bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk prediction model based on blood biomarkers for predicting moderate to severe endoscopic activity in patients with ulcerative colitis
Authors: Li Xiaojuan , Tang Zihui , Liu Yanbing , Zhu Xinyan , Liu Fei
Published: February 2023

Object

We explored developing an internal validation model to predict the moderate to severe endoscopic activity of ulcerative colitis (UC) patients based on non-invasive or minimally-invasive parameters.

Methods

Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo endoscopic subscore were performed for UC patients who met the criteria from January 2017 to August 2021 through the electronic database of our center. Logistic regression and a least absolute shrinkage and selection operator (Lasso) regression model were performed to screen the risk factors of moderate to severe UC activity. The nomogram was established subsequently. Discrimination of the model was evaluated using the concordance index (c-index), and the calibration plot and 1,000 Bootstrap were used to evaluate the model’s performance and conduct internal validation.

Results

Sixty-five UC patients were included in this study. According to UCEIS criteria,45 patients were moderate to severe endoscopic activity. 26 potential predictors of UC were analyzed by logistic and Lasso regression showed that vitamin D (Vit D), albumin (ALB), prealbumin (PAB), and fibrinogen (Fbg) were the best predictors of moderate to severe endoscopic activity of UC. We used these 4 variables to develop a dynamic nomogram prediction model. The c-index was 0.860, which means good discrimination. The calibration plot and Bootstrap analysis showed that the prediction model accurately distinguished the moderate to severe endoscopic activity in UC patients. The prediction model was verified using a cohort of UC patients with moderate to severe activity defined by the Mayo endoscopic subscore, and it was found that the model still had good discrimination and calibration (c-index = 0.891).

Conclusion

The model containing Vit D, ALB, PAB, and Fbg was a good tool for evaluating UC activity. The model is simple, accessible, and user-friendly, which has broad application prospects in clinical practice.
Correlation between human papillomavirus viral load and cervical lesions classification: A review of current research
Authors: Zhou Yilu , Shi Xiaoyu , Liu Jiaxin , Zhang Lina
Published: February 2023

Cervical cancer is the fourth largest malignant tumor among women in the world. Human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer. Active papillomavirus infection occurs when the infected basal cells replicate and fill a certain area. Persistent HPV infection can lead to squamous intraepithelial lesions, which are divided into CIN1, CIN2, and CIN3 according to how much epithelium is impacted. Different types of HPV have different possibilities of causing cervical cancer, and high-risk HPV is the main cause of cervical cancer. Research showed that viral load may be an indicator of the progression of cervical precancerous lesions, but this association does not seem to be universal. This article aims to summarize different genotypes, multiple infections, especially viral load, in cervical precancerous lesions, to guide early intervention.
Shifts in composition and function of bacterial communities reveal the effect of small barriers on nitrous oxide and methane accumulation in fragmented rivers
Authors: Xing Chong-Yang , Li Hang , Li Qi , Lu Lun-Hui , Li Zhe
Published: February 2023

Rivers are often blocked by barriers to form different habitats, but it is not clear whether this change will affect the accumulation of N2O and CH4 in rivers. Here, low barriers (less than 2 m, LB) increased N2O concentration by 1.13 times and CH4 decreased by 0.118 times, while high barriers (higher than 2 m, less than 5 m high, HB) increased N2O concentration by 1.19 times and CH4 by 2.76 times. Co-occurrence network analysis indicated LB and HB can promote the enrichment of Cyanobium and Chloroflexi, further limiting complete denitrification and increasing N2O accumulation. The LB promotes methanotrophs (Methylocystis, Methylophilus, and Methylotenera) to compete with denitrifiers (Pseudomonas) in water, and reduce CH4 accumulation. While the HB can promote the methanotrophs to compete with nitrifiers (Nitrosospira) in sediment, thus reducing the consumption of CH4. LB and HB reduce river velocity, increase water depth, and reduce dissolved oxygen (DO), leading to enrichment of nirS-type denitrifiers and the increase of N2O concentration in water. Moreover, the HB reduces DO concentration and pmoA gene abundance in water, which can increase the accumulation of CH4. In light of the changes in the microbial community and variation in N2O and CH4 accumulation, the impact of fragmented rivers on global greenhouse gas emissions merits further study.
Disease-gene prediction based on preserving structure network embedding
Authors: Ma Jinlong , Qin Tian , Xiang Ju
Published: February 2023

Many diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are caused by abnormalities or mutations of related genes. Many computational methods based on the network relationship between diseases and genes have been proposed to predict potential pathogenic genes. However, how to effectively mine the disease-gene relationship network to predict disease genes better is still an open problem. In this paper, a disease-gene-prediction method based on preserving structure network embedding (PSNE) is introduced. In order to predict pathogenic genes more effectively, a heterogeneous network with multiple types of bio-entities was constructed by integrating disease-gene associations, human protein network, and disease-disease associations. Furthermore, the low-dimension features of nodes extracted from the network were used to reconstruct a new disease-gene heterogeneous network. Compared with other advanced methods, the performance of PSNE has been confirmed more effective in disease-gene prediction. Finally, we applied the PSNE method to predict potential pathogenic genes for age-associated diseases such as AD and PD. We verified the effectiveness of these predicted potential genes by literature verification. Overall, this work provides an effective method for disease-gene prediction, and a series of high-confidence potential pathogenic genes of AD and PD which may be helpful for the experimental discovery of disease genes.
A deep learning approach to predict collateral flow in stroke patients using radiomic features from perfusion images
Authors: Tetteh Giles , Navarro Fernando , Meier Raphael , Kaesmacher Johannes , Paetzold Johannes C. , Kirschke Jan S. , Zimmer Claus , Wiest Roland , Menze Bjoern H.
Published: February 2023

