bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of neuro-optometric visual rehabilitation therapy in patients with visual snow syndrome
Authors: Tsang Terry , Shidlofsky Charles , Mora Vanessa 
Published: December 2022

ObjectiveThis study intends to evaluate the feasibility of Neuro-Optometric Rehabilitation Therapy (NORT) to treat Visual Snow Syndrome (VSS). This pilot study utilized the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) to assess quality of life (QOL) before and after treatment.MethodsTwenty-one participants were recruited as successive intake patients diagnosed with VSS at the clinics of Dr. Terry Tsang Optometry, Inc and Neuro-Vision Associates of North Texas. Participants completed the NEI Visual Function Questionnaire 25-2000 edition and performed NORT, conducted by a neuro-optometrist or a qualified vision therapist. The NEI-VFQ-25 was administered before, at 6 weeks, and at 12 weeks of NORT to evaluate the effects of treatment on patient QOL.ResultsThe participants demonstrated an improvement in QOL composite and subscale scores after 6 and 12 weeks of NORT treatment. The NEI-VFQ-25 composite scores from the pre-test (M = 68, SD = 18) and at 6 weeks of treatment (M = 75, SD = 17) indicate an improvement in QOL [t (20) = 4.0, p = 0.0007]. The NEI-VFQ-25 composite scores from pretest to 12 weeks of treatment showed further improvements. This trend of improvement on NEI-VFQ-25 composite scores continued into the 12th week (M = 77, SD = 17) of treatment [t (20) = 4.5, p = 0.0002]. The subscales of general vision, distance activities, near activities, social functioning, mental health, role difficulties and dependency also showed improvement.ConclusionOur results suggest that patients with VSS experience improvement in QOL in as little as 6 weeks, with further improvement by 12 weeks of NORT. This suggests NORT is an effective treatment option for managing the condition and improving QOL in patients with VSS, although a reduction in specific symptoms has yet to be demonstrated. This study provides justification that NORT warrants further investigation on VSS symptom reduction.
The novel subclusters based on cancer-associated fibroblast for pancreatic adenocarcinoma
Authors: Zhao Guojie , Wang Changjing , Jiao Jian , Zhang Wei , Yang Hongwei 
Published: December 2022

IntroductionPancreatic adenocarcinoma (PAAD) is a fatal disease characterized by promoting connective tissue proliferation in the stroma. Activated cancer-associated fibroblasts (CAFs) play a key role in fibrogenesis in PAAD. CAF-based tumor typing of PAAD has not been explored.MethodsWe extracted single-cell sequence transcriptomic data from GSE154778 and CRA001160 datasets from Gene Expression Omnibus or Tumor Immune Single-cell Hub to collect CAFs in PAAD. On the basis of Seurat packages and new algorithms in machine learning, CAF-related subtypes and their top genes for PAAD were analyzed and visualized. We used CellChat package to perform cell–cell communication analysis. In addition, we carried out functional enrichment analysis based on clusterProfiler package. Finally, we explored the prognostic and immunotherapeutic value of these CAF-related subtypes for PAAD.ResultsCAFs were divided into five new subclusters (CAF-C0, CAF-C1, CAF-C2, CAF-C3, and CAF-C4) based on their marker genes. The five CAF subclusters exhibited distinct signaling patterns, immune status, metabolism features, and enrichment pathways and validated in the pan-cancer datasets. In addition, we found that both CAF-C2 and CAF-C4 subgroups were negatively correlated with prognosis. With their top genes of each subclusters, the sub-CAF2 had significantly relations to immunotherapy response in the patients with pan-cancer and immunotherapy.DiscussionWe explored the heterogeneity of five subclusters based on CAF in signaling patterns, immune status, metabolism features, enrichment pathways, and prognosis for PAAD.
Isolation and characterization of head and neck cancer-derived peritumoral and cancer-associated fibroblasts
Authors: Zhou Jiefu , Schwenk-Zieger Sabina , Kranz Gisela , Walz Christoph , Klauschen Frederik , Dhawan Sharduli , Canis Martin , Gires Olivier , Haubner Frank , Baumeister Philipp , Kohlbauer Vera 
Published: December 2022

