bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of gut microbiota under different nutritional methods in elderly patients with severe COVID-19 and their relationship with prognosis
Authors: Zhang Jiawei , Deng Jiaxin , Li Juan , Su Yuping , Hu Jiancong , Lin Dezheng , Su Mingli , Chen Yongcheng , Liao Sen , Bai Xuhao , Lv Miwei , Xu Tian , Zhong Qinghua , Guo Xuefeng
Published: September 2023

Background

The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes.

Results

A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis.

Conclusions

This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.
The economic performance of mango integrated pest management practices at different scales of production
Authors: Mulungu Kelvin , Muriithi Beatrice Wambui , Kassie Menale , Khamis Fathiya Mbarak
Published: September 2023

Integrated pest management (IPM) strategies are being promoted to suppress tephritid fruit fly infestation and reduce economic damage in mango production. However, research on their economic performance across different mango production scales (measured by the number of mango trees) is limited. This study estimated the economic benefits of IPM practices (parasitoids, orchard sanitation, food bait, biopesticides, male annihilation technique, and their combinations) in Kenya’s small-, medium-, and large-scale mango production systems. We used the value–cost ratio (VCR) and net present value methods to estimate the heterogeneous economic performance of IPM practices using data from two unique farm surveys. On average, all IPM practices were profitable across various production scales. However, we found that these practices were more profitable for medium-scale farmers than for small- and large-scale farmers. The results show that farmers need a minimum of 9–17 trees, depending on the practice used, to break even and that there are little to no economic benefits to using IPM practices for farmers with more than 320 mango trees. The male annihilation technique was the most profitable practice, with a VCR of 36, and consequentially, the most adopted practice across all scales of production. Overall, we found significant heterogeneity in the profitability of IPM practices across different scales of production. The reason for the lack of profitability of IPM on large-scale farms remains unclear and warrants further investigation.
Temporal dynamics of zooplankton community in an oyster farming area of the Yellow Sea in China via metabarcoding
Authors: Qian Beibei , Miao Xiaojing , Xu Fei
Published: September 2023

Introduction

The coastal ecosystem is a hub of both marine organisms and human activities. It plays a crucial role in human food production and affects facilities through biofouling. Long-read amplicon sequencing provides more accurate species identification and demonstrates numerous advantages in community diversity studies, making it an effective tool for ecological monitoring.

Methods

To investigate the zooplankton community characteristics in the oyster aquaculture area, the composition and temporal dynamics of zooplankton near Longwan Bay, Qingdao, China, were determined by the 18S rRNA gene long reads sequencing technique.

Results

A total of 89 zooplankton species were identified, among which copepods were the most abundant. Zooplankton composition and proportional abundances showed significant seasonal variations. The species richness in summer was the highest, while the species abundance in spring was the highest. Oyster farming showed weak influence on the zooplankton community variation. Paracalanus parvus abundance was higher in most assayed months. Chthamalus stellatus showed a strong temporal preference, with the highest percentage in May. Sea water temperature and species-species interactions were revealed to be the main contributors to the shifts in the community composition.

Discussion

The ubiquitous positive correlation between zooplankton suggests that species interactions are important in adaptation to the changing environment. The results reveal the seasonal occurrence of several major biofouling organisms and help improve biofouling management efficiency.
Analysis of the evolution of the Yellow River Delta coastline and the response of the tidal current field
Authors: Zhang Lili , Shi Hongyuan , Xing Hao , Li Pingping , Ma Pengcheng
Published: September 2023

The coastline of the Yellow River Delta has undergone continual alterations due to both natural forces and human activity. Studying these changes is crucial for promoting economic growth and preserving the region’s ecological balance. Based on imagery captured by the Landsat5 and Landsat8 satellites, this study uses statistical data from the Digital Shoreline Analysis System (DSAS), including Net Shoreline Movement (NSM), End Point Rate (EPR), and Linear Regression Rate (LRR), to analyze the changes in the Yellow River Delta coastline from 2009 to 2019. This being the case, a hydrodynamic model under different shoreline conditions was established using Delft3D to compare and analyze the impact of shoreline changes on the tidal current field. From 2009 to 2019, the coastline in the study area exhibited an average movement distance of 1285m (NSM) and an annual change rate of 127.7m/a (LRR). The average increase in the area of the current estuary was 7.68km2/a, while the average decrease in the area of the old estuary was 4.91km2/a. Shoreline evolution is primarily influenced by the influx of water and sediment into the ocean. Following the implementation of water and sediment regulation, the existing estuary’s shoreline experienced a rapid initial accumulation of silt, which subsequently decelerated over time. Conversely, the former estuary has consistently undergone erosion. The greater the change in shoreline, the closer to the coast, and the greater the change in the tide. From 2009 to 2019, flow velocity and direction in the Yellow River Delta generally showed a decreasing trend, with changes ranging from 0.34% to 25.94%. The residual flow velocity near the current estuary gradually increased by about 2cm/s, while that near the abandoned old estuary gradually decreased by about 1cm/s, with no significant changes offshore. The sediment transported by the Yellow River is deposited at the current estuary, causing the coastline to move northeastward. In the abandoned estuary, there is erosion, causing the coastline to retreat.
A study of the feeding characteristics of a small and medium-sized copepod species (Sinocalanus tenellus) using genetic analysis techniques: seasonal comparison of potential/eaten food sources focused on phytoplankton
Authors: Chae Yeon-Ji , Oh Hye-Ji , Kwak Ihn-Sil , Chang Kwang-Hyeon , Jo Hyunbin
Published: September 2023

