang
Published: May 2022

The research and clinical application of the noninvasive brain stimulation (NIBS) technique in the treatment of neuropathic pain (NP) are increasing. In this review article, we outline the effectiveness and limitations of the NIBS approach in treating common central neuropathic pain (CNP). This article summarizes the research progress of NIBS in the treatment of different CNPs and describes the effects and mechanisms of these methods on different CNPs. Repetitive transcranial magnetic stimulation (rTMS) analgesic research has been relatively mature and applied to a variety of CNP treatments. But the optimal stimulation targets, stimulation intensity, and stimulation time of transcranial direct current stimulation (tDCS) for each type of CNP are still difficult to identify. The analgesic mechanism of rTMS is similar to that of tDCS, both of which change cortical excitability and synaptic plasticity, regulate the release of related neurotransmitters and affect the structural and functional connections of brain regions associated with pain processing and regulation. Some deficiencies are found in current NIBS relevant studies, such as small sample size, difficulty to avoid placebo effect, and insufficient research on analgesia mechanism. Future research should gradually carry out large-scale, multicenter studies to test the stability and reliability of the analgesic effects of NIBS.
Widely Targeted Metabolomics Analysis of the Changes to Key Non-volatile Taste Components in Stropharia rugosoannulata Under Different Drying Methods
Authors: Liu Yi , Meng Fangbo , Tang Pengyu , Huang Daomei , Li Qixing , Lin Mao
Published: May 2022

Stropharia rugosoannulata is an extremely perishable edible fungi product, and drying can delay its deterioration, however, drying will affect its flavor, especially the non-volatile taste substances dominated by amino acids, nucleotides, organic acids and carbohydrates. Currently, which drying method is the most suitable for the drying of S. rugosoannulata remains unknown, we need to fully consider the economic efficiency of the method and the impact on flavor. But we have limited comprehensive knowledge of the changed non-volatile taste metabolites as caused by drying processes. Here, an LC-MS/MS-based widely targeted metabolome analysis was conducted to investigate the transformation mechanism of S. rugosoannulata non-volatile taste components after undergoing hot air drying (HAD), vacuum freeze drying (VFD), and microwave vacuum drying (MVD). A total of 826 metabolites were identified, 89 of which—48 amino acids, 25 nucleotides, 8 organic acids, and 8 carbohydrates—were related to non-volatile taste. The drying method used and the parts of S. rugosoannulata (stipe and pileus) influenced the differences found in these metabolites. The possible mechanisms responsible for such chemical alterations by different drying methods were also investigated by a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Amino acid metabolism (alanine, aspartate, and glutamate metabolism; glycine, serine, and threonine metabolism; arginine and proline metabolism; valine, leucine, and isoleucine biosynthesis) was the main metabolic pathway involved. Pathway enrichment analysis also identified differences in non-volatile taste components among three drying methods that may be closely related to the applied drying temperature. Altogether, the results indicated that as an economical and convenient drying method, HAD is conducive to improving the flavor of S. rugosoannulata and thus it harbors promising potential for practical applications.
Dietary Eggshell Membrane Powder Improves Survival Rate and Ameliorates Gut Dysbiosis in Interleukin-10 Knockout Mice
Authors: Yang Yongshou , Jia Huijuan , Lyu Weida , Furukawa Kyohei , Li Xuguang , Hasebe Yukio , Kato Hisanori
Published: May 2022

Inflammatory bowel disease (IBD) is known to be associated with compositional and metabolic changes in the gut microbiota. The aim of this study was to investigate whether dietary eggshell membrane (ESM) improves survival rate or ameliorates gut dysbiosis in a spontaneous IBD model of interleukin-10 knockout (IL10−/−) mice. Female C57BL/6J wild-type (WT) and IL10−/− mice (KO) were fed an AIN-93G basal diet or an ESM diet (KOE) for 19 weeks. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and short-chain fatty acids in cecal content were analyzed with high-performance liquid chromatography. The results demonstrated that ESM supplementation significantly improved the survival rate and body composition in KO mice. Alpha diversity analysis of the microbiota revealed that ESM supplementation significantly increased gut microbial diversity, which was decreased in IL10−/− mice. The Firmicutes/Bacteroidetes ratio was recovered to a normal level by ESM supplementation, suggesting that ESM helps maintain the compositional balance of the gut microbiota. ESM increased relative abundance of commensal bacterial Ruminococcus and Bacteroidales S24-7 and reduced the abundance of the proinflammatory-related bacterium, Enterobacteriaceae. Additionally, ESM supplementation promoted the production of butyrate in cecal contents and downregulated the expression of proinflammatory genes, including interleukin-1β (Il-1β) and tumor necrosis factor-α (Tnf-α) in IL10−/− mice colon, indicating anti-inflammatory functions. These findings suggest that ESM may be used as a beneficial dietary intervention for IBD.
Cellular and Molecular Biomarkers Predictive of Response to Immunotherapy in Acute Myeloid Leukemia
Authors: Wiatrowski Kyle , Kim Tae Hee , Przespolewski Amanda
Published: May 2022

