bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya
Authors: Bao Xiang-Yang , Fan Yan-Na , Wang Qian-Nan , Wang Xiao-Peng , Yang Ri-Miao , Zou Zheng-Xing , Zhang Qian , Li De-Sheng , Duan Lian , Yu Xin-Guang
Published: April 2022

Background and Purpose

To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD).

Methods

An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated.

Results

Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group.

Conclusions

These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.
Non-Invasive and Minimally-Invasive Cerebral Autoregulation Assessment: A Narrative Review of Techniques and Implications for Clinical Research
Authors: Sainbhi Amanjyot Singh , Gomez Alwyn , Froese Logan , Slack Trevor , Batson Carleen , Stein Kevin Y. , Cordingley Dean M. , Alizadeh Arsalan , Zeiler Frederick A.
Published: April 2022

The process of cerebral vessels regulating constant cerebral blood flow over a wide range of systemic arterial pressures is termed cerebral autoregulation (CA). Static and dynamic autoregulation are two types of CA measurement techniques, with the main difference between these measures relating to the time scale used. Static autoregulation looks at the long-term change in blood pressures, while dynamic autoregulation looks at the immediate change. Techniques that provide regularly updating measures are referred to as continuous, whereas intermittent techniques take a single at point in time. However, a technique being continuous or intermittent is not implied by if the technique measures autoregulation statically or dynamically. This narrative review outlines technical aspects of non-invasive and minimally-invasive modalities along with providing details on the non-invasive and minimally-invasive measurement techniques used for CA assessment. These non-invasive techniques include neuroimaging methods, transcranial Doppler, and near-infrared spectroscopy while the minimally-invasive techniques include positron emission tomography along with magnetic resonance imaging and radiography methods. Further, the advantages and limitations are discussed along with how these methods are used to assess CA. At the end, the clinical considerations regarding these various techniques are highlighted.
Temporal Dispersion and Duration of the Distal Compound Muscle Action Potential Do Not Distinguish Diabetic Sensorimotor Polyneuropathy From Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Alcantara Monica , Ngo Mylan , de la Cruz James , Menon Deepak , Barnett-Tapia Carolina , Katzberg Hans , Bril Vera
Published: April 2022

Objective

To investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP.

Methods

We performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline.

Results

We included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP.

Conclusion

Measures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation.

Significance

There are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients.
Long Noncoding RNA MALAT1 and Colorectal Cancer: A Propensity Score Analysis of Two Prospective Cohorts
Authors: Li Heng , Zhang Yuxue , Liu Yanlong , Qu Zhangyi , Liu Yupeng , Qi Jiping
Published: April 2022

Background

Previous researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independent external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort.

Methods

The prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI).

Results

There was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95% CI, 0.752-1.355, P=0.950) and 1.170 (95% CI, 0.910-1.502, P=0.220) for OS and DFS, respectively.

Conclusions

MALAT1 expression status is not associated with prognostic outcomes of CRC patients. However, additional larger population studies are needed to further validate these findings.
A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma
Authors: Martens Marvin , Kreidl Franziska , Ehrhart Friederike , Jean Didier , Mei Merlin , Mortensen Holly M. , Nash Alistair , Nymark Penny , Evelo Chris T. , Cerciello Ferdinando
Published: April 2022

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses. Given the growing complexity and technological spread of biological knowledge in MPM, there is an increasing need for an integrating tool that may allow scientists to access the information and analyze data in a simple and interactive way. We envisioned that a platform to capture this widespread and fast-growing body of knowledge in a machine-readable and simple visual format together with tools for automated large-scale data analysis could be an important support for the work of the general scientist in MPM and for the community to share, critically discuss, distribute and eventually advance scientific results. Toward this goal, with the support of experts in the field and informed by existing literature, we have developed the first version of a molecular pathway model of MPM in the biological pathway database WikiPathways. This provides a visual and interactive overview of interactions and connections between the most central genes, proteins and molecular pathways known to be involved or altered in MPM. Currently, 455 unique genes and 247 interactions are included, derived after stringent manual curation of an initial 39 literature references. The pathway model provides a directly employable research tool with links to common databases and repositories for the exploration and the analysis of omics data. The resource is publicly available in the WikiPathways database (Wikipathways : WP5087) and continues to be under development and curation by the community, enabling the scientists in MPM to actively participate in the prioritization of shared biological knowledge.
A Predictive Model for Prognosis and Therapeutic Response in Hepatocellular Carcinoma Based on a Panel of Three MED8-Related Immunomodulators
Authors: Jin Xiaojun , Song Yongfei , An Zhanglu , Wu Shanshan , Cai Dihui , Fu Yin , Zhang Chuanjing , Chen Lichao , Tang Wen , Zheng Zequn , Lu Hongsheng , Lian Jiangfang
Published: April 2022

