bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver Failure of Wilson's Disease With Manifestations Similar to Porphyria and Uncommon ATP7B Gene Mutation: A Case Report and Literature Review
Authors: Zou Ju , Wang Ying-Hao , Wang Ling , Chen Ruo-Chan
Published: July 2021

Background: Wilson's disease (WD) is a rare condition; its diagnosis is challenging owing to a wide spectrum of ATP7B genotypes and variable clinical phenotypes, along with environmental factors. Few cases of WD with presentation of skin lesions and acute neurovisceral symptoms have been reported in the literature. To our knowledge, this is the first reported case of WD with an uncommon ATP7B gene mutation and rare symptoms of photosensitivity, sensation abnormality, and skin eruption occurring in a 19-year-old woman.

Case presentation: We report the case of a 19-year-old woman with WD presenting with liver failure, skin manifestations, and acute neurovisceral symptoms.The rare mutation in intron 1 of ATP7B (c.51+2T > G) was further confirmed by gene sequencing. The patients' symptoms improved after administration of penicillamine and zinc therapy combined with plasma exchange. She received long-term penicillamine treatment, and her liver function was within the normal range at 1 year after discharge. However, she underwent liver transplantation at 1.5 years after discharge.

Conclusions: We present a case of WD with a novel ATP7B gene mutation that may serve as a reference to generalists and specialists in hepatology or neurology of the rare clinical characteristics of WD, to prevent misdiagnosis and aid in the early diagnosis and treatment of the condition.
Validity Evidence for the Research Category, “Cognitively Unimpaired – Declining,” as a Risk Marker for Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Langhough Koscik Rebecca , Hermann Bruce P. , Allison Samantha , Clark Lindsay R. , Jonaitis Erin M. , Mueller Kimberly D. , Betthauser Tobey J. , Christian Bradley T. , Du Lianlian , Okonkwo Ozioma , Birdsill Alex , Chin Nathaniel , Gleason Carey , Johnson Sterling C.
Published: July 2021

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.
Age-Related Olfactory Decline Is Associated With Levels of Exercise and Non-exercise Physical Activities
Authors: Sollai Giorgia , Crnjar Roberto
Published: July 2021

Objective: This cross-sectional study evaluates the impact of active or non-active lifestyle in terms of physical, cognitive and social activity on the olfactory function in Elderly Subjects (ES) and aims at looking for a correlation between the time devoted to life activities and the score obtained during the olfactory tests by each individual.

Methods: One hundred and twenty-two elderly volunteers were recruited in Sardinia (Italy) and divided into active ES (n = 60; 17 men, 43 women; age 67.8 ± 1.12 years) and inactive ES (n = 62; 21 men, 41 women, age 71.1 ± 1.14 years) based on their daily physical activities. The olfactory function was evaluated using the “Sniffin’s Sticks” battery test, while the assessment of daily activities was made by means of personal interviews.

Results: A significant effect of active or inactive lifestyle was found on the olfactory function of ES (F(1,120) > 10.16; p < 0.005). A positive correlation was found between the olfactory scores and the number of hours per week dedicated to physical activities (Pearson’s r > 0.32, p ≤ 0.014) in both active and inactive ES.

Conclusions: High levels of exercise and non-exercise physical activity are strongly associated with the olfactory function and, consequently, with the quality of life of the elderly. Given the limited physical exercise of elderly people, they can benefit from a more active lifestyle by increasing non-exercise physical activities.
Gait Speed Trajectory During the Six-Minute Walk Test in Multiple Sclerosis: A Measure of Walking Endurance
Authors: Chen Shanshan , Sierra Salvador , Shin Yongyun , Goldman Myla D.
Published: July 2021

Background: The six-minute walk (6MW) test is a validated assessment method in Multiple Sclerosis (MS) research. While the total distance covered during six minutes (6MWTD) is often used as the standard measurement of gait capacity (i.e., the maximum distance one can achieve), we hypothesize that endurance (i.e., ability to maintain speed over a prolonged time) can be inferred by the gait speed trajectory (GST) during the 6MW test (6MWGST).

Objective: To characterize group differences in 6MWGST between MS patients and healthy controls (HCs), and to assess information added by 6MWGST for discerning between MS patients and HCs.

Methods: We performed a secondary data analysis on a cross-sectional cohort of 40 MS and 20 HC subjects with three repeated 6MW tests. We modeled 6MWGST using a linear mixed-effects model with time in minutes and replicated walks nested within individuals. We compared the discernibility of 6MWGST with that of conventional metrics using likelihood ratio tests and receiver operating characteristic (ROC) analysis on logistic regression models.

Results: MS subjects showed a concave, quadratic GST during 6MW tests, slowing down more than the HC subjects, especially at the beginning of 6MW tests. Despite accelerating at the end of the 6MW, MS subjects were unable to attain or surpass their initial 6MW gait speeds. 6MWGST added useful information (p = 0.002) to the conventional metrics (e.g., 6MWTD) for discerning between MS and HC subjects, and increased the area under the ROC curve from 0.83 to 0.93 (p = 0.037).

