bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhythmic oscillations in the midbrain dopaminergic nuclei in mice
Authors: Oberto Virginie J. , Matsumoto Jumpei , Pompili Marco N. , Todorova Ralitsa , Papaleo Francesco , Nishijo Hisao , Venance Laurent , Vandecasteele Marie , Wiener Sidney I. 
Published: June 2023

IntroductionDopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates.MethodsWe recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks.ResultsRayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1–2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals.DiscussionThese data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.
The growing burden of generalized myasthenia gravis: a population-based retrospective cohort study in Taiwan
Authors: Herr Keira Joann , Shen Shih-Pei , Liu Yanfang , Yang Chih-Chao , Tang Chao-Hsiun 
Published: June 2023

BackgroundThe prevalence of myasthenia gravis is increasing in many countries, including Asia. As treatment options expand, population-based information about the disease burden can inform health technology assessments.MethodsWe conducted a population-based retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to describe the epidemiology, disease burden and treatment patterns of generalized myasthenia gravis (gMG) from 2009 to 2019. Episodes of hepatitis B virus (HBV) infection or reactivation were explored.ResultsThe number of patients with gMG increased from 1,576 in 2009 to 2,638 in 2019 and the mean (standard deviation) age from 51.63 (17.32) to 55.38 (16.29) years. The female:male ratio was 1.3:1. Frequently reported co-morbidities were hypertension (32–34% of patients), diabetes mellitus (16–21%) and malignancies (12–17%). The prevalence of patients with gMG increased annually from 6.83/100,000 population in 2009 to 11.18/100,000 population in 2019 (p &lt; 0.0001). There was no temporal trend in all-cause fatality rates (range 2.76–3.79/100 patients annually) or gMG incidence rates (2.4–3.17/100,000 population annually). First-line treatment was with pyridostigmine (82%), steroids (58%), and azathioprine (11%). There was minimal change in treatment patterns over time. Among 147 new HBV infections, 32 (22%) received ≥4 weeks of antiviral therapy suggesting chronic infection. The HBV reactivation rate was 7.2%.ConclusionThe epidemiology of gMG in Taiwan is evolving rapidly, with higher prevalence rates and increasing involvement of older age-groups suggesting a growing burden of disease and associated healthcare costs. HBV infection or reactivation may pose a previously unrecognized recognized risk for patients with gMG receiving immunosuppressants.
Dose-dependent effects of GAT107, a novel allosteric agonist-positive allosteric modulator (ago-PAM) for the α7 nicotinic cholinergic receptor: a BOLD phMRI and connectivity study on awake rats
Authors: Brems Brittany M. , Sullivan Erin E. , Connolly Jenna G. , Zhang Jingchun , Chang Arnold , Ortiz Richard , Cantwell Lucas , Kulkarni Praveen , Thakur Ganesh A. , Ferris Craig F. 
Published: June 2023

BackgroundAlpha 7 nicotinic acetylcholine receptor (α7nAChR) agonists have been developed to treat schizophrenia but failed in clinical trials due to rapid desensitization. GAT107, a type 2 allosteric agonist-positive allosteric modulator (ago-PAM) to the α7 nAChR was designed to activate the α7 nAChR while reducing desensitization. We hypothesized GAT107 would alter the activity of thalamocortical neural circuitry associated with cognition, emotion, and sensory perception.MethodsThe present study used pharmacological magnetic resonance imaging (phMRI) to evaluate the dose-dependent effect of GAT107 on brain activity in awake male rats. Rats were given a vehicle or one of three different doses of GAT107 (1, 3, and 10 mg/kg) during a 35 min scanning session. Changes in BOLD signal and resting state functional connectivity were evaluated and analyzed using a rat 3D MRI atlas with 173 brain areas.ResultsGAT107 presented with an inverted-U dose response curve with the 3 mg/kg dose having the greatest effect on the positive BOLD volume of activation. The primary somatosensory cortex, prefrontal cortex, thalamus, and basal ganglia, particularly areas with efferent connections from the midbrain dopaminergic system were activated as compared to vehicle. The hippocampus, hypothalamus, amygdala, brainstem, and cerebellum showed little activation. Forty-five min post treatment with GAT107, data for resting state functional connectivity were acquired and showed a global decrease in connectivity as compared to vehicle.DiscussionGAT107 activated specific brain regions involved in cognitive control, motivation, and sensory perception using a BOLD provocation imaging protocol. However, when analyzed for resting state functional connectivity there was an inexplicable, general decrease in connectivity across all brain areas.
Physicochemical, technofunctional, in vitro antioxidant, and in situ muscle protein synthesis properties of a sprat (Sprattus sprattus) protein hydrolysate
Authors: Shekoohi Niloofar , Naik Azza Silotry , Amigo-Benavent Miryam , Harnedy-Rothwell Pádraigín A. , Carson Brian P. , FitzGerald Richard J. 
Published: June 2023

