bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and prognostic value of PRDX family in colon adenocarcinoma by integrating comprehensive analysis and in vitro and in vivo validation
Authors: Zhou He , Li Lifa , Chen Jia , Hou Songlin , Zhou Tong , Xiong Yongfu 
Published: March 2023

BackgroundThe peroxiredoxin family, a crucial regulator of redox reactions, is strongly associated with various tumorigenesis. However, the role of peroxiredoxin4 (PRDX4) in colon adenocarcinoma (COAD) remains poorly understood.MethodsMulticenter databases, including GEPIA, HPA, UALCAN, cBioPortal, cancerSEA, STRING, CCLE, and LinkedOmics, comprehensively analyzed transcriptional expression, prognostic value, genetic alterations, signaling pathways, and associated genes of the PRDXs in COAD patients. Colony formation, transwell, flow cytometry, sphere formation, and xenograft assays were performed to validate further in vitro and in vivo.ResultsMembers of the PRDX family were differentially expressed in COAD, with each member showing varying degrees of genetic alterations. Intriguingly, only PRDX4 significantly correlated with COAD prognosis and stage. The single-cell sequencing suggested that PRDX4 is positively correlated with proliferation, apoptosis, and invasion, whereas negatively correlated with stemness. Moreover, PRDX4 involved in a series of critical biological processes, such as cell growth. Furthermore, in vivo and in vitro analyses indicated that knocking down PRDX4 inhibits the proliferation and invasion of HCT116 cells while promoting apoptosis and stemness.ConclusionsWe identified PRDX4 expression as a novel potential prognostic marker in COAD.
A novel conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan in the autologous stem cell transplantation of aggressive T-cell lymphoma
Authors: Zeng Qiang , Zhang Hang , Kuang Pu , Li Jian , Chen Xinchuan , Dong Tian , Wu Qiuhui , Zhang Chuanli , Chen Chunping , Niu Ting , Liu Ting , Liu Zhigang , Ji Jie 
Published: March 2023

BackgroundThe prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT).MethodsPatients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen’s safety. The survival curve was estimated via the Kaplan-Meier method.ResultsTwenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8–13 days) and 13 days (9–31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable.ConclusionsChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.
The impacts of physical activity on psychological and behavioral problems, and changes in physical activity, sleep and quality of life during the COVID-19 pandemic in preschoolers, children, and adolescents: A systematic review and meta-analysis
Authors: Pang Johnson C. Y. , Chan Eric L. S. , Lau Herman M. C. , Reeves Kara K. L. , Chung Tina H. Y. , Hui Heidi W. L. , Leung Alfred H. L. , Fu Allan C. L. 
Published: March 2023

BackgroundThe COVID-19 pandemic has greatly affected the level of physical activity (PA). However, little is known about its effect on health outcomes.MethodsArticles without language restrictions published from the database inception through March 16, 2022, were retrieved using the CINAHL Complete, Cochrane Library, EMBASE, Medline, PubMed, and PsycINFO databases. High-quality articles assessing the effect of PA on psychological and behavioral problems. Additionally, PA, QoL, and/or sleep problems before and during the pandemic were included. Articles without data regarding PA or involving non-general populations were excluded. The PRISMA and MOOSE guidelines were followed. Data quality of the selected articles was assessed using the Newcastle-Ottawa Scale and GRADE approach. Data were pooled using a random-effects model and sensitivity analysis if heterogenicity was high (I2 ≥ 50%). The relationship between PA and psychological and behavioral problems; and changes in PA, QoL, and sleeping patterns before and during the pandemic in preschoolers, children, and adolescents were investigated. A meta-analysis was conducted; odds ratios (ORs), mean differences (MD), and standardized MDs (SMDs) were calculated.ResultsThirty-four articles involving 66,857 participants were included. The results showed an overall significant protective effect between PA and psychological and/or behavioral problems (OR = 0.677; 95% CI = 0.630, 0.728; p-value &lt;0.001; I2 = 59.79%). This relationship was also significant in the subgroup analysis of children (OR = 0.690; 95% CI = 0.632, 0.752; p-value &lt;0.001; I2 = 58.93%) and adolescents (OR = 0.650; 95% CI = 0.570, 0.741; p-value &lt;0.001; I2 = 60.85%); however, no data on the relationship in preschoolers were collected. In addition, the overall time spent on PA significantly decreased by 23.2 min per day during the COVID-19 pandemic (95% CI = −13.5, −32.9; p-value &lt;0.001; I2 = 99.82%). Moreover, the results showed an overall significant decrease in QoL (SMD = −0.894, 95% CI = −1.180, −0.609, p-value &lt;0.001, I2 = 96.64%). However, there was no significant difference in sleep duration during the COVID-19 pandemic (MD = 0.01 h per day, 95% CI = −0.027, 0.225; p-value = 0.125; I2 = 98.48%).ConclusionDuring the pandemic, less PA was contributed to poor QoL and sleep quality. However, increases in PA are associated with reduced occurrences of psychological and behavioral problems. Implementing recovery plans to address the health effect of the pandemic is essential.
Adequacy of sedation analgesia to support the comfort of neonates undergoing therapeutic hypothermia and its impact on short-term neonatal outcomes
Authors: Nakhleh-Philippe Pauline , Zores Claire , Stern-Delfils Amélie , Escande Benoît , Astruc Dominique , Severac François , Kuhn Pierre 
Published: March 2023

