bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension and Cognitive Impairment: A Review of Mechanisms and Key Concepts
Authors: Canavan Michelle , O'Donnell Martin J.
Published: February 2022

Cognitive impairment, and dementia, are major contributors to global burden of death and disability, with projected increases in prevalence in all regions of the world, but most marked increases in low and middle-income countries. Hypertension is a risk factor for both Vascular Cognitive Impairment and Alzheimer's disease, the two most common causes of dementia, collectively accounting for 85% of cases. Key end-organ pathological mechanisms, for which hypertension is proposed to be causative, include acute and covert cerebral ischemia and hemorrhage, accelerated brain atrophy, cerebral microvascular rarefaction and endothelial dysfunction, disruption of blood-brain barrier and neuroinflammation that affects amyloid pathologies. In addition to the direct-effect of hypertension on brain structure and microvasculature, hypertension is a risk factor for other diseases associated with an increased risk of dementia, most notably chronic kidney disease and heart failure. Population-level targets to reduce the incidence of dementia are a public health priority. Meta-analyses of blood pressure lowering trials report a significant reduction in the risk of dementia, but the relative (7–11%) and absolute risk reductions (0.4% over 4 years) are modest. However, given the high lifetime prevalence of both conditions, such relative risk reduction would translate into important population-level reductions in dementia globally with effective screening and control of hypertension. Optimal blood pressure target, especially in older adults with orthostatic hypotension, and antihypertensive agent(s) are uncertain. In this review article, we will detail the observational and interventional evidence linking hypertension with cognitive impairment, summarizing the mechanisms through which hypertension causes cognitive decline.
Posture Deficits and Recovery After Unilateral Vestibular Loss: Early Rehabilitation and Degree of Hypofunction Matter
Authors: Lacour Michel , Tardivet Laurent , Thiry Alain
Published: February 2022

Postural instability and balance impairment are disabling symptoms in patients with acute unilateral peripheral vestibular hypofunction (UVH). Vestibular rehabilitation (VR) is known to improve the vestibular compensation process, but (1) its effect on posture recovery remains poorly understood, (2) little is known about when VR must be done, and (3) whether the degree of vestibular loss matters is uncertain. We analyzed posture control under static (stable support) and dynamic (unstable support) postural tasks performed in different visual conditions [eye open (EO); eyes closed (EC); and optokinetic stimulation] using dynamic posturography. Non-linear analyses of the postural performance (wavelet transform, diffusion analysis, and fractal analysis) were performed in two groups of patients with UVH subjected to the same VR program based on the unidirectional rotation paradigm and performed either early (first 2 weeks) or later (fifth to the sixth week) after vertigo attack. Distribution of the angular horizontal vestibulo-ocular reflex (aVOR) gain values recorded on the hypofunction side before rehabilitation differentiated two distinct sub-groups (cluster analysis) with aVOR gains below or above 0.20. The postural performance of the four sub-groups of patients with UVH (early rehabilitation with aVOR gain <0.20: n = 25 or gain >0.20: n = 19; late rehabilitation with aVOR gain <0.20: n = 15 or gain >0.20: n = 10) tested before VR showed significantly altered postural parameters compared with healthy controls. Greater instability, higher energy to control posture, larger sway without feedback corrections, and lower time of automatic control of posture were observed in static conditions. The four sub-groups recovered near-normal postural performance after VR in the EO and EC conditions, but still exhibited altered postural performance with optokinetic stimulation. In dynamic posturography conditions and before VR, the percentage of patients able to perform the postural tasks with EC and optokinetic stimulation was significantly lower in the two sub-groups with aVOR gain <0.20. After VR, the improvement of the postural parameters depended on the stage of rehabilitation and the degree of vestibular hypofunction. The best balance function recovery was found in the sub-group with early VR and pre-rehabilitation aVOR gain above 0.20, the worst in the sub-group with late rehabilitation and aVOR gain below 0.20. These differences were seen when the vestibular input remains the main sensory cue to control balance, that is, on unstable support without vision or altered visual motion cues. These findings extend to dynamic balance recovery the crucial roles of early rehabilitation and degree of vestibular hypofunction which we have already highlighted for vestibulo-ocular reflex recovery.
Diffusion Tensor Imaging Technology to Quantitatively Assess Abnormal Changes in Patients With Thyroid-Associated Ophthalmopathy
Authors: Rui Li , Jing Li , Zhenchang Wang
Published: February 2022

Objective

We aim to investigate the feasibility of using diffusion tensor imaging (DTI) to evaluate changes in extraocular muscles (EOMs) and lacrimal gland (LG) in patients with thyroid-associated ophthalmopathy (TAO) and to evaluate disease severity.

Materials and Methods

A total of 74 participants, including 17 healthy controls (HCs), 22 patients with mild TAO, and 35 patients with moderate-severe TAO, underwent 3-Tesla DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) of the EOMs and LG. Ophthalmological examinations, including visual acuity, exophthalmos, intraocular pressure, and fundoscopy, were performed. FA and MD values were compared among patients with different disease severity. Multiple linear regression was adopted to predict the impact of clinical variables on DTI parameters of orbital soft tissue.

