bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydroepiandrosterone (DHEA) increases undirected singing behavior and alters dopaminergic regulation of undirected song in non-breeding male European starlings (Sturnus vulgaris)
Authors: Heimovics Sarah , Rubin Nathan , Ford Morgan
Published: May 2023

Introduction

It has been proposed that in species that defend territories across multiple life history stages, brain metabolism of adrenal dehydroepiandrosterone (DHEA) regulates aggressive behavior at times when gonadal androgen synthesis is low (i.e. the non-breeding season). To date, a role for DHEA in the regulation of other forms of social behavior that are expressed outside of the context of breeding remains unknown.

Methods

In this experiment, we used the European starling (Sturnus vulgaris) model system to investigate a role for DHEA in the neuroendocrine regulation of singing behavior by males in non-breeding condition. Starling song in a non-breeding context is spontaneous, not directed towards conspecifics, and functions to maintain cohesion of overwintering flocks.

Results

Using within-subjects design, we found that DHEA implants significantly increase undirected singing behavior by non-breeding condition male starlings. Given that DHEA is known to modulate multiple neurotransmitter systems including dopamine (DA) and DA regulates undirected song, we subsequently used immunohistochemistry for phosphorylated tyrosine hydroxylase (pTH, the active form of the rate-limiting enzyme in DA synthesis) to investigate the effect of DHEA on dopaminergic regulation of singing behavior in a non-breeding context. Pearson correlation analysis revealed a positive linear association between undirected singing behavior and pTH immunoreactivity in the ventral tegmental area and midbrain central gray of DHEA-implanted, but not control-implanted, males.

Discussion

Taken together, these data suggest that undirected singing behavior by non-breeding starlings is modulated by effects of DHEA on dopaminergic neurotransmission. More broadly, these data expand the social behavior functions of DHEA beyond territorial aggression to include undirected, affiliative social communication.
A multi-objective optimization model for the coordinated operation of hydropower and renewable energy
Authors: Liu Benxi , Peng Zihan , Liao Shengli , Liu Tengyuan , Lu Jia
Published: May 2023

The rapid growth of wind and solar energy sources in recent years has brought challenges to power systems. One challenge is surging wind and solar electric generation, understanding how to consume such generation is important. Achieving the complementarity of hydropower and renewable energies such as wind and solar power by utilizing the flexible regulation performance of hydropower is helpful to provide firm power to help renewable energy consumption. However, the multi-energy complementary operation mode will change the traditional hydropower operation mode, causing challenges to the comprehensive utilization of hydropower. In this paper, a multi-objective optimal scheduling model is built by considering coordinated hydro-wind-solar system peak shaving and downstream navigation. First, the Gaussian mixture model is adopted to quantify the uncertainty of wind and solar power. Then, a hydro-wind-solar coordinated model was built to obtain the standard deviation of the residual load and the standard deviation of the downstream water level. Finally, the ε-constraint method is used to solve for the Pareto optimality. The results demonstrate the following: 1) The proposed model can effectively determine hydropower output schemes that can coordinate wind and solar power output to reconcile peak shaving and navigation; 2) The downstream hydropower stations’ reverse regulation of the upstream hydropower station is a positive factor in reconciling conflicts; and 3) Reasonable planning of wind power and solar power is helpful for hydro-wind solar power complement operation.
How will industrial collaborative agglomeration affect the efficiency of regional green development?
Authors: Liu Baoliu , Luo Jian , Zheng Kengcheng , Wu Feng , Zhao Xiongfei
Published: May 2023

The integrated development of various industries in China is essential for promoting long-term sustainable development and achieving carbon neutrality. In this study, we analyze panel data from 30 Chinese provinces (excluding Tibet, Hong Kong, Macao, and Taiwan) covering the period between 2005 and 2020 to investigate the impact of collaborative agglomeration between productive service and manufacturing industries on green development efficiency. We utilize a mediation effect model to examine the role of technological innovation in driving the relationship between industrial collaborative agglomeration and regional green development efficiency. Our findings reveal that the collaborative agglomeration of the productive service and manufacturing industries has a significant positive effect on improving regional green development efficiency. We also identify a non-linear relationship, indicating a double threshold effect. Technological innovation plays an important role in facilitating industrial collaborative agglomeration and promoting the efficiency of regional green development. Moreover, our results demonstrate significant regional heterogeneity in the impact of industrial collaborative agglomeration on regional green development efficiency. Based on these findings, we propose several policy recommendations to achieve high-quality regional economic development, including improving the quality of industrial synergy and agglomeration between regions, strengthening the intermediary promotion role of technological innovation, and enhancing regional green productivity.
Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing
Authors: Chung An-Ko , Lin Ro-Ting , Yeh Chun-Chieh , Yang Chi-Ying , Wu Chang-Jiun , Chen Pei-Lung , Lin Jaw-Town
Published: May 2023

Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected.
Minimal residual disease status improved the response evaluation in patients with Waldenström’s macroglobulinemia
Authors: Xiong Wenjie , Wang Zanzan , Wang Tingyu , Yu Ying , Huang Yanshan , Sun Hao , Chen Jiawen , Lyu Rui , Wang Huijun , Yan Yuting , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Huang Wenyang , Zou Dehui , Xiao Zhijian , Wang Jianxiang , Ouyang Guifang , Qiu Lugui , Yi Shuhua
Published: May 2023

Introduction

Minimal residual disease (MRD) has been recognized as an important prognostic factor of survival in patients with hematological malignancies. However, the prognostic value of MRD in Waldenström macroglobulinemia (WM) remains unexplored.

Methods

We analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed for MRD by multiparameter flow cytometry (MFC) using bone marrow samples.

Results

Of the total patients, 34 (31.5%) achieved undetectable MRD (uMRD). A hemoglobin level of >115 g/L (P=0.03), a serum albumin level of >35 g/L (P=0.01), a β2-MG level of ≤3 mg/L (P=0.03), and a low-risk International Prognostic Scoring System for WM (IPSSWM) stage (P<0.01) were associated with a higher rate of uMRD. Improvements in monoclonal immunoglobulin (P<0.01) and hemoglobin (P=0.03) levels were more evident in uMRD patients compared with that in MRD-positive patients. The 3-year progression-free survival (PFS) was better in uMRD patients compared with that in MRD-positive patients (96.2% vs. 52.8%; P=0.0012). Landmark analysis also showed that uMRD patients had better PFS compared with MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that of patients with MRD-positive PR (62.6%, P=0.029). Multivariate analysis showed that MRD positivity was an independent factor of PFS (HR: 2.55, P=0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD assessment had a higher 3-year AUC compared with the IWWM-6 criteria alone (0.71 vs. 0.67).

Discussion

MRD status assessed by MFC is an independent prognostic factor for PFS in patients with WM, and its determination could improve the precision of response evaluation, especially in patients who achieved PR.
Low-dose post-transplant cyclophosphamide with G-CSF/ATG based haploidentical protocol provides favorable outcomes for SAA patients
Authors: Ma Xiaodi , Xu Zhengli , Han Tingting , Zhang Yuanyuan , Han Wei , Fu Haixia , Zhang Xiaohui , Lin Fan , Huang Xiaojun , Xu Lanping
Published: May 2023

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11–20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.
Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice
Authors: Czárán Domonkos , Sasvári Péter , Horváth Ádám István , Ella Krisztina , Sűdy Ágnes Réka , Borbély Éva , Rusznák Kitti , Czéh Boldizsár , Mócsai Attila , Helyes Zsuzsanna , Csépányi-Kömi Roland
Published: May 2023

Objective

Despite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis.

Methods

Wild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were treated i.p. with the K/BxN arthritogenic or control serum, and the severity of inflammation and pain-related behavior was measured. Histology was prepared, leukocyte infiltration, cytokine production, myeloperoxidase activity, and superoxide production were determined, and comprehensive western blot analysis was conducted.

Results

In the absence of ARHGAP25, the severity of inflammation, joint destruction, and mechanical hyperalgesia significantly decreased, similarly to phagocyte infiltration, IL-1β, and MIP-2 levels in the tibiotarsal joint, whereas superoxide production or myeloperoxidase activity was unchanged. We observed a significantly mitigated phenotype in KO bone marrow chimeras as well. In addition, fibroblast-like synoviocytes showed comparable expression of ARHGAP25 to neutrophils. Significantly reduced ERK1/2, MAPK, and I-κB protein signals were detected in the arthritic KO mouse ankles.

Conclusion

Our findings suggest that ARHGAP25 has a key role in the pathomechanism of autoantibody-induced arthritis in which it regulates inflammation via the I-κB/NF-κB/IL-1β axis with the involvement of both immune cells and fibroblast-like synoviocytes.
Microwave-assisted biosynthesis of nano silver and its synergistic antifungal activity against Curvularia lunata
Authors: Xiao Xiuhua , Zheng Zirui , Yu Haibing , Huang Weidong , Ji Wenchao
Published: May 2023