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for bias and inconsistency in the final grade assigned to a patient depending on the experience level of the clinician. We present a multi-stage deep learning approach to predict collateral flow grading in stroke patients based on radiomic features extracted from MR perfusion data. First, we formulate a region of interest detection task as a reinforcement learning problem and train a deep learning network to automatically detect the occluded region within the 3D MR perfusion volumes. Second, we extract radiomic features from the obtained region of interest through local image descriptors and denoising auto-encoders. Finally, we apply a convolutional neural network and other machine learning classifiers to the extracted radiomic features to automatically predict the collateral flow grading of the given patient volume as one of three severity classes - no flow (0), moderate flow (1), and good flow (2). Results from our experiments show an overall accuracy of 72% in the three-class prediction task. With an inter-observer agreement of 16% and a maximum intra-observer agreement of 74% in a similar experiment, our automated deep learning approach demonstrates a performance comparable to expert grading, is faster than visual inspection, and eliminates the problem of grading bias.
An overview of clinical cerebral microdialysis in acute brain injury
Authors: Stovell Matthew G. , Helmy Adel , Thelin Eric P. , Jalloh Ibrahim , Hutchinson Peter J. , Carpenter Keri L. H.
Published: February 2023

Cerebral microdialysis may be used in patients with severe brain injury to monitor their cerebral physiology. In this article we provide a concise synopsis with illustrations and original images of catheter types, their structure, and how they function. Where and how catheters are inserted, their identification on imaging modalities (CT and MRI), together with the roles of glucose, lactate/pyruvate ratio, glutamate, glycerol and urea are summarized in acute brain injury. The research applications of microdialysis including pharmacokinetic studies, retromicrodialysis, and its use as a biomarker for efficacy of potential therapies are outlined. Finally, we explore limitations and pitfalls of the technique, as well as potential improvements and future work that is needed to progress and expand the use of this technology.
Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers
Authors: Martín-González Candelaria , Godoy-Reyes Ana María , Abreu-González Pedro , Fernández-Rodríguez Camino María , Martín-Ponce Esther , Sánchez-Pérez María José , Alvisa-Negrín Julio César , Rodríguez-Gaspar Melchor , González-Reimers Emilio
Published: February 2023

Objective

Heavy alcohol consumption causes several organic complications, including vessel wall calcification. Vascular damage may be involved in the development of brain atrophy and cognitive impairment. Recently, sclerostin (whose levels may be altered in alcoholics) has emerged as a major vascular risk factor. The objective of the present study is to analyze the prevalence of vascular calcifications in alcoholics, and the relationships of these lesions with brain atrophy, as well as the role of sclerostin on these alterations.

Patients and methods

A total of 299 heavy drinkers and 32 controls were included. Patients underwent cranial computed tomography, and several indices related to brain atrophy were calculated. In addition, patients and controls underwent plain radiography and were evaluated for the presence or absence of vascular calcium deposits, cardiovascular risk factors, liver function, alcohol intake, serum sclerostin, and routine laboratory variables.

Results

A total of 145 (48.47%) patients showed vascular calcium deposits, a proportion significantly higher than that observed in controls (χ2 = 16.31; p < 0.001). Vascular calcium deposits were associated with age (t = 6.57; p < 0.001), hypertension (t = 5.49; p < 0.001), daily ethanol ingestion (Z = 2.18; p = 0.029), duration of alcohol consumption (Z = 3.03; p = 0.002), obesity (χ2 = 4.65; p = 0.031), total cholesterol (Z = 2.04; p = 0.041), triglycerides (Z = 2.05; p = 0.04), and sclerostin levels (Z = 2.64; p = 0.008). Calcium deposits were significantly related to Bifrontal index (Z = 2.20; p = 0.028) and Evans index (Z = 2.25; p = 0.025). Serum sclerostin levels were related to subcortical brain atrophy, assessed by cella media index (Z = 2.43; p = 0.015) and Huckmann index (ρ = 0.204; p = 0.024). Logistic regression analyses disclosed that sclerostin was the only variable independently related to brain atrophy assessed by altered cella media index. Sclerostin was also related to the presence of vascular calcifications, although this relationship was displaced by age if this variable was also included.