ObjectivesWe aimed to evaluate (1) whether sedation analgesia (SA) used during therapeutic hypothermia (TH) was efficient to support the wellbeing of neonates with hypoxic-ischemic encephalopathy, (2) the SA level and its adjustment to clinical pain scores, and (3) the impact of inadequate SA on short-term neonatal outcomes evaluated at discharge.MethodsThis was an observational retrospective study performed between 2011 and 2018 in two level III centers in Alsace, France. We analyzed the wellbeing of infants by using the COMFORT-Behavior (COMFORT-B) clinical score and SA level during TH, according to which we classified infants into four groups: those with excess SA, adequate SA, lack of SA, and variability of SA. We analyzed the variations in doses of SA and their justification. We also determined the impact of inadequate SA on neonatal outcomes at discharge by multivariate analyses with multinomial regression, with adequate SA as the reference.ResultsA total of 110 patients were included, 89 from Strasbourg university hospital and 21 from Mulhouse hospital. The COMFORT-B score was assessed 95.5% of the time. Lack of SA was mainly found on the first day of TH (15/110, 14%). In all, 62 of 110 (57%) infants were in excess of SA over the entire duration of TH. Most dose variations were related to clinical pain scores. Inadequate SA was associated with negative short-term consequences. Infants with excess of SA had a longer duration of mechanical ventilation [mean ratio 1.46, 95% confidence interval (CI), 1.13–1.89, p = 0.005] and higher incidence of abnormal neurological examination at discharge (odds ratio 2.61, 95% CI, 1.10–6.18, p = 0.029) than infants with adequate SA.DiscussionAdequate SA was not easy to achieve during TH. Close and regular monitoring of SA level may help achieve adequate SA. Excess of SA can be harmful for newborns with hypoxic-ischemic encephalopathy who are undergoing TH.
Discomfort relief after paracetamol administration in febrile children admitted to a third level paediatric emergency department
Authors: Chiappini Elena , Bestetti Matilde , Masi Stefano , Paba Teresa , Venturini Elisabetta , Galli Luisa 
Published: March 2023

Backgroundinternational guidelines recommend treating fever in children not at a predefined body temperature limit but based on the presence of discomfort. However few studies evaluated discomfort relief after administration of antipyretics in children.MethodsBetween 1st January and 30th September 2021 a single-center prospective observational study was performed in febrile children consecutively admitted to a pediatric emergency department and treated with paracetamol orally. For each child, body temperature, presence and severity of discomfort, defined using a previously published semiquantitative likert scale, were evaluated at baseline and 60 min after administration of paracetamol, and differences were analyzed.Results172 children (males: 91/172; 52.9%; median age: 41.7 months) were included. Significant reductions in body temperature (median body temperature at T0: 38.9 °C; IQR: 38.3–39.4, median body temperature at T60: 36.9 °C; IQR: 36.4–37.5; P &lt; 0.0001), and in the level of discomfort (proportion of children with severe discomfort at T0: 85% and at T60:14%; P &lt; 0.0001) were observed. Severe discomfort at T60 persisted in a minority of children (24/172; 14%) and it was not related to body temperature values.Conclusionsparacetamol in febrile children is associated not only with significantly reduction in body temperature but also with discomfort relief.
Validation of a scale to assess adherence to oral chemotherapy based on the experiences of patients and healthcare professionals (EXPAD-ANEO)
Authors: Talens Amparo , LÓpez-Pintor Elsa , Guilabert Mercedes , Cantó-Sancho Natalia , Aznar María Teresa , Lumbreras Blanca 
Published: March 2023

