bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Endovascular Rescue Therapy on the Clinical and Radiological Outcome After Aneurysmal Subarachnoid Hemorrhage: A Safe and Effective Treatment Option for Hemodynamically Relevant Vasospasm?
Authors: Mielke Dorothee , Döring Katja , Behme Daniel , Psychogios Marios Nikos , Rohde Veit , Malinova Vesna
Published: May 2022

Objective

Cerebral vasospasm (CVS) represents one of the multiple contributors to delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Especially the management of CVS, refractory to medical treatment, is a challenging task during the acute phase after aSAH. Endovascular rescue therapies (ERT), such as medical and mechanical dilation, are possible treatment options on an individual basis. However, data about the influence on the patients' functional outcomes are limited. This study aims to assess the impact of ERT on the long-term functional outcome in aSAH-patients with refractory CVS.

Methods

We performed a retrospective analysis of aSAH patients treated between 2012 and 2018. CVS was considered refractory, if it persisted despite oral/intravenous nimodipine application and induced hypertension. The decision to perform ETR was made on an individual basis, according to the detection of “tissue at risk” on computed tomography perfusion (CTP) scans and CVS on computed tomography angiography (CTA) or digital subtraction angiography (DSA). The functional outcome was assessed according to the modified Rankin scale (mRS) 3 months after the ictus, whereas an mRS ≤ 2 was considered as a good outcome.

Results

A total of 268 patients were included. Out of these, 205 patients (76.5%) were treated without ERT (group 1) and 63 patients (23.5%) with ERT (group 2). In 20 patients (31.8%) balloon dilatation was performed, in 23 patients (36.5%) intra-arterial nimodipine injection alone, and in 20 patients (31.8%) both procedures were combined. Considering only the patient group with DCI, the patients who were treated with ERT had a significantly better outcome compared to the patients without ERT (Mann–Whitney test, p = 0.02).

Conclusion

Endovascular rescue therapies resulted in a significantly better functional outcome in patients with DCI compared to the patient group treated without ETR. CTP and CTA-based identification of “tissue at risk” might be a reliable tool for patient selection for performing ERT.
Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study
Authors: Weber Martin S. , Buttmann Mathias , Meuth Sven G. , Dirks Petra , Muros-Le Rouzic Erwan , Eggebrecht Julius C. , Hieke-Schulz Stefanie , Leemhuis Jost , Ziemssen Tjalf
Published: May 2022

Background

Real-world relapsing multiple sclerosis (RMS) and primary progressive MS (PPMS) populations may be more diverse than in clinical trials. Here, we present a first analysis of safety, adherence and persistence data from a real-world cohort of patients newly treated with ocrelizumab.

Methods

CONFIDENCE (ML39632, EUPAS22951) is an ongoing multicenter, non-interventional post authorization safety study assessing patients with RMS or PPMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. For this analysis, patients newly treated with ocrelizumab were analyzed in subgroups by MS phenotype and age over a mean ~1 year of exposure totaling 2,329 patient years [PY]).

Results

At data cutoff (14 October 2020), 1,702 patients with RMS and 398 patients with PPMS were treated with ≥1 dose of ocrelizumab. At baseline, the mean ages (SD) of patients with RMS and PPMS were 41.59 (11.24) and 50.95 (9.88) years and the mean EDSS (Expanded Disability Status Scale) was 3.18 (1.87) and 4.41 (1.59), respectively. The most common adverse events (AEs) and serious AEs across both phenotypes were infections and infestations, with infection SAE rates of 2.8 events/100 PY and 1.5 events/100 PY in patients with RMS and PPMS, respectively. Across all phenotypes, ocrelizumab persistence was 92% at 24 months; median time between doses was ~6 months.

Conclusions

The ocrelizumab safety profile observed in the CONFIDENCE real-world MS population was consistent to the one observed in pivotal clinical trials. High treatment persistence and adherence were observed.

Trial Registration

ML39632, EUPAS22951
Macroglossia Associated With Clobazam Administration: A Case Report and Literature Review
Authors: Zhang Jeff F. , Nickerson Kevin , Piryani Ravi , Farooq Osman , Swayampakula Anil K.
Published: May 2022

Clobazam is a benzodiazepine derivative used as an antiepileptic agent for the treatment of focal and generalized seizures and drug-resistant epilepsy associated with Lennox-Gastaut Syndrome. While somnolence and mood-related side effects are commonly observed, acute macroglossia following initiation of Clobazam therapy has not been previously reported in the medical literature. In this case report, we present a female pediatric patient who developed significant tongue swelling with protrusion beyond the oral cavity after initiation of Clobazam for treatment-resistant epilepsy. Symptoms were unresponsive to antihistamines and steroids but resolved gradually in the days following discontinuation of Clobazam with no lingering sequelae.
Disrupted Spatiotemporal Complexity of Resting-State Electroencephalogram Dynamics Is Associated With Adaptive and Maladaptive Rumination in Major Depressive Disorder
Authors: Wang Jing , Liu Qi , Tian Feng , Zhou Shuzhe , Parra Mario Alfredo , Wang Huali , Yu Xin
Published: May 2022