Conclusion

Prevalence of vascular calcification in alcoholics is very high. Vascular calcium deposits are related to brain atrophy. Serum sclerostin is strongly related to brain shrinkage and also shows a significant relationship with vascular calcifications, only displaced by advanced age.
Patterns of developmental regression and associated clinical characteristics in SLC6A1-related disorder
Authors: Kalvakuntla Sanjana , Lee MinJae , Chung Wendy K. , Demarest Scott , Freed Amber , Horning Kyle J. , Bichell Terry Jo , Iannaccone Susan T. , Goodspeed Kimberly
Published: February 2023

Introduction

SLC6A1-related disorder is a genetic neurodevelopmental disorder that is caused by loss of function variants in the SLC6A1 gene. Solute Carrier Family 6 Member 1 (SLC6A1) gene encodes for gamma-aminobutyric acid (GABA) transporter type 1 (GAT1), which is responsible for reuptake of GABA from the synaptic cleft. Tight regulation of GABA levels plays an important role in brain development by balancing inhibitory and excitatory neuronal signaling. Consequently, individuals with SLC6A1-related disorder can have manifestations such as developmental delay, epilepsy, autism spectrum disorder, and a subset have developmental regression.

Methods

In this study, we identified patterns of developmental regression among a cohort of 24 patients with SLC6A1-related disorder and assessed for clinical characteristics associated with regression. We reviewed medical records of patients with SLC6A1-related disorder and divided subjects into two groups: 1) regression group and 2) control group. We described the patterns of developmental regression including whether there was a trigger prior to the regression, multiple episodes of regression, and whether or not skills were recovered. We assessed the relationship of clinical characteristics among the regression and control groups including demographic factors, seizures, developmental milestone acquisition, gastrointestinal problems, sleep problems, autism spectrum disorder, and behavioral problems.

Results

Individuals with developmental regression had a loss of skills that were previously mastered in developmental domains including speech and language, motor, social, and adaptive skills. The mean age at regression was 2.7 years and most subjects had regression of language or motor skills triggered by seizures, infection, or spontaneously. Although there was no significant difference in clinical characteristics between the two groups, there was a higher prevalence of autism and severe language impairment in the regression group.

Discussion

Future studies of a larger cohort of patients are required to make definitive conclusions. Developmental regression is often a sign of severe neurodevelopmental disability in genetic syndromes, but it is poorly understood in SLC6A1-related disorder. Understanding the patterns of developmental regression and the associated clinical characteristics in this rare disorder will be important to medical management, prognostication, and could impact the design of future clinical trials.
Caught off guard and beaten: The Ukraine war and food security in the Middle East
Authors: Al-Saidi Mohammad
Published: February 2023

The Ukraine war has led to a severe global food crisis due to complex supply disruptions and price increases of agricultural inputs. Countries of the Middle East have been directly affected because of their high dependence on food imports from Russia and Ukraine. Furthermore, this food crisis comes at times of high baseline vulnerability due to the compound impacts of COVID-19, repeated food shocks, and weakened states due to political-economic difficulties. This paper provides a detailed analysis of the food-related vulnerability of Middle Eastern countries in the wake of the Ukraine war. It contextualizes the varying impacts of this crisis in the region, and highlights country-level response strategies. The analysis shows a concerning and deepened crisis in the case of highly exposed and politically fragile countries with weakened food sectors; e.g., Lebanon, Sudan, and Yemen. Political-economic instabilities, limited domestic agriculture, and the lack of reliable grain reserves have aggravated the current food crisis in some countries. At the same time, indigenous short-term responses related to regional aid and cooperation have emerged, particularly in the Gulf countries, which have witnessed soaring revenues from higher energy prices. Alongside more regional frameworks for collaboration on food security, future action to mitigate such food crises should include the strengthening of local sustainable agriculture, storage capacities, and grain procurement strategies from international suppliers.
The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation
Authors: Zhang Qi , Wang Changli , Li Ruijia , Liu Jingjing , Wang Jiyu , Wang Tianyi , Wang Bing
Published: February 2023

Background

B-cell receptor–associated protein 31 (BAP31) has been recognized as a tumor-associated protein and has largely been shown to promote metastasis in a variety of cancers. Cancer metastasis arises through multistep pathways, and the induction of angiogenesis is shown to be a rate-limiting step in the process of tumor metastasis.

Methods and results

This study explored the effect of BAP31 on colorectal cancer (CRC) angiogenesis by regulating the tumor microenvironment. First, exosomes from BAP31-regulated CRCs affected the transition of normal fibroblasts to proangiogenic cancer-associated fibroblasts (CAFs) in vivo and in vitro. Next, microRNA sequencing was performed to analyze the microRNA expression profile of exosomes secreted from BAP31- overexpressing CRCs. The results indicated that the expression of BAP31 in CRCs significantly altered the levels of exosomal microRNAs, such as miR-181a- 5p. Meanwhile, an in vitro tube formation assay showed that fibroblasts with high levels of miR-181a-5p significantly promoted endothelial cell angiogenesis. Critically, we first identified that miR-181a-5p directly targeted the 3'-untranslated region (3′UTR) of reversion-inducing cysteine-rich protein with kazal motifs (RECK) using the dual-luciferase activity assay, which drove fibroblast transformation into proangiogenic CAFs by upregulating matrix metalloproteinase-9 (MMP-9) and phosphorylation of mothers against decapentaplegic homolog 2/Mothers against decapentaplegic homolog 3 (Smad2/3).

