bluuebunny/crossref_metadata_2025 huggingface dataset:
The crosstalk between FGF21 and GH leads to weakened GH receptor signaling and IGF1 expression and is associated with growth failure in very preterm infants
Authors: Mistry Jayna N. , Silvennoinen Sanna , Zaman Farasat , Sävendahl Lars , Mariniello Katia , Hall Charlotte , Howard Sasha R. , Dunkel Leo , Sankilampi Ulla , Guasti Leonardo
Published: May 2023

Background

Fibroblast growth factor 21 (FGF21) is an essential metabolic regulator that adapts to changes in nutritional status. Severe childhood undernutrition induces elevated FGF21 levels, contributing to growth hormone (GH) resistance and subsequent linear growth attenuation potentially through a direct action on chondrocytes.

Methods

In this study, we assessed expression of the components of both GH and FGF21 pathways in rare and unique human growth plates obtained from children. Moreover, we investigated the mechanistic interplay of FGF21 on GH receptor (GHR) signaling in a heterologous system.

Results

Chronic FGF21 exposure increased GH-induced GHR turnover and SOCS2 expression, leading to the inhibition of STAT5 phosphorylation and IGF-1 expression. The clinical significance of FGF21 signaling through GH receptors was tested in nutritionally driven growth failure seen in very preterm (VPT) infants right after birth. VPT infants display an immediate linear growth failure after birth followed by growth catch-up. Consistent with the in vitro model data, we show that circulating FGF21 levels were elevated during deflection in linear growth compared to catch-up growth and were inversely correlated with the length velocity and circulating IGF1 levels.

Conclusions

This study further supports a central role of FGF21 in GH resistance and linear growth failure and suggests a direct action on the growth plate.
Plant diversity patterns along an elevation gradient: the relative impact of environmental and spatial variation on plant diversity and assembly in arid and semi-arid regions
Authors: He Xinrui , Arif Muhammad , Zheng Jie , Ni Xilu , Yuan Zhongxun , Zhu Qiang , Wang Jifei , Ding Dongdong , Li Changxiao
Published: May 2023

The spatial distribution pattern of species diversity and its driving variables are essential to understanding how biodiversity will respond to the threat of future climatic instability. This study examines how the alpha and beta diversity indices vary along the elevation gradient and which factors are more responsible for arid and semi-arid plant diversity and community assembly. There were 121 species from 90 genera and 42 families found at elevations ranging from 1,200 to 2,600 m within the Ningxia Helan Mountain National Nature Reserve in China. These were primarily shrubs and herbs with characteristics adapted to extreme temperatures. The diversity of both the shrub layer and the herb layer was highest at mid-elevation, underscoring the importance of protecting mid-elevation ecosystems. Climatic distance and topographic distance were more influential than spatial distance in driving the species composition change of shrubs and herbs. In the herb layer, climatic, topographic, and spatial factors contributed more to community assembly than shrub communities. In this case, improving the environment in the community or introducing herbs could help the restoration of these places. These findings provide insight into biogeographic patterns, biodiversity growth mechanisms, and community formation processes. Moreover, it can improve projections of climate change within and across ecosystems and provide the scientific basis for the use and management of plant resources in arid and semi-arid regions.
A simple biochemical plasma test as an indicator of maternal energy balance predicts offspring survival in bighorn sheep
Authors: Laliberte Connor , Devan-Song Anne , Burco Julia D. , Couch Claire E. , Gentzkow Morgan F. , Spaan Robert S. , Epps Clinton W. , Beechler Brianna R.
Published: May 2023

In species where offspring survival is highly variable relative to adult survival, such as bighorn sheep (Ovis canadensis), physiological indicators of maternal investment could clarify the functional mechanisms of life history trade-offs and serve as important predictors of population dynamics. From a management perspective, simple predictors of juvenile survival measured non-lethally from maternal samples could aid in identifying at-risk populations or individuals before significant mortality occurs. Blood biochemical parameters can offer low-cost insights into animal health and physiology, therefore we sought to develop a simple biochemical predictor of juvenile survival based on maternal blood samples. We measured biochemical indicators of energy balance in adult bighorn sheep at a single time point in January or February, and then monitored survival through August of the same year to assess how those measures related to survival of individual adults and their juvenile offspring. Juvenile survival was lower over the subsequent spring and summer when maternal adult serum beta-hydroxybutyric acid (β-HBA) concentration was high, indicating a negative energy balance in the mothers. However, serum β-HBA did not correlate with adult survival over the same period. Our findings suggest that even when maternal body condition is high, short-term caloric deficit may be sufficient trigger to decrease investment in offspring survival. This mechanism could protect adult females from investing heavily in juvenile survival when resources become too limited to support population growth. Our study suggests that β-HBA could be a powerful monitoring tool for bighorn sheep and other threatened ruminant populations under resource limitation.
A new Drosophila melanogaster fly that expresses GFP-tagged Orco
Authors: Jain Kalpana , Stieber Regina , Kaltofen Sabine , Hansson Bill S. , Wicher Dieter
Published: May 2023

