bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Diagnostic Value of a Combined Indicator of Vitamin B12 Status (cB12) Throughout Pregnancy
Authors: Dib Marie-Joe , Gumban-Marasigan Maria , Yoxall Rozzie , Andrew Toby , Harrington Dominic J. , Sobczyńska-Malefora Agata , Ahmadi Kourosh R.
Published: January 2022

Background

Inadequate provision of vitamin B12 during pregnancy is associated with a number of adverse maternal and fetal outcomes. We set out to (1) suggest pregnancy-specific reference ranges for a range of biomarkers of vitamin B12; (2) assess the temporal behaviors of these markers over the course of pregnancy; and (3) test whether any biomarkers, including the genetic marker HIBCH rs291466 strongly associated with MMA measured early in pregnancy could reliably and significantly predict future B12 status within a healthy UK population of pregnant women.

Materials and Methods

We used existing biobank samples from the placebo arm of the UK Selenium in PRegnancy Intervention (SPRINT) study, to generate biochemical data for serum folate, B12, holotranscobalamin (HoloTC), total homocysteine (tHcy), and MMA, calculate cB12, and genotyped the polymorphism rs291466 in gene HIBCH on a total of n=114 women across trimesters 1–3 of their pregnancy. We performed a series of exploratory cross-sectional and longitudinal analyses to investigate levels at each trimester, suggest references ranges, evaluate changes and correlations between the B12 biomarkers, and assess the predictive capabilities of each biomarker from 12-weeks to 35-weeks of gestation.

Results

Significant changes in all vitamin B12 biomarker values were observed over the three trimesters (P < 0.05). Our study shows that cB12 values were largely constant and stable throughout trimester 1 (T1) and T2 (i.e., up to week 20), but declined significantly in T3 (−66% | P < 0.001). Yet, cB12 generally remained within the normal boundaries. We identified pregnancy and trimester-specific reference ranges for each biomarker at each trimester, notably for total serum B12. This marker fell below the recommended cut-offs in 1/3 of the cohort at the third trimester, contrasting other markers (mostly normal). Our multivariate analyses indicated that none of the biomarkers could reliably and accurately predict any other biomarkers than themselves later in pregnancy. Yet, HoloTC seems to be a promising predictor within the limitations of our cohort, constituted of B12-replete individuals. Most notably, cB12 did not significantly predict itself between trimesters. Finally, we show that the HIBCH variant has little predictive power for MMA or cB12 as it does not explain the significant increase in MMA concentrations nor the decline of cB12 throughout pregnancy.

Conclusion

Trimester-specific reference ranges for biomarkers of vitamin B12 in normal pregnancy are suggested. However, these biomarkers have limited predictive value in identifying mothers at elevated risk of vitamin B12 insufficiency/deficiency during pregnancy.
Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients
Authors: Borges Leandro , Gennari-Felipe Matheus , Dias Beatriz Belmiro , Hatanaka Elaine
Published: January 2022

The use of nutraceutical approaches may regulate the immune system, performing a potential strategy to contain the worst outcomes of COVID-19. We reviewed the current evidence surrounding nutritional/nutraceutical approaches for the therapy in patients with COVID-19. We searched the PubMed database to report randomized controlled trials (RCTs) and observational research that used melatonin, zinc, or vitamin C supplementation as an intervention for COVID-19 treatment. To date, we found only three concluded studies that assessed zinc supplementation and melatonin therapy in patients with COVID-19, but with inconclusive data, relatively small sample size, and early termination of the trial. On the other hand, vitamin C therapy appears to reduce hyperinflammation and improve the oxygen support status of patients with COVID-19. However, a large part of this research involves pilot trials, and there are still conflicting data regarding mortality rate, mechanical ventilation, and duration of symptoms of patients with COVID-19. Melatonin, zinc, and vitamin C supplementation should be investigated further on the nutritional status-immune response, and data from ongoing trials are needed to understand these molecules as a therapy strategy in patients COVID-19.
Efficacy of Probiotics in Children and Adolescents With Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Andrade Paula Danielle Santa Maria Albuquerque de , Maria e Silva Jorgete , Carregaro Vanessa , Sacramento Laís Amorim , Roberti Luciana Rodrigues , Aragon Davi Casale , Carmona Fabio , Roxo-Junior Pérsio
Published: January 2022

Objective

To evaluate the clinical efficacy of a mixture of probiotics (Lactobacillus and Bifidobacterium) in children and adolescents with atopic dermatitis (AD) and the effects on sensitization, inflammation, and immunological tolerance.

Methods

In this double-blind, randomized, placebo-controlled clinical trial, we enrolled 60 patients aged between 6 months and 19 years with mild, moderate, or severe AD, according to the criteria proposed by Hanifin and Rajka. Patients were stratified to receive one gram per day of probiotics or placebo for 6 months. The primary outcome was a decrease in SCORing Atopic Dermatitis (SCORAD). Secondary outcomes were to assess the role of probiotics on the use of topical and oral medicines (standard treatment), serum IgE levels, skin prick test (SPT), and tolerogenic and inflammatory cytokines. Background therapy was maintained.