In aquatic ecosystem, the food web structure based on composition and abundance of prey species influences the feeding characteristics of predators, resulting in changes to the structure and function of the entire food web. Zooplankton mainly feed on phytoplankton, but the method of analyzing the feed source through visual and microscopic identification of gut contents has limitations in applicable species and the low resolution of the analysis results. In this study, potential vs. eaten food sources of Sinocalanus tenellus, a small and medium-sized copepod species dominant in brackish waters, were analyzed based on phytoplankton operational taxonomic units detected from the habitat’s raw water and treated whole bodies of S. tenellus. The alpha diversity and dominant/subdominant species of each potential and eaten food source were identified, and they were compared across seasons. At the same time, the feeding selectivity index (Ei) was calculated by identifying overlapping species in the potential vs. eaten food source pool. As a result, it was confirmed that not all surrounding potential food sources are fed on by S. tenellus, and that its diet can vary depending on the presence/absence of preferred prey. Metabarcoding techniques is considered to be an effective way to identify fluctuations in major food sources of zooplankton at the genus or species level. If uncertainties such as incomplete species identification as identified from the results of this study are improved through improving of analysis methods such as application of species-specific primers in the future, it will be useful for securing information on the feeding characteristics of small to medium-sized zooplankton.
Thiamine as a metabolic resuscitator in septic shock: a meta-analysis of randomized controlled trials with trial sequential analysis
Authors: Sangla Frédéric , Verissimo Thomas , Faivre Anna , Glauser Térence , Cheah Saw Kian , Assouline Benjamin , Sgardello Sebastian , Legouis David
Published: September 2023

Objective

Septic shock is one of the most common reasons for admission to the Intensive Care Unit (ICU) and is associated with high mortality. Fundamentally, its management rests on antibiotics, fluid therapy and vasopressor use while many adjunctive therapies have shown disappointing results. Thiamine has recently gained interest as a metabolic resuscitator, though recent trials have tempered this enthusiasm, more specifically when thiamine is associated with ascorbic acid. However, thiamine use alone has been poorly investigated.

Design

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in septic shock patients to assess the effects of thiamine without ascorbic acid as an adjunctive therapy.

Setting

PubMed, Embase and the Cochrane library databases were searched from inception to April of 2023. Data were extracted independently by two authors. The main outcome was mortality.

Subjects

We included RCTs comparing standard care using thiamine alone, to standard care or placebo, in patients admitted to the ICU with sepsis or septic shock.

Main results

We included 5 RCTs (n = 293 patients). In this analysis, use of thiamine alone did not significantly change mortality, RR 0.87 (95%CI 0.65; 1.16, I2 = 21%) p = 0.34.

Conclusion

Current RCTs did not show an improvement in mortality when using thiamine in septic shock patients as an adjunctive therapy. However, these trials are largely underpowered for a definitive conclusion to be drawn. Further studies are therefore needed to assess the effects of thiamine without ascorbic acid as an adjunctive therapy.
Research is still limited on nutrition and quality of life among older adults
Authors: Arensberg Mary Beth , Gahche Jaime , Clapes Raquel , Kerr Kirk W. , Merkel Joyce , Dwyer Johanna T.
Published: September 2023

Introduction

Globally, the number of older adults is growing exponentially. Yet, while living longer, people are not necessarily healthier. Nutrition can positively impact healthy aging and quality of life (QoL). Two decades ago, nutrition and diet were rarely viewed as key QoL domains, were not part of QoL screening, and QoL studies frequently used unvalidated tools. It is unclear how the nutrition and QoL research area may have since evolved.

Methods

A scoping review was conducted in Pubmed of research with community-living older adults (aged ≥65) from developed economies that included 1 of 29 common, valid QoL instruments, nutrition indices, and was published between 1/2000–12/2022. The review followed published methodology guidance and used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram to document identified studies and record number of included/excluded studies (based on scoping review’s pre-specified criteria).

Results

Of 258 studies identified initially, 37 fully met scoping review inclusion criteria; only 2 were QoL studies, 30 focused on nutrition, 3 on measurement tool validation/testing, and 2 were other study types. Most studies (n = 32) were among populations outside of North America; majority were conducted in Europe (n = 22) where the EuroQol 5 Dimension (Eq5D) was used in >1/2 the studies. Of 5 North American studies, the 36-Item Short Form Survey (SF-36) was most frequently used (n = 4). Myriad nutrition indices described various aspects of eating, dietary intake, and nutrition status, making comparability between studies difficult. Studies included several different nutrition questionnaires; Mini Nutritional Assessment (MNA) (n = 8) or Mini Nutritional Assessment Short Form (MNA-SF) (n = 5) were used most frequently. The most frequent anthropometric measure reported was Body Mass Index (BMI) (n = 28). Nutrition-related biochemical indices were reported infrequently (n = 8).

