bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Neuroimaging and Omics Datasets for Disease Classification Using Graph Neural Networks
Authors: Chan Yi Hao , Wang Conghao , Soh Wei Kwek , Rajapakse Jagath C.
Published: May 2022

Both neuroimaging and genomics datasets are often gathered for the detection of neurodegenerative diseases. Huge dimensionalities of neuroimaging data as well as omics data pose tremendous challenge for methods integrating multiple modalities. There are few existing solutions that can combine both multi-modal imaging and multi-omics datasets to derive neurological insights. We propose a deep neural network architecture that combines both structural and functional connectome data with multi-omics data for disease classification. A graph convolution layer is used to model functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data simultaneously to learn compact representations of the connectome. A separate set of graph convolution layers are then used to model multi-omics datasets, expressed in the form of population graphs, and combine them with latent representations of the connectome. An attention mechanism is used to fuse these outputs and provide insights on which omics data contributed most to the model's classification decision. We demonstrate our methods for Parkinson's disease (PD) classification by using datasets from the Parkinson's Progression Markers Initiative (PPMI). PD has been shown to be associated with changes in the human connectome and it is also known to be influenced by genetic factors. We combine DTI and fMRI data with multi-omics data from RNA Expression, Single Nucleotide Polymorphism (SNP), DNA Methylation and non-coding RNA experiments. A Matthew Correlation Coefficient of greater than 0.8 over many combinations of multi-modal imaging data and multi-omics data was achieved with our proposed architecture. To address the paucity of paired multi-modal imaging data and the problem of imbalanced data in the PPMI dataset, we compared the use of oversampling against using CycleGAN on structural and functional connectomes to generate missing imaging modalities. Furthermore, we performed ablation studies that offer insights into the importance of each imaging and omics modality for the prediction of PD. Analysis of the generated attention matrices revealed that DNA Methylation and SNP data were the most important omics modalities out of all the omics datasets considered. Our work motivates further research into imaging genetics and the creation of more multi-modal imaging and multi-omics datasets to study PD and other complex neurodegenerative diseases.
Dissecting the Prefrontal Network With Pathway-Selective Manipulation in the Macaque Brain—A Review
Authors: Oguchi Mineki , Sakagami Masamichi
Published: May 2022

Macaque monkeys are prime animal models for studying the neural mechanisms of decision-making because of their close kinship with humans. Manipulation of neural activity during decision-making tasks is essential for approaching the causal relationship between the brain and its functions. Conventional manipulation methods used in macaque studies are coarse-grained, and have worked indiscriminately on mutually intertwined neural pathways. To systematically dissect neural circuits responsible for a variety of functions, it is essential to analyze changes in behavior and neural activity through interventions in specific neural pathways. In recent years, an increasing number of studies have applied optogenetics and chemogenetics to achieve fine-grained pathway-selective manipulation in the macaque brain. Here, we review the developments in macaque studies involving pathway-selective operations, with a particular focus on applications to the prefrontal network. Pathway selectivity can be achieved using single viral vector transduction combined with local light stimulation or ligand administration directly into the brain or double-viral vector transduction combined with systemic drug administration. We discuss the advantages and disadvantages of these methods. We also highlight recent technological developments in viral vectors that can effectively infect the macaque brain, as well as the development of methods to deliver photostimulation or ligand drugs to a wide area to effectively manipulate behavior. The development and dissemination of such pathway-selective manipulations of macaque prefrontal networks will enable us to efficiently dissect the neural mechanisms of decision-making and innovate novel treatments for decision-related psychiatric disorders.
Very Low-Carbohydrate High-Fat Diet Improves Risk Markers for Cardiometabolic Health More Than Exercise in Men and Women With Overfat Constitution: Secondary Analysis of a Randomized Controlled Clinical Trial
Authors: Cipryan Lukas , Litschmannova Martina , Maffetone Philip B. , Plews Daniel J. , Dostal Tomas , Hofmann Peter , Laursen Paul B.
Published: May 2022

Purpose

This randomized controlled parallel-group study examined the effects of a very low-carbohydrate high-fat (VLCHF) diet and high-intensity interval training (HIIT) program over 12-weeks on cardiometabolic risk factors in individuals with overfat constitution.

Methods

Ninety-one participants out of 109 completed the study. The participants were randomly allocated to the HIIT (N = 22), VLCHF (N = 25), VLCHF+HIIT (N = 25), or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4 and 12 weeks. The analyzed outcomes included complete blood count, glucose, insulin, glycated hemoglobin, triglycerides (TG), cholesterol, high- and low-density lipoprotein (HDL-C and LDL-C), lipoprotein(a), adiponectin (Adpn), leptin (Lep), tumor necrosis factor α (TNF-α), other interleukins (hs-IL-6, IL-1β, and IL-10), and IL-1RA. The homeostasis model assessment of insulin resistance (HOMA-IR), Adpn/Lep ratio, TG/HDL-C ratio, and TyG index were calculated and analyzed. Blood pressure was measured before the intervention, after 4, 8, and 12 weeks (ClinicalTrials.gov: NCT03934476).