Results

Forty patients completed the study (24 probiotics, 16 placebo). After treatment for six months, the clinical response was significantly better in the probiotics group; the SCORAD decreased [mean difference (MD) 27.69 percentage points; 95% confidence interval (CI), 2.44–52.94], even after adjustment for co-variables (MD 32.33 percentage points; 95%CI, 5.52–59.13), especially from the third month of treatment on. The reduction of the SCORAD in probiotic group persisted for three more months after the treatment had been discontinued, even after adjustment for co-variables (MD 14.24 percentage points; 95%CI, 0.78–27.70). Patients in the probiotics group required topical immunosuppressant less frequently at 6 and 9 months. No significant changes were found for IgE levels, SPT and cytokines.

Conclusions

Children and adolescents with AD presented a significant clinical response after 6 months with a mixture of probiotics (Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus paracasei, and Bifidobacterium lactis. However, this clinical benefit is related to treatment duration. Probiotics should be considered as an adjuvant treatment for AD.
Role of CD133/NRF2 Axis in the Development of Colon Cancer Stem Cell-Like Properties
Authors: Park Jimin , Kim Seung Ki , Hallis Steffanus Pranoto , Choi Bo-Hyun , Kwak Mi-Kyoung
Published: January 2022

Cancer stem cells (CSCs) exhibit intrinsic therapy/stress resistance, which often cause cancer recurrence after therapy. In this study, we investigated the potential relationship between the cluster of differentiation (CD)-133, a CSC marker of colon cancer, and nuclear factor erythroid 2-like 2 (NFE2L2; NRF2), a master transcription factor for the regulation of multiple antioxidant genes. In the first model of CSC, a sphere culture of the colorectal cell line HCT116, showed increased levels of CD133 and NRF2. Silencing of CD133 reduced the levels of CSC markers, such as Kruppel-like factor 4 (KLF4) and ATP-binding cassette subfamily G member 2 (ABCG2), and further suppressed the expression levels of NRF2 and its target genes. As a potential molecular link, CD133-mediated activation of phosphoinositide 3-kinase/serine-threonine kinase (PI3K/AKT) signaling appears to increase the NRF2 protein levels via phosphorylation and the consequent inhibition of glycogen synthase kinase (GSK)-3β. Additionally, NRF2-silenced HCT116 cells showed attenuated sphere formation capacity and reduced CSC markers expression, indicating the critical role of the NRF2 pathway in the development of CSC-like properties. As a second model of CSC, the CD133high cell population was isolated from HCT116 cells. CSC-like properties, including sphere formation, motility, migration, colony formation, and anticancer resistance, were enhanced in the CD133high population compared to CD133low HCT116 cells. Levels of NRF2, which were elevated in CD133high HCT116, were suppressed by CD133-silencing. In line with these, the analysis of The Cancer Genome Atlas (TCGA) database showed that high levels of CD133 expression are correlated with increased NRF2 signaling, and alterations in CD133 gene or expression are associated with unfavorable clinical outcome in colorectal carcinoma patients. These results indicate that the CD133/NRF2 axis contributes to the development of CSC-like properties in colon cancer cells, and that PI3K/AKT signaling activation is involved in CD133-mediated NRF2 activation.
Phenethyl Isothiocyanate Enhances the Cytotoxic Effects of PARP Inhibitors in High-Grade Serous Ovarian Cancer Cells
Authors: Jia Yaxun , Wang Min , Sang Xiaolin , Liu Pixu , Gao Jingchun , Jiang Kui , Cheng Hailing
Published: January 2022

While PARP inhibitor (PARPi) therapies have shown promising results in the treatment of high-grade serous ovarian cancer (HGSOC) harboring homologous recombination deficiencies, primary resistance to PARPi frequently occurs and even initial responders may eventually become resistant. Therefore, the development of novel effective combinatorial strategies to treat HGSOC is urgently needed. Here, we report that H2O2-induced oxidative stress sensitized HGSOC cells to PARPi BMN 673. Furthermore, Phenethyl isothiocyanate (PEITC) as a ROS-inducing agent significantly enhanced the cytotoxic effects of BMN 673. Mechanistically, combined use of PEITC and BMN 673 resulted in ROS overproduction and accumulation, enhanced DNA damage, G2/M arrest and apoptosis, all of which were significantly reversed by the ROS scavenger N-Acetyl-L-cysteine. We also showed that while PEITC did not further enhance the ability of BMN 673 on PARP1 trapping in HGSOC cells, the therapeutic effects of the PEITC/BMN 673 combination were at least in part dependent on the presence of PARP1. Importantly, the PEITC/BMN 673 combination potently abrogated the growth of HGSOC tumor spheroids and patient-derived organoid models of HGSOC and cervical cancer. Our findings provide a basis for further investigation of the utility of PARPi combination regimen in HGSOC and cervical cancer through ROS-mediated mechanisms.
Development and Validation of a Radiomics Nomogram for Predicting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions
Authors: Li Tianping , Sun Linna , Li Qinghe , Luo Xunrong , Luo Mingfang , Xie Haizhu , Wang Peiyuan
Published: January 2022

Purpose

To develop and validate a radiomics nomogram for the prediction of clinically significant prostate cancer (CsPCa) in Prostate Imaging-Reporting and Data System (PI-RADS) category 3 lesions.