The current tumor-node-metastasis (TNM) system is limited in predicting the survival and guiding the treatment of hepatocellular carcinoma (HCC) patients since the TNM system only focuses on the anatomical factors, regardless of the intratumoral molecule heterogeneity. Besides, the landscape of intratumoral immune genes has emerged as a prognostic indicator. The mediator complex subunit 8 (MED8) is a major polymerase regulator and has been described as an oncogene in renal cell carcinoma, but its pathophysiological significance of HCC and its contribution to the prognosis of HCC remain unclear. Here, we aimed to discuss the expression profile and clinical correlation of MED8 in HCC and construct a predictive model based on MED8-related immunomodulators as a supplement to the TNM system. According to our analyses, MED8 was overexpressed in HCC tissues and increased expression of MED8 was an indicator of poor outcome in HCC. The knockdown of MED8 weakened the proliferation, colony forming, and migration of HepG2 and Huh7 cells. Subsequently, a predictive model was identified based on a panel of three MED8-related immunomodulators using The Cancer Genome Atlas (TCGA) database and further validated in International Cancer Genome Consortium (ICGC) database. The combination of the predictive model and the TNM system could improve the performance in predicting the survival of HCC patients. High-risk patients had poor overall survival in TCGA and ICGC databases, as well as in subgroup analysis with early clinicopathology classification. It was also found that high-risk patients had a higher probability of recurrence in TCGA cohort. Furthermore, low-risk score indicated a better response to immunotherapy and drug therapy. This predictive model can be served as a supplement to the TNM system and may have implications in prognosis stratification and therapeutic guidance for HCC.
Aggressiveness of Differentiated Thyroid Carcinoma in Pediatric Patients Younger Than 16 years: A Propensity Score-Matched Analysis
Authors: Kim Soo Young , Yun Hyeok Jun , Chang Hojin , Kim Seok-Mo , Jeon Soyoung , Lee Sujee , Lee Yong Sang , Chang Hang-Seok , Park Cheong Soo
Published: April 2022

Background

The biological behavior of thyroid cancer in children has been known to be different from that in adults. We sought to understand the differences between DTC presentation in pediatric (<16 years) and adult patients, to guide better prognosis and clinical treatments.

Methods

This retrospective study included 48 pediatric patients younger than 16 years who underwent initial thyroid surgery and were diagnosed with DTC between January 1992 and December 2014 at Yonsei University in Seoul, South Korea. For a 1:4 propensity score-matched analysis, adult patients with matched sex and cancer size were included.

Results

The mean age was 12.54 ± 3.01 years. Total thyroidectomy (70.8%) without lateral lymph node dissection (47.9%) was the most commonly performed surgery. Central (73.9%) and lateral neck node metastases (62.5%) were common; distant metastasis was observed in 2 (4.2%) patients and recurrence occurred in 11 (22.9%). In propensity score-matched analysis, central lymph node metastasis and lateral neck node metastasis were significantly more frequent in pediatric patients. Symptoms were more common in the pediatric group than in the adult group (p < 0.001). In stratified cox regression, pediatric patients were more likely to experience recurrence [HR 5.339 (1.239–23.007)]. In stratified log-rank analysis, recurrence-free survival was significantly different between the adult and pediatric groups (p = 0.0209).

Conclusion

DTC in the pediatric group revealed more aggressive patterns than in the adult group with the same cancer size. Central lymph node metastasis and lateral neck node metastasis were more frequent. Stratified log-rank analysis revealed that recurrence was significantly higher in pediatric patients than in matched adult patients.
Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis
Authors: Balakumar Niveditha , Sendi Prithvi , Totapally Balagangadhar R.
Published: April 2022

Objectives

Neonatal hemophagocytic lymphohistiocytosis (HLH) is a rare entity. The objective of the study was to describe the prevalence, clinical characteristics, interventions and outcomes of neonates diagnosed with HLH in the United States.

Methods

A retrospective analysis of 2009, 2012, and 2016 Kids' Inpatient Database was performed. Neonates discharged/died with a diagnosis of HLH were identified and analyzed.

Results

Among 11,130,055 discharges, 76 neonates had a diagnosis of HLH. Fifty-two percent (95% CI: 38.6–63.6) were males and 54% (95% CI: 39.7–68.5) were white. Herpes simplex infection was present in 16% (95% CI: 9.2–28.1). 24.4% (95% CI: 14.5–37.9) received chemotherapy, 11.5% (95% CI: 5.2–23.6) IVIG and 3.6% (95% CI: 0.8–14.4) allogenic hemopoietic stem cell transplantation. Organ dysfunction was commonly seen and severe sepsis was documented in 26.6% (95% CI: 16.4–39.9). Median LOS was 16 (IQR 7–54) days. The mortality was 42% (95% CI: 30.8–55).