Patients with major depressive disorder (MDD) exhibit abnormal rumination, including both adaptive and maladaptive forms. However, the neural substrates of rumination in depression remain poorly understood. We hypothesize that divergent spatiotemporal complexity of brain oscillations would be associated with the levels of rumination in MDD. We employed the multi-scale entropy (MSE), power and phase-amplitude coupling (PAC) to estimate the complexity of rhythmic dynamics from the eye-closed high-density electroencephalographic (EEG) data in treatment-naive patients with MDD (n = 24) and healthy controls (n = 22). The depressive, brooding, and reflective subscales of the Ruminative Response Scale were assessed. MDD patients showed higher MSE in timescales finer than 5 (cluster P = 0.038) and gamma power (cluster P = 0.034), as well as lower PAC values between alpha/low beta and gamma bands (cluster P = 0.002- 0.021). Higher reflective rumination in MDD was region-specifically associated with the more localized EEG dynamics, including the greater MSE in scales finer than 8 (cluster P = 0.008), power in gamma (cluster P = 0.018) and PAC in low beta-gamma (cluster P = 0.042), as well as weaker alpha-gamma PAC (cluster P = 0.016- 0.029). Besides, the depressive and brooding rumination in MDD showed the lack of correlations with global long-range EEG variables. Our findings support the disturbed neural communications and point to the spatial reorganization of brain networks in a timescale-dependent migration toward local during adaptive and maladaptive rumination in MDD. These findings may provide potential implications on probing and modulating dynamic neuronal fluctuations during the rumination in depression.
Transcription Pause and Escape in Neurodevelopmental Disorders
Authors: Eigenhuis Kristel N. , Somsen Hedda B. , van den Berg Debbie L. C.
Published: May 2022

Transcription pause-release is an important, highly regulated step in the control of gene expression. Modulated by various factors, it enables signal integration and fine-tuning of transcriptional responses. Mutations in regulators of pause-release have been identified in a range of neurodevelopmental disorders that have several common features affecting multiple organ systems. This review summarizes current knowledge on this novel subclass of disorders, including an overview of clinical features, mechanistic details, and insight into the relevant neurodevelopmental processes.
Heterogeneous Ensemble-Based Spike-Driven Few-Shot Online Learning
Authors: Yang Shuangming , Linares-Barranco Bernabe , Chen Badong
Published: May 2022

Spiking neural networks (SNNs) are regarded as a promising candidate to deal with the major challenges of current machine learning techniques, including the high energy consumption induced by deep neural networks. However, there is still a great gap between SNNs and the few-shot learning performance of artificial neural networks. Importantly, existing spike-based few-shot learning models do not target robust learning based on spatiotemporal dynamics and superior machine learning theory. In this paper, we propose a novel spike-based framework with the entropy theory, namely, heterogeneous ensemble-based spike-driven few-shot online learning (HESFOL). The proposed HESFOL model uses the entropy theory to establish the gradient-based few-shot learning scheme in a recurrent SNN architecture. We examine the performance of the HESFOL model based on the few-shot classification tasks using spiking patterns and the Omniglot data set, as well as the few-shot motor control task using an end-effector. Experimental results show that the proposed HESFOL scheme can effectively improve the accuracy and robustness of spike-driven few-shot learning performance. More importantly, the proposed HESFOL model emphasizes the application of modern entropy-based machine learning methods in state-of-the-art spike-driven learning algorithms. Therefore, our study provides new perspectives for further integration of advanced entropy theory in machine learning to improve the learning performance of SNNs, which could be of great merit to applied developments with spike-based neuromorphic systems.
Timing and Distribution of Mitotic Activity in the Retina During Precocial and Altricial Modes of Avian Development
Authors: Álvarez-Hernán Guadalupe , de Mera-Rodríguez José Antonio , Hernández-Núñez Ismael , Acedo Abel , Marzal Alfonso , Gañán Yolanda , Martín-Partido Gervasio , Rodríguez-León Joaquín , Francisco-Morcillo Javier
Published: May 2022

During development of the vertebrate retina, mitotic activity is defined as apical when is located at the external surface of the neuroepithelium or as non-apical when is found in more internal regions. Apical mitoses give rise to all retinal cell types. Non-apical mitoses are linked to committed horizontal cell precursors that subsequently migrate vitreo-sclerally, reaching their final position in the outer surface of the inner nuclear layer, where they differentiate. Previous studies have suggested differences in the timing of retinal maturation between altricial and precocial bird species. In the present study we analyze qualitatively and quantitatively the mitotic activity in the developing retina of an altricial (zebra finch,Taeniopygia guttata) and a precocial (Japanese quail,Coturnix coturnix) bird species. We found that pHisH3-immunoreactive apical and non-apical mitoses were abundant in theT. guttataretina at the hatching stage. In contrast, pHisH3 immunoreactivity almost disappeared from the quail retina at the embryonic day 10 (E10). Furthermore, we also found that the onset of the appearance of non-apical mitoses occurred at later stages in the altricial bird species than in the precocial one. The disappearance of apical mitoses and the spatiotemporal distribution of non-apical mitoses followed central to peripheral and dorsal to ventral gradients, similar to gradients of cell differentiation described in the retina of birds. Therefore, these results suggest that retinal neurogenesis is active at the hatching stage inT. guttata, and that horizontal cell differentiation is delayed in the altricial bird species compared to the precocial one. Together, this study reveals important insights into the timing differences that regulate bird retinal maturation and provides a better understanding of the evolution of avian altriciality and precociality.
Did It Change Your Mind? Neural Substrates of Purchase Intention Change and Product Information
Authors: Kim Hesun Erin , Kwon Joon Hee , Kim Jae-Jin
Published: May 2022