Conclusion

Exosomes from BAP31-overexpressing/BAP31-knockdown CRCs are found to manipulate the transition of fibroblasts into proangiogenic CAFs by the miR-181a-5p/RECK axis.
Haploidentical hematopoietic stem cell transplantation as individual treatment option in pediatric patients with very high-risk sarcomas
Authors: Eichholz Thomas , Döring Michaela , Giardino Stefano , Gruhn Bernd , Seitz Christian , Flaadt Tim , Schwinger Wolfgang , Ebinger Martin , Holzer Ursula , Mezger Markus , Teltschik Heiko-Manuel , Sparber-Sauer Monika , Koscielniak Ewa , Abele Michael , Handgretinger Rupert , Lang Peter
Published: February 2023

Background

Prognosis of children with primary disseminated or metastatic relapsed sarcomas remains dismal despite intensification of conventional therapies including high-dose chemotherapy. Since haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of hematological malignancies by mediating a graft versus leukemia effect, we evaluated this approach in pediatric sarcomas as well.

Methods

Patients with bone Ewing sarcoma or soft tissue sarcoma who received haplo-HSCT as part of clinical trials using CD3+ or TCRα/β+ and CD19+ depletion respectively were evaluated regarding feasibility of treatment and survival.

Results

We identified 15 patients with primary disseminated disease and 14 with metastatic relapse who were transplanted from a haploidentical donor to improve prognosis. Three-year event-free survival (EFS) was 18,1% and predominantly determined by disease relapse. Survival depended on response to pre-transplant therapy (3y-EFS of patients in complete or very good partial response: 36,4%). However, no patient with metastatic relapse could be rescued.

Conclusion

Haplo-HSCT for consolidation after conventional therapy seems to be of interest for some, but not for the majority of patients with high-risk pediatric sarcomas. Evaluation of its future use as basis for subsequent humoral or cellular immunotherapies is necessary.
Primary retroperitoneal nodal endometrioid carcinoma associated with Lynch syndrome: A case report
Authors: Fischerova Daniela , Scovazzi Umberto , Sousa Natacha , Hovhannisyan Tatevik , Burgetova Andrea , Dundr Pavel , Němejcová Kristýna , Bennett Rosalie , Vočka Michal , Frühauf Filip , Kocian Roman , Indrielle-Kelly Tereza , Cibula David
Published: February 2023

We report a rare case of primary nodal, poorly differentiated endometrioid carcinoma associated with Lynch syndrome. A 29-year-old female patient was referred by her general gynecologist for further imaging with suspected right-sided ovarian endometrioid cyst. Ultrasound examination by an expert gynecological sonographer at tertiary center revealed unremarkable findings in the abdomen and pelvis apart from three iliac lymph nodes showing signs of malignant infiltration in the right obturator fossa and two lesions in the 4b segment of the liver. During the same appointment ultrasound guided tru-cut biopsy was performed to differentiate hematological malignancy from carcinomatous lymph node infiltration. Based on the histological findings of endometrioid carcinoma from lymph node biopsy, primary debulking surgery including hysterectomy and salpingo-oophorectomy was performed. Endometrioid carcinoma was confirmed only in the three lymph nodes suspected on the expert scan and primary nodal origin of endometroid carcinoma developed from ectopic Müllerian tissue was considered. As a part of the pathological examination immunohistochemistry analysis for mismatch repair protein (MMR) expression was done. The findings of deficient mismatch repair proteins (dMMR) led to additional genetic testing, which revealed deletion of the entire EPCAM gene up to exon 1-8 of the MSH2 gene. This was unexpected considering her insignificant family history of cancer. We discuss the diagnostic work-up for patients presenting with metastatic lymph node infiltration by cancer of unknown primary and possible reasons for malignant lymph node transformation associated with Lynch syndrome.
Efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: A retrospective study
Authors: Xu Yuyan , Zou Haizhou , Shao Zhenyong , Zhang Xuebang , Ren XiaoLin , He Huijuan , Zhang Dahai , Du Dexi , Zou Changlin
Published: February 2023

Background

This study aims to compare the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) with different radiotherapy doses (45Gy and 50.4Gy) in patients with locally advanced rectal cancer (LARC).

Methods

Herein, 120 patients with LARC were retrospectively enrolled between January 2016 and June 2021. All patients underwent two courses of induction chemotherapy (XELOX), chemoradiotherapy, and total mesorectum excision (TME). A total of 72 patients received a radiotherapy dose of 50.4 Gy, while 48 patients received a dose of 45 Gy. Surgery was then performed within 5-12 weeks following nCRT.

Results

There was no statistically significant difference between the baseline characteristics of the two groups. The rate of good pathological response in the 50.4Gy group was 59.72% (43/72), while in the 45Gy group achieved 64.58% (31/48) (P>0.05). The disease control rate (DCR) in the 50.4Gy group was 88.89% (64/72), compared to 89.58% (43/48) in the 45Gy group (P>0.05). The incidence of adverse reactions for radioactive proctitis, myelosuppression, and intestinal obstruction or perforation differed significantly between the two groups (P<0.05). The anal retention rate in the 50.4Gy group was significantly higher in contrast to the 45Gy group (P<0.05).

