bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pituitary carcinoma - case series and review of the literature
Authors: Du Four Stephanie , Van Der Veken Jorn , Duerinck Johnny , Vermeulen Elle , Andreescu Corina E. , Bruneau Michael , Neyns Bart , Velthoven Van , Velkeniers Brigitte 
Published: September 2022

Although pituitary adenomas (PAs) account for 15% of intracranial tumors, pituitary carcinomas (PCs) are a rare entity. Most commonly, PCs evolve from aggressive PAs invading the surrounding structures and eventually leading to metastatic lesions. Due to the low incidence, the diagnosis and treatment remains challenging. We report a case series of five patients with pituitary carcinoma (PC) treated in our center. At first diagnosis 3 patients had an ACTH-producing adenoma, 1 a prolactinoma and 1 a double secreting adenoma (GH and prolactin). The mean time interval from initial diagnosis to diagnosis of PC was 10.7 years (range 5-20 years). All patients underwent multiple surgical resections and radiotherapy. Four patients were treated with temozolomide for metastatic disease. One patient with concomitant radiochemotherapy for local recurrence. Temozolomide led to a stable disease in 2 patients. One patient had a progressive disease after 9 cycles of temozolomide. In absence of standard treatment, immunotherapy was initiated, resulting in a stable disease.We report five cases of PCs. Three patients obtained a stable disease after tailored multidisciplinary treatment. Additionally, one patient was treated with immunotherapy, opening a new treatment option in PCs. Overall, PCs are rare intracranial neoplasms occurring several years after the initial diagnosis of aggressive PAs. Currently, the absence of predictive factors for an aggressive clinical course, provokes a challenging management.
Visceral adiposity measures are strongly associated with cardiovascular disease among female participants in Southwest China: A population-based prospective study
Authors: Wang Yingying , Zhao Xiaodeng , Chen Yun , Yao Yuntong , Zhang Yixia , Wang Na , Liu Tao , Fu Chaowei 
Published: September 2022

Background and aimsControversy remains regarding the prediction effects of different adiposity measure indicators for the risk of cardiovascular disease (CVD). Our study aimed to assess the associations of three traditional anthropometric indicators, namely, waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) as well as three non-traditional anthropometric indicators, namely, the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and body shape index (ABSI), with the risk of CVD among Southwest Chinese population.MethodsOur study was based on the Guizhou Population Health Cohort Study (GPHCS) conducted from 2010 to 2020. A total of 9,280 participants were recruited from 12 areas in Guizhou Province, China, from November 2010 to December 2012, and followed up for major chronic diseases until December 2020. A total of 7,837 individuals with valid data were included in this analysis. The gender-specific associations of WC, WHtR, BMI, CVAI, LAP, and ABSI with CVD were evaluated using Cox proportional hazards models. Receiver operating characteristic (ROC) curve analysis was used to estimate the prediction powers of different indicators for CVD.ResultsNo association of six indicators with CVD was observed among male participants. Female participants with either WC-based central obesity (HR: 1.82, 95% CI: 1.12–2.97) or WHtR-based central obesity (HR: 1.68, 95% CI: 1.07–2.64) had a higher risk of CVD, after adjusted for age, area, ethnic group, smoking, alcohol drinking, MET, previous history of diabetes, hypertension and dyslipidemia, medication use, and nutraceutical intake. Compared with female participants in the lowest quartile (Q1), those in the highest quartile (Q4) of WHtR (HR: 2.24, 95% CI: 1.17–4.27), CVAI (HR: 3.98, 95% CI: 1.87–8.49), and ABSI (HR: 1.94, 95% CI: 1.06–3.52) had an increased risk for incident CVD. CAVI showed the maximum predictive power of CVD with the biggest AUC of 0.687 (95% CI: 0.654–0.720) compared to other indicators in female participants.ConclusionsVisceral adiposity measures, especially CVAI, are stronger predictive indicators of CVD among female and not male participants in Southwest China. Different anthropometric indexes need to be combined to comprehensively assess health risks.
Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in Chinese with type 2 diabetes
Authors: Wang Zongyi , Tang Jiyang , Jin Enzhong , Ren Chi , Li Siying , Zhang Linqi , Zhong Yusheng , Cao Yu , Wang Jianmin , Zhou Wei , Zhao Mingwei , Huang Lvzhen , Qu Jinfeng 
Published: September 2022

PurposeTo identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical applicationMethodsThis case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups.ResultMean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA.ConclusionThis is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.
Human placenta-based genome-wide mRNA sequencing to identify TEK/IGF1/CSF1/ANGPT2 as crucial segments in the pathogenesis of pre-eclampsia
Authors: Wang Lifeng , Zhang Lin , Fan Yuqin , Peng Yanjie , Song Dandan , Fu Jinfeng , Wang Xietong 
Published: September 2022

