bluuebunny/crossref_metadata_2025 huggingface dataset:
IV-Thrombolysis in Ischemic Stroke With Unknown Time of Onset—Safety and Outcomes in Posterior vs. Anterior Circulation Stroke
Authors: Macha Kosmas , Hoelter Philip , Siedler Gabriela , Wang Ruihao , Knott Michael , Stoll Svenja , Engelhorn Tobias , Doerfler Arnd , Schwab Stefan , Mühlen Iris , Kallmünzer Bernd
Published: September 2021

Background: rt-PA for ischemic stroke in the unknown or extended time window beyond the first 4. 5 h after symptom onset is safe and effective for certain patients after selection by multimodal neuroimaging. However, the evidence for this approach comes mainly from patients with anterior circulation stroke (ACS), while the data on posterior circulation stroke (PCS) are scarce.

Methods: Ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window between January 2011 and May 2019 were identified from an institutional registry. The patients were categorized into PCS or ACS based on clinico-radiological findings. We analyzed the hemorrhagic complications, clinical and imaging efficacy outcomes, and mortality rates by comparing the PCS and ACS patient groups. Adjusted outcome analyses were performed after propensity score matching for the relevant factors.

Results: Of the 182 patients included, 38 (20.9%) had PCS and 144 (79.1%) had ACS. Symptomatic acute large vessel occlusion (LVO) was present in 123 patients on admission [27 (22.0%) PCS and 96 (78.0%) ACS]. The score on the National Institutes of Health Stroke Scale (NIHSS), the time from last seen normal, and the door-to-needle times were similar in PCS and ACS. In patients with LVO, the NIHSS score was lower [8 (5–15) vs. 14 (9–18), p = 0.005], and infarction visible on follow-up imaging was less common [70.4 vs. 87.5%; aRD, −18.9% (−39.8 to −2.2%)] in the PCS patient group. There was a trend toward a lower risk for intracranial hemorrhage (ICH) following intravenous thrombolysis in PCS vs. ACS, without reaching a statistical significance [5.3 vs. 16.9%; aRD, −10.4% (−20.4 to 4.0%)]. The incidence of symptomatic ICH [according to the ECASS III criteria: 2.6 vs. 3.5%; aRD, −2.9% (−10.3 to 9.2%)], efficacy outcomes, and mortality rates were similar in PCS and ACS patients.

Conclusions: In this real-world clinical cohort, the safety and the efficacy of rt-PA for ischemic stroke in the unknown or extended time window did not show relevant differences between PCS and ACS, with a trend toward less hemorrhagic complications in PCS. The findings reconfirm the clinician in the usage of rt-PA beyond the first 4.5 h also in selected patients with PCS.
Social Cognition and Behavioral Assessments Improve the Diagnosis of Behavioral Variant of Frontotemporal Dementia in Older Peruvians With Low Educational Levels
Authors: Custodio Nilton , Montesinos Rosa , Cruzado Lizardo , Herrera-Perez Eder , Failoc-Rojas Virgilio E. , Pintado-Caipa Maritza , Seminario G Wendy , Cuenca José , Gamboa Carlos , Diaz Monica M.
Published: September 2021

Background: The behavioral variant of frontotemporal dementia (bvFTD), characterized by early behavioral abnormalities and late memory impairment, is a neurodegenerative disorder with a detrimental impact on patients and their caregivers. bvFTD is often difficult to distinguish from other neurodegenerative diseases, such as Alzheimer's disease (AD), using brief cognitive tests. Combining brief socio-cognitive and behavioral evaluations with standard cognitive testing could better discriminate bvFTD from AD patients. We sought to evaluate the diagnostic accuracy of brief socio-cognitive tests that may differentiate bvFTD and AD patients with low educational levels.

Methods: A prospective study was performed on 51 individuals over the age of 50 with low educational levels, with bvFTD or AD diagnosed using published criteria, and who were receiving neurological care at a multidisciplinary neurology clinic in Lima, Peru, between July 2017 and December 2020. All patients had a comprehensive neurological evaluation, including a full neurocognitive battery and brief tests of cognition (Addenbrooke's Cognitive Examination version III, ACE-III), social cognition (Mini-social Cognition and Emotional Assessment, Mini-SEA), and behavioral assessments (Frontal Behavioral Inventory, FBI; Interpersonal Reactivity Index—Emphatic Concern, IRI-EC; IRI—Perspective Taking, IRI-PT; and Self-Monitoring Scale—revised version, r-SMS). Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was performed to compare the brief screening tests individually and combined to the gold standard of bvFTD and AD diagnoses.

Results: The AD group was significantly older than the bvFTD group (p < 0.001). An analysis of the discriminatory ability of the ACE-III to distinguish between patients with AD and bvFTD (AUC = 0.85) and the INECO Frontal Screening (IFS; AUC = 0.78) shows that the former has greater discriminatory ability. Social and behavioral cognition tasks were able to appropriately discriminate bvFTD from AD. The Mini-SEA had high sensitivity and high moderate specificity (83%) for discriminating bvFTD from AD, which increased when combined with the brief screening tests ACE-III and IFS. The FBI was ideal with high sensitivity (83%), as well as the IRI-EC and IRI-PT that also were adequate for distinguishing bvFTD from AD.