Results

Absolute changes in HOMA-IR, Adpn/Lep ratio, LDL-C, and diastolic blood pressure after 12 weeks differed by study groups (p < 0.05). The most pronounced changes were revealed in the VLCHF (ΔM [95% CI]; HOMA-IR: −0.75 [−1.13; −0.55]; Adpn/Lep: 9.34 [6.33; 37.39]; LDL-C: 0.06 [−0.12; 0.50] mmol/l) and VLCHF+HIIT (HOMA-IR: −0.44 [−1.14; 0.12]; Adpn/Lep: 4.26 [2.24; 13.16]; LDL-C: 0.25 [−0.04; 0.50] mmol/l) groups.

Conclusions

A 12-week VLCHF diet intervention in individuals with overfat constitution is effective for favorable changes in HOMA-IR (compared to HIIT), Adpn/Lep ratio, and diastolic blood pressure. HIIT, or HIIT combined with the VLCHF diet, had no additional benefits for the analyzed variables. No adverse side effects were observed.
The Dietary Branched-Chain Amino Acids Transition and Risk of Type 2 Diabetes Among Chinese Adults From 1997 to 2015: Based on Seven Cross-Sectional Studies and a Prospective Cohort Study
Authors: Yu Lianlong , Song Pengkun , Zhu Qianrang , Li Yuqian , Jia Shanshan , Zhang Shixiu , Wang Zhihong , Zhang Jian
Published: May 2022

Background

The situation is grim for the prevention and control of type 2 diabetes (T2D) and prediabetes in China. Serum and dietary branched-chain amino acids (BCAAs) were risk factors for T2D. However, there is a lack of information on trends in consumption of BCAAs and the risk of T2D associated with BCAAs intake, based on nationally representative data in China. Thus, we aimed to comprehensively describe the dietary BCAAs transition and risk of T2D, at a national level among Chinese adults from 1997 to 2015.

Methods

The data sources were the China Health and Nutrition Survey (CHNS) and China Nutrition and Health Survey (CNHS). Cross-sectional data on intake were obtained from CHNS (1997, n = 9,404), CHNS (2000, n = 10,291), CHNS (2004, n = 9,682), CHNS (2006, n = 9,553), CHNS (2009, n = 9,811), CHNS (2011, n = 12,686) and CNHS (2015, n = 71,695). Prospective cohort data were obtained CHNS (1997–2015, n = 15,508).

Results

From 1997 to 2015, there was a significant decreasing trend in the BCAAs intake of Chinese adults in all subgroups (P < 0.0001) except for Leu in 80 or older, and a decreasing trend in the consumption of BCAAs after 40 years old (P < 0.05). The mean intake of BCAAs in the population of cohort study was 11.83 ± 3.77g/day. The 95% CI was above the HR of 1.0, when the consumptions were higher than 14.01, 3.75, 6.07, 4.21 g/day in BCAAs, Ile, Leu and Val, based on RCS curves. According to the Cox proportional hazards models, Compared with individuals with BCAAs consumption of 10.65–12.37 g/day, the multivariable-adjusted HR for diabetes was 2.26 (95% CI 1.45 to 3.51) for individuals with consumption of BCAAs more than 18.52 g/day. A statistically significant positive association between BCAAs intake and risk of T2D was observed in males or participants aged 45 years and older, but not in females or participants younger than 45 years.

Conclusion

Our results reveal a trend toward decreased BCAAs intake in Chinese from 1997 to 2015. After 40 years of age, consumption of BCAAs declined with increasing age. Higher BCAAs intake was associated with higher risk of T2D. This relationship is more stable among men and middle-aged and elderly people.
Targeted Metabolomics With a Chemometric Study of Oxygenated Heterocyclic Aglycones as a Tool for Preliminary Authenticity Assessment of Orange and Grapefruit Juices
Authors: Han Leng , Cheng Yujiao , Zhang Tenghui , Zhou Qi , Zhang Wanchao , Li Yongan , Li Guijie
Published: May 2022

Profiles of citrus juice oxygenated heterocyclic aglycones (OHAs), which are notable marker secondary metabolites, were used to assess the authenticity of sweet orange and grapefruit juices in situations where mandarin and pomelo juices might be adulterants. Thirty-nine known OHAs, including 10 methoxyflavones, 13 coumarins, and 16 furanocoumarins, as well as 13 tentatively screened OHAs, were analyzed in orange, mandarin, grapefruit and pomelo juices using our newly developed high-resolution HPLC-UV and fluorescence detection method. Quantitative OHA profiles from 158 pure juice samples were obtained to establish a purity discriminant model using an omics strategy. Reduction of OHA variables showed that three important methoxyflavones, i.e. isosinensetin, tangeretin and sinensetin provided the best discrimination ability between sweet orange and mandarin juices. There are two subtypes of pomelos, Shatianyou Group and Wendan Group, of which juices should be separately compared to grapefruit juice. Five OHAs, namely meranzin, 3,5,6,7,8,3',4'-heptamethoxyflavone, osthole, 6',7'-epoxybergamottin, and bergamottin were found to discriminate Shatianyou Group of pomelo juice from grapefruit juice; whereas three OHAs, namely bergaptol, isomeranzin, and 6',7'-dihydroxybergamottin were able to discriminate Wendan Group of pomelo juice from grapefruit juice. The established partial least squares discriminant analysis (PLS-DA) models were capable of detecting as little as 10% mandarin juice in sweet orange juice and 10% pomelo juice in grapefruit juice, allowing for fast prescreening of excess addition with good reliability (root mean square error of prediction, RMSEP < 5%).
Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
Authors: Teofilović Ana , Vratarić Miloš , Veličković Nataša , Vojnović Milutinović Danijela , Mladenovic Aleksandra , Prvulovic Milica , Djordjevic Ana
Published: May 2022

Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.
Carboxypeptidase N2 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma
Authors: Xu Ting , Zhang Zhe , Chen Hongqiang , Cai Ruili , Yang Qian , Liu Qi , Fan Yahan , Liu Wenbin , Yao Chunyan
Published: May 2022

Carboxypeptidase N2 (CPN2) is a plasma metallo-protease that cleaves basic amino acids from the C-terminal of peptides and proteins. Emerging evidence showed that carboxypeptidases perform many diverse functions in the body and play key roles in tumorigenesis. However, the clinical significance and biological functions of CPN2 in lung adenocarcinoma remain unclear. Our study aimed to explore the potential role and functions of CPN2 in lung adenocarcinoma. The results showed that the transcription level of CPN2 was significantly increased in the tumor tissues of lung adenocarcinoma patients compared to the adjacent normal tissues in The Cancer Genome Atlas cohort (P < 0.05). The survival plots showed that the overall survival of patients with a high expression of CPN2 was significantly lower than that of patients with a low expression of CPN2, both in the Kaplan–Meier database and the clinical sample cohort (P < 0.05). The tissue microarray analysis found that CPN2 protein expression was significantly positively correlated with node status and tumor stage as well as tumor malignancy (P < 0.05). Further univariate and multivariate Cox regression analyses showed that CPN2 may act as an independent prognostic factor in patients with lung adenocarcinoma (P < 0.05). In addition, the analysis of co-expression genes from LinkedOmics showed that CPN2 was positively associated with many genes of fibrillar collagen family members and the PI3K-Akt pathway. The gene set enrichment analysis showed that a higher expression of CPN2 may participate in mTOR, TGF-BETA, NOTCH, TOLL-like-receptor, WNT, and MAPK signaling pathway in lung adenocarcinoma. Notably, the knockdown of CPN2 significantly inhibited the ability of cell proliferation, clone formation, invasion, and migration. Our findings suggested that the upregulation of CPN2 is associated with a worse clinical outcome in lung adenocarcinoma and cancer-related pathways, which laid the foundation for further research on CPN2 during carcinogenesis.
The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression
Authors: Xiao Lin , Karsa Mawar , Ronca Emma , Bongers Angelika , Kosciolek Angelika , El-Ayoubi Ali , Revalde Jezrael L. , Seneviratne Janith A. , Cheung Belamy B. , Cheung Laurence C. , Kotecha Rishi S. , Newbold Andrea , Bjelosevic Stefan , Arndt Greg M. , Lock Richard B. , Johnstone Ricky W. , Gudkov Andrei V. , Gurova Katerina V. , Haber Michelle , Norris Murray D. , Henderson Michelle J. , Somers Klaartje
Published: May 2022

Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome. Driven by the unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that the novel anti-cancer agent, curaxin CBL0137, induces decondensation of chromatin in cancer cells, delays leukemia progression and potentiates standard of care chemotherapies in preclinical KMT2A-rearranged leukemia models. Based on the promising potential of histone deacetylase (HDAC) inhibitors as targeted anti-cancer agents for KMT2A-rearranged leukemia and the fact that HDAC inhibitors also decondense chromatin via an alternate mechanism, we investigated whether CBL0137 could potentiate the efficacy of the HDAC inhibitor panobinostat in KMT2A-rearranged leukemia models. The combination of CBL0137 and panobinostat rapidly killed KMT2A-rearranged leukemia cells by apoptosis and significantly delayed leukemia progression and extended survival in an aggressive model of MLL-AF9 (KMT2A:MLLT3) driven murine acute myeloid leukemia. The drug combination also exerted a strong anti-leukemia response in a rapidly progressing xenograft model derived from an infant with KMT2A-rearranged acute lymphoblastic leukemia, significantly extending survival compared to either monotherapy. The therapeutic enhancement between CBL0137 and panobinostat in KMT2A-r leukemia cells does not appear to be mediated through cooperative effects of the drugs on KMT2A rearrangement-associated histone modifications. Our data has identified the CBL0137/panobinostat combination as a potential novel targeted therapeutic approach to improve outcome for KMT2A-rearranged leukemia.
MRI/Transrectal Ultrasound Fusion-Guided Targeted Biopsy and Transrectal Ultrasound-Guided Systematic Biopsy for Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis
Authors: Xie Jianfeng , Jin Chunchun , Liu Mengmeng , Sun Kun , Jin Zhanqiang , Ding Zhimin , Gong Xuehao
Published: May 2022

Purpose

For men suspected of having prostate cancer (PCa), the transrectal ultrasound (TRUS)-guided systematic biopsy (SB) was performed. MRI/TRUS fusion guided-targeted biopsy (MRI-TB) could enhance PCa detection, allowing sampling of sites at higher risk which were not obvious with TRUS alone. The aim of this systematic review and meta-analysis was to compare the detection rates of prostate cancer by MRI-TB or MRI-TB plus SB versus SB, mainly for diagnosis of high-risk PCa.

