bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic signature for hepatocellular carcinoma based on 4 pyroptosis-related genes
Authors: Duan Sainan , Gao Jianying , Lou Weiming , Zhang Yize , Deng Ying , Wang Cong , Huang Haiyue , Xu Hui , Guo Sixuan , Lai Shuhui , Xi Feiyang , Li Zhangwang , Deng Libin , Zhong Yuanbin 
Published: July 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Many recent studies have suggested that pyroptosis is important in tumour progression. However, the role of pyroptosis-related genes (PRGs) in HCC remains unclear.

Materials and methods
We identified differentially expressed PRGs in tumours versus normal tissues. Through univariate, LASSO, and multivariate Cox regression analyses, a prognostic PRG signature was established. The signature effectiveness was evaluated by time-dependent receiver operating characteristic (t-ROC) curve and Kaplan–Meier (KM) survival analysis. The signature was validated in the ICGC (LIRI-JP) cohort. In addition, single-sample gene enrichment analysis (ssGSEA) showed the infiltration of major immune cell types and the activity of common immune pathways in different subgroups.

Results
Twenty-nine pyroptosis-related DEGs from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were detected, and four genes (CTSV, CXCL8, MKI67 and PRF1) among them were selected to construct a prognostic signature. Then, the patients were divided into high- and low-risk groups. The pyroptosis-related signature was significantly associated with overall survival (OS). In addition, the patients in the high-risk group had lower levels of immune infiltration.

Conclusion
The prognostic signature for HCC based on 4 pyroptosis-related genes has reliable prognostic and predictive value for HCC patients.
Behavioural side effects of inhaled corticosteroids among children and adolescents with asthma
Authors: Bodum Karoline S. , Hjerrild Britta E. , Dalsgaard Søren , Rubak Sune L. M. 
Published: July 2022

Abstract
Background
Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor’s clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors.

Methods
First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region.

Results
EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA.

Conclusion
Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.
CEBPD modulates the airway smooth muscle transcriptomic response to glucocorticoids
Authors: Kan Mengyuan , Sun Maoyun , Jiang Xiaofeng , Diwadkar Avantika R. , Parikh Vishal , Cao Gaoyuan , Gebski Eric , Jester William , Lan Bo , Panettieri Reynold A. , Koziol-White Cynthia , Lu Quan , Himes Blanca E. 
Published: July 2022

Abstract
Background
CCAAT/Enhancer Binding Protein D (CEBPD), a pleiotropic glucocorticoid-responsive transcription factor, modulates inflammatory responses. Of relevance to asthma, expression of CEBPD in airway smooth muscle (ASM) increases with glucocorticoid exposure. We sought to characterize CEBPD-mediated transcriptomic responses to glucocorticoid exposure in ASM by measuring changes observed after knockdown of CEBPD and its impact on asthma-related ASM function.

Methods
Primary ASM cells derived from four donors were transfected with CEBPD or non-targeting (NT) siRNA and exposed to vehicle control, budesonide (100 nM, 18 h), TNFα (10 ng/ml, 18 h), or both budesonide and TNFα. Subsequently, RNA-Seq was used to measure gene expression levels, and pairwise differential expression results were obtained for exposures versus vehicle and knockdown versus control conditions. Weighted gene co-expression analysis was performed to identify groups of genes with similar expression patterns across the various experimental conditions (i.e., CEBPD knockdown status, exposures).

Results
CEBPD knockdown altered expression of 3037 genes under at least one exposure (q-value < 0.05). Co-expression analysis identified sets of 197, 152 and 290 genes that were correlated with CEBPD knockdown status, TNFα exposure status, and both, respectively. JAK-STAT signaling pathway genes, including IL6R and SOCS3, were among those influenced by both TNFα and CEBPD knockdown. Immunoblot assays revealed that budesonide-induced IL-6R protein expression and augmented IL-6-induced STAT3 phosphorylation levels were attenuated by CEBPD knockdown in ASM.