Conclusions: Our study supports the integration of socio-behavioral measures to the standard global cognitive and social cognition measures utilized for screening for bvFTD in a population with low levels of education.
Clinical and Radiological Characteristics of Non-Benign Pineal Cyst Lesions in Children
Authors: Arkar Ula , Kučan Rok , Perković Benedik Mirjana , Hostnik Tadeja , Vipotnik Vesnaver Tina , Loboda Tanja , Bošnjak Roman , Osredkar Damjan
Published: September 2021

Background: With the increasing availability and advances in brain imaging, pineal cyst lesions (PCL) are becoming a common finding in the pediatric population. In the absence of evidence-based guidelines, optimal diagnostic and therapeutic approaches have not been established, and there is a risk of under- or overtreatment of these patients.

Objectives: The aim of our study was to evaluate the clinical presentation and radiological features of PCL in a cohort of pediatric patients and to identify clinical parameters more commonly associated with neoplasms in the pineal region. In addition, the prevalence of PCL in the pediatric population of Slovenia was estimated.

Methods: In this observational, cohort study, children treated at University Children's Hospital, Ljubljana, Slovenia in the period 1997–2016 were included if PCL was found on brain imaging. We analyzed indications for referral to a neurologist, clinical signs and symptoms, radiological features, treatment and outcome.

Results: The cohort consisted of 143 children with PCL. Pineocytoma was suspected in 31 children (21.7%). Six children underwent surgery – pineocytoma was confirmed in two cases and germinoma in one (2/3 of these children had signs of increased intracranial pressure (ICP), while PCL was benign in the remaining 4 cases. Only 2 PCL enlarged during the study period, both <2mm, none of these children developed neoplasm. Two children had PCL >20mm in diameter; both showed signs of increased ICP, one patient was found to have a germinoma of the pineal region, while the other had no neoplasm.

Conclusions: Most PCL do not change their features during radiological follow-up and even atypical PCL are very rarely associated with a malignant neoplasm of the pineal region. A PCL larger than 20 mm and signs of increased ICP were identified as potential markers for selecting patients at risk.
Relationship Between Epilepsy and Dreaming: Current Knowledge, Hypotheses, and Perspectives
Authors: de la Chapelle Aurélien , Frauscher Birgit , Valomon Amandine , Ruby Perrine Marie , Peter-Derex Laure
Published: September 2021

The interactions between epilepsy and sleep are numerous and the impact of epilepsy on cognition is well documented. Epilepsy is therefore likely to influence dreaming as one sleep-related cognitive activity. The frequency of dream recall is indeed decreased in patients with epilepsy, especially in those with primary generalized seizures. The content of dreams is also disturbed in epilepsy patients, being more negative and with more familiar settings. While several confounding factors (anti-seizure medications, depression and anxiety disorders, cognitive impairment) may partly account for these changes, some observations suggest an effect of seizures themselves on dreams. Indeed, the incorporation of seizure symptoms in dream content has been described, concomitant or not with a focal epileptic discharge during sleep, suggesting that epilepsy might directly or indirectly interfere with dreaming. These observations, together with current knowledge on dream neurophysiology and the links between epilepsy and sleep, suggest that epilepsy may impact not only wake- but also sleep-related cognition.
Considerations for Neuromorphic Supercomputing in Semiconducting and Superconducting Optoelectronic Hardware
Authors: Primavera Bryce A. , Shainline Jeffrey M.
Published: September 2021

Any large-scale spiking neuromorphic system striving for complexity at the level of the human brain and beyond will need to be co-optimized for communication and computation. Such reasoning leads to the proposal for optoelectronic neuromorphic platforms that leverage the complementary properties of optics and electronics. Starting from the conjecture that future large-scale neuromorphic systems will utilize integrated photonics and fiber optics for communication in conjunction with analog electronics for computation, we consider two possible paths toward achieving this vision. The first is a semiconductor platform based on analog CMOS circuits and waveguide-integrated photodiodes. The second is a superconducting approach that utilizes Josephson junctions and waveguide-integrated superconducting single-photon detectors. We discuss available devices, assess scaling potential, and provide a list of key metrics and demonstrations for each platform. Both platforms hold potential, but their development will diverge in important respects. Semiconductor systems benefit from a robust fabrication ecosystem and can build on extensive progress made in purely electronic neuromorphic computing but will require III-V light source integration with electronics at an unprecedented scale, further advances in ultra-low capacitance photodiodes, and success from emerging memory technologies. Superconducting systems place near theoretically minimum burdens on light sources (a tremendous boon to one of the most speculative aspects of either platform) and provide new opportunities for integrated, high-endurance synaptic memory. However, superconducting optoelectronic systems will also contend with interfacing low-voltage electronic circuits to semiconductor light sources, the serial biasing of superconducting devices on an unprecedented scale, a less mature fabrication ecosystem, and cryogenic infrastructure.
Higher Serum Bilirubin Levels in Response to Higher Carbohydrate Intake During Early Pregnancy and Lower Gestational Diabetes Mellitus Occurrence in Overweight and Obese Gravidae
Authors: He Wennan , Wang Liping , Zhang Yi , Jiang Yuan , Chen Xiaotian , Wang Yin , Dou Yalan , Chen Hongyan , Yan Weili
Published: September 2021

Background and Aim: Serum bilirubin levels are recently shown to be a novel protector of gestational diabetes mellitus (GDM), yet whether they could be affected by carbohydrate quality is unclear. We aimed to examine the associations between dietary carbohydrate parameters and serum bilirubin levels during early pregnancy, with further exploration on a potential mediating role of serum bilirubin levels on carbohydrate parameters-GDM pathways.