Conclusions: The distinctive 6MWGST pattern of MS patients provided increased discernibility compared with currently used gait metrics. Both gait capacity measured by the 6MWTD, and gait endurance measured by parameters of 6MWGST, are significant functional indicators for the MS population.
Invasive Electrophysiology for Circuit Discovery and Study of Comorbid Psychiatric Disorders in Patients With Epilepsy: Challenges, Opportunities, and Novel Technologies
Authors: Balzekas Irena , Sladky Vladimir , Nejedly Petr , Brinkmann Benjamin H. , Crepeau Daniel , Mivalt Filip , Gregg Nicholas M. , Pal Attia Tal , Marks Victoria S. , Wheeler Lydia , Riccelli Tori E. , Staab Jeffrey P. , Lundstrom Brian Nils , Miller Kai J. , Van Gompel Jamie , Kremen Vaclav , Croarkin Paul E. , Worrell Gregory A.
Published: July 2021

Intracranial electroencephalographic (iEEG) recordings from patients with epilepsy provide distinct opportunities and novel data for the study of co-occurring psychiatric disorders. Comorbid psychiatric disorders are very common in drug-resistant epilepsy and their added complexity warrants careful consideration. In this review, we first discuss psychiatric comorbidities and symptoms in patients with epilepsy. We describe how epilepsy can potentially impact patient presentation and how these factors can be addressed in the experimental designs of studies focused on the electrophysiologic correlates of mood. Second, we review emerging technologies to integrate long-term iEEG recording with dense behavioral tracking in naturalistic environments. Third, we explore questions on how best to address the intersection between epilepsy and psychiatric comorbidities. Advances in ambulatory iEEG and long-term behavioral monitoring technologies will be instrumental in studying the intersection of seizures, epilepsy, psychiatric comorbidities, and their underlying circuitry.
Preferential Cochleotoxicity of Cisplatin
Authors: Prayuenyong Pattarawadee , Baguley David M. , Kros Corné J. , Steyger Peter S.
Published: July 2021

Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin treatment has been consistently reported in the current literature. Inner ear hair cells seem to have intrinsic characteristics that make them susceptible to direct exposure to cisplatin. The existing literature suggests, however, that cisplatin might have different patterns of drug trafficking across the blood-labyrinth-barrier, or different degrees of cisplatin uptake to the hair cells in the cochlear and vestibular compartments. This review proposes an explanation for the preferential cochleotoxicity of cisplatin based on current evidence as well as the anatomy and physiology of the inner ear. The endocochlear potential, generated by the stria vascularis, acting as the driving force for hair cell mechanoelectrical transduction might also augment cisplatin entry into cochlear hair cells. Better understanding of the stria vascularis might shed new light on cochleotoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin associated ototoxicity.
Prognostic Value of Tumor Regression Grading in Patients Treated With Neoadjuvant Chemotherapy Plus Surgery for Gastric Cancer
Authors: Xie Jian-Wei , Lu Jun , Xu Bin-bin , Zheng Chao-Hui , Li Ping , Wang Jia-Bin , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Truty Mark J. , Huang Chang-Ming
Published: July 2021

Objective

To validate the prognostic value of tumor regression grading (TRG) and to explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery.

Methods

Two hundred forty-nine AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting tumor regression grading.

Results

For patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively (p<0.001). TRGs were independent risk factors for OS. Similar findings were observed in RFS. Multivariable analysis revealed that an oxaliplatin-based regimen (p=0.017) was an independent predictor of TRG. The oxaliplatin-based regimen was superior to the nonoxaliplatin-based regimen for OS (38.4 months vs 19.5 months, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in nonsignet ring cell carcinoma compared to the nonoxaliplatin-based regimen (53.7 months vs 19.5 months, respectively; p=0.011). However, similar findings were not observed in RFS.

Conclusion

TRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with nonsignet ring cell carcinoma.
The Impact of Foundation Medicine Testing on Cancer Patients: A Single Academic Centre Experience
Authors: Karol Dalia , McKinnon Mathieu , Mukhtar Lenah , Awan Arif , Lo Bryan , Wheatley-Price Paul
Published: July 2021

Background

The use of Next-Generation Sequencing (NGS) has recently allowed significant improvements in cancer treatment. Foundation Medicine® (FM) provides a genomic profiling test based on NGS for a variety of cancers. However, it is unclear if the Foundation Medicine test would result in a better outcome than the standard on-site molecular testing. In this retrospective chart review, we identified the FM cases from an academic Canadian hospital and determined whether these test results improved treatment options for those patients.

Materials and Methods

A retrospective analysis was performed on patients with solid tumors who had FM testing between May 1, 2014 and May 1, 2018. Clinical factors and outcomes were measured using descriptive statistics using Microsoft Excel® Software.