Conclusions
CEBPD modulates glucocorticoid responses in ASM, in part via modulation of IL-6 receptor signaling.
Prognostic biomarker IL17A correlated with immune infiltrates in head and neck cancer
Authors: Yu Meng , Qian Xing Xing , Li Guang , Cheng Zexing , Lin Zhijie 
Published: July 2022

Abstract
Background
The underlying functions and mechanisms of the Th17 pathway in Head and neck squamous cell carcinoma (HNSCC) progression and tumor immunology are still unclear. We investigated the correlation between IL17A expression and certain clinical parameters, tumor-infiltrating immune cells (TIICs) in TCGA HNSCC samples.

Methods
HNSCC files from the TCGA database were analyzed to obtain data on immune system infiltrates, gene expression, and related clinical information. R (Version 3.6.3) software, GEPIA, and TIMER online analysis tools were used to profile the relationship between the expression of IL17A and the prognosis, clinical stages, survival status and immune cell tumor-infiltrating levels of HNSCC patients. GEPIA and TIMER online analysis tools were used to verify the data.

Results
The expression of IL17A was significantly decreased in tumor tissues from HNSCC. IL17A expression was associated with M, N stage, lymphovascular invasion, and patients OS event. GSEA revealed that IL17A was closely related to humoral immune response, T cells response, and cytokine signal. TCGA database and TIMER online analysis indicated that the B cells and T cells levels were correlated with IL17A. The correlation between IL17A expression and correlated genes was analyzed.

Conclusions
IL-17A plays a key role in HNSCC. The levels of IL17A are important values for the determination of the occurrence and development of the HNSCC. The IL17A and correlated genes may be potential immunotherapeutic targets for HNSCC.
Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis
Authors: Rungjirajittranon Tarinee , Owattanapanich Weerapat , Chinthammitr Yingyong , Ruchutrakool Theera , Suwanawiboon Bundarika 
Published: July 2022

Abstract
Background
The association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.

Methods
Two investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method.

Results
A total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84–2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24–2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49–1.04; P = 0.08; I2 = 0%).

Conclusions
The current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.

Trial registration
INPLASY202180113.
Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders
Authors: Winstone Joanna K. , Pathak Khyatiben V. , Winslow Wendy , Piras Ignazio S. , White Jennifer , Sharma Ritin , Huentelman Matthew J. , Pirrotte Patrick , Velazquez Ramon 
Published: July 2022

Abstract
Background
Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer’s disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood–brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα.

Methods
Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC–MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome.

Results
Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development.

Conclusions
Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
Mapping Colombians’ positions on sentencing for substance offenses
Authors: del Rio Forero Daniel , Marín Claudia Pineda , Sastre María Teresa Muñoz , Kpanake Lonzozou , Mullet Etienne 
Published: July 2022

AbstractBackgroundIn Colombia, a person caught in possession of an illicit substance is not judicially sanctioned as long as the quantity does not exceed the maximum allowable amounts. Given that the public is divided on the appropriateness of this policy, an examination of the various public positions was undertaken.MethodA convenience sample of 302 adults were presented with 48 vignettes depicting a situation of everyday life easily recognizable by all in Colombia; that of a male person who is apprehended in the street by the police because he is suspected of illicit trafficking. These vignettes were created by orthogonal variation of four factors: Type of substance, amount of substance, type of charge against the offender, and offender’s age.ResultsThrough cluster analysis, six qualitatively different positions were found. These positions corresponded to three distinct, classical philosophies (a) a libertarian, free-market philosophy – punishment should never be extremely severe because the trade in psychotropic substances is a trade like any other (6%), (b) a moralistic, conservative philosophy – punishment should always be extremely severe except perhaps in certain cases (52%), and (c) a progressive, human rights-inspired philosophy – punishment should always be proportional to the seriousness of the facts (42%).ConclusionHalf of Colombian people supported a control policy according to which the use of psychotropic substances is considered profoundly immoral. Most of the other segment of the population express views similar to those of international organizations. It is therefore desirable that legislators rely on progressive international legislation to support domestic policies that are not strictly moralistic and conservative.
NBAS, a gene involved in cytotoxic degranulation, is recurrently mutated in pediatric hemophagocytic lymphohistiocytosis
Authors: Bi Xiaoman , Zhang Qing , Chen Lei , Liu Dan , Li Yueying , Zhao Xiaoxi , Zhang Ya , Zhang Liping , Liu Jingkun , Wu Chaoyi , Li Zhigang , Zhao Yunze , Ma Honghao , Huang Gang , Liu Xin , Wang Qian-fei , Zhang Rui 
Published: July 2022