It is necessary to explore eco-friendly antimicrobial agents to resolve problems such as pathogen resistance and pesticide residues. In this study, Mentha haplocalyx leaf extract was applied to biosynthesize nano silver using a microwave-assisted method. The detailed properties of the nano silver were systematically revealed by several analytical methods. The antifungal activity of nano silver and synergistic antifungal effects of nano silver conjugated with pesticides against Curvularia lunata were determined. Pathogen invasion was significantly inhibited (57.3%) on detached and intravital maize leaves when the concentration of nano silver was 200 μg mL−1, with an inhibition zone diameter of 12.5 ± 1.18 mm. In addition, a clear synergistic antifungal effect of nano silver conjugated with epoxiconazole was observed at volume ratios of 8:2 and 9:1, while the toxicity ratios were 1.18 and 1.11, respectively. These results not only provide a new avenue for pathogen management, but also enable reduced dosages of antibiotics and pesticides to mitigate or avoid emergence of drug-resistant pathogens.
Synchronized extracorporeal shockwave lithotripsy may still affect the heart: a case report of perioperative ST-segment elevation myocardial infarction
Authors: Li Yi Hong , Hsu Chao Yu , Liu Chih Tsung , Lin Yi Sheng , Ou Yen Chuan , Tung Min Che
Published: May 2023

Extracorporeal shockwave lithotripsy (ESWL) is widely used as a primary treatment for urolithiasis and is performed as an elective outpatient surgical procedure because of its ease of use. However, patients undergoing this treatment rarely develop cardiac complications. In this article, we present the case of a 45-year-old male patient who presented with ST-elevation myocardial infarction during ESWL. Moreover, atypical symptoms and electrocardiogram patterns were recognized by the nursing staff. Early primary evaluation and intervention resulted in favorable outcomes along with patent coronary artery flow following stent placement for stenosis, and no complications were noted.
Whole-genome sequencing of Listeria innocua recovered from retail milk and dairy products in Egypt
Authors: Ramadan Hazem , Al-Ashmawy Maha , Soliman Ahmed M. , Elbediwi Mohammed , Sabeq Islam , Yousef Mona , Algammal Abdelazeem M. , Hiott Lari M. , Berrang Mark E. , Frye Jonathan G. , Jackson Charlene R.
Published: May 2023

The similarity of the Listeria innocua genome with Listeria monocytogenes and their presence in the same niche may facilitate gene transfer between them. A better understanding of the mechanisms responsible for bacterial virulence requires an in-depth knowledge of the genetic characteristics of these bacteria. In this context, draft whole genome sequences were completed on five L. innocua isolated from milk and dairy products in Egypt. The assembled sequences were screened for antimicrobial resistance and virulence genes, plasmid replicons and multilocus sequence types (MLST); phylogenetic analysis of the sequenced isolates was also performed. The sequencing results revealed the presence of only one antimicrobial resistance gene, fosX, in the L. innocua isolates. However, the five isolates carried 13 virulence genes involved in adhesion, invasion, surface protein anchoring, peptidoglycan degradation, intracellular survival, and heat stress; all five lacked the Listeria Pathogenicity Island 1 (LIPI-1) genes. MLST assigned these five isolates into the same sequence type (ST), ST-1085; however, single nucleotide polymorphism (SNP)-based phylogenetic analysis revealed 422–1,091 SNP differences between our isolates and global lineages of L. innocua. The five isolates possessed an ATP-dependent protease (clpL) gene, which mediates heat resistance, on a rep25 type plasmids. Blast analysis of clpL-carrying plasmid contigs showed approximately 99% sequence similarity to the corresponding parts of plasmids of L. monocytogenes strains 2015TE24968 and N1-011A previously isolated from Italy and the United States, respectively. Although this plasmid has been linked to L. monocytogenes that was responsible for a serious outbreak, this is the first report of L. innocua containing clpL-carrying plasmids. Various genetic mechanisms of virulence transfer among Listeria species and other genera could raise the possibility of the evolution of virulent strains of L. innocua. Such strains could challenge processing and preservation protocols and pose health risks from dairy products. Ongoing genomic research is necessary to identify these alarming genetic changes and develop preventive and control measures.
Resources and tools for rare disease variant interpretation
Authors: Licata Luana , Via Allegra , Turina Paola , Babbi Giulia , Benevenuta Silvia , Carta Claudio , Casadio Rita , Cicconardi Andrea , Facchiano Angelo , Fariselli Piero , Giordano Deborah , Isidori Federica , Marabotti Anna , Martelli Pier Luigi , Pascarella Stefano , Pinelli Michele , Pippucci Tommaso , Russo Roberta , Savojardo Castrense , Scafuri Bernardina , Valeriani Lucrezia , Capriotti Emidio
Published: May 2023

Collectively, rare genetic disorders affect a substantial portion of the world’s population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging. However, the application of recent advancements in genome sequencing/analysis technologies and computer-aided tools for predicting phenotype-genotype associations can bring significant benefits to this field. In this review, we highlight the most relevant online resources and computational tools for genome interpretation that can enhance the diagnosis, clinical management, and development of treatments for rare disorders. Our focus is on resources for interpreting single nucleotide variants. Additionally, we present use cases for interpreting genetic variants in clinical settings and review the limitations of these results and prediction tools. Finally, we have compiled a curated set of core resources and tools for analyzing rare disease genomes. Such resources and tools can be utilized to develop standardized protocols that will enhance the accuracy and effectiveness of rare disease diagnosis.
The role of sex differences in depression in pathologically defined Alzheimer’s disease
Authors: Tremblay Cécilia , Choudhury Parichita , Belden Christine M. , Goldfarb Danielle , Lorenzini Ileana , Beach Thomas G. , Serrano Geidy E.
Published: May 2023

