bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil-to-Lymphocyte Ratio Is Associated With Circumferential Wall Enhancement of Unruptured Intracranial Aneurysm
Authors: Wu Xiao-Bing , Zhong Jing-Lian , Wang Sheng-Wen , Su Yun , Chen Pei-Sheng , Li Zhong-Jun , Xiang Chun , Cai Wang-Qing , Shi Zhong-Song
Published: May 2022

Background and Purpose

Neutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA.

Methods

We analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs.

Results

The study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P < 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149–4.088) and size (odds ratio, 1.370; 95% CI, 1.126–1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (<7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86.

Conclusion

NLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.
Multiomics Data Analysis and Identification of Immune-Related Prognostic Signatures With Potential Implications in Prognosis and Immune Checkpoint Blockade Therapy of Glioblastoma
Authors: Ma Shuai , Wang Fang , Wang Nan , Jin Jiaqi , Ba Yixu , Ji Hang , Du Jianyang , Hu Shaoshan
Published: May 2022

Background

In recent years, glioblastoma multiforme (GBM) has been a concern of many researchers, as it is one of the main drivers of cancer-related deaths worldwide. GBM in general usually does not responding well to immunotherapy due to its unique microenvironment.

Methods

To uncover any further informative immune-related prognostic signatures, we explored the immune-related distinction in the genetic or epigenetic features of the three types (expression profile, somatic mutation, and DNA methylation). Twenty eight immune-related hub genes were identified by Weighted Gene Co-Expression Network Analysis (WGCNA). The findings showed that three genes (IL1R1, TNFSF12, and VDR) were identified to construct an immune-related prognostic model (IRPM) by lasso regression. Then, we used three hub genes to construct an IRPM for GBM and clarify the immunity, mutation, and methylation characteristics.

Results

Survival analysis of patients undergoing anti-program cell death protein 1 (anti-PD-1) therapy showed that overall survival was superior in the low-risk group than in the high-risk group. The high-risk group had an association with epithelial-mesenchymal transition (EMT), high immune cell infiltration, immune activation, a low mutation number, and high methylation, while the low-risk group was adverse status.

Conclusions

In conclusion, IRPM is a promising tool to distinguish the prognosis of patients and molecular and immune characteristics in GBM, and the IRPM risk score can be used to predict patient sensitivity to checkpoint inhibitor blockade therapy. Thus, three immune-related signatures will guide us in improving treatment strategies and developing objective diagnostic tools.
Models of Care in Multiple Sclerosis: A Survey of Canadian Health Providers
Authors: Marrie Ruth Ann , Donkers Sarah J. , Jichici Draga , Hrebicek Olinka , Metz Luanne , Morrow Sarah A. , Oh Jiwon , Pétrin Julie , Smyth Penelope , Devonshire Virginia
Published: May 2022

Objective

Little work has evaluated integrated models of care in multiple sclerosis (MS) and the composition of MS care teams across Canada is largely unknown. We aimed to gather information regarding existing models of MS care across Canada, and to assess the perceptions of health care providers (HCPs) regarding the models of care required to fully meet the needs of the person with MS.

Methods

We conducted an anonymous online survey targeting Canadian HCPs working in MS Clinics, and neurologists delivering MS care whether or not they were based in an MS Clinic. We queried the types of HCPs delivering care within formal MS Clinics, wait times for HCPs, the perceived importance of different types of HCPs for good quality care, assessments conducted, and whether clinic databases were used. We summarized survey responses using descriptive statistics.

Results

Of the 716 HCPs to whom the survey was distributed, 100 (13.9%) people responded. Of the 100 respondents, 85 (85%) indicated that their clinical practice included people with MS and responded to specific questions about clinical care. The most common types of providers within MS Clinics with integrated models of care were neurologists and MS nurses. Of 23 responding MS Clinics, 10 (43.5%) indicated that there were not enough neurologists, and 16 (69.6%) indicated that there were not enough non-neurologist HCPs to provide adequate care. More than 50% of clinics reported wait times exceeding 3 months for physiatrists, physiotherapists, psychiatrists, psychologists, neuropsychologists and urologists; in some clinics wait times for these providers exceeded 1 year. Multiple disciplines were identified as important or very important for delivering good quality MS care. Over 90% of respondents thought it was important for neurologists, nurse practitioners, MS nurses and psychiatrists to be co-located within MS Clinics.

Conclusion

Canadian HCPs viewed the ideal MS service as being multidisciplinary in nature and ideally integrated. Efforts are needed to improve timely access to specialized MS care in Canada, and to evaluate how outcomes are influenced by access to care.
Eryngium Species as a Potential Ally for Treating Metabolic Syndrome and Diabetes
Authors: Pérez-Muñoz Eréndira Patricia , Antunes-Ricardo Marilena , Martínez-Ávila Mariana , Guajardo-Flores Daniel
Published: May 2022