Methods

We retrospectively enrolled 306 patients within PI-RADS 3 lesion from January 2015 to July 2020 in institution 1; the enrolled patients were randomly divided into the training group (n = 199) and test group (n = 107). Radiomics features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) imaging, and dynamic contrast-enhanced (DCE) imaging. Synthetic minority oversampling technique (SMOTE) was used to address the class imbalance. The ANOVA and least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection and radiomics signature building. Then, a radiomics score (Rad-score) was acquired. Combined with serum prostate-specific antigen density (PSAD) level, a multivariate logistic regression analysis was used to construct a radiomics nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate radiomics signature and nomogram. The radiomics nomogram calibration and clinical usefulness were estimated through calibration curve and decision curve analysis (DCA). External validation was assessed, and the independent validation cohort contained 65 patients within PI-RADS 3 lesion from January 2020 to July 2021 in institution 2.

Results

A total of 75 (24.5%) and 16 (24.6%) patients had CsPCa in institution 1 and 2, respectively. The radiomics signature with SMOTE augmentation method had a higher area under the ROC curve (AUC) [0.840 (95% CI, 0.776–0.904)] than that without SMOTE method [0.730 (95% CI, 0.624–0.836), p = 0.08] in the test group and significantly increased in the external validation group [0.834 (95% CI, 0.709–0.959) vs. 0.718 (95% CI, 0.562–0.874), p = 0.017]. The radiomics nomogram showed good discrimination and calibration, with an AUC of 0.939 (95% CI, 0.913–0.965), 0.884 (95% CI, 0.831–0.937), and 0.907 (95% CI, 0.814–1) in the training, test, and external validation groups, respectively. The DCA demonstrated the clinical usefulness of radiomics nomogram.

Conclusion

The radiomics nomogram that incorporates the MRI-based radiomics signature and PSAD can be conveniently used to individually predict CsPCa in patients within PI-RADS 3 lesion.
Stereotactic Body Radiotherapy Immunological Planning—A Review With a Proposed Theoretical Model
Authors: Swamy Kumara
Published: January 2022

In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward an “immunological radiation plan”, i.e., radiation scheduling with abscopal effect as a vital endpoint as well. The literature review of part A enumerates the advantages of the intermediate dose of SBRT 6–10 Gy per fraction, appropriate use of dose painting, proper timing with immunotherapy, and the potential of immunoadjuvants to maximize cell kill in the irradiated lesions, found to have improved the abscopal effects. Part B summarizes part A, primarily the findings of animal trials, forming the basis of the tenets of the proposed model given in part C to realize the true abscopal potential of the SBRT tumor cell kill of the index lesions. Part C proposes a theoretical model highlighting tumor vasculature integrity as the central theme for converting “abscopal effect by chance” to “abscopal effect by design” using a harmonized combinatorial approach. The proposed model principally deals with the use of SBRT in strategizing increased cell kill in irradiated index tumors along with immunomodulators as a basis for improving the consistency of the abscopal effect. Included is the possible role of integrating immunotherapy just after SBRT, “cyclical” antiangiogenics, and immunoadjuvants/immune metabolites as abscopal effect enhancers of SBRT tumor cell kill. The proposed model suggests convergence research in adopting existing numerous SBRT abscopal enhancing strategies around the central point of sustained vascular integrity to develop decisive clinical trial protocols in the future.
Pevonedistat Suppresses Pancreatic Cancer Growth via Inactivation of the Neddylation Pathway
Authors: Xu Junfeng , Li Zheng , Zhuo Qifeng , Ye Zeng , Fan Guixiong , Gao Heli , Ji Shunrong , Yu Xianjun , Xu Xiaowu , Liu Wensheng , Xu Wenyan
Published: January 2022

Background

The neddylation pathway is aberrantly overactivated in multiple human cancers and has been indicated as an effective target for anticancer therapy in clinical trials. We aimed to study whether the neddylation pathway is upregulated in pancreatic cancer and whether pevonedistat, a first-in-class anticancer agent specifically targeting this pathway, will suppress cancer tumorigenesis and progression.

Methods

We evaluated the expression pattern of neddylation pathway components in 179 pancreatic adenocarcinoma (PAAD) compared with 171 normal tissues from The Cancer Genome Atlas (TCGA) dataset and further assessed PAAD patient prognosis with high neddylation pathway expression via Gene Expression Profiling Interactive Analysis (GEPIA). We then analyzed malignant cancer phenotypes both in vitro and in vivo, as well as intrinsic molecular mechanisms upon pevonedistat treatment.