Conclusions

HLH is a rare diagnosis and carries a high mortality in neonates. Herpes simplex virus is the most common infection associated with neonatal HLH. HLH should be considered in the differential diagnosis in neonates presenting with multi-organ dysfunction or sepsis.
Anti-infective Medicines Use in Children and Neonates With Pre-existing Kidney Dysfunction: A Systematic Review
Authors: Minotti Chiara , Barbieri Elisa , Doni Denis , Impieri Cristina , Giaquinto Carlo , Donà Daniele
Published: April 2022

Background

Dosing recommendations for anti-infective medicines in children with pre-existing kidney dysfunction are derived from adult pharmacokinetics studies and adjusted to kidney function. Due to neonatal/pediatric age and kidney impairment, modifications in renal clearance and drug metabolism make standard anti-infective dosing for children and neonates inappropriate, with a risk of drug toxicity or significant underdosing. The aim of this study was the systematic description of the use of anti-infective medicines in pediatric patients with pre-existing kidney impairment.

Methods

A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, Medline and Cochrane databases were searched on September 21st, 2021. Studies in all languages reporting data on pre-defined outcomes (pharmacokinetics-PK, kidney function, safety and efficacy) regarding the administration of anti-infective drugs in children up to 18 years with pre-existing kidney dysfunction were included.

Results

29 of 1,792 articles were eligible for inclusion. There were 13 case reports, six retrospective studies, nine prospective studies and one randomized controlled trial (RCT), reporting data on 2,168 pediatric patients. The most represented anti-infective class was glycopeptides, with seven studies on vancomycin, followed by carbapenems, with five studies, mostly on meropenem. Antivirals, aminoglycosides and antifungals counted three articles, followed by combined antibiotic therapy, cephalosporins, lipopeptides with two studies, respectively. Penicillins and polymixins counted one study each. Nine studies reported data on patients with a decreased kidney function, while 20 studies included data on kidney replacement therapy (KRT). Twenty-one studies reported data on PK. In 23 studies, clinical outcomes were reported. Clinical cure was achieved in 229/242 patients. There were four cases of underdosing, one case of overdosing and 13 reported deaths.

Conclusion

This is the first systematic review providing evidence of the use of anti-infective medicines in pediatric patients with impaired kidney function or requiring KRT. Dosing size or interval adjustments in pediatric patients with kidney impairment vary according to age, critical illness status, decreased kidney function and dialysis type. Our findings underline the relevance of population PK in clinical practice and the need of developing predictive specific models for critical pediatric patients.
Factors Influencing Background Incidence Rate Calculation: Systematic Empirical Evaluation Across an International Network of Observational Databases
Authors: Ostropolets Anna , Li Xintong , Makadia Rupa , Rao Gowtham , Rijnbeek Peter R. , Duarte-Salles Talita , Sena Anthony G. , Shaoibi Azza , Suchard Marc A. , Ryan Patrick B. , Prieto-Alhambra Daniel , Hripcsak George
Published: April 2022

Objective: Background incidence rates are routinely used in safety studies to evaluate an association of an exposure and outcome. Systematic research on sensitivity of rates to the choice of the study parameters is lacking.

Materials and Methods: We used 12 data sources to systematically examine the influence of age, race, sex, database, time-at-risk, season and year, prior observation and clean window on incidence rates using 15 adverse events of special interest for COVID-19 vaccines as an example. For binary comparisons we calculated incidence rate ratios and performed random-effect meta-analysis.

Results: We observed a wide variation of background rates that goes well beyond age and database effects previously observed. While rates vary up to a factor of 1,000 across age groups, even after adjusting for age and sex, the study showed residual bias due to the other parameters. Rates were highly influenced by the choice of anchoring (e.g., health visit, vaccination, or arbitrary date) for the time-at-risk start. Anchoring on a healthcare encounter yielded higher incidence comparing to a random date, especially for short time-at-risk. Incidence rates were highly influenced by the choice of the database (varying by up to a factor of 100), clean window choice and time-at-risk duration, and less so by secular or seasonal trends.