Insects perceive countless odors with the help of odorant receptors (ORs) expressed by olfactory sensory neurons (OSNs). OR complexes are composed of odor-specific proteins OrX and olfactory co-receptor proteins Orco, with both extracellular C-terminus and intracellular N-terminus. Here, we generated a genetically modified Drosophila melanogaster fly line that expresses Orco proteins with an N-terminally fused green fluorescent protein (GFP). We generated four genotypes (homozygous and heterozygous) for which we performed antennal cryosectioning and immunolabeling to determine which genotype would show high GFP labeling intensity in the dendritic areas of OSNs. We found that fluorescent intensity was the highest in homozygous flies. As Orco is known to guide OrX proteins to the OSN dendrites, we checked whether the fusion of GFP to the Orco N-terminus may affect such trafficking and thereby OR function. Using single sensillum recording (SSR), we found no difference in the olfactory capability of homozygous flies compared with wild-type flies. As future application, we want to use this transgenic fly line to resolve the structure of OR complexes using Cryo electron microscopy (cryo-EM).
Landscape ecological risk assessment and influencing factor analysis of basins in suburban areas of large cities – A case study of the Fuchunjiang River Basin, China
Authors: Cheng Xiaomeng , Zhang Yaping , Yang Guofu , Nie Wenbin , Wang Yinyi , Wang Jing , Xu Bin
Published: May 2023

Landscape ecological risk reflects the impact of human activities or natural hazards on landscape patterns, functions, and processes in a region. The scientific assessment of its evolutionary trends can play an essential role in maintaining and improving regional human wellbeing. This study focused on the Fuchunjiang River Basin in the suburbs of Hangzhou, a large city in China with a high degree of landscape heterogeneity and rapid economic growth. Based on land use data from 1990 to 2020, an ecological risk assessment model and geodetector tools were combined to study the spatiotemporal variation characteristics and influencing factors of landscape ecological risk in the basin. The results showed the following: (1) from 1990 to 2020, the landscape pattern of various land use types showed a general trend of an increasing degree of agglomeration and decreasing loss index; (2) the spatial distribution pattern of landscape ecological risk was “high in the northwest and low in the southeast.” From basin to township scales, landscape ecological risk showed a decreasing trend on long time scales, although the changes were relatively drastic in short time periods; (3) GDP, human interference, area of urban and rural residential land, area of arable land transferred in, and area of arable land transferred out were the dominant influencing factors of landscape ecological risk; (4) the coupling between landscape ecological risk and GDP in 2020 exhibited an inverted “U” shaped relationship, indicating that the environmental Kuznets curve (EKC) may have the same applicability in the ecological risk management; (5) according to the main functions of different risk agglomerations, targeted ecological risk management strategies were proposed. In short, this study carried out the landscape ecological risk assessment at the township scale for the first time, quantitatively analyzed the relationship between economic development and ecological risk, and proposed targeted risk prevention strategies, which are instructive for other basin areas that are experiencing rapid urbanization in the world.
Identification of hsa-miR-619-5p and hsa-miR-4454 in plasma-derived exosomes as a potential biomarker for lung adenocarcinoma
Authors: Feng Linxiang , Feng Zian , Hu Jie , Gao Jiahui , Li Ang , He Xiaodong , Liu Liu , Shen Zuojun
Published: May 2023

Introduction: Lung cancer has long been at the forefront of all cancers in terms of incidence and mortality. Lung adenocarcinoma is the most common type of lung cancer, accounting for 40% of all lung cancer types. Exosomes can act as biomarkers of tumors and thus play an important role.

Methods: In this article, high-throughput sequencing of miRNAs in plasma exosomes from lung adenocarcinoma patients and healthy individuals was performed to obtain 87 upregulated miRNAs, which were then combined with data from the GSE137140 database uploaded by others for screening. The database included 1566 preoperative lung cancer patients, 180 postoperative patients, and 1774 non-cancerous controls. We overlapped the miRNAs upregulated in the serum of lung cancer patients in the database relative to those of non-cancer controls and post-operative patients with the upregulated miRNAs obtained from our next-generation sequencing to obtain nine miRNAs. Two miRNAs that were not reported as tumor markers in lung cancer, hsa-miR-4454 and hsa-miR-619-5p, were selected from them and then validated by qRT-PCR, and further analysis of miRNAs was performed using bioinformatics.

Results: Real-time quantitative PCR showed that the expression levels of hsa-miR-4454 and hsa-miR-619-5p in plasma exosomes of patients with lung adenocarcinoma were significantly up-regulated. The AUC values of hsa-miR-619-5p and hsa-miR-4454 were 0.906 and 0.975, respectively, both greater than 0.5, showing good performance. The target genes of miRNAs were screened by bioinformatics methods, and the regulatory network between miRNAs and lncRNAs and mRNAs was studied.