Medicinal plants possess natural compounds that can be used as an alternative for synthetic medicines that may cause long-term side effects on patients such as neurocognitive effects, muscular and hepatic toxicity. Metabolic Syndrome is associated with increased risk of several diseases such as diabetes, cardiovascular disease, dyslipidemia, and hypertension thus, becoming the greatest challenge as a growing public health concern worldwide. Latin-American countries possess a wide diversity of medicinal plants that have been used to treat different health conditions since pre-Hispanic times. Eryngium spp. has been studied due to their beneficial properties mainly to treat diabetes, dyslipidemia, blood pressure, and digestive problems. This review gives an update mainly on the pharmacological activities of the Eryngium spp., summarizing the biological activities and plausible mechanism of action of their bioactive components toward metabolic syndrome. For instance, flavonoids and tannins proved to increase the levels of HDL and reduced the levels of VLDL, LDL. On the other hand, phenolic acids improved glucose metabolism through the inhibition of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase (G6Pase) and reestablished the impaired activity of enzymes related to glucose oxidation and glycogen synthesis. The terpenes and sesquiterpenes like β-farnese, β-pinene, and calamenene exhibited a protective effect by reducing the oxidizing damage by the regulation of the Reactive Oxygen Species (ROS). Saponins controlled the dyslipidemia by reducing the serum concentrations of lipids, triglycerides and total cholesterol. Finally, the aerial parts of Eryngium had the capacity of inhibiting dietary carbohydrate digestive enzymes, thus controlling glucose levels. The Eryngium plant is normally consumed as an infusion to obtain the benefits of the plants, however novel technologies such as cavitation, ultrasound assisted, microwave assisted, and supercritical fluid have been applied to improve the extraction yields and selectivity of bioactive compounds. The common treatment to control diabetic dyslipidemia are synthetic medicines such as metformin and ezetimibe, which allows the regulation of glucose, cholesterol and insulin resistance. However, patients that take these medications may present side effects such as muscular toxicity, hepatic toxicity, neurocognitive effects, just to name a few. More studies regarding the efficacy and safety of the use of traditional medicinal herbs are required. However, these materials may be used in the treatment of diabetes related conditions to ensure life quality and reduce side effects among the diabetic population
Food Nitrogen Footprint of the Indian Subcontinent Toward 2050
Authors: Dhar Aurup Ratan , Oita Azusa , Matsubae Kazuyo
Published: May 2022

Substantial loss of nitrogen (N) in reactive forms (nitrogen species except for N2) induced by agro–food system is a cause of the environmental degradation and harms human health. The main factors influencing the food N footprint of the Indian Subcontinent (ISC) are the nitrogen use efficiency (NUE) of crop cultivation and religious dietary cultures. In this study, we assess the food N footprint of the ISC and establish reduction scenarios toward 2050. We used a religion-sensitive N-Calculator method and food consumption data from the Food and Agriculture Organization of the United Nations to estimate the food N footprint of the ISC of different religious communities. We developed four reduction scenarios as follows: The business-as-usual scenario; a 30% increase in the crop cultivation NUE; altered protein supplies to the healthy EAT–Lancet reference diet considering religious food taboos; and an integrated approach with a 30% increase in the NUE increase and the altered diet. We used the long short-term memory recurrent neural network approach to predict the future. The study revealed that the average food N footprint per-capita per-year increased from 7.94 kg-N in the 1960s to 8.43 kg-N in the early 2010s, and the crop cultivation NUE was reduced to less than 40%. Buddhists had the lowest footprint over the period. An increase in the NUE of the crop cultivation and an altered diet results in a 13% reduction in the N footprint compared to the business-as-usual scenario. We conclude that improved crop cultivation NUEs and an altered religion-specific healthy diet would reduce the N footprint.
Associations Between Vitamin D Levels and Risk of Heart Failure: A Bidirectional Mendelian Randomization Study
Authors: Gao Ning , Li Xuebiao , Kong Minjian , Ni Ming , Wei Dongdong , Zhu Xian , Wang Yifan , Hong Ze , Dong Aiqiang
Published: May 2022

Background

Although studies suggest that concentrations of serum 25-hydroxyvitamin D (25(OH)D) are lower in individuals with Heart Failure (HF), the beneficial effects of vitamin D supplementation are controversial. Therefore, in this study, we aimed to determine whether there is a causal relationship between serum Vitamin D (VD) levels and HF.

Methods

We obtained genetic instruments from the largest available genome-wide association study (GWAS) of European descent for 25(OH)D (443, 734 individuals) to investigate the association with HF (47,309 cases, 930,014 controls), and vice versa. Two-sample bidirectional Mendelian Randomization (MR) analysis was performed to infer the causality. In addition to the primary analysis using inverse variance-weighted (IVW) MR, we applied five additional methods to control for pleiotropy [MR-Egger, weighted median, Maximum-likelihood, MR-robust adjusted profile score (MR-RAPS) and MR-pleiotropy residual sum and outlier (MR-PRESSO)] and compared their respective MR estimates. We also performed a sensitivity analysis to ensure that our results were robust.

Results

Mendelian randomized analysis showed that increased serum 25(OH)D was associated with a lower risk of HF in the IVW method (odds ratio [OR] = 0. 81;95%CI, 0.70–0.94, P = 0.006). In the reverse MR analyses, the genetic predisposition to HF was negatively correlated with serum 25(OH)D level (OR = 0. 89;95%CI, (0.82–0.97), P = 0.009).