Results

TAO patients’ EOMs and LG showed significantly lower FA values and higher MD compared to HCs’ (P < 0.05). Moderate-severe TAO patients’ EOMs and LG had dramatically lower FA and higher MD compared with HCs (P < 0.05). In addition, only the DTI parameters of the medial rectus were considerably different between mild and moderate-severe TAO patients (P = 0.017, P = 0.021). Multiple linear regression showed that disease severity had a significant impact on the DTI parameters of orbital soft tissue.

Conclusion

DTI is a useful tool for detecting microstructural changes in TAO patients’ orbital soft tissue. DTI findings, especially medial rectus DTI parameters, can help to indicate the disease severity in TAO patients.
Force Distribution Within Spinal Tissues During Posterior to Anterior Spinal Manipulative Therapy: A Secondary Analysis
Authors: Funabashi Martha , Breen Alexander Cleveland , De Carvalho Diana , Pagé Isabelle , Nougarou François , Descarreaux Martin , Kawchuk Gregory N.
Published: February 2022

Background

Previous studies observed that the intervertebral disc experiences the greatest forces during spinal manipulative therapy (SMT) and that the distribution of forces among spinal tissues changes as a function of the SMT parameters. However, contextualized SMT forces, relative to the ones applied to and experienced by the whole functional spinal unit, is needed to understand SMT’s underlying mechanisms.

Aim

To describe the percentage force distribution between spinal tissues relative to the applied SMT forces and total force experienced by the functional unit.

Methods

This secondary analysis combined data from 35 fresh porcine cadavers exposed to a simulated 300N SMT to the skin overlying the L3/L4 facet joint via servo-controlled linear motor actuator. Vertebral kinematics were tracked optically using indwelling bone pins. The functional spinal unit was then removed and mounted on a parallel robotic platform equipped with a 6-axis load cell. The kinematics of the spine during SMT were replayed by the robotic platform. By using serial dissection, peak and mean forces induced by the simulated SMT experienced by spinal structures in all three axes of motion were recorded. Forces experienced by spinal structures were analyzed descriptively and the resultant force magnitude was calculated.

Results

During SMT, the functional spinal unit experienced a median peak resultant force of 36.4N (IQR: 14.1N) and a mean resultant force of 25.4N (IQR: 11.9N). Peak resultant force experienced by the spinal segment corresponded to 12.1% of the total applied SMT force (300N). When the resultant force experienced by the functional spinal unit was considered to be 100%, the supra and interspinous ligaments experienced 0.3% of the peak forces and 0.5% of the mean forces. Facet joints and ligamentum flavum experienced 0.7% of the peak forces and 3% of the mean forces. Intervertebral disc and longitudinal ligaments experienced 99% of the peak and 96.5% of the mean forces.

Conclusion

In this animal model, a small percentage of the forces applied during a posterior-to-anterior SMT reached spinal structures in the lumbar spine. Most SMT forces (over 96%) are experienced by the intervertebral disc. This study provides a novel perspective on SMT force distribution within spinal tissues.
Development of a Food Frequency Questionnaire for Assessing Habitual Intake of Free Sugar Among Children in Saudi Arabia
Authors: Mumena Walaa Abdullah , Kutbi Hebah Alawi
Published: February 2022

The World Health Organization emphasizes the urgency to assess and limit the intake of free sugar (FS) among individuals in order to prevent several non-communicable diseases. However, data regarding intake of FS are lacking in Saudi Arabia and in the Middle East. A reliable valid tool is needed to assess children's habitual intake of FS. Thus, we aimed to develop and validate a food frequency questionnaire (FFQ) that assesses children's habitual intake of FS in Saudi Arabia. In this cross-sectional study, 424 healthy Saudi children ages 6–12 years were included using river sampling method. Sociodemographic data and contact information were collected from mothers using an online survey. Dietary data were collected using 24-h dietary recalls (reference method) and a semi-quantitative FFQ through phone interviews. Items and food groups included in the initial draft of the FFQ were adopted from previous work. Content validity was done to the FFQ with total of 12 food groups and 41 food items. Next, a pilot study was conducted to estimate the sample size needed for the study and to ensure that all items reported in the 24-h dietary recalls were included in the final draft of the FFQ. Finally, data were collected to assess the validity and reliability of the FFQ at the population level. Mean intake of FS assessed by the FFQ was significantly higher than that assessed by the 24-h dietary recalls. Spearman's correlation between total FS assessed by the FFQ and 24-h dietary recall was positively low (rs = 0.30, p < 0.001). The coefficient alpha indicated an acceptable level of internal consistency (α = 0.74, p < 0.001). Test-retest reliability for total FS intake assessed by the FFQ was positively high (rs = 0.82). A slight agreement between FS intake assessed by the FFQ and the 24-h dietary recall was seen among the study sample (κ = 0.21, p < 0.001). The newly developed FFQ was found to be reasonably valid in assessing children's habitual intake of FS in Saudi Arabia. Validating the instrument among older population in Saudi Arabia is warranted.
Integrated Analysis of Metabolome and Transcriptome Data for Uncovering Flavonoid Components of Zanthoxylum bungeanum Maxim. Leaves Under Drought Stress
Authors: Hu Haichao , Fei Xitong , He Beibei , Luo Yingli , Qi Yichen , Wei Anzhi
Published: February 2022