Discussion: Our work demonstrated that hsa-miR-4454 and hsa-miR-619-5p have the potential to be used as biomarkers for the early diagnosis of lung adenocarcinoma.
Recent advancements in the breeding of sorghum crop: current status and future strategies for marker-assisted breeding
Authors: Baloch Faheem Shehzad , Altaf Muhammad Tanveer , Liaqat Waqas , Bedir Mehmet , Nadeem Muhammad Azhar , Cömertpay Gönül , Çoban Nergiz , Habyarimana Ephrem , Barutçular Celaleddin , Cerit Ibrahim , Ludidi Ndomelele , Karaköy Tolga , Aasim Muhammad , Chung Yong Suk , Nawaz Muhammad Amjad , Hatipoğlu Rüştü , Kökten Kağan , Sun Hyeon-Jin
Published: May 2023

Sorghum is emerging as a model crop for functional genetics and genomics of tropical grasses with abundant uses, including food, feed, and fuel, among others. It is currently the fifth most significant primary cereal crop. Crops are subjected to various biotic and abiotic stresses, which negatively impact on agricultural production. Developing high-yielding, disease-resistant, and climate-resilient cultivars can be achieved through marker-assisted breeding. Such selection has considerably reduced the time to market new crop varieties adapted to challenging conditions. In the recent years, extensive knowledge was gained about genetic markers. We are providing an overview of current advances in sorghum breeding initiatives, with a special focus on early breeders who may not be familiar with DNA markers. Advancements in molecular plant breeding, genetics, genomics selection, and genome editing have contributed to a thorough understanding of DNA markers, provided various proofs of the genetic variety accessible in crop plants, and have substantially enhanced plant breeding technologies. Marker-assisted selection has accelerated and precised the plant breeding process, empowering plant breeders all around the world.
Anti-tumor efficacy of anti-GD2 CAR NK-92 cells in diffuse intrinsic pontine gliomas
Authors: Zuo Pengcheng , Li Yaopeng , He Chi , Wang Tantan , Zheng Xu , Liu Hao , Wu Zhen , Zhang Junting , Liao Xuebin , Zhang Liwei
Published: May 2023

Background

Diffuse intrinsic pontine gliomas (DIPGs) are rare and fatal pediatric brainstem gliomas with no cure. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have been proven effective in treating glioblastoma (GBM) in preclinical studies. However, there are no relevant studies on the CAR-NK treatment for DIPG. Our study is the first to evaluate the anti-tumor activity and safety of GD2-CAR NK-92 cells treatment for DIPG.

Methods

Five patient-derived DIPG cells and primary pontine neural progenitor cell (PPC) were used to access disialoganglioside GD2 expression. Cell killing activity of GD2-CAR NK-92 cells was analyzed by in vitro cytotoxicity assays. Two DIPG patient-derived xenograft models were established to detect the anti-tumor efficacy of GD2-CAR NK-92 cells in vivo.

Results

Among the five patient-derived DIPG cells, four had high GD2 expression, and one had low GD2 expression. In in vitro assays, GD2-CAR NK-92 cells could effectively kill DIPG cells with high GD2 expression while having limited activity against DIPG cells with low GD2 expression. In in vivo assays, GD2-CAR NK-92 cells could inhibit tumor growth in TT150630 DIPG patient-derived xenograft mice (high GD2 expression) and prolong the overall survival of the mice. However, GD2-CAR NK-92 showed limited anti-tumor activity for TT190326DIPG patient-derived xenograft mice (low GD2 expression).

Conclusion

Our study demonstrates the potential and safety of GD2-CAR NK-92 cells for adoptive immunotherapy of DIPG. The safety and anti-tumor effect of this therapy need to be further demonstrated in future clinical trials.
Enhancing the therapeutic activity of hyperimmune IgG against chikungunya virus using FcγRIIIa affinity chromatography
Authors: Fox Julie M. , Roy Vicky , Gunn Bronwyn M. , Bolton Glen R. , Fremont Daved H. , Alter Galit , Diamond Michael S. , Boesch Austin W.
Published: May 2023

Introduction

Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown. Here, we evaluated the protective efficacy of CHIKV-immune IgG enriched for binding to Fc-gamma receptor IIIa (FcγRIIIa) to select for IgG with enhanced Fc effector functions.

Methods

Total IgG was isolated from CHIKV-immune convalescent donors with and without additional purification by FcγRIIIa affinity chromatography. The enriched IgG was characterized in biophysical and biological assays and assessed for therapeutic efficacy during CHIKV infection in mice.

Results

FcγRIIIa-column purification enriched for afucosylated IgG glycoforms. In vitro characterization showed the enriched CHIKV-immune IgG had enhanced human FcγRIIIa and mouse FcγRIV affinity and FcγR-mediated effector function without reducing virus neutralization in cellular assays. When administered as post-exposure therapy in mice, CHIKV-immune IgG enriched in afucosylated glycoforms promoted reduction in viral load.