Discussion

The paucity of studies over the last two decades suggests research on nutrition and QoL among community-living older adults remains underdeveloped. Valid QoL instruments and nutrition indices are now available. To ensure greater comparability among studies it is important to develop consensus on core indices of QoL and particularly nutrition. Greater agreement on these indices will advance further research to support healthy aging and improve QoL for community-dwelling older adults.
Enhanced biodegradation of phenanthrene and anthracene using a microalgal-bacterial consortium
Authors: Hoque Mubasher Zahir , Alqahtani Abdulrahman , Sankaran Saravanan , Anand Deepak , Musa Musa M. , Nzila Alexis , Guerriero Gea , Siddiqui Khawar Sohail , Ahmad Irshad
Published: September 2023

Polycyclic aromatic hydrocarbons (PAHs) are chemicals that are released into the environment during activities of the petroleum industry. The bioaccumulation, carcinogenic and mutagenic potential of PAHs necessitates the bioremediation of these contaminants. However, bioremediation of PAHs has a number of limitations including the inability of a single microbe to degrade all of the PAH fraction’s environmental constituents. Therefore, a different paradigm, employing microalgal-bacterial consortium (MBC), may be used to effectively remove PAHs contaminants. In this type of interaction, the microalgae and bacteria species in the consortium work together in a way that enhances the overall performance of the MBC. Bacterial species in the consortium provide essential nutrients or growth factors by degrading toxic substances and provide these to microalgae, while the microalgae species provide organic carbon for the bacterial species to grow. For the first time, the ability of Gonium pectorale (G. pectorale) microalgae to break down phenanthrene (PHE) and anthracene (ANT) was investigated. Phenanthrene was shown to be more effectively degraded by G. pectorale (98%) as compared to Bacillus licheniformis (B. licheniformis) 19%. Similarly, G. pectorale has effectively degrade anthracene (98%) as compared with B. licheniformis (45%). The consortia of G. pectorale and B. licheniformis has shown a slight increase in the degradation of PHE (96%) and ANT (99%). Our findings show that B. licheniformis did not inhibit the growth of G. pectorale and in the consortia has effectively eliminated the PAHs from the media. Therefore G. pectorale has a tremendous potential to remove PAHs from the polluted environment. Future research will be conducted to assess Gonium’s capacity to eliminate PAHs that exhibit high molar masses than that of PHE and ANT.
Epidemiological investigation and pathogenicity of porcine reproductive and respiratory syndrome virus in Sichuan, China
Authors: Jiang Dike , Tu Teng , Zhou You , Li Yanwei , Luo Yan , Yao Xueping , Yang Zexiao , Ren Meishen , Wang Yin
Published: September 2023

Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) lineage 8 was first detected in mainland China in 2006 and has since rapidly spread to become the primary epidemic strain in the country. In this study, samples such as lung tissue, hilar lymph nodes, abortion fetuses, and blood were collected from large-scale pig farms across 11 prefecture-level cities in Sichuan province between 2019 and 2020 for antigen detection and PRRS virus isolation. The antigen detection results indicated that the positive rate of HP-PRRSV (JXA1-Like strain) was 44.74% (51/114), NADC30-Like PRRSV was 17.54% (20/114), and classical PRRSV (VR2332-Like strain) was 37.72% (43/114). The predominant strain was HP-PRRSV. Positive samples were further inoculated into Marc-145 cells for virus isolation and identification, leading to the isolation of a new JXA1-Like PRRSV strain named SCSN2020. The strain was characterized by RT-qPCR, indirect immunofluorescence assay (IFA), plaque purification, electron microscopy, and whole genome sequencing. The total length of the viral genome was determined to be approximately 15,374 bp. A comparison of the SCSN2020 genome with VR2332 revealed that both strains had the same discontinuous 30-amino acid deletion on the Nsp2 gene. ORF5 genotyping classified the SCSN2020 strain as sublineage 8.7, with a whole genome sequence identity of 99.34% with JXA1. Furthermore, we evaluated the pathogenicity of the SCSN2020 strain in 28-day-old piglets and observed persistent fever from day 4 to day 10, weight loss started on day 7, dyspnea and severe lung lesions began started on day 14. The results of this study highlight the current PRRSV epidemic situation in Sichuan province and provide a scientific reference for subsequent prevention and control measures.
Successful full-length genomic cloning and characterization of site-specific nick structures of Phytophthora endornaviruses 2 and 3 in yeast, Saccharomyces cerevisiae
Authors: Sakuta Kohei , Uchida Keiko , Fukuhara Toshiyuki , Komatsu Ken , Okada Ryo , Moriyama Hiromitsu
Published: September 2023