AbstractHemophagocytic lymphohistiocytosis (HLH), particularly primary HLH (pHLH), is a rare, life-threatening disease. Germline genetic deficiency of 12 known HLH genes impairs cytotoxic degranulation in natural killer (NK) cells or cytotoxic T lymphocytes (CTLs) and contributes to pHLH development. However, no pathogenic mutations in these HLH genes are found in nearly 10% of HLH patients, despite a strong suspicion of pHLH, suggesting that the underlying genetic basis of HLH is still unclear. To discover novel susceptibility genes, we first selected 13 children with ppHLH (presumed primary HLH patients in the absence of detectable known HLH gene variants) and their parents for initial screening. Whole-genome sequencing (WGS) in one trio and whole-exome sequencing (WES) in twelve trios revealed that two ppHLH patients carried biallelic NBAS variants, a gene that is involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport upstream of the degranulation pathway. Additionally, two candidate genes, RAB9B and KLC3, showed a direct relationship with known HLH genes in protein-protein interaction (PPI) network analysis. We analyzed NBAS, RAB9B, KLC3 and known HLH genes in an independent validation cohort of 224 pediatric HLH patients. Only biallelic NBAS variants were identified in three patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-deficient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus. According to our findings, NBAS is the second most frequently mutated gene (2.11%) in our HLH cohort after PRF1. NBAS deficiency may contribute to the development of HLH via a dysregulated lytic vesicle transport pathway.
Increasing illness severity is associated with global myocardial dysfunction in the first 24 hours of sepsis admission
Authors: Ehrman Robert R. , Bredell Bryce X. , Harrison Nicholas E. , Favot Mark J. , Haber Brian D. , Welch Robert D. , Levy Philip D. , Sherwin Robert L. 
Published: July 2022

Abstract
Background
Septic cardiomyopathy was recognized more than 30 years ago, but the early phase remains uncharacterized as no existing studies captured patients at the time of Emergency Department (ED) presentation, prior to resuscitation. Therapeutic interventions alter cardiac function, thereby distorting the relationship with disease severity and outcomes. The goal of this study was to assess the impact of illness severity on cardiac function during the first 24 h of sepsis admission.

Methods
This was a pre-planned secondary analysis of a prospective observational study of adults presenting to the ED with suspected sepsis (treatment for infection plus either lactate > 2 mmol/liter or systolic blood pressure < 90 mm/Hg) who received < 1L IV fluid before enrollment. Patients had 3 echocardiograms performed (presentation, 3, and 24 h). The primary outcome was the effect of increasing sepsis illness severity, defined by ED Sequential Organ Failure Assessment (SOFA) score, on parameters of cardiac function, assessed using linear mixed-effects models. The secondary goal was to determine whether cardiac function differed between survivors and non-survivors, also using mixed-effects models.

Results
We enrolled 73 patients with a mean age of 60 (SD 16.1) years and in-hospital mortality of 23%. For the primary analysis, we found that increasing ED SOFA score was associated with worse cardiac function over the first 24 h across all assessed parameters of left-ventricular systolic and diastolic function as well as right-ventricular systolic function. While baseline strain and E/e' were better in survivors, in the mixed models analysis, the trajectory of Global Longitudinal Strain and septal E/e′ over the first 24 h of illness differed between survivors and non-survivors, with improved function at 24 h in non-survivors.