Discussion

Our study provides evidence that, in mice, increasing Fc engagement of FcγRs on effector cells, by leveraging FcγRIIIa-affinity chromatography, enhanced the antiviral activity of CHIKV-immune IgG and reveals a path to produce more effective therapeutics against these and potentially other emerging viruses.
Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology
Authors: Wang Man , Yu Fei , Chang Wenguang , Zhang Yuan , Zhang Lei , Li Peifeng
Published: May 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a contagious respiratory virus that is the cause of the coronavirus disease 2019 (COVID-19) pandemic which has posed a serious threat to public health. COVID-19 is characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to mild cold-like symptoms, severe pneumonia or even death. Inflammasomes are supramolecular signaling platforms that assemble in response to danger or microbial signals. Upon activation, inflammasomes mediate innate immune defense by favoring the release of proinflammatory cytokines and triggering pyroptotic cell death. Nevertheless, abnormalities in inflammasome functioning can result in a variety of human diseases such as autoimmune disorders and cancer. A growing body of evidence has showed that SARS-CoV-2 infection can induce inflammasome assembly. Dysregulated inflammasome activation and consequent cytokine burst have been associated with COVID-19 severity, alluding to the implication of inflammasomes in COVID-19 pathophysiology. Accordingly, an improved understanding of inflammasome-mediated inflammatory cascades in COVID-19 is essential to uncover the immunological mechanisms of COVID-19 pathology and identify effective therapeutic approaches for this devastating disease. In this review, we summarize the most recent findings on the interplay between SARS-CoV-2 and inflammasomes and the contribution of activated inflammasomes to COVID-19 progression. We dissect the mechanisms involving the inflammasome machinery in COVID-19 immunopathogenesis. In addition, we provide an overview of inflammasome-targeted therapies or antagonists that have potential clinical utility in COVID-19 treatment.
The manipulation of cell suspensions from zebrafish intestinal mucosa contributes to understanding enteritis
Authors: Zhao Xuyang , Liu Yuhang , Xie Jiayuan , Zhang Lei , Zhu Qingsong , Su Lian , Guo Cheng , Li Heng , Wang Guangxin , Zhang Wanting , Cheng Yingyin , Wu Nan , Xia Xiao-Qin
Published: May 2023

Background

Although zebrafish are commonly used to study intestinal mucosal immunity, no dedicated procedure for isolating immune cells from zebrafish intestines is currently available. A speedy and simple operating approach for preparing cell suspension from mucosa has been devised to better understanding of intestinal cellular immunity in zebrafish.

Methods and results

The mucosal villi were separated away from the muscle layer by repeated blows. The complete deprivation of mucosa was done and evidenced by HE and qPCR results. Higher expression of both innate (mpeg1, mpx, and lck) and adaptive immune genes (zap70, blnk, foxp3a, and foxp3b) was revealed compared to cells obtained by typical mesh rubbing. The cytometric results also revealed that the tested operation group had a higher concentration and viability. Further, fluorescent-labelled immune cells from 3mo Tg(lyz:DsRED2), Tg(mpeg1:EGFP), Tg(Rag2:DsRED), and Tg(lck:EGFP), were isolated and evaluated for the proportion, and immune cells’ type could be inferred from the expression of marker genes. The transcriptomic data demonstrated that the intestinal immune cell suspension made using the new technique was enriched in immune-related genes and pathways, including il17a/f, il22, cd59, and zap70, as well as pattern recognition receptor signaling and cytokine-cytokine receptor interaction. In addition, the low expression of DEG for the adherent and close junctions indicated less muscular contamination. Also, lower expression of gel-forming mucus-associated genes in the mucosal cell suspension was consistent with the current less viscous cell suspension. To apply and validate the developed manipulation, enteritis was induced by soybean meal diet, and immune cell suspensions were analyzed by flow cytometry and qPCR. The finding that in enteritis samples, there was inflammatory increase of neutrophils and macrophages, was in line with upregulated cytokines (il8 and il10) and cell markers (mpeg1 and mpx).

Conclusion

As a result, the current work created a realistic technique for studying intestinal immune cells in zebrafish. The immune cells acquired may aid in further research and knowledge of intestinal illness at the cellular level.
Modulation of innate immunity in airway epithelium for host-directed therapy
Authors: Myszor Iwona T. , Gudmundsson Gudmundur Hrafn
Published: May 2023

Innate immunity of the mucosal surfaces provides the first-line defense from invading pathogens and pollutants conferring protection from the external environment. Innate immune system of the airway epithelium consists of several components including the mucus layer, mucociliary clearance of beating cilia, production of host defense peptides, epithelial barrier integrity provided by tight and adherens junctions, pathogen recognition receptors, receptors for chemokines and cytokines, production of reactive oxygen species, and autophagy. Therefore, multiple components interplay with each other for efficient protection from pathogens that still can subvert host innate immune defenses. Hence, the modulation of innate immune responses with different inducers to boost host endogenous front-line defenses in the lung epithelium to fend off pathogens and to enhance epithelial innate immune responses in the immunocompromised individuals is of interest for host-directed therapy. Herein, we reviewed possibilities of modulation innate immune responses in the airway epithelium for host-directed therapy presenting an alternative approach to standard antibiotics.
OSL dating of coastal dunes on the southeastern coast of Hainan Island, China
Authors: Zhou Liang , Yang Yang , Li Gaocong , Tong Changliang
Published: May 2023