Results

We found that the neddylation pathway was hyperactivated in pancreatic cancer. Patients with high neddylation pathway expression exhibited worse prognoses. Pevonedistat significantly inhibited the cancer cell cycle, cell growth, and proliferation; increased cell apoptosis; and decreased cancer cell xenografts in a mouse model. Mechanistically, pevonedistat treatment and the siRNA knockdown neddylation pathway were able to remarkably induce the accumulation of Wee1, p27, and p21. Further mechanistic studies revealed that pevonedistat mainly impaired the ubiquitination level and delayed the protein degradation of Wee1, p27, and p21.

Conclusions

Our results showed that pevonedistat targeted the overexpression of the neddylation pathway in pancreatic cancer to induce cell growth suppression by inducing the accumulation of the cell cycle regulators Wee1, p27, and p21, which provides sound evidence for the clinical trial of pevonedistat for pancreatic cancer therapy.
Sociodemographic Differences in Pain Medication Usage and Healthcare Provider Utilization Among Adults With Chronic Low Back Pain
Authors: Allen-Watts Kristen , Sims Andrew M. , Buchanan Taylor L. , DeJesus Danica J. B. , Quinn Tammie L. , Buford Thomas W. , Goodin Burel R. , Rumble Deanna D.
Published: January 2022

Chronic low back pain (cLBP) is the most common reason for individual suffering and health care utilization in adults. Ample evidence suggests sociodemographic variables and socioeconomic status (SES) influence pain. However, a framework informing associations on race, SES, and the utilization of pharmacologic therapies and provider type are limited—particularly in cLBP. Thus, this study examined the extent to which sociodemographic (i.e., age, race, and gender) and socioeconomic factors (i.e., national area deprivation index, NADI) influence pain treatment (i.e., NSAIDs, opioids, antidepressants, and non-NSAIDs) and provider utilization for cLBP (i.e., no provider care, primary care, or tertiary care). Eligible participants with cLBP completed a series of questionnaires. Of the 174 participants, 58% were women, 59% were non-Hispanic Black (NHB), and the mean age was 46.10 (SD 13.58). Based on NADI distributions by race, NHB participants lived in more socioeconomically disadvantaged neighborhoods (p < 0.001) than non-Hispanic White (NHW) adults. Results suggested that the use of one or more pharmacologic therapies was associated with race (p = 0.021). Specifically, NHW adults were two times more likely to take one or more pharmacologic therapies than NHBs (p = 0.009). NHWs were also more likely to use NSAIDs (p = 0.041) and antidepressants (p < 0.001) than NHBs. Furthermore, provider utilization was significantly associated with gender (p = 0.037) and age (p = 0.018); which suggests older women were more likely to use primary or tertiary care. Findings from this study expand on the existing literature as it relates to associations between disparities in access to healthcare providers and access to medications. Future research should seek to understand differences in age and utilization of primary or tertiary care providers and continue to examine the influence of sociodemographic and SES factors to cLBP and compare with other types of chronic pain.
Case Report: A Relatively Mild Phenotype Produced by Novel Mutations in the SEPSECS Gene
Authors: Rong Tingyu , Yao Ruen , Deng Yujiao , Lin Qingmin , Wang Guanghai , Wang Jian , Jiang Fan , Jiang Yanrui
Published: January 2022

Mutations in the human O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase gene (SEPSECS) are associated with progressive cerebello-cerebral atrophy (PCCA), also known as pontocerebellar hypoplasia type 2D (PCH2D). Early-onset profound developmental delay, progressive microcephaly, and hypotonia that develops toward severe spasticity have been previously reported with SEPSECS mutations. Herein we report a case with severe global developmental delay, myogenic changes in the lower limbs, and insomnia, but without progressive microcephaly and brain atrophy during infancy and toddlerhood in a child harboring the SEPSECS missense variant c.194A>G (p. Asn65Ser) and a novel splicing mutation c.701+1G>A. With these findings we communicate the first Chinese SEPSECS mutant case, and our report indicates that SEPSECS mutations can give rise to a milder phenotype.
Diagnostic Accuracy of Infection Markers to Diagnose Infections in Neonates and Children Receiving Extracorporeal Membrane Oxygenation
Authors: Doo Irene , Staub Lukas P. , Mattke Adrian , Haisz Emma , Seidler Anna Lene , Alphonso Nelson , Schlapbach Luregn J.
Published: January 2022

Background

Infections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO.

Methods

Retrospective single center observational study including neonates and children <18 years treated with ECMO in 2015 and 2016. Daily data on PCT, CRP and WCC were assessed in relation to microbiologically confirmed, and clinically suspected infection on ECMO using operating characteristics (ROC) curves.

Results

Sixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66–0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61–0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59–0.81) for confirmed and AUC of 0.66 (0.57–0.75) for confirmed and suspected infections. PCT was non-discriminatory.

