bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD146+ mural cells from infantile hemangioma display proangiogenic ability and adipogenesis potential in vitro and in xenograft models
Authors: Chen Jialin , Chen Qianyi , Qiu Yajing , Chang Lei , Yu Zhang , Li Yuanbo , Chang Shih-jen , Chen Zongan , Lin Xiaoxi 
Published: April 2023

ObjectiveInfantile hemangioma (IH), the most common infantile vascular neoplasm, is uniquely characterized by rapid proliferation followed by slow spontaneous involution lasting for years. In IH lesions, perivascular cells are the most dynamic cell subset during the transition from the proliferation phase to the involution phase, and we aimed to systematically study this kind of cell.Methods and resultsCD146-selective microbeads were used to isolate IH-derived mural-like cells (HemMCs). Mesenchymal markers of HemMCs were detected by flow cytometry, and the multilineage differentiation potential of HemMCs was detected by specific staining after conditioned culture. CD146-selected nonendothelial cells from IH samples showed characteristics of mesenchymal stem cells with distinct angiogenesis-promoting effects detected by transcriptome sequencing. HemMCs spontaneously differentiated into adipocytes 2 weeks after implantation into immunodeficient mice, and almost all HemMCs had differentiated into adipocytes within 4 weeks. HemMCs could not be induced to differentiate into endothelial cells in vitro. However, 2 weeks after implantation in vivo, HemMCs in combination with human umbilical vein endothelial cells (HUVECs) formed GLUT1+ IH-like blood vessels, which spontaneously involuted into adipose tissue 4 weeks after implantation.ConclusionsIn conclusion, we identified a specific cell subset that not only showed behavior consistent with the evolution of IH but also recapitulated the unique course of IH. Thus, we speculate that proangiogenic HemMCs may be a potential target for the construction of hemangioma animal models and the study of IH pathogenesis.
Predictive value of intratumoral-metabolic heterogeneity derived from 18F-FDG PET/CT in distinguishing microsatellite instability status of colorectal carcinoma
Authors: Zhang Li , Liu Yu , Ding Ying , Deng Yinqian , Chen Huanyu , Hu Fan , Fan Jun , Lan Xiaoli , Cao Wei 
Published: April 2023

Purpose/backgroundMicrosatellite instability (MSI) status is a significant biomarker for the response to immune checkpoint inhibitors, response to 5-fluorouracil-based adjuvant chemotherapy, and prognosis in colorectal carcinoma (CRC). This study investigated the predictive value of intratumoral-metabolic heterogeneity (IMH) and conventional metabolic parameters derived from 18F-FDG PET/CT for MSI in patients with stage I–III CRC.MethodsThis study was a retrospective analysis of 152 CRC patients with pathologically proven MSI who underwent 18F-FDG PET/CT examination from January 2016 to May 2022. Intratumoral-metabolic heterogeneity (including heterogeneity index [HI] and heterogeneity factor [HF]) and conventional metabolic parameters (standardized uptake value [SUV], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) of the primary lesions were determined. MTV and SUVmean were calculated on the basis of the percentage threshold of SUVs at 30%–70%. TLG, HI, and HF were obtained on the basis of the above corresponding thresholds. MSI was determined by immunohistochemical evaluation. Differences in clinicopathologic and various metabolic parameters between MSI-High (MSI-H) and microsatellite stability (MSS) groups were assessed. Potential risk factors for MSI were assessed by logistic regression analyses and used for construction of the mathematical model. Area under the curve (AUC) were used to evaluate the predictive ability of factors for MSI.ResultsThis study included 88 patients with CRC in stages I–III, including 19 (21.6%) patients with MSI-H and 69 (78.4%) patients with MSS. Poor differentiation, mucinous component, and various metabolic parameters including MTV30%, MTV40%, MTV50%, and MTV60%, as well as HI50%, HI60%, HI70%, and HF in the MSI-H group were significantly higher than those in the MSS group (all P &lt; 0.05). In multivariate logistic regression analyses, post-standardized HI60% by Z-score (P = 0.037, OR: 2.107) and mucinous component (P &lt; 0.001, OR:11.394) were independently correlated with MSI. AUC of HI60% and our model of the HI60% + mucinous component was 0.685 and 0.850, respectively (P = 0.019), and the AUC of HI30% in predicting the mucinous component was 0.663.ConclusionsIntratumoral-metabolic heterogeneity derived from 18F-FDG PET/CT was higher in MSI-H CRC and predicted MSI in stage I–III CRC patients preoperatively. HI60% and mucinous component were independent risk factors for MSI. These findings provide new methods to predict the MSI and mucinous component for patients with CRC.
Radiotherapy or chemotherapy: a real-world study of the first-time relapsed and refractory primary central nervous system lymphoma
Authors: Yang Yu , Li Qing , Ma Jingjing , Kang Hui , Lin Zhiguang , Wang Yang , Ma Yan , Chen Bobin 
Published: April 2023