Methods: 260 healthy but overweight or obese gravidae (BMI ≥24 kg/m2) derived from a historical cohort in two hospitals in China were included. The associations between carbohydrate parameters (total carbohydrate intake, glycemic index GI, fiber intake, glycemic load GL) and serum bilirubin levels (total bilirubin, TB and direct bilirubin, DB) and GDM were evaluated by multivariable regression analysis. Generalized structural equation modeling was then applied to perform adjusted mediation analysis.

Results: Increased serum bilirubin levels (mmol/L) and decreased GDM occurrence were observed following dietary carbohydrate intake (%E) and GL (g/1,000 kcal) in highest tertile compared to the lowest tertile [carbohydrate: TB: β = 0.926 (95%CI: 0.069, 1.782), DB: β = 0.554 (95%CI: 0.192, 0.916);GL:TB: β = 1.170 (95%CI: 0.339, 2.001); DB: β = 0.369 (95%CI: 0.016, 0.700); carbohydrate: adjusted OR = 0.43 (95%CI:0.19–0.99); GL: adjusted OR = 0.36 (95%CI:0.16, 0.84)]. The mediating effect of carbohydrate intake and GL on GDM through bilirubin levels was evaluated as modest (carbohydrate: 6.2% for TB, 1.3% for DB; GL: 8.7% for TB, 2.3% for DB). No association was observed regarding GI and fiber.

Conclusions: Mildly elevated serum bilirubin levels appeared to be in response to higher energies consumed from carbohydrate during early pregnancy in healthy overweight or obese gravidae. However, the mediating effect of bilirubin levels on carbohydrate-GDM pathways is not evident. Larger investigation is further needed for solid evidence.
Caloric Restriction May Help Delay the Onset of Frailty and Support Frailty Management
Authors: Liu Pan , Li Yun , Ma Lina
Published: September 2021

Frailty is an age-related clinical syndrome that may increase the risk of falls, disability, hospitalization, and death in older adults. Delaying the progression of frailty helps improve the quality of life in older adults. Caloric restriction (CR) may extend lifespan and reduce the risk of age-related diseases. However, few studies have explored the relationship between CR and frailty. In this review, we focused on the impact of CR on frailty and aimed to identify potential associated mechanisms. Although CR may help prevent frailty, further studies are required to determine the underlying mechanisms and specific CR regimens suitable for use in humans.
Huge Trichilemmal Carcinoma With Metastasis Presenting With Two Distinct Histological Morphologies: A Case Report
Authors: Xie Yao , Wang Lin , Wang Tingting
Published: September 2021

Background

Trichilemmal carcinoma (TC) is a rare malignancy of cutaneous adnexal carcinoma, with only 136 cases reported in the literature to date. It usually has an indolent course and benign clinical evolution, and only four cases with regional and distant metastasis have been reported. Tumor cells present with the characteristics of trichilemmal differentiation on both histological and immunohistological examination.

Case Presentation

We report a case of TC on the scalp with an aggressive course and metastasis to the ipsilateral neck. Moreover, the lesions presented with two distinct histological morphologies.

Conclusion

Despite an indolent course and benign clinical evolution, TC has the potential for local invasion and recurrence, which implies that accurate early diagnosis and careful follow-up are very important for these patients. More than one specimen should be obtained for histopathological examinations when the lesion is very large and characterized by different morphologies.
Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report
Authors: Qing Defeng , Peng Luxing , Cen Feng , Huang Xinjun , Wei Qiang , Lu Heming
Published: September 2021

Background

Primary small cell neuroendocrine carcinoma (SCNEC) in the ureter is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes have not yet been thoroughly understood. Here we present a patient with advanced SCNEC in the ureter who was treated by multimodal strategies. To the best of our knowledge, this is the first literature report about the clinical outcomes of the combination of programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) and radiotherapy in patient with primary ureteral SCNEC.

Case Presentation

A 71-year old male presented with right flank pain and gross hematuria. A laparoscopic right nephroureterectomy was performed. He was diagnosed with primary ureteral SCNEC, pT3N0M0. Following the surgery, 4 cycles of adjuvant chemotherapy with carboplatin and etoposide (CE) were administered, with disease-free survival (DFS) of 10.1 months. He was then offered 4 cycles of palliative first-line chemotherapy with nedaplatin and irinotecan. The disease was continuously progressed, with progression-free survival (PFS) of 3.7 months. The patient subsequently received second-line treatment with PD-L1 ICI combined with radiotherapy. Unfortunately, hyperprogressive disease was found at the end of treatment. MRI and CT scan showed bilateral pubic bones, right acetabulum, and liver metastases. Without further intervention, the patient died from extensive metastatic disease 2 months after diagnosis, with overall survival (OS) of 18.2 months.