Conclusion

The diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO.
Effects and Mechanisms of Taohong Siwu Decoction on the Prevention and Treatment of Myocardial Injury
Authors: Shao Chang-Le , Cui Guo-Hong , Guo Hai-Dong
Published: January 2022

Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis. With the continuous in-depth excavation in basic and clinical research, it has been found that THSWD has made greater progress in the prevention and treatment of cardiovascular diseases. Mechanisms of the current studies have shown that it could prevent and treat the myocardial injury by inhibiting inflammatory reaction, antioxidant stress, inhibiting platelet aggregation, prolonging clotting time, anti-fibrosis, reducing blood lipids, anti-atherosclerosis, improving hemorheology and vascular pathological changes, regulating related signal pathways and other mechanisms to prevent and treat the myocardial injury, so as to protect cardiomyocytes and improve cardiac function. Many clinical studies have shown that THSWD is effective in the prevention and treatment of cardiovascular diseases related to myocardial injuries, such as coronary heart disease angina pectoris (CHD-AP), and myocardial infarction. In clinical practice, it is often used by adding and subtracting prescriptions, the combination of compound prescriptions and combinations of chemicals and so on. However, there are some limitations and uncertainties in both basic and clinical research of prescriptions. According to the current research, although the molecular biological mechanism of various active ingredients needs to be further clarified, and the composition and dose of the drug have not been standardized and quantified, this study still has exploration for scientific research and clinical practice. Therefore, this review mainly discusses the basic mechanisms and clinical applications of THSWD in the prevention and treatment of the myocardial injury caused by CHD-AP and myocardial infarction. The authors hope to provide valuable ideas and references for researchers and clinicians.
Three-Carbon Linked Dihydroartemisinin-Isatin Hybrids: Design, Synthesis and Their Antiproliferative Anticancer Activity
Authors: Dong Min , Zheng Guili , Gao Feng , Li Min , Zhong Chen
Published: January 2022

Fifteen dihydroartemisinin-isatin hybrids (5a-e and 6a-j) linked with three-carbon were designed, synthesized. The antiproliferative activity against lung cancer cell lines including drug-sensitive A549, doxorubicin-resistant A549 (A549/DOX) and cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was tested. The cytotocivity towards normal lung epithelial BEAS-2B cell line was also investigated. From the structure-activity relationship (SAR), it was found that hydrogen bond donors (especially hydroxime and thiosemicarbazide) at C-3 position and electron-withdrawing groups (fluoro and chloro) at C-5 position of isatin moiety were beneficial for the activity. A significant part of them (half maximal inhibitory concentration/IC50: 5.72–55.52 μM) demonstrated considerable antiproliferative activity, and the activity was superior to that of dihydroartemisinin (IC50: 69.42–88.03 μM) and artemisinin (IC50: >100 μM). In particular, two hybrids 6a, e (IC50: 5.72–9.84 μM) were not inferior to doxorubicin (IC50: 4.06 μM) and cisplatin (IC50: 9.38 μM) against drug-sensitive A549 cells and were more potent than doxorubicin (IC50: 54.32 and 15.10 μM) and cisplatin (IC50: 19.74 and 66.89 μM) against multidrug-resistant A549/DOX and A549/DDP lung cancer cell lines. In addition, hybrids 6a, e (IC50: >100 μM) showed no toxicity towards BEAS-2B cells, proving their excellent selectivity profile. Furthermore, hybrid 6a also possessed good stability in mouse and human microsomes, as well as excellent pharmacokinetic properties. Accordingly, hybrid 6a could serve as a promising anti-lung cancer chemotherapeutic candidate for further preclinical evaluations.
Application of Long Short-Term Memory (LSTM) on the Prediction of Rainfall-Runoff in Karst Area
Authors: Fang Longzhang , Shao Dongguo
Published: January 2022

In actual engineering fields, the bearing capacity of a rock is closely related to the pore water pressure in the rock. Studies have shown that the pore water in the rock has a great relationship with the change in runoff. Thus, it has crucial meaning to accurately evaluate and quantitate the property of the rainfall–runoff, and many traditional classic models are proposed to study the characteristic of rainfall–runoff. While considering the high uncertainty and randomness of the rainfall–runoff property, more and more artificial neural networks (ANN) are used for the rainfall–runoff modeling as well as other fields. Among them, the long short-term memory (LSTM), which can be trained for sequence generation by processing real data sequences one step at a time and has good prediction results in other engineering fields, is adopted in this study to investigate the changes of rainfall–runoff values and make a prediction. In order to ensure the accuracy of the trained model, the cross-validation method is used in this study. The training data set is divided into 12 parts. The monthly forecast results from 2014 to 2015 show that the model can well reflect the peaks and troughs. In a recent study, the relationship between the rainfall–runoff and discharge are commonly based on the current measured data, while the prediction results are adopted to analyze the relation of these parameters, and considering that the existing methods have fuzzy relationship between runoff and discharge, which leads to a high risk of forecasting and dispatching. A method of modeling analysis and parameter estimation of hydrological runoff and discharge relationship based on machine learning is designed. From the experimental results, the average risk of this method is 61.23%, which is 15.104% and 13.397% less than that of the other two existing methods, respectively. It proves that the method of hydrological runoff relationship modeling and parameter estimation integrated with machine learning has better practical application effect.
Generalized Su-Schrieffer-Heeger Model in One Dimensional Optomechanical Arrays
Authors: Xu Xun-Wei , Zhao Yan-Jun , Wang Hui , Chen Ai-Xi , Liu Yu-Xi
Published: January 2022