IntroductionSprat (Sprattus sprattus) is an underutilized fish species that may act as an economic and sustainable alternative source of protein due to its good amino acid (AA) profile along with its potential to act as a source of multiple bioactive peptide sequences.Method and resultsThis study characterized the physicochemical, technofunctional, and in vitro antioxidant properties along with the AA profile and score of a sprat protein enzymatic hydrolysate (SPH). Furthermore, the impact of the SPH on the growth, proliferation, and muscle protein synthesis (MPS) in skeletal muscle (C2C12) myotubes was examined. The SPH displayed good solubility and emulsion stabilization properties containing all essential and non-essential AAs. Limited additional hydrolysis was observed following in vitro-simulated gastrointestinal digestion (SGID) of the SPH. The SGID-treated SPH (SPH-SGID) displayed in vitro oxygen radical antioxidant capacity (ORAC) activity (549.42 μmol TE/g sample) and the ability to reduce (68%) reactive oxygen species (ROS) production in C2C12 myotubes. Muscle growth and myotube thickness were analyzed using an xCELLigence™ platform in C2C12 myotubes treated with 1 mg protein equivalent.mL−1 of SPH-SGID for 4 h. Anabolic signaling (phosphorylation of mTOR, rpS6, and 4E-BP1) and MPS (measured by puromycin incorporation) were assessed using immunoblotting. SPH-SGID significantly increased myotube thickness (p &lt; 0.0001) compared to the negative control (cells grown in AA and serum-free medium). MPS was also significantly higher after incubation with SPH-SGID compared with the negative control (p &lt; 0.05).ConclusionsThese preliminary in situ results indicate that SPH may have the ability to promote muscle enhancement. In vivo human studies are required to verify these findings.
Perioperative nutritional risk and its influencing factors in patients with oral cancer: a longitudinal study
Authors: Wang Guifen , Ou Meijun , Chen Hong , Zhu Shujuan , Chen Yongyi , Xu Xianghua 
Published: June 2023