Methods

A literature Search was performed on PubMed, Cochrane Library, and Embase databases. We searched from inception of the databases up to January 2021.

Results

A total of 5831 patients from 26 studies were included in the present meta-analysis. Compared to traditional TRUS-guided biopsy, MRI-TB had a significantly higher detection rate of clinically significant PCa (RR=1.27; 95%CI 1.15-1.40; p<0.001) and high-risk PCa (RR=1.41; 95% CI 1.22-1.64; p<0.001), while the detection rate of clinically insignificant PCa was lower (RR=0.65; 95%CI 0.55-0.77; p<0.001). MRI-TB and SB did not significantly differ in the detection of overall prostate cancer (RR=1.04; 95%CI 0.95-1.12; p=0.41). Compared with SB alone, we found that MRI-TB plus SB diagnosed more cases of overall, clinically significant and high-risk PCa (p<0.001).

Conclusion

Compared with systematic protocols, MRI-TB detects more clinically significant and high-risk PCa cases, and fewer clinically insignificant PCa cases. MRI-TB combined with SB enhances PCa detection in contrast with either alone but did not reduce the diagnosis rate of clinically insignificant PCa.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/#searchadvanced, CRD42021218475.
Establishment of Organoids From Human Epithelioid Sarcoma With the Air-Liquid Interface Organoid Cultures
Authors: Wakamatsu Toru , Ogawa Hisataka , Yoshida Keiichi , Matsuoka Yukiko , Shizuma Kazuko , Imura Yoshinori , Tamiya Hironari , Nakai Sho , Yagi Toshinari , Nagata Shigenori , Yui Yoshihiro , Sasagawa Satoru , Takenaka Satoshi
Published: May 2022

Background

Although biological resources are essential for basic and preclinical research in the oncological field, those of sarcoma are not sufficient for rapid development of the treatment. So far, some sarcoma cell lines have been established, however, the success rate was low and the established sarcoma types were frequently biased. Therefore, an efficient culture method is needed to determine the various types of sarcomas. Organoid culture is a 3-dimentional culture method that enables the recapitulation of the tumor microenvironment and the success rate reported is higher than the 2-dimentional culture. The purpose of this study was to report our newly established organoids from human epithelioid sarcoma using the air-liquid interface organoid culture method.

Methods

We treated 2 patients with epithelioid sarcoma in our institute. The remaining sarcoma specimens after surgical resection were embedded in collagen type 1 gels according to the air-liquid interface organoid culture method. After serial passages, we xenografted the organoids to NOD-scid IL2Rgnull (NSG) mice. Using the developed tumors, we performed histological and genomic analyses to compare the similarities and differences with the original epithelioid sarcoma from the patient.

Results

Organoids from the epithelioid sarcoma could be serially cultured and maintained in collagen type 1 gels for more than 3 passages. Developed orthotopic tumor xenografts were detected in the NSG mice. After the process was repeated severally, the patient derived organoid lines from the epithelioid sarcoma were established. The established organoids showed loss of integrase interactor 1 expression with polymerase chain reaction and immunohistochemical analyses. The xenografted organoids of the epithelioid sarcoma had histologically similar phenotypes with the original tumor and genetically resembled it to some degree.

Conclusions

The present study demonstrated 2 novel established organoid models of epithelioid sarcoma, and our organoid models could be used to investigate the molecular pathogenesis and develop a novel treatment.
ERH Gene and Its Role in Cancer Cells
Authors: Pang Kun , Li Mei-li , Hao Lin , Shi Zhen-duo , Feng Harry , Chen Bo , Ma Yu-yang , Xu Hao , Pan Deng , Chen Zhe-Sheng , Han Cong-hui
Published: May 2022

Cancer is a major public health problem worldwide. Studies on oncogenes and tumor-targeted therapies have become an important part of cancer treatment development. In this review, we summarize and systematically introduce the gene enhancer of rudimentary homolog (ERH), which encodes a highly conserved small molecule protein. ERH mainly exists as a protein partner in human cells. It is involved in pyrimidine metabolism and protein complexes, acts as a transcriptional repressor, and participates in cell cycle regulation. Moreover, it is involved in DNA damage repair, mRNA splicing, the process of microRNA hairpins as well as erythroid differentiation. There are many related studies on the role of ERH in cancer cells; however, there are none on tumor-targeted therapeutic drugs or related therapies based on the expression of ERH. This study will provide possible directions for oncologists to further their research studies in this field.
Aggressive Natural Killer Cell Leukemia in an Adolescent Patient: A Case Report and Literature Review
Authors: Yang Rong , Ai Yuan , Liu Chuan , Lu Xiaoxi
Published: May 2022