BackgroundPrimary central nervous system lymphoma (PCNSL) is an uncommon variant of non-Hodgkin lymphoma (NHL) with high aggressiveness and poor prognosis. Although complete remission (CR) could be achieved with therapy, some patients remain refractory or recurrently with a worse response to salvage treatment and poor prognosis. No consensus on rescue therapy has been established currently. This study is aimed to evaluate the efficacy of radiotherapy or chemotherapy in first-time relapsed or refractory progressed PCNSL (R/R PCNSL) and analysis the prognostic factors, to explore differences between relapsed and refractory PCNSL.MethodsTotally 105 R/R PCNSL patients from Huashan Hospital between 1 January 2016 and 31 December 2020 were enrolled, underwent salvage radiotherapy or chemotherapy and received response assessments after each course. PFS1 was defined as the time from diagnosis to the first time of recurrence or refractory progression. Statistical analysis was performed with SPSS version 26.0.ResultsResponse and survival were analyzed over a 17.5months (median) follow-up. Compared to relapsed PCNSL (n = 42), refractory PCNSL (n = 63) had a shorter median PFS1 related to deep lesions. 82.4% of cases were discovered as the second relapse or progression. ORR and PFS were both higher in relapsed PCNSL than those in refractory PCNSL. ORR of radiotherapy in both relapsed and refractory PCNSL was higher than that of chemotherapy. Elevated CSF protein and ocular involvement were related to PFS and OS after recurrence respectively in relapsed PCNSL. Age ≥ 60y was unfavorable to OS-R (OS after recurrence or progression) in refractory PCNSL.ConclusionsOur results indicate that relapsed PCNSL responds well to inducing and salvage therapy and has a better prognosis compared to refractory PCNSL. Radiotherapy is effective for PCNSL after the first relapse or progression. Age, CSF protein level, and ocular involvement could be potential factors to predict prognosis.
125I Radiotherapy combined with metronomic chemotherapy may boost the abscopal effect, leading to complete regression of liver metastasis in an SCLC patient with a 58.5-month OS: a case report
Authors: Lu Linlin , Wang Yu , Li Lei , Yu Lan , Liu Li , Qu Baozhen , Zhang Xiaotao 
Published: April 2023

The liver is the most common and lethal metastatic site in patients with extensive-stage small-cell lung cancer (ES-SCLC), and median survival with current standard treatment is only 9–10 months from diagnosis. Clinical observations show that a complete response (CR) is extremely rare in ES-SCLC patients with liver metastasis. Moreover, to the best of our knowledge, complete regression of liver metastasis induced by the abscopal effect, boosted primarily by permanent radioactive iodine-125 seeds implantation (PRISI), combined with a low-dose metronomic temozolomide (TMZ) regimen, has not been recorded. Here, we present the case of a 54-year-old male patient who developed multiple liver metastases from ES-SCLC after multiple lines of chemotherapy. The patient was given partial PRISI therapy (two out of six tumor lesions; 38 iodine-125 seeds in one dorsal lesion and 26 seeds in one ventral lesion), which was combined with TMZ metronomic chemotherapy (50 mg/m2/day, days 1–21, every 28 days). The abscopal effect was observed for 1 month after PRISI treatment. After about 1 year, all the liver metastases had completely disappeared, and the patient experienced no relapse. The patient eventually died of malnutrition caused by a non-tumor intestinal obstruction and had an overall survival of 58.5 months after diagnosis. PRISI combined with TMZ metronomic chemotherapy might be considered a potential therapy to trigger the abscopal effect in patients with liver metastases.
The molecular mechanism for inhibiting the growth of nasopharyngeal carcinoma cells using polymethoxyflavonoids purified from pericarp of Citrus reticulata ‘Chachi’ via HSCCC
Authors: Yang Wanling , Liang Yiyao , Liu Yujie , Chen Baizhong , Wang Kanghui , Chen Xiaojing , Yu Zhiqian , Yang Depo , Cai Yi , Zheng Guodong 
Published: April 2023