Immunotherapy has without question revolutionized the treatment of both hematologic and solid malignancies. Over the last several years novel strategies are being developed to incorporate these groundbreaking therapies into the care of patients with AML. Here we present an overview of the recent developments in immunotherapy for AML with a focus on biomarkers of response. Topics reviewed include antibody drug conjugates, BiTEs, DARTs, checkpoint inhibitors, and cellular therapy as well as the development of biomarkers predictive of response in each class.
A Theoretical Study on the Medicinal Properties and Eletronic Structures of Platinum(IV) Anticancer Agents With Cl Substituents
Authors: Yan Xiaoyang , Gao Hongwei
Published: May 2022

In this paper, we selected Pt(en)Cl4, Pt(dach)Cl4, and Pt(bipy)Cl4 with gradually increasing ligands to explore the ligand effect on the properties of platinum(IV) anticancer drugs. The electronic structures and multiple drug properties of these three complexes were studied at the LSDA/SDD level using the density functional theory (DFT) method. By comparing the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), electron affinity, atomic charge population, and natural bond orbital (NBO), we found that the order of reducibility is Pt(bipy)Cl4 > Pt(en)Cl4 > Pt(dach)Cl4. Our research can provide the theoretical basis for the development of anticancer drugs.
Changes in Neutrophil to Lymphocyte Ratio, Lymphocyte to Monocyte Ratio, and Platelet to Lymphocyte Ratio During Palliative Radiotherapy May Predict Efficacy of Immune Checkpoint Inhibitor as Re-Challenge Treatment in Advanced Gastric Cancer: A Case Report
Authors: Chen Jianxin , Wu Xilin , Zhu Shijian , Wang Junhui
Published: May 2022

Introduction

Immunotherapy with programmed death-1 (PD-1) inhibitors has emerged as frontline option in patients with advanced or metastatic gastric cancer. However, two-thirds of patients who received PD-1 inhibitors treatment still had disease progression in 1 year. Subsequent treatment strategies as salvage options always lead to limited efficacy.

Case Description

Herein, we presented a case of recurrent metastatic gastric adenocarcinoma that had progressed on first-line treatment with nivolumab, in which systematic inflammation parameters with neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) were significantly changed by palliative radiotherapy on metastatic lymph nodes. The patient achieved persistent response to the re-challenge of immune checkpoint inhibitor, which resulted in survival time reaching 52 months, and is still in extension.

Conclusions

We supposed that the palliative radiotherapy may lead to the correction of NLR, LMR, and PLR and finally contribute to the efficacy of the re-challenge treatment by PD-1 inhibitor.
Risk Prediction of Second Primary Malignancies in Primary Early-Stage Ovarian Cancer Survivors: A SEER-Based National Population-Based Cohort Study
Authors: Xu Jiaqin , Huang Chen , Wu Zhenyu , Xu Huilin , Li Jiong , Chen Yuntao , Wang Ce , Zhu Jingjing , Qin Guoyou , Zheng Xueying , Yu Yongfu
Published: May 2022

Purpose

This study aimed to characterize the clinical features of early-stage ovarian cancer (OC) survivors with second primary malignancies (SPMs) and provided a prediction tool for individualized risk of developing SPMs.

Methods

Data were obtained from the Surveillance, Epidemiology and End Results (SEER) database during 1998–2013. Considering non-SPM death as a competing event, the Fine and Gray model and the corresponding nomogram were used to identify the risk factors for SPMs and predict the SPM probabilities after the initial OC diagnosis. The decision curve analysis (DCA) was performed to evaluate the clinical utility of our proposed model.