Background: Lack of adherence to Oral antineoplastic agents (OAAs) treatment has important clinical, social and economic consequences.Objective: To develop and validate a novel instrument for assessing adherence to OAAs, based on the reported experiences of people with cancer in relation to their treatment and the opinions of the healthcare professionals who care for them.Methods: We performed a multicenter validation study of a scale designed to assess adherence to OAAs. First, a steering committee developed the items for an initial scale, based on the results of a qualitative study that evaluated patients’ and professionals’ experiences with this treatment. We then assessed the validity and reliability of the initial scale in a sample of 268 outpatients with cancer who received their OAAs from four Spanish hospitals.Results: The mean age of the sample of 268 outpatients was 64.1 (standard deviation [SD] 12.4) years, and 47% of participants were women. With the results of this analysis, we developed the EXPAD-ANEO scale, which has 2 factors, one for beliefs and expectations and another for behavior. Both factors explain 52% of the explained common variance. Good reliability was obtained, with a McDonald’s omega of 0.7 for the first factor and 0.6 for the second factor. The fit indices were optimal (Root Mean Square Error of Approximation = 0.02, Comparative Fit Index = 0.99, Tucker Lexis Index = 0.99 and Standardized Root Mean Squared Residual = 0.03), which verifies the appropriateness of the items to the model. We measured EXPAD-ANEO criterion validity against pill count, obtaining a specificity of 80%. We measured convergent validity with the Morisky-Green test and found a significant association (p &lt; 0.001). We measured divergent validity with questions on health literacy from the 16-item European Health Literacy Survey and found no correlation (p = 0.153).Conclusion: EXPAD-ANEO is the first validated instrument for evaluating patients’ experiences with and adherence to OAAs, providing valuable information that can help health professionals to establish individual strategies or collective programs for improving therapeutic results and reducing healthcare costs.
Acute pharmacological profile of 2C-B-Fly-NBOMe in male Wistar rats—pharmacokinetics, effects on behaviour and thermoregulation
Authors: Syrová Kateřina , Šíchová Klára , Danda Hynek , Lhotková Eva , Jorratt Pascal , Pinterová-Leca Nikola , Vejmola Čestmír , Olejníková-Ladislavová Lucie , Hájková Kateřina , Kuchař Martin , Horáček Jiří , Páleníček Tomáš 
Published: March 2023

Introduction:N-2-methoxy-benzylated (“NBOMe”) analogues of phenethylamine are a group of new psychoactive substances (NPS) with reported strong psychedelic effects in sub-milligram doses linked to a number of severe intoxications, including fatal ones. In our present work, we provide a detailed investigation of pharmacokinetics and acute behavioural effects of 2C-B-Fly-NBOMe (2-(8-bromo-2,3,6,7-tetrahydrobenzo [1,2-b:4,5-b′]difuran-4-yl)-N-[(2-methoxybenzyl]ethan-1-amine), an analogue of popular psychedelic entactogen 2C-B (4-Bromo-2,5-dimethoxyphenethylamine).Methods: All experiments were conducted on adult male Wistar rats. Pharmacokinetic parameters of 2C-B-Fly-NBOMe (1 mg/kg subcutaneously; s. c.) in blood serum and brain tissue were analysed over 24 h using liquid chromatography-mass spectrometry (LC/MS). For examination of behavioural parameters in open field test (OFT) and prepulse inhibition (PPI) of acoustic startle reaction (ASR), 2C-B-Fly-NBOMe (0.2, 1 and 5 mg/kg s. c.) was administered in two temporal onsets: 15 and 60 min after administration. Thermoregulatory changes were evaluated in individually and group-housed animals over 8 h following the highest dose used in behavioural experiments (5 mg/kg s. c.).Results: Peak drug concentrations were detected 30 and 60 min after the drug application in serum (28 ng/ml) and brain tissue (171 ng/g), respectively. The parental compound was still present in the brain 8 h after administration. Locomotor activity was dose-dependently reduced by the drug in both temporal testing onsets. ASR was also strongly disrupted in both temporal onsets, drug’s effect on PPI was weaker. 2C-B-Fly-NBOMe did not cause any significant thermoregulatory changes.Discussion: Our results suggest that 2C-B-Fly-NBOMe penetrates animal brain tissue in a relatively slow manner, induces significant inhibitory effects on motor performance, and attenuates sensorimotor gating. Its overall profile is similar to closely related analogue 2C-B and other NBOMe substances.
Factors influencing medication adherence in multi-ethnic Asian patients with chronic diseases in Singapore: A qualitative study
Authors: Yoon Sungwon , Kwan Yu Heng , Yap Wei Liang , Lim Zhui Ying , Phang Jie Kie , Loo Yu Xian , Aw Junjie , Low Lian Leng 
Published: March 2023