Zanthoxylum bungeanum Maxim. leaves (ZBLs) are rich in flavonoids and have become popular in nutrition, foods and medicine. However, the flavonoid components in ZBLs and the mechanism of flavonoid biosynthesis under drought stress have received little attention. Here, we performed an integrative analysis of the metabolome and transcriptome of ZBLs from HJ (Z. bungeanum cv. “Hanjiao”) and FJ (Z. bungeanum cv. “Fengjiao”) at four drought stages. A total of 231 individual flavonoids divided into nine classes were identified and flavones and flavonols were considered the most abundant flavonoid components in ZBLs. The total flavonoid content of ZBLs was higher in FJ; it increased in FJ under drought stress but decreased in HJ. Nine-quadrant analysis identified five and eight differentially abundant flavonoids in FJ and HJ leaves, respectively, under drought stress. Weighted gene correlation network analysis (WGCNA) identified nine structural genes and eight transcription factor genes involved in the regulation of flavonoid biosynthesis. Moreover, qRT-PCR results verified the accuracy of the transcriptome data and the reliability of the candidate genes. Taken together, our results reveal the flavonoid components of ZBLs and document changes in flavonoid metabolism under drought stress, providing valuable information for nutrition value and food utilization of ZBLs.
Large Animal Models of Breast Cancer
Authors: Mondal Pinaki , Bailey Katie L. , Cartwright Sara B. , Band Vimla , Carlson Mark A.
Published: February 2022

In this mini review the status, advantages, and disadvantages of large animal modeling of breast cancer (BC) will be discussed. While most older studies of large animal BC models utilized canine and feline subjects, more recently there has been interest in development of porcine BC models, with some early promising results for modeling human disease. Widely used rodent models of BC were briefly reviewed to give context to the work on the large animal BC models. Availability of large animal BC models could provide additional tools for BC research, including availability of human-sized subjects and BC models with greater biologic relevance.
A Multi-Compartment Model of Glioma Response to Fractionated Radiation Therapy Parameterized via Time-Resolved Microscopy Data
Authors: Liu Junyan , Hormuth David A. , Yang Jianchen , Yankeelov Thomas E.
Published: February 2022

Purpose

Conventional radiobiology models, including the linear-quadratic model, do not explicitly account for the temporal effects of radiation, thereby making it difficult to make time-resolved predictions of tumor response to fractionated radiation. To overcome this limitation, we propose and validate an experimental-computational approach that predicts the changes in cell number over time in response to fractionated radiation.

Methods

We irradiated 9L and C6 glioma cells with six different fractionation schemes yielding a total dose of either 16 Gy or 20 Gy, and then observed their responseviatime-resolved microscopy. Phase-contrast images and Cytotox Red images (to label dead cells) were collected every 4 to 6 hours up to 330 hours post-radiation. Using 75% of the total data (i.e., 262 9L curves and 211 C6 curves), we calibrated a two-species model describing proliferative and senescent cells. We then applied the calibrated parameters to a validation dataset (the remaining 25% of the data, i.e., 91 9L curves and 74 C6 curves) to predict radiation response. Model predictions were compared to the microscopy measurements using the Pearson correlation coefficient (PCC) and the concordance correlation coefficient (CCC).

Results

For the 9L cells, we observed PCCs and CCCs between the model predictions and validation data of (mean ± standard error) 0.96 ± 0.007 and 0.88 ± 0.013, respectively, across all fractionation schemes. For the C6 cells, we observed PCCs and CCCs between model predictions and the validation data were 0.89 ± 0.008 and 0.75 ± 0.017, respectively, across all fractionation schemes.

Conclusion

By proposing a time-resolved mathematical model of fractionated radiation response that can be experimentally verifiedin vitro, this study is the first to establish a framework for quantitative characterization and prediction of the dynamic radiobiological response of 9L and C6 gliomas to fractionated radiotherapy.
Combined Microscopic and Endoscopic Surgery for Pineal Region Meningiomas Using the Occipital-Parietal Transtentorial Approach
Authors: Ding Yu , Sun Liang , Hu Yukun , Zhai Weiwei , Zhang Liexiang , Yu Zhengquan , Wu Jiang , Chen Gang
Published: February 2022

Objective

Pineal region meningiomas are deeply located and adjacent to critical neurovascular structures, making them one of the most challenging areas to access. The authors presented a combined microscopic and endoscopic surgery and investigated its value in resecting pineal region meningiomas.

Methods

Twelve patients with pineal region meningiomas from February 2017 to December 2020 were retrospectively reviewed. All patients underwent combined microscopic and endoscopic surgery using the occipital-parietal transtentorial approach. Perioperative clinical, surgical, and radiographic data were collected.

Results

The endoscope provided a wider view and increased visualization of residual tumors. All tumors were completely resected, and none of the patients died. Total resection was believed to have been achieved in four patients, but the residual tumor was detected after endoscopic exploration and was completely resected with an endoscope. Only one patient had transient visual field deficits. No recurrence was observed during follow-up.

Conclusions

Combined microscopic-endoscopic surgery for pineal region meningiomas eliminates microscopic blind spots, thus compensating for the shortcomings of the traditional occipital transtentorial approach. It is a promising technique for minimally invasive maximal resection of pineal region meningiomas.
Construction and Validation of a Prognostic Risk Model for Triple-Negative Breast Cancer Based on Autophagy-Related Genes
Authors: Yan Cheng , Liu Qingling , Jia Ruoling
Published: February 2022

Background

Autophagy plays an important role in triple-negative breast cancer (TNBC). However, the prognostic value of autophagy-related genes (ARGs) in TNBC remains unknown. In this study, we established a survival model to evaluate the prognosis of TNBC patients using ARGs signature.