Introduction

Sex differences in Alzheimer’s disease (AD) may contribute to disease heterogeneity and affect prevalence, risk factors, disease trajectories and outcomes. Depression impacts a large number of patients with AD and has been reported to be more prevalent in women. We aimed to better understand the interaction between sex, depression and AD neuropathology, which could have implications for detection of symptoms, earlier diagnosis, therapeutic management, and enhanced quality of life.

Methods

We compared 338 cases with clinicopathologically confirmed AD (46% women) to 258 control cases (50% women), without dementia, parkinsonism or a significant pathological diagnosis. Depression was assessed both, using the Hamilton Depression Scale (HAM-D), and as being reported in their medical history combined with treatment with antidepressant medication.

Results

In the control group, women showed a higher depression severity, and a higher proportion of women were found to meet the cut-off score for depression on the HAM-D (32 vs. 16%) and having an history of depression (33 vs. 21%), while these sex differences were not observed in AD. Further, in both groups, female sex independently predicted the presence of depression, with covariates for age and cognitive status. AD subjects had higher mean HAM-D scores, were more likely to meet cutoff scores for depression (41 vs. 24%) and have a history of depression than controls (47 vs. 27%). When comparing the increase in frequency of depression in controls versus AD, the difference was significantly greater in men (AD men - control men: 24%) than in women (AD women - control women: 9%). Although subjects with depression were more likely to have higher levels of AD neuropathology, these differences were not observed when investigating the control or AD group separately.

Discussion

Control women had a higher likelihood and severity of depression than control men, but this sex difference was not noted when considering only those with pathologically defined AD, emphasizing the importance of considering sex in aging studies. AD was associated with higher rates of depression and men may be more likely to report or be diagnosed with depression once they develop AD indicating the importance of more frequent depression screenings in men.
Association between short-term air pollution exposure and traumatic intracranial hemorrhage: pilot evidence from Taiwan
Authors: Liao Kuo-Hsing , Chan Ta-Chien , Wu Chia-Chieh , Huang Wen-Cheng , Hsu Chin-Wang , Chuang Hsiao-Chi , Wiratama Bayu Satria , Chiu Wen-Ta , Lam Carlos
Published: May 2023

Introduction

The detrimental effects of air pollution on the brain are well established. However, few studies have examined the effect of air pollution on traumatic brain injury (TBI). This pilot study evaluated the association between short-term air pollution exposure and traumatic intracranial hemorrhage (TIH).

Methods

Hospital data of patients with TBI following road traffic accidents were retrospectively collected from the electronic medical records at five trauma centers in Taiwan between 1 January and 31 December 2017. TIH was employed as an outcome measure. All road accident locations were geocoded, and air quality data were collected from the nearest monitoring stations. Air pollutants were entered into five multivariable models. A sensitivity analysis was performed on patients who are vulnerable to suffering TBI after road accidents, including motorcyclists, bicyclists, and pedestrians.

Results

Among 730 patients with TBI, 327 had TIH. The ages of ≥65 [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.85–5.70], 45–64 (OR, 2.61; 95% CI, 1.64–4.15), and 25–44 (OR, 1.79; 95% CI, 1.13–2.84) years were identified as significant risk factors in the multivariable analysis. In the best-fit multivariable model, exposure to higher concentrations of particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) was associated with an elevated TIH risk (OR, 1.50; 95% CI, 1.17–1.94). The concentration of nitrogen oxides (NOX) did not increase the risk of TIH (OR, 0.45; 95% CI, 0.32–0.61). After categorizing the air pollution concentration according to quartile, the trend tests in the multivariate model showed that the concentrations of PM2.5 and NOX were significant (p = 0.017 and p < 0.001, respectively). There was a negative borderline significant association between temperature and TIH risk (OR, 0.75; 95% CI, 0.56–1.00, p = 0.05). Notably, the single-vehicle crash was a significant risk factor (OR, 2.11; 95% CI, 1.30–3.42) for TIH.

Discussion

High PM2.5 concentrations and low temperatures are risk factors for TIH in patients with TBI. High NOX concentrations are associated with a lower TIH risk.
Movement patterns in tuba playing: comparison of an embouchure dystonia case with healthy professional tuba players using real-time MRI imaging
Authors: Nelkenstock Robert , Iltis Peter W. , Voit Dirk , Frahm Jens , Passarotto Edoardo , Altenmüller Eckart
Published: May 2023

Introduction

Musculoskeletal problems in professional brass musicians are very common and often involve the muscles of the embouchure. In rare cases, embouchure dystonia (EmD), a task-specific movement disorder with a wide symptomatic and phenotypic variability, occurs. Following trumpeters and horn players, professional tuba players with and without EmD have now been studied using the latest real-time MRI technology to better understand the underlying pathophysiology.