Conclusion: Comparing background to observed rates requires appropriate adjustment and careful time-at-risk start and duration choice. Results should be interpreted in the context of study parameter choices.
Codonopsis pilosula Polysaccharide Improved Spleen Deficiency in Mice by Modulating Gut Microbiota and Energy Related Metabolisms
Authors: Cao Lingya , Du Changli , Zhai Xiaolu , Li Jiankuan , Meng Jingyi , Shao Yunyun , Gao Jianping
Published: April 2022

Codonopsis Radix (CR) is an important traditional Chinese medicine used for the treatment of spleen deficiency syndrome (SDS). Codonopsis pilosula polysaccharides (CPP) in CR are considered to be responsible for tonifying the spleen function; however, the mechanisms of the polysaccharides have remained unclear. This study aimed to investigate the treatment mechanisms of CPP in SDS mice using a combinational strategy of 16S rRNA gene sequencing and targeted metabolomics. Here, studies demonstrated that CPP had invigorating effect in vivo in Sennae Folium-induced SDS in mice by organ indexes, D-xylose determination, gastrointestinal hormones levels and goblet cells observation. Antibiotic treatment revealed that the intestinal microbiota was required for the invigorating spleen effect of CPP. Furthermore, gut microbiota analysis found that CPP significantly enriched probiotic Lactobacillus and decreased the abundance of some opportunistic pathogens, such as Enterococcus and Shigella. The metabolic profile analysis of the colonic content revealed that 25 chemicals were altered significantly by CPP, including amino acids, organic acids, fatty acids, carbohydrates and carnitine etc., which are mainly related to “energy conversion” related processes such as amino acids metabolism, tricarboxylic acid cycle, and nitrogen metabolism. Spearman’s correlation assays displayed there were strong correlations among biochemical indicators-gut microbiota-metabolomics. In summary, these results provided a new perspective for CPP improving SDS by regulating energy metabolism related bacteria and pathways.
Idiopathic Pulmonary Fibrosis Mortality Risk Prediction Based on Artificial Intelligence: The CTPF Model
Authors: Wu Xuening , Yin Chengsheng , Chen Xianqiu , Zhang Yuan , Su Yiliang , Shi Jingyun , Weng Dong , Jiang Xing , Zhang Aihong , Zhang Wenqiang , Li Huiping
Published: April 2022

Background: Idiopathic pulmonary fibrosis (IPF) needs a precise prediction method for its prognosis. This study took advantage of artificial intelligence (AI) deep learning to develop a new mortality risk prediction model for IPF patients.

Methods: We established an artificial intelligence honeycomb segmentation system that segmented the honeycomb tissue area automatically from 102 manually labeled (by radiologists) cases of IPF patients’ CT images. The percentage of honeycomb in the lung was calculated as the CT fibrosis score (CTS). The severity of the patients was evaluated by pulmonary function and physiological feature (PF) parameters (including FVC%pred, DLco%pred, SpO2%, age, and gender). Another 206 IPF cases were randomly divided into a training set (n = 165) and a verification set (n = 41) to calculate the fibrosis percentage in each case by the AI system mentioned previously. Then, using a competing risk (Fine–Gray) proportional hazards model, a risk score model was created according to the training set’s patient data and used the validation data set to validate this model.

Result: The final risk prediction model (CTPF) was established, and it included the CT stages and the PF (pulmonary function and physiological features) grades. The CT stages were defined into three stages: stage I (CTS≤5), stage II (5 < CTS<25), and stage III (≥25). The PF grades were classified into mild (a, 0–3 points), moderate (b, 4–6 points), and severe (c, 7–10 points). The AUC index and Briers scores at 1, 2, and 3 years in the training set were as follows: 74.3 [63.2,85.4], 8.6 [2.4,14.8]; 78 [70.2,85.9], 16.0 [10.1,22.0]; and 72.8 [58.3,87.3], 18.2 [11.9,24.6]. The results of the validation sets were similar and suggested that high-risk patients had significantly higher mortality rates.

Conclusion: This CTPF model with AI technology can predict mortality risk in IPF precisely.
ROS and Endoplasmic Reticulum Stress in Pulmonary Disease
Authors: Cui Xiangning , Zhang Yang , Lu Yingdong , Xiang Mi
Published: April 2022

Pulmonary diseases are main causes of morbidity and mortality worldwide. Current studies show that though specific pulmonary diseases and correlative lung-metabolic deviance own unique pathophysiology and clinical manifestations, they always tend to exhibit common characteristics including reactive oxygen species (ROS) signaling and disruptions of proteostasis bringing about accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). ER is generated by the unfolded protein response. When the adaptive unfolded protein response (UPR) fails to preserve ER homeostasis, a maladaptive or terminal UPR is engaged, leading to the disruption of ER integrity and to apoptosis, which is called ER stress. The ER stress mainly includes the accumulation of misfolded and unfolded proteins in lumen and the disorder of Ca2+ balance. ROS mediates several critical aspects of the ER stress response. We summarize the latest advances in of the UPR and ER stress in the pathogenesis of pulmonary disease and discuss potential therapeutic strategies aimed at restoring ER proteostasis in pulmonary disease.
Selinexor and COVID-19: The Neglected Warden
Authors: Mostafa-Hedeab Gomaa , Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Welson Nermeen N. , El-Saber Batiha Gaber , Conte-Junior Carlos Adam
Published: April 2022

