bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Disorders in Rett Syndrome and Rett-Related Disorders: A Narrative Review
Authors: Tascini Giorgia , Dell'Isola Giovanni Battista , Mencaroni Elisabetta , Di Cara Giuseppe , Striano Pasquale , Verrotti Alberto
Published: March 2022

Rett Syndrome (RTT) is a rare and severe X-linked developmental brain disorder that occurs primarily in females, with a ratio of 1:10.000.De novomutations in the Methyl-CpG Binding protein 2 (MECP2) gene on the long arm of X chromosome are responsible for more than 95% cases of classical Rett. In the remaining cases (atypical Rett), other genes are involved such as the cyclin-dependent kinase-like 5 (CDKL5) and the forkhead box G1 (FOXG1). Duplications of the MECP2 locus cause MECP2 duplication syndrome (MDS) which concerns about 1% of male patients with intellectual disability. Sleep disorders are common in individuals with intellectual disability, while the prevalence in children is between 16 and 42%. Over 80% of individuals affected by RTT show sleep problems, with a higher prevalence in the first 7 years of life and some degree of variability in correlation to age and genotype. Abnormalities in circadian rhythm and loss of glutamate homeostasis play a key role in the development of these disorders. Sleep disorders, epilepsy, gastrointestinal problems characterize CDKL5 Deficiency Disorder (CDD). Sleep impairment is an area of overlap between RTT and MECP2 duplication syndrome along with epilepsy, regression and others. Sleep dysfunction and epilepsy are deeply linked. Sleep deprivation could be an aggravating factor of epilepsy and anti-comitial therapy could interfere in sleep structure. Epilepsy prevalence in atypical Rett syndrome with severe clinical phenotype is higher than in classical Rett syndrome. However, RTT present a significant lifetime risk of epilepsy too. Sleep disturbances impact on child's development and patients' families and the evidence for its management is still limited. The aim of this review is to analyze pathophysiology, clinical features, the impact on other comorbidities and the management of sleep disorders in Rett syndrome and Rett-related syndrome.
A Retrospective Study of Rare Listeria Meningoencephalitis in Immunocompetent Children in China
Authors: Mo Tingting , Wu Fang , Dou Xiangjun , Wang Dong , Xia Han , Li Xia
Published: March 2022

Objectives

Listeria meningoencephalitis (LMM) is very rare in healthy children. We aimed to assess the clinical features, differential diagnosis, treatment options, and outcomes of LMM in immunocompetent children through a retrospective study.

Methods

The clinical symptoms, laboratory findings, imaging features, antibiotic use, and metagenomic next-generation sequencing (mNGS) results of the cerebrospinal fluid (CSF) were obtained from immunocompetent children who were diagnosed with LMM and admitted to the Xi'an Children's Hospital from May 2018 to July 2020.

Results

The data from 8 immunocompetent children were retrospectively analyzed in this study. The cohort included data from 5 males and 3 females who were aged from 1 year and 7 months to 16 years and 6 months. A total of 4 patients had chilled food before onset. The complications included hyponatremia (3/8), hydrocephalus (2/8), and hemophagocytic syndrome (1/8). In total, 8 patients were diagnosed with Listeria monocytogenes by positive CSF culture or mNGS results. The positive rate of CSF culture was 62.5% (5/8). A total of 5 patients conducted CSF mNGS, and the results of the mNGS were positive in 4 patients (80%, 4/5) and suspected in 1 patient. A total of 7 patients changed their therapeutic regimen to combined antibacterial therapies that included linezolid and meropenem (5/8), or ampicillin and meropenem (2/8). A total of 5 patients had favorable outcomes (Glasgow Outcome Scale, GOSE = 5) while two patients had unfavorable outcomes (GOSE = 1) and were complicated with hyponatremia and hydrocephalus.

Conclusions

Listeria meningoencephalitis (LMM) can occur in children with normal immune function and is commonly mistaken for other central nervous system infections. L. monocytogenes can be quickly and accurately detected by mNGS. Hyponatremia and hydrocephalus may indicate unfavorable outcomes.
Psychometric Properties of the Revised Dysexecutive Questionnaire in a Non-clinical Population
Authors: Wakely Hannah , Radakovic Ratko , Bateman Andrew , Simblett Sara , Fish Jessica , Gracey Fergus
Published: March 2022

Aims

The aim of this study was to assess the psychometric properties of the revised self-rated version of the Dysexecutive Questionnaire (DEX-R) within a non-clinical sample.

Methods

The study was hosted online, with 140 participants completing the DEX-R, GAD-2 and PHQ-2. Sixty participants also completed the FrSBe, with 99 additionally completing the DEX-R again 3 weeks later. Correlations with demographic factors and symptoms of anxiety and depression were conducted. Rasch and factor analysis were also used to explore underlying subconstructs.

