bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Alterations in Impaired Mitochondrial Dynamics Due to Neurodegeneration
Authors: Ashraf Ghulam Md , Chatzichronis Stylianos , Alexiou Athanasios , Firdousi Gazala , Kamal Mohammad Amjad , Ganash Magdah
Published: July 2022

Alzheimer’s disease is still an incurable disease with significant social and economic impact globally. Nevertheless, newly FDA-approved drugs and non-pharmacological techniques may offer efficient disease treatments. Furthermore, it is widely accepted that early diagnosis or even prognosis of Alzheimer’s disease using advanced computational tools could offer a compelling alternative way of management. In addition, several studies have presented an insight into the role of mitochondrial dynamics in Alzheimer’s development. In combination with diverse dietary and obesity-related diseases, mitochondrial bioenergetics may be linked to neurodegeneration. Considering the probabilistic expectations of Alzheimer’s disease development or progression due to specific risk factors or biomarkers, we designed a Bayesian model to formulate the impact of diet-induced obesity with an impaired mitochondrial function and altered behavior. The applied probabilities are based on clinical trials globally and are continuously subject to updating and redefinition. The proposed multiparametric model combines various data types based on uniform probabilities. The program simulates all the variables with a uniform distribution in a sample of 1000 patients. First, the program initializes the variable age (30–95) and the four different diet types (“HFO_diet,” “Starvation,” “HL_diet,” “CR”) along with the factors that are related to prodromal or mixed AD (ATP, MFN1, MFN2, DRP1, FIS1, Diabetes, Oxidative_Stress, Hypertension, Obesity, Depression, and Physical_activity). Besides the known proteins related to mitochondrial dynamics, our model includes risk factors like Age, Hypertension, Oxidative Stress, Obesity, Depression, and Physical Activity, which are associated with Prodromal Alzheimer’s. The outcome is the disease progression probability corresponding to a random individual ID related to diet choices and mitochondrial dynamics parameters. The proposed model and the programming code are adjustable to different parameters and values. The program is coded and executed in Python and is fully and freely available for research purposes and testing the correlation between diet type and Alzheimer’s disease progression regarding various risk factors and biomarkers.
Altered Prefrontal Blood Flow Related With Mild Cognitive Impairment in Parkinson's Disease: A Longitudinal Study
Authors: Wang Jian , Zhang Wei , Zhou Ying , Jia Jia , Li Yuanfang , Liu Kai , Ye Zheng , Jin Lirong
Published: July 2022

Cognitive impairment is a common non-motor symptom in Parkinson's disease (PD), with executive dysfunction being an initial manifestation. We aimed to investigate whether and how longitudinal changes in the prefrontal perfusion correlate with mild cognitive impairment (MCI) in patients with PD. We recruited 49 patients with PD with normal cognition and 37 matched healthy control subjects (HCs). Patients with PD completed arterial spin labeling MRI (ASL–MRI) scans and a comprehensive battery of neuropsychological assessments at baseline (V0) and 2-year follow-up (V1). HCs completed similar ASL–MRI scans and neuropsychological assessments at baseline. At V1, 10 patients with PD progressed to MCI (converters) and 39 patients remained cognitively normal (non-converters). We examined differences in the cerebral blood flow (CBF) derived from ASL–MRI and neuropsychological measures (a) between patients with PD and HCs at V0 (effect of the disease), (b) between V1 and V0 in patients with PD (effect of the disease progression), and (c) between converters and non-converters (effect of the MCI progression) using t-tests or ANOVAs with false discovery rate correction. We further analyzed the relationship between longitudinal CBF and neuropsychological changes using multivariate regression models with false discovery rate correction, focusing on executive functions. At V0, no group difference was found in prefrontal CBF between patients with PD and HCs, although patients with PD showed worse performances on executive function. At V1, patients with PD showed significantly reduced CBF in multiple prefrontal regions, including the bilateral lateral orbitofrontal, medial orbitofrontal, middle frontal, inferior frontal, superior frontal, caudal anterior cingulate, and rostral anterior cingulate. More importantly, converters showed a more significant CBF reduction in the left lateral orbitofrontal cortex than non-converters. From V0 to V1, the prolonged completion time of Trail Making Test-B (TMT-B) negatively correlated with longitudinal CBF reduction in the right caudal anterior cingulate cortex. The decreased accuracy of the Stroop Color-Word Test positively correlated with longitudinal CBF reduction in the left medial orbitofrontal cortex. In addition, at V1, the completion time of TMT-B negatively correlated with CBF in the left caudal anterior cingulate cortex. Our findings suggest that longitudinal CBF reduction in the prefrontal cortex might impact cognitive functions (especially executive functions) at the early stages of PD.
Mixed Comparison of Different Exercise Interventions for Function, Respiratory, Fatigue, and Quality of Life in Adults With Amyotrophic Lateral Sclerosis: Systematic Review and Network Meta-Analysis
Authors: Zhu Yining , Xu Yining , Xuan Rongrong , Huang Jialu , István Bíró , Fekete Gusztáv , Gu Yaodong
Published: July 2022

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease whose primary hallmark is the progressive degeneration of motor neurons in the brainstem, spinal cord, and cerebral cortex that leads to weakness, spasticity, fatigue, skeletal muscle atrophy, paralysis, and even death. Exercise, as a non-pharmacological tool, may generally improve muscle strength, cardiovascular function, and quality of life. However, there are conflicting reports about the effect of exercise training in adults with ALS.