Price and customer ratings are perhaps the two most important pieces of information consumers rely on when shopping online. This study aimed to elucidate the neural mechanism by which the introduction of these two types of information influences the purchase intention of potential consumers for hedonic products. Participants performed a lip-care product shopping task during functional magnetic resonance imaging, in which they re-disclosed purchase intentions referring to the information of price or rating provided about the products that they had previously disclosed their purchase intentions without any information. Data from 38 young female participants were analyzed to identify the underlying neural regions associated with the intention change and product information. The bilateral frontopolar cortex, bilateral dorsal anterior cingulate cortex (dACC), and left insula activated higher for the unchanged than changed intention condition. The right dACC and bilateral insula also activated more toward the price than the rating condition, whereas the medial prefrontal cortex and bilateral temporoparietal junction responded in the opposite direction. These results seem to reflect the shift to exploratory decision-making strategies and increased salience in maintaining purchase intentions despite referring to provided information and to highlight the involvement of social cognition-related regions in reference to customer ratings rather than price.
Oat β Glucan Ameliorates Renal Function and Gut Microbiota in Diabetic Rats
Authors: Wang Ruoyu , Zhang Zhaofeng , Aihemaitijiang Sumiya , Ye Chen , Halimulati Mairepaiti , Huang Xiaojie , Qin Haoyuan
Published: May 2022

Diabetic nephropathy is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Therefore, we must find effective prevention and treatment approaches to the problem. Oat has a long history of use for its nutritional and medicinal properties, such as maintaining physiological blood glucose levels. Oat β glucan is one of the major bioactive substances produced by oat. However, the protective effects of oat β glucan on diabetic nephropathy are still unclear. This study generated a rat model of diabetic nephropathy to explore the potent therapeutic ability and mechanism of oat β glucan in renal function by 16S rRNA genes sequencing. Diabetic nephropathy model was established in forty rats by left nephrectomy and single intraperitoneal injection of streptozotocin. These rats were randomly divided into the model group and three oat β glucan intervention groups. Twenty rats underwent sham operation and were randomly divided into normal control group and oat β glucan control group. Animals were treated by oral gavage for 8 consecutive weeks. The results showed that oat β glucan reduced blood glucose level and improved renal function (P < 0.05). Oat β glucan significantly improved serum inflammatory levels (P < 0.05). The diversity of intestinal microflora in diabetic nephropathy rats decreased with time prolongation, while oat β-glucan reversed the result. Compared with the model group at week 8, the abundances of Eubacterium, Butyricicoccus, and Ruminococcus were elevated significantly after oat β glucan intervention (P < 0.05). Correlation analysis indicated that abundances of Eubacterium, Butyricicoccus, and Ruminococcus were significantly negatively correlated with the levels of renal impairment markers. In summary, the findings of this study showed that oat β glucan can increase the diversity of intestinal flora, regulate the composition of intestinal flora, modulate intestinal flora metabolism, alleviate the inflammatory response, and further delay the development of diabetic nephropathy. Therefore, oat β glucan has the potential to be developed into the novel and safe drug for diabetic nephropathy.
Multifocal Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIA/DIG): An Institutional Series Report and a Clinical Summary of This Rare Tumor
Authors: Wang Qiguang , Meng Jinli , Cheng Jian , Zhang Si , Hui Xuhui , Li Qiang , Liu Wenke , Ju Yan , Sun Lin
Published: May 2022

Aim

Multifocal desmoplastic infantile ganglioglioma/astrocytoma (DIA/DIG) has rarely been reported. Here, two cases have been presented, reviewing the literature and proposed treatment algorithms for this rare tumor.

Patients and Methods

We report two patients diagnosed with multifocal DIA/DIGs in West China Hospital. In addition, a literature review was performed, in October 2019, on case reports of DIA/DIGs with multifocal lesions. The clinical and radiological features, treatment, and outcome of this rare disease were discussed.

Results

DIA/DIGs with multifocal locations were rare, and only thirteen cases (including ours) had been reported. This series included 8 males and 5 females with a mean age of 31.4 ± 45.7 months (range, 3-144 months). The supratentorial hemisphere, suprasellar region, posterior cranial fossa, and spinal cord were frequently involved. Ten patients (76.9%) received surgical resection for the symptomatic lesions and three patients (23.1%) underwent biopsy. Seven patients received chemotherapy postoperatively. Six individuals had tumor recurrences during the follow-up period, while three patients had tumors that spontaneously regressed. Finally, two patients died of tumor progression and one patient died of respiratory insufficiency and hypothalamic dysfunction.