IntroductionWe aimed to investigate the nutritional risk status and dynamic changes in patients with perioperative oral cancer at different stages and analyze the factors influencing nutritional risk and the correlation among body mass index, nutrition-related symptoms, and nutritional risk.MethodsIn total, 198 patients with oral cancer who were hospitalized in the Head &amp; Neck Surgery Departments of a tertiary cancer hospital in Hunan Province, China, from May 2020 to January 2021, were selected as participants. The Nutritional Risk Screening 2002 scale and Head and Neck Patient Symptom Checklist were used to assess patients on admission day, 7 days post-surgery, and 1 month post-discharge. Multivariate analysis of variance, paired t-test, and generalized estimating equation were used to analyze the trajectory and influencing factors of nutritional risk in patients with perioperative oral cancer. Spearman’s correlation analysis was used to explore the correlation among body mass index, symptoms, and nutritional risk.ResultsThe nutritional risk scores of patients with oral cancer at the three time points were 2.30 ± 0.84, 3.21 ± 0.94, and 2.11 ± 0.84, respectively, and the differences were significant (p &lt; 0.05). The incidences of nutritional risk were 30.3, 52.5, and 37.9%, respectively. The factors influencing nutritional risk included education level, smoking status, clinical stage, flap repair, and tracheotomy (β = −0.326, 0.386, 0.387, 0.336, and 0.240, respectively, p &lt; 0.05). Nutritional risk was negatively correlated with body mass index (rs = −0.455, p &lt; 0.01) and positively correlated with pain, loss of appetite, sore mouth, bothersome smells, swallowing difficulty, taste changes, depression, chewing difficulty, thick saliva, and anxiety (rs = 0.252, 0.179, 0.269, 0.155, 0.252, 0.212, 0.244, 0.384, 0.260, and 0.157, respectively, p &lt; 0.05).ConclusionThe incidence of nutritional risk in patients with perioperative oral cancer was high, and the trajectory of nutritional risk changed over time. Strengthening the nutritional monitoring and management of postoperative patients or those with low education level, advanced-stage cancer, flap repair, tracheotomy, and low body mass index; strengthening tobacco control management; and controlling nutrition-related discomfort symptoms in perioperative oral cancer patients are necessary.
Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution
Authors: Liu Jun , Ji Yaxin , Weng Xiaodan , Shao Wei , Zhao Jiaping , Chen Hanlin , Shen Lu , Wang Fufeng , Meng Qi , Wu Xue , Wang Xiaonan , Ou Qiuxiang , Ke Honggang 
Published: June 2023

BackgroundLung cancer is the deadliest and most diagnosed type of cancer worldwide. The 5-year survival rate of lung adenocarcinoma (LUAD) dropped significantly when tumor stages advanced. Patients who received surgically resecting at the pre-invasive stage had a 5-year survival rate of nearly 100%. However, the study on the differences in gene expression profiles and immune microenvironment among pre-invasive LUAD patients is still lacking.MethodsIn this study, the gene expression profiles of three pre-invasive LUAD stages were compared using the RNA-sequencing data of 10 adenocarcinoma in situ (AIS) samples, 12 minimally invasive adenocarcinoma (MIA) samples, and 10 invasive adenocarcinoma (IAC) samples.ResultsThe high expression levels of PTGFRN (Hazard Ratio [HR] = 1.45; 95% Confidence Interval [CI]: 1.08-1.94; log-rank P = 0.013) and SPP1 (HR = 1.44; 95% CI: 1.07-1.93; log-rank P = 0.015) were identified to be associated with LUAD prognosis. Moreover, the early LUAD invasion was accompanied by the enhancement of antigen presentation ability, reflected by the increase of myeloid dendritic cells infiltration rate (Cuzick test P &lt; 0.01) and the upregulation of seven important genes participating in the antigen presentation, including HLA-A (Cuzick test P = 0.03), MICA (Cuzick test P = 0.01), MICB (Cuzick test P = 0.01), HLA-DPA1 (Cuzick test P = 0.04), HLA-DQA2 (Cuzick test P &lt; 0.01), HLA-DQB1 (Cuzick test P = 0.03), and HLA-DQB2 (Cuzick test P &lt; 0.01). However, the tumor-killing ability of the immune system was inhibited during this process, as there were no rising cytotoxic T cell activity (Cuzick test P = 0.20) and no increasing expression in genes encoding cytotoxic proteins. ConclusionIn all, our research elucidated the changes in the immune microenvironment during early-stage LUAD evolution and may provide a theoretical basis for developing novel early-stage lung cancer therapeutic targets.
Concordance between microsatellite instability and mismatch repair protein expression in colorectal cancer and their clinicopathological characteristics: a retrospective analysis of 502 cases
Authors: Ye Meihua , Ru Guoqing , Yuan Hang , Qian Lili , He Xianglei , Li Shuangshuang 
Published: June 2023