Methods

A total of 222 autophagy-related genes were downloaded from The Human Autophagy Database. The RNA-sequencing data and corresponding clinical data of TNBC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed autophagy-related genes (DE-ARGs) between normal samples and TNBC samples were determined by the DESeq2 package. Then, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were performed. According to the LASSO regression results based on univariate Cox, we identified a prognostic signature for overall survival (OS), which was further validated by using the Gene Expression Omnibus (GEO) cohort. We also found an independent prognostic marker that can predict the clinicopathological features of TNBC. Furthermore, a nomogram was drawn to predict the survival probability of TNBC patients, which could help in clinical decision for TNBC treatment. Finally, we validated the requirement of an ARG in our model for TNBC cell survival and metastasis.

Results

There are 43 DE-ARGs identified between normal and tumor samples. A risk model for OS using CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74, and VAMP3 was established based on univariate Cox regression and LASSO regression analysis. Overall survival of TNBC patients was significantly shorter in the high-risk group than in the low-risk group for both the training and validation cohorts. Using the Kaplan–Meier curves and receiver operating characteristic (ROC) curves, we demonstrated the accuracy of the prognostic model. Multivariate Cox regression analysis was used to verify risk score as an independent predictor. Subsequently, a nomogram was proposed to predict 1-, 3-, and 5-year survival for TNBC patients. The calibration curves showed great accuracy of the model for survival prediction. Finally, we found that depletion of EIF4EBP1, one of the ARGs in our model, significantly reduced cell proliferation and metastasis of TNBC cells.

Conclusion

Based on six ARGs (CDKN1A, CTSD, CTSL, EIF4EBP1, TMEM74, and VAMP3), we developed a risk prediction model that can help clinical doctors effectively predict the survival status of TNBC patients. Our data suggested that EIF4EBP1 might promote the proliferation and migration in TNBC cell lines. These findings provided a novel insight into the vital role of the autophagy-related genes in TNBC and may provide new therapeutic targets for TNBC.
Megakaryocyte Diversity in Ontogeny, Functions and Cell-Cell Interactions
Authors: Khatib-Massalha Eman , Méndez-Ferrer Simón
Published: February 2022

Hematopoietic stem cells (HSCs) rely on local interactions in the bone marrow (BM) microenvironment with stromal cells and other hematopoietic cells that facilitate their survival and proliferation, and also regulate their functions. HSCs and multipotent progenitor cells differentiate into lineage-specific progenitors that generate all blood and immune cells. Megakaryocytes (Mks) are hematopoietic cells responsible for producing blood platelets, which are essential for normal hemostasis and blood coagulation. Although the most prominent function of Mks is platelet production (thrombopoiesis), other increasingly recognized functions include HSC maintenance and host immune response. However, whether and how these diverse programs are executed by different Mk subpopulations remains poorly understood. This Perspective summarizes our current understanding of diversity in ontogeny, functions and cell-cell interactions. Cumulative evidence suggests that BM microenvironment dysfunction, partly caused by mutated Mks, can induce or alter the progression of a variety of hematologic malignancies, including myeloproliferative neoplasms (MPNs) and other disorders associated with tissue scarring (fibrosis). Therefore, as an example of the heterogeneous functions of Mks in malignant hematopoiesis, we will discuss the role of Mks in the onset and progression of BM fibrosis. In this regard, abnormal interactions between of Mks and other immune cells might directly contribute to fibrotic diseases. Overall, further understanding of megakaryopoiesis and how Mks interact with HSCs and immune cells has potential clinical implications for stem cell transplantation and other therapies for hematologic malignancies, as well as for treatments to stimulate platelet production and prevent thrombocytopenia.
The Consensus Definition of Bronchopulmonary Dysplasia Is an Adequate Predictor of Lung Function at Preschool Age
Authors: Rite Segundo , Martín de Vicente Carlos , García-Iñiguez Juan P. , Couce María L. , Samper María P. , Montaner Alicia , Ruiz de la Cuesta Carmen
Published: February 2022

Background

Recent attempts to refine the definition bronchopulmonary dysplasia (BPD) have based its predictive capacity on respiratory outcome in the first 2 years of life, eliminating the pre-existing requirement of 28 days of oxygen therapy prior to 36 weeks postmenstrual age (PMA). The objective of this study was to assess the utility of the 2001 consensus definition in predicting impaired lung function at preschool age.

Methods

This cohort study included children aged 4–6 years old who were born at gestational age (GA) <32 weeks or bodyweight <1500 g. Univariate and multivariate analyses were performed to assess differences in antenatal and neonatal variables between BPD and non-BPD children. All participants underwent incentive spirometry. Lung function parameters were contrasted with the Global Lung Function Initiative (GLI-2012) reference equations and, together with antenatal and neonatal variables, compared among the different subgroups (no BPD, mild BPD, and moderate-to-severe BPD). A multivariate model was generated to identify independent risk factors for impaired lung function.