Results

Out of 66 FM tests, eight patients (= 12%) had a direct change in therapy based on the FM tests. Identified were 285 oncogenic mutations (median 1, range 0–31); where TP53 (n = 31, 10.9%), CDKN2A (n = 19, 6.7%), KRAS (n = 16, 5.6%) and APC (n = 9, 3.2%) were the most common FM mutations identified.

Conclusion

A small proportion of FM reports identified actionable mutations and led to direct treatment change. FM testing is expensive and a few of the identified mutations are now part of routine on-site testing. NGS testing is likely to become more widespread, but this research suggests that its true clinical impact may be restricted to a minority of patients.
Combinatorial Strategies to Target Molecular and Signaling Pathways to Disarm Cancer Stem Cells
Authors: Catara Giuliana , Colanzi Antonino , Spano Daniela
Published: July 2021

Cancer is an urgent public health issue with a very huge number of cases all over the world expected to increase by 2040. Despite improved diagnosis and therapeutic protocols, it remains the main leading cause of death in the world. Cancer stem cells (CSCs) constitute a tumor subpopulation defined by ability to self-renewal and to generate the heterogeneous and differentiated cell lineages that form the tumor bulk. These cells represent a major concern in cancer treatment due to resistance to conventional protocols of radiotherapy, chemotherapy and molecular targeted therapy. In fact, although partial or complete tumor regression can be achieved in patients, these responses are often followed by cancer relapse due to the expansion of CSCs population. The aberrant activation of developmental and oncogenic signaling pathways plays a relevant role in promoting CSCs therapy resistance. Although several targeted approaches relying on monotherapy have been developed to affect these pathways, they have shown limited efficacy. Therefore, an urgent need to design alternative combinatorial strategies to replace conventional regimens exists. This review summarizes the preclinical studies which provide a proof of concept of therapeutic efficacy of combinatorial approaches targeting the CSCs.
Assessment of Systemic Inflammation and Nutritional Indicators in Predicting Recurrence-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors
Authors: Lu Zhenhua , Li Rui , Cao Xianglong , Liu Chengyu , Sun Zhen , Shi Xiaolei , Shao Weiwei , Zheng Yangyang , Song Jinghai
Published: July 2021

Background

Recent studies have shown that the systemic inflammation and nutritional indicators are prognostic for a variety of malignancies. However, only limited data have so far demonstrated their usefulness in gastrointestinal mesenchymal tumors (GIST).

Methods

We retrospectively analyzed the data of GIST patients who underwent radical surgery in Beijing hospital from October 2004 to July 2018. The area under the receiver operating characteristic curve (AUC) was used to compare several commonly used inflammatory and nutritional indicators. The indicators with largest AUC were further analysis. Optimal cut-off values of those indicators in predicting recurrence-free survival (RFS) were determined. Kaplan-Meier curve and the time-dependent receiver operating characteristic (ROC) curve were used to assess the prognostic values. We then used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with RFS.

Results

In total, 160 patients who underwent surgery for GIST were included in the study. The median survival time was 34.5 months, with 1-, 3-, and 5-year RFS rates of 96.1%, 84.7%, and 80.8%, respectively. The inflammatory and nutritional indicators with largest AUC were Systemic immunoinflammatory Index (SII) and Geriatric Nutrition Risk Index (GNRI), reached 0.650 and 0.713, respectively. The optimal cutoff of GNRI and SII were 98.3, and 820.0, respectively. Univariate analysis showed that GNRI, SII, KI67, surgery method, tumor location, tumor size, and mitotic index were all significant prognostic indicators of RFS. After multivariate Cox analysis, independent prognostic factors for RFS in GIST included tumor location, mitotic index, tumor size, and GNRI (HR=2.802,95% CI: 1.045 to 7.515, p = 0.041). Besides, SII also tended to be associated with RFS (HR = 2.970, 95% CI: 0.946 to 9.326, p = 0.062).

Conclusions

High GNRI is an independent prognostic factor for RFS in GIST, while SII can be considered as a prognostic factor. GNRI and SII can be used as tools to evaluate the prognosis of patients before surgery, helping doctors to better treat high-risk patients.
CaMKII Inhibition is a Novel Therapeutic Strategy to Prevent Diabetic Cardiomyopathy
Authors: Veitch Christopher R. , Power Amelia S. , Erickson Jeffrey R.
Published: July 2021