Results

The DEX-R correlated highly with the FrSBe, indicating sound concurrent validity. Internal consistency, split-half reliability and test-retest reliability were excellent. Age and symptoms of depression and anxiety correlated with DEX-R scores, with older age associated with less dysexecutive problems. The Rasch analysis confirmed the multidimensionality of the rating scale, and a three-factor structure was found relating to activation-self-regulatory, cognitive and social-emotional processes. Frequencies of responses on DEX-R items varied, many were not fully endorsed indicating specific relevance of most but not all items to patients.

Conclusion

Interpretations of DEX-R ratings of dysexecutive problems should consider mood and individual variation. Systematic comparison of DEX-R responses between healthy and clinical groups could help identify a suitable cut off for dysexecutive symptoms.
Visual Motion Coherence Responses in Human Visual Cortex
Authors: Rina Andriani , Papanikolaou Amalia , Zong Xiaopeng , Papageorgiou Dorina T. , Keliris Georgios A. , Smirnakis Stelios M.
Published: March 2022

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here, we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in the area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in the area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in the area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury.
Healthy and Sustainable Food Shopping: A Survey of Intentions and Motivations
Authors: Blanke Julia , Billieux Joël , Vögele Claus
Published: March 2022

Objectives

To determine the relationship between sustainable and healthy food shopping behavior comparing general motivation with the immediate intention to act.

Method

We conducted an online survey of 144 staff at the Cork Institute of Technology, Ireland, using a questionnaire based on the Theory of Planned Behavior and the Self-Determination Theory to compute the Behavioral Intention score and the Relative Autonomy Index in relation to healthy and sustainable grocery shopping.

Results

The intention to shop healthy food was higher (p < 0.001, Cohen's d = 0.56) than the intention to shop in a sustainable way. A significant intention-action gap was observed for both healthy (p < 0.001, Cohen's d = 0.97) and sustainable grocery shopping (p < 0.001, Cohen's d = 1.78). While there was a significant correlation (p < 0.001) between the longer-term motivations to act in a healthy and sustainable way, this association was not significant (p = 0.16) for the more short-term Behavioral Intention scores.

Conclusion and Implications

Health was identified as a more important driver for dietary behavior compared to sustainability. While longer-term motivation shows a stronger correlation between healthy and sustainable grocery shopping, short-term intentions do not follow this pattern as strongly. A significant intention-action gap exists for both, which is stronger for sustainability than for health.
RDAU-Net: Based on a Residual Convolutional Neural Network With DFP and CBAM for Brain Tumor Segmentation
Authors: Wang Jingjing , Yu Zishu , Luan Zhenye , Ren Jinwen , Zhao Yanhua , Yu Gang
Published: March 2022

Due to the high heterogeneity of brain tumors, automatic segmentation of brain tumors remains a challenging task. In this paper, we propose RDAU-Net by adding dilated feature pyramid blocks with 3D CBAM blocks and inserting 3D CBAM blocks after skip-connection layers. Moreover, a CBAM with channel attention and spatial attention facilitates the combination of more expressive feature information, thereby leading to more efficient extraction of contextual information from images of various scales. The performance was evaluated on the Multimodal Brain Tumor Segmentation (BraTS) challenge data. Experimental results show that RDAU-Net achieves state-of-the-art performance. The Dice coefficient for WT on the BraTS 2019 dataset exceeded the baseline value by 9.2%.
Determinants of Non-Participation in Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis
Authors: Ding Lilu , Wang J. , Greuter M. J. W. , Goossens M. , Van Hal Guido , de Bock Geertruida H.
Published: March 2022

Background

Breast cancer (BC) screening can be performed in a screening program (BCSP) or in opportunistic screening. The existing reviews on the determinants of non-participation depend on self-reported data which may be biased. Furthermore, no distinction was made between the probably different determinants of both screening strategies.

Objective

To find the determinants of non-participation in BCSP by means of a meta-analysis.

Methods

PubMed, Embase, and Web of Science were searched for observational studies which quantified factors associated with non-participation in BCSP in a general population. Studies on opportunistic screening and studies using self-reported data were excluded. A random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by stratification of the results.

Results

Twenty-nine studies with in a total of 20,361,756 women were included. Low income (OR: 1.20, 95% CI: 1.10–1.30), low education (OR: 1.18, 95% CI: 1.05–1.32), living far from an assigned screening unit (OR: 1.15, 95% CI: 1.07–1.24), being immigrant (OR: 2.64, 95% CI: 2.48–2.82), and having a male family doctor (OR: 1.43, 95% CI: 1.20–1.61) was associated with higher non-participation in screening. Reminders sent to non-attenders and estimations of ORs (adjusted or not) partly explained substantial heterogeneity.

Conclusion

In this meta-analysis excluding studies on the non-participation in opportunistic screening, or with self-reported data on non-participation, the well-known determinants for non-participation are still significant, but less strong. This analysis only supports the relevance of meta-analysis of studies with registered non-participation in a BCSP.