Conclusion

Physicians must be aware of this rare and aggressive carcinoma at its initial presentation. Special attention should be paid to the potential likelihood of hyperprogression during the treatment.
Construction and Characterization of Long Non-Coding RNA-Associated Networks to Reveal Potential Prognostic Biomarkers in Human Lung Adenocarcinoma
Authors: Zhou Wenting , Bai Chen , Long Chaojun , Hu Li , Zheng Yanfei
Published: September 2021

Lung adenocarcinoma (LUAD) is one type of the malignant tumors with high morbidity and mortality. The molecular mechanism of LUAD is still unclear. Studies demonstrate that lncRNAs play crucial roles in LUAD tumorigenesis and can be used as prognosis biomarkers. Thus, in this study, to identify more robust biomarkers of LUAD, we firstly constructed LUAD-related lncRNA-TF network and performed topological analyses for the network. Results showed that the network was a scale-free network, and some hub genes with high clinical values were identified, such as lncRNA RP11-173A16 and TF ZBTB37. Module analysis on the network revealed one close lncRNA module, which had good prognosis performance in LUAD. Furthermore, through integrating ceRNAs strategy and TF regulatory information, we identified some lncRNA-TF positive feedback loops. Prognostic analysis revealed that ELK4- and BDP1-related feedback loops were significant. Secondly, we constructed the lncRNA-m6A regulator network by merging all the high correlated lncRNA-m6A regulator pairs. Based on the network analysis results, some key m6A-related lncRNAs were identified, such as MIR497HG, FENDRR, and RP1-199J3. We also investigated the relationships between these lncRNAs and immune cell infiltration. Results showed that these m6A-related lncRNAs were high correlated with tumor immunity. All these results provide a new perspective for the diagnostic biomarker and therapeutic target identification of LUAD.
Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C)
Authors: Fernández-Sarmiento Jaime , Flórez Steffanie , Alarcón-Forero Laura C. , Salazar-Peláez Lina María , Garcia-Casallas Julio , Mulett Hernando , Acevedo Lorena , Salamanca Carolina
Published: September 2021

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.
Treatment for Severe Lupus Nephritis: A Cost-Effectiveness Analysis in China
Authors: Dai Zonglin , Zhang Xi , Wong Irene OL , Lau Eric HY , Lin Zhiming
Published: September 2021

Background: Lupus nephritis (LN) is the most common secondary glomerular diseases that will cause end-stage renal disease (ESRD) and renal-related death. The cost-effectiveness of various treatments for LN recommended by official guidelines has not been investigated in China. Our study is to evaluate clinical prognosis and cost-effectiveness of the current treatments for severe LN.

Methods: A Markov model was simulated for 1,000 LN patients of 30 years old, over a 3-years and 30-years lifetime horizon respectively. We assessed the cost-effectiveness of six therapeutic strategies from a societal perspective, with cyclophosphamide (CYC) or mycophenolate mofetil (MMF) induction therapy followed by CYC, MMF or azathioprine (AZA) maintenance therapy. Main outcomes included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER) and clinical prognosis. One and three times gross domestic product (GDP) per capita were used as the willingness-to-pay (WTP) thresholds. We also carried out sensitivity analysis under a lifetime horizon.

Results: Compared with the baseline strategy of CYC induction and maintenance, for a 3-years horizon the most cost-effective strategy was CYC induction and AZA maintenance with $448 per QALY gained, followed by MMF induction and AZA maintenance which however was not cost-effective under the one times GDP per capita WTP threshold. For a lifetime horizon, CYC induction and AZA maintenance remained the most cost-effective strategy but MMF induction and maintenance became cost-effective under the one times GDP per capita WTP threshold and achieved a higher complete remission rate (57.2 versus 48.9%) and lower risks of ESRD (3.3 versus 5.8%) and all-cause mortality (36.0 versus 40.8%). The risk of developing ESRD during maintenance was the most influential parameter affecting ICER.

Conclusions: The strategy of CYC induction followed by AZA maintenance was the most cost-effective strategy in China for short-term treatment, while the strategy of MMF in both induction and maintenance became cost-effective and yielded more desirable clinical outcomes for lifetime treatment. The uncertainty analysis supported the need for monitoring the progression to ESRD.
Chinese Herbal Medicine Combined With First-Generation EGFR-TKIs in Treatment of Advanced Non-Small Cell Lung Cancer With EGFR Sensitizing Mutation: A Systematic Review and Meta-Analysis
Authors: Lu Yan , Sun Chenbing , Jiao Lijing , Liu Yu , Gong Yabin , Xu Ling
Published: September 2021

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve prognosis of advanced NSCLC patients harboring EGFR sensitizing mutation. However, acquired resistance to EGFR-TKIs limits the good outcomes. Chinese herbal medicine (CHM) has been used for NSCLC patients receiving EGFR-TKIs for more than 10°years as an adjuvant treatment.