Conclusions

Multifocal DIA/DIGs have more aggressive clinical behavior and poor outcome despite benign histology. DIA/DIGs should be included in the differential diagnosis of multifocal brain tumors in children. The mainstay of treatment is surgical resection; adjuvant treatment with chemotherapeutic drugs is unknown and requires additional research.
A Crucial Angiogenesis-Associated Gene MEOX2 Could Be a Promising Biomarker Candidate for Breast Cancer
Authors: Wang Huxia , Tang Yanan , Yang Xiaomin , Wang Weiyi , Han Pihua , Zhao Jing , He Sai , Liu Peijun
Published: May 2022

Background

Angiogenesis plays a critical role in the growth and metastasis of breast cancer and angiogenesis inhibition has become an effective strategy for cancer therapy. Our study aimed to clarify the key candidate genes and pathways related to breast cancer angiogenesis.

Methods

Differentially expressed genes (DEGs) in the raw breast cancer (BRCA) gene dataset from the Cancer Genome Atlas (TCGA) database were identified and gene ontology analysis of the DEGs was performed. Hub genes were subsequently determined using the Gene Expression Omnibus database. The expression of the mesenchyme homeobox 2 (MEOX2) in breast cancer cells and tissues was assessed by quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. The prognostic value of the MEOX2 gene in breast cancer tissue was evaluated with the Kaplan-Meier plotter.

Results

A total of 61 angiogenesis-related DEGs were identified in the TCGA dataset, among which the gene MEOX2 was significantly down-regulated. GO functional annotation and pathway enrichment analyses showed that MEOX2 was significantly enriched in the regulation of vasculature development. The IHC results confirmed that MEOX2 expression was repressed in breast cancer tissues and the relatively low level indicated the tissue was densely vascularized. Moreover, MEOX2 expression was significantly elevated in breast cancer cells after treatment with cisplatin (DDP) and epirubicin (EPI). Finally, the Kaplan-Meier plotter confirmed that higher expression levels of MEOX2 were related to better overall survival.

Conclusion

Our study revealed that the angiogenesis-associated gene MEOX2 can be used as a novel biomarker for breast cancer diagnosis and clinical therapy.
RNA Sequencing of Tumor-Educated Platelets Reveals a Three-Gene Diagnostic Signature in Esophageal Squamous Cell Carcinoma
Authors: Liu Tiejun , Wang Xin , Guo Wei , Shao Fei , Li Zitong , Zhou Yang , Zhao Zhihong , Xue Liyan , Feng Xiaoli , Li Yin , Tan Fengwei , Zhang Kai , Xue Qi , Gao Shugeng , Gao Yibo , He Jie
Published: May 2022

There is no cost-effective, accurate, and non-invasive method for the detection of esophageal squamous cell carcinoma (ESCC) in clinical practice. We aimed to investigate the diagnostic potential of tumor-educated platelets in ESCC. In this study, seventy-one ESCC patients and eighty healthy individuals were enrolled and divided into a training cohort (23 patients and 27 healthy individuals) and a validation cohort (48 patients and 53 healthy individuals). Next-generation RNA sequencing was performed on platelets isolated from peripheral blood of all participants, and a support vector machine/leave-one-out cross validation (SVM/LOOCV) approach was used for binary classification. A diagnostic signature composed of ARID1A, GTF2H2, and PRKRIR discriminated ESCC patients from healthy individuals with 91.3% sensitivity and 85.2% specificity in the training cohort and 87.5% sensitivity and 81.1% specificity in the validation cohort. The AUC was 0.924 (95% CI, 0.845–0.956) and 0.893 (95% CI, 0.821–0.966), respectively, in the training cohort and validation cohort. This 3-gene platelet RNA signature could effectively discriminate ESCC from healthy control. Our data highlighted the potential of tumor-educated platelets for the noninvasive diagnosis of ESCC. Moreover, we found that keratin and collagen protein families and ECM-related pathways might be involved in tumor progression and metastasis of ESCC, which might provide insights to understand ESCC pathobiology and advance novel therapeutics.
Primary Leiomyosarcoma of the Glans
Authors: Costa Junior Raimundo Nonato Gois da , Teixeira Júnior Antonio Augusto Lima , Rocha Thalita Moura Silva , Sobrinho Thaís Bastos Moraes , Barbosa Liseana de Oliveira , Silva Rafael Campos , Corrêa Rita da Graça Carvalhal Frazão , Alencar Junior Antonio Machado , Nascimento Francisco Sergio Moura Silva , Melo Syomara Pereira da Costa , Calixto José Ribamar Rodrigues , Silva Gyl Eanes Barros
Published: May 2022

Penile leiomyosarcoma isz an extremely uncommon entity that rarely occurs in the glans. Due to the limited number of cases described in literature, guidelines regarding non-surgical treatment, prognosis, and management remain equivocal. Among the mesenchymal tumors of the penis, leiomyosarcoma has the highest propensity for recurrence. It originates in the smooth muscle cells from two distinct locations: superficial and deep. The deep subtype is the most aggressive and has the highest potential for metastasis. Surgical treatment should be implemented early and must be locally aggressive. Herein, we present a rare case of a 54-year-old patient with deep localized leiomyosarcoma of the glans, albeit with superficial characteristics. A review of the main histopathological, clinical, immunohistochemical, and therapeutic aspects of this unusual entity is presented.
Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?
Authors: Yang Ge , Xu Siyu , Mei Haibo , Zhu Guanghui , Liu Yaoxi , Tan Qian , Yu Hui
Published: May 2022

Background:

Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT.