We propose an implementation of a generalized Su-Schrieffer-Heeger (SSH) model based on optomechanical arrays. The topological properties of the generalized SSH model depend on the effective optomechanical interactions which can be controlled by strong driving fields. Three phases including one trivial and two distinct topological phases are found in the generalized SSH model. The phase transition can be observed by turning the strengths and phases of the effective optomechanical interactions via adjusting the driving fields. Moreover, four types of edge states can be created in generalized SSH model of an open chain under single-particle excitation, and the dynamical behaviors of the excitation in the open chain are related to the topological properties under the periodic boundary condition. We show that the edge states can be pumped adiabatically along the optomechanical arrays by periodically modulating the amplitude and frequency of the driving fields, and the state pumping is robust against small disorders. The generalized SSH model based on the optomechanical arrays provides us a controllable platform to engineer topological phases for photons and phonons, which may have potential applications in controlling the transport of photons and phonons.
The Contributions of Extracellular Matrix and Sarcomere Properties to Passive Muscle Stiffness in Cerebral Palsy
Authors: Konno Ryan N. , Nigam Nilima , Wakeling James M. , Ross Stephanie A.
Published: January 2022

Cerebral palsy results from an upper motor neuron lesion and significantly affects skeletal muscle stiffness. The increased stiffness that occurs is partly a result of changes in the microstructural components of muscle. In particular, alterations in extracellular matrix, sarcomere length, fibre diameter, and fat content have been reported; however, experimental studies have shown wide variability in the degree of alteration. Many studies have reported changes in the extracellular matrix, while others have reported no differences. A consistent finding is increased sarcomere length in cerebral palsy affected muscle. Often many components are altered simultaneously, making it difficult to determine the individual effects on muscle stiffness. In this study, we use a three dimensional modelling approach to isolate individual effects of microstructural alterations typically occurring due to cerebral palsy on whole muscle behaviour; in particular, the effects of extracellular matrix volume fraction, stiffness, and sarcomere length. Causation between the changes to the microstructure and the overall muscle response is difficult to determine experimentally, since components of muscle cannot be manipulated individually; however, utilising a modelling approach allows greater control over each factor. We find that extracellular matrix volume fraction has the largest effect on whole muscle stiffness and mitigates effects from sarcomere length.
The Landscape of Aminoacyl-tRNA Synthetases Involved in Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Feng Yajuan , Tang Kang , Lai Qi , Liang Jingxian , Feng Min , Zhou Zhong-Wei , Cui Haissi , Du Xiangjun , Zhang Han , Sun Litao
Published: January 2022

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in translation by linking amino acids onto their cognate tRNAs during protein synthesis. During evolution, aaRSs develop numerous non-canonical functions that expand the roles of aaRSs in eukaryotic organisms. Although aaRSs have been implicated in viral infection, the function of aaRSs during infections with coronaviruses (CoVs) remains unclear. Here, we analyzed the data from transcriptomic and proteomic database on human cytoplasmic (cyto) and mitochondrial (mt) aaRSs across infections with three highly pathogenic human CoVs, with a particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found an overall downregulation of aaRSs at mRNA levels, while the protein levels of some mt-aaRSs and the phosphorylation of certain aaRSs were increased in response to SARS-CoV-2 infection. Strikingly, interaction network between SARS-CoV-2 and human aaRSs displayed a strong involvement of mt-aaRSs. Further co-immunoprecipitation (co-IP) experiments confirmed the physical interaction between SARS-CoV-2 M protein and TARS2. In addition, we identified the intermediate nodes and potential pathways involved in SARS-CoV-2 infection. This study provides an unbiased, overarching perspective on the correlation between aaRSs and SARS-CoV-2. More importantly, this work identifies TARS2, HARS2, and EARS2 as potential key factors involved in COVID-19.
Sex-Specific Computational Models of Kidney Function in Patients With Diabetes
Authors: Swapnasrita Sangita , Carlier Aurélie , Layton Anita T.
Published: January 2022