Methods: Studies were searched from China BioMedical Literature, Chinese National Knowledge Infrastructure, Cqvip Database, Wanfang Database, MEDLINE (PubMed), EMBASE (Ovid), Google Scholar, and Cochrane Library from inception to March, 2021. Randomized controlled clinical trials (RCT) comparing EGFR-TKIs + CHM (TKIs + CHM) versus EGFR-TKIs with/without placebo (TKIs ± placebo) in participants with advanced NSCLC harboring EGFR sensitizing mutation were included in this study. Two authors screened all references, assessed the risk of bias and extracted data independently. Data were summarized using hazard ratio (HR) and risk ratios (RR), with 95% confidence intervals (CI) for binary outcomes. Meta-analysis was performed using random effects model. Overall quality of evidence was assessed using GRADE.

Results: A total of 9 RCTs (1137 participants, 581 in the TKIs + CHM group and 556 in the TKIs ± placebo group) were included in this review. Only first-generation EGFR-TKIs were included. Most trials included used oral CHM preparations to tonify Qi and/or Yin. Treatment lasted from enrollment until disease progression (PD) or intolerable adverse events (AE). Combination of CHM with EGFR-TKIs improved median progression-free survival (mPFS) (HR,0.59; 95% CI, 0.52–0.68; P < 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13–1.34; P < 0.00001) compared with used of EGFR-TKIs ± placebo. CHM reduced AE associated with EGFR-TKIs such as cutaneous toxicity (RR, 0.58; 95% CI, 0.46–0.73; P < 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30–0.60; P < 0.00001).

Conclusion: Combination therapy of CHM and EGFR-TKIs significantly delays acquired resistance while improving ORR to EGFR-TKIs. Furthermore, CHM reduces AE induced by EGFR-TKIs. More international multi-centered, double-blinded, placebo-controlled, well-designed clinical trials are needed in future research.
Evidence and Potential Mechanisms of Jin-Gui Shen-Qi Wan as a Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Hu Zhipeng , Liu Xiaoke , Yang Maoyi
Published: September 2021

Background: Type 2 diabetes mellitus (T2DM) is a subtype of diabetes mellitus characterized by progressive dysfunction of β-cell insulin secretion and insulin resistance. Jīn-Guì Shèn-Qì Wán (JGSQW) has for many years been widely used in clinical practice as a treatment for T2DM. However, its effect remains unknown.

Objectives: This study aims to summarize the clinical evidence of the effect of JGSQW on glucose and lipid metabolism in T2DM and the potential mechanisms underlying this effect.

Methods: Six databases were searched without language or publication status restrictions. Data were extracted to a predefined template for synthesis.

Results: Fourteen studies with 1586 participants were included in this meta-analysis. All 14 studies were judged to be at high risk of bias. JGSQW is safe for T2DM patients. Pooled results indicated that combination treatment results in a reduction in glycated hemoglobin (HbA1c) (mean difference (MD) −0.49%; 95% CI −0.67 to −0.31), fasting blood glucose (FBG) (MD −0.84; 95% CI −1.19 to −0.49), and 2-hour postprandial glucose 2hBG (MD −1.38; 95% CI −1.60 to −1.16). No significant difference in glucose metabolism was observed between JGSQW and hypoglycemic agents. The available evidence was insufficient to determine the effects on lipid metabolism. Sensitivity analyses indicated that these results were robust.

Conclusion: By combining the available evidence, we found that JGSQW is safe for T2DM patients. Compared with hypoglycemic agents alone, combination treatment with JGSQW enhances the effect on glucose metabolism in patients with T2DM. We found no difference in the efficacy of JGSQW alone compared to hypoglycemic agents alone. In terms of lipid metabolism, the current evidence is insufficient and too inconsistent for us to draw firm conclusions, so further studies are needed.
Clemastine Fumarate Attenuates Myocardial Ischemia Reperfusion Injury Through Inhibition of Mast Cell Degranulation
Authors: Meng Shuqi , Sun Xiaotong , Juan Zhaodong , Wang Mingling , Wang Ruoguo , Sun Lina , Li Yaozu , Xin Anran , Li Shuping , Li Yao
Published: September 2021

Mast cell (MC) activation is associated with myocardial ischemia reperfusion injury (MIRI). Suppression of MC degranulation might be a target of anti-MIRI. This study aimed to determine whether clemastine fumarate (CLE) could attenuate MIRI by inhibiting MC degranulation. A rat ischemia and reperfusion (I/R) model was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Compound 48/80 (C48/80) was used to promote MC degranulation. The protective effect of CLE by inhibiting MC degranulation on I/R injury was detected by cardiac function, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, arrhythmia, and myocardial enzyme detection. Inflammatory factor mRNA levels, such as TNF-α, interleukin (IL)-1β, and IL-6, were detected. Cultured RBL-2H3 mast cells were pretreated with CLE and subjected to C48/80 treatment to determine whether CLE suppressed MC degranulation. Degranulation of MCs was visualized using tryptase release, Cell Counting Kit-8 (CCK-8), and cell toluidine blue (TB) staining. RBL cells were conditionally cultured with H9C2 cells to explore whether CLE could reverse the apoptosis of cardiomyocytes induced by MC degranulation. Apoptosis of H9C2 cells was detected by CCK-8, the LDH Cytotoxicity Assay Kit (LDH), TUNEL staining, and protein expression of BAX and Bcl-2. We found that CLE pretreatment further inhibited cardiac injury manifested by decreased infarct size, histopathological changes, arrhythmias, MC degranulation, and myocardial enzyme levels, improving cardiac function compared with that in the I/R group. C48/80 combined with I/R exacerbated these changes. However, pretreatment with CLE for C48/80 combined with I/R significantly reversed these injuries. In addition, CLE pretreatment improved the vitality of RBL cells and reduced tryptase release in vitro. Similarly, the supernatant of RBL cells pretreated with CLE decreased the cytotoxicity, TUNEL-positive cell rate, and BAX expression of conditioned H9C2 cells and increased the cell vitality and expression of Bcl-2. These results suggested that pretreatment with CLE confers protection against I/R injury by inhibiting MC degranulation.
Qiangjing Tablets Regulate Apoptosis and Oxidative Stress via Keap/Nrf2 Pathway to Improve the Reproductive Function in Asthenospermia Rats
Authors: Li Guangsen , Zhang Peihai , You Yaodong , Chen Diang , Cai Jian , Ma Ziyang , Huang Xiaopeng , Chang Degui
Published: September 2021