Systematic Review Registration

PROSPERO, CRD42020154016.
Comprehensive Atlas of Circulating Rare Cells Detected by SE-iFISH and Image Scanning Platform in Patients With Various Diseases
Authors: Hu Binjie , Gong Yanping , Wang Yulan , Xie Jianzhu , Cheng Jin , Huang Qian
Published: March 2022

Objective

Circulating rare cells (CRCs) are known as a crucial nucleated cellular response to pathological conditions, yet the landscape of cell types across a wide variety of diseases lacks comprehensive understanding. This study aimed at detecting and presenting a full spectrum of highly heterogeneous CRCs in clinical practice and further explored the characterization of CRC subtypes in distinct biomarker combinations and aneuploid chromosomes among various disease groups.

Methods

Peripheral blood was obtained from 2,360 patients with different cancers and non-neoplastic diseases. CRC capture and identification were accomplished using a novel platform integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) strategy with a high-throughput automated image scanning system, on which hemocyte, tumor, epithelial, endothelial, mesenchymal, and stemness biomarkers were immunostained and displayed simultaneously. Double chromosome enumeration probe (CEP8 and CEP12) co-detection was performed on isolated CRCs from an extended trial for two chromosome ploidy patterns.

Results

A comprehensive atlas categorizing the diverse CRCs into 71 subtypes outlining was mapped out. The presence of epithelial–mesenchymal transition (EMT) or endothelial–mesenchymal transition (EndoMT), the cells with progenitor property, hematologic CRCs expressing multiple biomarkers, CRCs at “naked nuclei” status, and the rarely reported aneuploid mesenchymal epithelial–endothelial fusion cluster were described. Circulating tumor cells (CTCs) were detected in 2,157 (91.4%) patients; the total numbers of CTCs and circulating tumor-derived endothelial cells (CTECs) were relatively higher in several digestive system cancer types and non-neoplastic infectious diseases (p < 0.05). Co-detection combining CEP8 and CEP12 showed a higher diagnostic specificity on account of 57.27% false negativity of CRC detection through a single probe of CEP8.

Conclusions

The alternative biomarkers and chromosomes to be targeted by SE-iFISH and the image scanning platform, along with the comprehensive atlas, offer insight into the heterogeneity of CRCs and reveal potential contributions to specific disease diagnosis and therapeutic target cell discovery.
Lymphocytes Infiltration and Expression of PD-1 and PD-L1 in Colorectal Cancer Between HIV-Infected and Non-HIV-Infected Patients: A Propensity Score Matched Cohort Study
Authors: Cao Ye , Wu Qian , Lian Shixian , Deng Li
Published: March 2022

Background

Tumor-infiltrating lymphocytes (TILs) and expression of programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) are crucial for antitumor immunity. However, the status remains undetermined in HIV-infected colorectal cancer (CRC), limiting the use of immunotherapy in HIV-infected CRC patients.

Methods

We examined 27 HIV-infected patients and 120 non-HIV-infected patients with CRC from 2015-2020 at Shanghai Public Health Clinical Center. After matching the propensity score, 13 paired patients in the two groups were also compared. The expression of PD-1/PD-L1 as well as tumor-infiltrating CD4, CD8, and CD56 immune cells was examined using multiplex immunofluorescent analysis. The cell density for positive staining was calculated (cells/mm2) and compared between HIV-infected and non-HIV-infected groups. In addition, the co-expression of PD-1 on immune cells and PD-L1 on tumor cells was compared in these two groups.

Results

The mean densities of tumor-infiltrating CD4, CD8, CD56 immune cells were 620.2, 261.2, and 0.2 cells/mm2, respectively, in HIV-infected colorectal tumors compared with 698.6, 243, and 14 cells/mm2 in non-HIV-infected tumors. PD-1 expression was 227 cells/mm2 in HIV-infected tumors and 365.2 cells/mm2 in non-HIV-infected tumors. Besides, PD-L1 expression was 108.5 cells/mm2 in HIV-infected tumors and 126.8 cells/mm2 in non-HIV-infected tumors, and no significant difference was found between the two groups. Similarly, there were no significant differences in the expression of PD-1 on TILs and PD-L1 on tumor cells.

Conclusion

HIV-infected CRC patients had similar tumor-infiltrating lymphocytes (CD4 and CD8 T cells) compared to non-HIV-infected controls and substantially similar PD-1 expression on TILs and PD-L1 expression on tumors. These results support the inclusion of HIV-infected CRC patients in future immunotherapy trials.
Lisinopril Mitigates Radiation-Induced Mitochondrial Defects in Rat Heart and Blood Cells
Authors: Ortiz de Choudens Saryleine , Sparapani Rodney , Narayanan Jayashree , Lohr Nicole , Gao Feng , Fish Brian L. , Zielonka Monika , Gasperetti Tracy , Veley Dana , Beyer Andreas , Olson Jessica , Jacobs Elizabeth R. , Medhora Meetha
Published: March 2022