Results

GA, hemodynamically significant patent ductus arteriosus, and late sepsis were independent risk factors for the development of BPD. A total of 119 children underwent incentive spirometry. All lung function parameters were significantly altered relative to reference values. Greater impairment of lung function was observed in the mild BPD vs. the no BPD group (forced expiratory volume in the first 0.75 seconds [FEV0.75]: −1.18 ± 0.80 vs. −0.55 ± 1.13; p = 0.010), but no difference in forced vital capacity (FVC) was observed (−0.32 ± 0.90 vs. −0.18 ± 1; p = 0.534). The moderate-to-severe BPD group exhibited the most severe FEV0.75 reduction (FEV0.75: −2.63 ± 1.18 vs. −0.72 ± 1.08; p = 0.000) and was the only condition with FVC impairment (FVC: −1.82 ± 1.12 vs. −0.22 ± 0.87; p = 0.000). The multivariate analysis identified a diagnosis of moderate-to-severe BPD as an independent risk factor for lung function impairment.

Conclusion

The 2001 consensus definition of BPD has adequate predictive capacity for lung function measured by spirometry at 4–6 years of age. Moderate-to-severe BPD was the best predictor of respiratory impairment. Children with mild BPD showed greater alteration of FEV0.75 than those without BPD.
Comparison of Herbal Medicines Used for Women’s Menstruation Diseases in Different Areas of the World
Authors: Jiao Majing , Liu Xinqiao , Ren Yongshen , Wang Yingzhou , Cheng Long , Liang Yunhui , Li Yanqiu , Zhang Tianpei , Wang Wen , Mei Zhinan
Published: February 2022

Aims: This review aims to compare the use of herbal medicine used to treat women’s menstruation and the prevalence of menstrual diseases in different regions, which reveal the use of herbal medicine globally and provide scientific guidance for improving women’s health.

Materials and Methods: The information available on herbal medicines for women between the years 2000 and 2021 was systematically collected via the library and electronic search systems such as Google Scholar, PubMed, ScienceDirect, and Web of Science as well as secondary resources including books and conference proceedings.

Results: Totally, 571 ethnic medicines commonly used for women’s menstruation health in Asia, Europe, Oceania, Africa, and America were accounted. Zingiber officinale Roscoe (Ginger), Ruta graveolens L. (Common rue), Angelica sinensis (Oliv.) Diels (Angelica sinensis), Foeniculum vulgare Mill (Fennel), Catharanthus roseus (L.) G. Don (Catharanthus roseus) and other medicines which have obvious advantages and long-term usage are utilized in the treatment of menstrual diseases. Family Asteraceae, Lamiaceae, Apiaceae, Fabaceae, and Zingiberaceae are the most common medicinal plant families used for such treatments. In many instances, the application of fresh parts of plants was observed because of the healers’ belief regarding the higher efficiency of the medicine made from fresh plants. Edible plants are used in a wide range of countries.

Conclusion: Women’s menstruation health is directly related to their health condition. Traditional medicines of most ethnic groups have contributed to women’s health care and treatment of gynecological diseases. Practitioners in this field have gained elaborate experience in treatments and medication, and assembled a large number of effective drugs and prescriptions. These experiences have also been inherited and developed by modern clinical application and scientific research. However, the basic research on these drugs is not sufficient, the knowledge of drug use has not been fully popularized, the advantages of drugs have not been fully utilized, and the guiding potential to modern drug research continues to be insufficient. As such, it is necessary to further promote and make a significant contribution to women’s health.
Characteristics and Spectrum of Cardiotoxicity Induced by Various Antipsychotics: A Real-World Study From 2015 to 2020 Based on FAERS
Authors: He Luyao , Yu Yimin , Wei Yumei , Huang Jingjing , Shen Yifeng , Li Huafang
Published: February 2022

Objective: This study aimed to investigate the characteristics and spectrum of cardiotoxicity induced by various antipsychotics based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database.

Methods: Data of the FAERS database from the first quarter of 2015 to the fourth quarter of 2020 were downloaded for disproportionality analysis. The significant signal was evaluated by reporting odds ratios and information components with statistical shrinkage transformation.

Results: A total of 2,361,487 records were extracted for disproportionality analysis. Among the 10 antipsychotics, clozapine and amisulpride performed strong cardiotoxicity. Cardiomyopathy, cardiac arrhythmia, and Torsade de pointes/QT prolongation were the common cardiac adverse event induced by antipsychotics. Different characteristics of the spectrum of cardiotoxicity in various APs were discovered after further data mining. Moreover, evidence of the association between antipsychotics and eosinophilic myocarditis, peripartum cardiomyopathy was provided in this study.

Conclusion: Antipsychotics presented cardiotoxicity in different degrees, and more cardiac examinations should be monitored in patients with antipsychotics.
Pentagalloyl Glucose, a Major Compound in Mango Seed Kernel, Exhibits Distinct Gastroprotective Effects in Indomethacin-Induced Gastropathy in Rats via Modulating the NO/eNOS/iNOS Signaling Pathway
Authors: Mahmoud Mona F. , Nabil Mohamed , Hasan Rehab A. , El-Shazly Assem M. , El-Ansari Mohamed A. , Sobeh Mansour
Published: February 2022