Asthenozoospermia (AZS), is a common cause of male infertility. Currently, most drugs for azoospermia lack desirable therapeutic efficiency, therefore developing new drug therapy is important. Qiangjing tablets could enhance renal function and improve sperm quality. The purpose of this study was to examine whether Qiangjing tablets could improve the reproductive function in azoospermia rats through activating the Nrf2/ARE pathway, and how to regulate energy metabolism and oxidative stress in this process. Sperm motility, sperm concentration and sperm viability were detected by WLJY-9000 Weili Digital Color Sperm Quality Detection System. HE staining was used to observe the pathological condition of testis in AZS rats. Cell apoptosis was analyzed by Tunnel staining and flow cytometry. The changes of mitochondrial membrane potential were detected by JC-1. The levels of Estradiol, testosterone and luteinizing hormone, activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and content of malondialdehyde (MDA) and glutathione (GSH) were detected by ELISA. The effects of Qiangjing Tablets on GC-1 spgs and Nrf2 protein were investigated through CCK-8 assay and western blot. The expression levels of HO-1, Keap1, and P-Nrf2 were detected by western blot. The results demonstrated that Qiangjing tablets upregulated levels of sperm motility, sperm concentration and sperm viability, which was shown to significantly increase levels of HO-1, Keap1, P-Nrf2, Estradiol and testosterone, along with increasing the activity of SOD, GSH-Px and GSH and suppressing the MDA content, luteinizing hormone and Vimentin level. Qiangjing tablets could significantly inhibit spermatogenic cells apoptosis and promote GC-1 spgs viability, increase PE/FITC ratio, mitochondrial membrane potential and reduc oxidative stress. Qiangjing tablets protected spermatogenic cell to upregulate male sex hormoneto, improved the sperm quality and reproductive function in AZS rats via activating the Keap/Nrf2 signaling pathway.
Neuropeptide Y: An Update on the Mechanism Underlying Chronic Intermittent Hypoxia-Induced Endothelial Dysfunction
Authors: Li Mei-mei , Zheng Yan-li , Wang Wan-da , Lin Shu , Lin Hui-li
Published: September 2021

Endothelial dysfunction (ED) is a core pathophysiological process. The abnormal response of vascular endothelial (VE) cells to risk factors can lead to systemic consequences. ED caused by intermittent hypoxia (IH) has also been recognized. Neuropeptide Y (NPY) is an important peripheral neurotransmitter that binds to different receptors on endothelial cells, thereby causing ED. Additionally, hypoxia can induce the release of peripheral NPY; however, the involvement of NPY and its receptor in IH-induced ED has not been determined. This review explains the definition of chronic IH and VE function, including the relationship between ED and chronic IH-related vascular diseases. The results showed that that the effect of IH on VE injury is mediated by the VE-barrier structure and endothelial cell dysfunction. These findings offer new ideas for the prevention and treatment of obstructive sleep apnea syndrome and its complications.
Fatigue in Aviation: Safety Risks, Preventive Strategies and Pharmacological Interventions
Authors: Wingelaar-Jagt Yara Q. , Wingelaar Thijs T. , Riedel Wim J. , Ramaekers Johannes G.
Published: September 2021

Fatigue poses an important safety risk to civil and military aviation. In addition to decreasing performance in-flight (chronic) fatigue has negative long-term health effects. Possible causes of fatigue include sleep loss, extended time awake, circadian phase irregularities and work load. Despite regulations limiting flight time and enabling optimal rostering, fatigue cannot be prevented completely. Especially in military operations, where limits may be extended due to operational necessities, it is impossible to rely solely on regulations to prevent fatigue. Fatigue management, consisting of preventive strategies and operational countermeasures, such as pre-flight naps and pharmaceuticals that either promote adequate sleep (hypnotics or chronobiotics) or enhance performance (stimulants), may be required to mitigate fatigue in challenging (military) aviation operations. This review describes the pathophysiology, epidemiology and effects of fatigue and its impact on aviation, as well as several aspects of fatigue management and recommendations for future research in this field.
Early Response to Dehydration Six-Like Transporter Family: Early Origin in Streptophytes and Evolution in Land Plants
Authors: Slawinski Lucie , Israel Abir , Paillot Caroline , Thibault Florence , Cordaux Richard , Atanassova Rossitza , Dédaldéchamp Fabienne , Laloi Maryse
Published: September 2021