The kidney plays an essential role in homeostasis, accomplished through the regulation of pH, electrolytes and fluids, by the building blocks of the kidney, the nephrons. One of the important markers of the proper functioning of a kidney is the glomerular filtration rate. Diabetes is characterized by an enlargement of the glomerular and tubular size of the kidney, affecting the afferent and efferent arteriole resistance and hemodynamics, ultimately leading to chronic kidney disease. We postulate that the diabetes-induced changes in kidney may exhibit significant sex differences as the distribution of renal transporters along the nephron may be markedly different between women and men, as recently shown in rodents. The goals of this study are to (i) analyze how kidney function is altered in male and female patients with diabetes, and (ii) assess the renal effects, in women and men, of an anti-hyperglycemic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish these goals, we have developed computational models of kidney function, separate for male and female patients with diabetes. The simulation results indicate that diabetes enhances Na+ transport, especially along the proximal tubules and thick ascending limbs, to similar extents in male and female patients, which can be explained by the diabetes-induced increase in glomerular filtration rate. Additionally, we conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Model simulations also suggest that SGLT2 inhibition raises luminal [Cl–] at the macula densa, twice as much in males as in females, and could indicate activation of the tubuloglomerular feedback signal. By inducing osmotic diuresis in the proximal tubules, SGLT2 inhibition reduces paracellular transport, eventually leading to diuresis and natriuresis. Those effects on urinary excretion are blunted in women, in part due to their higher distal transport capacity.
Comparative Elucidation of Age, Diameter, and “Pockmarks” in Roots of Paeonia lactiflora Pall. (Shaoyao) by Qualitative and Quantitative Methods
Authors: Zheng Xiaowen , Yin Minzhen , Chu Shanshan , Yang Mei , Yang Zhengyang , Zhu Yuejian , Huang Luqi , Peng Huasheng
Published: January 2022

Paeonia lactiflora Pall. is a world-famous ornamental plant, whose roots have been used as an important traditional Chinese medicine, Shaoyao, to treat diseases for more than 1,000 years. Because of the excellent curative effect of Shaoyao, its quality has attracted wide attention, however, there is a lack of comprehensive research on the different influencing factors of quality of Shaoyao. In this study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and high-performance liquid chromatography with diode-array detection (HPLC-DAD) were utilized to systematically analyze the Shaoyao of different ages, diameters and roots with “pockmarks.” 60 metabolites were detected and identified from Shaoyao using the UPLC-Q/TOF-MS, of which 20 potential quality markers of dissected roots with and without “pockmarks” were selected for the first time using the orthogonal partial least squares discriminant analysis (OPLS-DA) and the variable importance for projection (VIP) plot. Then, a selective and accurate HPLC-DAD quantitative assay has been developed for the simultaneous determination of 11 bioactive components in Shaoyao. The results showed that the total content of five monoterpene glycosides including oxypaeoniflorin, albiflorin, paeoniflorin, lactiflorin, and benzoylpaeoniflorin and six phenols including gallic acid, catechin, methyl gallate, ethyl gallate, apiopaeonoside and benzoic acid in the 3-year-old Shaoyao was higher than that of 4-year-old and 5-year-old Shaoyao. In Shaoyao of the same age, the total content of five monoterpene glycosides and six phenols decreased with an increase in diameter. In addition, regardless of whether it is a whole or a divided root, the contents of five monoterpene glycosides and six phenols in Shaoyao with “pockmarks” were higher than those of Shaoyao without “pockmarks.” In summary, this work has explored several factors that might affect the quality of Shaoyao, and provide a guide for more comprehensive quality evaluation in its further production, processing, and rational utilization.
Image-Based Automated Recognition of 31 Poaceae Species: The Most Relevant Perspectives
Authors: Rzanny Michael , Wittich Hans Christian , Mäder Patrick , Deggelmann Alice , Boho David , Wäldchen Jana
Published: January 2022

Poaceae represent one of the largest plant families in the world. Many species are of great economic importance as food and forage plants while others represent important weeds in agriculture. Although a large number of studies currently address the question of how plants can be best recognized on images, there is a lack of studies evaluating specific approaches for uniform species groups considered difficult to identify because they lack obvious visual characteristics. Poaceae represent an example of such a species group, especially when they are non-flowering. Here we present the results from an experiment to automatically identify Poaceae species based on images depicting six well-defined perspectives. One perspective shows the inflorescence while the others show vegetative parts of the plant such as the collar region with the ligule, adaxial and abaxial side of the leaf and culm nodes. For each species we collected 80 observations, each representing a series of six images taken with a smartphone camera. We extract feature representations from the images using five different convolutional neural networks (CNN) trained on objects from different domains and classify them using four state-of-the art classification algorithms. We combine these perspectives via score level fusion. In order to evaluate the potential of identifying non-flowering Poaceae we separately compared perspective combinations either comprising inflorescences or not. We find that for a fusion of all six perspectives, using the best combination of feature extraction CNN and classifier, an accuracy of 96.1% can be achieved. Without the inflorescence, the overall accuracy is still as high as 90.3%. In all but one case the perspective conveying the most information about the species (excluding inflorescence) is the ligule in frontal view. Our results show that even species considered very difficult to identify can achieve high accuracies in automatic identification as long as images depicting suitable perspectives are available. We suggest that our approach could be transferred to other difficult-to-distinguish species groups in order to identify the most relevant perspectives.
Industry-Based Misconceptions Regarding Cross-Pollination of Cannabis spp.
Authors: Olejar Kenneth J. , Park Sang-Hyuck
Published: January 2022