Methods

A total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements.

Results

74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (−0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification.

Conclusions

We found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.
Effects of Chang-Kang-Fang Formula on the Microbiota-Gut-Brain Axis in Rats With Irritable Bowel Syndrome
Authors: Ling Xiwen , Peng Siyuan , Zhong Jingbin , Guo Lirong , Xu Yaqin , Jin Xiaobao , Chu Fujiang
Published: May 2022

Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicine, has been used in clinical settings to treat irritable bowel syndrome (IBS). Recent studies show that 5.0 g/kg/d CKF can alleviate the symptoms of IBS rats by modulating the brain-gut axis through the production of brain-gut peptides (BGPs), thus relieving pain, and reversing the effects of intestinal propulsion disorders. However, the exact mechanisms underlying the therapeutic effects of CKF in IBS remain unclear. The microbiota-gut-brain axis (MGBA) is central to the pathogenesis of IBS, regulating BGPs, depression-like behaviors, and gut microbiota. Given that CKF ameliorates IBS via the MGBA, we performed metabolomic analyses, evaluated the gut microbiota, and system pharmacology to elucidate the mechanisms of action of CKF. The results of intestinal tract motility, abdominal withdrawal reflex (AWR), sucrose preference test (SPT), and the forced swimming test (FST) showed that the male Sprague–Dawley rats subjected to chronic acute combining stress (CACS) for 22 days exhibited altered intestinal motility, visceral hypersensitivity, and depression-like behaviors. Treatment of IBS rats with CKF normalized dysfunctions of CACS-induced central and peripheral nervous system. CKF regulated BDNF and 5-HT levels in the colon and hippocampus as well as the expressions of the related BGP pathway genes. Moreover, the system pharmacology assays were used to assess the physiological targets involved in the action of CKF, with results suggesting that CKF putatively functioned through the 5-HT-PKA-CREB-BDNF pathway. LC-MS-based metabolomics identified the significantly altered 5-HT pathway-related metabolites in the CKF treatment group, and thus, the CKF-related signaling pathways were further examined. After pyrosequencing-based analysis of bacterial 16S rRNA (V3 + V4 region) using rat feces, the Lefse analysis of gut microbiota suggested that CKF treatment could induce structural changes in the gut microbiota, thereby regulating it by decreasing Clostridiales, and the F-B ratio while increasing the levels of Lactobacillus. Furthermore, the integrated analysis showed a correlation of CKF-associated microbes with metabolites. These findings showed that CKF effectively alleviated IBS, which was associated with the altered features of the metabolite profiles and the gut microbiota through a bidirectional communication along the microbiota-gut-brain axis.
Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages
Authors: Wang Peile , Xie Hongchang , Zhang Qiwen , Tian Xueke , Feng Yi , Qin Zifei , Yang Jing , Shang Wenjun , Feng Guiwen , Zhang Xiaojian
Published: May 2022

Mycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal transplant patients in the early and stable post-transplant stages and to simulate an optimal dosing regimen for patients at different stages. A total of 51 patients in the early post-transplant period (1 week after surgery) and 48 patients in the stable state (5.5–10 years after surgery) were included in the study. In the two-compartment population PK model, CL/F (23.36 L/h vs. 10.25 L/h) and V/F (78.07 vs. 16.24 L) were significantly different between the two stages. The dose-adjusted area under the concentration time curve (AUCss,12h/dose) for patients in the early stage were significantly lower than those for patients in the stable state (40.83 ± 22.26 mg h/L vs. 77.86 ± 21.34 mg h/L; p < 0.001). According to Monte Carlo simulations, patients with 1.0–1.5 g of mycophenolate mofetil twice daily in the early phase and 0.50–0.75 g twice daily in the stable phase had a high probability of achieving an AUCss,12h of 30–60 mg h/L. In addition, limited sampling strategies showed that two 4-point models (C0-C1-C2-C4 and C1-C2-C3-C6) performed well in predicting MPA exposure by both Bayesian estimate and regression equation and could be applied in clinical practice to assist therapeutic drug monitoring of MPA.
Medicinal Plants and Fungi Traditionally Used by Dulong People in Northwest Yunnan, China
Authors: Cheng Zhuo , Hu Xian , Lu Xiaoping , Fang Qiong , Meng Yuan , Long Chunlin
Published: May 2022