Two endornaviruses, Phytophthora endornavirus 2 (PEV2) and Phytophthora endornavirus 3 (PEV3), have been discovered in pathogens targeting asparagus. In this study, we analyzed the nick structure in the RNA genomes of PEV2 and PEV3 in the host oomycetes. Northern blot hybridization using positive and negative strand-specific RNA probes targeting the 5′ and 3′ regions of PEV2 and PEV3 RNA genomes revealed approximately 1.0 kilobase (kb) RNA fragments located in the 5′ regions of the two genomes. 3’ RACE analysis determined that the size of the RNA fragments were 958 nucleotides (nt) for PEV2 and 968 nt for PEV3. We have successfully constructed full-length cDNA clones of the entire RNA genomes of PEV2 and PEV3 using a homologous recombination system in the yeast, Saccharomyces cerevisiae. These full-length cDNA sequences were ligated downstream of a constitutive expression promoter (TDH3) or a galactose-inducing promoter (GAL1) in the shuttle vector to enable the production of the full-length RNA transcripts of PEV2 and PEV3 in yeast cells. Interestingly, a 1.0 kb RNA fragment from the PEV3 positive-strand transcript was also detected with a 5′-region RNA probe, indicating that site-specific cleavage also occurred in yeast cells. Further, when PEV2 or PEV3 mRNA was overexpressed under the GAL1 promoter, yeast cell growth was suppressed. A fusion protein combining EGFP to the N-terminus of the full-length PEV2 ORF or C-terminus of the full-length PEV3 ORF was expressed, and allowed PEV2 and PEV3 ORFs to be successfully visualized in yeast cells. Expression of the fusion protein also revealed presence of heterogeneous bodies in the cells.
Effects of alcohol on the symptoms of gouty arthritis and taxonomic structure of gut microbiota in C57BL/6 mice
Authors: Feng Yu , Sun Haihui , Zhu Ruilou , Tao Jianxing , Su Rui , Sun Yundong , Wang Dawei
Published: September 2023

Gout is an acute arthritis caused by the elevated levels of serum uric acid (UA), and its prevalence has been rapidly increasing. Alcohol abuse could lead to a series of health problems. Multiple pieces of evidence suggest that alcohol intake affects the development and progression of gout, while the gut microbiota plays an important role in the development of gout and the long-term alcohol consumption could affect the stability of the gut microbiota. This study aimed to explore the effects of alcohol intake at different concentrations on gouty arthritis based on the gut microbiota. We investigated the effects of different concentrations of alcohol on gouty arthritis in mouse models of acute gouty arthritis established by injection of monosodium urate (MSU) crystals into C57BL/6 mice. The results indicated that the high-alcohol consumption not only exacerbated joint swelling and pain, increased the levels of UA, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), but also showed dramatic effects on the composition and structure of the gut microbiota in gouty mice. Two key microorganisms, Parasutterella and Alistipes, could aggravate gout symptoms through lipopolysaccharide biosynthesis, riboflavin metabolism, phenylalanine metabolism, and arginine and proline metabolisms. In conclusion, our study suggested that high-concentrations of alcohol altered the gut microbiota structure in gouty mice induced by MSU crystals, which could exacerbate gouty symptoms by enhancing pro-inflammatory pathways.
Sex differences in the structural rich-club connectivity in patients with Alzheimer’s disease
Authors: Kim Soo-Jong , Bae Youn Jung , Park Yu Hyun , Jang Hyemin , Kim Jun Pyo , Seo Sang Won , Seong Joon-Kyung , Kim Geon Ha
Published: September 2023

Background and objectives

Alzheimer’s disease (AD) is more prevalent in women than in men; however, there is a discrepancy in research on sex differences in AD. The human brain is a large-scale network with hub regions forming a central core, the rich-club, which is vital to cognitive functions. However, it is unknown whether alterations in the rich-clubs in AD differ between men and women. We aimed to investigate sex differences in the rich-club organization in the brains of patients with AD.

Methods

In total, 260 cognitively unimpaired individuals with negative amyloid positron emission tomography (PET) scans, 281 with prodromal AD (mild cognitive impairment due to AD) and 285 with AD dementia who confirmed with positive amyloid PET scans participated in the study. We obtained high-resolution T1-weighted and diffusion tensor images and performed network analysis.

Results

We observed sex differences in the rich-club and feeder connections in patients with AD, suggesting lower structural connectivity strength in women than in men. We observed a significant group-by-sex interaction in the feeder connections, particularly in the thalamus. In addition, the connectivity strength of the thalamus in the feeder connections was significantly correlated with general cognitive function in only men with prodromal AD and women with AD dementia.

Conclusion

Our findings provide important evidence for sex-specific alterations in the structural brain network related to AD.
The γ-Adducin 1–357 fragment promotes tau pathology
Authors: Yu Honglu , Xiong Min , Liu Congcong , Xia Danhao , Meng Lanxia , Zhang Zhentao
Published: September 2023

Background

Tau phosphorylation is a pathological hallmark of Alzheimer’s disease (AD). Previously, we reported that the γ-adducin 1–357 fragment is present in the brains of AD patients. However, it remains unknown how γ-adducin regulates tau phosphorylation.