IntroductionHead and neck squamous cell carcinomas (HNSCC) are characterized by strong cellular and molecular heterogeneity and treatment resistance entailing poor survival. Besides cell-intrinsic properties, carcinoma cells receive important cues from non-malignant cells within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a major component of the TME that impact on the molecular make-up of malignant cells and have a decisive function in tumor progression. However, the potential functionality of fibroblasts within tumor-adjacent, macroscopically normal tissue remains poorly explored.MethodsHere, we isolated primary peritumoral fibroblasts (PtFs) from macroscopically normal tissue in vicinity of primary human papillomavirus-negative and -positive oropharyngeal HNSCC and compared their phenotype and functionality with matched CAFs (n = 5 pairs) and with human oral fibroblasts (hOFs).ResultsExpression patterns of CD90, CD73, CD105, smooth muscle actin, Vimentin, and S100A4 were comparable in PtFs, CAFs, and hOFs. Cell proliferation and doubling times of CAFs and PtFs were heterogeneous across patients (n =2 PtF&gt;CAF; n = 1 CAF&gt;PtF; n = 2 CAF=PtF) and reflected inferior growth than hOFs. Furthermore, PtFs displayed an reduced heterogeneity in cell size compared to matched CAFs, which were characterized by the presence of single large cells. Overall, conditioned supernatants from CAFs had more frequently growth-promoting effects on a panel of carcinoma cell lines of the upper aerodigestive tract carcinoma cell lines (Cal27, Cal33, FaDu, and Kyse30), whereas significant differences in migration-inducing effects demonstrated a higher potential of PtFs. Except for Kyse30, CAFs were significantly superior to hOFs in promoting proliferation, while PtFs induced stronger migration than hOFs in all carcinoma lines tested. Analysis of soluble factors demonstrated significantly increased VEGF-A production in CAFs (except in pat.8), and significantly increased PDGF-BB production in PtFs of two patients. Tube formation assays confirmed a significantly enhanced angiogenic potential of conditioned supernatants from CAFs compared to hOFs on human umbilical vascular endothelial cells (HUVECs) in vitro.DiscussionHence, matched CAFs and PtFs present in HNSCC patients are heterogeneous in their proliferation-, migration-, and angiogenesis-promoting capacity. Despite this heterogeneity, CAFs induced stronger carcinoma cell proliferation and HUVEC tube formation overall, whereas PtFs promoted migration of tumor cells more strongly.
Kidney injury molecule type-1, interleukin-18, and insulin-like growth factor binding protein 7 levels in urine to predict acute kidney injury in pediatric sepsis
Authors: Ganda Idham Jaya , Kasri Yusriwanti , Susanti Maya , Hamzah Fitrayani , Rauf Syarifuddin , Albar Husein , Aras Jusli , Fikri Bahrul , Lawang Sitti Aizah , Daud Dasril , Laompo Amiruddin , Massi Muhammad Nasrum 
Published: December 2022