The genetic bases and disparate responses to radiotherapy are poorly understood, especially for cardiotoxicity resulting from treatment of thoracic tumors. Preclinical animal models such as the Dahl salt-sensitive (SS) rat can serve as a surrogate model for salt-sensitive low renin hypertension, common to African Americans, where aldosterone contributes to hypertension-related alterations of peripheral vascular and renal vascular function. Brown Norway (BN) rats, in comparison, are a normotensive control group, while consomic SSBN6 with substitution of rat chromosome 6 (homologous to human chromosome 14) on an SS background manifests cardioprotection and mitochondrial preservation to SS rats after injury. In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background.
Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF–LIF Interaction
Authors: Ke Ning , Chen Lin , Liu Qing , Xiong Haibo , Chen Xinke , Zhou Xiyuan
Published: March 2022

Purpose

To investigate the role of the miR-211-5p-GDNF signaling pathway in carboplatin resistance of retinoblastoma Y79 cells and what factors it may be affected by.

Methods

A carboplatin-resistant retinoblastoma cell line (Y79R) was established in vitro. RNA-seq and microRNA-seq were constructed between Y79 and Y79R cells. RNA interference, RT-PCR, Western blot (WB), and flow cytometry were used to verify the expression of genes and proteins between the two cell lines. The TargetScan database was used to predict the microRNAs that regulate the target genes. STING sites and Co-Immunoprecipitation (COIP) were used to study protein–protein interactions.

Results

GDNF was speculated to be the top changed gene in the drug resistance in Y79R cell lines. Moreover, the speculation was verified by subsequent RT-PCR and WB results. When the expression of GDNF was knocked down, the IC50 of the Y79R cell line significantly reduced. GDNF was found to be the target gene of miR-211-5p. Downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells. MiR-211-5p can regulate the expression of GDNF. Our further research also found that GDNF can bind to LIF which is also a secreted protein.

Conclusion

Our results suggest that downregulation of miR-211-5p promotes carboplatin resistance in human retinoblastoma Y79 cells, and this process can be affected by GDNF–LIF interaction. These results can provide evidence for the reversal of drug resistance of RB.
ZDQ-0620, a Novel Phosphatidylinositol 3-Kinase Inhibitor, Inhibits Colorectal Carcinoma Cell Proliferation and Suppresses Angiogenesis by Attenuating PI3K/AKT/mTOR Pathway
Authors: Qin Xiaochun , Liu Mingyue , Xu Chang , Xing Bo , Xu Xiangbo , Wu Yuting , Ding Huaiwei , Zhao Qingchun
Published: March 2022

The PI3K/AKT pathway plays a central role in human cancers, aberrant activation of this pathway is associated with tumorigenesis, cancer progression and angiogenesis. Based on the importance of the PI3K/AKT pathway in malignancies, we developed a 4-aminoquinazoline derivative, ZDQ-0620, initially envisioned as a novel pan-PI3K inhibitor. This study aimed to evaluate the potential target of ZDQ-0620 and its anticancer effect in human colorectal carcinoma (CRC). PI3K-kinase activity test showed IC50 of ZDQ-0620 against PI3Ka was 0.5 nM; molecular docking, CETSA assay and western blotting was further performed to predict ZDQ-0620 was a PI3K/AKT pathway inhibitor by targeting PI3K. To identify the effect of ZDQ-0620 on CRC cells, Sulforhodamine B (SRB) assay, flow cytometry, and Cell morphology analysis were conducted. The results showed that ZDQ-0620 inhibited the proliferation, migration and invasion of CRC cells, induced apoptosis through G0/G1 cell cycle arrest and mitochondrial pathway. Additionally, ZDQ-0620 inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). In vivo, neovascularization of rat aortic ring and chick chorioallantoic membrane (CAM) induced by VEGF was diminished when treated with ZDQ-0620. These results indicate that ZDQ-0620 induce apoptosis and anti-angiogenesis via inhibits the PI3K/AKT pathway. We suggest that the great potential of ZDQ-0620 as an effective treatment candidate against CRC.
A Comparative Study of Systems Pharmacology and Gene Chip Technology for Predicting Targets of a Traditional Chinese Medicine Formula in Primary Liver Cancer Treatment
Authors: Li Songzhe , Sun Yang , Sun Yue
Published: March 2022

Background: The systems pharmacology approach is a target prediction model for traditional Chinese medicine and has been used increasingly in recent years. However, the accuracy of this model to other prediction models is yet to be established.

Objective: To compare the systems pharmacology modelwithexperimental gene chip technology by using these models to predict targets of a traditional Chinese medicine formulain the treatment of primary liver cancer.

Methods: Systems pharmacology and gene chip target predictions were performed for the traditional Chinese medicine formula ZhenzhuXiaojiTang (ZZXJT). A third square alignment was performed with molecular docking.

Results: Identification of systems pharmacology accounted for 17% of targets, whilegene chip-predicted outcomes accounted for 19%.Molecular docking showed that the top ten targets (excludingcommon targets) of the system pharmacology model had better binding free energies than the gene chip model using twocommon targets as a benchmark. For both models, the core drugs predictions were more consistent than the core small molecules predictions.