Aims

This systematic review and network meta-analysis aim to conduct a mixed comparison of different exercise interventions for function, respiratory, fatigue, and quality of life in adults with ALS.

Methods

Randomized controlled trials with ALS participants were screened and included from the databases of PubMed, Medline, and Web of Science. Physical exercise interventions were reclassified into aerobic exercise, resistance training, passive exercise, expiratory muscle exercise, and standard rehabilitation. Patient-reported outcome measures would be reclassified from perspectives of function, respiratory, fatigue, and quality of life. The effect size would be transferred into the percentage change of the total score.

Result

There were 10 studies included, with the agreement between authors reaching a kappa-value of 0.73. The network meta-analysis, which was conducted under the consistency model, identified that a combined program of aerobic exercise, resistance exercise, and standard rehabilitation showed the highest potential to improve quality of life (0.64 to be the best) and reduce the fatigue (0.39 to be the best) for ALS patients, while exercise program of aerobic and resistance training showed the highest potential (0.51 to be the best) to improve ALS patients' physical function. The effect of exercise on the respiratory was still unclear.

Conclusion

A multi-modal exercise and rehabilitation program would be more beneficial to ALS patients. However, the safety and guide for practice remain unclear, and further high-quality randomized controlled trials (RCTs) with a larger sample are still needed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253442, CRD42021253442.
Dopamine Transporter Knockout Rats Show Impaired Wellbeing in a Multimodal Severity Assessment Approach
Authors: Mallien Anne Stephanie , Becker Laura , Pfeiffer Natascha , Terraneo Federica , Hahn Melissa , Middelman Anthonieke , Palme Rupert , Creutzberg Kerstin Camile , Begni Veronica , Riva Marco Andrea , Leo Damiana , Potschka Heidrun , Fumagalli Fabio , Homberg Judith R. , Gass Peter
Published: July 2022

In preclinical psychiatry research, animals are central to modeling and understanding biological mechanisms of behavior and psychiatric disorders. We here present the first multimodal severity assessment of a genetically modified rat strain used in psychiatric research, lacking the dopamine transporter (DAT) gene and showing endophenotypes of several dopamine-associated disorders. Absence of the DAT leads to high extracellular dopamine (DA) levels and has been associated with locomotor hyperactivity, compulsive behaviors and stereotypies in the past. The German Animal Welfare Law, which is based on the EU Directive (2010/63/EU), requires a prospective severity assessment for every animal experiment, depending on the extent of the expected degree of pain, suffering, distress or lasting harm that the animals will experience. This should consider all procedures but also the impact of the genotype on the phenotype. Therefore, we examined multiple parameters indicating animal welfare, like burrowing behavior, social interaction, saccharin preference, baseline stress hormone levels and nesting behavior. Additionally, a footprint analysis was performed and home cage activity was analyzed for a more detailed characterization of locomotion. DAT KO rats demonstrated reduced burrowing, social interaction and saccharin preference. We also found pronounced stereotypies and alterations in the gait analysis in DAT KO rats. Moreover, we confirmed the hyperactivity and the impaired sensorimotor gating mechanisms to assure that our rats are exhibiting the correct phenotype. In conclusion, we provide evidence that DAT KO rats show alterations in natural behavior patterns and deduce that the marked stereotypies are a sign for coping difficulties, both indicating a negative influence of the genotype on wellbeing. We suggest to assess further rat models in an objectified severity assessment as previously done in mice to create a relative severity assessment based on scientific evidence. Until then, we propose the classification of homozygous DAT KO rats as “moderate” in accordance with the criteria of the EU directive 2010/63.
Prefrontal Dopaminergic Regulation of Cue-Guided Risky Decision-Making Performance in Rats
Authors: Yang Minzhe , Fu Qiangpei , Ma Chaolin , Li Baoming
Published: July 2022

Risky decision-making is the decision made by individuals when they know the probability of each outcome. In order to survive in unpredictable environments, it is necessary for individuals to assess the probability of events occurring to an make appropriate decisions. There are few studies on the neural basis of risky decision-making behavior guided by external cues, which is related to the relative paucity of animal behavioral paradigms. Previous studies have shown that the prefrontal cortex (PFC) plays a key role in risk-based decision-making. The PFC receives projections from the dopamine (DA) system from the ventral tegmental area of the midbrain. The mesocorticolimbic DA system regulates the judgments of reward and value in decision-making. However, the specific receptor mechanism for prefrontal DA regulation of cue-guided risky decision-making behavior remains unclear. Here we established a cue-guided risky decision-making behavioral paradigm (RDM task) to detect the behavior of rats making decisions between a small certain reward and a large uncertain reward in a self-paced manner. The D1 receptor antagonist SCH-23390 (5 mM) or agonist SKF-82958 (5 mM), and the D2 receptor antagonist thioridazine hydrochloride (5 mM) or agonist MLS-1547 (5 mM) was injected into the mPFC, respectively, to investigate how the behavior in the RDM task was changed. The results showed that: (1) rats were able to master the operation of the cue-guided RDM task in a self-paced way; (2) a majority of rats were inclined to choose risk rather than a safe option when the reward expectations were equal; and (3) risk selection was reduced upon inhibition of D1 receptors or stimulation of D2 receptors, but increased upon stimulation of D1 receptors or inhibition of D2 receptors, suggesting that the RDM performance is regulated by D1 and D2 receptors in the mPFC. The present results suggest that DA receptors in the mPFC of rats are involved in regulating cue-guided RDM behavior, with differential involvement of D1 and D2 receptors in the regulation.
Dynamics of Microglia Activation in the Ischemic Brain: Implications for Myelin Repair and Functional Recovery
Authors: Raffaele Stefano , Fumagalli Marta
Published: July 2022