BackgroundThis study aimed to observe the role of urinary kidney injury molecule (KIM-1), interleukin (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP-7) levels in predicting acute kidney injury (AKI) in children with sepsis.Material and MethodsThis prospective cohort observational study was conducted at Dr. RSUP. Wahidin Sudirohusodo, Makassar, South Sulawesi, from January to December 2021. Inclusion criteria were septic patients treated in the pediatric intensive care unit (PICU) aged 1 month to 18 years with normal serum creatinine or normal urine output (&gt;5 ml/kg/body weight (BW)/h in 6–12 h). Patients with a history of kidney disease, prior urinary tract infection, or history of using nephrotoxic drugs were excluded.ResultsThere was a significant difference in urinary KIM-1, IL-18, and IGFBP-7 levels between septic patients with and without AKI. The cut-off point for urinary KIM-1 level in sepsis with and without AKI was 1.666 ng/ml, with sensitivity of 82.5%, specificity of 82.2%, and a relative risk (RR) [95% confidence interval (CI)] of 6.866 (95% CI, 3.329–14.165). The cut-off point for urinary IL-18 levels was 3.868 ng/ml, with sensitivity of 92.50%, specificity of 91.78%, and RR of 20.078 (95%CI, 6.593–61.142). The cut-off point for urinary IGFBP-7 levels was ≥0.906 ng/ml with a sensitivity of 75.00%, specificity of 75.34%, and RR of 4.063 (95% CI, 2.206–7.483).ConclusionUrinary KIM-1, IL-8, and IGFBP-7 levels could be used to predict AKI in septic patients. Urinary IL-8 has a higher sensitivity and specificity as a predictor of AKI in patients with sepsis.
Factors related to employment in childhood cancer survivors in Japan: A preliminary study
Authors: Kobayashi Kyoko , Ishida Yasushi , Gunji Michiyo , Nagase Kyoko , Yoshimoto-Suzuki Yuri , Hosoya Yosuke , Hasegawa Daisuke , Manabe Atsushi , Ohde Sachiko , Ozawa Miwa 
Published: December 2022

PurposePrevious research has revealed vocational and academic difficulties in childhood cancer survivors, and explored impact of survivors' medical history and physical function on vocational and academic status. However, we often encounter survivors with similar diagnoses and late effects but different academic or employment statuses. This raises the question of what affects academic attainment and employment other than treatment or late effects. This study aimed to explore factors associated with childhood cancer survivors' employment status and academic achievement.MethodsComprehensive health check-up and questionnaire survey were conducted for 69 survivors who were over the age of 18 and participated in St. Luke's Lifetime cohort study. We obtained survivors' biological function using comprehensive health check-up, neurocognitive states, quality of life, transition readiness, and family function. We conducted univariate analysis (Mann–Whitney U tests or chi-square tests) to compare the differences between the regular workers/students and non-regular workers/unemployed groups. The variables with p-values &lt;0.1 were used as independent variables multivariate logistic regression to explore predictors of employment status and academic attainment.ResultsResult of the univariate analysis, intelligence quotient, SF-8 PCS, transition readiness, family function were used for multivariate logistic regression as independent variables. The stepwise likelihood method was conducted; intelligence quotient (odds ratio [OR] = 1.100; 95% confidence interval [CI] 1.015–1.193; p = 0.021), transition readiness (OR = 0.612; 95% CI 0.396–0.974; p = 0.038), and family function (OR = 2.337; 95% CI 1.175–4.645; p = 0.015) were found to be associated with survivors' regular workers/students in the final regression model.ConclusionLong-term follow-up of pediatric cancer survivors requires the provision of total care, which supports physical, psychological, and social functions to improve health, readiness for transition to self-management, and family functioning.
Decreased xCT activity in patients associated with Helicobacter pylori infection
Authors: Wang Ling , Li Wen-Qun , Liu Fen , Li Yuan-Jian , Du Jie 
Published: December 2022

Objective: In animals, Helicobacter pylori (Hp)-induced gastric injury is accompanied by a decrease in the activity of the cysteine/glutamate transporter (xCT), which regulates extracellular glutamate levels. However, the impact of xCT activity in patients with Hp infection remains unclear. This study aims to investigate variations of xCT activity in the gastric mucosa of patients with Hp infection and to provide a clinical basis for identifying targets related to Hp infection.Methods: Our study included a total of 67 patients with gastritis, which consisted of 44 Hp-negative and 23 Hp-positive peptic ulcer cases. The inclusion criteria used to select patients were as follows: gastric histology was determined with a gastroscope, antral biopsies were taken for urease tests, and pathology and culture were performed for analysis of Hp-colonization. The clinical characteristics of the patients were obtained, the expressions of microRNAs and xCT protein were detected using immune histochemical analysis, and the concentration of glutamate in their gastric secretion was determined.Results: The findings revealed that xCT expression was significantly lower in Hp-positive patients as compared to Hp-negative individuals, which was accompanied by a decrease in glutamate concentration in gastric juice. We also discovered a high expression of microRNAs that have been shown to negatively regulate xCT expression, in Hp-positive patients.Conclusion: Reduced xCT activity in patients may play an important role in gastric ulcers caused by Hp infection. Our findings suggest that the microRNA/xCT pathway could be a potential treatment target for Hp-infection-related ulcers.
Curcumae Rhizoma - combined with Sparganii Rhizoma in the treatment of liver cancer: Chemical analysis using UPLC-LTQ-Orbitrap MSn, network analysis, and experimental assessment
Authors: Wei Jing , Wang Xiaoping , Dong Ying , Zhong Xiangjian , Ren Xueyang , Song Ruolan , Ma Jiamu , Yu Axiang , Fan Qiqi , Yao Jianling , Shan Dongjie , Lv Fang , Zheng Yuan , Deng Qingyue , Li Xianxian , He Yingyu , Fan Shusheng , Zhao Chongjun , Wang Xiuhuan , Yuan Ruijuan , She Gaimei 
Published: December 2022