Conclusion:In this study, the identified targets of systems pharmacology weredissimilar to those identified by gene chip technology; whereas the core drug and small molecule predictions were similar.
Neoplasm Risk in Patients With Rheumatoid Arthritis Treated With Fostamatinib: A Systematic Review and Meta-analysis
Authors: Chen Yuehong , Liu Huan , Tian Yunru , Luo Zhongling , Yin Geng , Xie Qibing
Published: March 2022

Objective: This study aimed to assess neoplasm risk in patients with rheumatoid arthritis (RA) treated with fostamatinib.

Methods: Studies were collected from electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that reported neoplasms in patients with RA treated with fostamatinib. Study selection was repeated by two reviewers based on the study selection criteria. Data were collected and methodological quality assessment was performed. Data were pooled using the Peto odds ratio (OR) with a 95% confidence interval (CI). Subgroup analyses of the fostamatinib dose, trial duration, neoplasm nature, and neoplasm-originating systems were conducted. A funnel plot was used to estimate publication bias, and sensitivity analysis was performed to test the robustness of the results.

Results: Seven trials involving 4,971 participants showing low to moderate risk of bias were included. Compared with the placebo, fostamatinib use was not associated with the risks of overall neoplasms (Peto OR = 2.62, 95%CI 0.97–7.10), malignant neoplasms (Peto OR = 3.08, 95%CI 0.96–9.91), or benign neoplasms (Peto OR = 1.71, 95%CI 0.26–11.36). Nevertheless, compared with the placebo, a longer duration of fostamatinib use had a higher risk of malignant neoplasms (Peto OR = 4.49, 95%CI 1.03–19.60) at 52 weeks. As for malignant neoplasms in the digestive system, lower doses of fostamatinib reduced the neoplasm risk (100 mg bid vs 150 mg qd: Peto OR = 0.06, 95%CI 0.01–0.59). Sensitivity analysis showed no significant differences in the effective trends, and no publication bias was found.

Conclusion: Fostamatinib is not associated with the risks of overall neoplasms as compared to placebo. Nevertheless, a longer duration of fostamatinib use may be associated with a risk of malignant neoplasms and higher doses of fostamatinib may increase malignant neoplasms in the digestive system. Further well-planned cohort studies with a larger study population are needed to elucidate these outcomes.

Systematic ReviewRegistration: PROSPERO (CRD42020202121).
Understanding Kratom Use: A Guide for Healthcare Providers
Authors: Swogger Marc T. , Smith Kirsten E. , Garcia-Romeu Albert , Grundmann Oliver , Veltri Charles A. , Henningfield Jack E. , Busch Lorna Y.
Published: March 2022

Kratom (Mitragyna speciosa Korth., Rubiaceae) is a plant native to Southeast Asia, where it has been used for centuries as a mild stimulant and as medicine for various ailments. More recently, as kratom has gained popularity in the West, United States federal agencies have raised concerns over its safety leading to criminalization in some states and cities. Some of these safety concerns have echoed across media and broad-based health websites and, in the absence of clinical trials to test kratom’s efficacy and safety, considerable confusion has arisen among healthcare providers. There is, however, a growing literature of peer-reviewed science that can inform healthcare providers so that they are better equipped to discuss kratom use with consumers and people considering kratom use within the context of their overall health and safety, while recognizing that neither kratom nor any of its constituent substances or metabolites have been approved as safe and effective for any disease. An especially important gap in safety-related science is the use of kratom in combination with physiologically active substances and medicines. With these caveats in mind we provide a comprehensive overview of the available science on kratom that has the potential to i clarity for healthcare providers and patients. We conclude by making recommendations for best practices in working with people who use kratom.
Induction of Apoptosis by Metabolites of Rhei Radix et Rhizoma (Da Huang): A Review of the Potential Mechanism in Hepatocellular Carcinoma
Authors: Jiang Huanyu , Tang Wuyinuo , Song Yang , Jin Wei , Du Quanyu
Published: March 2022

Liver cancer is a global disease with a high mortality rate and limited treatment options. Alternations in apoptosis of tumor cells and immune cells have become an important method for detailing the underlying mechanisms of hepatocellular carcinoma (HCC). Bcl-2 family, Caspase family, Fas and other apoptosis-related proteins have also become antagonistic targets of HCC. Da Huang (Rhei Radix et Rhizoma, RR), a traditional Chinese herb, has recently demonstrated antitumor behaviors. Multiple active metabolites of RR, including emodin, rhein, physcion, aloe-emodin, gallic acid, and resveratrol, can successfully induce apoptosis and inhibit HCC. However, the underlying mechanisms of these metabolites inhibiting the occurrence and development of HCC by inducing apoptosis is complicated owing to the multi-target and multi-pathway characteristics of traditional Chinese herbs. Accordingly, this article reviews the pathways of apoptosis, the relationship between HCC and apoptosis, the role and mechanism of apoptosis induced by mitochondrial endoplasmic reticulum pathway and death receptor pathway in HCC and the mechanism of six RR metabolites inhibiting HCC by inducing apoptosis.
Long-Term Biocompatibility of a Highly Viscously Thiol-Modified Cross-Linked Hyaluronate as a Novel Vitreous Body Substitute
Authors: Hurst Jose , Rickmann Annekatrin , Heider Nele , Hohenadl Christine , Reither Charlotte , Schatz Andreas , Schnichels Sven , Januschowski Kai , Spitzer Martin S.
Published: March 2022