Ischemic stroke is a neurological disorder representing a leading cause of death and permanent disability world-wide, for which effective regenerative treatments are missing. Oligodendrocyte degeneration and consequent myelin disruption are considered major contributing factors to stroke-associated neurological deficits. Therefore, fostering myelin reconstruction by oligodendrocyte precursor cells (OPCs) has emerged as a promising therapeutic approach to enhance functional recovery in stroke patients. A pivotal role in regulating remyelination is played by microglia, the resident immune cells of the brain. Early after stroke, microglial cells exert beneficial functions, promoting OPC recruitment toward the ischemic lesion and preserving myelin integrity. However, the protective features of microglia are lost during disease progression, contributing to remyelination failure. Unveiling the mechanisms driving the pro-remyelination properties of microglia may provide important opportunities for both reducing myelin damage and promoting its regeneration. Here, we summarize recent evidence describing microglia activation kinetics in experimental models of ischemic injury, focusing on the contribution of these innate immune cells to myelin damage and repair. Some molecular signals regulating the pro-regenerative functions of microglia after stroke have been highlighted to provide new possible therapeutic targets involved in the protective functions of these cells. Finally, we analyzed the impact of microglia-to-OPCs communication via extracellular vesicles on post-stroke remyelination and functional recovery. The results collected in this review underline the importance of supporting the pro-remyelination functions of microglial cells after stroke.
Magnetic Resonance Spectroscopy May Help Diagnose Sporadic Meningioangiomatosis Associated With Meningioma: A Case Report
Authors: Liu Linfeng , Liang Feng
Published: July 2022

Herein, we have presented the clinical features of meningioangiomatosis associated with meningioma, which is considered to be a rare neoplastic lesion. Magnetic resonance spectroscopy (MRS) demonstrated a remarkably decreased N-acetylaspartate peak and an increase in the choline peak of the lesion, suggesting neuronal injury and active cell proliferation. These findings substantially differed from those observed in the case of pure meningioangiomatosis.
Plasma PRPC Levels Correlate With Severity and Prognosis of Intracerebral Hemorrhage
Authors: Wu Xiaoyu , Liu Ming , Yan Tian , Wang Zefan , Yu Wenhua , Du Quan , Hu Wei , Zheng Yongke , Zhang Zuyong , Wang Keyi , Dong Xiaoqiao
Published: July 2022

Background

Cellular prion protein (PRPC) exerts brain-protective effects. We determined the relationship between plasma PRPC levels and disease severity plus clinical outcome after acute intracerebral hemorrhage (ICH).

Methods

A total of 138 ICH patients and 138 healthy controls were included in this prospective, observational study. Hematoma volume and Glasgow coma scale (GCS) score were used to assess disease severity. Glasgow outcome scale (GOS) scores of 1–3 and 4–5 at 90 days after stroke were defined as a poor outcome and good outcome, respectively. Using multivariate analysis, we discerned the relation of plasma PRPC levels to disease severity and poor outcome. The receiver operating characteristic (ROC) curve was built to evaluate the prognostic predictive capability.

Results

Plasma PRPC levels in ICH patients were significantly higher than those in healthy controls (median, 4.20 vs. 2.02 ng/ml; P < 0.001), and were independently correlated with GCS score (r = −0.645, P < 0.001) and hematoma volume (r = 0.627, P < 0.001). Plasma PRPC levels were highly correlated with GOS score (r = −0.762, P < 0.001), and were substantially higher in patients with poor outcomes than in those with the good outcomes. Using maximum Youden index, plasma PRPC levels >3.893 ng/ml distinguished the risk of poor outcome at 90 days, with a sensitivity of 86.4% and a specificity of 65.8% (area under the curve, 0.809; 95% confidence interval (CI), 0.737–0.881, P < 0.001). Plasma PRPC levels >3.893 ng/ml were independently associated with a poor 90-day outcome with an odds ratio of 12.278 (95% CI, 5.101–29.554).