A novel severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed as the cause of the global pandemic coronavirus disease 2019 (COVID-19). Different repurposed drugs have been trialed and used in the management of COVID-19. One of these agents was the anti-cancer Selinexor (SXR). SXR is an anti-cancer drug that acts by inhibition of nuclear exportin-1 (XPO1), which inhibits transport of nuclear proteins from the nucleus to the cytoplasm, leading to the induction of cell-cycle arrest and apoptosis. XPO1 inhibitors had antiviral effects, mainly against respiratory syncytial virus (RSV) and influenza virus. SXR inhibits transport of SARS-CoV-2 nuclear proteins to the cytoplasm with further inhibition of SARS-CoV-2 proliferation. SXR has the ability to prevent the development of a cytokine storm in COVID-19 by inhibiting the release of pro-inflammatory cytokines with the augmentation release of anti-inflammatory cytokines. In conclusion, SARS-CoV-2 infection is linked with activation of XPO1, leading to the triggering of inflammatory reactions and oxidative stress. Inhibition of XPO1 by Selinexor (SXR), a selective inhibitor of nuclear export (SINE), can reduce the proliferation of SARS-CoV-2 and associated inflammatory disorders. Preclinical and clinical studies are warranted in this regard.
The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases
Authors: Zhou Xun , Chen Hui , Li Jinqing , Shi Yingfeng , Zhuang Shougang , Liu Na
Published: April 2022

Methylation can occur in both histones and non-histones. Key lysine and arginine methyltransferases under investigation for renal disease treatment include enhancer of zeste homolog 2 (EZH2), G9a, disruptor of telomeric silencing 1-like protein (DOT1L), and protein arginine methyltransferases (PRMT) 1 and 5. Recent studies have shown that methyltransferases expression and activity are also increased in several animal models of kidney injury, such as acute kidney injury(AKI), obstructive nephropathy, diabetic nephropathy and lupus nephritis. The inhibition of most methyltransferases can attenuate kidney injury, while the role of methyltransferase in different animal models remains controversial. In this article, we summarize the role and mechanism of lysine methyltransferase and arginine methyltransferase in various kidney diseases and highlight methyltransferase as a potential therapeutic target for kidney diseases.
In-Vivo Imaging of Ocular Microvasculature Using Swept-Source Optical Coherence Tomography Angiography in Seven Types of Lab Animals
Authors: Wu Xuan , Chua Jacqueline , Ho Candice , Yao Xinwen , Muralidharan Arumugam R. , Najjar Raymond P. , Tan Gavin , Tamm Ernst R. , Schmetterer Leopold , Barathi Veluchamy A. , Tan Bingyao
Published: April 2022

The purpose of this study is to characterize the retinal and choroidal vascular networks in some of the most common animal species using swept-source optical coherence tomography angiography (SS-OCTA). Retinal angiographic images were acquired from healthy, anesthetized animals of seven species (mouse, rat, pig, rabbit, guinea pig, chicken, and non-human primate). We generated the enface angiograms to visualize the different retinal vascular plexuses and the choroidal vascular plexus. Quantitative OCTA metrics, including perfusion density, vessel density, and fractal dimension, were compared amongst the different species. There was a noticeable difference in the OCTA enface maps of the distinct vascular layers amongst the various species. Specifically, the non-human primate retina has the highest level of perfusion density and vessel density, whereas the rabbit retina exhibited the lowest level of vessel density. The mouse and the rat retina shared similar vascular patterns, and there was no difference in the OCTA metrics. Using one specific SS-OCTA system for all experiments eliminated multiple instrument-dependent factors, but the lateral resolution was still affected by eye size. Effects of varying lateral resolution on vascular metrics were investigated via a simulation. Overall, we achieved a large field of view of the distinct retinal and choroidal vascular plexuses and quantified the vascular metrics in multiple species, which could serve as protocol guidance and atlas to study the retinal and choroidal vascular abnormalities and their roles in ocular diseases resembling in-vivo histology.
Exploring the Effect of Spreading Fake News Debunking Based on Social Relationship Networks
Authors: Wang Xin , Chao Fan , Ma Ning , Yu Guang
Published: April 2022