Purpose: In surgical ophthalmology, the treatment of complicated retinal and vitreous diseases is one of the central challenges. For this purpose, the vitreous body is removed as part of the standard therapy and replaced by a temporary tamponade to stabilize the position of the retina. Since the tamponading properties of previous materials such as silicone oils, gases, or semi-fluorinated alkanes are a combination of their surface tension and their buoyancy vector, they cannot completely fill the vitreous cavity. The aim of this work was to test in vivo a novel vitreous body substitute (ViBos strong) based on cross-linked hyaluronic acid for its compatibility.

Methods: A pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of 18 pigmented rabbits, with subsequent injection of ViBos strong. Follow-up examination included slit-lamp examination, funduscopy, intraocular pressure measurements (IOP), optical coherence tomography (OCT), and electroretinogram (ERG) measurements. The rabbits were sacrificed at three different time points (1, 3, and 6 months; each 6 animals) and examined macroscopically and prepared for histological examination (HE staining) and immunohistochemistry (Brn3a and glial fibrillary acidic protein (GFAP)).

Results: ViBos strong demonstrated good intraoperative handling and remained stable for at least 1 month and degraded slowly over 6 months. IOP was within clinical acceptable values at all follow-up examinations. Retinal function was well preserved after instillation of the hydrogel and comparable to the untreated eye after 6 months in OCT, ERG, and histological examinations. An increase in the GFAP expression was found in the surgery eyes, with a peak in the 3-month group. The Brn3a expression was not significantly affected by vitrectomy with ViBos strong.

Conclusion: Highly viscously thiol-modified cross-linked hyaluronate showed a good biocompatibility in rabbit eyes over 6 months after vitrectomy, making it a promising potential as a vitreous substitute.
Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders
Authors: Issa Shaza S. , Shaimardanova Alisa A. , Valiullin Victor V. , Rizvanov Albert A. , Solovyeva Valeriya V.
Published: March 2022

Lysosomal storage diseases (LSDs) are a group of approximately 50 genetic disorders caused by mutations in genes coding enzymes that are involved in cell degradation and transferring lipids and other macromolecules. Accumulation of lipids and other macromolecules in lysosomes leads to the destruction of affected cells. Although the clinical manifestations of different LSDs vary greatly, more than half of LSDs have symptoms of central nervous system neurodegeneration, and within each disorder there is a considerable variation, ranging from severe, infantile-onset forms to attenuated adult-onset disease, sometimes with distinct clinical features. To date, treatment options for this group of diseases remain limited, which highlights the need for further development of innovative therapeutic approaches, that can not only improve the patients’ quality of life, but also provide full recovery for them. In many LSDs stem cell-based therapy showed promising results in preclinical researches. This review discusses using mesenchymal stem cells for different LSDs therapy and other neurodegenerative diseases and their possible limitations.
Frequency-to-Time Mapping Technique for Direct Spectral Characterization of Biphoton States From Pulsed Spontaneous Parametric Processes
Authors: Khodadad Kashi Anahita , Sader Lynn , Haldar Raktim , Wetzel Benjamin , Kues Michael
Published: March 2022

The well-established frequency-to-time mapping technique is employed as a convenient and time-efficient method to directly characterize the spectral correlations of biphoton states from a pulsed-excited spontaneous parametric down-conversion process. We were enabled by this technique to implement for the first time, the spectral Hanbury-Brown and Twiss measurement, revealing directly the single frequency-mode bandwidth of the biphoton state.
Design Concept for a Future Super Proton-Proton Collider
Authors: Tang Jingyu
Published: March 2022

Following the discovery of the Higgs boson at the LHC in 2012, new large colliders are being considered and studied by the international high-energy community to explore the Higgs boson in details and to probe new physics beyond the Standard Model. In China, a two-stage circular collider project, CEPC-SPPC was proposed and is under study. The first stage, CEPC (Circular Electron Positron Collier, a so-called Higgs factory) is focused on the Higgs physics, and the second stage, SPPC (Super Proton-Proton Collider) will be an energy frontier collider and a discovery machine beyond the LHC. The two colliders will share a same tunnel of 100 km in circumference, with a goal of 250 GeV in center-of-mass for CEPC and 75 TeV for SPPC Phase-I and 125–150 TeV for the SPPC ultimate goal. This article presents the design concept of the SPPC and some study results about the key accelerator physics problems and technical issues, which include luminosity optimization, beam collimation, beam-beam effects, longitudinal beam dynamics, high-field magnets and beam screen.
Estimation of Cerebral Hemodynamics and Oxygenation During Various Intensities of Rowing Exercise: An NIRS Study
Authors: Hiura Mikio , Shirai Yusuke , Shibutani Hirohide , Funaki Akio , Takahashi Katsumi , Katayama Yoichi
Published: March 2022

Purpose

This study aimed to investigate changes in cerebral hemodynamics and oxygenation at moderate, heavy, maximal and supramaximal intensities of rowing exercise. It also examined whether these changes reflect alterations in sensation of effort and mood. We also aimed to examine the effects of peak pulmonary oxygen consumption (V.O2peak) on cerebral oxygenation.