Conclusion

Our study revealed the possible causal role of 25(OH)D on decreasing the risk for HF. Meanwhile, reverse MR analysis suggested that HF may be associated with lower vitamin D levels, it could be the potential implications for dietary recommendations.
Low Vitamin D Status Predicts Poor Clinical Outcome in Advanced Melanoma Treated With Immune Checkpoint or BRAF/MEK Inhibitors: A Prospective Non-Interventional Side-by-Side Analysis
Authors: Reichrath Jörg , Biersack Florian , Wagenpfeil Stefan , Schöpe Jakob , Pföhler Claudia , Saternus Roman , Vogt Thomas
Published: May 2022

In melanoma and other malignancies, low vitamin D status is associated with increased risk and poor prognosis. However, there are limited data of the impact of 25(OH)D serum concentration (s.c.) on clinical outcome in advanced melanoma. We tested the hypothesis that vitamin D status is predictive of efficacy and safety in patients treated for metastasized melanoma with B-rapidly accelerated fibrosarcoma (BRAF), mitogen-activated protein kinase kinase (MEK), cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and/or programmed cell death protein-1 (PD-1) inhibitors. Severe vitamin D deficiency [defined as 25(OH)D s.c. <10 ng/ml] was associated with markedly reduced overall (OS) and progress-free (PFS) survival, with increased tumor load [TL; measured as s.c. of S100 protein or lactate dehydrogenase (LDH)], and with a trend for higher frequency of adverse events (AEs). An increase in average 25(OH)D s.c. of 1 ng/ml was associated with a 3.9% reduced risk for progressive disease [hazard ratio (HR) = 0.961, p = 0.044], with a reduction of LDH s.c. of 3.86 U/l (p = 0.034, indicating a reduction of TL), and with a trend for reduced frequency of AEs (AE ratio -0.005; p = 0.295). Patients with average 25(OH)D s.c. ≥10 ng/ml and BRAF-mutant melanoma showed a trend for a higher frequency of AEs as compared to individuals with BRAF wild-type melanomas. Our data indicate that vitamin D deficiency is associated with poor clinical outcome in patients treated for metastasized melanoma with BRAF/MEK inhibitors or immunotherapy. Although it needs to be proven in future interventional trials whether optimizing serum 25(OH)D improves clinical outcome in these patients, we recommend that 25(OH)D s.c. should be analyzed and vitamin D deficiency treated in all patients with advanced melanoma.
Diagnostic Accuracy of Arterial Spin Labeling in Comparison With Dynamic Susceptibility Contrast-Enhanced Perfusion for Brain Tumor Surveillance at 3T MRI
Authors: Lavrova Anna , Teunissen Wouter H. T. , Warnert Esther A. H. , van den Bent Martin , Smits Marion
Published: May 2022

Purpose

We aimed to compare arterial spin labeling (ASL) with dynamic susceptibility contrast (DSC) enhanced perfusion MRI for the surveillance of primary and metastatic brain tumors at 3T, both in terms of lesion perfusion metrics and diagnostic accuracy.

Methods

In this retrospective study, we included 115 patients, who underwent both ASL and DSC perfusion in the same 3T MRI scanning session between 1 January and 31 December 2019. ASL-derived cerebral blood flow (CBF) maps and DSC-derived relative cerebral blood volume (rCBV) maps, both uncorrected and corrected for leakage, were created with commercially available software. Lesions were identified as T2-/T2-FLAIR hyperintensity with or without contrast enhancement. Measurements were done by placing a region of interest in the visually determined area of highest perfusion, copying to the contralateral normal appearing white matter (NAWM), and then propagating to the other perfusion maps. Pearson’s correlation coefficients were calculated between the CBF and rCBV ratios of tumor versus NAWM. Accuracy for diagnosing tumor progression was calculated as the area under the receiver operating characteristics (ROC) curve (AUC) for the ASL-CBF and leakage corrected DSC-rCBV ratios.

Results

We identified 178 lesions, 119 with and 59 without contrast enhancement. Correlation coefficients between ASL-derived CBF versus DSC-derived rCBV ratios were 0.60–0.67 without and 0.72–0.78 with leakage correction in all lesions (n = 178); these were 0.65–0.80 in enhancing glioma (n = 80), 0.58–0.73 in non-enhancing glioma, and 0.14–0.40 in enhancing metastasis (n = 31). No significant correlation was found in enhancing (n = 8) or non-enhancing (n = 7) lymphomas. The areas under the ROC curves (AUCs) for all patients were similar for ASL and DSC (0.73–0.78), and were higher for enhancing glioma (AUC = 0.78–0.80) than for non-enhancing glioma (AUC = 0.56–0.62). In brain metastasis, the AUC was lower for ASL-derived CBF (AUC = 0.72) than for DSC-derived rCBV ratios (AUC = 0.87–0.93).

Conclusion

We found that ASL and DSC have more or less the same diagnostic accuracy. Our findings suggest that ASL can be used as an alternative to DSC to measure perfusion in enhancing and non-enhancing gliomas and brain metastasis at 3T. For lymphoma, this should be further investigated in a larger population.
Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated With Stereotactic Radiosurgery
Authors: Park Christine , Buckley Evan D. , Van Swearingen Amanda E. D. , Giles Will , Herndon James E. , Kirkpatrick John P. , Anders Carey K. , Floyd Scott R.
Published: May 2022

Background

There is a concern that HER2-directed systemic therapies, when administered concurrently with stereotactic radiosurgery (SRS), may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ breast cancer brain metastasis (BCBrM).