Objective

The aim of this project is to investigate the effects of the γ-adducin 1–357 fragment on tau phosphorylation and the kinases involved in this process.

Methods

Full-length γ-adducin or the γ-adducin 1–357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length γ-adducin or γ-adducin 1–357 fragment to determine the phosphorylation of tau.

Results

The γ-adducin 1–357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the γ-adducin 1–357 fragment leads to the activation of glycogen synthase kinase-3β (GSK-3β). This effect was mitigated by the GSK-3β inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8).

Conclusion

The γ-adducin 1–357 fragment enhances tau phosphorylation by activating GSK3β. These results support that the fragmentation of γ-adducin may play a pivotal role in tau pathology.
Replenished microglia partially rescue schizophrenia-related stress response
Authors: Yan Ling , Xuan Fang-Ling , Chen Song , Gou Mengzhuang , Chen Wenjin , Li Yanli , Wang Zhiren , Wang Leilei , Xie Ting , Fan Fengmei , Zharkovsky Alexander , Tan Yunlong , Tian Li
Published: September 2023

Background

Microglia play an important role in the maintenance of brain and behavioral homeostasis. The protective effect of microglial replenishment was reported in neurological diseases, but whether microglial therapy would benefit psychiatric disorders such as schizophrenia has been unclear. As schizophrenia is a stress-vulnerable disorder and psychosocial stress promotes inflammation and microglial activation, we aim to understand how microglial replenishment works in stress-associated schizophrenia.

Methods

We used a CSF1R-mediated pharmacological approach to study repopulated microglia (repMg) in a cohort of mice (n = 10/group) undergoing chronic unpredictable stress (CUS). We further studied a cohort of first-episode schizophrenia (FES, n = 74) patients who had higher perceived stress scores (PSS) than healthy controls (HCs, n = 68).

Results

Reborn microglia attenuated CUS-induced learned hopelessness and social withdrawal but not anxiety in mice. Compared to control, CUS- or repMg-induced differentially expressed genes (DEGs) in the prefrontal cortex regulated nervous system development and axonal guidance. CUS also caused microglial hyper-ramification and increased engulfment of synaptophysin and vesicular glutamate transporter-2 by microglia and astrocytes, which were recovered in CUS + repMg (all p < 0.05). Moreover, FES patients had smaller hippocampal fimbria than HCs (p < 1e-7), which were negatively associated with PSS (r = −0.397, p = 0.003). Blood DEGs involved in immune system development were also associated with PSS and the right fimbria more prominently in FES patients than HCs (Zr, p < 0.0001). The KCNQ1 was a partial mediator between PSS and fimbria size (β = −0.442, 95% CI: −1.326 ~ −0.087).

Conclusion

Microglial replenishment may potentially benefit psychiatric disorders such as schizophrenia.
Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
Authors: Bigotte Maxime , Groh Adam M. R. , Marignier Romain , Stratton Jo Anne
Published: September 2023

Ependymal cells make up the epithelial monolayer that lines the brain ventricles and the spinal cord central canal that are filled with cerebrospinal fluid. The ependyma has several functions, including regulating solute exchange between the cerebrospinal fluid and parenchyma, controlling microcirculation of cerebrospinal fluid via coordinated ciliary beating, and acting as a partial barrier. Dysregulation of these functions can lead to waste clearance impairment, cerebrospinal fluid accumulation, hydrocephalus, and more. A role for ependymal cells in a variety of neurological disorders has been proposed, including in neuromyelitis optica and multiple sclerosis, two autoimmune demyelinating diseases of the central nervous system, where periventricular damage is common. What is not known is the mechanisms behind how ependymal cells become dysregulated in these diseases. In neuromyelitis optica, it is well established that autoantibodies directed against Aquaporin-4 are drivers of disease, and it has been shown recently that these autoantibodies can drive ependymal cell dysregulation. We propose a similar mechanism is at play in multiple sclerosis, where autoantibodies targeting a glial cell protein called GlialCAM on ependymal cells are contributing to disease. GlialCAM shares high molecular similarities with the Epstein–Barr virus (EBV) protein EBNA1. EBV has recently been shown to be necessary for multiple sclerosis initiation, yet how EBV mediates pathogenesis, especially in the periventricular area, remains elusive. In this perspective article, we discuss how ependymal cells could be targeted by antibody-related autoimmune mechanisms in autoimmune demyelinating diseases and how this is implicated in ventricular/periventricular pathology.
Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs
Authors: Buddington Randal K. , Wong Thomas , Buddington Karyl K. , Mikkelsen Torben S. , Cao Xueyuan , Howard Scott C.
Published: September 2023

Introduction

Early identification of compromised renal clearance caused by high-dose methotrexate (HDMTX) is essential for initiating timely interventions that can reduce acute kidney injury and MTX-induced systemic toxicity.