Methods

Eleven rowers, consisting out of six athletes and five recreational rowers [two female; age, 27 ± 9 years; height, 171 ± 7 cm, body mass, 67 ± 9 kg;V.O2peak, 53.5 ± 6.5 mL min–1kg–1] rowed a 13-min session separated by 10 and 3 min, at 70 (Ex70%) and 80% ofV.O2peak(Ex80%), respectively, on a rowing ergometer, followed by three sessions of 1-min supramaximal exercise (ExSp). After a warm-up at 60% ofV.O2peak(ExM), seven male rowers performed a 2,000 m all-out test (Ex2000). Cardiovascular and respiratory variables were measured. Cerebral oxygenation was investigated by near-infrared time-resolved spectroscopy (TRS) to measure cerebral hemoglobin oxygen saturation (ScO2) and total hemoglobin concentration ([HbT]) in the prefrontal cortex (PFC) quantitatively. We estimated the relative changes from rest in cerebral metabolic rate for oxygen (rCMRO2) using TRS at all intensities. During Ex70%and Ex80%, ratings of perceived exertion (RPE) were monitored, and alteration of the subject’s mood was evaluated using a questionnaire of Positive-and-Negative-Affect-Schedule after Ex70%and Ex80%.

Results

When exercise intensity changed from Ex70%to Ex80%, the sense of effort increased while ScO2decreased. [HbT] remained unchanged. After Ex70%and Ex80%, a negative mood state was less prominent compared to rest and was accompanied by increases in both ScO2and [HbT]. At termination of Ex2000, ScO2decreased by 23% compared to rest. Changes in ScO2correlated withV.O2peakonly during Ex2000(r= −0.86;p= 0.01). rCMRO2did not decrease at any intensities.

Conclusion

Our results suggest that alterations in the sense of effort are associated with oxygenation in the PFC, while positive changes in mood status are associated with cerebral perfusion and oxygen metabolism estimated by TRS. At exhaustion, the cerebral metabolic rate for oxygen is maintained despite a decrease in ScO2.
Sex Differences in Metabolic and Behavioral Responses to Exercise but Not Exogenous Osteocalcin Treatment in Mice Fed a High Fat Diet
Authors: Winberg Jordan , Rentz Jesse , Sugamori Kim , Swardfager Walter , Mitchell Jane
Published: March 2022

Background

Exercise helps improve glucose handling in diabetes and has been shown to improve mood and cognition in other conditions. Osteocalcin, a protein produced by bone osteoblasts, was reported to have endocrine actions to improve both metabolism and also improve age-related cognitive deficits in mice.

Methods

This study was designed to compare the effects of daily treadmill running exercise with injection of osteocalcin in high fat diet (HFD) induced diabetes in male and female C57BL/6J mice. Following established glucose intolerance and treatment for 8 weeks, mice were assessed for anxiety on an elevated plus maze, motivation by tail suspension test and cognition and memory in a puzzle box. Endogenous osteocalcin was measured by ELISA.

Results

Mice on HFD had high weight gain, glucose intolerance and increased white fat. Exercise increased circulating osteocalcin levels in female mice but decreased them in male mice. Exercise also decreased weight gain and improved glucose tolerance in female but not male mice; however, treatment with osteocalcin made no metabolic improvements in either males or females. HFD induced anxiety only in female mice and this was not improved by osteocalcin. Exercise induced anxiety only in male mice. HFD also increased depressive-like behavior in both sexes, and this was improved by either exercise or osteocalcin treatment. Cognitive deficits were seen in both male and female mice on HFD. Exercise improved cognitive performance in female but not male mice, while osteocalcin treatment improved cognitive performance in both sexes.