Methods

This was a single-institution, retrospective study including patients >18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 and with at least 12-month post-SRS follow-up. Presence of RN was determined via imaging at one-year post-SRS, with confirmation by biopsy in some patients. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks pre- to four weeks post-SRS) and type of systemic therapy (e.g., chemotherapy, HER2-directed) were evaluated.

Results

Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not based on imaging criteria. Of the 11 patients who underwent biopsy, 10/10 (100%) who were diagnosed with RN on imaging were confirmed to be RN positive on biopsy and 1/1 (100%) who was not diagnosed with RN was confirmed to be RN negative on biopsy. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (including total dose, fractionation, CTV and size target volume, all p>0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p=0.97) did not differ between patients who did or did not develop RN. However, there was a trend for patients who developed RN to have received more than one agent of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p=0.08). Moreover, a significantly higher proportion of those who developed RN received more than one agent of HER2-directed therapy during SRS treatment compared to those who did not develop RN (35.7% vs 5.6%, p=0.047).

Conclusions

Patients with HER2 BCBrM who receive multiple HER2-directed therapies during SRS for BCBrM may be at higher risk of RN. Collectively, these data suggest that, in the eight-week window around SRS administration, if HER2-directed therapy is medically necessary, it is preferable that patients receive a single agent.
Case Report: New Onset Lymphadenopathy After Immune Checkpoint Inhibitor Therapy Presents a Clinicopathological and Radiological Challenge
Authors: Scarlotta Matthew , Avery Robin , Baraban Ezra , Maleki Zahra , Ged Yasser
Published: May 2022

The use of immune-checkpoint inhibitor (ICI) therapy has significantly improved patient outcomes in a wide variety of cancers and has become a cornerstone in the treatment of renal cell carcinoma. However, ICI treatment has the potential to cause a variety of immune-related adverse events (irAEs) that can affect any tissue or organ. This report describes the diagnostic dilemma of a patient with both RCC and diffuse large B-cell lymphoma who developed acute onset of fever and diffuse lymphadenopathy following treatment with combined ipilimumab and nivolumab. While diagnostic considerations included worsening lymphoma, hyperprogression of RCC, sarcoid-like reaction from immunotherapy, and fungal infection, his lymphadenopathy eventually resolved with treatment for histoplasmosis and discontinuation of immunotherapy. Despite only receiving two doses of immunotherapy, he has not required additional systemic therapy for RCC. This case demonstrates both the effectiveness of ICI therapy and the need for multidisciplinary approach to potential irAEs.
Berberine: A Promising Treatment for Neurodegenerative Diseases
Authors: Cheng Ziqian , Kang Chenglan , Che Songtian , Su Jingyun , Sun Qihan , Ge Tongtong , Guo Yi , Lv Jiayin , Sun Zhihui , Yang Wei , Li Bingjin , Li Xin , Cui Ranji
Published: May 2022

Berberine, as a natural alkaloid compound, is characterized by a diversity of pharmacological effects. In recent years, many researches focused on the role of berberine in central nervous system diseases. Among them, the effect of berberine on neurodegenerative diseases has received widespread attention, for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and so on. Recent evidence suggests that berberine inhibits the production of neuroinflammation, oxidative, and endoplasmic reticulum stress. These effects can further reduce neuron damage and apoptosis. Although the current research has made some progress, its specific mechanism still needs to be further explored. This review provides an overview of berberine in neurodegenerative diseases and its related mechanisms, and also provides new ideas for future research on berberine.
Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art
Authors: Lambuk Lidawani , Mohd Lazaldin Mohd Aizuddin , Ahmad Suhana , Iezhitsa Igor , Agarwal Renu , Uskoković Vuk , Mohamud Rohimah
Published: May 2022

Retinal ganglion cells (RGCs) are neurons of the visual system that are responsible for transmitting signals from the retina to the brain via the optic nerve. Glaucoma is an optic neuropathy characterized by apoptotic loss of RGCs and degeneration of optic nerve fibers. Risk factors such as elevated intraocular pressure and vascular dysregulation trigger the injury that culminates in RGC apoptosis. In the event of injury, the survival of RGCs is facilitated by neurotrophic factors (NTFs), the most widely studied of which is brain-derived neurotrophic factor (BDNF). Its production is regulated locally in the retina, but transport of BDNF retrogradely from the brain to retina is also crucial. Not only that the interruption of this retrograde transport has been detected in the early stages of glaucoma, but significantly low levels of BDNF have also been detected in the sera and ocular fluids of glaucoma patients, supporting the notion that neurotrophic deprivation is a likely mechanism of glaucomatous optic neuropathy. Moreover, exogenous NTF including BDNF administration was shown reduce neuronal loss in animal models of various neurodegenerative diseases, indicating the possibility that exogenous BDNF may be a treatment option in glaucoma. Current literature provides an extensive insight not only into the sources, transport, and target sites of BDNF but also the intracellular signaling pathways, other pathways that influence BDNF signaling and a wide range of its functions. In this review, the authors discuss the neuroprotective role of BDNF in promoting the survival of RGCs and its possible application as a therapeutic tool to meet the challenges in glaucoma management. We also highlight the possibility of using BDNF as a biomarker in neurodegenerative disease such as glaucoma. Further we discuss the challenges and future strategies to explore the utility of BDNF in the management of glaucoma.
Exploiting Extracellular Vesicles Strategies to Modulate Cell Death and Inflammation in COVID-19
Authors: Bortot Barbara , Romani Arianna , Ricci Giuseppe , Biffi Stefania
Published: May 2022