Microsatellite instability (MSI) is one of the hallmarks of colorectal cancer (CRC). Mismatch repair (MMR) protein expression may reflect MSI status. To analyze the concordance between MSI and MMR expression in CRC and their clinicopathological characteristics, 502 CRC patients were retrospectively collected in this study. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was used to measure MSI, and MMR expression was determined by immunohistochemistry (IHC). The causes of non-concordance were analyzed. Chi-square test was used to find the correlation between MSI and various clinicopathological parameters. PCR-CE results showed 64 (12.7%) patients had high microsatellite instability (MSI-H); low microsatellite instability (MSI-L) and microsatellite stable (MSS) cases were 19 (3.8%)and 419 (83.5%), respectively. With regard to IHC, 430 (85.7%) showed proficient mismatch repair (pMMR) and 72 (14.3%) showed deficient mismatch repair (dMMR). The coincidence rate of MSI and MMR expression in CRC was 98.4% (494/502), with good concordance (Kappa = 0.932). Using PCR-CE as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of IHC were 100%, 98.2%, 88.9%, and 100%, respectively. MSI-H was more common in women, right colon, tumors ≥ 5 cm, ulcerative type, mucinous adenocarcinoma, poor differentiation, T stage I/II, and without lymph node or distant metastasis for CRC patients. In summary, MSI exhibited some typical clinicopathological characteristics. MSI and MMR expression in CRC had good concordance. However, it is still extremely necessary to perform PCR-CE. We recommend that testing packages of different sizes should be developed in clinical practice to create a testing echelon, to facilitate comprehensive selection according to experimental conditions, clinical diagnosis, and treatment needs.
Integrated gut microbiota and metabolome analysis reveals the mechanism of Xiaoai Jiedu recipe in ameliorating colorectal cancer
Authors: Qiu Wenli , Xie Hui , Chen Haibin , Zhou Hongli , Wang Zhongqiu , Zhou Hongguang 
Published: June 2023

IntroductionXiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action.MethodsWe investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson’s correlation analysis.ResultsXJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)−HpETE, DL−Arginine, and Lysopc 18:2, which was different from the beneficial bacteria.DiscussionThe regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.
Ureteral dilation recovery after intravesical reimplantation in children with primary obstructive megaureter
Authors: He Yan , Wu Xuemin , Xu Yingrui , Liu Zhaoquan , Du Guoqiang , Wu Xiangyu , Liu Wei , Wu Rongde 
Published: June 2023

BackgroundTo observe the postoperative recovery following ureteral dilation in primary obstructive megaureter (POM) after ureteral implantation, and evaluate the risk factors affecting ureter diameter resolution.Materials and MethodsA retrospective study was performed in patients with POM who underwent ureteral reimplantation using the Cohen procedure. Patient characteristics, perioperative parameters, and postoperative outcomes were also analysed. A widest ureteral diameter of &lt;7 mm was defined as a normal shape and outcome. Survival time was defined as the time from surgery to ureteral dilation recovery or to the last follow-up.ResultsA total of 49 patients (54 ureters) were included in the analysis. The survival time ranged from 1 to 53 months. The shapes of a total of 47 (87.04%) megaureters recovered, and most (29/47) resolutions happened within 6 months after surgery. In the univariate analysis, bilateral ureterovesical reimplantation (p = 0.015), ureteral terminal tapering (p = 0.019), weight (p = 0.036), and age (p = 0.015) were associated with the recovery time of ureteral dilation. A delayed recovery of ureteral diameter was noted in bilateral reimplantation (HR = 0.336, p = 0.017) using multivariate Cox regression.ConclusionsUreteral dilation in POM mostly returned to normal within six postoperative months. Moreover, bilateral ureterovesical reimplantation is a risk factor for delayed postoperative recovery of ureter dilation in POM.
Impact of the 2017 AAP clinical guideline on the prevalence of high blood pressure among adolescents in Lagos, Nigeria
Authors: Atoh Ifeoma , Ezeogu Joseph , Ekure Ekanem , Omokhodion Samuel Ilenre , Njokanma Fidelis Olisamedua 
Published: June 2023