Conclusion

Elevated plasma PRPC levels are significantly associated with disease severity and poor 90-day outcome in ICH patients, indicating that plasma PRPC may be used as a potential prognostic biomarker after ICH.
Clinical Importance of the Persistent Primitive Trigeminal Artery in Vascular Lesions and Its Role in Endovascular Treatment
Authors: Wang Yiheng , Yu Jinlu
Published: July 2022

The persistent primitive trigeminal artery (PPTA) extends from the internal carotid artery to the basilar artery between the origins of the anterior inferior cerebellar artery and superior cerebellar artery. PPTAs have complex anatomical characteristics. Salas and Saltzman classifications are most often used in PPTAs. The PPTA can play many roles in vascular lesions, including intracranial aneurysms, brain arteriovenous malformations, trigeminal artery-cavernous fistulas, Moyamoya disease, and large vessel occlusion. For these lesions, surgical treatment is difficult due to the deep location and complex anatomy of the PPTA, but endovascular treatment (EVT) has emerged as a good alternative. Currently, a complete review of the clinical importance of the PPTA in terms of its role in the development and EVT of vascular lesions is lacking. Therefore, we conducted a PubMed search, performed a review of the relevant extracted literature and cataloged our experience with PPTAs. By review, we found that a thorough understanding of the anatomical and angiographic features of this PPTA is of utmost importance when making therapeutic decisions for any of these pathological conditions.
Nutritional Counseling of Stroke Patients by Neurology Residents, a Call to Action
Authors: Benameur Karima , Gandrakota Nikhila , Ali Mohammed K.
Published: July 2022

Background

Poor diet quality has been found to be an independent risk factor for mortality in stroke. However, it is unknown to what extent Neurologists are trained and are comfortable enough to provide dietary counseling to stroke patients.

Objective

To assess the knowledge, attitudes, and practices of neurology residents relating to dietary counseling of stroke patients.

Methods

An online anonymous survey was administered to neurology residents throughout the country between August and November 2019 among a total of 109 (68%) US neurology programs. Self-reported practices and knowledge regarding stroke prevention through nutritional counseling were queried using validated questionnaires.

Results

453 responses out of a potential 672 were received. A minority of residents (12.3%) consistently offered nutritional counseling to stroke patients. 47.7% considered that it was not the neurologist's role to provide nutritional counseling to stroke patients. 83.4% of residents felt that it was the responsibility of the dietician to provide nutritional counseling, yet only 21.4% of residents consistently referred stroke patients to a dietician. 77.9% of respondents felt nutritional counseling is important for stroke patients, yet 65.6% felt they were not adequately trained to provide nutritional counseling.

Conclusion

Neurologists in training believe diet to be an important part of stroke prevention, but practical knowledge and training in nutrition are suboptimal. This study suggests the need to include nutrition as an integral part of neurology training, to ensure neurologists feel empowered to be an important part of the team providing nutritional counseling to stroke patients.
Temperature and Impedance Variations During Tumor Treating Fields (TTFields) Treatment
Authors: Gentilal Nichal , Abend Eyal , Naveh Ariel , Marciano Tal , Balin Igal , Telepinsky Yevgeniy , Miranda Pedro Cavaleiro
Published: July 2022

Tumor Treating Fields (TTFields) is an FDA-approved cancer treatment technique used for glioblastoma multiforme (GBM). It consists in the application of alternating (100–500 kHz) and low-intensity (1–3 V/cm) electric fields (EFs) to interfere with the mitotic process of tumoral cells. In patients, these fields are applied via transducer arrays strategically positioned on the scalp using the NovoTAL™ system. It is recommended that the patient stays under the application of these fields for as long as possible. Inevitably, the temperature of the scalp increases because of the Joule effect, and it will remain above basal values for most part of the day. Furthermore, it is also known that the impedance of the head changes throughout treatment and that it might also play a role in the temperature variations. The goals of this work were to investigate how to realistically account for these increases and to quantify their impact in the choice of optimal arrays positions using a realistic head model with arrays positions obtained through NovoTAL™. We also studied the impedance variations based on the log files of patients who participated in the EF-14 clinical trial. Our computational results indicated that the layouts in which the arrays were very close to each other led to the appearance of a temperature hotspot that limited how much current could be injected which could consequently reduce treatment efficacy. Based on these data, we suggest that the arrays should be placed at least 1 cm apart from each other. The analysis of the impedance showed that the variations seen during treatment could be explained by three main factors: slow and long-term variations, array placement, and circadian rhythm. Our work indicates that both the temperature and impedance variations should be accounted for to improve the accuracy of computational results when investigating TTFields.
Driving With Hemianopia X: Effects of Cross Traffic on Gaze Behaviors and Pedestrian Responses at Intersections
Authors: Xu Jing , Baliutaviciute Vilte , Swan Garrett , Bowers Alex R.
Published: July 2022

Purpose

We conducted a driving simulator study to investigate the effects of monitoring intersection cross traffic on gaze behaviors and responses to pedestrians by drivers with hemianopic field loss (HFL).

Methods

Sixteen HFL and sixteen normal vision (NV) participants completed two drives in an urban environment. At 30 intersections, a pedestrian ran across the road when the participant entered the intersection, requiring a braking response to avoid a collision. Intersections with these pedestrian events had either (1) no cross traffic, (2) one approaching car from the side opposite the pedestrian location, or (3) two approaching cars, one from each side at the same time.