Polymethoxyflavonoids (PMFs), the main bioactive compounds naturally occurring in the pericarp of Citrus reticulata ‘Chachi’ (CRCP), possess significant antitumor action. However, the action of PMFs in nasopharyngeal carcinoma (NPC) is currently unknown. The present research study was conducted to investigate the inhibitory mechanisms of PMFs from CRCP on NPC growth in vivo and in vitro. In our research, we used high-speed counter-current chromatography (HSCCC) to separate four PMFs (nobiletin (NOB), 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), tangeretin (TGN), and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone (5-HPMF)) from CRCP. CCK-8 assay was used to preliminarily screen cell viability following exposure to the four PMFs. Colony formation, Hoechst-33258 staining, transwell, and wound scratch assays were performed to assess the anti-proliferation, invasion, migration, and apoptosis-inducing effects of HMF on NPC cells. NPC tumors in xenograft tumor transplantation experiments were also established to explore the effect of HMF (100 and 150 mg/kg/day) on NPC. The histopathological changes in the treated rats were observed by H&amp;E staining and Ki-67 detection by immunohistochemical techniques. The expressions of P70S6K, p-P70S6K, S6, p-S6, COX-2, p53, and p-p53 were measured by Western blot. The four PMFs were obtained with high purity (&gt;95.0%). The results of the preliminary screening by CCK-8 assay suggested that HMF had the strongest inhibitory effect on NPC cell growth. The results of the colony formation, Hoechst-33258 staining, transwell, and wound scratch assays indicated that HMF had significant anti-proliferation, invasion, migration, and apoptosis-inducing ability in NPC cells. Moreover, HMF suppressed NPC tumor growth in xenograft tumor transplantation experiments. Further investigation suggested that HMF regulated NPC cells proliferation, apoptosis, migration, and invasion by activating AMPK-dependent signaling pathways. In conclusion, HMF-induced AMPK activation inhibited NPC cell growth, invasion, and metastatic potency by downregulating the activation of the mTOR signaling pathway and COX-2 protein levels, as well as enhancing the p53 phosphorylation level. Our study provides a crucial experimental basis for the clinical treatment of NPC, as well as the development and utilization of PMFs from CRCP.
Heparanase-2 protein and peptides have a protective effect on experimental glomerulonephritis and diabetic nephropathy
Authors: Buijsers Baranca , Garsen Marjolein , de Graaf Mark , Bakker-van Bebber Marinka , Guo Chunming , Li Xue , van der Vlag Johan 
Published: April 2023

Introduction: The endothelial glycocalyx degrading enzyme heparanase-1 (HPSE1) is a major contributor to kidney diseases, such as glomerulonephritis and diabetic nephropathy. Therefore, inhibition of HPSE1 could be an interesting therapeutic strategy to treat glomerular diseases. A possible HPSE1 inhibitor is heparanase-2 (HPSE2) because HPSE2 is a structural homolog of HPSE1 without enzymatic activity. The importance of HPSE2 has been recently demonstrated in HPSE2-deficient mice, since these mice developed albuminuria and died within a few months after birth. We postulate that inhibition of HPSE1 activity by HPSE2 is a promising therapeutic strategy to target albuminuria and resulting renal failure.Methods: First, we evaluated the regulation of HPSE2 expression in anti-GBM and LPS-induced glomerulonephritis, streptozotocin-induced diabetic nephropathy, and adriamycin nephropathy by qPCR and ELISA. Second, we measured the HPSE1 inhibiting capacity of HPSE2 protein and 30 different HPSE2 peptides and assessed their therapeutic potential in both experimental glomerulonephritis and diabetic nephropathy using kidney function and cortical mRNA expression of HPSE1 and cytokines as outcome parameters.Results: HPSE2 expression was downregulated under inflammatory and diabetic conditions, whereas this effect on HPSE2 expression was absent with HPSE1 inhibition and in HPSE1-deficient mice. Both HPSE2 protein and a mixture of the three most potent HPSE1 inhibitory HPSE2 peptides could prevent LPS and streptozotocin induced kidney injury.Discussion: Taken together, our data suggest a protective effect of HPSE2 in (experimental) glomerular diseases and support the therapeutic potential of HPSE2 as HPSE1 inhibitor in glomerular diseases.
Individualized approach to elexacaftor/tezacaftor/ivacaftor dosing in cystic fibrosis, in response to self-reported anxiety and neurocognitive adverse events: A case series
Authors: Ibrahim Hisham , Danish Hammad , Morrissey David , Deasy Kevin F. , McCarthy Mairead , Dorgan James , Fleming Claire , Howlett Ciara , Twohig Sarah , Vagg Tamara , Murphy Desmond M. , Maher Michael , Plant Barry J. 
Published: April 2023

The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of −39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4–6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients’ preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.
An analysis of teachers’ instructions and feedback at a contemporary dance university
Authors: Soerel Benjamin F. , Plaatsman Larissa A. , Kegelaers Jolan , Stubbe Janine H. , van Rijn Rogier M. , Oudejans Raôul R. D. 
Published: April 2023