Increasing prevalence of diabetes mellitus worldwide has pushed the complex disease state to the foreground of biomedical research, especially concerning its multifaceted impacts on the cardiovascular system. Current therapies for diabetic cardiomyopathy have had a positive impact, but with diabetic patients still suffering from a significantly greater burden of cardiac pathology compared to the general population, the need for novel therapeutic approaches is great. A new therapeutic target, calcium/calmodulin-dependent kinase II (CaMKII), has emerged as a potential treatment option for preventing cardiac dysfunction in the setting of diabetes. Within the last 10 years, new evidence has emerged describing the pathophysiological consequences of CaMKII activation in the diabetic heart, the mechanisms that underlie persistent CaMKII activation, and the protective effects of CaMKII inhibition to prevent diabetic cardiomyopathy. This review will examine recent evidence tying cardiac dysfunction in diabetes to CaMKII activation. It will then discuss the current understanding of the mechanisms by which CaMKII activity is enhanced during diabetes. Finally, it will examine the benefits of CaMKII inhibition to treat diabetic cardiomyopathy, including contractile dysfunction, heart failure with preserved ejection fraction, and arrhythmogenesis. We intend this review to serve as a critical examination of CaMKII inhibition as a therapeutic strategy, including potential drawbacks of this approach.
Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy
Authors: Chang Meiying , Yang Bin , Li Liusheng , Si Yuan , Zhao Mingming , Hao Wei , Zhao Jinning , Zhang Yu
Published: July 2021

Modified Huangqi Chifeng decoction (MHCD) has been used to reduce proteinuria in immunoglobulin A nephropathy (IgAN) for many years. Previously, we have demonstrated its protective role in glomerular mesangial cells. Podocyte injury, another key factor associated with proteinuria in IgAN, has also attracted increasing attention. However, whether MHCD can reduce proteinuria by protecting podocytes remains unclear. The present study aimed to investigate the protective effects of MHCD against podocyte injury in a rat model of IgAN. To establish the IgAN model, rats were administered bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. MHCD in three doses or telmisartan was administered once daily for 8 weeks (n = 10 rats/group). Rats with IgAN developed proteinuria at week 6, which worsened over time until drug intervention. After drug intervention, MHCD reduced proteinuria and had no effect on liver and kidney function. Furthermore, MHCD alleviated renal pathological lesions, hyperplasia of mesangial cells, mesangial matrix expansion, and podocyte foot process fusion. Western blot analysis revealed that MHCD increased the expression of the podocyte-associated proteins nephrin and podocalyxin. Additionally, we stained podocyte nuclei with an antibody for Wilms’ tumor protein one and found that MHCD increased the podocyte number in rats with IgAN. In conclusion, these results demonstrate that MHCD attenuates proteinuria by reducing podocyte injury.
Antibiotics Attenuate Methamphetamine-Induced Hepatotoxicity by Regulating Oxidative Stress and TLR4/MyD88/Traf6 Axis
Authors: Chen Li-Jian , He Jie-Tao , Pan Ming , Liu Jia-Li , Zhang Kai-Kai , Li Jia-Hao , Wang Li-Bin , Xu Ling-Ling , Chen Yu-Kui , Zhang Qin-Yao , Li Dong-Ri , Xu Jing-Tao , Xie Xiao-Li
Published: July 2021

Methamphetamine (METH) is a major psychostimulant drug of abuse worldwide, and its neurotoxicity has been studied extensively. In addition to neurotoxicity, METH can also induce hepatotoxicity. The underlying mechanism of intestinal microorganisms in METH-induced hepatotoxicity remains unclear. In this study, mice have received antibiotics intragastrically or PBS once each day for 1 week, followed by METH or saline. The antibiotics attenuated METH-induced hepatotoxicity as evidenced by histopathological observation and biochemical analysis; furthermore, they alleviated METH-induced oxidative stress. The effect of antibiotics on METH-induced hepatotoxicity was investigated using RNA-sequencing (RNA-seq). The RNA-seq results demonstrated that antibiotics could regulate 580 differentially expressed genes (DEGs), of which 319 were upregulated after METH treatment and then downregulated with antibiotic pretreatment and 237 were first downregulated after METH administration and then upregulated after antibiotic pretreatment, in addition to 11 upregulated and 13 downregulated ones simultaneously in METH and antibiotic-pretreated groups. RNA-seq analyses revealed that TLR4 is one of the hub genes. Western blot analysis indicated that antibiotics inhibited the increase of TLR4, MyD88 and Traf6 induced by METH. This research suggests that antibiotics may play an important role in preventing METH-induced liver injury by regulating oxidative stress and TLR4/MyD88/Traf6 axis, though further investigation is required.
The G2A Receptor Deficiency Aggravates Atherosclerosis in Rats by Regulating Macrophages and Lipid Metabolism
Authors: Cui Xueqin , Xing Roumei , Tian Yue , Wang Man , Sun Yue , Xu Yongqian , Yang Yiqing , Zhao Yongliang , Xie Ling , Xiao Yufang , Li Dali , Zheng Biao , Liu Mingyao , Chen Huaqing
Published: July 2021