Materials and methods

In the present study, the tongue movement patterns of 11 healthy professional artists and one subject suffering from EmD were compared. The tongue position in the anterior, intermediary and posterior oral cavity were converted into pixel positions based on seven previously generated profile lines, using the established software MATLAB. These data allow a structured comparison of tongue movement patterns between the patient and the healthy subjects, as well as between individual exercises. The main focus of the analysis was on an ascending 7-note harmonic series performed in different playing techniques (slurred, tongued, tenuto and staccato).

Results

Playing the ascending harmonics, a noticeable ascending tongue movement could be observed in the anterior part of the oral cavity in healthy tubists. In the posterior region, there was a slight decrease in oral cavity space. In the EmD patient, hardly any movement was observed at the tongue apex, but in the middle and posterior regions of the oral cavity there was an increase in size the higher the tone became. These distinct differences are relevant for the characterization and a better understanding of the clinical presentation of EmD. Concerning different playing techniques, it was apparent, that notes played slurred or staccato resulted in a larger oral cavity when compared to notes played tongued or tenuto, respectively.

Conclusion

By using real-time MRI videos, the tongue movements of tuba players can be clearly observed and analyzed. The differences between healthy and diseased tuba players demonstrate the great effects of movement disorders in a small area of the tongue. In order to better understand the compensation of this motor control dysfunction, further studies should investigate further parameters of tone production in all brass players with a larger number of EmD patients additional to the observed movement patterns.
Seeing in my way or your way: impact of intelligence, attention, and empathy on brain reactivity
Authors: Montandon Marie-Louise , Rodriguez Cristelle , Herrmann François R. , Eytan Ariel , Pegna Alan J. , Haller Sven , Giannakopoulos Panteleimon
Published: May 2023

Previous studies showed that neurotypical adults are able to engage in unconscious analyses of others’ mental states in the context of automatic perspective taking and experience systematic difficulties when judging the conflicts between their own (Self) and another’s (Other) perspective. Several functional MRI (fMRI) studies reported widespread activation of mentalizing, salience, and executive networks when adopting the Other compared to Self perspective. This study aims to explore whether cognitive and emotional parameters impact on brain reactivity in dot perspective task (dPT). We provide here an fMRI analysis based on individual z-scores in eighty-two healthy adults who underwent the Samson’s dPT after detailed assessment of fluid intelligence, attention, levels of alexithymia and social cognition abilities. Univariate regression models were used to explore the association between brain activation patterns and psychological variables. There was a strong positive association between Wechsler Adult Intelligence Scale (WAIS) and fMRI z-scores in Self perspective. When the Other perspective is taken, Continuous Performance Test (CPT)-II parameters were negatively associated with fMRI z-scores. Individuals with higher Toronto Alexithymia scale (TAS) score and lower scores in mini-Social cognition and Emotional Assessment (SEA) displayed significantly higher egocentric interference-related fMRI z-scores. Our data demonstrate that brain activation when focusing on our own perspective depends on the levels of fluid intelligence. Decreased attentional recruitment and decreased inhibitory control affects the brain efforts to adopt the Other perspective. Egocentric interference-associated brain fMRI activation was less marked in cases with better empathy abilities but the opposite was true for persons who experience increased difficulties in the recognition of emotions.
The month of walking alone and BDNF level differ between drug-naive first-episode schizophrenia patients and healthy controls
Authors: Zhang Zhenmei , Fan Lejia , Yuan Liu , Li Zongchang , Ouyang Lijun , Ma Xiaoqian , Yang Zihao , Lv Jingyan , Chen Shuting , Chen Xiaogang , He Ying
Published: May 2023

Introduction

Schizophrenia is a neurodevelopmental disorder, characterized by impairment in reasoning, affectivity, and social relationships. Previous studies have shown delayed motor development and Brain-Derived Neurotrophic Factor (BDNF) level change in individuals with schizophrenia. We researched the month of walking alone (MWA) and BDNF level between drug-naive first-episode schizophrenia patients (FEP) and healthy control (HC), as well as how they behave in neurocognitive function and severity of symptoms. Predictors of schizophrenia were further explored too.

Methods

We researched the MWA and BDNF levels between FEP and HCs in the Second Xiangya Hospital of Central South University from August 2017 to January 2020, as well as how they behave in neurocognitive function and the severity of symptoms. A binary logistic regression analysis was used to examine the risk factors affecting the onset and treatment outcome of schizophrenia.