Results

Overall, HFL drivers made more (p < 0.001) and larger (p = 0.016) blind- than seeing-side scans and looked at the majority (>80%) of cross-traffic on both the blind and seeing sides. They made more numerous and larger gaze scans (p < 0.001) when they fixated cars on both sides (compared to one or no cars) and had lower rates of unsafe responses to blind- but not seeing-side pedestrians (interaction, p = 0.037). They were more likely to demonstrate compensatory blind-side fixation behaviors (faster time to fixate and longer fixation durations) when there was no car on the seeing side. Fixation behaviors and unsafe response rates were most similar to those of NV drivers when cars were fixated on both sides.

Conclusion

For HFL participants, making more scans, larger scans and safer responses to pedestrians crossing from the blind side were associated with looking at cross traffic from both directions. Thus, cross traffic might serve as a reminder to scan and provide a reference point to guide blind-side scanning of drivers with HFL. Proactively checking for cross-traffic cars from both sides could be an important safety practice for drivers with HFL.
Genetic Elements at the Alpha-Synuclein Locus
Authors: Prahl Jordan , Coetzee Gerhard A.
Published: July 2022

Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson’s disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that SNCA is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus. Recent evidence has shown that the risk associated with the top GWAS-identified variant within this locus is independent of SNCA expression, calling into question the validity of assigning function to the nearest gene, SNCA. In this review, we examine additional genes and risk variants present at the SNCA locus and how they may contribute to Parkinson’s disease. Using the SNCA locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.
Physical Fitness and Dietary Intake Improve Mental Health in Chinese Adolescence Aged 12–13
Authors: Liang Wenjie , Fu Jian , Tian Xin , Tian Jiaxue , Yang Yu , Fan Wencui , Du Zijuan , Jin Zheyu
Published: July 2022

Background

Mental health has become a major public health issue worldwide. Biological and epidemiological studies have suggested that diet and physical fitness play a role in the prevention or cure of mental disorders. However, further research is required to elucidate the relationship between diet, physical fitness, and mental health. The study aims to provide a theoretical basis for promoting an adolescent healthy lifestyle and preventing mental problems by exploring the relationship between physical fitness, calcium intake, calorie intake, and adolescent mental health.

Methods

A cross-sectional study of a sample of adolescents (N = 253, 12–13 years) was conducted. The study involved adolescents from three middle schools in Central Jiangsu Province, including 136 boys and 117 girls. Weight, height, and body mass index were measured. Physical fitness was scored using the Chinese National Student Physical Fitness Standard. Diet data were collected using a weighed 7-day food diary to estimate energy intake and dietary calcium intake. The mental health status of the participants was assessed using the Chinese Middle School Student Mental Health Scale. A T-test and analysis of variance were used to analyze the differences of variables between different genders and body mass index, and Pearson correlation and stepwise multiple regression were used to explore the relationship between physical fitness, dietary intake, and mental health.

Results

The height (165.13 ± 8.07), weight (55.24 ± 13.00), and strength quality (64.93 ± 21.66) of boys are higher than those of girls (161.67 ± 6.44,48.99 ± 8.97, 58.40 ± 23.75, P < 0.05), and the flexibility quality (74.59 ± 14.75) of girls is higher than that of boys (68.30 ± 20.84) (P < 0.05). There were significant differences in the total scores of speed and physical fitness (F values were 4.02187.73, 3.07, 5.95, 10.33, and 9.52, respectively, P < 0.05). There was a significant positive correlation between calcium intake, cardiopulmonary fitness, and mental health (r = 0.276, P < 0.01; r = 0.159, P < 0.05). Calcium intake and cardiopulmonary fitness could explain 8.4% of the changes in the mental health of adolescents aged 12–13(ΔR2 = 0.084, P < 0.05).

Conclusion

Adequate calcium intake and the improvement of cardiopulmonary fitness in adolescents aged 12–13 are essential for the good development of their mental health. Future research in this field should examine the prospective associations between multiple measures of physical fitness composition and other nutrients ingested and mental health outcomes, as well as intervention studies that seek to provide evidence of causality.
Prognostic Nomograms Combined Adjuvant Lenvatinib for Hepatitis B Virus–related Hepatocellular Carcinoma With Microvascular Invasion After Radical Resection
Authors: Bai Shilei , Hu Lei , Liu Jianwei , Sun Minmin , Sun Yanfu , Xue Feng
Published: July 2022

Background and Aim

Microvascular invasion (MVI) has been established as one of the most important contributors to the prognosis of primary hepatocellular carcinoma (HCC). The objective of this study was to investigate the potential effect of postoperative adjuvant therapy with lenvatinib on the long-term prognosis after radical resection in hepatitis B virus (HBV)-related HCC patients with MVI, as well as to predict the long-term survival based on nomograms.

Methods

Data from 293 HBV-related hepatocellular carcinoma patients with histologically confirmed MVI who underwent R0 resection at Eastern Hepatobiliary Surgery Hospital (EHBH) was retrospectively analyzed. 57 patients received postoperative adjuvant therapy with lenvatinib, while 236 patients did not. The survival outcome of patients who received postoperative adjuvant lenvatinib versus those who did not was analyzed.

