bluuebunny/crossref_metadata_2025 huggingface dataset:
On the relationship between rhythm-based temporal expectations and endogenous spatial attention in simple reaction-time tasks
Authors: Charras Pom , Chica Ana B. , Capizzi Mariagrazia
Published: June 2023

Introduction

Recent evidence suggests that the temporal expectations afforded by a regular rhythmic structure operate independently from endogenous spatial attention in simple reaction-time tasks. The most common manipulation followed in previous studies consisted of presenting a target stimulus either “in-time” or “out-of-time” (earlier or later) with a preceding rhythm. However, contrary to the proposal of entrainment models predicting a behavioral advantage for in-time compared to both early and late targets, responses were still faster for late targets, according to the so-called “foreperiod effect”. This finding makes it difficult to fully disentangle the impact of rhythm and the benefits afforded by the passage of time on the relationship between rhythm-based temporal and endogenous spatial attention.

Methods

To shed more light on this issue, we combined a spatial orienting task with a rhythmic manipulation, in which two placeholders flanking the fixation cross flickered at either a regular or irregular pace. Spatial orienting to the target location was deployed by symbolic color cues that were displayed independently of the rhythm (independent cues) or were integrated with the temporal rhythmic cues (integrated cues). Crucially, for both independent and integrated cues, and for regular and irregular rhythms, the interval between the rhythm and the target (i.e., the foreperiod) was kept fixed in Experiments 1–3 to control for the foreperiod effect, while the effect of foreperiod was explored in Experiment 4.

Results

Results showed a more beneficial effect of rhythms with independent cues as compared to integrated cues. Additionally, the benefit of rhythms was slightly but significantly larger at valid, compared to invalid, spatial locations, regardless of the foreperiod.

Discussion

Our results extend previous studies by showing that interactive effects of rhythms and endogenous spatial attention may emerge in low-demanding detection tasks.
Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study
Authors: Han Q. Joyce , Forfia Paul , Vaidya Anjali , Ramani Gautam , deKemp Robert A. , Mach Robert H. , Mankoff David A. , Bravo Paco E. , DiCarli Marcelo , Chan Stephen Y. , Waxman Aaron B. , Han Yuchi
Published: June 2023

Introduction

Right ventricular (RV) function is a major determinant of outcome in patients with precapillary pulmonary hypertension (PH). We studied the effect of ranolazine on RV function over 6 months using multi-modality imaging and biochemical markers in patients with precapillary PH (groups I, III, and IV) and RV dysfunction [CMR imaging ejection fraction (EF) < 45%] in a longitudinal, randomized, double-blinded, placebo-controlled, multicenter study of ranolazine treatment.

Methods

Enrolled patients were assessed using cardiac magnetic resonance (CMR) imaging,11C-acetate and18-F-FDG positron emission tomography (PET), and plasma metabolomic profiling, at baseline and at the end of treatment.

Results

Twenty-two patients were enrolled, and 15 patients completed all follow-up studies with 9 in the ranolazine arm and 6 in the placebo arm. RVEF and RV/Left ventricle (LV) mean glucose uptake were significantly improved after 6 months of treatment in the ranolazine arm. Metabolomic changes in aromatic amino acid metabolism, redox homeostasis, and bile acid metabolism were observed after ranolazine treatment, and several changes significantly correlated with changes in PET and CMR-derived fluid dynamic measurements.

Discussion

Ranolazine may improve RV function by altering RV metabolism in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.
Analysis of landscape influencing factors of urban waterfront greenways based on the scenic beauty estimation method, taking Tongjian Lake in Hangzhou as an example
Authors: Hu Xiujun , Zou Xun , Fan Haiyan
Published: June 2023

In order to assess the unique beauty of Tongjian Lake in Hangzhou, 80 sample photographs were selected for landscape beauty degree assessment using the Scenic Beauty Estimation method. The 14 characteristic influencing factors of landscape photos were extracted according to the Scenic Beauty Estimation value, and the influencing factors with insignificant differences and small bias correlation coefficients were eliminated through multiple linear regression analysis. The results showed that the main factors affecting the expression of the beauty of Tongjian Lake were water ecology, greenway morphology, landscape openness, water area ratio, vegetation color richness, and vignette matching. Combining the abovementioned analysis results, the two-dimensional plan, isometric map, and three-dimensional space are combined to show the main factors in a visual way, and on this basis, the corresponding optimization strategy is proposed. It provides a reference for future urban waterfront greenway landscape creation.
Erectile dysfunction and associated factors among patients with diabetes attending follow-up at a public hospital, Harar, Eastern Ethiopia. A cross-sectional study design
Authors: Gobena Matebu Bekele , Abdosh Tekabe , Dheresa Merga , Dechasa Deribe Bekele
Published: June 2023

Background

The global prevalence of erectile dysfunction among patients with diabetes is high. It is the most underestimated problem but has a great physical, psychological, and social impact on the individual with the disease, family, and society in general. Thus, this study aimed to assess the magnitude of erectile dysfunction and associated factors among patients with diabetes attending follow-up at a public hospital, Harar, Eastern Ethiopia.