Fake news spreads rapidly on social networks; the aim of this study is to compare the characteristics of the social relationship networks (SRNs) of refuters and non-refuters to provide a scientific basis for developing effective strategies for debunking fake news. First, based on six types of fake news published on Sina Weibo (a Chinese microblogging website) during 2015–2019 in China, a deep learning method was used to build text classifiers for identifying debunked posts (DPs) and non-debunked posts (NDPs). Refuters and non-refuters were filtered out, and their follower–followee relationships on social media were obtained. Second, the differences between DPs and NDPs were compared in terms of the volume and growth rate of the posts across various types of fake news. The SRNs of refuters and non-refuters and the k-core decompositions of these SRNs were constructed, and the differences in the growth rates between DPs and NDPs were explored. Business-related fake news was revealed to be debunked better; society-related fake news, the most widely spread in China, was debunked poorly; and science- and politics-related fake news was debunked the worst. Additionally, more celebrity accounts, larger node sizes with follower-followee relationships in the SRNs, and more weakly connected components were found to lead to a faster growth rate in the dissemination of posts, regardless of whether the posts were DPs or NDPs. This study can help practitioners develop more effective strategies for debunking fake news on social media in China.
Lower FSH With Normal Fertility in Male Mice Lacking Gonadotroph Kisspeptin Receptor
Authors: Ma Yaping , Awe Olubusayo , Radovick Sally , Yang Xiaofeng , Divall Sara , Wolfe Andrew , Wu Sheng
Published: April 2022

The kisspeptin receptor, crucial for hypothalamic control of puberty and reproduction, is also present in the pituitary gland. Its role in the pituitary gland is not defined. Kisspeptin signaling via the Kiss1r could potentially regulate reproductive function at the level of pituitary gonadotrope. Using Cre/Lox technology, we deleted the Kiss1r gene in pituitary gonadotropes (PKiRKO). PKiRKO males have normal genital development (anogenital distance WT: 19.1 ± 0.4 vs. PKiRKO: 18.5 ± 0.4 mm), puberty onset, testes cell structure on gross histology, normal testes size, and fertility. PKiRKO males showed significantly decreased serum FSH levels compared to WT males (5.6 ± 1.9 vs. 10.2 ± 1.8 ng/ml) with comparable LH (1.1 ± 0.2 vs. 1.8 ± 0.4 ng/ml) and testosterone levels (351.8 ± 213.0 vs. 342.2 ± 183.0 ng/dl). PKiRKO females have normal puberty onset, cyclicity, LH and FSH levels and fertility. Overall, these findings indicate that absence of pituitary Kiss1r reduces FSH levels in male mice without affecting testis function. PKiRKO mice have normal reproductive function in both males and females.
Leveraging National Germplasm Collections to Determine Significantly Associated Categorical Traits in Crops: Upland and Pima Cotton as a Case Study
Authors: Restrepo-Montoya Daniel , Hulse-Kemp Amanda M. , Scheffler Jodi A. , Haigler Candace H. , Hinze Lori L. , Love Janna , Percy Richard G. , Jones Don C. , Frelichowski James
Published: April 2022

Observable qualitative traits are relatively stable across environments and are commonly used to evaluate crop genetic diversity. Recently, molecular markers have largely superseded describing phenotypes in diversity surveys. However, qualitative descriptors are useful in cataloging germplasm collections and for describing new germplasm in patents, publications, and/or the Plant Variety Protection (PVP) system. This research focused on the comparative analysis of standardized cotton traits as represented within the National Cotton Germplasm Collection (NCGC). The cotton traits are named by ‘descriptors’ that have non-numerical sub-categories (descriptor states) reflecting the details of how each trait manifests or is absent in the plant. We statistically assessed selected accessions from three major groups ofGossypiumas defined by the NCGC curator: (1) “Stoneville accessions (SA),” containing mainly Upland cotton (Gossypium hirsutum) cultivars; (2) “Texas accessions (TEX),” containing mainlyG. hirsutumlandraces; and (3)Gossypium barbadense(Gb), containing cultivars or landraces of Pima cotton (Gossypium barbadense). For 33 cotton descriptors we: (a) revealed distributions of character states for each descriptor within each group; (b) analyzed bivariate associations between paired descriptors; and (c) clustered accessions based on their descriptors. The fewest significant associations between descriptors occurred in the SA dataset, likely reflecting extensive breeding for cultivar development. In contrast, the TEX and Gb datasets showed a higher number of significant associations between descriptors, likely correlating with less impact from breeding efforts. Three significant bivariate associations were identified for all three groups,bract nectaries:boll nectaries,leaf hair:stem hair, andlint color:seed fuzz color. Unsupervised clustering analysis recapitulated the species labels for about 97% of the accessions. Unexpected clustering results indicated accessions that may benefit from potential further investigation. In the future, the significant associations between standardized descriptors can be used by curators to determine whether new exotic/unusual accessions most closely resemble Upland or Pima cotton. In addition, the study shows how existing descriptors for large germplasm datasets can be useful to inform downstream goals in breeding and research, such as identifying rare individuals with specific trait combinations and targeting breakdown of remaining trait associations through breeding, thus demonstrating the utility of the analytical methods employed in categorizing germplasm diversity within the collection.
Continuous Flat Pressing of MDF Quality Control Model Framework and Collaborative Programming Approach Based on Wood Fiber Hot Pressing Mechanism
Authors: Lv Yunlei , Liu Yaqiu , Jing Weipeng
Published: April 2022