Results

The 1-year, 2-year recurrence rates and survival rates of the lenvatinib group were improved compared to the non-lenvatinib group (15.9%, 43.2% vs 40.1%, 57.2%, P=0.002; 85.8%, 71.2% vs 69.6%, 53.3%, P=0.009, respectively). Similar findings were also observed after Propensity Score Matching (PSM) compared to non-PSM analyses The 1-year, 2-year recurrence rates and survival rates were more favorable for the lenvatinib group compared to the non-lenvatinib group (15.9%, 43.2% vs 42.1%, 57.4%, P=0.028; 85.8%, 71.2% vs 70.0%, 53.4%, P=0.024, respectively). As shown by univariate and multivariate analyses, absence of adjuvant lenvatinib treatment was identified as an independent risk factor for recurrence and survival. The established nomograms displayed good performance for the prediction of recurrence and survival, with a C-index of 0.658 and 0.682 respectively.

Conclusions

Postoperative adjuvant therapy with lenvatinib was associated with improved long-term prognosis after R0 Resection in HBV-related HCC patients with MVI, which could be accurately predicted from nomograms.
Treatment of Pediatric Intercondylar Humerus Fracture With External Fixation and Percutaneous Pinning After Closed Reduction
Authors: Shu Wen , Zhao Rong , Yang ZiMo , Li XiangRui , Jiang GuoYong , Rai Saroj , Zhong Haobo , Tang Xin
Published: July 2022

Background

It is uncommon for young children to suffer an intercondylar fracture of the distal humerus. Although many approaches have been described to manage, there is no specific and accepted treatment protocol for such fracture patterns. This study aimed to identify the incidence of intercondylar fracture of the distal humerus in the pediatric population and report the clinical outcome of external fixation and percutaneous pinning in such injury patterns.

Methods

Pediatric patients under the age of 14 years who had an intercondylar fracture of the distal humerus treated with external fixation and percutaneous pinning between January 2013 and December 2018 at the author’s Wuhan Union Hospital were retrospectively evaluated. The detailed baseline information of the patients, operating time, time to union time, and carrying angle difference (CAD) of the injured extremity were collected. During the follow-up visit, clinical results were evaluated using the Mayo Elbow Performance Score (MEPS) and the Flynn criteria.

Results

A total of eight patients (2 women and 6 men) with an average age of 8 years (5–12 years) who had an intercondylar fracture of the distal humerus (1 C2 and 7 C1) were included. All the patients achieved union, and the average MEPS score was 95 points 24 months after the surgery.

Conclusion

The intercondylar fracture of the distal humerus in children is rare, and closed reduction and external fixation is a viable treatment option, especially for the C1 type of fracture pattern.
Glomerular IgA Deposition and Serum Antineutrophil Cytoplasmic Antibody Positivity in a Child With Dystrophic Epidermolysis Bullosa: Case Report and Literature Review
Authors: Yu Ling , Huang Guoping , Lu Zhihong , Wang Jingjing , Gu Weizhong , Li Junping , Mao Jianhua
Published: July 2022

Patients with epidermolysis bullosa (EB) could develop significant urological complications, such as hydroureteronephrosis, renal amyloidosis and IgA nephropathy (IgAN). Here, we presented a 12-year-old boy carrying pathogenic COL7A1 mutation with diagnosis of dystrophic epidermolysis bullosa (DEB). The patient had concomitant gross hematuria and proteinuria. Pathological examinations and immunostaining of renal biopsy showed glomeruli with mesangial hypercellularity and deposition of IgA, which were indicative of IgAN. Interestingly, serological evaluation showed antineutrophil cytoplasmic antibody (ANCA) directed against myeloperoxidase and proteinase 3. Treatment with glucocorticoid, immunosuppressants, angiotensin-converting enzyme inhibitor and antibiotics efficiently improved hemato-proteinuria, and ANCAs became negative as well. This case of DEB presented a unique collection of clinical manifestations and pathological alterations. IgAN and serum positive ANCA were possibly associated with sustained infection secondary to DEB, and can be managed by empirical treatment for primary IgAN.
Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion
Authors: Zhu Xiaodong , Shen Xiaogang , Lin Bo , Fang Jiaxi , Jin Juan , He Qiang
Published: July 2022

Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Its pathological features include IgA immune complex deposition, accompanied by mesangial cell proliferation and mesangial matrix expansion. This study was conducted to investigate the effects of Liuwei Dihuang pills (LWDHW) on IgAN in mice and human podocytes, as well as to determine their underlying mechanisms of action.

Methods: For in vitro experiments, podocytes were exposed to the human mesangial cell culture medium supernatant of glomerular cells treated with aggregated IgA1 (aIgA1) and LWDHW-containing serum. Cell viability and the proportion of positive cells were evaluated using CCK-8 and flow apoptosis kits, respectively. The cells were collected for western blot analysis. Twenty-four mice with IgAN induced by oral bovine serum albumin administration combined with tail vein injection of staphylococcal enterotoxin B were randomly divided into four groups of six mice each: untreated model group, model + LWDHW group, model + rapamycin group, and model + LWDHW + rapamycin group. The normal control group contained six mice. The red blood cell count in the urine, urine protein, blood urea nitrogen, serum creatinine, and IgA deposition were determined, and TUNEL and western blotting were performed in the mouse kidney tissues.