The orphan G protein-coupled receptor G2A has been linked to atherosclerosis development. However, available data from mouse models are controversial. Rat G2A receptor bears more similarities with its human homolog. We proposed that the atherosclerosis model established from Ldlr–/– rat, which has been reported to share more similar phenotypes with the human disease, may help to further understand this lipid receptor. G2A deletion was found markedly aggravated in the lipid disorder in the rat model, which has not been reported in mouse studies. Examination of aortas revealed exacerbated atherosclerotic plaques in G2A deficient rats, together with increased oxidative stress and macrophage accumulation. In addition, consistently promoted migration and apoptosis were noticed in G2A deficient macrophages, even in macrophages from G2A single knockout rats. Further analysis found significantly declined phosphorylation of PI3 kinase (PI3K) and AKT, together with reduced downstream genes Bcl2 and Bcl-xl, suggesting possible involvement of PI3K/AKT pathway in G2A regulation to macrophage apoptosis. These data indicate that G2A modulates atherosclerosis by regulating lipid metabolism and macrophage migration and apoptosis. Our study provides a new understanding of the role of G2A in atherosclerosis, supporting it as a potential therapeutic target.
Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D3 Supplementation in High Iodide Intake–Induced Hypothyroid Offspring Rats
Authors: Liu Qing , Zhang Yue , Zhao Hailing , Yao Xiaomei
Published: July 2021

Aim: This study aimed to investigate the potential role of fatty acids in high iodide intake–induced hypothyroidism and its complications and also in the intervention of iodide intake adjustment and 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] supplementation.

Methods: Pregnant rats were allocated to two groups, namely, normal iodide (NI, 7.5 μg/day) intake and 100 times higher-than-normal iodide (100 HI, 750 μg/day) intake. The offspring were continuously administered potassium iodide from weaning [i.e., postnatal day 21 (PN21)] to PN90. After PN90, the offspring were either administered iodide intake adjustment (7.5 μg/day) or 1,25(OH)2D3 supplementation (5 μg·kg−1·day−1), or both, for 4 weeks. Thyroid function tests (free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibody, and thyroglobulin antibody), blood lipids (triglyceride, total cholesterol, free fatty acid, and low-density lipoprotein cholesterol), and vitamin D3 (VD3) levels were detected by ELISA. Cardiac function was measured by echocardiography. Blood pressure was measured using a non-invasive tail-cuff system. The serum fatty acids profile was analyzed by liquid chromatography–mass spectrometry.

Results: In the offspring rats with continued 100 HI administration, the levels of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET) and thromboxane B2 (TXB2) were decreased, while those of prostaglandin J2 (PGJ2), prostaglandin B2 (PGB2), 4-hydroxydocosahexaenoic acid (4-HDoHE), 7-HDoHE, 8-HDoHE, and 20-HDoHE were increased. Significant correlations were found between PGB2, 8,9-DHET, 7-HDoHE levels and thyroid dysfunction, between PGJ2, 20-HDoHE, PGB2, 8,9-DHET levels and cardiac dysfunction, between PGJ2, 20-HDoHE levels and hypertension, between 4-HDoHE, 8-HDoHE, TXB2 levels and dyslipidemia, and between PGB2 and decreased VD3 level. After the treatment of iodide intake adjustment and 1,25(OH)2D3 supplementation, the levels of 16-hydroxyeicosatetraenoic acids (16-HETE), 18-HETE, 5,6-epoxyeicosatrienoic acid (5,6-EET), 8,9-EET, 11,12-EET, 14,15-EET, PGE2, 5-oxo-ETE, and 15-oxo-ETE were increased. The significant associations between PGE2, 16-HETE, 18-HETE and improved thyroid function and also between 5,6-EET, 11,12-EET, 14,15-EET, 16-HETE, 15-oxo-ETE and attenuated dyslipidemia were detected.

Conclusion: Increased levels of prostaglandins (PGs) and HDoHEs and decreased levels of 8,9-DHET and TXB2 might occur in the progression of cardiac dysfunction, hypertension, and dyslipidemia in high iodide intake–induced hypothyroidism. The increased levels of EETs and HETEs might help to ameliorate these complications after iodide intake adjustment and 1,25(OH)2D3 supplementation.
Acute and Long-Term Effects of Aortic Compliance Decrease on Central Hemodynamics: A Modeling Analysis
Authors: Pagoulatou Stamatia , Adamopoulos Dionysios , Rovas Georgios , Bikia Vasiliki , Stergiopulos Nikolaos
Published: July 2021

Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave’s contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus −3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A (“old”) to Type C (“young”) phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.
Flower Color Evolution and the Evidence of Pollinator-Mediated Selection
Authors: Trunschke Judith , Lunau Klaus , Pyke Graham H. , Ren Zong-Xin , Wang Hong
Published: July 2021