Methods

Facility-based cross-sectional study was conducted on selected 210 adult male patients with diabetes attending follow-up at a public hospital, Harar, Eastern Ethiopia, from 1 February to 30 March 2020. Simple random sampling was used to select study participants. A pre-tested interviewer-administered structured questionnaire was used to collect the data. The data were entered to EpiData version 3.1 and exported to SPSS version 20 for analysis. Bivariate and multivariable binary logistic regression were carried out, and a P-value of <0.05 was taken as statistically significant.

Result

A total of 210 adult male patients with diabetes participated in the study. The overall magnitude of erectile dysfunction was 83.8%, with 26.7% suffering from mild, 37.5% mild to moderate, 29% moderate, and 6.8% severe erectile dysfunctions. Age 46–59 years [adjusted odds ratio (AOR): 2.560; 95% confidence interval (CI) (1.73, 6.53)], age ≥ 60 years [AOR: 2.9; 95% CI (1.48, 5.67)], and poor glycemic control [AOR: 2.140; 95% CI (1.9, 7.44)] were significantly associated with erectile dysfunction among patients with diabetes.

Conclusion

The present study revealed a high magnitude of erectile dysfunction among population with diabetes. The age categories of 46–59 and ≥60 and having poor glycemic control were the only variables significantly associated with erectile dysfunction. Thus, routine screening and management for erectile dysfunction in patients with diabetes should be part of routine medical care particularly for adult male patients and those with poor glycemic control.
Utilization of glucagon-like peptide-1 receptor agonists in children and adolescents in China: a real-world study
Authors: Yan Yilong , Gong Ying , Jiang Meizhu , Gao Yiming , Guo Shanshan , Huo Jiping , Zhao Zhigang , Li Cao
Published: June 2023

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used in treating type 2 diabetes mellitus (T2DM) and obesity in adults, but scientific research about the indication in children and adolescents is scarce. The current study aims to explore the prescriptions of GLP-1RAs in children and adolescents in China and to evaluate its rationality.

Methods

GLP-1RA prescriptions of children and adolescents were retrospectively obtained from the Hospital Prescription Analysis Cooperative Project. The study extracted information on patient’s demographic characteristics, monotherapy and combination therapy of GLP-1RAs, and trends in GLP-1RA usage from 2016 to 2021. The rationality of GLP-1RA prescriptions was comprehensively assessed based on the indications approved by China National Medical Products Administration (NMPA), the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), and published randomized controlled trials (RCTs).

Results

A total of 234 prescriptions from 46 hospitals were included, with a median age of 17 years old. The majority of patients were diagnosed with overweight/obesity or prediabetes/diabetes, accounting for 43.59% and 46.15%, respectively. There were 88 patients on GLP-1RA monotherapy. GLP-1RAs plus metformin was the most common combination therapy (38.89%). 12.39% of patients were found a co-administration with orlistat. The share of overweight/obesity prescriptions increased from 27% in 2016 to 54% in 2021, whereas prediabetes/diabetes prescriptions declined from 55% to 42%. The prescriptions were divided into appropriate and questionable groups according to the diagnosis, and the potentially questionable prescription was related to age (p = 0.017), department visited (p = 0.002), and any hospitalization (p < 0.001).

Conclusions

This study described the prescribing of GLP-1RAs in children and adolescents. Our findings indicated that the utilization of GLP-1RAs has increased from 2016 to 2021. There was a strong basis for administering GLP-1RAs in overweight/obesity and prediabetes/diabetes, whereas the evidence was insufficient in other conditions. It is crucial to demand robust and sustained efforts to enhance the awareness of the safety of utilization of GLP-1RAs in children and adolescents.
Optimal allocation of distributed renewable generations in low-carbon distribution system considering impact of natural disasters
Authors: Liao Wang , Weng Jiaming , Liu Dong , Wu Yufeng
Published: June 2023

With global climate change, increasingly frequent natural disasters have brought great challenges to the safe and reliable power supply and low-carbon transition of power distribution systems. Most of the existing researches on the distribution system under the impact of natural disasters only focus on the improvement of power supply reliability, but have not consider the impact of disaster severity and disaster response measures on carbon emissions. In order to juggle the load restoration and carbon emission mitigation of distribution system under natural disasters, this paper proposes an optimal allocation method of distributed renewable generations (DRGs) considering carbon emission for multi-scenario natural disasters based on the framework of cyber-physical-social system in energy (CPSSE), and establishes a three-stage optimization model of pre-disaster prevention-disaster attack-post-disaster restoration. For the purpose of ensuring the practicability and robustness of the allocation results, the disaster scenario is modeled and the selection method of the worst fault scenario under disaster is proposed. The progressive hedging algorithm (PHA) is adopted to solve the proposed multi-scenario optimization problem. Finally, the simulation results indicate that the proposed method can restore more lost load at a lower cost of carbon emissions.
How government green investment affects the carbon emission reduction process: empirical evidence from prefecture-level cities in China
Authors: Pan Ruoxi , Hu Yiguo , Xu Xiangbo , Yuan Naixiu , Zhou Kai
Published: June 2023