Coastal dune sediments and landforms offer a unique opportunity to understand climate change and sea level change on the centennial-millennial time scale. However, there is a paucity of chronological studies on the effects of storms on the evolution of coastal dunes along the temperate coastline of China. In this study, optically stimulated luminescence (OSL) dating of sand dunes was conducted to investigate the process and mechanism of coastal dune evolution on the southeastern coast of Hainan Island, China. The results show that the coastal dune evolution experienced three rapid accumulation periods: 28-21 ka, 14-4 ka, and 3.0 ka-present. The three rapid accumulation periods correspond to the last glacial maximum, the late Pleistocene/early-mid Holocene, and the late Holocene climatic dry-cold period, respectively. Sea level change and the East Asian winter monsoon, in conjunction with the enhanced storminess, play a key role in driving the sand dune evolution on the south-eastern coast of Hainan Island. These findings are of great significance for regional planning and coastal defense schemes.
Physical properties and in situ geoacoustic properties of seafloor surface sediments in the East China Sea
Authors: Wang Jingqiang , Kan Guangming , Li Guanbao , Meng Xiangmei , Zhang Linqing , Chen Mujun , Liu Chenguang , Liu Baohua
Published: May 2023

Seafloor sediment acoustics is a burgeoning field of marine scientific research. In situ measurement technique is a key technique for investigating sediment acoustic properties. Establishing a correlation between in situ acoustic parameters and physical parameters is of great scientific significance for advancing the theory of seafloor acoustics. This study employed an in situ sediment acoustic measurement system to measure the sound speed and attenuation of various types of sediment, such as sand, silty sand, silty clay, and clayey silt. The results showed that in situ sound speed and attenuation were strongly curvilinear correlated with physical properties, such as wet bulk density, porosity, and mean grain size. Empirical regression relationships between in situ acoustic properties and physical properties were derived. These findings supplement the in situ measurement data of acoustic properties of seafloor sediments, compensate for the lack of an empirical relationship of in situ attenuation in previous studies, and broaden the predicting theory and method of the acoustic properties of seafloor sediments.
The consumption of fermented Chinese herbs has resulted in better intestinal health and increased resistance to Aeromonas hydrophila in juvenile largemouth bass (Micropterus salmoides)
Authors: Jiang Li , Zhou Xinhong , Bao Songsong , Wu Qiuhong , Li Jin , Wang Yachao , Liu Bo
Published: May 2023

Introduction

This research aimed to assess the impact of Fermented Chinese herbs (FCHM) on the intestinal barrier, immunity, and protection against Aeromonas hydrophila (A. hydrophila) infection in largemouth bass (Micropterus salmoides).

Methods

Four experimental diets were formulated, including H0 (basal diet), H1, H2, and H3, which contained 1%, 3%, and 5% FCHM added to the basal diet, respectively. The fish were randomly allocated to four treatment groups, each with 3 parallel per treatment, consisting of 20 fish per replicate and were raised for 56 days.

Results and discussion

The experiment revealed that: compared with the control group, adding 1% FCHM significantly improved the weight gain rate (WGR) and specific growth rate (SGR) of the juvenile largemouth bass (P< 0.05). The ingestion of FCHM substantially elevated the activities of CAT, SOD, GSH-PX, APK, ACP, and LZM, and T-AOC level in the gut region of largemouth bass, while decreasing the MDA content in intestine (P< 0.05). Supplementation with FCHM enhanced the intestinal villus height and relative mRNA expression of intestinal barrier genes ZO-1, Claudin, and Occludin in juvenile largemouth bass. After injecting A.hydrophila, all groups of largemouth bass experienced mortality, but the consumption of FCHM resulted in a decrease in cumulative mortality. After infected with A.hydrophila, the antioxidant enzymes and immune enzymes activities of all test groups were enhanced compared to those before infection, and the antioxidant enzymes and immune enzymes activities of all groups were considerably higher than the control after feeding FCHM (P< 0.05). After infected with A.hydrophila, the intestinal MDA content of largemouth bass was higher compared with that before infection in all cases (P< 0.05), but after feeding FCHM, the MDA content was lower than the control (P< 0.05). Upon consuming FCHM, the mRNA relative expressions of pro-inflammatory biomarkers IL-1β, TNF-α, IL-15 and IL-8 in largemouth bass infected with A.hydrophila were decreased in comparison to the control group. In contrast, the mRNA expression of the anti-inflammatory biomarkers TGF-β and IL-10 were significantly elevated (P< 0.05). In summary, FCHM could improve the intestinal morphology, immunity, and antioxidant capacity of juvenile largemouth bass, and enhance it against A.hydrophila, with a better effect at 1% addition.
Early detection of Parkinson’s disease through enriching the electronic health record using a biomedical knowledge graph
Authors: Soman Karthik , Nelson Charlotte A. , Cerono Gabriel , Goldman Samuel M. , Baranzini Sergio E. , Brown Ethan G.
Published: May 2023

Introduction

Early diagnosis of Parkinson’s disease (PD) is important to identify treatments to slow neurodegeneration. People who develop PD often have symptoms before the disease manifests and may be coded as diagnoses in the electronic health record (EHR).

Methods

To predict PD diagnosis, we embedded EHR data of patients onto a biomedical knowledge graph called Scalable Precision medicine Open Knowledge Engine (SPOKE) and created patient embedding vectors. We trained and validated a classifier using these vectors from 3,004 PD patients, restricting records to 1, 3, and 5 years before diagnosis, and 457,197 non-PD group.