Objective:Curcumae Rhizoma–Sparganii Rhizoma (CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.Method: The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MSn. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model in vivo for the first time and detected by the HepG2 cell model in vitro. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.Results: In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs in vitro and in vivo, and the order of activity was CR-SR &gt; CR &gt; SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP).Conclusion: Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.
Short-term effect of sacubitril/valsartan on endothelial dysfunction and arterial stiffness in patients with chronic heart failure
Authors: Cassano Velia , Armentaro Giuseppe , Magurno Marcello , Aiello Vincenzo , Borrello Francesco , Miceli Sofia , Maio Raffaele , Perticone Maria , Marra Alberto M. , Cittadini Antonio , Hribal Marta L. , Andreozzi Francesco , Sesti Giorgio , Sciacqua Angela 
Published: December 2022

Heart failure (HF) is associated to endothelial dysfunction that promotes the increase of arterial stiffness thus augmenting myocardial damage. Sacubitril/Valsartan is used in the treatment of HF reduced ejection fraction (HFrEF) and has been proven effective in reducing cardiovascular disease (CVD) progression and all-cause mortality. The aim of this study was to evaluate the effect of Sacubitril/Valsartan on endothelial dysfunction, arterial stiffness, oxidative stress levels and platelets activation in patients with HFrEF, at baseline and after 6 months of treatment. We enrolled 100 Caucasian patients. Endothelial function was evaluated by the reactive hyperemia index (RHI) and arterial stiffness (AS) by the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). At baseline, among enrolled outpatients, 43% showed a NYHA class II and 57% a NYHA class III. At 6 months, there was a significant improvement of several hemodynamic, clinical and metabolic parameters with a significant reduction in oxidative stress indices such as 8-isoprostane (p &lt; 0.0001) and Nox-2 (p &lt; 0.0001), platelets activity biomarkers such as sP-selectin (p &lt; 0.0001) and Glycoprotein-VI (p &lt; 0.0001), and inflammatory indices. Moreover, we observed a significant improvement in arterial stiffness parameters and in endothelial function indices. Our study demonstrated that 6 months treatment with Sacubitril/Valsartan, in patients with HFrEF, improves endothelial dysfunction and arterial stiffness, by reducing oxidative stress, platelet activation and inflammation circulating biomarkers, without adverse effects.
Pomalidomide enhances the maturation of dendritic cells derived from healthy donors and multiple myeloma patients
Authors: Wang Xi , Dai Jingying , Xia Jingyi , Ye Zichen , Huang Xiaobing , Cao Wanjun , Xiao Rong , He Lin 
Published: December 2022