Methods

We induced acute kidney injury (AKI) by infusing 42 juvenile pigs with 4 g/kg (80 g/m2) of MTX over 4 hours without high-volume alkalinizing hydration therapy. Concentrations of serum creatinine and MTX were measured at 15 time points up to 148 hours, with 10 samples collected during the first 24 hours after the start of the HDMTX infusion.

Results

During the first 28 hours, 81% of the pigs had increases in the concentrations of serum creatinine in one or more samples indicative of AKI (i.e., > 0.3g/dL increase). A rate of plasma MTX clearance of less than 90% during the initial 4 hours after the HDMTX infusion and a total serum creatinine increase at 6 and 8 hours after starting the infusion greater than 0.3 g/dL were predictive of AKI at 28 hours (p < 0.05 and p < 0.001, respectively). At conclusion of the infusion, pigs with a creatinine concentration more than 0.3 g/dL higher than baseline or serum MTX greater than 5,000 μmol/L had an increased risk of severe AKI.

Conclusions

Our findings suggest that serum samples collected at conclusion and shortly after HDMTX infusion can be used to predict impending AKI. The pig model can be used to identify biological, environmental, and iatrogenic risk factors for HDMTX-induced AKI and to evaluate interventions to preserve renal functions, minimize acute kidney injury, and reduce systemic toxicity.
The characteristics and alteration of peripheral immune function in patients with multiple system atrophy
Authors: Wang Minghui , Yan Zhaofen , Wang Jing , Yang Yujiao , Deng Qinqin , Han Yixian , Zhang Liping , Yang Huajun , Pan Jiali , Wang Mengyang
Published: September 2023

Objective

Multiple system atrophy (MSA) is a degenerative disease. Immune dysfunction found to play a crucial role in the pathogenesis of this disease in the literature, while the characteristics of peripheral immune function remain unclear. This study aimed to investigate the characteristics and alterations of peripheral immune function in patients with MSA.

Methods

A case–control study was conducted between January 2021 to December 2022 at SanBo Brain Hospital, Capital Medical University, Beijing, China. A total of 74 participants were recruited, including 47 MSA patients and 27 non-MSA participants. Peripheral blood samples were collected from each participant. A total of 29 types of immune cells were measured using the flow cytometry analysis technology. Single-factor analysis and multiple-factor analysis (multiple linear regression models) were performed to determine the differences and risk factors in immune cells between the MSA and non-MSA groups.

Results

Alterations of the count or percentage of CD19+ B lymphocytes and CD3−CD56+ B lymphocytes in MSA patients were found in this study. The reductions of the count and percentage of CD19+ B lymphocytes were still robust after adjusting for variables of age, gender, body mass index, albumin, and hemoglobin. Furthermore, the reductions in the count and percentage of CD19+ B lymphocytes in the MSA patients were more significant in women and individuals aged 60 years old or above than in the non-MSA participants.

Conclusion

Our findings suggested that MSA patients may be influenced by B lymphocytes, particularly CD19+ cells. Therefore, the reductions in immune cells should be considered in the diagnosis and treatment of MSA. Further studies are warranted to confirm and expand upon these findings.
Retest reliability of repetitive transcranial magnetic stimulation over the healthy human motor cortex: a systematic review and meta-analysis
Authors: Kanig Carolina , Osnabruegge Mirja , Schwitzgebel Florian , Litschel Karsten , Seiberl Wolfgang , Mack Wolfgang , Schoisswohl Stefan , Schecklmann Martin
Published: September 2023

Introduction

Repetitive transcranial magnetic stimulation (rTMS) is used to induce long-lasting changes (aftereffects) in cortical excitability, which are often measured via single-pulse TMS (spTMS) over the motor cortex eliciting motor-evoked potentials (MEPs). rTMS includes various protocols, such as theta-burst stimulation (TBS), paired associative stimulation (PAS), and continuous rTMS with a fixed frequency. Nevertheless, subsequent aftereffects of rTMS are variable and seem to fail repeatability. We aimed to summarize standard rTMS procedures regarding their test–retest reliability. Hereby, we considered influencing factors such as the methodological quality of experiments and publication bias.

Methods

We conducted a literature search via PubMed in March 2023. The inclusion criteria were the application of rTMS, TBS, or PAS at least twice over the motor cortex of healthy subjects with measurements of MEPs via spTMS as a dependent variable. The exclusion criteria were measurements derived from the non-stimulated hemisphere, of non-hand muscles, and by electroencephalography only. We extracted test–retest reliability measures and aftereffects from the eligible studies. With the Rosenthal fail-safe N, funnel plot, and asymmetry test, we examined the publication bias and accounted for influential factors such as the methodological quality of experiments measured with a standardized checklist.

Results

A total of 15 studies that investigated test–retest reliability of rTMS protocols in a total of 291 subjects were identified. Reliability measures, i.e., Pearson's r and intraclass correlation coefficient (ICC) applicable from nine studies, were mainly in the small to moderate range with two experiments indicating good reliability of 20 Hz rTMS (r = 0.543) and iTBS (r = 0.55). The aftereffects of rTMS procedures seem to follow the heuristics of respective inhibition or facilitation, depending on the protocols' frequency, and application pattern. There was no indication of publication bias and the influence of methodological quality or other factors on the reliability of rTMS.