Results

We find that FEP showed a walking delay and lower BDNF levels compared to HCs, which were associated with cognitive impairment and severity of symptoms. According to the difference and correlation analysis results, and combined with the appropriate application conditions for binary logistic regression, Wechsler Intelligence Scale Picture completion, Hopkins Verbal Learning Test-Revised, and Trail Making Test: part A were added to the binary logistic regression analysis to distinguish FEP and HCs.

Conclusion

Our study has shown delayed motor development and changes in BDNF levels in schizophrenia, extending insight into the early identification of patients with schizophrenia versus healthy populations.
Characteristics of resistance training-based protocols in older adults with sarcopenic obesity: a scoping review of training procedure recommendations
Authors: Silva Leonardo Santos Lopes da , Gonçalves Leonardo da Silva , Abdalla Pedro Pugliesi , Benjamim Cícero Jonas Rodrigues , Tasinafo Márcio Fernando , Venturini Ana Cláudia Rossini , Bohn Lucimere , Mota Jorge , Marcos-Pardo Pablo Jorge , Kemmler Wolfgang , dos Santos André Pereira , Machado Dalmo Roberto Lopes
Published: May 2023

Background

Sarcopenic obesity (SO) is a clinical and functional disease characterized by the coexistence of obesity and sarcopenia. Resistance training (RT) characteristics for older adults with sarcopenia or obesity are already well established in the scientific literature. Nonetheless, we still do not know how detailed the RT protocols are described for older adults with SO. Therefore, we aimed to analyze the characteristics of RT programs, including each of their variables, recommended for older adults with SO.

Methods

This is a scoping review study that was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews. The search was carried out until November 2022 in PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus, LILACS, Google Scholar, and medRxiv databases. The studies included SO diagnosis and RT as an intervention strategy. The RT variables analyzed were as follows: exercise selection, the volume of sets, the intensity of load, repetition cadence, rest interval between sets, and weekly frequency.

Results

A total of 1,693 studies were identified. After applying the exclusion criteria, 15 studies were included in the final analysis. The duration of the RT intervention ranged from 8 to 24 weeks. All studies included full-body routines, with single/multi-joint exercises. Regarding the volume of sets, some studies fixed it in three sets, whereas others varied between one and three sets. The load was reported by repetition range and the weight lifted, elastic-band color/resistance, percentage of one repetition maximum, or perceived exertion scale. Repetition cadence was fixed in some studies, while it was self-selected between concentric and eccentric phases in others. The interval between sets of rest varied from 30 to 180 s. All studies reported progression overload during the interventions. Not all studies reported how the exercise selection, repetition cadence, and rest interval were made.

Conclusion

The characteristics of RT protocols and their variables prescribed in the literature for older adults with SO were mapped. The lack of detail on some training variables (i.e., exercise selection, repetition cadence, and rest interval) was identified. RT protocols are heterogeneous and described only partially among studies. The recommendations for RT prescription details in older adults with SO are provided for future studies.

Systematic review registration

https://osf.io/wzk3d/.
Value of non-coding RNAs to assess lymph node status in cervical cancer
Authors: Dabi Yohann , Favier Amelia , Razakamanantsoa Léo , Suisse Stéphane , Marie Yannick , Touboul Cyril , Ferrier Clément , Bendifallah Sofiane , Daraï Emile
Published: May 2023

Cervical cancer (CC) is the fourth cancer in women and is the leading cause of cancer death in 42 countries. Lymph node metastasis is a determinant prognostic factor, as underlined in the latest FIGO classification. However, assessment of lymph node status remains difficult, despite the progress of imaging such as PET-CT and MRI. In the specific setting of CC, all data underlined the need for new biomarkers easily available to assess lymph node status. Previous studies have underlined the potential value of ncRNA expression in gynecological cancers. In this review, we aimed to evaluate the contribution of ncRNAs in tissue and biofluid samples to determine lymph node status in CC with potential impact on both surgical and adjuvant therapies. In tissue samples, our analysis found that there are arguments to support the role of ncRNAs in physiopathology, differential diagnosis from normal tissue, preinvasive and invasive tumors. In biofluids, despite small studies especially concerning miRNAs expression, promising data opens up new avenue to establish a non-invasive signature for lymph node status as well as a tool to predict response to neo- and adjuvant therapies, thus improving management algorithm of patients with CC.
Enhancing gastric cancer conventional chemotherapy effects by triple angiokinase inhibitor nintedanib in preclinical models
Authors: Awasthi Niranjan , Schwarz Margaret A. , Kaurich Quinn , Zhang Changhua , Hilberg Frank , Schwarz Roderich E.
Published: May 2023

Background

Gastric adenocarcinoma (GAC) is the fourth leading cause of cancer death worldwide. Systemic chemotherapy is a preferred treatment option for advanced and recurrent GAC, but response rates and survival prolongation remain limited. Tumor angiogenesis plays a critical role in GAC growth, invasion and metastasis. We investigated the antitumor efficacy of nintedanib, a potent triple angiokinase inhibitor for VEGFR-1/2/3, PDGFR-α/β and FGFR-1/2/3, alone or in combination with chemotherapy, in preclinical models of GAC.