Conclusions

Patients receiving a radiotherapy dose of 50.4Gy have a better anal retention rate but also a higher incidence of adverse events such as radioactive proctitis, myelosuppression, and intestinal obstruction or perforation, and a comparable prognosis to patients treated with a radiotherapy dose of 45Gy.
The road to breast cancer screening with diffusion MRI
Authors: Iima Mami , Le Bihan Denis
Published: February 2023

Breast cancer is the leading cause of cancer in women with a huge medical, social and economic impact. Mammography (MMG) has been the gold standard method until now because it is relatively inexpensive and widely available. However, MMG suffers from certain limitations, such as exposure to X-rays and difficulty of interpretation in dense breasts. Among other imaging methods, MRI has clearly the highest sensitivity and specificity, and breast MRI is the gold standard for the investigation and management of suspicious lesions revealed by MMG. Despite this performance, MRI, which does not rely on X-rays, is not used for screening except for a well-defined category of women at risk, because of its high cost and limited availability. In addition, the standard approach to breast MRI relies on Dynamic Contrast Enhanced (DCE) MRI with the injection of Gadolinium based contrast agents (GBCA), which have their own contraindications and can lead to deposit of gadolinium in tissues, including the brain, when examinations are repeated. On the other hand, diffusion MRI of breast, which provides information on tissue microstructure and tumor perfusion without the use of contrast agents, has been shown to offer higher specificity than DCE MRI with similar sensitivity, superior to MMG. Diffusion MRI thus appears to be a promising alternative approach to breast cancer screening, with the primary goal of eliminating with a very high probability the existence of a life-threatening lesion. To achieve this goal, it is first necessary to standardize the protocols for acquisition and analysis of diffusion MRI data, which have been found to vary largely in the literature. Second, the accessibility and cost-effectiveness of MRI examinations must be significantly improved, which may become possible with the development of dedicated low-field MRI units for breast cancer screening. In this article, we will first review the principles and current status of diffusion MRI, comparing its clinical performance with MMG and DCE MRI. We will then look at how breast diffusion MRI could be implemented and standardized to optimize accuracy of results. Finally, we will discuss how a dedicated, low-cost prototype of breast MRI system could be implemented and introduced to the healthcare market.
Capsulotomy opening diameter outcomes in aphakic eyes after primary congenital cataract removal and its association
Authors: Zhao Qihui , Chang Pingjun , Zhao Yinying , Wang Dandan , Zhao Yune
Published: February 2023

Aim

To observe the change of capsulotomy opening diameter (COD) in aphakic eyes after primary congenital cataract removal and investigate its influencing factors.

Methods

Ocular parameters, including corneal diameter (CD), axial length (AL), anterior and posterior COD (ACOD, PCOD), and age at surgery were recorded at primary congenital cataract removal and secondary intraocular lens implantation. The concentrations of 15 kinds of cytokines in aqueous humor samples collected at the primary surgery were detected. The change (Δ) of COD between two surgeries were described, and its association was analyzed.

Results

Fifty eyes from 33 patients with congenital cataract who underwent primary and secondary surgery were enrolled. The changes in ACOD and PCOD were not statistically significant on the whole. ΔACOD was positively correlated with ΔCD and the concentrations of PDGF-AA, VEGF and TGF-β1. The concentration of FGF-2 and the interval between two surgeries showed negative correlations with ΔACOD and ΔPCOD.

Conclusion

COD in aphakic eyes kept changing after primary surgery. The positive correlation between ΔACOD and ΔCD manifested the enlargement of ACOD was influenced by lateral eye growth. Meanwhile, ΔACOD was also associated with cytokines, indicating postoperative inflammation promoted the ACOD constriction.
The pharmacogenetics of CYP2D6 and CYP2C19 in a case series of antidepressant responses
Authors: Kee Ping Siu , Maggo Simran D. S. , Kennedy Martin A. , Chin Paul K. L.
Published: February 2023

Pharmacogenetics has potential for optimizing use of psychotropics. CYP2D6 and CYP2C19 are two clinically relevant pharmacogenes in the prescribing of antidepressants. Using cases recruited from the Understanding Drug Reactions Using Genomic Sequencing (UDRUGS) study, we aimed to evaluate the clinical utility of genotyping CYP2D6 and CYP2C19 in antidepressant response. Genomic and clinical data for patients who were prescribed antidepressants for mental health disorders, and experienced adverse reactions (ADRs) or ineffectiveness, were extracted for analysis. Genotype-inferred phenotyping of CYP2D6 and CYP2C19 was carried out as per Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A total of 52 patients, predominantly New Zealand Europeans (85%) with a median age (range) of 36 years (15–73), were eligible for analysis. Thirty-one (60%) reported ADRs, 11 (21%) ineffectiveness, and 10 (19%) reported both. There were 19 CYP2C19 NMs, 15 IMs, 16 RMs, one PM and one UM. For CYP2D6, there were 22 NMs, 22 IMs, four PMs, three UMs, and one indeterminate. CPIC assigned a level to each gene-drug pair based on curated genotype-to-phenotype evidence. We analyzed a subgroup of 45 cases, inclusive of response type (ADRs/ineffectiveness). Seventy-nine (N = 37 for CYP2D6, N = 42 for CYP2C19) gene-drug/antidepressant-response pairs with CPIC evidence levels of A, A/B, or B were identified. Pairs were assigned as ‘actionable’ if the CYP phenotypes potentially contributed to the observed response. We observed actionability in 41% (15/37) of CYP2D6-antidepressant-response pairs and 36% (15/42) of CYP2C19-antidepressant-response pairs. In this cohort, CYP2D6 and CYP2C19 genotypes were actionable for a total of 38% pairs, consisting of 48% in relation to ADRs and 21% in relation to drug ineffectiveness.
Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease
Authors: Wang Jie , Liu Yong-Mei , Hu Jun , Chen Cong
Published: February 2023