The coronavirus disease (COVID-19) is responsible for more than 5 million deaths worldwide, with respiratory failure being the most common clinical presentation. COVID-19 complications still present a considerable burden on healthcare systems, and signs of the post-COVID syndrome are concerns for potential long-term damages. An increasing body of evidence highlights extracellular vesicles’ (EVs) relevance in modulating inflammation and cell death in the diseases related to these processes. Several types of EVs-based investigational new drugs against COVID-19 have been approved by the US Food and Drug Administration to initiate a Phase I/II trial under an Investigational New Drug protocol. EVs can be employed as natural drug delivery nanoparticle-based systems due to their inherent potential in transferring material between cells, their natural origin, and their capability to encapsulate various biological molecules, offering an exciting alternative for administering drugs acting on the cell cycle control. In this context, small-molecule inhibitors of Mouse Double Minute 2 (MDM2) such as Nutlin-3 and Idasanutlin by promoting p53 survival and its antiviral activity might be helpful to modulate the IFN signalling pathway and reduce the overall pro-inflammatory burden.
Metabolomic Profiling for Histologically Fibrotic Stage in Chronic Drug-Induced Liver Injury
Authors: He Xian , Zhou Ming-Xi , Cheng Cheng , Li Shan-Shan , Gao Yuan , Ma Zhi-Tao , Song Xin-Hua , Bai Zhao-Fang , Zou Zheng-Sheng , Xiao Xiao-He , Wang Jia-Bo , Lu Ya-Wen
Published: May 2022

Background and aims: Chronic drug-induced liver injury (DILI) is a rare but under-researched adverse drug reaction–related disease, which is highly likely to progress into liver fibrosis and even cirrhosis. In this study, metabolomics was used to screen out characteristic metabolites related to the histological progression of fibrosis in chronic DILI and analyze the metabolic changes during the development of fibrosis to explain the underlying mechanism.

Methods: Chronic DILI patients who underwent liver biopsy were divided into different fibrosis grades. Serum was analyzed by untargeted metabolomics to find serological characteristic metabolite fingerprints. The screened fingerprints were validated by the validation group patients, and the identification ability of fingerprints was compared using FibroScan.

Results: A total of 31 metabolites associated with fibrosis and 11 metabolites associated with advanced fibrosis were identified. The validation group confirmed the accuracy of the two metabolite fingerprints [area under the curve (AUC) value 0.753 and 0.944]. In addition, the fingerprints showed the ability to distinguish the grades of fibrosis by comparing using FibroScan. The metabolite fingerprint pathway showed that bile acid synthesis is disturbed while lipid metabolism is extremely active, resulting in an overload of lipid metabolites in the occurrence and development of chronic DILI–associated fibrosis.

Conclusions: Our metabolomic analysis reveals the unique metabolomic fingerprints associated with chronic DILI fibrosis, which have potential clinical diagnostic and prognostic significances. The metabolomic fingerprints suggest the disturbance of the lipid metabolites as the most important factor in the development of DILI fibrosis.
COVID-19 Vaccine-Associated Transient Global Amnesia: A Disproportionality Analysis of the WHO Safety Database
Authors: Merino Diane , Gérard Alexandre O. , Van Obberghen Elise K. , Ben Othman Nouha , Ettore Eric , Giordana Bruno , Viard Delphine , Rocher Fanny , Destere Alexandre , Benoit Michel , Drici Milou-Daniel
Published: May 2022

Coronavirus disease 2019 (COVID-19) spread rapidly, resulting in a global pandemic for which vaccines were quickly developed. As their safety continues to be monitored, cases of transient global amnesia (TGA) following mRNA vaccination with elasomeran have been reported. TGA is characterized by sudden onset of anterograde amnesia with preservation of other cognitive functions and resolution within 24 h. We aimed to investigate the potential link of TGA with COVID-19 vaccines. We queried the World Health Organization VigiBase® for all reports of “Transient global amnesia”, up to 6 December 2021. Disproportionality analysis relied on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI) and the Information Component (IC). A positive lower end of the 95% CI of the IC (IC025) is used to statistically detect a signal. Of all TGA cases, 289 were associated with a COVID-19 vaccine, representing the most frequent association. Tozinameran was mostly represented (147, 50.8%), followed by AZD1222 (69, 23,8%), elasomeran (60, 20.8%), and JNJ-78436735 (12, 4.2%). With an IC025 > 0, COVID-19 vaccines showed a significant ROR (5.1; 95%CI 4.4–6.0). Tozinameran reached the strongest ROR (4.6; 95%CI 3.9–5.0), followed by elasomeran (4.4; 95%CI 3.4–6.0), AZD1222 (3.8; 95%CI 3.0–5.0), and JNJ-78436735 (3.7; 95%CI 2.1–6.0). Our analysis of COVID-19 vaccines-related TGA reports shows significant disproportionality. Cerebrovascular, inflammatory, or migrainous mechanisms may underlie this association. Yet, numerous confounding factors cannot be tackled with this approach, and causality cannot be ascertained. The identification of this trigger of TGA may help the clinician in his etiological research.
Metabolomic Profiling Analysis of Physiological Responses to Acute Hypoxia and Reoxygenation in Juvenile Qingtian Paddy Field Carp Cyprinus Carpio Var Qingtianensis
Authors: Jiang Yuhan , Qi Ming , Zhang Jinpeng , Wen Yuanlin , Sun Jiamin , Liu Qigen
Published: May 2022