Objective: To explore the effect of pomalidomide on the maturation of monocyte-derived dendritic cells (moDCs) from healthy donors (HDs) and multiple myeloma (MM) patients.Methods: MoDCs were generated by the incubation of monocytes from peripheral blood mononuclear cells (PBMCs) for 7 days in a medium consisting of 800 U/ml granulocyte-macrophage colony stimulating factor (GM-CSF), 500 U/ml interleukin-4 (IL-4), RPMI 1,640 medium, 5% human serum, 100 U/ml penicillin and 0.1 mg/ml streptomycin. Meanwhile, the incubation system was administrated with 10 µM pomalidomide or 1 × PBS as the control group. On the eighth day, cells were harvested and analyzed by flow cytometry. The CD80+CD86+ cell population in total cells was gated as moDCs in the FACS analyzing system. After that, the expression of CD40 and HLA-DR on moDCs was analyzed. Meanwhile, the supernatant from the incubation system was evaluated for the secretion of cytokines interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein 1α (MIP-1α) by enzyme-linked immunosorbent assay (ELISA).Results: When analyzing all the HD-moDCs together (n = 15), pomalidomide significantly increased the mean fluorescence intensity (MFI) of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.003, p = 0.040). Meanwhile, the proportion of CD40+ moDCs and HLA-DR+ moDCs in total moDCs was significantly higher in the pomalidomide group than in the control group (p = 0.008, p = 0.032). When analyzing all MM patient-moDCs together (n = 11), pomalidomide significantly increased the MFI of CD40 expression and HLA-DR expression on moDCs compared with the control group (p = 0.047, p = 0.006). Meanwhile, the proportion of HLA-DR+ moDCs in total DCs was significantly higher in the pomalidomide group than in the control group (p &lt; 0.001). Moreover, HD-moDCs (n = 8) treated with pomalidomide secreted 192% IL-12, 110% TNF-α, and 112% MIP-1α of the untreated moDCs (p = 0.020, p = 0.006, p = 0.055). However, when analyzing MM patient-moDCs (n = 10) together, the secretion of IL-12, TNF-α and MIP-1α from moDCs showed no significant difference between the pomalidomide group and the control group (p = 0.458, p = 0.377, p = 0.248).Conclusion:In vitro, 10 µM pomalidomide enhances the maturation of moDCs derived from both HDs and MM patients. Pomalidomide shows potential to be applied as a DC adjuvant for DC-based immunotherapy, such as the DC vaccine and DC cell therapy in MM.
Estrogen receptors, ERK1/2 phosphorylation and reactive oxidizing species in red blood cells from patients with rheumatoid arthritis
Authors: Di Franco Manuela , Vona Rosa , Gambardella Lucrezia , Cittadini Camilla , Favretti Martina , Gioia Chiara , Straface Elisabetta , Pietraforte Donatella 
Published: December 2022

Red blood cells (RBCs) are recognized to be important pathogenetic determinants in several human cardiovascular diseases (CVD). Undergoing to functional alterations when submitted to risk factors, RBCs modify their own intracellular signaling and the redox balance, shift their status from antioxidant defense to pro-oxidant agents, become a potent atherogenic stimulus playing a key role in the dysregulation of the vascular homeostasis favoring the developing and progression of CVD. Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality with a prevalence from two to five more likely in woman, mainly attributed to accelerated atherosclerosis. The purpose of this study was to correlate the RA disease activity and the RBCs functional characteristics. Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. The disease activity, measured as the number of swollen and painful joints (DAS-28), was correlated with 1) the expression of RBCs estrogen receptors, which modulate the RBC intracellular signaling, 2) the activation of the estrogen-linked kinase ERK½, which is a key regulator of RBC adhesion and survival, and 3) the levels of inflammatory- and oxidative stress-related biomarkers, such as the acute-phase reactants, the antioxidant capacity of plasma, the reactive oxidizing species formation and 3-nitrotyrosine. All the biomarkers were evaluated in RA patients at baseline and 6 months after treatment with disease-modifying anti-rheumatic drugs (DMARDs). We found, for the first times, that in RA patients 1) the DAS-28 correlated with RBC ER-α expression, and did not correlate with total antioxidant capacity of plasma; 2) the RBC ER-α expression correlated with systemic inflammatory biomarkers and oxidative stress parameters, as well as ERK½ phosphorylation; and 3) the DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. These findings represent an important advance in the study of RA determinants favoring the developing of CVD, because strongly suggest that RBCs could also participate in the vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.