Conclusion

The reliability of rTMS appears to be in the small to moderate range overall. Due to a limited number of studies reporting test–retest reliability values and heterogeneity of dependent measures, we could not provide generalizable results. We could not identify any protocol as superior to the others.
Twenty-five years of natural products research in NuBBE
Authors: Mannochio-Russo Helena , Pires dos Santos Ana Letícia , Bueno Paula Carolina Pires , Vieira Rafael , Ferreira Pinto Meri Emili , Silva Queiroz Suzana Aparecida , Dutra Luiz Antonio , Gaspareto Felippe Lidiane , Nastri de Luca Batista Andrea , de Souza-Moreira Tatiana Maria , Valli Marilia , Previate Medina Rebeca , Araujo Angela Regina , Pilon Alan Cesar , Castro-Gamboa Ian , Cavalheiro Alberto José , Silva Dulce Helena Siqueira , Furlan Maysa , da Silva Bolzani Vanderlan
Published: September 2023

The richness of Brazilian biodiversity translates into a valuable collection of molecules with biological properties that range from ecological functions to pharmacological properties. For over 25 years, the Nucleus of Bioassays, Biosynthesis, and Ecophysiology of Natural Products (NuBBE) has conducted extensive investigations into the chemical entities of numerous plant and microorganism species, resulting in the discovery of over a thousand natural compounds spanning various chemical classes (such as shikimate derivatives, phenylpropanoids, terpenoids, alkaloids, and peptides). The research goals within the natural products field encompass phytochemical studies, investigations of endophytic fungi and marine organisms, biosynthetic studies, medicinal chemistry, and the development of innovative methodologies. This comprehensive review article aims to offer valuable insights into the multifaceted research endeavors conducted in NuBBE. In this way, accomplishments, perspectives, and opportunities for advancing natural products research in Brazil are highlighted, seeking to inspire and motivate other research groups in the field of natural products–especially those located in emerging countries with rich biodiversity.
Development of a multi-feature-combined model: proof-of-concept with application to local failure prediction of post-SBRT or surgery early-stage NSCLC patients
Authors: Yang Zhenyu , Wang Chunhao , Wang Yuqi , Lafata Kyle J. , Zhang Haozhao , Ackerson Bradley G. , Kelsey Christopher , Tong Betty , Yin Fang-Fang
Published: September 2023

Objective

To develop a Multi-Feature-Combined (MFC) model for proof-of-concept in predicting local failure (LR) in NSCLC patients after surgery or SBRT using pre-treatment CT images. This MFC model combines handcrafted radiomic features, deep radiomic features, and patient demographic information in an integrated machine learning workflow.

Methods

The MFC model comprised three key steps. (1) Extraction of 92 handcrafted radiomic features from the GTV segmented on pre-treatment CT images. (2) Extraction of 512 deep radiomic features from pre-trained U-Net encoder. (3) The extracted handcrafted radiomic features, deep radiomic features, along with 4 patient demographic information (i.e., gender, age, tumor volume, and Charlson comorbidity index), were concatenated as a multi-dimensional input to the classifiers for LR prediction. Two NSCLC patient cohorts from our institution were investigated: (1) the surgery cohort includes 83 patients with segmentectomy or wedge resection (7 LR), and (2) the SBRT cohort includes 84 patients with lung SBRT (9 LR). The MFC model was developed and evaluated independently for both cohorts, and was subsequently compared against the prediction models based on only handcrafted radiomic features (R models), patient demographic information (PI models), and deep learning modeling (DL models). ROC with AUC was adopted to evaluate model performance with leave-one-out cross-validation (LOOCV) and 100-fold Monte Carlo random validation (MCRV). The t-test was performed to identify the statistically significant differences.

Results

In LOOCV, the AUC range (surgery/SBRT) of the MFC model was 0.858-0.895/0.868-0.913, which was higher than the three other models: 0.356-0.480/0.322-0.650 for PI models, 0.559-0.618/0.639-0.682 for R models, and 0.809/0.843 for DL models. In 100-fold MCRV, the MFC model again showed the highest AUC results (surgery/SBRT): 0.742-0.825/0.888-0.920, which were significantly higher than PI models: 0.464-0.564/0.538-0.628, R models: 0.557-0.652/0.551-0.732, and DL models: 0.702/0.791.