Methods

Animal survival studies were performed in peritoneal dissemination xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and KATO-III. Tumor growth inhibition studies were performed in subcutaneous xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and SNU-5. The mechanistic evaluation involved Immunohistochemistry analyses in tumor tissues obtained from subcutaneous xenografts. In vitro cell viability assays were performed using a colorimetric WST-1 reagent.

Results

In MKN-45 GAC cell-derived peritoneal dissemination xenografts, animal survival was improved by nintedanib (33%), docetaxel (100%) and irinotecan (181%), while oxaliplatin, 5-FU and epirubicin had no effect. The addition of nintedanib to docetaxel (157%) or irinotecan (214%) led to a further extension in animal survival. In KATO-III GAC cell-derived xenografts carrying FGFR2 gene amplification, nintedanib extended survival by 209%. Again, the addition of nintedanib further enhanced the animal survival benefits of docetaxel (273%) and irinotecan (332%). In MKN-45 subcutaneous xenografts, nintedanib, epirubicin, docetaxel and irinotecan reduced tumor growth (range: 68-87%), while 5-FU and oxaliplatin had a smaller effect (40%). Nintedanib addition to all chemotherapeutics demonstrated a further reduction in tumor growth. Subcutaneous tumor analysis revealed that nintedanib attenuated tumor cell proliferation, reduced tumor vasculature and increased tumor cell death.

Conclusion

Nintedanib showed notable antitumor efficacy and significantly improved taxane or irinotecan chemotherapy responses. These findings indicate that nintedanib, alone and in combination with a taxane or irinotecan, has the potential for improving clinical GAC therapy.
Regulation of tumor angiogenesis by the crosstalk between innate immunity and endothelial cells
Authors: Ebeling Svenja , Kowalczyk Anita , Perez-Vazquez Diego , Mattiola Irene
Published: May 2023

Endothelial cells and immune cells are major regulators of cancer progression and prognosis. Endothelial cell proliferation and angiogenesis are required for providing nutrients and oxygen to the nascent tumor and infiltration of immune cells to the tumor is dependent on endothelial cell activation. Myeloid cells and innate lymphocytes have an important role in shaping the tumor microenvironment by crosstalking with cancer cells and structural cells, including endothelial cells. Innate immune cells can modulate the activation and functions of tumor endothelial cells, and, in turn, endothelial cell expression of adhesion molecules can affect immune cell extravasation. However, the mechanisms underlying this bidirectional crosstalk are not fully understood. In this review, we will provide an overview of the current knowledge on the pathways regulating the crosstalk between innate immune cells and endothelial cells during tumor progression and discuss their potential contribution to the development of novel anti-tumor therapeutic approaches.
Recent advances in understanding DNA methylation of prostate cancer
Authors: Shin Hyun Jin , Hua Junjie T. , Li Haolong
Published: May 2023

Epigenetic modifications, such as DNA methylation, is widely studied in cancer. DNA methylation patterns have been shown to distinguish between benign and malignant tumors in various cancers, including prostate cancer. It may also contribute to oncogenesis, as it is frequently associated with downregulation of tumor suppressor genes. Aberrant patterns of DNA methylation, in particular the CpG island hypermethylator phenotype (CIMP), have shown associative evidence with distinct clinical features and outcomes, such as aggressive subtypes, higher Gleason score, prostate-specific antigen (PSA), and overall tumor stage, overall worse prognosis, as well as reduced survival. In prostate cancer, hypermethylation of specific genes is significantly different between tumor and normal tissues. Methylation patterns could distinguish between aggressive subtypes of prostate cancer, including neuroendocrine prostate cancer (NEPC) and castration resistant prostate adenocarcinoma. Further, DNA methylation is detectable in cell-free DNA (cfDNA) and is reflective of clinical outcome, making it a potential biomarker for prostate cancer. This review summarizes recent advances in understanding DNA methylation alterations in cancers with the focus on prostate cancer. We discuss the advanced methodology used for evaluating DNA methylation changes and the molecular regulators behind these changes. We also explore the clinical potential of DNA methylation as prostate cancer biomarkers and its potential for developing targeted treatment of CIMP subtype of prostate cancer.
Single-cell RNA sequencing and traditional RNA sequencing reveals the role of cancer-associated fibroblasts in oral squamous cell carcinoma cohort
Authors: Wu Lin , Yang Jun , She Peng , Kong Fanzhi , Mao Zhenwei , Wang Shengjun
Published: May 2023