Results

The classifier predicted PD diagnosis with moderate accuracy (AUC = 0.77 ± 0.06, 0.74 ± 0.05, 0.72 ± 0.05 at 1, 3, and 5 years) and performed better than other benchmark methods. Nodes in the SPOKE graph, among cases, revealed novel associations, while SPOKE patient vectors revealed the basis for individual risk classification.

Discussion

The proposed method was able to explain the clinical predictions using the knowledge graph, thereby making the predictions clinically interpretable. Through enriching EHR data with biomedical associations, SPOKE may be a cost-efficient and personalized way to predict PD diagnosis years before its occurrence.
Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya
Authors: Mengich Isabella , Rajput Sheerien , Malkit Riyat , Moloo Zahir , Kagotho Elizabeth , Lalani El-Nasir , Mwirigi Anne
Published: May 2023

Introduction

Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously.

Methods

A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher’s exact test was used to determine the association between the immunophenotypic markers and categorical variables.

Results

Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden.

Conclusion

Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.
Preventive effects of quercetin against foot-and-mouth disease virus in vitro and in vivo by inducing type I interferon
Authors: Lee Gyeongmin , Kang Hyo Rin , Kim Aro , Park Jong-Hyeon , Lee Min Ja , Kim Su-Mi
Published: May 2023

Foot-and-mouth disease (FMD) is an acute contagious infectious disease that affects cloven-hoofed animals. Although current emergency FMD vaccines only take effect 7 days after vaccination, antiviral agents, such as quercetin, which is a common flavonoid, could reduce the spread of FMD virus (FMDV) during outbreaks. We investigated the in vitro and in vivo antiviral effects of quercetin against FMDV. Analysis of viral copy numbers showed that quercetin had a dose-dependent inhibitory effect on FMDV at concentrations between 19.5 and 1,250 μM in porcine cells. In addition, we observed a quercetin-induced interferon (IFN)-α protein and interferon-stimulated gene (ISG) upregulation in swine cells. Enzyme-linked immunosorbent assay of sera revealed that quercetin induces the production of IFN-α, IFN-β, IFN-γ, interleukin (IL)-12, and IL-15 in mice. Inoculation of mice with quercetin or a combination of quercetin with an inactivated FMD vaccine enhanced both the survival rate and neutralizing antibody titer. Therefore, we suggest the use of quercetin as a novel and effective antiviral agent for controlling FMDV infection; however, further investigation of its application in livestock is required.
Actinobacillus pleuropneumoniae FliY and YdjN are involved in cysteine/cystine utilization, oxidative resistance, and biofilm formation but are not determinants of virulence
Authors: Zhao Fan , Xu Huan , Chen Yubing , Xiao Juan , Zhang Miao , Li Zhuo , Liu Jinlin , Qi Chao
Published: May 2023

Introduction

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a member of Actinobacillus in family Pasteurellaceae. It is the causative agent of porcine pleuropneumonia, which has caused huge economic losses to pig industry over the world. Cysteine is a precursor of many important biomolecules and defense compounds in the cell. However, molecular mechanisms of cysteine transport in A. pleuropneumoniae are unclear.

Methods

In this study, gene-deleted mutants were generated and investigated, to reveal the roles of potential cysteine/cystine transport proteins FliY and YdjN of A. pleuropneumoniae.

Results

Our results indicated that the growth of A. pleuropneumoniae was not affected after fliY or ydjN single gene deletion, but absence of both FliY and YdjN decreased the growth ability significantly, when cultured in the chemically defined medium (CDM) supplemented with cysteine or cystine as the only sulfur source. A. pleuropneumoniae double deletion mutant ΔfliYΔydjN showed increased sensitivity to oxidative stress. Besides, trans-complementation of YdjN into ΔfliYΔydjN and wild type leads to increased biofilm formation in CDM. However, the virulence of ΔfliYΔydjN was not attenuated in mice or pigs.

Discussion

These findings suggest that A. pleuropneumoniae FliY and YdjN are involved in the cysteine/cystine acquisition, oxidative tolerance, and biofilm formation, but not contribute to the pathogenicity of A. pleuropneumoniae.
Inactivation of foodborne viruses by novel organic peroxyacid-based disinfectants
Authors: Bouchard Simon , Paniconi Teresa , Jubinville Éric , Goulet-Beaulieu Valérie , Goetz Coralie , Marchand Patrick , Jean Julie
Published: May 2023

Viruses are responsible for most enteric foodborne illnesses worldwide. The foods most frequently involved are fresh fruits and vegetables since they undergo little or no processing. Washing with a chemical disinfectant is a convenient way of inactivating viruses on foods. Peracetic acid, widely used as a disinfectant in the food industry, has the drawback of leaving a strong odor and is ineffective alone against some foodborne viruses. In this study, four disinfectants, namely per levulinic acid with or without sodium dodecyl sulfate, peracetic acid and a commercial peracetic acid-based disinfectant were tested on murine norovirus 1 (MNV-1), hepatitis A virus (HAV), and hepatitis E virus (HEV). Disinfectant concentrations were 50, 80, 250, 500, and 1000 mg l–1 and contact times were 0.5, 1, 5, and 10 min. Under these conditions, per levulinic acid supplemented with 1% SDS reduced MNV-1 infectious titer by 3 log cycles vs. 2.24 log cycles by peracetic acid within 0.5 min. On stainless steel at 80 ppm, only peracetic acid produced 3-log reductions within 0.5 min. None of these peroxyacids was able to reduce infectious titers of HAV or HEV by even 2 log cycles at any concentration or time-tested. This study will guide the development of new chemical formulas that will be more effective against major foodborne viruses and will have less impact on food quality and the environment.
Catabolite repression control protein antagonist, a novel player in Pseudomonas aeruginosa carbon catabolite repression control
Authors: Sonnleitner Elisabeth , Bassani Flavia , Cianciulli Sesso Anastasia , Brear Paul , Lilic Branislav , Davidovski Lovro , Resch Armin , Luisi Ben F. , Moll Isabella , Bläsi Udo
Published: May 2023