Conclusion

We successfully developed an MFC model that combines feature information from multiple sources for proof-of-concept prediction of LR in patients with surgical and SBRT early-stage NSCLC. Initial results suggested that incorporating pre-treatment patient information from multiple sources improves the ability to predict the risk of local failure.
Case report: Severe hypertension-induced priapism in an infant with unrecognized autosomal recessive polycystic kidney disease
Authors: Konopásek Patrik , Ptáčníková Natálie , Toni Ledjona , Zieg Jakub
Published: September 2023

Priapism is a urologic emergency requiring prompt management. There are three types of priapism: stuttering (intermittent), non-ischemic (high-flow/arterial), and ischemic (low-flow/veno-occlusive). Here, we present the first case of an infant with recurrent non-ischemic priapism as the first sign of severe hypertension. An 11-month-old infant was admitted to the hospital for high-flow priapism. On admission, he was found to have severe hypertension that required a combination of five antihypertensive drugs; abdominal ultrasound showed polycystic kidneys, splenomegaly, and a parenchymal liver lesion. The priapism resolved spontaneously and did not recur again after the initiation of antihypertensive treatment. Genetic analysis confirmed autosomal recessive polycystic kidney disease (ARPKD). We found no other explanation for the priapism, such as genital trauma, hematologic disease, or anything else. Decreased nitric oxide (NO) bioavailability seen in patients with hypertension seems to be the principal mechanism of hypertension causing priapism. This hypothesis is supported by animal models of genetically modified mice lacking nitric oxide synthase. The same mechanism is thought to be the genesis of priapism and other complications, such as pulmonary hypertension, in patients with sickle cell disease. We present a case of severe hypertension-associated priapism in a child with unrecognized ARPKD. The endothelial dysfunction with decreased NO bioavailability seen in patients with hypertension may be the principal pathogenic mechanism.
Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv)
Authors: Picó Catalina , Lurbe Empar , Keijer Jaap , Kopecky Jan , Landrier Jean-François , Álvarez-Pitti Julio , Martin Jean Charles , Oliver Paula , Palou Andreu , Palou Mariona , Zouhar Petr , Ribot Joan , Rodríguez Ana M. , Sánchez Juana , Serra Francisca , Bonet M. Luisa
Published: September 2023

Background

Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and device-based measures of PA make it difficult to obtain consistent results regarding PA and its health effects. Moreover, PA may produce different health effects depending on the type, intensity, duration, and frequency of activities and individual factors such as age, sex, body weight, early life conditions/exposures, etc. Appropriate biomarkers relating the degree of PA level with its effects on health, especially in children and adolescents, are required and missing. The main objective of the INTEGRActiv study is to identify novel useful integrative biomarkers of PA and its effects on the body health in children and adolescents, who represent an important target population to address personalized interventions to improve future metabolic health.

Methods/design

The study is structured in two phases. First, biomarkers of PA and health will be identified at baseline in a core cohort of 180 volunteers, distributed into two age groups: prepubertal (n = 90), and postpubertal adolescents (n = 90). Each group will include three subgroups (n = 30) with subjects of normal weight, overweight, and obesity, respectively. Identification of new biomarkers will be achieved by combining physical measures (PA and cardiorespiratory and muscular fitness, anthropometry) and molecular measures (cardiovascular risk factors, endocrine markers, cytokines and circulating miRNA in plasma, gene expression profile in blood cells, and metabolomics profiling in plasma). In the second phase, an educational intervention and its follow-up will be carried out in a subgroup of these subjects (60 volunteers), as a first validation step of the identified biomarkers.

Discussion

The INTEGRActiv study is expected to provide the definition of PA and health-related biomarkers (PA-health biomarkers) in childhood and adolescence. It will allow us to relate biomarkers to factors such as age, sex, body weight, sleep behavior, dietary factors, and pubertal status and to identify how these factors quantitatively affect the biomarkers’ responses. Taken together, the INTEGRActiv study approach is expected to help monitor the efficacy of interventions aimed to improve the quality of life of children/adolescents through physical activity.

Clinical Trial Registration

ClinicalTrials.gov, Identifier NCT05907785.
MixSeg: a lightweight and accurate mix structure network for semantic segmentation of apple leaf disease in complex environments
Authors: Lu Bibo , Lu Jiangwen , Xu Xinchao , Jin Yuxin
Published: September 2023

Introduction

Semantic segmentation is effective in dealing with complex environments. However, the most popular semantic segmentation methods are usually based on a single structure, they are inefficient and inaccurate. In this work, we propose a mix structure network called MixSeg, which fully combines the advantages of convolutional neural network, Transformer, and multi-layer perception architectures.

Methods

Specifically, MixSeg is an end-to-end semantic segmentation network, consisting of an encoder and a decoder. In the encoder, the Mix Transformer is designed to model globally and inject local bias into the model with less computational cost. The position indexer is developed to dynamically index absolute position information on the feature map. The local optimization module is designed to optimize the segmentation effect of the model on local edges and details. In the decoder, shallow and deep features are fused to output accurate segmentation results.

Results

Taking the apple leaf disease segmentation task in the real scene as an example, the segmentation effect of the MixSeg is verified. The experimental results show that MixSeg has the best segmentation effect and the lowest parameters and floating point operations compared with the mainstream semantic segmentation methods on small datasets. On apple alternaria blotch and apple grey spot leaf image datasets, the most lightweight MixSeg-T achieves 98.22%, 98.09% intersection over union for leaf segmentation and 87.40%, 86.20% intersection over union for disease segmentation.

Discussion

Thus, the performance of MixSeg demonstrates that it can provide a more efficient and stable method for accurate segmentation of leaves and diseases in complex environments.