The evolution of floral traits in animal-pollinated plants involves the interaction between flowers as signal senders and pollinators as signal receivers. Flower colors are very diverse, effect pollinator attraction and flower foraging behavior, and are hypothesized to be shaped through pollinator-mediated selection. However, most of our current understanding of flower color evolution arises from variation between discrete color morphs and completed color shifts accompanying pollinator shifts, while evidence for pollinator-mediated selection on continuous variation in flower colors within populations is still scarce. In this review, we summarize experiments quantifying selection on continuous flower color variation in natural plant populations in the context of pollinator interactions. We found that evidence for significant pollinator-mediated selection is surprisingly limited among existing studies. We propose several possible explanations related to the complexity in the interaction between the colors of flowers and the sensory and cognitive abilities of pollinators as well as pollinator behavioral responses, on the one hand, and the distribution of variation in color phenotypes and fitness, on the other hand. We emphasize currently persisting weaknesses in experimental procedures, and provide some suggestions for how to improve methodology. In conclusion, we encourage future research to bring together plant and animal scientists to jointly forward our understanding of the mechanisms and circumstances of pollinator-mediated selection on flower color.
Characterization of the Liriodendron Chinense MYB Gene Family and Its Role in Abiotic Stress Response
Authors: Wu Weihuang , Zhu Sheng , Zhu Liming , Wang Dandan , Liu Yang , Liu Siqin , Zhang Jiaji , Hao Zhaodong , Lu Ye , Cheng Tielong , Shi Jisen , Chen Jinhui
Published: July 2021

Liriodendron chinense (Lchi) is a Magnoliaceae plant, which is a basic angiosperm left behind by the Pleistocene and mainly distributed in the south of the Yangtze River. Liriodendron hybrids has good wood properties and is widely used in furniture and in other fields. It is not clear if they can adapt to different environmental conditions, such as drought and high and low temperatures, and the molecular mechanisms for this adaptation are unknown. Among plant transcription factors (TFs), the MYB gene family is one of the largest and is often involved in stress or adversity response signaling, growth, and development. Therefore, studying the role of MYBTFs in regulating abiotic stress signaling, growth, and development in Lchi is helpful to promote afforestation in different environments. In our research, a genome-wide analysis of the LchiMYB gene family was performed, including the phylogenetic relationship tree, gene exon-intron structure, collinearity, and chromosomal position. According to the evolutionary tree, 190 LchiMYBs were divided into three main branches. LchiMYBs were evenly distributed across 19 chromosomes, with their collinearity, suggesting that segment duplication events may have contributed to LchiMYB gene expansion. Transcriptomes from eight tissues, 11 stages of somatic embryogenesis, and leaves after cold, heat, and drought stress were used to analyze the function of the MYB gene family. The results of tissue expression analysis showed that most LchiMYB genes regulated bark, leaf, bud, sepal, stigma, and stamen development, as well as the four important stages (ES3, ES4, ES9, and PL) of somatic embryogenesis. More than 60 LchiMYBs responded to heat, cold, and drought stress; some of which underwent gene duplication during evolution. LchiMYB3 was highly expressed under all three forms of stress, while LchiMYB121 was strongly induced by both cold and heat stress. Eight genes with different expression patterns were selected and verified by quantitative real-time PCR (qRT-PCR) experiments. The results suggested that these LchiMYBs may regulate Lchi growth development and resistance to abiotic stress. This study shows the cross-regulatory function of LchiMYBs in the growth and development, asexual reproduction, and abiotic resistance of Lchi. This information will prove pivotal to directing further studies on the biological function of Lchi MYBTFs in genetic improvement and abiotic stress response.
Genome-Wide Identification of Triticum aestivum Xylanase Inhibitor Gene Family and Inhibitory Effects of XI-2 Subfamily Proteins on Fusarium graminearum GH11 Xylanase
Authors: Liu Yang , Han Nannan , Wang Sheng , Chen Can , Lu Jie , Riaz Muhammad Waheed , Si Hongqi , Sun Genlou , Ma Chuanxi
Published: July 2021

Triticum aestivum xylanase inhibitor (TaXI) gene plays an important role in plant defense. Recently, TaXI–III inhibitor has been shown to play a dual role in wheat resistance to Fusarium graminearum infection. Thus, identifying the members of the TaXI gene family and clarifying its role in wheat resistance to stresses are essential for wheat resistance breeding. However, to date, no comprehensive research on TaXIs in wheat (Triticum aestivum L.) has been conducted. In this study, a total of 277 TaXI genes, including six genes that we cloned, were identified from the recently released wheat genome database (IWGSC RefSeq v1.1), which were unevenly located on 21 chromosomes of wheat. Phylogenetic analysis divided these genes into six subfamilies, all the six genes we cloned belonged to XI-2 subfamily. The exon/intron structure of most TaXI genes and the conserved motifs of proteins in the same subfamily are similar. The TaXI gene family contains 92 homologous gene pairs or clusters, 63 and 193 genes were identified as tandem replication and segmentally duplicated genes, respectively. Analysis of the cis-acting elements in the promoter of TaXI genes showed that they are involved in wheat growth, hormone-mediated signal transduction, and response to biotic and abiotic stresses. RNA-seq data analysis revealed that TaXI genes exhibited expression preference or specificity in different organs and developmental stages, as well as in diverse stress responses, which can be regulated or induced by a variety of plant hormones and stresses. In addition, the qRT-PCR data and heterologous expression analysis of six TaXI genes revealed that the genes of XI-2 subfamily have double inhibitory effect on GH11 xylanase of F. graminearum, suggesting their potential important roles in wheat resistance to F. graminearum infection. The outcomes of this study not only enhance our understanding of the TaXI gene family in wheat, but also help us to screen more candidate genes for further exploring resistance mechanism in wheat.
Different Wood Anatomical and Growth Responses in European Beech (Fagus sylvatica L.) at Three Forest Sites in Slovenia
Authors: Arnič Domen , Gričar Jožica , Jevšenak Jernej , Božič Gregor , von Arx Georg , Prislan Peter
Published: July 2021