Conclusion

There were sex differences in the effects of exercise on endogenous osteocalcin regulation that correlated with improvements in cognitive but not metabolic outcomes. Exogenous osteocalcin did not improve metabolism but was effective in improving HFD-induced cognitive deficits. Sex is an important variable in hormonal and cognitive responses to exercise in diabetes.
Translocation of Foliar Absorbed Zn in Sunflower (Helianthus annuus) Leaves
Authors: Li Cui , Wang Linlin , Wu Jingtao , Blamey F. Pax C. , Wang Nina , Chen Yanlong , Ye Yin , Wang Lei , Paterson David J. , Read Thea L. , Wang Peng , Lombi Enzo , Wang Yuheng , Kopittke Peter M.
Published: March 2022

Foliar zinc (Zn) fertilization is an important approach for overcoming crop Zn deficiency, yet little is known regarding the subsequent translocation of this foliar-applied Zn. Using synchrotron-based X-ray fluorescence microscopy (XFM) and transcriptome analysis, the present study examined the translocation of foliar absorbed Zn in sunflower (Helianthus annuus) leaves. Although bulk analyses showed that there had been minimal translocation of the absorbed Zn out of the leaf within 7 days, in situ analyses showed that the distribution of Zn in the leaf had changed with time. Specifically, when Zn was applied to the leaf for 0.5 h and then removed, Zn primarily accumulated within the upper and lower epidermal layers (when examined after 3 h), but when examined after 24 h, the Zn had moved to the vascular tissues. Transcriptome analyses identified a range of genes involved in stress response, cell wall reinforcement, and binding that were initially upregulated following foliar Zn application, whereas they were downregulated after 24 h. These observations suggest that foliar Zn application caused rapid stress to the leaf, with the initial Zn accumulation in the epidermis as a detoxification strategy, but once this stress decreased, Zn was then moved to the vascular tissues. Overall, this study has shown that despite foliar Zn application causing rapid stress to the leaf and that most of the Zn stayed within the leaf over 7 days, the distribution of Zn in the leaf had changed, with Zn mostly located in the vascular tissues 24 h after the Zn had been applied. Not only do the data presented herein provide new insight for improving the efficiency of foliar Zn fertilizers, but our approach of combining XFM with a transcriptome methodological system provides a novel approach for the study of element translocation in plants.
Optimizing Crop Planting Schedule Considering Planting Window and Storage Capacity
Authors: Sajid Saiara Samira , Hu Guiping
Published: March 2022

Technology advancement has contributed significantly to productivity improvement in the agricultural sector. However, field operation and farm resource utilization remain a challenge. For major row crops, designing an optimal crop planting strategy is crucial since the planting dates are contingent upon weather conditions and storage capacity. This manuscript proposes a two-stage decision support system to optimize planting decisions, considering weather uncertainties and resource constraints. The first stage involves creating a weather prediction model for Growing Degree Units (GDUs). In the second stage, the GDUs prediction from the first stage is incorporated to formulate an optimization model for the planting schedule. The efficacy of the proposed model is demonstrated through a case study based on Syngenta Crop Challenge (2021). It has been shown that the 1D-CNN model outperforms other prediction models with an RRMSE of 7 to 8% for two different locations. The decision-making model in the second stage provides an optimal planting schedule such that weekly harvested quantities will be evenly allocated utilizing a minimum number of harvesting weeks. We analyzed the model performance for two scenarios: fixed and flexible storage capacity at multiple geographic locations. Results suggest that the proposed model can provide an optimized planting schedule considering planting window and storage capacity. The model has also demonstrated its robustness under multiple scenarios.
Influence of Elevated Temperatures on Resistance Against Phoma Stem Canker in Oilseed Rape
Authors: Noel Katherine , Qi Aiming , Gajula Lakshmi Harika , Padley Craig , Rietz Steffen , Huang Yong-Ju , Fitt Bruce D. L. , Stotz Henrik U.
Published: March 2022

Cultivar resistance is an important tool in controlling pathogen-related diseases in agricultural crops. As temperatures increase due to global warming, temperature-resilient disease resistance will play an important role in crop protection. However, the mechanisms behind the temperature-sensitivity of the disease resistance response are poorly understood in crop species and little is known about the effect of elevated temperatures on quantitative disease resistance. Here, we investigated the effect of temperature increase on the quantitative resistance of Brassica napus against Leptosphaeria maculans. Field experiments and controlled environment inoculation assays were done to determine the influence of temperature on R gene-mediated and quantitative resistance against L. maculans; of specific interest was the impact of high summer temperatures on the severity of phoma stem canker. Field experiments were run for three consecutive growing seasons at various sites in England and France using twelve winter oilseed rape breeding lines or cultivars with or without R genes and/or quantitative resistance. Stem inoculation assays were done under controlled environment conditions with four cultivars/breeding lines, using avirulent and virulent L. maculans isolates, to determine if an increase in ambient temperature reduces the efficacy of the resistance. High maximum June temperature was found to be related to phoma stem canker severity. No temperature effect on stem canker severity was found for the cultivar ES Astrid (with only quantitative resistance with no known R genes). However, in the controlled environmental conditions, the cultivar ES Astrid had significantly smaller amounts of necrotic tissue at 20°C than at 25°C. This suggests that, under a sustained temperature of 25°C, the efficacy of quantitative resistance is reduced. Findings from this study show that temperature-resilient quantitative resistance is currently available in some oilseed cultivars and that efficacy of quantitative resistance is maintained at increased temperature but not when these elevated temperatures are sustained for a long period.