Results

A total of 14,314 qualified patients were enrolled. The diagnosis rate and the cumulative incidence of SPMs were 7.9% and 13.6% [95% confidence interval (CI) = 13.5% to 13.6%], respectively, during the median follow-up of 8.6 years. The multivariable competing risk analysis suggested that older age at initial cancer diagnosis, white race, epithelial histologic subtypes of OC (serous, endometrioid, mucinous, and Brenner tumor), number of lymph nodes examined (<12), and radiotherapy were significantly associated with an elevated SPM risk. The DCA revealed that the net benefit obtained by our proposed model was higher than the all-screening or no-screening scenarios within a wide range of risk thresholds (1% to 23%).

Conclusion

The competing risk nomogram can be potentially helpful for assisting physicians in identifying patients with different risks of SPMs and scheduling risk-adapted clinical management. More comprehensive data on treatment regimens and patient characteristics may help improve the predictability of the risk model for SPMs.
HuR Affects the Radiosensitivity of Esophageal Cancer by Regulating the EMT-Related Protein Snail
Authors: Hu Yan , Li Qing , Yi Ke , Yang Chi , Lei Qingjun , Wang Guanghui , Wang Qianyun , Xu Xiaohui
Published: May 2022

Purpose

We previously found that Hu antigen R (HuR) can regulate the proliferation and metastasis of esophageal cancer cells. This study aims to explore the effects of HuR on the radiosensitivity of esophageal cancer.

Materials and Method

Analyses of CCK-8, colony formation assay, Western blot, immunofluorescence, flow cytometry, reactive oxygen species (ROS), and mitochondrial membrane potential were conducted to characterize the esophageal cancer cells. Nude mouse models were used to detect the effects of HuR in a combination of X-ray treatment on the subcutaneous xenografts of esophageal cancer. In addition, a luciferase assay was used to detect the direct interaction of HuR with Snail mRNA 3’-UTR.

Results

The down-regulation of HuR combined with X-ray can significantly inhibit the proliferation and colony formation of esophageal cancer cells. Flow cytometry data showed that the down-regulation of HuR could induce a G1 phase cell cycle block in esophageal cancer cells, and aggravate X-ray-induced apoptosis, indicated by the increases of apoptosis-related proteins Bax, caspase-3 and caspase-9. Moreover, the down-regulation of HuR could significantly impair the mitochondrial membrane potential and increase the ROS production and DNA double-strand break marker γH2AX expression in esophageal cancer cells that were exposed to X-rays. In vivo data showed that the down-regulation of HuR combined with radiation significantly decreased the growth of subcutaneous xenograft tumors. Furthermore, HuR could interact with Snail. Up-regulation of Snail can reverse the EMT inhibitory effects caused by HuR down-regulation, and attenuate the tumor-inhibiting and radiosensitizing effects caused by HuR down-regulation.

Conclusion

In summary, our data demonstrate that HuR effectively regulates the radiosensitivity of esophageal cancer, which may be achieved by stabilizing Snail. Thus, HuR/Snail axis is a potentially therapeutic target for the treatment of esophageal cancer.
The Biological and Molecular Function of LINC00665 in Human Cancers
Authors: Zhang Cheng , Xu Shu-Ning , Li Ke , Chen Jing-Hong , Li Qun , Liu Ying
Published: May 2022

Long non-coding RNAs (lncRNAs) are more than 200 nucleotides in length and are implicated in the development of human cancers, without protein-coding function. Mounting evidence indicates that cancer initiation and progression are triggered by lncRNA dysregulation. Recently, a growing number of studies have found that LINC00665, a long intergenic non-protein coding RNA, may be associated with various cancers, including gastrointestinal tumors, gynecological tumors, and respiratory neoplasms. LINC00665 was reported to be significantly dysregulated in cancers and has an important clinical association. It participates in cell proliferation, migration, invasion, and apoptosis through different biological pathways. In this review, we summarize the current findings on LINC00665, including its biological roles and molecular mechanisms in various cancers. LINC00665 may be a potential prognostic biomarker and novel therapeutic target for cancers.