Pre-eclampsia is a pregnancy-specific disease commonly occurring in late pregnancy and has always been threatening maternal and fetal lives, yet the etiology and pathogenesis of pre-eclampsia are still uncertain. To depict the overall changes of genes at the genome-wide level and identify potential biomarkers for early diagnosis of pre-eclampsia, we conducted this study by collecting placenta samples donated by six pregnancy women, among whom three healthy women were included as controls and three women were diagnosed with pre-eclampsia. The placental sample tissues were then subjected to high-throughput sequencing. Furthermore, we proceeded with bioinformatics analysis and formulated the hypothesis of pre-eclampsia development and verified the potential targets of pre-eclampsia by immunohistochemistry. Demographically, we found that the baseline characteristics of study subjects were highly homogeneous except for gestational weeks and blood pressure, where the blood pressure was higher and gestational weeks were shorter in the pre-eclampsia group (systolic blood pressure 123.33 ± 4.62 vs. 148.67 ± 3.79 mmHg, p = 0.046; diastolic blood pressure 79.00 ± 5.20 vs. 88.33 ± 2.89 mmHg, p = 0.068; gestational weeks 39.33 ± 1.03 vs. 35.76 ± 2.41, p = 0.050). Specific pathological changes were identified, shown as syncytial knots, fibrinoid necrosis, perivillous fibrin deposition, and vasculitis. For high-throughput sequencing, a total of 1,891 dysregulated genes were determined, of which 960 genes were downregulated and 931 genes were upregulated. The bioinformatics analysis indicated that these genes, with different molecular functions in different parts of cells, were primarily responsible for endothelium development and vascular process in the circulatory system, and more than 10 signaling pathways were involved. By focusing on the PI3K-Akt signaling pathway, Rap1 signaling pathway, and disease enrichment analysis item pre-eclampsia, TEK, CSF1, IGF1, and ANGPT2 were identified to promote the development of pre-eclampsia. After confirming the placental expression of these genes at the protein level, we proposed the pathogenesis of pre-eclampsia as follows: the downregulation of TEK, CSF1, IGF1, and ANGPT2 may inhibit trophoblast proliferation and affect the remodeling of spiral arteries, causing maternal and fetal malperfusion and impeding nutrient exchange, thereby leading to clinical manifestations of pre-eclampsia.
Exposure to salinity induces oxidative damage and changes in the expression of genes related to appetite regulation in Nile tilapia (Oreochromis niloticus)
Authors: Martins Amanda W. S. , Dellagostin Eduardo N. , Blödorn Eduardo B. , Silveira Tony Leandro R. , Sampaio Luis A. , Komninou Eliza R. , Varela Junior Antonio S. , Corcini Carine D. , Nunes Leandro S. , Remião Mariana H. , Collares Gilberto L. , Domingues William B. , Campos Vinicius F. 
Published: September 2022

Variations in water salinity and other extrinsic factors have been shown to induce changes in feeding rhythms and growth in fish. However, it is unknown whether appetite-related hormones mediate these changes in Nile tilapia (Oreochromis niloticus), an important species for aquaculture in several countries. This study aimed to evaluate the expression of genes responsible for appetite regulation and genes related to metabolic and physiological changes in tilapia exposed to different salinities. Moreover, the study proposed to sequence and to characterize the cart, cck, and pyy genes, and to quantify their expression in the brain and intestine of the fish by quantitative polymerase chain reaction (qPCR). The animals were exposed to three salinities: 0, 6, and 12 parts per thousand (ppt) of salt for 21 days. Furthermore, lipid peroxidation, reactive oxygen species, DNA damage, and membrane fluidity in blood cells were quantified by flow cytometry. The results indicated an increased expression of cart, pyy, and cck and a decreased expression of npy in the brain, and the same with cck and npy in the intestine of fish treated with 12 ppt. This modulation and other adaptive responses may have contributed to the decrease in weight gain, specific growth rate, and final weight. In addition, we showed oxidative damage in blood cells resulting from increasing salinity. These results provide essential data on O. niloticus when exposed to high salinities that have never been described before and generate knowledge necessary for developing biotechnologies that may help improve the production of economically important farmed fish.
The regulatory roles of T helper cells in distinct extracellular matrix characterization in breast cancer
Authors: Tian Qi , Gao Huan , Ma Yingying , Zhu Lizhe , Zhou Yan , Shen Yanwei , Wang Bo 
Published: September 2022

BackgroundTumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The ECM has been recognized as an important determinant of breast cancer progression and prognosis. Recent studies have revealed a strong link between ECM remodeling and immune cell infiltration in a variety of tumor types. However, the landscape and specific regulatory mechanisms between ECM and immune microenvironment in breast cancer have not been fully understood.MethodsUsing genomic data and clinical information of breast cancer patients obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted an extensive multi-omics analysis to explore the heterogeneity and prognostic significance of the ECM microenvironment. Masson and Sirius red staining were applied to quantify the contents of collagen in the ECM microenvironment. Tissue immunofluorescence (IF) staining was applied to identify T helper (Th) cells.ResultsWe classified breast cancer patients into two ECM-clusters and three gene-clusters by consensus clustering. Significant heterogeneity in prognosis and immune cell infiltration have been found in these distinct clusters. Specifically, in the ECM-cluster with better prognosis, the expression levels of Th2 and regulatory T (Treg) cells were reduced, while the Th1, Th17 and T follicular helper (Tfh) cells-associated activities were significantly enhanced. The correlations between ECM characteristics and Th cells infiltration were then validated by clinical tissue samples from our hospital. The ECM-associated prognostic model was then constructed by 10 core prognostic genes and stratified breast cancer patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of breast cancer patients in the high-risk group was significantly worse than that of the low-risk group. The risk scores for breast cancer patients obtained from our prognostic model were further confirmed to be associated with immune cell infiltration, tumor mutation burden (TMB) and stem cell indexes. Finally, the half-maximal inhibitory concentration (IC50) values of antitumor agents for patients in different risk groups were calculated to provide references for therapy targeting distinct ECM characteristics.ConclusionOur findings identify a novel strategy for breast cancer subtyping based on the ECM characterization and reveal the regulatory roles of Th cells in ECM remodeling. Targeting ECM remodeling and Th cells hold potential to be a therapeutic alternative for breast cancer in the future.
Benzodiazepines and Z-hypnotics consumption in long-COVID-19 patients: Gender differences and associated factors
Authors: Carrasco-Garrido Pilar , Fernández-de-Las-Peñas Cesar , Hernández-Barrera Valentín , Palacios-Ceña Domingo , Jiménez-Trujillo Isabel , Gallardo-Pino Carmen 
Published: September 2022

BackgroundPsychotropic drug consumption has increased during the COVID-19 pandemic. We describe here the prevalence and identifying factors associated with Benzodiazepine (BZD) and Z-hypnotics use among a sample of Spanish adults suffering from long-COVID-19 syndrome, from a gender perspective.Materials and methodsData were anonymously collected between 15th December 2021 and 15th March 2022. The collection form consisted of several questions gathering sociodemographic information, post-COVID symptom, health profile, and pharmacological drug intake. Using logistic multivariate regression models, we estimated the independent effect of each of these variables on self-medicated consumption. Three models were generated (female, male, and both gender).ResultsPrevalence of BZD and Z-hypnotics use was 44.9% (46.5% for women; 37.8% for men). Zolpidem was the most consumed drug among male (20.7%), and lorazepam in female (31.1%). Patterns of drug consumption among female were related with number of post-COVID symptoms and smoking habit (AOR 2.76, 95%CI 1.16–6.52). Males under 40 years of age are more likely to consume BZD and Z-hypnotics (AOR 5.52, 95%CI 1.08–28.27).ConclusionThe prevalence of consumption of BZD and Z-hypnotics in those subjects with long-COVID-19 in our study reaches values of 44.9%. Women with long-COVID-19 declare a higher prevalence of consumption than men. Predictors of BZD and Z-hypnotic in men were, age and number of medication use. Smoking habit and the number of post-COVID symptoms were predictive variables in women.
Perceptions and experiences of undergraduate pharmacy students and alumni toward research after exposure to undergraduate research courses
Authors: Mukhalalati Banan , Elshami Sara , Adlan Ola , Elshazly Marwa , Awaisu Ahmed , Stewart Derek , Al-Badriyeh Daoud , Alali Feras 
Published: September 2022