Government green investment (GGI) is one of the effective tools for reducing carbon emissions (CEs). This is of great significance for the realization of “carbon peaking and carbon neutrality.” This study innovatively considers the multidimensional CE reduction (CER) process indexes to explore the impact mechanism of GGI on China’s CER process. At the same time, CER is particularly critical in resource-dependent regions. This study incorporates this perspective to explore the CER effect of GGI in these regions. This paper developed a multidimensional evaluation system for China’s CER process, using panel data of 269 prefecture-level cities from 2008 to 2019 to explore the impact of GGI on China’s CER process. The results indicated that 1) GGI promotes CER in China as a whole and effectively inhibits CEs,per capitaCEs, and CE intensity; 2) GGI promotes CER to some extent by enhancing the energy efficiency and total factor productivity; 3) it plays a larger role in CER in regions with a high energy endowment; and 4) the impact of GGI on CER is heterogeneous in geographical regions, city sizes, and economic development levels. This study makes policy recommendations for reducing CEs, including intensifying GGI and playing its investment-pulling role, thereby increasing the investment related to improving energy efficiency and total factor productivity and promoting government intervention in areas with high energy endowments.
Case report: Anti-IgLON5 disease and anti-LGI1 encephalitis following COVID-19
Authors: Li Yanfei , Jia Yanjie
Published: June 2023

Anti-IgLON family member 5 (IgLON5) disease is a rare autoimmune encephalitis, characterized by sleep problems, cognitive decline, gait abnormalities, and bulbar dysfunction. Anti–leucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis is characterized by cognitive dysfunction, mental disorders, faciobrachial dystonic seizures (FBDS), and hyponatremia. Various studies report that coronavirus disease 2019 (COVID-19) have an effect on the nervous system and induce a wide range of neurological symptoms. Autoimmune encephalitis is one of the neurological complications in severe acute respiratory syndrome coronavirus 2 infection. Until now, autoimmune encephalitis with both anti-IgLON5 and anti-LGI1 receptor antibodies following COVID-19 is rarely reported. The case report described a 40-year-old man who presented with sleep behavior disorder, daytime sleepiness, paramnesia, cognitive decline, FBDS, and anxiety following COVID-19. Anti-IgLON5 and anti-LGI1 receptor antibodies were positive in serum, and anti-LGI1 receptor antibodies were positive in cerebrospinal fluid. The patient presented with typical symptoms of anti-IgLON5 disease such as sleep behavior disorder, obstructive sleep apnea, and daytime sleepiness. Moreover, he presented with FBDS, which is common in anti-LGI1 encephalitis. Therefore, the patient was diagnosed with anti-IgLON5 disease and anti-LGI1 autoimmune encephalitis. The patient turned better after high-dose steroid and mycophenolate mofetil therapy. The case serves to increase the awareness of rare autoimmune encephalitis after COVID-19.
Fine-scale variability in coral bleaching and mortality during a marine heatwave
Authors: Yadav Shreya , Roach Ty N. F. , McWilliam Michael J. , Caruso Carlo , de Souza Mariana Rocha , Foley Catherine , Allen Corinne , Dilworth Jenna , Huckeba Joel , Santoro Erika P. , Wold Renee , Simpson Jacquelyn , Miller Spencer , Hancock Joshua R. , Drury Crawford , Madin Joshua S.
Published: June 2023

Coral bleaching and mortality can show significant spatial and taxonomic heterogeneity at local scales, highlighting the need to understand the fine-scale drivers and impacts of thermal stress. In this study, we used structure-from-motion photogrammetry to track coral bleaching, mortality, and changes in community composition during the 2019 marine heatwave in Kāneʻohe Bay, Hawaiʻi. We surveyed 30 shallow reef patches every 3 weeks for the duration of the bleaching event (August-December) and one year after, resulting in a total of 210 large-area, high-resolution photomosaics that enabled us to follow the fate of thousands of coral colonies through time. We also measured environmental variables such as temperature, sedimentation, depth, and wave velocity at each of these sites, and extracted estimates of habitat complexity (rugosity R and fractal dimension D) from digital elevation models to better understand their effects on patterns of bleaching and mortality. We found that up to 80% of corals experienced moderate to severe bleaching in this period, with peak bleaching occurring in October when heat stress (Degree Heating Weeks) reached its maximum. Mortality continued to accumulate as bleaching levels dropped, driving large declines in more heat-susceptible species (77% loss of Pocillopora cover) and moderate declines in heat-tolerant species (19% and 23% for Porites compressa and Montipora capitata, respectively). Declines in live coral were accompanied by a rapid increase in algal cover across the survey sites. Spatial differences in bleaching were significantly linked to habitat complexity and coral species composition, with reefs that were dominated by Pocillopora experiencing the most severe bleaching. Mortality was also influenced by species composition, fractal dimension, and site-level differences in thermal stress. Our results show that spatial heterogeneity in the impacts of bleaching are driven by a mix of environmental variation, habitat complexity, and differences in assemblage composition.
The evaluation of government subsidy policies on carbon emissions in the port collection and distribution network: a case study of Guangzhou Port
Authors: Jiang Liupeng , Tang Shuangshi , Wang Guangsheng , Yu Tong , Yuan Jiaqi
Published: June 2023