In the opportunistic human pathogen Pseudomonas aeruginosa (Pae), carbon catabolite repression (CCR) orchestrates the hierarchical utilization of N and C sources, and impacts virulence, antibiotic resistance and biofilm development. During CCR, the RNA chaperone Hfq and the catabolite repression control protein Crc form assemblies on target mRNAs that impede translation of proteins involved in uptake and catabolism of less preferred C sources. After exhaustion of the preferred C-source, translational repression of target genes is relieved by the regulatory RNA CrcZ, which binds to and acts as a decoy for Hfq. Here, we asked whether Crc action can be modulated to relieve CCR after exhaustion of a preferred carbon source. As Crc does not bind to RNA per se, we endeavored to identify an interacting protein. In vivo co-purification studies, co-immunoprecipitation and biophysical assays revealed that Crc binds to Pae strain O1 protein PA1677. Our structural studies support bioinformatics analyzes showing that PA1677 belongs to the isochorismatase-like superfamily. Ectopic expression of PA1677 resulted in de-repression of Hfq/Crc controlled target genes, while in the absence of the protein, an extended lag phase is observed during diauxic growth on a preferred and a non-preferred carbon source. This observations indicate that PA1677 acts as an antagonist of Crc that favors synthesis of proteins required to metabolize non-preferred carbon sources. We present a working model wherein PA1677 diminishes the formation of productive Hfq/Crc repressive complexes on target mRNAs by titrating Crc. Accordingly, we propose the name CrcA (catabolite repression control protein antagonist) for PA1677.
The role of homocysteine levels as a risk factor of ischemic stroke events: a systematic review and meta-analysis
Authors: Pinzon Rizaldy Taslim , Wijaya Vincent Ongko , Veronica Vanessa
Published: May 2023

Introduction

Among numerous risk factors, homocysteine (Hcy) has been linked to cerebral infarction; however, results have been inconsistent. This review aimed to conduct a meta-analysis of published studies to investigate the relationship between plasma Hcy levels and the risk of ischemic stroke.

Methods

A systematic literature search was conducted until November 2022 to obtain articles reporting Hcy levels in ischemic stroke patients. Review Manager software was used to perform all statistical analyses (version 5.3).

Results

Initial investigation yielded 283 articles. The final evaluation included 21 articles, including two prospective studies, one retrospective cohort, and 18 case–control studies. These studies included 9888 participants, of which 5031 were admitted patients with ischemic stroke. An integrated analysis revealed that ischemic stroke patients had significantly higher levels of Hcy than controls (mean difference (MD) = +3.70, 95% confidence interval (CI) = 2.42–5.81, p < 0.001).

Conclusion

This meta-analysis and systematic review indicate that ischemic stroke patients have significantly higher homocysteine levels than controls. Detecting hyperhomocysteinemia and reducing homocysteine levels should be explored among individuals at increased risk for ischemic stroke.
Diagnostic potential of routine brain MRI and high-resolution, multi-contrast vessel wall imaging in the detection of internal carotid artery dissection
Authors: Xie Shanshan , Ran Yuncai , Wang Xiao , Zhang Yong , Fu Qichang , Ren Yanan , Liu Juanfang , Teng Zhongzhao , Cheng Jingliang
Published: May 2023

Objective

Cervical artery dissection (CAD) is one of the major causes of stroke and most commonly occurs at the site of the extracranial internal carotid artery (ICA). This study aimed to assess the value of routine brain MRI, clinical information, and high-resolution, multi-contrast vessel wall MR imaging (hrVWI) for the timely detection of ICA dissection.

Methods

A total of 105 patients with CAD and 105 without CAD were recruited for this study. The lesion type in the patients was determined based on images from different modalities, including brain MRI, magnetic resonance angiography (MRA), computed tomography angiography (CTA), digital subtraction angiography (DSA), ultrasonography, and hrVWI and clinical information. Each lesion was reviewed to determine the type following a stepwise procedure by referring to (1) brain MRI only; (2) brain MRI and clinical information; (3) hrVWI only; and (4) hrVWI, CTA, DSA, and clinical information.

Results

Typical clinical presentations of patients with potential CAD include headache, neck pain, and/or Horner's syndrome. Representative imaging signs in the brain MRI included a crescentic or circular iso- or hyperintensity around the lumen, a curvilinear and isointense line crossing the lumen, or aneurysmal vessel dilation. Based on brain MRI alone, 54.3% (57/105) of the patients with CAD were correctly classified, and the accuracy increased to 73.3% (77/105) when clinical information was combined (P < 0.001) with high specificity and low sensitivity. Further analysis showed that hrVWI had the superior capability in detecting CAD, with a sensitivity and a specificity of 95.1% and 97.0%, respectively.