The increasing demand for forestry resources is driving the need for smarter systems capable of saving and protecting forests that can optimize agile forestry production. This study uses the continuous hot-pressing process of wooden medium-density fiberboard (MDF) to investigate the possibility of automatic quality control of the continuous flat pressing process. For this purpose, conceptual digital twin modeling for mechanism and sequence parameter control was conducted based on the cellular automata (CA) theory. A distributed coordination mode framework was constructed, and a craft control programming method was proposed for the quality control of MDF continuous flat pressing. Based on the MDF continuous flat press craft mechanism and control standards, a framework of five distributed flat press cooperative control mode elements for the cylinder array of the continuous panel system (CPS) was defined. To satisfy the distributed distance servo and pressure servo demands of the multi-stage hot pressing craft design, five kinds of synergy collaborative control modes of multiple rack groups were constructed using mode elements: For the four types of typical deviations in slab production, i.e., thickness, slope, depression, and bulge, a multi-zone mutual cooperative mode craft control sequence was programmed. According to the type and intensity of real-time deviation, the corresponding regulation sequence was applied. This effectively counteracts the deviation caused by the uncertainty interference due to the multi-field coupling effect in actual production. The application tests demonstrate that the adjustment and response time of the continuous flat press were greatly improved, and the quality superiority rate is controlled above 95%, thereby confirming the effectiveness of the control strategy.
N Addition Overwhelmed the Effects of P Addition on the Soil C, N, and P Cycling Genes in Alpine Meadow of the Qinghai-Tibetan Plateau
Authors: Xiao Jiannan , Dong Shikui , Shen Hao , Li Shuai , Wessell Kelly , Liu Shiliang , Li Wei , Zhi Yangliu , Mu Zhiyuan , Li Hongbo
Published: April 2022

Although human activities have greatly increased nitrogen (N) and phosphorus (P) inputs to the alpine grassland ecosystems, how soil microbial functional genes involved in nutrient cycling respond to N and P input remains unknown. Based on a fertilization experiment established in an alpine meadow of the Qinghai-Tibetan Plateau, we investigated the response of the abundance of soil carbon (C), N, and P cycling genes to N and P addition and evaluated soil and plant factors related to the observed effects. Our results indicated that the abundance of C, N, and P cycling genes were hardly affected by N addition, while P addition significantly increased most of them, suggesting that the availability of P plays a more important role for soil microorganisms than N in this alpine meadow ecosystem. Meanwhile, when N and P were added together, the abundance of C, N, and P cycling genes did not change significantly, indicating that the promoting effects of P addition on microbial functional genes abundances were overwhelmed by N addition. The Mantel analysis and the variation partitioning analysis revealed the major role of shoot P concentration in regulating the abundance of C, N, and P cycling genes. These results suggest that soil P availability and plant traits are key in governing C, N, and P cycling genes at the functional gene level in the alpine grassland ecosystem.
New Schemes for Investment in of Small and Medium-Sized Enterprises of China: Role of Access to Finance, Innovation, and Sustainability
Authors: Tang Xuelian
Published: April 2022

Firm innovation relies heavily on financing, which is why it is a hot topic in the fields of finance and innovation management. Organizations can make strategic investments in production factors to develop competitive advantages because they have access to financial resources. This study investigated how financial literacy, innovativeness, and environmental sustainability influence the sustainability of small and medium-sized enterprises (SMEs). This was set as the primary objective in order to better understand the nature of the impact of financial literacy and innovation on the sustainability of SME firms. To test the hypotheses, structural equation modeling (SEM) was applied using data collected from 300 small businesses firms in China. The results revealed that financial literacy and innovativeness significantly influence small firms’ sustainability. Additionally, social inclusion significantly affects small firms’ sustainability, and sequentially has a significant effect on their performance. Research findings suggested that small businesses incorporate sustainability models into their operations and enhance financial knowledge in order to maintain sustainability.
Triple Burden of Neurocognitive Impairment and Co-occurring Depression and Anxiety Among People Living With HIV in Bahir Dar, Ethiopia: A Multicenter Study
Authors: Tareke Minale , Belete Tilahun , Ergetie Temesgen , Tadesse Meseret , Menberu Melak , Ketemaw Asmamaw
Published: April 2022

Background

Neurocognitive impairment is associated with psychological morbidities, such as depression and anxiety, among people living with HIV. The presence of these comorbidities affects viral load suppression, treatment adherence, quality of life, treatment outcomes, and functionality. Despite this fact, there is a dearth of studies that examined the triple burden of neurocognitive impairment and co-occurring depression and anxiety among antiretroviral therapy attendees in Ethiopia. This study aimed to assess the magnitude of HIV-associated neurocognitive impairment and co-occurring depression and anxiety at the same time among people living with HIV/AIDS.