The collection and distribution network of ports is the main cause of carbon emissions. The carbon peak is a basic policy in China, and the subsidy policy is one of the common measures used by the government to incentivize carbon reduction. We analyzed the transportation methods and the flow direction of a port and proposed a carbon emission calculation method based on emission factors. Based on the transportation time and the cost, a generalized transportation utility function was constructed, and the logit model was used to analyze the impacts of subsidy policies on transportation, thus calculating the effects of the subsidies on carbon reduction. We used Guangzhou Port as a case study, and calculated the carbon reduction effects in six different subsidy policy scenarios and concluded that the absolute carbon reduction value was proportional to the subsidy intensity. In addition, we constructed a subsidy carbon reduction efficiency index and found that the Guangzhou Port collection and distribution network had higher subsidy carbon reduction efficiency in low-subsidy scenarios. Finally, a sensitivity analysis was conducted on the subsidy parameters, and scenario 8 was found to have the highest subsidy carbon reduction efficiency. This achievement can provide decision support for the carbon emission strategy of the port collection and distribution network.
Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review
Authors: Molk Neza , Bitenc Mojca , Urlep Darja , Zerjav Tansek Mojca , Bertok Sara , Trebusak Podkrajsek Katarina , Sustar Ursa , Kovac Jernej , Battelino Tadej , Debeljak Marusa , Groselj Urh
Published: June 2023

Background

Familial hypobetalipoproteinemia (FHBL) is an autosomal semi-dominant disorder usually caused by variants in the APOB gene that frequently interferes with protein length. Clinical manifestations include malabsorption, non-alcoholic fatty liver disease, low levels of lipid-soluble vitamins, and neurological, endocrine, and hematological dysfunction.

Methods

Genomic DNA was isolated from the blood samples of the pediatric patient with hypocholesterolemia and his parents and brother. Next-generation sequencing (NGS) was performed, and an expanded dyslipidemia panel was employed for genetic analysis. In addition, a systematic review of the literature on FHBL heterozygous patients was performed.

Case report

Genetic investigation revealed the presence of a heterozygous variant in the APOB (NM_000384.3) gene c.6624dup[=], which changes the open reading frame and leads to early termination of translation into the p.Leu2209IlefsTer5 protein (NP_000375.3). The identified variant was not previously reported. Familial segregation analysis confirmed the variant in the mother of the subject, who also has a low level of low-density lipoprotein and non-alcoholic fatty liver disease. We have introduced therapy that includes limiting fats in the diet and adding lipid-soluble vitamins E, A, K, and D and calcium carbonate. We reported 35 individuals with APOB gene variations linked to FHBL in the systematic review.

Conclusion

We have identified a novel pathogenic variant in the APOB gene causing FHBL in pediatric patients with hypocholesterolemia and fatty liver disease. This case illustrates the importance of genetic testing for dyslipidemias in patients with significant decreases in plasma cholesterol as we can avoid damaging neurological and ophthalmological effects by sufficient vitamin supplementation and regular follow-ups.
Myositis interstitial lung disease and autoantibodies
Authors: Chaudhry Shire , Christopher-Stine Lisa
Published: June 2023

The aim of this review is to examine and evaluate published literature associated with idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) based on myositis specific autoantibodies (MSA) and the potential clinical significance of each autoantibody subtype for the practicing clinician. The review is a comprehensive search of literature published in PubMed from the year 2005 and onward coinciding with the surge in the discovery of new MSAs. Additionally, we comment on recommended multidisciplinary longitudinal care practices for patients with IIM-ILD with regard to imaging and other testing. Treatment is not covered in this review.
Renal glomerular and tubular responses to glutaraldehyde- polymerized human hemoglobin
Authors: Williams Matthew C. , Zhang Xiaoyuan , Baek Jin Hyen , D’Agnillo Felice
Published: June 2023

Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and volume replacement therapeutics, however, their molecular and cellular effects on the vasculature and different organ systems are not fully defined. Using a guinea pig transfusion model, we examined the renal glomerular and tubular responses to PolyHeme, a highly characterized glutaraldehyde-polymerized human hemoglobin with low tetrameric hemoglobin content. PolyHeme-infused animals showed no major changes in glomerular histology or loss of specific markers of glomerular podocytes (Wilms tumor 1 protein, podocin, and podocalyxin) or endothelial cells (ETS-related gene and claudin-5) after 4, 24, and 72 h. Relative to sham controls, PolyHeme-infused animals also showed similar expression and subcellular distribution of N-cadherin and E-cadherin, two key epithelial junctional proteins of proximal and distal tubules, respectively. In terms of heme catabolism and iron-handling responses, PolyHeme induced a moderate but transient expression of heme oxygenase-1 in proximal tubular epithelium and tubulointerstitial macrophages that was accompanied by increased iron deposition in tubular epithelium. Contrary to previous findings with other modified or acellular hemoglobins, the present data show that PolyHeme does not disrupt the junctional integrity of the renal glomerulus and tubular epithelium, and triggers moderate activation of heme catabolic and iron sequestration systems likely as part of a renal adaptive response.
Repertoire and abundance of secreted virulence factors shape the pathogenic capacity of Pseudomonas syringae pv. aptata
Authors: Nikolić Ivan , Glatter Timo , Ranković Tamara , Berić Tanja , Stanković Slaviša , Diepold Andreas
Published: June 2023