The Dulong, an ethnic group living in the isolated Northwest Yunnan of Southwest China, have directly used a wide of plants to serve their needs and have accumulated rich traditional knowledge about medicinal plants over years. Unfortunately, little has been reported about the medicinal plants used by the Dulong people. Ethnobotanical data were collected through semi-structured interviews, guided field trips, and quantitative analysis. Prior informed consent was obtained before each interview. The surveys allowed for the collection of sociodemographic data and traditional knowledge about medicinal plants and their uses. This study used relative frequency of citation (RFC) to identify the most culturally significant medicinal plants and used informant consensus factor (FIC) to evaluate agreement among informants. A total of 105 medicinal plant species belonging to 69 families were recorded. Amongst these 69 families, Asteraceae (8 species), Polygonaceae, Ranunculaceae, and Rosaceae (4 species each) were the dominant families. The whole plants were the most frequently used part in the preparation of medicines. The most common preparation method was decoction and the most frequent application route was oral administration. Coptis teeta (0.15), Acorus calamus (0.12), Ophiocordyceps sinensis (0.11), Tanacetum tatsienense var. tanacetopsis (0.11), and Paris polyphylla var. yunnanensis (0.08) were shown to be the most useful plants as indicated by their relatively high RFC values. Among the usage types of medicinal plants, the highest FIC values were recorded for the circulatory system (FIC = 0.91), the immune system (FIC = 0.89), and the nervous system (FIC = 0.85). Furthermore, sixty-two medicinal plants utilized by the Dulong for medicinal purposes also have dietary use. Traditional knowledge associated with medicinal plants has been seriously threatened in recent decades. In the future, modern approaches should be used to demystify traditional medicine. However, significant measures need to be taken to protect from loss the important traditional knowledge gained by the Dulong through their experience and inheritance. A collective effort should be made to promote and conserve the important traditional medicinal knowledge and outline a plan for sustainable use of medicinal plants and improve local economic development under the premise of protection.
Spatial and Temporal Oscillations of Surface Tension Induced by an A + B → C Traveling Front
Authors: Tiani Reda , Rongy Laurence
Published: May 2022

This work describes a new mechanism for the emergence of oscillatory dynamics driven by the interaction of hydrodynamic flows and reaction-diffusion processes with no autocatalytic feedback nor prescribed hydrodynamic instability involved. To do so, we study the dynamics of an A+ B → C reaction-diffusion front in the presence of chemically-driven Marangoni flows for arbitrary initial concentrations of reactants and diffusion coefficients of all species. All the species are assumed to affect the solution surface tension thereby inducing Marangoni flows at the air-liquid interface. The system dynamics is studied by numerically integrating the incompressible Navier-Stokes equations coupled to reaction-diffusion-convection equations for the three chemical species. We report spatial and temporal oscillations of surface tension triggered by differential diffusion effects of surfactant species coupled to the chemically-induced Marangoni effect. Such oscillations are related to the discontinuous traveling of the front along the surface leading to the progressive formation of local extrema in the surface tension profiles as time evolves.
Three-Dimensional Manipulation for Self-Focusing Behavior via the State of Polarization
Authors: Lu Lu , Wang Zhiqiang , Lin Rong , Cai Yangjian
Published: May 2022

In this work, the controllable self-focusing behavior is first investigated by manipulating the state of polarization (SoP), that is, the phase difference between two polarized components at the initial optical field, which can be used to realize the three-dimensional manipulation of self-focusing behavior. Furthermore, the properties of self-focusing propagation (including intensity distribution, propagation dynamics, and Stokes parameters) are researched in detail, which are beneficial to select the reasonable initial SoP for further theoretical and experimental exploration. Particularly, the radially polarized beam as a laser source not only prolongs the self-focusing length but also improves the power density of self-focusing spots on the target. These findings may have potential in the multidimensional optical manipulation, the optical information transmission, the high-power long-range laser atmospheric propagation, and related applications.
The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis
Authors: Xing Chuan , Zhao Han , Zhang Jiaqi , He Bing
Published: May 2022

Objective: To elucidate the relationship between CYP17A1/CYP19A1/SHBG gene polymorphisms and PCOS susceptibility.

Methods: We searched multiple databases from inception to December 2020 and meta analysis was conducted to elucidate the relationship between gene polymorphisms and PCOS risk.

Results: 26 studies were included, comprising 4860 PCOS and 4043 controls. CYP17A1 rs743572 polymorphisms were found to be negatively associated with PCOS risk under dominant model (p = 0.017, OR = 0.83, 95%CI 0.72–0.97, I2 = 74.80%, Pheterogeneity = 0.000) in the general population while neither CYP19A1 rs2414096 polymorphisms (p = 0.578, OR = 0.87, 95%CI 0.54–1.41, I2 = 95.90%, Pheterogeneity = 0.000) nor SHBG rs6529 polymorphisms (p = 0.752, OR = 0.99, 95%CI 0.94–1.05, I2 = 60.90%, Pheterogeneity = 0.012) was associated with PCOS susceptibility under dominant model in the general population.