Gastric ulcers are a common health disorder that affect up to 10% of the world’s population. The gastroprotective potential of pentagalloyl glucose (PGG) against indomethacin-induced ulcer in rats and the possible underlying mechanisms were investigated. Gastric ulceration was induced by indomethacin (single dose, 60 mg/kg). Pretreatment with PGG (100 or 200 mg/kg, orally) for 8 days prior to the administration of indomethacin furnished significant reductions in gastric mucosal lesions as well as a significant increase in mucus concentration. Also, PGG significantly declined the elevations in gastric mucosal MDA, TNF-α, IL-6, PECAM-1, VEGF, and iNOS expression. It also mitigated the decrease in GSH and GPx and eNOS expression observed with indomethacin. The protective effects furnished by PGG were comparable to that of famotidine. The obtained results suggested that the anti-ulcer effects of PGG are mediated by increasing mucus production, scavenging free radicals, decreasing inflammation, and attenuating the NO/NOS signaling in favor of eNOS. To sum up, PGG could provide a potential therapy for gastric ulcer after evaluating its efficacy and effectiveness.
Therapeutic Potential and Molecular Mechanisms of Echinacoside in Neurodegenerative Diseases
Authors: Li Jin , Yu Hongni , Yang Chuan , Ma Tao , Dai Yuan
Published: February 2022

Echinacoside (ECH) is a natural phenylethanoid glycoside (PhG) in Cistanche tubulosa. A large number of studies have shown that ECH has very promising potential in the inhibition of neurodegenerative disease progression. Experimental studies strongly suggest that ECH exhibits a variety of beneficial effects associated with in neuronal function, including protecting mitochondrial function, anti-oxidative stress, anti-inflammatory, anti-endoplasmic reticulum stress (ERS), regulating autophagy and so on. The aim of this paper is to provide an extensive and actual summarization of ECH and its neuroprotective efficacy in prevention and treatment of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and so on, based on published data from both in vivo and in vitro studies. There is a growing evidence that ECH may serve as an efficacious and safe substance in the future to counteract neurodegenerative disease.
Physical Exercise Repairs Obstructive Jaundice-Induced Damage to Intestinal Mucosal Barrier Function via H2S-Mediated Regulation of the HMGB1/Toll Like Receptors 4/Nuclear Factor Kappa B Pathway
Authors: Shao Changfeng , Li Ye , Chen Jiaqin , Zheng Lan , Chen Wei , Peng Qi , Chen Rui , Yuan Afang
Published: February 2022

The present study aimed to determine the effect of aerobic exercise on improving damage to intestinal mucosal barrier function caused by obstructive jaundice (OJ) and explore the mechanism. Fifty male KM mice were divided into five groups: sham operation group (S), model group (M), exercise group (TM), DL-propargylglycine + exercise (PT) group, and sodium hydrosulfide + exercise (NT) group. Additionally, mice in S group underwent common bile duct ligation for 48 h to establish a murine obstructive jaundice model. In PT group, propargylglycine (40 mg/kg) was intraperitoneally injected 7 days after surgery. NaHS (50 μmol/kg) was intraperitoneally injected into mice in the NT group 7 days after surgery. The TM group, NT group and PT group exercised on a slope of 0% at a speed of 10 m/min without weight training (30 min/day). HE staining showed that the intestinal mucosa of group M was atrophied and that the villi were broken. The intestinal mucosal structure of mice in the TM group was improved. Serum assays showed that H2S levels were higher in the TM group than in the M group; compared with the levels in the TM group, the PT group levels were decreased and the NT group levels were increased. In addition, aerobic exercise inhibits the HMGB1/TLR4/NF-κB signaling pathway by promoting endogenous H2S production, thereby exerting a protective effect on the intestinal mucosal barrier.
Comparison Between Contract–Relax Stretching and Antagonist Contract–Relax Stretching on Gastrocnemius Medialis Passive Properties
Authors: Fukaya Taizan , Konrad Andreas , Sato Shigeru , Kiyono Ryosuke , Yahata Kaoru , Yasaka Koki , Onuma Remi , Yoshida Riku , Nakamura Masatoshi
Published: February 2022

Antagonist contract-relax stretching and contract-relax stretching is commonly used in sports practice and rehabilitation settings. To date, no study has compared these modalities regarding muscle stiffness and stretch tolerance. This study aimed to investigate the effects of contract-relax and antagonist contract-relax stretching on dorsiflexion range of motion (ROM), stretch tolerance, and shear elastic modulus. Forty healthy participants (24 men and 16 women) took part in the study. Participants were randomly assigned to perform either contract-relax stretching or antagonist contract-relax stretching for 2 min. Outcomes were assessed on ROM, stretch tolerance, and shear elastic modulus before and after stretching. The ROM and stretch tolerance significantly increased after both contract-relax stretching (+ 5.4 ± 5.8°, p < 0.05; + 3.5 ± 8.0 Nm, p < 0.05) and antagonist contract-relax stretching (+ 6.1 ± 4.9°, p < 0.05; + 4.2 ± 6.4 Nm, p < 0.05); however, no significant difference was found between the two groups. Alternatively, the shear elastic modulus significantly decreased after both contract-relax (–31.1 ± 22.6 kPa, p < 0.05) and antagonist contract-relax stretching (–11.1 ± 22.3 kPa, p < 0.05); however, contract-relax stretching (–41.9 ± 19.6%) was more effective than antagonist contract-relax stretching (–12.5 ± 61.6%). The results of this study suggest that contract-relax stretching instead of antagonist contract-relax stretching should be conducted to decrease muscle stiffness. However, either contract-relax or antagonist contract-relax stretching can increase ROM.
Transcriptome Responses to Defined Insecticide Selection Pressures in the German Cockroach (Blattella germanica L.)
Authors: Scharf Michael E. , Wolfe Zachery M. , Raje Kapil R. , Fardisi Mahsa , Thimmapuram Jyothi , Bhide Ketaki , Gondhalekar Ameya D.
Published: February 2022