Results:In vitro experiments showed that LWDHW promoted autophagy by regulating the PI3K/Akt/mTOR signalling pathway and improved the damage to podocytes caused by the aIgA1-treated mesangial cell supernatant. This study demonstrates the effectiveness of LWDHW for treating IgAN. In the animal experiments, LWDHW significantly reduced the urine red blood cell count, serum creatinine and urea nitrogen contents, and 24 h urinary protein function and improved IgA deposition in the kidney tissues, glomerular volume, glomerular cell proliferation and polysaccharide deposition, and glomerular cell apoptosis. The pills also reversed the changes in the LC3II/I ratio and p62 content in the kidney tissues. The combination of LWDHW and rapamycin showed stronger inhibitory effects compared to those of LWDHW or rapamycin alone.

Conclusion: LWDHW may improve regulation of the PI3K-Akt-mTOR pathway and inhibit autophagy in podocytes, as well as alleviate IgA nephropathy by directly altering mesangial cell exosomes.
Peroxisomal Proliferator-Activated Receptor β/δ Deficiency Induces Cognitive Alterations
Authors: Espinosa-Jiménez Triana , Busquets Oriol , Cano Amanda , Sánchez-López Elena , Verdaguer Ester , Parcerisas Antoni , Olloquequi Jordi , Auladell Carme , Folch Jaume , Wahli Walter , Vázquez-Carrera Manuel , Camins Antoni , Ettcheto Miren
Published: July 2022

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), the most PPAR abundant isotype in the central nervous system, is involved in microglial homeostasis and metabolism, whose disturbances have been demonstrated to play a key role in memory impairment. Although PPARβ/δ function is well-established in metabolism, its contribution to neuronal and specifically memory process is underexplored. Therefore, the aim of the study is to determine the role of PPARβ/δ in the neuropathological pathways involved in memory impairment and as to whether a risk factor implicated in memory loss such as obesity modulates neuropathological markers. To carry out this study, 6-month-old total knock-out for the Ppard gene male mice with C57BL/6X129/SV background (PPARβ/δ-/-) and wild-type (WT) littermates with the same genetic background were used. Animals were fed, after the weaning (at 21 days old), and throughout their growth, either conventional chow (CT) or a palmitic acid-enriched diet (HFD). Thus, four groups were defined: WT CT, WT HFD, PPARβ/δ-/- CT, and PPARβ/δ-/- HFD. Before sacrifice, novel object recognition test (NORT) and glucose and insulin tolerance tests were performed. After that, animals were sacrificed by intracardiac perfusion or cervical dislocation. Different techniques, such as GolgiStain kit or immunofluorescence, were used to evaluate the role of PPARβ/δ in memory dysfunction. Our results showed a decrease in dendritic spine density and synaptic markers in PPARβ/δ-/- mice, which were corroborated in the NORT. Likewise, our study demonstrated that the lack of PPARβ/δ receptor enhances gliosis in the hippocampus, contributing to astrocyte and microglial activation and to the increase in neuroinflammatory biomarkers. Additionally, alterations in the hippocampal insulin receptor pathway were found. Interestingly, while some of the disturbances caused by the lack of PPARβ/δ were not affected by feeding the HFD, others were exacerbated or required the combination of both factors. Taken together, the loss of PPARβ/δ-/- affects neuronal and synaptic structure, contributing to memory dysfunction, and they also present this receptor as a possible new target for the treatment of memory impairment.
Toxicological Evaluation of Acetylsalicylic Acid in Non-Target Organisms: Chronic Exposure on Mytilus galloprovincialis (Lamarck, 1819)
Authors: Pagano M. , Savoca S. , Impellitteri F. , Albano M. , Capillo G. , Faggio C.
Published: July 2022

Pharmaceuticals are now considered to be established contaminants, and their presence in water poses a real risk not only to the marine ecosystem, as they may adversely affect non-target organisms that are exposed to them, but also indirectly to humans. This is particularly true for the model organism considered in this work, Mytilus galloprovincialis (Lamarck, 1819), a suspensivore and bioaccumulating organism that enters the human food chain. Among the most commonly used over-the-counter medicines, anti-inflammatory drugs certainly feature prominently, with acetylsalicylic acid (ASA) at the top. In this work, M. galloprovincialis specimens were exposed to two concentrations of ASA (10 and 100 μg/L) for 10 and 20 days to evaluate possible alterations in the decrease in regulatory volume (RVD) in digestive gland cells and cell viability of both these cells and hemocytes. In addition, the histopathological condition index of the gills and digestive gland was evaluated. The data obtained showed that chronic exposure to ASA did not alter the cell viability of hemocytes and digestive gland cells but alters the physiological mechanisms of volume regulation in the digestive gland and, in addition, a time-dose reaction to ASA in the gills and digestive gland showing numerous alterations such as lipofuscin deposits and hemocyte infiltration was found. These results confirm the potential toxicity to the marine biota, highlighting the necessity to deepen the knowledge regarding the link between over-the-counter pharmaceuticals and non-target organisms.
Leaf Damage Based Phenotyping Technique and Its Validation Against Fall Armyworm, Spodoptera frugiperda (J. E. Smith), in Maize
Authors: Soujanya P. Lakshmi , Sekhar J. C. , Yathish K. R. , Karjagi Chikkappa G. , Rao K. Sankara , Suby S. B. , Jat S. L. , Kumar Bhupender , Kumar Krishan , Vadessery Jyothilakshmi , Subaharan K. , Patil Jagadish , Kalia Vinay K. , Dhandapani A. , Rakshit Sujay
Published: July 2022