Conclusion: CYP17A1 rs7435721 polymorphisms might be protective factors against PCOS in general populations.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD4202122640.
Characterization and Valuation of the Uncertainty of Calibrated Parameters in Microsimulation Decision Models
Authors: Alarid-Escudero Fernando , Knudsen Amy B. , Ozik Jonathan , Collier Nicholson , Kuntz Karen M.
Published: May 2022

Background:We evaluated the implications of different approaches to characterize the uncertainty of calibrated parameters of microsimulation decision models (DMs) and quantified the value of such uncertainty in decision making.

Methods:We calibrated the natural history model of CRC to simulated epidemiological data with different degrees of uncertainty and obtained the joint posterior distribution of the parameters using a Bayesian approach. We conducted a probabilistic sensitivity analysis (PSA) on all the model parameters with different characterizations of the uncertainty of the calibrated parameters. We estimated the value of uncertainty of the various characterizations with a value of information analysis. We conducted all analyses using high-performance computing resources running the Extreme-scale Model Exploration with Swift (EMEWS) framework.

Results:The posterior distribution had a high correlation among some parameters. The parameters of the Weibull hazard function for the age of onset of adenomas had the highest posterior correlation of −0.958. When comparing full posterior distributions and the maximum-a-posteriori estimate of the calibrated parameters, there is little difference in the spread of the distribution of the CEA outcomes with a similar expected value of perfect information (EVPI) of $653 and $685, respectively, at a willingness-to-pay (WTP) threshold of $66,000 per quality-adjusted life year (QALY). Ignoring correlation on the calibrated parameters’ posterior distribution produced the broadest distribution of CEA outcomes and the highest EVPI of $809 at the same WTP threshold.

Conclusion:Different characterizations of the uncertainty of calibrated parameters affect the expected value of eliminating parametric uncertainty on the CEA. Ignoring inherent correlation among calibrated parameters on a PSA overestimates the value of uncertainty.
Down-Regulation of P450 Genes Enhances Susceptibility to Indoxacarb and Alters Physiology and Development of Fall Armyworm, Spodoptera frugipreda (Lepidoptera: Noctuidae)
Authors: Hafeez Muhammad , Li Xiaowei , Ullah Farman , Zhang Zhijun , Zhang Jinming , Huang Jun , Fernández-Grandon G. Mandela , Khan Muhammad Musa , Siddiqui Junaid Ali , Chen Limin , Ren Xiao Yun , Zhou Shuxing , Lou Yonggen , Lu Yaobin
Published: May 2022

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is a pest of many important crops globally. Effective control is challenging, with the pest exhibiting resistance to different synthetic pesticides across various groups. However, the mechanisms employed by resistant insects for overexpression of relevant detoxification genes remain unclear. The activity of detoxification enzymes was investigated in this study. Additionally, using RNA interference (RNAi), a functional analysis was completed of two P450s genes in an indoxacarb resistant population of fall armyworms. Elevated resistance levels (resistance ratio = 31.37-fold) in indoxacarb-selected populations of FAW were observed after 14 generations. The qRT-PCR showed higher expression of two cytochrome P450 genes, CYP321A7 and CYP6AE43, in this selected population compared to the control population. RNAi was applied to knock down the P450 dsCYP321A7 and dsCYP6AE43 genes in the FAW larvae. Droplet feeding of the dsRNAs (CYP321A7 and CYP6AE43) via an artificial diet significantly increased mortality rates in the indoxacarb treated population. A shorter larval developmental time of FAW was detected in all dsRNAs-fed larvae. Correspondingly, larval mass was reduced by dsRNAs in indoxacarb resistant populations of fall armyworm. Larval feeding assays demonstrate that dsRNAs targeting, specifically of CYP321A7 and CYP6AE43 enzymes, could be a beneficial technique in the management of indoxacarb resistant populations. Further study on the potential use of dsRNA and its application should be conducted in efforts to counter the development of resistance in FAW against various insecticides in the field.
Ultrastructural Assessment and Proteomic Analysis in Myofibrillogenesis in the Heart Primordium After Heartbeat Initiation in Rats
Authors: Ichise Nobutoshi , Sato Tatsuya , Fusagawa Hiroyori , Yamazaki Hiroya , Kudo Taiki , Ogon Izaya , Tohse Noritsugu
Published: May 2022