The Qingtian paddy field carp (Cyprinus carpio var qingtianensis) is a local carp cultivated in the rice field of Qingtian county, Zhejiang province, China. The paddy field environment is distinct from the pond environment. Due to the inability to artificially increase oxygen, the dissolved oxygen greatly changes during the day. Therefore, investigating the physiological regulation to the changes of acute dissolved oxygen in Qingtian paddy field carp (PF-carp) will dramatically clarify how it adapts to the paddy breeding environment. The high tolerance of Qingtian paddy field carp to hypoxia makes it an ideal organism for studying molecular regulatory mechanisms during hypoxia process and reoxygenation following hypoxia in fish. In this study, we compared the changes of metabolites in the hepatopancreas during hypoxia stress and the following reoxygenation through comparative metabolomics. The results showed 131 differentially expressed metabolites between the hypoxic groups and control groups. Among them, 95 were up-regulated, and 36 were down-regulated. KEGG Pathway enrichment analysis showed that these differential metabolites were mainly involved in regulating lipid, protein, and purine metabolism PF-carps could require energy during hypoxia by enhancing the gluconeogenesis pathway with core glutamic acid and glutamine metabolism. A total of 63 differentially expressed metabolites were screened by a comparison between the reoxygenated groups and the hypoxic groups. Specifically, 15 were up-regulated, and 48 were down-regulated. The KEGG Pathway enrichment analysis supported that PF-carp could continue to gain energy by consuming glutamic acid and the glutamine accumulated during hypoxia and simultaneously weaken the ammonia-transferring effect of amino acids and the toxicity of ammonia. By consuming glycerophospholipids and maintaining the Prostaglandin E content, cell damage was improved, sphingosinol synthesis was reduced, and apoptosis was inhibited. Additionally, it could enhance the salvage synthesis and de novo synthesis of purine, reduce purine accumulation, promote the synthesis of nucleotide and energy carriers, and assist in recovering physiological metabolism. Overall, results explained the physiological regulation mechanism of PF-carp adapting to the acute changes of dissolved oxygen at the metabolic level and also provided novel evidence for physiological regulation of other fish in an environment with acute changes in dissolved oxygen levels.
Efficacy of Utilization of All-Plant-Based and Commercial Low-Fishmeal Feeds in Two Divergently Selected Strains of Rainbow Trout (Oncorhynchus mykiss): Focus on Growth Performance, Whole-Body Proximate Composition, and Intestinal Microbiome
Authors: Biasato Ilaria , Rimoldi Simona , Caimi Christian , Bellezza Oddon Sara , Chemello Giulia , Prearo Marino , Saroglia Marco , Hardy Ronald , Gasco Laura , Terova Genciana
Published: May 2022

The present study aimed to investigate the growth performance, whole-body proximate composition, and intestinal microbiome of rainbow trout strains when selected and non-selected for weight gain on all-plant protein diets. A 2x2 factorial design was applied, where a selected (United States) and a non-selected (ITA) rainbow trout strain were fed using either an all-plant protein (PP) or a commercial low-FM diet (C). Diets were fed to five replicates of 20 (PP) or 25 (C) fish for 105 days. At the end of the trial, growth parameters were assessed, and whole fish (15 pools of three fish/diet) and gut samples (six fish/diet) were collected for whole-body proximate composition and gut microbiome analyses, respectively. Independent of the administered diet, the United States strain showed higher survival, final body weight, weight gain, and specific growth rate when compared to the ITA fish (p < 0.001). Furthermore, decreased whole-body ether extract content was identified in the PP-fed United States rainbow trout when compared to the ITA strain fed the same diet (p < 0.001). Gut microbiome analysis revealed the Cetobacterium probiotic-like genus as clearly associated with the United States rainbow trout, along with the up-regulation of the pathway involved in starch and sucrose metabolism. In summary, the overall improvement in growth performance and, to a lesser extent, whole-body proximate composition observed in the selected rainbow trout strain was accompanied by specific, positive modulation of the intestinal microbiome.
Effectiveness and Acceptability of e- and m-Health Interventions to Promote Physical Activity and Prevent Falls in Nursing Homes—A Systematic Review
Authors: Diener Jonathan , Rayling Sabine , Bezold Jelena , Krell-Roesch Janina , Woll Alexander , Wunsch Kathrin
Published: May 2022