Method

We conducted an institution-based multicenter cross-sectional study in Bahir Dar, Northwest Ethiopia. A total of 410 study participants were selected using a systematic random sampling technique. Neurocognitive impairment was assessed using the International HIV Dementia Scale. Co-occurring depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. A semi-structured questionnaire was applied to collect data on sociodemographic and clinical-related characteristics. Data were analyzed using descriptive statistics and univariate and multivariable logistic regression.

Results

Two-thirds (66.8%) of the people living with HIV had neurocognitive impairment. The prevalence of co-occurring depression and anxiety was found in 39.8%. Women with HIV, people with comorbid chronic medical illness, and those under a second-line treatment regimen were factors associated with neurocognitive impairment. Furthermore, pill burden, second-line treatment regimen, HIV clinical stages, social support, HIV-perceived stigma, and neurocognitive impairment were associated factors with co-occurring depression and anxiety.

Conclusions

We found a high prevalence of neurocognitive impairment and co-occurring depression and anxiety among people living with HIV/AIDs. Further research is needed to assess the clinical course of neurocognitive impairment and co-occurring depression and anxiety.
Association Between Clinical Competencies and Mental Health Symptoms Among Frontline Medical Staff During the COVID-19 Outbreak: A Cross-Sectional Study
Authors: Chang Qing , Su Han , Xia Yang , Gao Shanyan , Zhang Ming , Ma Xiaoyu , Liu Yashu , Zhao Yuhong
Published: April 2022

Background

In China, mental health of frontline medical staff might be influenced by clinicians' ability to handle the outbreak of coronavirus disease 2019 (COVID-19). Few studies to-date have addressed the association between clinicians' competencies and mental health in this context. This cross-sectional study was to examine the prevalence of mental health symptoms among frontline medical staff that fought against the COVID-19 outbreak, and explore the associations between their competencies, and separate and concurrent depressive and anxiety symptoms.

Methods

A total of 623 frontline medical staff was included in this study. Competencies, depressive symptoms, and anxiety symptoms were assessed using a self-reported short form of the Chinese clinical physicians' competency model, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 questionnaire, respectively. Logistic regression models were used to evaluate the associations between one SD increase in competency scores and the prevalence of mental health problems.

Results

The prevalence of depressive, anxiety, and comorbid depressive and anxiety symptoms was 40.93, 31.78, and 26.00%, respectively. Among the medical staff with higher total competency scores, the prevalence of depressive [odds ratios (ORs) = 0.67, 95% confidence intervals (CIs): 0.55–0.81], anxiety (OR = 0.68, 95% CI: 0.56–0.83), and comorbid anxiety and depressive symptoms (OR = 0.69, 95% CI: 0.55–0.83) was lower than among their lower-scoring counterparts. Subgroup analyses stratified by core competency scores revealed similar associations as the main analyses.

Conclusion

The present findings highlight the association between high core competency scores and lower prevalence of depressive, anxiety, and comorbid anxiety and depressive symptoms.
“Our Patients Are Different”: Predictors of Seclusion and Restraint in 31 Psychiatric Hospitals
Authors: Flammer Erich , Hirsch Sophie , Thilo Nancy , Steinert Tilman
Published: April 2022

Background

Research in recent years has demonstrated that the use of coercive measures such as seclusion and restraint differs very much between hospitals within a country. In 2015, a central register for all coercive measures in the German federal state of Baden-Wuerttemberg has been established for 32 hospitals treating involuntary patients. The objective of the present study was to identify factors that determine the differences between these hospitals.

Methods

Data on coercive measures and diagnoses from the central register in 2015–2017 were linked with structural data of the 32 hospitals and their supply areas.

Results

On average, coercive measures were applied in 6.7% of cases (SD = 2.8%; Min–Max = 0.35–12.0%). The proportion of affected cases was significantly correlated with the proportion of involuntary patients (r = 0.56), the proportion of cases with affective or neurotic, stress-related and somatoform disorders (r = −0.42), number of hospital beds (r = 0.44), a sheltered home associated with the hospital (r = 0.43) and number of addiction counseling centers per 100,000 inhabitants in the service area (r = −0.39). The final regression model only included the proportion of involuntary cases as a significant predictor (standardized beta = 0.55, adjusted R2 = 0.27).

Conclusions

The predominating part of the considerable variance observed between hospitals could not be explained by structural variables. The proportion of involuntary patients had a significant impact, but a considerable amount of unexplained variance due to different practices within psychiatric hospitals remains.