Conclusion

The combination of brain MRI and clinical information could be used for the diagnosis of CAD; however, hrVWI should be sought for uncertain cases.
Comparison of radiological abnormalities between the jugular bulb and the vestibular aqueduct in patients with Ménière’s disease
Authors: Xia Kaijun , Lei Ping , Liu Yingzhao , Li Jing , Wang Miao , Leng Yangming , Liu Bo
Published: May 2023

Objective

Anatomical variations of the inner ear may contribute to the development of Ménière’s disease (MD), which is a complex inner ear disorder histopathologically characterized by idiopathic endolymphatic hydrops (ELH). Abnormalities of the vestibular aqueduct (VA) and the jugular bulb (JB) have been suggested as predisposing factors. Yet, few studies have investigated the correlation between JB abnormalities and VA variations as well as its clinical relevance in these patients. In this retrospective study, we investigated the differences in the incidence of radiological abnormalities of the VA and JB in patients with definite MD.

Methods

Anatomical variations of JB and VA were evaluated based on high-resolution CT (HRCT) in a series of 103 patients with MD (93 unilateral cases and 10 bilateral cases). JB-related indices included JB anteroposterior and mediolateral diameter, JB height, JB type regarding to Manjila classification system, and incidences of JB diverticulum (JBD), JB related inner ear dehiscence (JBID), and inner ear adjacent JB (IAJB). VA-related indices included CT-VA visibility, CT-VA morphology (funnel, tubular, filiform, hollow, and obliterated-shaped type), and peri-VA pneumatization. Radiological indices were compared between MD ears and control ears.

Results

Radiological JB abnormalities were comparable between MD ears and control ears. As for VA-related indices, the CT-VA visibility was lower in MD ears than in control ears (p = 0.004). The distribution of CT-VA morphology was significantly different between MD and control ears (p = 0.013), with a higher proportion of obliterated-shaped type in MD ears (22.1%) than in control ears (6.6%).

Conclusion

Compared with JB abnormalities, the anatomical variations of VA are more likely to be an anatomically predisposing factor for MD.
A review on multiple sclerosis prognostic findings from imaging, inflammation, and mental health studies
Authors: Brasanac Jelena , Chien Claudia
Published: May 2023

Magnetic resonance imaging (MRI) of the brain is commonly used to detect where chronic and active lesions are in multiple sclerosis (MS). MRI is also extensively used as a tool to calculate and extrapolate brain health by way of volumetric analysis or advanced imaging techniques. In MS patients, psychiatric symptoms are common comorbidities, with depression being the main one. Even though these symptoms are a major determinant of quality of life in MS, they are often overlooked and undertreated. There has been evidence of bidirectional interactions between the course of MS and comorbid psychiatric symptoms. In order to mitigate disability progression in MS, treating psychiatric comorbidities should be investigated and optimized. New research for the prediction of disease states or phenotypes of disability have advanced, primarily due to new technologies and a better understanding of the aging brain.
Research hotspots and frontiers of post-stroke aphasia rehabilitation: a bibliometric study and visualization analysis
Authors: Wang Huan , Cai Ziping , Li Shengjuan , Zheng Jiaxing , Xie Yuyao , He Yuanyuan , Li Chen , Zheng Dongxiang
Published: May 2023

Background

Aphasia is a common complication of stroke and is associated with high morbidity and mortality rates. Rehabilitation plays a crucial role in the comprehensive management of post-stroke aphasia and its consequences. However, bibliometric analysis in the field of post-stroke aphasia rehabilitation is still lacking. This study aimed to comprehensively identify assistance networks, analyze research trends, focus on hot and cutting-edge health topics related to post-stroke aphasia rehabilitation, and inform future research guidelines.

Methods

The Web of Science Core Collection (WoSCC) electronic database was searched from inception to January 4, 2023 to identify studies related to post-stroke aphasia rehabilitation. Bibliometric analysis and visualization of country, institution, journal, author, reference, and keywords were performed using CiteSpace and VOSviewer software.

Results

A total of 2,325 papers were included in the analysis, with a progressive increase in the number of articles published each year. The USA was the country with the most publications (809 articles), and the University of Queensland was the institution with the most publications (137 articles). The subject area of post-stroke aphasia rehabilitation is dominated by clinical neurology (882 articles). Aphasiology was the journal with the most publications (254 articles) and the most cited journal (6,893 citations). Worrall L was the most prolific author (51 publications), and Frideriksson J was the most cited author (804 citations).

Conclusion

By using bibliometrics, we provided a comprehensive review of studies related to post-stroke aphasia rehabilitation. Future research hotspots on topics related to post-stroke aphasia rehabilitation will mainly focus on the plasticity mechanisms of neurolinguistics networks, language function assessment, language rehabilitation modalities, and patients’ rehabilitation needs and participation experiences in post-stroke aphasia. This paper provides systematic information that is worth exploring in the future.