Pseudomonas syringae pv. aptata is a member of the sugar beet pathobiome and the causative agent of leaf spot disease. Like many pathogenic bacteria, P. syringae relies on the secretion of toxins, which manipulate host-pathogen interactions, to establish and maintain an infection. This study analyzes the secretome of six pathogenic P. syringae pv. aptata strains with different defined virulence capacities in order to identify common and strain-specific features, and correlate the secretome with disease outcome. All strains show a high type III secretion system (T3SS) and type VI secretion system (T6SS) activity under apoplast-like conditions mimicking the infection. Surprisingly, we found that low pathogenic strains show a higher secretion of most T3SS substrates, whereas a distinct subgroup of four effectors was exclusively secreted in medium and high pathogenic strains. Similarly, we detected two T6SS secretion patterns: while one set of proteins was highly secreted in all strains, another subset consisting of known T6SS substrates and previously uncharacterized proteins was exclusively secreted in medium and high virulence strains. Taken together, our data show that P. syringae pathogenicity is correlated with the repertoire and fine-tuning of effector secretion and indicate distinct strategies for establishing virulence of P. syringae pv. aptata in plants.
Socioeconomic status of the elderly MS population compared to the general population: a nationwide Danish matched cross-sectional study
Authors: Wandall-Holm Malthe Faurschou , Holm Rolf Pringler , Pontieri Luigi , Sellebjerg Finn , Magyari Melinda
Published: June 2023

Introduction/objectives

Multiple sclerosis (MS) leads to physical and cognitive disability, which in turn impacts the socioeconomic status of the individual. The altered socioeconomic trajectory combined with the critical role of aging in MS progression could potentially lead to pronounced differences between MS patients and the general population. Few nations have the ability to connect long-term clinical and socioeconomic data at the individual level, and Denmark's robust population-based registries offer unique insights. This study aimed to examine the socioeconomic aspects of elderly Danish MS patients in comparison to matched controls from the general population.

Methods

A nationwide population-based study in Denmark was conducted, comprising all living MS patients aged 50 years or older as of 1 January 2021. Patients were matched 1:10 based on sex, age, ethnicity, and residence with a 25% sample of the total Danish population. Demographic and clinical information was sourced from the Danish Multiple Sclerosis Registry, while socioeconomic data were derived from national population-based registries containing details on education, employment, social services, and household characteristics. Univariate comparisons between MS patients and matched controls were then carried out.

Results

The study included 8,215 MS patients and 82,150 matched individuals, with a mean age of 63.4 years (SD: 8.9) and a 2:1 female-to-male ratio. For those aged 50–64 years, MS patients demonstrated lower educational attainment (high education: 28.3 vs. 34.4%, P < 0.001) and fewer received income from employment (46.0 vs. 78.9%, P < 0.001), and working individuals had a lower annual income (48,500 vs. 53,500€, P < 0.001) in comparison to the controls. Additionally, MS patients within this age group were more likely to receive publicly funded practical assistance (14.3 vs. 1.6%, P < 0.001) and personal care (10.5 vs. 0.8%, P < 0.001). Across the entire population, MS patients were more likely to live alone (38.7 vs. 33.8%, P < 0.001) and less likely to have one or more children (84.2 vs. 87.0%, P < 0.001).

Conclusion

MS presents significant socioeconomic challenges among the elderly population, such as unemployment, reduced income, and increased dependence on social care. These findings underscore the pervasive impact of MS on an individual's life course, extending beyond the clinical symptoms of cognitive and physical impairment.
Exploring the potential of mindfulness-based therapy in the prevention and treatment of neurodegenerative diseases based on molecular mechanism studies
Authors: Wu Congcong , Feng Yue
Published: June 2023

Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.
A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria
Authors: França Thássia Casado Lima , Muniz-Santos Renan , Caetano Luiz Carlos , Souza Gustavo H. M. F. , Goulart Henrique Fonseca , Assis Marcio , Bottino Altamiro , Bassini Adriana , Santana Antonio Euzébio Goulart , Prado Eduardo Seixas , Cameron L. C.
Published: June 2023