Aggressive natural killer cell leukemia (ANKL) is a rare malignant tumor, especially uncommon in children. ANKL has very aggressive clinical course and bad prognosis and is usually caused by Epstein-Barr virus infection. ANKL often has clinical manifestations of hemophagocytic lymphohistiocytosis (HLH) and can be easily treated as HLH, which might complicate this aggressive disease. Here we report an ANKL in adolescent whose clinical presentation was highly aggressive and response to L-asparaginase containing chemotherapy was very bad. Early-onset Flow cytometry of peripheral blood and bone marrow help make the diagnosis.
Increased Demand for Therapeutic Drugs in Pediatric Ulcerative Colitis Patients With Extraintestinal Manifestations
Authors: Kwon Yiyoung , Kim Eun Sil , Choe Yon Ho , Kim Mi Jin
Published: May 2022

Background

Ulcerative colitis (UC) is a systemic inflammatory disease with a gut predominance, which may involve other organs. The presence of extraintestinal manifestation (EIM) is an important symptom for clinicians as it alters the treatment decisions. In this study, we aimed to evaluate the initial clinical presentation and disease severity of pediatric UC patients with EIMs.

Methods

One hundred forty-two patients under the age of 18 years who were diagnosed with UC from January 2003 to November 2021 were included in this study. Forty-seven patients with confirmed EIMs and 95 patients without EIMs were divided into two groups and their differences were analyzed.

Results

The most common EIM was peripheral arthritis. The disease extent at the time of diagnosis shows a higher rate of pancolitis in the EIM-positive group (65.9%) than that of the EIM-negative group (33.7%) (p < 0.001). More than 90% of EIM-positive patients had moderate to severe disease activity on the Mayo endoscopic subscore. In the EIM-positive group, the cumulative use of systemic steroids, immunosuppressants, and biological agents from diagnosis to 1 year follow-up were significantly higher than those of the EIM-negative group (p = 0.009, 0.001, and < 0.001, respectively). About 80% of patients in the EIM-negative group reached remission, but only about 50% of the EIM-positive patients reached remission (p = 0.005). The relapse occurred more frequently in the EIM-positive group than in the EIM-negative group with statistical significance (p < 0.001).

Conclusion

Pediatric UC with EIMs had higher disease severity and often manifested upper gastrointestinal tract involvement. Despite EIMs treatment, the occurrence of new EIMs was observed repeatedly. Cumulative drug demand (steroids, immunosuppressants, and biological agents) for the treatment increased steadily over time, and frequent relapses occurred despite the combinatory use of therapeutic drugs.
Acute Kidney Disease in Hospitalized Pediatric Patients With Acute Kidney Injury in China
Authors: Deng Ying-Hao , Yan Ping , Zhang Ning-Ya , Luo Xiao-Qin , Wang Xiu-Fen , Duan Shao-Bin
Published: May 2022

Objective

The epidemiology and outcomes of acute kidney disease (AKD) after acute kidney injury (AKI) in hospitalized children are poorly described. The aim of this study is to investigate the prevalence, predictive factors, and clinical outcomes of AKD in hospitalized children with AKI.

Methods

Children (1 month–18 years) with AKI during hospitalization in the Second Xiangya Hospital from January 2015 to December 2020 were identified. AKD was defined based on the consensus report of the Acute Disease Quality Initiative 16 workgroup. The endpoints include adverse outcomes in 30 and 90 days. Multivariable logistic regression analyses were used to estimate the odds ratio of 30- and 90-day adverse outcomes associated with AKD and identify the risk factors of AKD.

Results

AKD was developed in 42.3% (419/990) of the study patients, with 186 in AKD stage 1, 107 in AKD stage 2, and 126 in AKD stage 3. Pediatric patients with AKD stages 2–3 had significantly higher rates of developing 30- and 90-day adverse outcomes than those with AKD stage 0 and 1. The adjusted odds ratio of AKD stage 2–3 was 12.18 (95% confidence interval (CI), 7.38 - 20.09) for 30-day adverse outcomes and decreased to 2.49 (95% CI, 1.26 - 4.91) for 90-day adverse outcomes. AKI stages 2 and 3, as well as glomerulonephritis, were the only predictive factors for AKD stage 2–3.