Age-related decreases in physical activity (PA) and a decline in physical functioning lead to increased fall risk. As falls are a major cause of accidental deaths and hospitalization in older adults, PA promotion and fall prevention are important measures, especially in nursing homes (NH). With advances in information and communication technology, e- and m-health solutions have been developed to positively influence various health-related factors. To date, only little research exists on the implementation of these technologies to promote health in NH. Therefore, the objective of this systematic review was to provide an overview of the effectiveness, acceptability, and feasibility of e- and m-health interventions aimed at promoting PA and preventing falls in NH. Additionally, the effectiveness of such interventions regarding the secondary outcomes physical function, cognitive function, neuropsychiatric symptoms, and psychosocial status was examined. A systematic literature search was performed in five databases and studies published until 15 November 2021, were considered for inclusion. All studies that examined the effectiveness and/or the acceptability and feasibility of e- or m-health interventions in promoting PA and preventing falls in NH, without restriction on language or date of publication, were included in the final synthesis. Of the 1,358 records retrieved, 28 studies were included in this systematic review. Twenty-four studies contained digital exergaming as an intervention or as a part of the intervention, the four additional studies on e-health interventions only examined a small number of outcomes. No m-health intervention study was identified. Data synthesis indicates that exergaming may be effective in reducing the number of falls and fall risk in NH residents. Several significant improvements were also reported regarding secondary outcomes albeit not consistent across studies. No conclusion can be drawn about the effects of exergaming and other e-health interventions on PA, as data is scarce. E-health interventions were mostly reported as feasible and well accepted by NH residents. However, these findings may not be applicable to NH residents with advanced physical and/or cognitive impairments, since they were excluded in many studies. Therefore, more research examining other digital solutions besides exergaming to promote PA in this specific population is critical.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021289488
Extracellular Matrix-Oriented Proteomic Analysis of Periodontal Ligament Under Mechanical Stress
Authors: Thant Lay , Kaku Masaru , Kakihara Yoshito , Mizukoshi Masaru , Kitami Megumi , Arai Moe , Kitami Kohei , Kobayashi Daiki , Yoshida Yutaka , Maeda Takeyasu , Saito Isao , Uoshima Katsumi , Saeki Makio
Published: May 2022

The periodontal ligament (PDL) is a specialized connective tissue that provides structural support to the tooth and is crucial for oral functions. The mechanical properties of the PDL are mainly derived from the tissue-specific composition and structural characteristics of the extracellular matrix (ECM). The ECM also plays key roles in determining cell fate in the cellular microenvironment thus crucial in the PDL tissue homeostasis. In the present study, we determined the comprehensive ECM profile of mouse molar PDL using laser microdissection and mass spectrometry-based proteomic analysis with ECM-oriented data curation. Additionally, we evaluated changes in the ECM proteome under mechanical loading using a mouse orthodontic tooth movement (OTM) model and analyzed potential regulatory networks using a bioinformatics approach. Proteomic changes were evaluated in reference to the novel second harmonic generation (SHG)-based fiber characterization. Our ECM-oriented proteomics approach succeeded in illustrating the comprehensive ECM profile of the mouse molar PDL. We revealed the presence of type II collagen in PDL, possibly associated with the load-bearing function upon occlusal force. Mechanical loading induced unique architectural changes in collagen fibers along with dynamic compositional changes in the matrisome profile, particularly involving ECM glycoproteins and matrisome-associated proteins. We identified several unique matrisome proteins which responded to the different modes of mechanical loading in PDL. Notably, the proportion of type VI collagen significantly increased at the mesial side, contributing to collagen fibrogenesis. On the other hand, type XII collagen increased at the PDL-cementum boundary of the distal side. Furthermore, a multifaceted bioinformatics approach illustrated the potential molecular cues, including PDGF signaling, that maintain ECM homeostasis under mechanical loading. Our findings provide fundamental insights into the molecular network underlying ECM homeostasis in PDL, which is vital for clinical diagnosis and development of biomimetic tissue-regeneration strategies.
Do Personality Traits Matter? Exploring Anti-drug Behavioral Patterns in a Computer-Assisted Situated Learning Environment
Authors: Huang Tien-Chi , Chen Yu-Jie
Published: May 2022

Drug abuse has been and continues to be, a common social issue worldwide, yet the efficiency of widely adopted sweeping speech for anti-drug campaigns has proven inefficient. To provide students with a safe and efficient learning situation related to drug refusal skills, we used a novel approach rooted in a serious learning game and concept map during a brief extracurricular period to help students understand drugs and their negative effects. The proposed game-based situational learning system allowed all students to participate simultaneously and individually in multiple scenarios of drug temptation posed by peers and classmates to practice responding and refusing drugs in school and community settings. Moreover, to explore whether different personality traits (such as the Big Five personality traits) result in different anti-drug responses, we used a serious game to conduct an anti-drug experiment on 53 junior middle school students aged 13–15. Each participant’s decision-making process was recorded in the serious game as behavioral patterns for lag sequential analysis (LSA). The outcomes revealed seven behavioral patterns including differentiation (D), acceptance (A), effective (ER) and ineffective responses (IR), effective (ES) and ineffective solution-seeking (IS), and failure to refuse (F). The GSEQ (Generalized Sequential Querier) which is a computer program for analyzing sequential observational data was used. The results indicated the following: (1) Neuroticism was performed at a relatively low level under the guidance of a concept map. (2) “Neuroticism” was associated with the lowest risk of accepting drugs. (3) Students with “openness to experiences” were at high risk of accepting drugs. (4) Almost all personality behavioral transition diagrams showed that failure to refuse (F) drugs was followed by inefficient seeking of help (SI) and inefficient refusal (RI). These findings provide reference points for designing adaptive anti-drug education programs.
Effect of Matching Between the Adopted Corporate Response Strategy and the Type of Hypocrisy Manifestation on Consumer Behavior: Mediating Role of Negative Emotions
Authors: Wang Zhigang , Liu Xintao , Zhang Lei , Wang Chao , Liu Rui
Published: May 2022