Tyrosine metabolism has an intense role in the synthesis of neurotransmitters. Our study used an untargeted, sportomics-based analysis of urine samples to investigate changes in metabolism during a soccer match in 30 male junior professional soccer players. Samples were collected before and after the match and analyzed using liquid chromatography and mass spectrometry. Results showed significant changes in tyrosine metabolism. Exercise caused a downregulation of the homogentisate metabolites 4-maleylacetoacetate and succinylacetone to 20% (p = 4.69E−5) and 16% (p = 4.25E−14), respectively. 4-Hydroxyphenylpyruvate, a homogentisate precursor, was found to be upregulated by 26% (p = 7.20E−3). The concentration of hawkinsin and its metabolite 4-hydroxycyclohexyl acetate increased ~six-fold (p = 1.49E−6 and p = 9.81E−6, respectively). Different DOPA metabolism pathways were also affected by exercise. DOPA and dopaquinone increased four-to six-fold (p = 5.62E−14 and p = 4.98E−13, respectively). 3-Methoxytyrosine, indole-5,6-quinone, and melanin were downregulated from 1 to 25%, as were dopamine and tyramine (decreasing to up to 5% or 80%; p= 5.62E−14 and p = 2.47E−2, respectively). Blood TCO2 decreased as well as urinary glutathione and glutamate (40% and 10% respectively) associated with a two-fold increase in pyroglutamate. Our study found unexpected similarities between exercise-induced changes in metabolism and the inherited disorder Hawkinsinuria, suggesting a possible transient condition called exercise-induced hawkinsinuria (EIh). Additionally, our research suggests changes in DOPA pathways may be involved. Our findings suggest that soccer exercise could be used as a model to search for potential countermeasures in Hawkinsinuria and other tyrosine metabolism disorders.
Application of indocyanine green-mediated fluorescence molecular imaging technology in liver tumors resection: a systematic review and meta-analysis
Authors: Zhu Gang , Qiu Xing , Zeng Longfei , Zou Zhirui , Yang Liu , Nie Shanmao , Wang Zuanyu , Zhang Xin , Tang Jinquan , Pan Yong , Tang Shaozhen , Wu Tao
Published: June 2023

Background

This meta-analysis was dedicated to evaluating the safety and effectiveness of indocyanine green (ICG) -mediated fluorescence molecular imaging (FMI) technology in liver tumors resection.

Methods

A literature search of PubMed, Embase databases, Cochrane Library, and Web of Science was performed to identify all clinical controlled studies exploring the effects of fluorescence imaging on liver tumors resection. Quality assessment and data extraction of studies were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.

Results

14 retrospective cohort studies (RCSs) involving a total of 1227 patients were finally included. The results showed that Fluorescence-assisted liver tumors resection could improve the R0 resection rate (OR = 2.63; 95% CI: 1.46~4.73, p = 0.001), reduce overall complications (OR = 0.66; 95% CI: 0.44~0.97, p = 0.04), biliary fistula (OR = 0.20; 95% CI: 0.05~0.77, p = 0.02), intraoperative blood loss (MD = −70.76, 95% CI: −106.11 to −35.41; p < 0.0001), and shortens hospital stay (MD = −1.41, 95% CI: −1.90 to −0.92; p < 0.00001). There were no significant differences in the incidences of operative time (MD = −8.68, 95% CI: −18.59 to −1.22; p = 0.09), complications of grade III or above (OR = 0.73; 95% CI: 0.43~1.25, p = 0.26), liver failure (OR = 0.86; 95% CI: 0.39~1.89, p = 0.71), and blood transfusion (OR = 0.66; 95% CI: 0.42~1.03, p = 0.07).

Conclusion

Current evidence suggests that ICG-mediated FMI technology could enhance the clinical effectiveness of patients with liver tumors resection and is clinically worthy of promotion.

Systematic review registration

PROSPERO, identifier CRD42022368387.
Metabolic bulk volume predicts survival in a homogeneous cohort of stage II/III diffuse large B-cell lymphoma patients undergoing R-CHOP treatment
Authors: Jin Hyun , Jin Myung , Lim Chae Hong , Choi Joon Young , Kim Seok-Jin , Lee Kyung-Han
Published: June 2023

Purpose

Accurate risk stratification can improve lymphoma management, but current volumetric 18F-fluorodeoxyglucose (FDG) indicators require time-consuming segmentation of all lesions in the body. Herein, we investigated the prognostic values of readily obtainable metabolic bulk volume (MBV) and bulky lesion glycolysis (BLG) that measure the single largest lesion.

Methods

The study subjects were a homogeneous cohort of 242 newly diagnosed stage II or III diffuse large B-cell lymphoma (DLBCL) patients who underwent first-line R-CHOP treatment. Baseline PET/CT was retrospectively analyzed for maximum transverse diameter (MTD), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), MBV, and BLG. Volumes were drawn using 30% SUVmax as threshold. Kaplan–Meier survival analysis and the Cox proportional hazards model assessed the ability to predict overall survival (OS) and progression-free survival (PFS).