Conclusion

AKD is frequent among hospitalized pediatric AKI patients. AKD stage 2–3 represents a high-risk subpopulation among pediatric AKI survivors and is independently associated with 30- and 90-day adverse outcomes. Awareness of the potential risks associated with AKD stage 2–3 and its risk factors may help improve outcomes through careful monitoring and timely intervention.
Impedance-Based Phenotypic Readout of Transporter Function: A Case for Glutamate Transporters
Authors: Sijben Hubert J. , Dall’ Acqua Laura , Liu Rongfang , Jarret Abigail , Christodoulaki Eirini , Onstein Svenja , Wolf Gernot , Verburgt Simone J. , Le Dévédec Sylvia E. , Wiedmer Tabea , Superti-Furga Giulio , IJzerman Adriaan P. , Heitman Laura H.
Published: May 2022

Excitatory amino acid transporters (EAAT/SLC1) mediate Na+-dependent uptake of extracellular glutamate and are potential drug targets for neurological disorders. Conventional methods to assess glutamate transport in vitro are based on radiolabels, fluorescent dyes or electrophysiology, which potentially compromise the cell’s physiology and are generally less suited for primary drug screens. Here, we describe a novel label-free method to assess human EAAT function in living cells, i.e., without the use of chemical modifications to the substrate or cellular environment. In adherent HEK293 cells overexpressing EAAT1, stimulation with glutamate or aspartate induced cell spreading, which was detected in real-time using an impedance-based biosensor. This change in cell morphology was prevented in the presence of the Na+/K+-ATPase inhibitor ouabain and EAAT inhibitors, which suggests the substrate-induced response was ion-dependent and transporter-specific. A mechanistic explanation for the phenotypic response was substantiated by actin cytoskeleton remodeling and changes in the intracellular levels of the osmolyte taurine, which suggests that the response involves cell swelling. In addition, substrate-induced cellular responses were observed for cells expressing other EAAT subtypes, as well as in a breast cancer cell line (MDA-MB-468) with endogenous EAAT1 expression. These findings allowed the development of a label-free high-throughput screening assay, which could be beneficial in early drug discovery for EAATs and holds potential for the study of other transport proteins that modulate cell shape.
Herb Formula (GCis) Prevents Pulmonary Infection Secondary to Intracerebral Hemorrhage by Enhancing Peripheral Immunity and Intestinal Mucosal Immune Barrier
Authors: Miao Yulu , Wang Bin , Hu Jing , Zhang Hanyu , Li Xiaojin , Huang Yingying , Zhuang Pengwei , Zhang Yanjun
Published: May 2022

Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.
Mammalian Sirtuins and Their Relevance in Vascular Calcification
Authors: Pan Xinyue , Pi Caixia , Ruan Xianchun , Zheng Hanhua , Zhang Demao , Liu Xiaoheng
Published: May 2022

Cardiovascular diseases are a group of diseases with high morbidity and mortality that affect millions of people each year. Vascular calcification (VC) is an active process that involves the mineral deposition of calcium-phosphate complexes. VC is closely related to cardiovascular diseases, such as hypertension, heart failure, and calcific aortic stenosis, and is a type of ectopic calcification that occurs in the vessel walls. The sirtuins (silent mating-type information regulation 2; SIRTs), are a family of histone deacetylases whose function relies on nicotinamide adenine dinucleotide (NAD+). They have non-negligible functions in the regulation of energy metabolism, senescence, apoptosis, and other biological processes. Sirtuins have important effects on bone homeostasis and VC processes that share many similarities with bone formation. Sirtuins have been confirmed to deacetylate a variety of target proteins related to the occurrence and development of VC, thereby affecting the process of VC and providing new possibilities for the prevention and treatment of cardiovascular diseases. To facilitate the understanding of vascular calcification and accelerate the development of cardiovascular drugs, we reviewed and summarized recent research progress on the relationship between different types of sirtuins and VC.
Mechanism Involved in Acute Liver Injury Induced by Intestinal Ischemia-Reperfusion
Authors: Jin Binghui , Li Guangyao , Zhou Lin , Fan Zhe
Published: May 2022

Intestinal ischemia-reperfusion (I/R) is a common pathophysiological process, which can occur in many conditions such as acute enteric ischemia, severe burns, small intestinal transplantation, etc,. Ischemia-reperfusion of the intestine is often accompanied by distal organ injury, especially liver injury. This paper outlined the signal pathways and cytokines involved in acute liver injury induced by intestinal I/R: the NF-κB Signaling Pathway, the P66shc Signaling Pathway, the HMGB1 Signaling Pathway, the Nrf2-ARE Signaling Pathway, the AMPK-SIRT-1 Signaling Pathway and other cytokines, providing new ideas for the prevention and treatment of liver injury caused by reperfusion after intestinal I/R.
A Hemodynamic Analysis of the Thrombosis Within Occluded Coronary Arterial Fistulas With Terminal Aneurysms Using a Blood Stasis Model
Authors: Jiang Xudong , Cao Haoyao , Zhang Zijian , Zheng Tinghui , Li Xiaoqiang , Wu Peng
Published: May 2022

Objective: The aim of this study is to numerically evaluate thrombosis risk within occluded coronary arterial fistulas (CAF) with terminal aneurysms, and provide guidance in choosing occlusion positions, with clinical observations as reference.

Method: Four patients with CAF were studied, with different occlusion positions in actual treatments. Hemodynamics simulations were conducted, with blood residue predicted using the blood stasis model. Three types of models (untreated model, aneurysm-reserved model and aneurysm-removed model) were studeid for each patient. Four metrics, i.e., proportion of high oscillatory shear index (OSI), area of high OSI, old blood volume fraction (OBVF)) and old blood volume (OBV) was obtained to distinguish the thrombosis risk of different treatments (proximal or distal occlusion), comparing with the follow-up CTA.