BackgroundGiven the demands posed by excessive practice quantities in modern dance, physical and mental health can be compromised. Therefore, there is a need to consider how quality of practice may be improved and possibly even reduce training times. Sports literature has shown that instructions and feedback given by coaches can have an effect on the quality of training and influence self-regulation and the performance of athletes. However, currently little is known about the use of instructions and feedback by dance teachers. The aim of the current study was, therefore, to examine the type of instructions and feedback given by dance teachers during various dance classes.MethodsA total of six dance teachers participated in this study. Video and audio recordings were made of six dance classes and two rehearsals at a contemporary dance university. The dance teacher’s coaching behavior was analyzed using the modified Coach Analysis and Intervention System (CAIS). Additionally, feedback and instructions were also examined in terms of their corresponding focus of attention. Absolute numbers, as well as times per minute (TPM) rates were calculated for each behavior before, during, and after an exercise. Absolute numbers were also used to calculate ratios of positive-negative feedback and open-closed questions.ResultsMost feedback comments were given after an exercise (472 out of 986 total observed behaviors). Improvisation had the highest positive-negative feedback ratio (29) and open-closed questions ratio (1.56). Out of the focus of attention comments, internal focus of attention comments were used most frequently (572 out of 900).Discussion/conclusionThe results make clear that there is a large variability in instructions and feedback over teachers and classes. Overall, there is room for improvement toward a higher positive-negative feedback ratio, a higher open-closed question ratio and producing more comments eliciting an external focus of attention.
Children’s total blindness as a risk factor for early parent-child relationships: preliminary findings from an Italian sample
Authors: Gui Anna , Perelli Debora , Rizzo Giulia , Ferruzza Emilia , Mercuriali Elena 
Published: April 2023

BackgroundVision provides crucial information for parent-child attunement that scaffolds social development from the first months of life. Congenital blindness might affect both parental wellbeing and children’s behavior during parent-child interaction. In this study, we compared families of young children with total versus partial blindness to understand the link between residual vision, parenting stress and perceived social support, and children’s behavior during parent-child interaction.MethodsParticipants were 42 white parents (21 fathers and 21 mothers) and their congenitally blind children (14 females, mean age = 14.81 months, SD = 10.46) with no co-occurring disability, recruited at the Robert Hollman Foundation rehabilitation centers in Italy. Parents’ scores on the Parenting Stress Index and Multidimensional Scale of Perceived Social Support questionnaires, as well as children’s behaviors signaling joint engagement during video-recorded episodes of parent-child interaction, were compared between the Total Blindness (TB,n= 12 children with no light perception or light perception in the dark but no quantifiable visual acuity) and Partial Blindness (PB,n= 9 children with a residual visual acuity below 3/60) groups.ResultsWe found that parents of TB children had higher parenting stress and lower perceived social support scores than parents of PB children. In fathers, total stress and stress linked to perceiving the child as difficult negatively correlated with perceived support from friends. There was no difference in the time TB and PB children spent displaying joint engagement behaviors during parent-child interaction. However, TB children directed their gaze and face less often toward their parents than PB children. We observed a trend of association between this behavior and maternal stress.ConclusionThese preliminary results suggest that the complete absence of vision from birth has adverse effects on stress linked to parenting and parental perceived social support. These findings support the importance of early family-centered interventions that extend to the parents’ communities and facilitate the parent-child dyad’s communication through non-visual behaviors. Replication is warranted in larger and more diverse samples.
A global scale COVID-19 variants time-series analysis across 48 countries
Authors: Chu Rachel Yui Ki , Szeto Kam Chiu , Wong Irene Oi Ling , Chung Pui Hong 
Published: April 2023

BackgroundThe coronavirus disease (COVID-19) pandemic is slowing down, and countries are discussing whether preventive measures have remained effective or not. This study aimed to investigate a particular property of the trend of COVID-19 that existed and if its variants of concern were cointegrated, determining its possible transformation into an endemic.MethodsBiweekly expected new cases by variants of COVID-19 for 48 countries from 02 May 2020 to 29 August 2022 were acquired from the GISAID database. While the case series was tested for homoscedasticity with the Breusch–Pagan test, seasonal decomposition was used to obtain a trend component of the biweekly global new case series. The percentage change of trend was then tested for zero-mean symmetry with the one-sample Wilcoxon signed rank test and zero-mean stationarity with the augmented Dickey–Fuller test to confirm a random COVID trend globally. Vector error correction models with the same seasonal adjustment were regressed to obtain a variant-cointegrated series for each country. They were tested by the augmented Dickey–Fuller test for stationarity to confirm a constant long-term stochastic intervariant interaction within the country.ResultsThe trend series of seasonality-adjusted global COVID-19 new cases was found to be heteroscedastic (p = 0.002), while its rate of change was indeterministic (p = 0.052) and stationary (p = 0.024). Seasonal cointegration relationships between expected new case series by variants were found in 37 out of 48 countries (p &lt; 0.05), reflecting a constant long-term stochastic trend in new case numbers contributed from different variants of concern within most countries.ConclusionOur results indicated that the new case long-term trends were random on a global scale and stable within most countries; therefore, the virus was unlikely to be eliminated but containable. Policymakers are currently in the process of adapting to the transformation of the pandemic into an endemic.