IntroductionAcademic institutions have a duty to equip health professional students with the requisite research skills to ensure the implementation of evidence-based practice. This study aims to determine the perceptions of pharmacy students and alumni toward research after completing Undergraduate Research in Pharmacy Courses (URPCs) at the College of Pharmacy–Qatar University (CPH–QU).MethodsA cross-sectional survey was conducted. All CPH-QU alumni (n = 238), and all third- and fourth-year professional students who had completed at least one URPC at the time of conducting the study (n = 42) were approached. The questionnaire contained items relating to research experience and perceptions of significance, confidence in conducting research, actual and anticipated outcomes, and motivation for future research. A Theoretical Domains Framework informed the development of selected items.ResultsThe response rate was 72.1% (202/280); however, the usable rate was 95.5% (193/202). The participants gave positive responses relating to their perceptions of research significance {Median = 5.0 [Interquartile range (IQR) = 1.0], Minimum–Maximum = 1–5}, confidence in conducting research [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5], actual and anticipated outcomes [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5], and motivation for future research plans [Median = 4.0 (IQR = 1.0), Minimum–Maximum = 1–5]. The majority of participants perceived non-confidence in using data analysis software [72 (39.4% non-confidence)] and a high proportion of participants were non-confident in conducting data analysis [45 (24.6% non-confidence)]. More than half reported publishing at least one peer-reviewed article [99 (54.4% agreement)] from their courses and were highly motivated to consider post-graduate degrees in pharmacy [132 (73.3% agreement)].ConclusionsIncorporating URPCs into CPH–QU curriculum has potentially improved students and alumni's perceptions of research. Action is needed to improve confidence in different aspects of research.
Frontal lobe hemodynamics detected by functional near-infrared spectroscopy during head-up tilt table tests in patients with electrical burns
Authors: Kim Yoo Hwan , Kim Youngmin , Yoon Jaechul , Cho Yong Suk , Kym Dohern , Hur Jun , Chun Wook , Kim Byung-Jo 
Published: September 2022

SignificanceElectrical burns can cause severe damage to the nervous system, resulting in autonomic dysfunction with reduced cerebral perfusion. However, few studies have investigated these consequences.AimTo elucidate changes in prefrontal cerebral hemodynamics using functional near-infrared spectroscopy (fNIRS) during the head-up tilt table test (HUT) for patients with electrical burns.ApproachWe recruited 17 patients with acute electrical burns within 1 week after their accidents and 10 healthy volunteers. The NIRS parameters acquired using an fNIRS device attached to the forehead were analyzed in five distinct HUT phases.ResultsBased on their HUT response patterns, patients with electrical burns were classified into the group with abnormal HUT results (APG, n = 4) or normal HUT results (NPG, n = 13) and compared with the healthy control (HC, n = 10) participants. We found trends in hemodynamic changes during the HUT that distinguished HC, NPG, and APG. Reduced cerebral perfusion and decreased blood oxygenation during the HUT were found in both the NPG and APG groups. Patients with electrical burns had autonomic dysfunction compared to the HC participants.ConclusionsUsing fNIRS, we observed that acute-stage electrical burn injuries could affect cerebral perfusion.
The learning-relative hemodynamic modulation of cortical plasticity induced by a force-control motor training
Authors: Wang Yongrong , Feng Shuai , Yang Rui , Hou Wensheng , Wu Xiaoying , Chen Lin 
Published: September 2022

BackgroundNovel motor skills are generally acquired through repetitive practices which are believed to be strongly related to neural plasticity mechanisms. This study aimed to investigate the learning-relative hemodynamic modulation of cortical plasticity induced by long-term motor training.MethodsAn 8-day participation-control program was conducted. Eighteen right-handed healthy participants were recruited and randomly assigned into the training (12) and control groups (6). The training group were arranged to undergo the 8-day block-designed motor training which required to repeat a visuomotor force-control task. The functional near-infrared spectroscopy (fNIRS) was used to continuously monitor the cortical hemodynamic response during training. Two transcranial magnetic stimulation (TMS) measurements were performed before and after training to evaluate the cortical excitability changes. The transfer effects of learning were also investigated.ResultsThe behavior performance was quantified via score execution accuracy to illustrate the fast/slow learning stages as experience cumulated. The cortical hemodynamic activations mapped by fNIRS exhibited a temporal evolution trends that agreed the expansion–renormalization model, which assumed the brain modulation against skill acquisition includes complex mechanisms of neural expansion, selection, and renormalization. Functional connectivity (FC) analysis showed the FC strength was maintained, while the measured homodynamic activation returned to baseline after certain level of skill acquisition. Furthermore, the TMS results demonstrated a significant increase of motor evoked potential (MEP) on the targeted muscle for the trained participants, who significantly outperformed the untrained subjects in learning transfer investigation.ConclusionThe study illustrated the expansion–renormalization trends during continuous motor training, and relative analysis showed the functional connectivity enhancement may be maintained after amplitude renormalization of cortical hemodynamic activations. The TMS findings further gave an implication of neural facilitations on the descending motor pathway when brain activation returned to renormalization status after certain level of learning stages was achieved, and the learning can transfer to enhance the performance while encountering similar tasks.