IntroductionAdolescent high blood pressure (HBP) can lead to several end-organ complications if it continues into adulthood. The 2017 AAP Guideline has lower blood pressure cut-off points and consequently leads to the identification of more people with high blood pressure. This study evaluated the impact of the 2017 American Academy of Pediatrics (AAP) Clinical Guideline on the prevalence of high blood pressure among adolescents when compared to the 2004 Fourth Report.MethodologyA descriptive cross-sectional study was conducted from August 2020 to December 2020. The selection of 1,490 students, 10–19 years old, was by a two-stage sampling technique. Socio-demographic information and relevant clinical data were obtained using a structured questionnaire. Blood pressure was measured according to standard protocol. Categorical and numerical variables were summarized using frequency, percentages, mean, and standard deviation. The McNemar-Bowker test of symmetry was used to compare the blood pressure values in the 2004 Fourth Report and the 2017 AAP Clinical Guideline. The Kappa statistic was used to test for the degree of agreement between the 2004 Fourth Report and the 2017 AAP Clinical Guideline.ResultsThe prevalence rates of high blood pressure, elevated blood pressure, and hypertension among adolescents were 26.7%, 13.8%, and 12.9%, respectively, using the 2017 AAP Clinical Guideline, and 14.5%, 6.1%, and 8.4%, respectively, using the 2004 Fourth Report. The degree of agreement between the 2004 and 2017 guidelines with respect to the classification of blood pressure was 84.8%. The Kappa statistic was 0.71 (CI: 0.67–0.75). The impact of this was a 12.2%, 7.7%, and 4.5% increase in the prevalence of high blood pressure, elevated blood pressure, and hypertension, respectively, using the 2017 AAP Clinical Guideline.ConclusionThe 2017 AAP Clinical Guideline detects a greater proportion of high blood pressure among adolescents. The adoption of this new guideline in clinical practice and its use in the routine screening of high blood pressure among adolescents is recommended.
Characteristics and risk factors for spontaneous and postoperative consecutive exotropia in children with esotropia
Authors: Wen Jing , Li Ruiying , Li Ruoshi , Li Xiaoqing , Zhu Dehai 
Published: June 2023

BackgroundTo investigate the risk factors for the development of consecutive exotropia (CXT) by comparing patients with spontaneous or postoperative CXT during follow-up with another group of patients who had no deviation or less than 10 prism dioptre (PD) esotropia.MethodsIn this retrospective cohort study, 6 patients with spontaneous CXT (group A), 13 patients with postoperative CXT (group B), and 39 patients with no exotropia (group C) were enrolled. Probable risk factors for CXT were evaluated among the groups. Kruskal-Wallis H test was used to determine if any significant differences were present among the groups. Fisher’s exact test or Mann-Whitney U test was used for univariate analyses to compare differences between case groups or between case and control groups. The Bonferroni method was used to conduct multiple comparisons.ResultsThe follow-up period of spontaneous CXT patients was significantly longer than that of postoperative CXT and nonconsecutive exotropia patients (p = 0.035 and p &lt; 0.001, respectively). The interval between alignment and CXT onset in spontaneous CXT patients was slightly longer than that in postoperative CXT patients, but not significantly difference (6.50 vs. 5.00 years, p = 0.072). Vertical deviation was associated with a high risk of postoperative CXT (p = 0.001). Most [38 (97.44%)] nonconsecutive exotropia patients had fusion; conversely, the absence of fusion function (p &lt; 0.001) as well as stereoacuity (p = 0.029) were associated with a high risk of CXT.ConclusionVertical deviation and poor binocular function are strongly associated with a high risk of CXT. Children with spontaneous CXT are highly recommended to be followed-up long-term, while they maintain long-term ocular alignment before developing consecutive exotropia from comitant esotropia (CE).