Atherosclerosis (AS) is the pathology of atherosclerotic cardiovascular diseases (ASCVD), characterized by persistent chronic inflammation in the vessel wall, in which monocytes/macrophages play a key role. It has been reported that innate immune system cells can assume a persistent proinflammatory state after short stimulation with endogenous atherogenic stimuli. The pathogenesis of AS can be influenced by this persistent hyperactivation of the innate immune system, which is termed trained immunity. Trained immunity has also been implicated as a key pathological mechanism, leading to persistent chronic inflammation in AS. Trained immunity is mediated via epigenetic and metabolic reprogramming and occurs in mature innate immune cells and their bone marrow progenitors. Natural products are promising candidates for novel pharmacological agents that can be used to prevent or treat cardiovascular diseases (CVD). A variety of natural products and agents exhibiting antiatherosclerotic abilities have been reported to potentially interfere with the pharmacological targets of trained immunity. This review describes in as much detail as possible the mechanisms involved in trained immunity and how phytochemicals of this process inhibit AS by affecting trained monocytes/macrophages.
Vitamin D supplementation is effective for olanzapine-induced dyslipidemia
Authors: Zhou Zijian , Nagashima Takuya , Toda Chihiro , Kobayashi Mone , Suzuki Takahide , Nagayasu Kazuki , Shirakawa Hisashi , Asai Satoshi , Kaneko Shuji
Published: February 2023

Olanzapine is an atypical antipsychotic drug that is clinically applied in patients with schizophrenia. It increases the risk of dyslipidemia, a disturbance of lipid metabolic homeostasis, usually characterized by increased low-density lipoprotein (LDL) cholesterol and triglycerides, and accompanied by decreased high-density lipoprotein (HDL) in the serum. In this study, analyzing the FDA Adverse Event Reporting System, JMDC insurance claims, and electronic medical records from Nihon University School of Medicine revealed that a co-treated drug, vitamin D, can reduce the incidence of olanzapine-induced dyslipidemia. In the following experimental validations of this hypothesis, short-term oral olanzapine administration in mice caused a simultaneous increase and decrease in the levels of LDL and HDL cholesterol, respectively, while the triglyceride level remained unaffected. Cholecalciferol supplementation attenuated these deteriorations in blood lipid profiles. RNA-seq analysis was conducted on three cell types that are closely related to maintaining cholesterol metabolic balance (hepatocytes, adipocytes, and C2C12) to verify the direct effects of olanzapine and the functional metabolites of cholecalciferol (calcifediol and calcitriol). Consequently, the expression of cholesterol-biosynthesis-related genes was reduced in calcifediol- and calcitriol-treated C2C12 cells, which was likely to be mediated by activating the vitamin D receptor that subsequently inhibited the cholesterol biosynthesis process via insulin-induced gene 2 regulation. This clinical big-data-based drug repurposing approach is effective in finding a novel treatment with high clinical predictability and a well-defined molecular mechanism.
The influence of age and sex on speed–strength performance in children between 10 and 14 years of age
Authors: Warneke Konstantin , Wagner Carl Maximilian , Konrad Andreas , Kadlubowski Björn , Sander Andre , Wirth Klaus , Keiner Michael
Published: February 2023

Introduction: Speed-strength performance is important during human movements such as jumping, sprinting, and change of direction (COD) tasks, which are a substantial part of sports practice. Sex and age seem to influence performance output in young persons; however, few studies have focused on the influence of sex and age measured via standard protocols of performance diagnostics.

Method: Therefore, the aim of this study was to investigate the influence of age and sex on linear sprint (LS), COD sprint, countermovement jump (CMJ) height, squat-jump (SJ) height, and drop-jump (DJ) height performance in untrained children and adolescents via a cross-sectional analysis. This study comprised 141 untrained male and female participants 10–14 years of age.

Results: The results showed the influence of age in male participants on speed-strength performance, while in female participants, age did not significantly influence performance parameters. Moderate to high correlations between sprint and jump performance (r = 0.69–0.72), sprint and COD sprint performance (r = 0.58–0.72), and jump and COD sprint performance (r = 0.56–0.58) were found.

Discussion: Based on the data from this study, it appears that the growth phase of age 10–14 does not necessarily lead to improvements in athletic performance. To ensure holistic motor development, female subjects in particular should be provided with specific training interventions with a focus on strength and power.
The acute effects of whole-body vibration on motor unit recruitment and discharge properties
Authors: Lecce E. , Nuccio S. , Del Vecchio A. , Conti A. , Nicolò A. , Sacchetti M. , Felici F. , Bazzucchi I.
Published: February 2023

Introduction: several studies have reported improved neuromuscular parameters in response to whole-body vibration (WBV). This is likely achieved by modulation of the central nervous system (CNS). Reduced recruitment threshold (RT), which is the % of Maximal Voluntary Force (%MVF) at which a given Motor Unit (MU) is recruited, may be responsible for the force/power improvements observed in several studies.