Cockroaches are important global urban pests from aesthetic and health perspectives. Insecticides represent the most cost-effective way to control cockroaches and limit their impacts on human health. However, cockroaches readily develop insecticide resistance, which can quickly limit efficacy of even the newest and most effective insecticide products. The goal of this research was to understand whole-body physiological responses in German cockroaches, at the metatranscriptome level, to defined insecticide selection pressures. We used the insecticide indoxacarb as the selecting insecticide, which is an important bait active ingredient for cockroach control. Six generations of selection with indoxacarb bait produced a strain with substantial (>20×) resistance relative to inbred control lines originating from the same parental stock. Metatranscriptome sequencing revealed 1,123 significantly differentially expressed (DE) genes in ≥two of three statistical models (81 upregulated and 1,042 downregulated; FDR P < 0.001; log2FC of ±1). Upregulated DE genes represented many detoxification enzyme families including cytochrome-P450 oxidative enzymes, hydrolases and glutathione-S-transferases. Interestingly, the majority of downregulated DE genes were from microbial and viral origins, indicating that selection for resistance is also associated with elimination of commensal, pathogenic and/or parasitic microbes. These microbial impacts could result from: (i) direct effects of indoxacarb, (ii) indirect effects of antimicrobial preservatives included in the selecting bait matrix, or (iii) selection for general stress response mechanisms that confer both xenobiotic resistance and immunity. These results provide novel physiological insights into insecticide resistance evolution and mechanisms, as well as novel insights into parallel fitness benefits associated with selection for insecticide resistance.
Phylogenetic Relationships Within the Hyper-Diverse Genus Eugenia (Myrtaceae: Myrteae) Based on Target Enrichment Sequencing
Authors: Giaretta Augusto , Murphy Bruce , Maurin Olivier , Mazine Fiorella F. , Sano Paulo , Lucas Eve
Published: February 2022

Eugenia is one of the most taxonomically challenging lineages of flowering plants, in which morphological delimitation has changed over the last few years resulting from recent phylogenetic study based on molecular data. Efforts, until now, have been limited to Sanger sequencing of mostly plastid markers. These phylogenetic studies indicate 11 clades formalized as infrageneric groups. However, relationships among these clades are poorly supported at key nodes and inconsistent between studies, particularly along the backbone and within Eugenia sect. Umbellatae encompasses ca. 700 species. To resolve and better understand systematic discordance, 54 Eugenia taxa were subjected to phylogenomic Hyb-Seq using 353 low-copy nuclear genes. Twenty species trees based on coding and non-coding loci of nuclear and plastid datasets were recovered using coalescent and concatenated approaches. Concordant and conflicting topologies were assessed by comparing tree landscapes, topology tests, and gene and site concordance factors. The topologies are similar except between nuclear and plastid datasets. The coalescent trees better accommodate disparity in the intron dataset, which contains more parsimony informative sites, while concatenated trees recover more conservative topologies, as they have narrower distribution in the tree landscape. This suggests that highly supported phylogenetic relationships determined in previous studies do not necessarily indicate overwhelming concordant signal. Congruence must be interpreted carefully especially in concatenated datasets. Despite this, the congruence between the multi-species coalescent (MSC) approach and concatenated tree topologies found here is notable. Our analysis does not support Eugenia subg. Pseudeugenia or sect. Pilothecium, as currently circumscribed, suggesting necessary taxonomic reassessment. Five clades are further discussed within Eugenia sect. Umbellatae progress toward its division into workable clades. While targeted sequencing provides a massive quantity of data that improves phylogenetic resolution in Eugenia, uncertainty still remains in Eugenia sect. Umbellatae. The general pattern of higher site coefficient factor (CF) than gene CF in the backbone of Eugenia suggests stochastic error from limited signal. Tree landscapes in combination with concordance factor scores, as implemented here, provide a comprehensive approach that incorporates several phylogenetic hypotheses. We believe the protocols employed here will be of use for future investigations on the evolutionary history of Myrtaceae.
Studies on Pure Mlb® (Multiple Left Border) Technology and Its Impact on Vector Backbone Integration in Transgenic Cassava
Authors: Sahab Sareena , Taylor Nigel
Published: February 2022

Imperfect T-DNA processing is common during Agrobacterium-mediated transformation, which integrates vector backbone sequences into the plant genome. However, regulatory restrictions prevent such transgenic plants from being developed for commercial deployment. The binary vector pCAMBIA2300 was modified by incorporating multiple left border (Mlb®) repeats and was tested in BY2 cells, tobacco, and cassava plants to address this issue. PCR analyses confirmed a twofold increase in the vector backbone free events in the presence of triple left borders in all three systems tested. Vector backbone read-through past the LB was reduced significantly; however, the inclusion of Mlbs® did not effectively address the beyond right border read-through. Also, Mlbs® increased the frequency of single-copy and vector backbone free events (clean events) twice compared to a single LB construct. Here, we briefly narrate the strength and limitations of using Mlb® technology and reporter genes in reducing the vector backbone transfer in transgenic events.
Effects of Soil Physico-Chemical Properties on Plant Species Diversity Along an Elevation Gradient Over Alpine Grassland on the Qinghai-Tibetan Plateau, China
Authors: Han Wangya , Chen Li , Su Xukun , Liu Dan , Jin Tiantian , Shi Songlin , Li Tao , Liu Guohua
Published: February 2022