Results

During a median follow-up period of 5.4 years (maximum of 12.7 years), events occurred in 85 patients, including progression, relapse, and death (65 deaths occurred at a median of 17.6 months). Receiver operating characteristic (ROC) analysis identified an optimal TMTV of 112 cm3, MBV of 88 cm3, TLG of 950, and BLG of 750 for discerning events. Patients with high MBV were more likely to have stage III disease; worse ECOG performance; higher IPI risk score; increased LDH; and high SUVmax, MTD, TMTV, TLG, and BLG. Kaplan–Meier survival analysis showed that high TMTV (p = 0.005 and < 0.001), MBV (both p < 0.001), TLG (p < 0.001 and 0.008), and BLG (p = 0.018 and 0.049) were associated with significantly worse OS and PFS. On Cox multivariate analysis, older age (> 60 years; HR, 2.74; 95% CI, 1.58–4.75; p < 0.001) and high MBV (HR, 2.74; 95% CI, 1.05–6.54; p = 0.023) were independent predictors of worse OS. Older age (hazard ratio [HR], 2.90; 95% CI, 1.74–4.82; p < 0.001) and high MBV (HR, 2.36; 95% CI, 1.15-6.54; p = 0.032) were also independent predictors of worse PFS. Furthermore, among subjects ≤60 years, high MBV remained the only significant independent predictor of worse OS (HR, 4.269; 95% CI, 1.03–17.76; p = 0.046) and PFS (HR, 6.047; 95% CI, 1.73–21.11; p = 0.005). Among subjects with stage III disease, only greater age (HR, 2.540; 95% CI, 1.22–5.30; p = 0.013) and high MBV (HR, 6.476; 95% CI, 1.20–31.9; p = 0.030) were significantly associated with worse OS, while greater age was the only independent predictor of worse PFS (HR, 6.145; 95% CI, 1.10–4.17; p = 0.024).

Conclusions

MBV easily obtained from the single largest lesion may provide a clinically useful FDG volumetric prognostic indicator in stage II/III DLBCL patients treated with R-CHOP.
Clonal evolution in tyrosine kinase inhibitor-resistance: lessons from in vitro-models
Authors: Kaehler Meike , Osteresch Pia , Künstner Axel , Vieth Stella Juliane , Esser Daniela , Möller Marius , Busch Hauke , Vater Inga , Spielmann Malte , Cascorbi Ingolf , Nagel Inga
Published: June 2023

Introduction

Resistance in anti-cancer treatment is a result of clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the hematopoietic neoplasm is predominantly caused by the formation of the BCR::ABL1 kinase. Evidently, treatment with tyrosine kinase inhibitors (TKIs) is tremendously successful. It has become the role model of targeted therapy. However, therapy resistance to TKIs leads to loss of molecular remission in about 25% of CML patients being partially due to BCR::ABL1 kinase mutations, while for the remaining cases, various other mechanisms are discussed.

Methods

Here, we established an in vitro-TKI resistance model against the TKIs imatinib and nilotinib and performed exome sequencing.

Results

In this model, acquired sequence variants in NRAS, KRAS, PTPN11, and PDGFRB were identified in TKI resistance. The well-known pathogenic NRAS p.(Gln61Lys) variant provided a strong benefit for CML cells under TKI exposure visible by increased cell number (6.2-fold, p < 0.001) and decreased apoptosis (-25%, p < 0.001), proving the functionality of our approach. The transfection of PTPN11 p.(Tyr279Cys) led to increased cell number (1.7-fold, p = 0.03) and proliferation (2.0-fold, p < 0.001) under imatinib treatment.

Discussion

Our data demonstrate that our in vitro-model can be used to study the effect of specific variants on TKI resistance and to identify new driver mutations and genes playing a role in TKI resistance. The established pipeline can be used to study candidates acquired in TKI-resistant patients, thereby providing new options for the development of new therapy strategies to overcome resistance.
Restoration of soil quality of degraded grassland can be accelerated by reseeding in an arid area of Northwest China
Authors: Lu Qi , Ma Hongbin , Zhou Yao , Liu Jindi , Shen Yan
Published: June 2023

Grassland restoration measures control soil degradation and improve soil quality (SQ) worldwide, but there is little knowledge about the effectiveness of restoration measures affecting SQ in arid areas, and the restoration rate of degraded grasslands to natural restoration grasslands and reseeded grasslands remains unclear. To establish a soil quality index (SQI) to evaluate the effects of different grassland restoration measures on SQ, continuous grazing grassland (CG) (as a reference), grazing exclusion grassland (EX), and reseeding grassland (RS) were selected and sampled in the arid desert steppe. Two soil indicator selection methods were conducted (total data set (TDS) and minimum data set (MDS)), followed by three SQ indices (additive soil quality index (SQIa), weighted additive soil quality index (SQIw), and Nemoro soil quality index (SQIn)). The results indicated that SQ was better assessed using the SQIw(R2 = 0.55) compared to SQIaand SQInfor indication differences among the treatments due to the larger coefficient of variance. The SQIw-MDS value in CG grassland was 46% and 68% lower than that of EX grassland and RS grassland, respectively. Our findings provided evidence that restoration practices of grazing exclusion and reseeding can significantly improve the SQ in the arid desert steppe, and native plant reseeded can accelerate soil quality restoration.
Social value of pathology: adapting primary health care to reduce stress and social anxiety in college students exposed to social distancing
Authors: Sava Ionel N.
Published: June 2023