Conclusions
In the first study to capture patients prior to the initiation of resuscitation, we found a direct relationship between sepsis severity and global myocardial dysfunction. Future studies are needed to confirm these results, to identify myocardial depressants, and to investigate the link with adverse outcomes so that therapeutic interventions can be developed.
Ethnic minority experiences of mental health services in the Netherlands: an exploratory study
Authors: Ilozumba Onaedo , Koster Tirsah S , Syurina Elena V , Ebuenyi Ikenna 
Published: July 2022

Abstract
Objective
Despite considerable spending on mental health in the Netherlands, access to mental health remains suboptimal, particularly for migrants and ethnic minorities. Addressing the growing mental health service needs requires an understanding of the experiences of all stakeholders, specifically minority populations. In this exploratory study, we sought to understand the perspectives and experience of mental health services by migrants and their provider. An exploratory qualitative study was conducted with 10 participants, five of whom were mental health service providers and the other five were clients who had utilized or currently utilized MHS in the Netherlands.

Results
We identified three themes that explained the experiences of clients and providers of MHS in the Netherlands (i) Perceptions of mental health service utilization (ii) Mismatch between providers (iii) Availability of services. The most significant factor that influenced participants experience was a service provider of a different cultural background. Minority populations accessing mental health services have multiple needs, including an expressed need for cultural understanding. Their experiences of mental health services could be improved for minority populations by addressing the diversity of health providers.
Microvascular decompression for trigeminal neuralgia caused by persistent trigeminal artery associated with craniosynostosis: a case report
Authors: Sun Tao , Huang Qinghao , Li Chuangfeng , Wang Wentao , He Longshuang , Liu Jinlong , Yang Chao 
Published: July 2022

Abstract
Background
Persistent trigeminal artery (PTA) is a rare arterial anastomosis between the basilar artery (BA) and internal carotid artery (ICA). It plays an indispensable role in a number of neurological disorders, including trigeminal neuralgia (TN).

Case presentation
We report a unique case of a 58-year-old Han female patient with TN caused by PTA associated with craniosynostosis. Preoperative three-dimensional time-of-flight (3D-TOF) magnetic resonance (MR) and 3D constructive inference in steady state (3D-CISS) imaging showed that the PTA run though Meckel’s cave. Complete pain relief was immediately achieved after microvascular decompression (MVD), without facial numbness and other complications. No recurrence was recorded at the 1-year follow up.

Conclusions
Microvascular decompression is a feasible option for the treatment of complex TN combined with other abnormalities. For patients deemed suitable for percutaneous balloon compression, PTA should be ruled out. Preoperative 3D-TOF and 3D-CISS MR imaging were essential to identify PTA neurovascular conflicts.
Neonatal cardiac tamponade, a life-threatening complication secondary to peripherally inserted central catheter: a case report
Authors: Zarkesh Mohammad Reza , Haghjoo Mokaram 
Published: July 2022

Abstract
Background
Although the use of a peripherally inserted central catheter (PICC) has many advantages for the treatment of neonates, catheter malposition may result in serious complications that could be life-threatening. We report the case of a 10-day-old neonate with cardiac tamponade secondary to a PICC line who was successfully treated by pericardiocentesis.

Case presentation
An Iranian (Asian) preterm male neonate was born by Cesarean section with a birth weight of 1190 g and a first-minute Apgar score of 7. Based on an increased respiratory distress syndrome (RDS) score from 4 to 7, resuscitation measures and intubation were performed at the neonatal intensive care unit (NICU). On day 3 after birth, a PICC line was inserted for parenteral therapy. A chest X-ray confirmed that the tip of the PICC line was in the appropriate position. Mechanical ventilation was discontinued 72 h post-NICU admission because of the improved respiratory condition. On the day 10 post-NICU admission, he suddenly developed hypotonia, apnea, hypoxia, hypotension, and bradycardia. Resuscitation and ventilation support were immediately started, and inotropic drugs were also given. Emergency echocardiography showed a severe pericardial effusion with tamponade. The PICC line was removed, and urgent pericardiocentesis was carried out. The respiratory situation gradually improved, the O2 saturation increased to 95%, and vital signs remained stable.

Conclusions
Dramatic improvement of the neonate's clinical responses after pericardial drainage and PICC removal were suggestive of PICC displacement, pericardial perforation, and cardiac tamponade.