Results: For all the postopertive models, the high OBVF, high OSI(>0.3) and low time-averaged wall shear stress (TAWSS) regions were mainly at the distal fistula, indicating these regions were prone to thrombosis. The regions where blood residue remains are roughly regions of high OSI, corresponding well with clinical observations. In contrast, TAWSS failed to distinguish the difference in thrombosis risk. Absolute values (area of high OSI, OBV) can better reflect the degree of thrombosis risk between treatment types compared with percentage values (proportion of high OSI, OBVF). By comparing with the actual clinical treatments and observations, the OBV is superior to the area of high OSI in determining treatment type.

Conclusion: The OBV, a volumetric parameter for blood stasis, can better account for the CAF thrombosis and reflect the degree of blood stasis compared with OSI or TAWSS, is a more appropriate metric for thrombosis in the fistula. Together with morphological parameters, the OBV could guide clinicians to formulate more appropriate surgical plans, which is of great significance for the preoperative evaluation and treatment prognosis of CAF patients.
Genetic Dissection of Three Major Quantitative Trait Loci for Spike Compactness and Length in Bread Wheat (Triticum aestivum L.)
Authors: Yu Qin , Feng Bo , Xu Zhibin , Fan Xiaoli , Zhou Qiang , Ji Guangsi , Liao Simin , Gao Ping , Wang Tao
Published: May 2022

Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat (Triticum aestivum L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00–28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as QSc/Sl.cib-2AS, QSc/Sl.cib-2AL, and QSc/Sl.cib-2D, respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that QSc/Sl.cib-2AS and QSc/Sl.cib-2AL were possibly two novel loci for SC and SL. QSc/Sl.cib-2AS and QSc/Sl.cib-2D showed pleiotropic effects on plant height and grain morphology, while QSc/Sl.cib-2AL showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, TraesCS2A03G0410600 and TraesCS2A03G0422300 for QSc/Sl.cib-2AS, and TraesCS2D03G1129300 and TraesCS2D03G1131500 for QSc/Sl.cib-2D were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.
Multiomics Analyses of Two Sorghum Cultivars Reveal the Molecular Mechanism of Salt Tolerance
Authors: Ren Genzeng , Yang Puyuan , Cui Jianghui , Gao Yukun , Yin Congpei , Bai Yuzhe , Zhao Dongting , Chang Jinhua
Published: May 2022

Sorghum [Sorghum bicolor (L.) Moench] is one of the most important cereal crops and contains many health-promoting substances. Sorghum has high tolerance to abiotic stress and contains a variety of flavonoids compounds. Flavonoids are produced by the phenylpropanoid pathway and performed a wide range of functions in plants resistance to biotic and abiotic stress. A multiomics analysis of two sorghum cultivars (HN and GZ) under different salt treatments time (0, 24, 48, and 72) was performed. A total of 45 genes, 58 secondary metabolites, and 246 proteins were recognized with significant differential abundances in different comparison models. The common differentially expressed genes (DEGs) were allocated to the “flavonoid biosynthesis” and “phenylpropanoid biosynthesis” pathways. The most enriched pathways of the common differentially accumulating metabolites (DAMs) were “flavonoid biosynthesis,” followed by “phenylpropanoid biosynthesis” and “arginine and proline metabolism.” The common differentially expressed proteins (DEPs) were mainly distributed in “phenylpropanoid biosynthesis,” “biosynthesis of cofactors,” and “RNA transport.” Furthermore, considerable differences were observed in the accumulation of low molecular weight nonenzymatic antioxidants and the activity of antioxidant enzymes. Collectively, the results of our study support the idea that flavonoid biological pathways may play an important physiological role in the ability of sorghum to withstand salt stress.
Simulating Pine Wilt Disease Dispersal With an Individual-Based Model Incorporating Individual Movement Patterns of Vector Beetles
Authors: Xia Chunlei , Chon Tae-Soo , Takasu Fugo , Choi Won Il , Park Young-Seuk
Published: May 2022

Individual movements of the insect vector pine sawyer beetles were incorporated into an individual-based model (IBM) to elucidate the dispersal of pine wilt disease (PWD) and demonstrate the effects of control practices. The model results were compared with the spatial data of infested pine trees in the Gijang-gun area of Busan, Republic of Korea. Step functions with long- and middle-distance movements of individual beetles effectively established symptomatic and asymptomatic trees for the dispersal of PWD. Pair correlations and pairwise distances were suitable for evaluating PWD dispersal between model results and field data at short and long scales, respectively. The accordance between model and field data was observed in infestation rates at 0.08 and 0.09 and asymptomatic rates at 0.16–0.17 for disease dispersal. Eradication radii longer than 20 m would effectively control PWD dispersal for symptomatic transmission and 20–40 m for asymptomatic transmission. However, the longer eradication radii were more effective at controlling PWD. Therefore, to maximize control effects, a longer radius of at least 40 m is recommended for clear-cutting eradication. The IBM of individual movement patterns provided practical information on interlinking the levels of individuals and populations and could contribute to the monitoring and management of forest pests where individual movement is important for population dispersal.
The “2.8 ka BP Cold Event” Indirectly Influenced the Agricultural Exploitation During the Late Zhou Dynasty in the Coastal Areas of the Jianghuai Region
Authors: Jia Xin , Zhao Dongsheng , Storozum Michael J. , Shi Hongwei , Bai Guozhu , Liu Zhen , Hu Zhujun , Sun Liqiang , Wang Qi , Li Haiming
Published: May 2022