Globally, maize is an important cereal food crop with the highest production and productivity. Among the biotic constraints that limit the productivity of maize, the recent invasion of fall armyworm (FAW) in India is a concern. The first line of strategy available for FAW management is to evaluate and exploit resistant genotypes for inclusion in an IPM schedule. Screening for resistant maize genotypes against FAW is in its infancy in India, considering its recent occurrence in the country. The present work attempts to optimize screening techniques suited to Indian conditions, which involve the description of leaf damage rating (LDR) by comparing injury levels among maize genotypes and to validate the result obtained from the optimized screening technique by identification of lines potentially resistant to FAW under artificial infestation. Exposure to 20 neonate FAW larvae at the V5phenological stage coupled with the adoption of LDR on a 1–9 scale aided in preliminary characterize maize genotypes as potentially resistant, moderately resistant, and susceptible. The LDR varies with genotype, neonate counts, and days after infestation. The genotypes,viz., DMRE 63, DML-163-1, CML 71, CML 141, CML 337, CML 346, and wild ancestorZea maysssp.parviglumisrecorded lower LDR ratings against FAW and can be exploited for resistance breeding in maize.
Initial Description of the Genome of Aeluropus littoralis, a Halophile Grass
Authors: Hashemi-Petroudi Seyyed Hamidreza , Arab Mozhdeh , Dolatabadi Behnaz , Kuo Yi-Tzu , Baez Mariana Alejandra , Himmelbach Axel , Nematzadeh Ghorbanali , Maibody Seyed Ali Mohammad Mirmohammady , Schmutzer Thomas , Mälzer Michael , Altmann Thomas , Kuhlmann Markus
Published: July 2022

The use of wild plant species or their halophytic relatives has been considered in plant breeding programs to improve salt and drought tolerance in crop plants. Aeluropus littoralis serves as halophyte model for identification and isolation of novel stress adaptation genes. A. littoralis, a perennial monocot grass, grows in damp or arid areas, often salt-impregnated places and wasteland in cultivated areas, can survive periodically high water salinity, and tolerate high salt concentrations in the soil up to 1,100 mM sodium chloride. Therefore, it serves as valuable genetic resource to understand molecular mechanisms of stress-responses in monocots. The knowledge can potentially be used for improving tolerance to abiotic stresses in economically important crops. Several morphological, anatomical, ecological, and physiological traits of A. littoralis have been investigated so far. After watering with salt water the grass is able to excrete salt via its salt glands. Meanwhile, a number of ESTs (expressed sequence tag), genes and promoters induced by the salt and drought stresses were isolated, sequenced and annotated at a molecular level. Transfer of stress related genes to other species resulted in enhanced stress resistance. Here we describe the genome sequence and structure of A. littoralis analyzed by whole genome sequencing and histological analysis. The chromosome number was determined to be 20 (2n = 2x = 20). The genome size was calculated to be 354 Mb. This genomic information provided here, will support the functional investigation and application of novel genes improving salt stress resistance in crop plants. The utility of the sequence information is exemplified by the analysis of the DREB-transcription factor family.
Comparison of the Effects of Potassium Sulphate and Potassium Chloride Fertilisation on Quality Parameters, Including Volatile Compounds, of Potato Tubers After Harvest and Storage
Authors: Wilmer Lisanne , Pawelzik Elke , Naumann Marcel
Published: July 2022

Potatoes are an important staple food with high yield potential and great nutritional value. Potassium (K) fertilisation can increase both tuber yield and quality, but its effects differ depending on the K fertilisation form. Potatoes are known to be chloride sensitive, since chloride ions can influence, for example, the starch content. Therefore, fertilisations shortly before planting using potassium sulphate (K2SO4) are often recommended instead of potassium chloride (KCl). However, the use of different fertilisation forms is contradictory, and the chloride sensitivity of potatoes remains unclear. To examine this issue in more detail, a 2-year field experiment using two cultivars, “Laura” and “Marabel,” was conducted. K fertilisation with 240 kg K2O as K2SO4 and KCl was applied, and the control remained unfertilised. Quality traits, including internal and external parameters, were analysed after harvest and after 5 months of storage at 6°C. The results revealed minor effects on yield, but the starch content and ascorbic acid concentration were reduced due to the KCl supply. Furthermore, the reducing sugar concentration in tubers increased during storage more after KCl compared to K2SO4 fertilisation. Moreover, volatile compounds were affected by the K fertilisation form, with higher levels of lipid-derived off-flavour compounds after KCl application. However, the effects of cultivation year, cultivar, and storage interacted with the influence of the fertilisation form. In summary, KCl fertilisation can disadvantageously influence several quality traits, but the use of potato cultivars should also be considered when recommending fertilisers.