Carbon management by plants involves the activity of many sugar transporters, which play roles in sugar subcellular partitioning and reallocation at the whole organism scale. Among these transporters, the early response to dehydration six-like (ESL) monosaccharide transporters (MSTs) are still poorly characterized although they represent one of the largest sugar transporter subfamilies. In this study, we used an evolutionary genomic approach to infer the evolutionary history of this multigenic family. No ESL could be identified in the genomes of rhodophytes, chlorophytes, and the brown algae Ectocarpus siliculosus, whereas one ESL was identified in the genome of Klebsormidium nitens providing evidence for the early emergence of these transporters in Streptophytes. A phylogenetic analysis using the 519 putative ESL proteins identified in the genomes of 47 Embryophyta species and being representative of the plant kingdom has revealed that ESL protein sequences can be divided into three major groups. The first and second groups originated in the common ancestor of all spermaphytes [ζ: 340 million years ago (MYA)] and of angiosperms (ε: 170–235 MYA), respectively, and the third group originated before the divergence of rosids and asterids (γ/1R: 117 MYA). In some eudicots (Vitales, Malpighiales, Myrtales, Sapindales, Brassicales, Malvales, and Solanales), the ESL family presents remarkable expansions of gene copies associated with tandem duplications. The analysis of non-synonymous and synonymous substitutions for the dN/dS ratio of the ESL copies of the genus Arabidopsis has revealed that ESL genes are evolved under a purifying selection even though the progressive increase of dN/dS ratios in the three groups suggests subdiversification phenomena. To further explore the possible acquisition of novel functions by ESL MSTs, we identified the gene structure and promoter cis-acting elements for Arabidopsis thaliana ESL genes. The expression profiling of Arabidopsis ESL unraveled some gene copies that are almost constitutively expressed, whereas other gene copies display organ-preferential expression patterns. This study provides an evolving framework to better understand the roles of ESL transporters in plant development and response to environmental constraints.
“Glocal” and Transversal Engagement in Youth Social Movements: A Twitter-Based Case Study of Fridays For Future-Barcelona
Authors: Terren Ludovic , Soler-i-Martí Roger
Published: September 2021

In the last decade, there has been a significant rise in the number of global social movements, generating claims of a new networked era of global social movements, in which young people often play a central role. Young generations and social movements tend to identify with a diverse set of social and political issues on both a global and local scale, while often displaying a progressive and transversal outlook. Among these youth social movements, we find Fridays For Future, a youth climate organization noted for its unique scope and tactics as well as for illustrating the prominence of environmental issues in youth activism. Since 2018, the movement has progressively grown into a network composed of many local and national groups across the world. Beyond analysis of the global character of the movement and the profile and motivations of its activists, it seems opportune to look at how—at the organizational level—these local groups evolve and position themselves. Based on a social network and a content analysis of Fridays For Future-Barcelona’s Twitter account since its creation, this article explores the organization’s “glocal” and transversal dynamics, the relationship that might exist between these two, and the potential influence of the COVID-19 pandemic on these processes. The results show that, stemming from a global preoccupation for climate change, this Youth Climate Movement organization has been increasingly oriented towards local-level networking, anchoring its activism in local struggles and realities. They also show a positively-associated process—reinforced by the COVID-19 pandemic—of increasing transversality, reflecting aspirations for global justice and the idea of an interdependency between climate change and other social, political and economic issues.
Persuasive Features of Scientific Explanations: Explanatory Schemata of Physical and Psychosocial Phenomena
Authors: Schoenherr Jordan Richard , Thomson Robert
Published: September 2021

Explanations are central to understanding the causal relationships between entities within the environment. Instead of examining basic heuristics and schemata that inform the acceptance or rejection of scientific explanations, recent studies have predominantly examined complex explanatory models. In the present study, we examined which essential features of explanatory schemata can account for phenomena that are attributed to domain-specific knowledge. In two experiments, participants judged the validity of logical syllogisms and reported confidence in their response. In addition to validity of the explanations, we manipulated whether scientists or people explained an animate or inanimate phenomenon using mechanistic (e.g., force, cause) or intentional explanatory terms (e.g., believes, wants). Results indicate that intentional explanations were generally considered to be less valid than mechanistic explanations and that ‘scientists’ were relatively more reliable sources of information of inanimate phenomena whereas ‘people’ were relatively more reliable sources of information of animate phenomena. Moreover, after controlling for participants’ performance, we found that they expressed greater overconfidence for valid intentional and invalid mechanistic explanations suggesting that the effect of belief-bias is greater in these conditions.
Mishearing as a Side Effect of Rational Language Comprehension in Noise
Authors: Van Os Marjolein , Kray Jutta , Demberg Vera
Published: September 2021