European beech (Fagus sylvatica L.) adapts to local growing conditions to enhance its performance. In response to variations in climatic conditions, beech trees adjust leaf phenology, cambial phenology, and wood formation patterns, which result in different tree-ring widths (TRWs) and wood anatomy. Chronologies of tree ring width and vessel features [i.e., mean vessel area (MVA), vessel density (VD), and relative conductive area (RCTA)] were produced for the 1960–2016 period for three sites that differ in climatic regimes and spring leaf phenology (two early- and one late-flushing populations). These data were used to investigate long-term relationships between climatic conditions and anatomical features of four quarters of tree-rings at annual and intra-annual scales. In addition, we investigated how TRW and vessel features adjust in response to extreme weather events (i.e., summer drought). We found significant differences in TRW, VD, and RCTA among the selected sites. Precipitation and maximum temperature before and during the growing season were the most important climatic factors affecting TRW and vessel characteristics. We confirmed differences in climate-growth relationships between the selected sites, late flushing beech population at Idrija showing the least pronounced response to climate. MVA was the only vessel trait that showed no relationship with TRW or other vessel features. The relationship between MVA and climatic factors evaluated at intra-annual scale indicated that vessel area in the first quarter of tree-ring were mainly influenced by climatic conditions in the previous growing season, while vessel area in the second to fourth quarters of tree ring width was mainly influenced by maximum temperature and precipitation in the current growing season. When comparing wet and dry years, beech from all sites showed a similar response, with reduced TRW and changes in intra-annual variation in vessel area. Our findings suggest that changes in temperature and precipitation regimes as predicted by most climate change scenarios will affect tree-ring increments and wood structure in beech, yet the response between sites or populations may differ.
Sequence of the Mitochondrial Genome of Lactuca virosa Suggests an Unexpected Role in Lactuca sativa’s Evolution
Authors: Fertet Arnaud , Graindorge Stéfanie , Koechler Sandrine , de Boer Gert-Jan , Guilloteau-Fonteny Emilie , Gualberto José M.
Published: July 2021

The involvement of the differentLactucaspecies in the domestication and diversification of cultivated lettuce is not totally understood.Lactuca serriolais considered as the direct ancestor and the closest relative toLactuca sativa, while the other wild species that can be crossed withL. sativa,Lactuca virosa, andLactuca saligna, would have just contributed to the latter diversification of cultivated typologies. To contribute to the study ofLactucaevolution, we assembled the mtDNA genomes of nineLactucaspp. accessions, among them three fromL. virosa, whose mtDNA had not been studied so far. Our results unveiled little to no intraspecies variation amongLactucaspecies, with the exception ofL. serriolawhere the accessions we sequenced diverge significantly from the mtDNA of aL. serriolaaccession already reported. Furthermore, we found a remarkable phylogenetic closeness between the mtDNA ofL. sativaand the mtDNA ofL. virosa, contrasting to theL. serriolaorigin of the nuclear and plastidial genomes. These results suggest that a cross betweenL. virosaand the ancestor of cultivated lettuce is at the origin of the actual mitochondrial genome ofL. sativa.
Mycotoxin Uptake in Wheat — Eavesdropping Fusarium Presence for Priming Plant Defenses or a Trojan Horse to Weaken Them?
Authors: Righetti Laura , Bhandari Dhaka Ram , Rolli Enrico , Tortorella Sara , Bruni Renato , Dall’Asta Chiara , Spengler Bernhard
Published: July 2021

Fusarium mycotoxins represent a major threat for cereal crops and food safety. While previous investigations have described plant biotransforming properties on mycotoxins or metabolic relapses of fungal infections in plants, so far, the potential consequences of radical exposure in healthy crops are mostly unknown. Therefore, we aimed at evaluating whether the exposure to mycotoxins, deoxynivalenol (DON) and zearalenone (ZEN), at the plant-soil interface may be considered a form of biotic stress capable of inducing priming or a potential initiation of fungal attack. To address this, we used atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging to investigate the activation or the inhibition of specific biosynthetic pathways and in situ localization of primary and secondary metabolites in wheat. According to our untargeted metabolomics investigation, the translocation of plant defense metabolites (i.e., hydroxycinnamic acid amide and flavones) follows the mycotoxin accumulation organs, which is the root for ZEN-treated plantlet and culm for DON-treated sample, suggesting a local “defense-on-demand response.” Therefore, it can be hypothesized that DON and ZEN are involved in the eavesdropping of Fusarium presence in soil and that wheat response based on secondary metabolites may operate on multiple organs with a potential interplay that involves masked mycotoxins.
Under-Vine Vegetation Mitigates the Impacts of Excessive Precipitation in Vineyards
Authors: Vanden Heuvel Justine , Centinari Michela
Published: July 2021