Methods: 14 men (25 ± 2.3 years; BMI = 23.3 ± 1.5 kg m2 MVF: 319.82 ± 45.74 N) performed trapezoidal isometric contractions of the tibialis anterior (TA) at 35-50-70 %MVF before and after three conditions: WBV, STAND (standing posture), and CNT (no intervention). The vibration was applied through a platform for targeting the TA. High-density surface electromyography (HDsEMG) recordings and analysis were used to detect changes in the RT and Discharge Rate (DR) of the MUs.

Results: Mean motor unit recruitment threshold (MURT) reached 32.04 ± 3.28 %MVF before and 31.2 ± 3.72 %MVF after WBV, with no significant differences between conditions (p > 0.05). Additionally, no significant changes were found in the mean motor unit discharge rate (before WBV: 21.11 ± 2.94 pps; after WBV: 21.19 ± 2.17 pps).

Discussion: The present study showed no significant changes in motor unit properties at the base of neuromuscular changes documented in previous studies. Further investigations are needed to understand motor unit responses to different vibration protocols and the chronic effect of vibration exposure on motor control strategies.
Comparative analysis of drought stress-induced physiological and transcriptional changes of two black sesame cultivars during anthesis
Authors: Wang Xiaohui , Wang Min , Yan Gui , Yang Huiyi , Wei Guangwei , Shen Tinghai , Wan Zehua , Zheng Wei , Fang Sheng , Wu Ziming
Published: February 2023

Sesame production is severely affected by unexpected drought stress during flowering stage. However, little is known about dynamic drought-responsive mechanisms during anthesis in sesame, and no particular attention was given to black sesame, the most common ingredient in East Asia traditional medicine. Herein, we investigated drought-responsive mechanisms of two contrasting black sesame cultivars (Jinhuangma, JHM, and Poyanghei, PYH) during anthesis. Compared to PYH, JHM plants showed higher tolerance to drought stress through the maintenance of biological membrane properties, high induction of osmoprotectants’ biosynthesis and accumulation, and significant enhancement of the activities of antioxidant enzymes. For instance, the drought stress induced a significant increase in the content of soluble protein (SP), soluble sugar (SS), proline (PRO), glutathione (GSH), as well as the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in leaves and roots of JHM plants compared to PYH plants. RNA sequencing followed by differentially expressed genes (DEGs) analysis revealed that more genes were significantly induced under drought in JHM than in PYH plants. Functional enrichment analyses disclosed that several pathways related to drought stress tolerance, such as photosynthesis, amino acids and fatty acid metabolisms, peroxisome, ascorbate and aldarate metabolism, plant hormone signal transduction, biosynthesis of secondary metabolites, and glutathione metabolism, were highly stimulated in JHM than in PYH plants. Thirty-one (31) key highly induced DEGs, including transcription factors and glutathione reductase and ethylene biosynthetic genes, were identified as potential candidate genes for improving black sesame drought stress tolerance. Our findings show that a strong antioxidant system, biosynthesis and accumulation of osmoprotectants, TFs (mainly ERFs and NACs), and phytohormones are essential for black sesame drought tolerance. Moreover, they provide resources for functional genomic studies toward molecular breeding of drought-tolerant black sesame varieties.
Genome-wide survey and expression analysis of Dof transcription factor family in sweetpotato shed light on their promising functions in stress tolerance
Authors: Zhang Chengbin , Dong Tingting , Yu Jing , Hong Haiting , Liu Siyuan , Guo Fen , Ma Hongting , Zhang Jianling , Zhu Mingku , Meng Xiaoqing
Published: February 2023

DNA-binding with one finger (Dof) transcription factors play a crucial role in plant abiotic stress regulatory networks, although massive Dofs have been systematically characterized in plants, they have not been identified in the hexaploid crop sweetpotato. Herein, 43 IbDof genes were detected to be disproportionally dispersed across 14 of the 15 chromosomes of sweetpotato, and segmental duplications were discovered to be the major driving force for the expansion of IbDofs. The collinearity analysis of IbDofs with their related orthologs from eight plants revealed the potential evolutionary history of Dof gene family. Phylogenetic analysis displayed that IbDof proteins were assigned into nine subfamilies, and the regularity of gene structures and conserved motifs was consistent with the subgroup classification. Additionally, five chosen IbDof genes were shown to be substantially and variably induced under various abiotic conditions (salt, drought, heat, and cold), as well as hormone treatments (ABA and SA), according to their transcriptome data and qRT-PCR experiments. Consistently, the promoters of IbDofs contained a number of cis-acting elements associated with hormone and stress responses. Besides, it was noted that IbDof2 had transactivation activity in yeasts, while IbDof-11/-16/-36 did not, and protein interaction network analysis and yeast two-hybrid experiments revealed a complicated interaction connection amongst IbDofs. Collectively, these data lay a foundation for further functional explorations of IbDof genes, especially with regards to the possible application of multiple IbDof members in breeding the tolerant plants.
Genome-edited TaTFL1-5 mutation decreases tiller and spikelet numbers in common wheat
Authors: Sun Jing , Bie Xiao Min , Chu Xiao Li , Wang Ning , Zhang Xian Sheng , Gao Xin-Qi
Published: February 2023