Background: Poor medication adherence can lead to adverse health outcomes and increased healthcare costs. Although reasons for medication adherence have been widely studied, less is explored about factors affecting medication adherence for patients in non-Western healthcare setting and from Asian cultures. This study aimed to explore cultural perspectives on factors influencing medication adherence among patients with chronic diseases in a multi-ethnic Asian healthcare setting.Methods: We conducted a qualitative study involving in-depth interviews with patients with chronic conditions purposively recruited from a community hospital in Singapore until data saturation was achieved. A total of 25 patients participated in this study. Interviews were transcribed and thematically analyzed. Themes were subsequently mapped into the World Health Organization (WHO) Framework of Medication Adherence.Results: Participants commonly perceived that sides effects (therapy-related dimension), poor understanding of medication (patient-related dimension), limited knowledge of condition (patient-related dimension), forgetfulness (patient-related dimension) and language issues within a multi-ethnic healthcare context (healthcare team and system-related dimension) as the main factors contributing to medication adherence. Importantly, medication adherence was influenced by cultural beliefs such as the notion of modern medicines as harms and fatalistic orientations towards escalation of doses and polypharmacy (patient-related dimension). Participants made various suggestions to foster adherence, including improved patient-physician communication, enhanced care coordination across providers, use of language familiar to patients, patient education and empowerment on the benefits of medication and medication adjustment.Conclusion: A wide range of factors influenced medication adherence, with therapy- and patient-related dimensions more pronounced compared to other dimensions. Findings demonstrated the importance of cultural beliefs that may influence medication adherence. Future efforts to improve medication adherence should consider a person-centered approach to foster more positive health expectations and self-efficacy on medication adherence, supplemented with routine reviews, development of pictograms and cultural competence training for healthcare professionals.
Comprehensive bioinformatic analysis constructs a CXCL model for predicting survival and immunotherapy effectiveness in ovarian cancer
Authors: Li Shuang , Zou Dawei , Liu Zhaoqian 
Published: March 2023

Background: Immunotherapy has limited effectiveness in ovarian cancer (OC) patients, highlighting the need for reliable biomarkers to predict the effectiveness of these treatments. The C-X-C motif chemokine ligands (CXCLs) have been shown to be associated with survival outcomes and immunotherapy efficacy in cancer patients. In this study, we aimed to evaluate the predictive value of 16 CXCLs in OC patients.Methods: We analyzed RNA-seq data from The Cancer Genome Atlas, Gene Expression Omnibus, and UCSC Xena database and conducted survival analysis. Consensus cluster analysis was used to group patients into distinct clusters based on their expression patterns. Biological pathway alterations and immune infiltration patterns were examined across these clusters using gene set variation analysis and single-sample gene set enrichment analysis. We also developed a CXCL scoring model using principal component analysis and evaluated its effectiveness in predicting immunotherapy response by assessing tumor microenvironment cell infiltration, tumor mutational burden estimation, PD-L1/CTLA4 expression, and immunophenoscore analysis (IPS).Results: Most CXCL family genes were overexpressed in OC tissues compared to normal ovarian tissues. Patients were grouped into three distinct CXCL clusters based on their CXCL expression pattern. Additionally, using differentially expressed genes among the CXCL clusters, patients could also be grouped into three gene clusters. The CXCL and gene subtypes effectively predicted survival and immune cell infiltration levels for OC patients. Furthermore, patients with high CXCL scores had significantly better survival outcomes, higher levels of immune cell infiltration, higher IPS, and higher expression of PD-L1/CTLA4 than those with low CXCL scores.Conclusion: The CXCL score has the potential to be a promising biomarker to guide immunotherapy in individual OC patients and predict their clinical outcomes and immunotherapy responses.
Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice
Authors: Moriyama Hiroshi , Nomura Sadahiro , Imoto Hirochika , Oka Fumiaki , Maruta Yuichi , Mori Naomasa , Fujii Natsumi , Suzuki Michiyasu , Ishihara Hideyuki 
Published: March 2023

Background: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a transient receptor potential melastatin 8 (TRPM8) agonist, reportedly suppressed penicillin G-induced cortical-focal EDs. However, the effects of TRPM8 agonists on FSs remain unknown. In this study, we aimed to clarify the effects of the TRPM8 agonist, and the absence of TRPM8 channels, on hyperthermia-induced FS by analyzing the fast ripple band.Methods: Hyperthermia (43°C for 30 min) induced by a heating pad caused FSs in postnatal day 7 wild-type (WT) and TRPM8 knockout (TRPM8KO) mice. FSs were defined as EDs occurring during behavioral seizures involving hindlimb clonus and loss of the righting reflex. Mice were injected with 1% dimethyl sulfoxide or 1 mM WS-3 20 min before the onset of hyperthermia, and electroencephalograms; movies; and rectal, brain and heating pad temperatures were recorded.Results: In wild-type mice, WS-3 reduced the fast ripple amplitude in the first FS without changing rectal and brain temperature thresholds. In contrast, the anti-FS effect induced by the TRPM8 agonist was not observed in TRPM8KO mice and, compared with wild-type mice, TRPM8 deficiency lowered the rectal and brain temperature thresholds for FSs, exacerbated the fast ripple amplitude, and prolonged the duration of the initial FS induced by hyperthermia.Conclusion: Our findings suggest that TRPM8 agonists can be used to treat hyperthermia-induced FSs.