Consumers may sense hypocrisy in corporate social responsibility (CSR) if they note inconsistency in enterprises’ words and deeds related to CSR. This inconsistency originates from the intentional selfish actions and unintentional actions of enterprises. Studies have revealed that consumers’ perception of hypocrisy has a negative influence on enterprise operation. However, studies have not examined how corporate responses to consumers’ hypocrisy perception affect consumers’ attitude and behavior. Therefore, the present study attempted to determine the measures that should be undertaken by enterprises to reduce consumers’ negative response to them when consumers perceive them to be hypocritical. We conducted a situational simulation experiment to explore the effect of the match between corporate hypocrisy manifestation (moral hypocrisy vs. behavioral hypocrisy) and the corporate response strategy (reactive CSR communication vs. proactive CSR communication) on consumers’ negative behaviors toward an enterprise and to test the mechanism influencing this effect. The results indicated that the interaction between the type of corporate hypocrisy and the corporate response strategy has a significant effect on consumers’ negative behaviors toward an enterprise. Consumers’ negative emotions have a mediating influence on the aforementioned effect. This study explored the response strategies of enterprises during a corporate hypocrisy crisis, classified corporate hypocrisy crises into two types (moral hypocrisy vs. behavioral hypocrisy) according to the different manifestations of corporate hypocrisy, and introduced situational crisis communication theory (SCCT) into research on corporate hypocrisy. The present results help expand knowledge on corporate hypocrisy.
How Does Hands-On Making Attitude Predict Epistemic Curiosity and Science, Technology, Engineering, and Mathematics Career Interests? Evidence From an International Exhibition of Young Inventors
Authors: Cui Yuting , Hong Jon-Chao , Tsai Chi-Ruei , Ye Jian-Hong
Published: May 2022

Whether the hands-on experience of creating inventions can promote Students’ interest in pursuing a science, technology, engineering, and mathematics (STEM) career has not been extensively studied. In a quantitative study, we drew on the attitude-behavior-outcome framework to explore the correlates between hands-on making attitude, epistemic curiosities, and career interest. This study targeted students who joined the selection competition for participating in the International Exhibition of Young Inventors (IEYI) in Taiwan. The objective of the invention exhibition is to encourage young students to make innovative projects by applying STEM knowledge and collaborative design. We collected 220 valid data from participants in the 2021 Taiwan IEYI selection competition and conducted a confirmatory factor analysis and structural equation modeling to test the hypotheses. Results indicated that: (1) hands-on making attitude was positively related to two types of epistemic curiosity; (2) interest-type epistemic curiosity (IEC) and deprivation-type epistemic curiosity (DEC) were positively associated with STEM career interest; additionally, DEC had a higher coefficient on STEM career interest than IEC; (3) both types of EC had a mediating role between hands-on making attitude and STEM career interest. It is expected that encouraging students to participate in invention exhibition competitions can raise both types of EC and increase their interest in pursuing STEM careers.
Attentional Competition and Semantic Integration in Low- and High-Span Readers
Authors: Guan Connie Qun , Fraundorf Scott H. , Gao Mingle , Zhang Chong , MacWhinney Brian
Published: May 2022

The goal of the current study is to investigate the effects of the distractive textual information on the activation of predictive inference online, and how the readers with high or low working memory capacity (WMC) differ in their online activation and text memory. To test the two hypothesis of attentional competition (AC) and semantic integration (SI), we conducted three experiments to investigate whether a local prediction (e.g., “The vase broke”) and a global prediction (e.g., “The wife left her husband”), both of which could be derived from the description of a critical event (e.g., “The angry husband throws the delicate porcelain vase against the brick wall”), are generated in the mind of the reader, and how this generation process is influenced by contextual and cognitive factors of the reader (e.g., working memory capacity). The results of Experiment 1 and 2 suggest that the elaboration of the global aspects in the narrative reduces the local prediction, but makes the global prediction more salient to occur. The evidence from Experiment 3 confirms the hypothesis that even automatic processes are constrained by distant contextual factors, in combination with differences in working memory, and examines how referentially local and global predictions are intertwined in text comprehension. Overall, these data support the immediate integration hypothesis across sentence boundaries at different representation levels (cf. Schmalhofer and Perfetti, 2007), as well as interaction assumptions of different processing levels within referentially local and referentially global processing contexts (cf. Yang et al., 2005).