Chronic inflammation of the alveolar bones and connective tissues supporting teeth causes periodontal disease, one of the most prevalent infectious diseases in humans. It was previously reported that oral cancer was the sixth most common cancer in the world, followed by squamous cell carcinoma. Periodontal disease has been linked to an increased risk for oral cancer in some studies, and these studies have found a positive relationship between oral cancer and periodontal disease. In this work, we aimed to explore the potential correlation between oral squamous cell carcinoma (OSCC) and Periodontal disease. The single-cell RNA sequence analysis was applied to explore the genes that were closely associated with cancer-associated fibroblasts (CAFs). the head and neck squamous cell carcinoma. The Single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was applied to explore the scores of CAFs. Subsequently, the differentially expressed analysis was applied to explore the CAFs-related genes that play a key role in the OSCC cohort. The LASSO regression analysis and the COX regression analysis were applied to construct the CAFs-based periodontal disease-related risk model. In addition, the correlation analysis was used to explore the correlation between the risk model and clinical features, immune-related cells, and immune-related genes. By using the single-cell RNA sequence analysis, we successfully obtained the biomarkers for the CAFs. Finally, we successfully obtained a six-CAFs-related genes risk model. The ROC curve and survival analysis revealed that the risk model showed good predictive value in OSCC patients. Our analysis successfully provided a new direction for the treatment and prognosis of OSCC patients.
Viral infection in chronic otitis media with effusion in children
Authors: Runge Annette , Straif Sonja , Banki Zoltan , Borena Wegene , Muellauer Brigitte , Brunner Juergen , Gottfried Timo , Schmutzhard Joachim , Dudas Jozsef , Risslegger Brigitte , Randhawa Avneet , Lass-Flörl Cornelia , von Laer Dorothee , Riechelmann Herbert
Published: May 2023

Background

The role of respiratory viruses in chronic otitis media with effusion (COME) in children is not clearly defined. In our study we aimed to investigate the detection of respiratory viruses in middle ear effusions (MEE) as well as the association with local bacteria, respiratory viruses in the nasopharynx and cellular immune response of children with COME.

Methods

This 2017–2019 cross-sectional study included 69 children aged 2–6 undergoing myringotomy for COME. MEE and nasopharyngeal swabs were analyzed via PCR and CT-values for the genome and loads of typical respiratory viruses. Immune cell populations and exhaustion markers in MEE related to respiratory virus detection were studied via FACS. Clinical data including the BMI was correlated.

Results

Respiratory viruses were detected in MEE of 44 children (64%). Rhinovirus (43%), Parainfluenzavirus (26%) and Bocavirus (10%) were detected most frequently. Average Ct values were 33.6 and 33.5 in MEE and nasopharynx, respectively. Higher detection rates correlated with elevated BMI. Monocytes were elevated in MEE (9.5 ± 7.3%/blood leucocytes). Exhaustion markers were elevated on CD4+ and CD8+ T cells and monocytes in MEE.

Conclusion

Respiratory viruses are associated with pediatric COME. Elevated BMI was associated with increased rates of virus associated COME. Changes in cell proportions of innate immunity and expression of exhaustion markers may be related to chronic viral infection.
Exploration of anti-stress mechanisms in high temperature exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling
Authors: Wang Yongjie , Bao Xiaokai , Wang Weijun , Xu Xiaohui , Liu Xiumei , Li Zan , Yang Jianmin , Yuan Tingzhu
Published: May 2023

Sepia esculenta is a cephalopod widely distributed in the Western Pacific Ocean, and there has been growing research interest due to its high economic and nutritional value. The limited anti-stress capacity of larvae renders challenges for their adaptation to high ambient temperatures. Exposure to high temperatures produces intense stress responses, thereby affecting survival, metabolism, immunity, and other life activities. Notably, the molecular mechanisms by which larval cuttlefish cope with high temperatures are not well understood. As such, in the present study, transcriptome sequencing of S. esculenta larvae was performed and 1,927 differentially expressed genes (DEGs) were identified. DEGs were subjected to functional enrichment analyses using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The top 20 terms of biological processes in GO and 20 high-temperature stress-related pathways in KEGG functional enrichment analysis were identified. A protein-protein interaction network was constructed to investigate the interaction between temperature stress-related genes. A total of 30 key genes with a high degree of participation in KEGG signaling pathways or protein-protein interactions were identified and subsequently validated using quantitative RT-PCR. Through a comprehensive analysis of the protein-protein interaction network and KEGG signaling pathway, the functions of three hub genes (HSP90AA1, PSMD6, and PSMA5), which belong to the heat shock protein family and proteasome, were explored. The present results can facilitate further understanding of the mechanism of high temperature resistance in invertebrates and provide a reference for the S. esculenta industry in the context of global warming.