Cross-pollination of commercial crops has been an ongoing issue in many species. Cannabis spp. encompasses the classifications of marijuana [high in Δ9-tetrahydrocannabinol (THC)] and hemp (below 0.3% THC). As such, cannabis is the most recent crop facing the dilemma of cross-pollination and is leading to litigation. These litigations are driven by the large misunderstanding of the impacts of cross-pollination within the cannabis industry. The misconception is that if hemp is cross-pollinated by high THC cannabis, the hemp will become “hot” (high in THC) thereby rendering the crop illegal under the 2018 Farm Bill. However, there are many factors that contribute to the amount of THC a plant may produce. This article examines and refutes the misconception of cross-pollination increasing THC levels by highlighting several methods of how THC may become high in a given hemp crop.
Parental Acculturation and Children’s Bilingual Abilities: A Study With Chinese American and Mexican American Preschool DLLs
Authors: Uchikoshi Yuuko , Lindblad Mayu , Plascencia Cecilia , Tran Helen , Yu Hallie , Bautista Krystal Jane , Zhou Qing
Published: January 2022

Previous studies support the link of parental acculturation to their children’s academic achievement, identity, and family relations. Prior research also suggests that parental language proficiency is associated with children’s vocabulary knowledge. However, few studies have examined the links of parental acculturation to young children’s oral language abilities. As preschool oral language skills have been shown to predict future academic achievement, it is critical to understand the relations between parental acculturation and bilingual abilities with young immigrant children. Furthermore, few studies have examined the links between parental acculturation and children’s bilingual ability among different immigrant groups who live in the same areas to understand possible similarities and differences. To address these gaps, this study examines these relations in two of the largest and fastest-growing immigrant populations in the United States, Chinese American and Mexican American families. A total of 119 dual language learners (DLLs; 64 Chinese Americans and 55 Mexican Americans) enrolled in Head Start programs in Northern California were recruited. DLLs were assessed on oral language measures in both their heritage language (HL) and English. Parental interviews were conducted to obtain parental acculturation and language proficiency. Results showed no significant group differences between Chinese American and Mexican American parents on the majority of their acculturation dimensions. Furthermore, there were no significant group differences in the bilingual abilities between Chinese American and Mexican American DLLs. Cluster analysis identified four groups of DLLs based on their bilingual ability: high language ability in both English and HL, low language ability in both, English-dominant, and HL-dominant. Results suggest that parental acculturation levels are more similar than different among the four groups. On average, parents in all four groups had stronger ties to their heritage culture and HL than to the American culture. Results also showed links between parental cultural identities and children’s language dominance. Parents of English-dominant children had significantly higher levels of American identity than the parents of children with high ability in both languages. Implications are discussed.
Validation and Psychometric Testing of the Chinese Version of the Mental Health Literacy Scale Among Nurses
Authors: Wang Anni , Jia Shoumei , Shi Zhongying , Sun Xiaomin , Zhu Yuan , Shen Miaoli
Published: January 2022

The Mental Health Literacy Scale (MHLS) is the most widely used and strong theory-based measurement tool to gain an understanding of mental health knowledge and ability. This study aimed to test the psychometric properties of the Chinese version of the Mental Health Literacy Scale (MHLS-C) and to document the norm and its influential factors of mental health literacy among nurses. The MHLS was translated following Brislin’s translation model and tested with a sample of 872 clinical registered nurses. The Jefferson Scale of Empathy-Health Professionals (JSE-HP), Patient Health Questionnaire-2 (PHQ-2), and Generalized Anxiety Disorder-2 (GAD-2) were administered to assess convergent validity. The minimum average partial test, parallel analysis and confirmatory factor analysis supported 4 first-order 2 second-order structure. The 4 factors were named “knowledge of mental disorder,” “ability to seek information and help,” “recognition of mental disorder,” and “acceptance of patients with mental illness,” with factor 1-3 were summarized into MHLS-Core (Core literacy subscale) and factor 4 as MHLS-SA (Social acceptance subscale). The MHLS-C was moderately negatively correlated with the PHQ-2 and GAD-2 (-0.111, -0.081) and highly positively correlated with JSE-HP (0.492). The Cronbach’s α was 0.85 for the overall scale and 0.89 and 0.93 for two subscales. The test-retest reliability was good, with intraclass correlation coefficients (ICCs) of 0.80 for the whole scale, and 0.79 and 0.94 for two subscales. As an approximately normal distribution, the 50th percentile for the MHLS-C was 99, with 50th percentiles of 74 and 20 for MHLS-Core and MHLS-SA. Higher position, higher professional credentials, higher hospital hierarchy, other specialist hospital, psychiatric hospital and unmarried status were positive predictors. The 29-item MHLS-C, with two subscales of MHLS-Core and MHLE-SA, is a stable and validated tool to measure mental health literacy. MHLS-Core could be used independently to measure the core content of mental health literacy. It may be applicable for Chinese health professionals, but need further validation among the general public. MHL curriculum and a targeted culturally appropriate program for acceptance for health professionals, especially for those in general hospitals and with less working tenure, may be recommended.