Excessive precipitation events have greatly increased in several grape growing regions due to human-caused climate change. These heavy downpours result in a myriad of problems in the vineyard including soil aggregate breakdown, soil runoff, nutrient leaching, excessive vine vegetative growth, and diseased fruit. The negative impacts of excessive precipitation events on vineyards are exacerbated by the maintenance of bare soil under the vines. Exposure of bare soil results in soil erosion and runoff which pollutes nearby watersheds; raindrops weaken and break apart soil aggregates, leading to increased soil erosivity and contributing to the formation of surface crusts. In addition to excessive precipitation events, some grape growing regions can be characterized by fertile soils. The availability of ample water and nutrients can lead to highly vigorous vines with shoot growth continuing through harvest. Long shoots and large leaves result in shaded fruit, a humid vine microclimate, and excessive cluster rot. In this review, we examined how either natural (i.e., resident) or seeded under-vine vegetation (UVV) can help mitigate many of the problems associated with excessive precipitation. Through providing vegetative coverage to reduce the force of raindrops, increasing soil organic matter and enhancing soil microbial diversity, UVV can reduce the soil degradation and off-site impacts caused by excessive precipitation events. Through competition for soil resources, UVV can reduce excessive vegetative growth of vines and decrease cluster rot incidence and severity, although grapevine response to UVV can be highly variable. We discussed recent advances in understanding below and aboveground vine response and acclimation to UVV and presented current evidence of factors influencing the impact of UVV on vine growth and productivity to assist practitioners in making informed decisions and maximize the ecosystem services provided by UVV.
Asymmetric Underlying Mechanisms of Relation-Based and Property-Based Noun–Noun Conceptual Combination
Authors: Choi Mingyeong , Yoon Sangsuk
Published: July 2021

Conceptual combination is a fundamental human cognitive ability by which people can experience infinite thinking by artfully combining finite knowledge. For example, one can instantly combine “cactus” and “fish” together as “prickly fish” even if one has never previously heard of a “cactus fish.” Although two major combinatorial types—property and relational combinations—have been identified, the underlying processes of each remain elusive. This study investigates the asymmetric processing mechanisms underlying property and relational combinations by examining differential semantic activation during noun–noun conceptual combination. Across two experiments utilizing each combinatorial process as semantic priming and implementing a lexical decision task immediately after combination, we measure and compare the semantic activation patterns of intrinsic and extrinsic semantic features in these two combinatorial types. We found converging evidence that property and relational combinations involve asymmetric semantic information and entail distinct processing mechanisms. In property combination, the intrinsic feature in the modifier concept showed greater activation than the semantic feature of the same dimension in the head concept. In contrast, in relational combination, the extrinsic semantic feature in the head concept and the whole modifier concept showed similar levels of activation. Moreover, our findings also showed that these patterns of semantic activation occurred only when the combinatorial process was complete, indicating that accessing the same lexical-semantic information is not sufficient to observe asymmetric patterns. These findings demonstrate that property combination involves replacing a specific semantic feature of the head noun with that of the modifier noun, whereas relational combination involves completing the semantic feature of the head noun with the whole modifier concept. We discuss the implications of these findings, research limitations, and future research directions.
Paternalistic Leadership and Safety Participation of High-Speed Railway Drivers in China: The Mediating Role of Leader–Member Exchange
Authors: Zhang Na , Liu Shuzhen , Pan Bowen , Guo Ming
Published: July 2021

This research aimed to examine the effects of paternalistic leadership on the safety participation of high-speed railway drivers. Survey data were collected from 601 drivers in major Chinese rail companies. Structural equation modeling was conducted to analyze the influence of paternalistic leadership on safety participation via leader–member exchange (LMX). The results indicated that moral leadership directly promotes safety participation. Besides, benevolent leadership was positively associated with safety participation. Also, LMX partially mediates the positive relationship between benevolent leadership, moral leadership, and safety participation. Therefore, paternalistic leadership promotes the safety participation of high-speed railway drivers.
Individual Differences in Print Exposure Predict Use of Implicit Causality in Pronoun Comprehension and Referential Prediction
Authors: Johnson Elyce , Arnold Jennifer E.
Published: July 2021

In three experiments, we measured individual patterns of pronoun comprehension (Experiments 1 and 2) and referential prediction (Experiment 3) in implicit causality (IC) contexts and compared these with a measure of participants’ print exposure (Author Recognition Task; ART). Across all three experiments, we found that ART interacted with verb bias, such that participants with higher scores demonstrated a stronger semantic bias, i.e., they tended to select the pronoun or predict the re-mention of the character that was congruent with an implicit cause interpretation. This suggests that print exposure changes the way language is processed at the discourse level, and in particular, that it is related to implicit cause sensitivity.