Elevation gradient can reflect the effects of soil physico-chemical properties on plant species diversity. Alpine grassland on the QTP has suffered from a serious decline in plant species diversity. In this study, we investigated 112 sites recording plant community characteristics and collecting soil samples along an elevation gradient (3,500–5,200 m asl) in alpine meadow on the QTP. We analyzed the effects of soil physico-chemical properties on plant species composition and diversity by canonical ordination and spatial regression along an elevation gradient. The results showed that species richness of the overall plant communities decreased with the increasing elevation, and the Simpson dissimilarity index (βsim) had a maximum at low elevation (3,500–4,000 m) with the value of 0.37. Soil available nitrogen content was the primary soil parameter affecting plant species composition and diversity in alpine grassland. The effect of soil available nitrogen content on plant species richness varied at different elevations. For Gramineae plants (G), plant species richness declined with the increase in soil available nitrogen content at low elevation (3,500–4,000 m), but rose at middle elevation (4,000–4,500 m). Soil available nitrogen content had a more significant limiting effect on species richness at high elevation (>4,500 m). These findings increase our understanding about the drivers of plant species diversity changes in alpine grassland on the QTP, and will provide insights into grassland restoration and sustainable management.
Genome-Wide Identification of Direct Targets of ZjVND7 Reveals the Putative Roles of Whole-Genome Duplication in Sour Jujube in Regulating Xylem Vessel Differentiation and Drought Tolerance
Authors: Li Meng , Hou Lu , Zhang Chenxing , Yang Weicong , Liu Xinru , Zhao Hanqing , Pang Xiaoming , Li Yingyue
Published: February 2022

The effects of whole-genome duplication span multiple levels. Previous study reported that the autotetraploid sour jujube exhibited superior drought tolerance than diploid. However, the difference in water transport system between diploids and autotetraploids and its mechanism remain unclear. Here, we found the number of xylem vessels and parenchyma cells in autotetraploid sour jujube increased to nearly twice that of diploid sour jujube, which may be closely related to the differences in xylem vessel differentiation-related ZjVND7 targets between the two ploidy types. Although the five enriched binding motifs are different, the most reliable motif in both diploid and autotetraploid sour jujube was CTTNAAG. Additionally, ZjVND7 targeted 236 and 321 genes in diploids and autotetraploids, respectively. More identified targeted genes of ZjVND7 were annotated to xylem development, secondary wall synthesis, cell death, cell division, and DNA endoreplication in autotetraploids than in diploids. SMR1 plays distinct roles in both proliferating and differentiated cells. Under drought stress, the binding signal of ZjVND7 to ZjSMR1 was stronger in autotetraploids than in diploids, and the fold-changes in the expression of ZjVND7 and ZjSMR1 were larger in the autotetraploids than in the diploids. These results suggested that the targeted regulation of ZjVND7 on ZjSMR1 may play valuable roles in autotetraploids in the response to drought stress. We hypothesized that the binding of ZjVND7 to ZjSMR1 might play a role in cell division and transdifferentiation from parenchyma cells to vessels in the xylem. This regulation could prolong the cell cycle and regulate endoreplication in response to drought stress and abscisic acid, which may be stronger in polyploids.
Reduced Child-Oriented Face Mirroring Brain Responses in Mothers With Opioid Use Disorder: An Exploratory Study
Authors: Swain James E. , Ho S. Shaun
Published: February 2022

While the prevalence of opioid use disorder (OUD) among pregnant women has multiplied in the United States in the last decade, buprenorphine treatment (BT) for peripartum women with OUD has been administered to reduce risks of repeated cycles of craving and withdrawal. However, the maternal behavior and bonding in mothers with OUD may be altered as the underlying maternal behavior neurocircuit (MBN) is opioid sensitive. In the regulation of rodent maternal behaviors such as licking and grooming, a series of opioid-sensitive brain regions are functionally connected, including the ventral pallidum (VP). In humans, these brain regions, interact with the supplementary motor area (SMA) to regulate maternal behaviors and are functionally dysregulated by opioids. It is unclear how these brain regions respond to the emotions of their child for mothers receiving BT. In this functional magnetic resonance imaging (fMRI) pilot study in 22 mothers within the first postpartum year, including six mothers receiving BT and 16 non-OUD mothers as a comparison group (CG), we devised a child face mirroring task in fMRI settings to assess maternal responses to pictures of facial expressions of own child and an unknown child in an empathic mirroring condition (Join) and a non-mirroring observation condition (Observe). In each condition, faces of neutral, ambiguous, distressed, and joyful expressions of each child were repeatedly displayed in a random order. The response of SMA during empathic mirroring (Join) vs. non-mirroring (Observe) of own child was reduced among BT/OUD vs. CG. Within MBN, the left VP, critical for parental sensitivity, had a similar deficit. This study outlines potential mechanisms for investigating the risks of deficits in the neural responses to actual maternal sensitivity and parenting behavior in mothers with OUD, and potential targets for interventions that reduce stress and augment maternal behavior and child outcome.