Language comprehension in noise can sometimes lead to mishearing, due to the noise disrupting the speech signal. Some of the difficulties in dealing with the noisy signal can be alleviated by drawing on the context – indeed, top-down predictability has shown to facilitate speech comprehension in noise. Previous studies have furthermore shown that strong reliance on the top-down predictions can lead to increased rates of mishearing, especially in older adults, which are attributed to general deficits in cognitive control in older adults. We here propose that the observed mishearing may be a simple consequence of rational language processing in noise. It should not be related to failure on the side of the older comprehenders, but instead would be predicted by rational processing accounts. To test this hypothesis, we extend earlier studies by running an online listening experiment with younger and older adults, carefully controlling the target and direct competitor in our stimuli. We show that mishearing is directly related to the perceptibility of the signal. We furthermore add an analysis of wrong responses, which shows that results are at odds with the idea that participants overly strongly rely on context in this task, as most false answers are indeed close to the speech signal, and not to the semantics of the context.
Infants’ Implicit Rhyme Perception in Child Songs and Its Relationship With Vocabulary
Authors: Hahn Laura E. , Benders Titia , Fikkert Paula , Snijders Tineke M.
Published: September 2021

Rhyme perception is an important predictor for future literacy. Assessing rhyme abilities, however, commonly requires children to make explicit rhyme judgements on single words. Here we explored whether infants already implicitly process rhymes in natural rhyming contexts (child songs) and whether this response correlates with later vocabulary size. In a passive listening ERP study, 10.5 month-old Dutch infants were exposed to rhyming and non-rhyming child songs. Two types of rhyme effects were analysed: (1) ERPs elicited by the first rhyme occurring in each song (rhyme sensitivity) and (2) ERPs elicited by rhymes repeating after the first rhyme in each song (rhyme repetition). Only for the latter a tentative negativity for rhymes from 0 to 200 ms after the onset of the rhyme word was found. This rhyme repetition effect correlated with productive vocabulary at 18 months-old, but not with any other vocabulary measure (perception at 10.5 or 18 months-old). While awaiting future replication, the study indicates precursors of phonological awareness already during infancy and with ecologically valid linguistic stimuli.
“The New State That We Are Building”: Authoritarianism and System-Justification in an Illiberal Democracy
Authors: Lönnqvist Jan-Erik , Szabó Zsolt Péter , Kelemen László
Published: September 2021

The authoritarian personality is characterized by unquestionining obedience and respect to authority. System justification theory (SJT) argues that people are motivated to defend, bolster, and justify aspects of existing social, economic, and political systems. Commitment to thestatus quois also a key characteristic of the authoritarian personality. It can be argued that the social context matters for how an underlying latent authoritarian character is expressed. This means that authoritarian regimes could be expected to lead to increased authoritarianism and stronger system-justification. We investigated this hypothesis in two representative samples of Hungarians, collected before (2010) and after (2018) 8 years of Fidesz’ rule (N= 1,000 in both samples). Moreover, the strong version of SJT argues that members of disadvantaged groups are likely to experience the most cognitive dissonance and that the need to reduce this dissonance makes them the most supportive of thestatus quo. This argument dovetails nicely with claims made by the political opposition to Fidesz, according to which Fidesz is especially popular among low-status members of society. We found that measures assessing authoritarian tendencies did not change between 2010 and 2018. However, more specific beliefs and attitudes did change, and these effects were especially pronounced among Fidesz supporters. Their belief in a just world and a just system has grown stronger, while their attitudes toward migrants had hardened. Low status was associated with lower levels of system-justifying ideologies. However, low status Fidesz voters justified the system more than high status opposition voters in 2018, lending some support for the strong version of SJT. Our results suggest that beliefs and attitudes of Hungarians have changed between 2010 and 2018, and that political leadership played a crucial role in this.
Clarifying the Implicit Assumptions of Two-Wave Mediation Models via the Latent Change Score Specification: An Evaluation of Model Fit Indices
Authors: Valente Matthew J. , Georgeson A. R. , Gonzalez Oscar
Published: September 2021

Statistical mediation analysis is used to investigate mechanisms through which a randomized intervention causally affects an outcome variable. Mediation analysis is often carried out in a pretest-posttest control group design because it is a common choice for evaluating experimental manipulations in the behavioral and social sciences. There are four different two-wave (i.e., pretest-posttest) mediation models that can be estimated using either linear regression or a Latent Change Score (LCS) specification in Structural Equation Modeling: Analysis of Covariance, difference and residualized change scores, and a cross-sectional model. Linear regression modeling and the LCS specification of the two-wave mediation models provide identical mediated effect estimates but the two modeling approaches differ in their assumptions of model fit. Linear regression modeling assumes each of the four two-wave mediation models fit the data perfectly whereas the LCS specification allows researchers to evaluate the model constraints implied by the difference score, residualized change score, and cross-sectional models via model fit indices. Therefore, the purpose of this paper is to provide a conceptual and statistical comparison of two-wave mediation models. Models were compared on the assumptions they make about time-lags and cross-lagged effects as well as statistically using both standard measures of model fit (χ2, RMSEA, and CFI) and newly proposed T-size measures of model fit for the two-wave mediation models. Overall, the LCS specification makes clear the assumptions that are often implicitly made when fitting two-wave mediation models with regression. In a Monte Carlo simulation, the standard model fit indices and newly proposed T-size measures of model fit generally correctly identified the best fitting two-wave mediation model.