As a global cooling event, many of the climatic and socio-cultural mechanisms that resulted in changes after the 2. 8 ka BP event remain unclear. In China, this period roughly corresponds with the Zhou Dynasty (1046-212 BC), a critical period when ancient Chinese civilization was experiencing significant cultural and technological changes, including the movement of people to modern-day Jiangsu Province, where they intensively used the natural resources found in this the coastal area. Recent archaeobotanical evidence, and two radiocarbon dates on wheat and foxtail millet, indicate that the Datongpu site, which dates around 2,600 cal a BP, was occupied during this period of transition around the 2.8 ka BP climate event. In total, our investigations recovered 3,399 carbonized seeds from seventy-four flotation samples, of which rice, foxtail millet, broomcorn millet, and wheat seeds where predominant along with 2,296 weed seeds. Additionally, we identified several rice spikelets and wheat rachises. The high number of carbonized rice grains indicates that rice farming was the primary crop in an otherwise mixed rice-dry farming system at Datongpu. In addition, we argue that the “2.8 ka BP cold event” probably influenced population growth and caused food shortages throughout Central China, leading people to migrate southeastward along the Huai River to the coastal areas of Jianghuai Region. We argue that this abrupt shift in the climate indirectly facilitated the exploitation and emergence of large-scale agriculture in this area. Our study provides an example for the indirect impact of climate change in areas with relatively favorable climate conditions.
Development and Application of Fruit Color-Related Expressed Sequence Tag-Simple Sequence Repeat Markers in Abelmoschus esculentus on the Basis of Transcriptome Sequencing
Authors: An Xia , Luo Xiahong , Liu Tingting , Li Wenlue , Zou Lina
Published: May 2022

Abelmoschus esculentus is a medicinal and edible plant that contains large amounts of active ingredients, including anthocyanins, polysaccharides, flavonoids, and terpenoids. However, because of a relative lack of molecular research, there are few molecular markers applicable for this plant species. In this study, on the basis of A. esculentus fruit color-related transcriptome sequencing data, we analyzed the patterns of simple sequence repeats (SSRs) in differentially expressed genes (DEGs) and revealed the biological processes and metabolic pathways associated with the related genes. We also designed primers for SSR loci to develop SSR molecular markers. Primers were synthesized using a DEG associated with a protein–protein interaction network. Polymorphic SSR markers were screened for the subsequent examination of A. esculentus germplasm resources and fruit color association analysis. The results indicated that 24.98% of the unigenes contained SSR motifs. Single-base (mononucleotide) repeats were the main SSRs, followed by trinucleotide and dinucleotide repeats. We selected 47 expressed sequence tag (EST)-SSR primer pairs for the genotyping of 153 A. esculentus varieties/lines. We ultimately obtained 21 EST-SSR markers suitable for genotyping. A generalized linear model-based association analysis detected two EST-SSR markers significantly associated with A. esculentus fruit color. In conclusion, several EST-SSR and SSR molecular markers in A. esculentus were developed in this study. The fruit color-associated markers may be useful for the molecular marker-assisted breeding of new A. esculentus varieties.
Maturation and Assembly of Iron-Sulfur Cluster-Containing Subunits in the Mitochondrial Complex I From Plants
Authors: López-López Alicia , Keech Olivier , Rouhier Nicolas
Published: May 2022

In plants, the mitochondrial complex I is the protein complex encompassing the largest number of iron-sulfur (Fe-S) clusters. The whole, membrane-embedded, holo-complex is assembled stepwise from assembly intermediates. The Q and N modules are combined to form a peripheral arm in the matrix, whereas the so-called membrane arm is formed after merging a carbonic anhydrase (CA) module with so-called Pp (proximal) and the Pd (distal) domains. A ferredoxin bridge connects both arms. The eight Fe-S clusters present in the peripheral arm for electron transfer reactions are synthesized via a dedicated protein machinery referred to as the iron-sulfur cluster (ISC) machinery. The de novo assembly occurs on ISCU scaffold proteins from iron, sulfur and electron delivery proteins. In a second step, the preformed Fe-S clusters are transferred, eventually converted and inserted in recipient apo-proteins. Diverse molecular actors, including a chaperone-cochaperone system, assembly factors among which proteins with LYR motifs, and Fe-S cluster carrier/transfer proteins, have been identified as contributors to the second step. This mini-review highlights the recent progresses in our understanding of how specificity is achieved during the delivery of preformed Fe-S clusters to complex I subunits.