Myofibrillogenesis is an essential process for cardiogenesis and is closely related to excitation-contraction coupling and the maintenance of heartbeat. It remains unclear whether the formation of myofibrils and sarcomeres is associated with heartbeat initiation in the early embryonic heart development. Here, we investigated the association between the ultrastructure of myofibrils assessed by transmission electron microscopy and their proteomic profiling assessed by data-independent acquisition mass spectrometry (DIA-MS) in the rat heart primordia before and after heartbeat initiation at embryonic day 10.0, when heartbeat begins in rats, and in the primitive heart tube at embryonic day 11.0. Bundles of myofilaments were scattered in a few cells of the heart primordium after heartbeat initiation, whereas there were no typical sarcomeres in the heart primordia both before and after heartbeat initiation. Sarcomeres with Z-lines were identified in cells of the primitive heart tube, though myofilaments were not aligned. DIA-MS proteome analysis revealed that only 43 proteins were significantly upregulated by more than 2.0 fold among a total of 7,762 detected proteins in the heart primordium after heartbeat initiation compared with that before heartbeat initiation. Indeed, of those upregulated proteins, 12 (27.9%) were constituent proteins of myofibrils and 10 (23.3%) were proteins that were accessories and regulators for myofibrillogenesis, suggesting that upregulated proteins that are associated with heartbeat initiation were enriched in myofibrillogenesis. Collectively, our results suggest that the establishment of heartbeat is induced by development of bundles of myofilaments with upregulated proteins associated with myofibrillogensis, whereas sarcomeres are not required for the initial heartbeat.
Non-invasive Estimation of Foliar Nitrogen Concentration Using Spectral Characteristics of Menthol Mint (Mentha arvensis L.)
Authors: Pandey Praveen , Singh Swati , Khan Mohammad Saleem , Semwal Manoj
Published: May 2022

Menthol mint (Mentha arvensis L., Family: Lamiaceae), popularly known as corn mint or Japanese mint, is an important industrial crop that is widely grown for its valued essential oil. Nitrogen (N) is an important macro-nutrient and an essential factor for optimizing the yield and quality of crops. Hence, rapid and accurate estimation of the N content is crucial for nutrient diagnosis in plants and to make precise N fertilizer recommendations. Generally, N concentration is estimated by destructive sampling methods; however, an indirect assessment may be possible based on spectral characteristics. This study aimed to compare the foliar N concentration based on non-destructive (reflectance) and destructive (laboratory analyses) methods in menthol mint. Foliar N concentration was measured through the Kjeldahl method and reflectance by Miniature Leaf Spectrometer C-710 (CID Bio-Science). Using reflectance data, several vegetation indices (VIs), that is, normalized difference red edge (NDRE), red edge normalized difference vegetation index (reNDVI), simple ratio (SR), green–red vegetation index (GRVI), canopy chlorophyll content index (CCCI), photochemical reflectance index (PRI), green chlorophyll index (CIGreen), red edge chlorophyll index (CIRed Edge), canopy chlorophyll index (CCI), normalized pigment chlorophyll ratio index (NPCI), and structure insensitive pigment index (SIPI), were developed to determine the foliar N concentration. The highest correlation (r) between VIs and foliar N concentrations was achieved by NDRE (0.89), followed by reNDVI (0.84), SR (0.83), GRVI (0.78), and CCCI (0.76). Among the VIs, the NDRE index has been found to be the most accurate index that can precisely predict the foliar N concentration (R2 = 0.79, RMSE = 0.18). In summary, the N deficiencies faced by the crop during its growth period can be detected effectively by calculating NDRE and reNDVI, which can be used as indicators for recommending precise management strategies for the application of nitrogenous fertilizers.
Zinc Nutrition Responses to Agronomic and Yield Traits, Kernel Quality, and Pollen Viability in Rice (Oryza sativa L.)
Authors: Kandil Essam E. , El-Banna Aly A. A. , Tabl Dalia M. M. , Mackled Marwa I. , Ghareeb Rehab Y. , Al-Huqail Asma A. , Ali Hayssam M. , Jebril Jebril , Abdelsalam Nader R.
Published: May 2022

Rice (Oryza sativa L.) is one of the major cereal crops worldwide with wheat and maize. A total of two field experiments were performed to evaluate the response of some rice cultivars to various foliar zinc (Zn) concentrations based on different measurements, such as agronomic, yield, yield compounds, and grain technological parameters. The experimental layout was a split plot in three replicates; the five rice cultivars (Skaha 101, Giza178, Yasmeen, Fourate, and Amber 33) were distributed in the main plots while the four foliar applications of Zn (1,500, 2,000, 2,500 mg/L besides spray water) were occupied the sub-plots. The findings showed significant differences among the five rice cultivars regarding plant height, grain yield, straw yield, biological yield, harvest index, 1,000-grain weight, panicle length, protein percentage, and grain Zn content. There is a significant effect of Zn on all plant attributes. A significant interaction between rice cultivars and foliar application of Zn was observed, whereas fertilizing Giza 178 with foliar application of Zn at the rate of 2,500 mg/L achieved the highest mean values of grain yield and straw yield, biological yield, harvest index, 1,000-grain weight, panicle length, protein %, and Zn content followed by Sakha 101 with Zn application at the rate of 2,000 mg/L, respectively, in both seasons. The rice cultivars significantly differed in hulling (%), broken (%), hardness, grain length, shape, amylose (%), gel consistency, and gelatinization temperature. Unfortunately, the commercial Zn product used was genotoxic to pollen grains with a higher rate of Zn. Aberrations were observed such as stickiness, ultrastructural changes in the exterior and interior walls, partially or fully degenerated grains, and shrunken and unfilled grains. This study concluded that using Zn application at the rate of 2,000 mg/L to protect human and environmental health, the side effects and toxicity of the local commercial Zn product market should be investigated before making recommendations to farmers.