Tillering is a critical agronomic trait of wheat (Triticum aestivum L.) that determines the shoot architecture and affects grain yield. TERMINAL FLOWER 1 (TFL1), encoding a phosphatidylethanolamine-binding protein, is implicated in the transition to flowering and shoot architecture in plant development. However, the roles of TFL1 homologs is little known in wheat development. CRISPR/Cas9-mediated targeted mutagenesis was used in this study to generate a set of wheat (Fielder) mutants with single, double or triple-null tatfl1-5 alleles. The wheat tatfl1-5 mutations decreased the tiller number per plant in the vegetative growth stage and the effective tiller number per plant and spikelet number per spike at maturity in the field. RNA-seq analysis showed that the expression of the auxin signaling–related and cytokinin signaling–related genes was significantly changed in the axillary buds of tatfl1-5 mutant seedlings. The results suggested that wheat TaTFL1-5s were implicated in tiller regulation by auxin and cytokinin signaling.
Assessing phonological short-term memory in Greek: Reliability and validity of a non-word repetition test
Authors: Talli Ioanna , Kotsoni Panagiota , Stavrakaki Stavroula , Sprenger-Charolles Liliane
Published: February 2023

This study explores the reliability and validity of a NWR task in a large cohort of 387 TD Greek-speaking children aged 7–13 years attending elementary (Grades 2–6) and secondary school (Grade 1), divided into six age groups. Further, the relationship between NWR and reading fluency skills as well as the predictive value of the NWR on reading fluency skills in TD children are examined. To investigate the external reliability of the NWR task, test-retest reliability was performed, and excellent test-retest reliability was found. Internal reliability was explored with Cronbach’s alpha coefficient and good reliability was found. To explore convergent validity, correlation analysis between NWR and reading fluency was conducted and significant and strong correlations were found for all age groups excepted 2 (ages 9-10 and 12-13). To examine predictive validity, regression analysis was conducted between these two variables and showed that performance on NWR contributed significantly to reading fluency skills, suggesting that NWR skills are a good predictor of reading skills. Finally, it was explored whether the relevant scores increase as a function of age and found significant differences between groups that differed in 2 years or more, while this difference was no longer significant after 10 years. This finding suggests that phonological STM increases in capacity along with age, but only until the age of 10, where it seems to reach a ceiling. In addition, linear regression analysis showed that age contributed significantly to performance on NWR test. To sum up, the present study provides normative data of a NWR test for a wide age range, which does not exist in the Greek language (particularly for ages over 9 years) and it can be concluded that the present NWR test can be successfully used as a reliable and valid measure of phonological STM in the age range that was examined in this study.
Does sense of work gain predict team creativity? The mediating effect of leader-member exchange and the moderating effect of work smoothness
Authors: Shi Kun , Zhang Zhifan , Zhang Hua
Published: February 2023

In the present study, we examined the link between the sense of work gain and team creativity and explored the mediating and moderating roles of Leader-member exchange (LMX) and work smoothness on it. The results of this study A moderated mediation model was constructed based on 484 valid samples from an on-line survey of a human resource company, revealed that the sense of work gain can positively predict team creativity, and LMX mediates the associations of the sense of work gain and team creativity. Moreover, work smoothness emerged as a significant moderator can moderate the associations between sense of work gain and team creativity, as well as moderating the relationship between LMX and team creativity. The findings provide a theoretical guidance for leaders and HR professionals who want to increase employee initiative and motivation.
Symptom distress and suicidal ideation among Chinese ovarian cancer patients: A moderated mediation model of depression and suicide resilience
Authors: Chen Jie , Zhang Yinying , Cheng Fang , Xie Jinzhi , Zhang Keke , Hu Deying
Published: February 2023

Objective

The aim of this study was to examine whether depression mediates the relationship between symptom distress and suicidal ideation in Chinese patients with ovarian cancer, and whether this mediating effect was moderated by suicide resilience.

Methods

From March to October 2022, this cross-sectional study was performed in a three Grade 3A hospital and an oncology specialty hospital in Wuhan, Hubei Province, China. Ultimately, 213 ovarian cancer patients completed anonymous self-report. Bootstrapping method was used for regression analysis to test the mediating and moderating effects.

Results

Among the 213 participants, 29.58% (n = 63) exhibited significant suicidal ideation. Symptom distress was positively associated with suicidal ideation, and depression partially mediated this relationship. Suicide resilience moderated the relationship between depression and suicidal ideation. In ovarian cancer patients with low suicide resilience, the effect of symptom distress on suicidal ideation through depression was greater, while in patients with high suicide resilience, this effect was attenuated.

Conclusion

Our study suggests that symptom distress could be more likely to lead to suicidal ideation as depression levels increase in ovarian cancer patients. Fortunately, suicide resilience could attenuate this negative effect.