This article examined the impact of online education on the wellbeing and emotional health of college students. It considered the social value of stress and anxiety pathology as “normal” side effects throughout the COVID-19 lockdown. Factors appropriate for educational technology were selected and submitted for evaluation to a sample of 114 college students in a semi-structured questionnaire. This research found that educational content and delivery methods, as well as increased homework and time spent online, have potentially contributed to heightened levels of stress, depression, and social anxiety disorder among approximately one-third of students who have engaged in digital learning. The results also prove that young people were particularly susceptible to stress and social anxiety disorders during the lockdown, making them one of the most vulnerable social groups. To enhance the educational experience, several suggestions have been proposed, including adapting educational content, expanding Internet accessibility, providing appropriate homework, and adjusting schedules to accommodate students' educational capabilities. Voluntary routine mental health assessments of students, teachers, and staff and customized online counseling for vulnerable subjects are recommended as primary health care measures during online education.
A survey on the challenges, limitations, and opportunities of online testing of infants and young children during the COVID-19 pandemic: using our experiences to improve future practices
Authors: Shore Montana J. , Bukovsky Danielle L. , Pinheiro Sylvia G. V. , Hancock Brendan M. , Liptrot Emma M. , Kuhlmeier Valerie A.
Published: June 2023

In developmental psychology, the widespread adoption of new methods for testing children does not typically occur over a matter of months. Yet, the COVID-19 pandemic and its associated social distancing requirements created a sudden need among many research groups to use a new method with which they had little or no experience: online testing. Here, we report results from a survey of 159 researchers detailing their early experiences with online testing. The survey approach allowed us to create a general picture of the challenges, limitations, and opportunities of online research, and it identified aspects of the methods that have the potential to impact interpretations of findings. We use the survey results to present considerations to improve online research practices.
Effects of handedness on brain oscillatory activity during imagery and execution of upper limb movements
Authors: Lajtos Melissa , Barradas-Chacón Luis Alberto , Wriessnegger Selina Christin
Published: June 2023

Brain activation during left- and right-hand motor imagery is a popular feature used for brain–computer interfaces. However, most studies so far have only considered right-handed participants in their experiments. This study aimed to investigate how handedness influences brain activation during the processes of imagining and executing simple hand movements. EEG signals were recorded using 32 channels while participants repeatedly squeezed or imagined squeezing a ball using their left, right, or both hands. The data of 14 left-handed and 14 right-handed persons were analyzed with a focus on event-related desynchronization/synchronization patterns (ERD/S). Both handedness groups showed activation over sensorimotor areas; however, the right-handed group tended to display more bilateral patterns than the left-handed group, which is in contrast to earlier research results. Furthermore, a stronger activation during motor imagery than during motor execution could be found in both groups.
Parent-implemented augmented communication intervention and young children with Down syndrome: an exploratory report
Authors: Romski MaryAnn , Sevcik Rose A. , Barton-Hulsey Andrea , Fisher Evelyn , King Marika , Albert Phebe , Kaldes Gal , Walters Casy
Published: June 2023

Introduction

Young children with Down syndrome (DS) present with speech and language impairments very early in childhood. Historically, early language intervention for children with DS included manual signs, though recently there has been an interest in the use of speech-generating devices (SGDs). This paper examines the language and communication performance of young children with DS who participated in parent-implemented communication interventions that included SGDs. Specifically, we compared the functional vocabulary usage and communication interaction skills of children with DS who received augmented communication interventions (AC) that included an SGD with those children with DS who received spoken communication intervention (SC).

Methods

Twenty-nine children with DS participated in this secondary data analysis. These children were part of one of two longitudinal RCT studies investigating the effectiveness of parent-implemented augmented communication interventions in a larger sample of 109 children with severe communication and language impairments.

Results

There were significant differences between children with DS in the AC and SC groups in terms of the number and proportion of functional vocabulary targets used and the total vocabulary targets provided during the intervention at sessions 18 (lab)and 24 (home).

Discussion

Overall, the AC interventions provided the children with a way to communicate via an SGD with visual-graphic symbols and speech output, while the children in the SC intervention were focused on producing spoken words. The AC interventions did not hinder the children’s spoken vocabulary development. Augmented communication intervention can facilitate the communication abilities of young children with DS as they are emerging spoken communicators.
Non-consciously processed physical activity for survival versus consciously deliberated exercise for health
Authors: Iso-Ahola Seppo E.
Published: June 2023

Humans evolved to become dependent on physical activity for their survival, but they have not evolved to exercise today. Because survival in modern society is heavily reliant on conscious thinking, most people (54%) have evolved away from physical activity and become occasional exercisers. This transition from non-conscious to conscious processing prevents people from capitalizing on evolution’s wisdom for survival and wellbeing as they consciously deliberate on the utility of health practices to achieve certain outcomes (e.g., weight loss). Unlike in early times, people today have a choice of not engaging in physical activity and yet surviving. As a result, they struggle with the question whether the gains from exercising are greater than losses from not doing it, weighing positive gains and losses against negative gains and losses. Such conscious deliberations, however, can easily be overridden by solving cognitive dissonance (e.g., “exercise is good for my health” vs. “I don’t exercise”) through conscious rationalizations and non-conscious dismissal. Today’s exercise problem can only be solved by individually acquiring the mindset of early times of evolution when the initiation of physical activity was largely a matter of non-conscious thoughts and feelings.