bluuebunny/crossref_metadata_2025 huggingface dataset:
ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma
Authors: Liu Fahui , Liang Jiadong , Long Puze , Zhu Lilan , Hou Wanyun , Wu Xueming , Luo Chunying
Published: January 2022

Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC.
Perspectives and Expertise in Establishing a Therapeutic Drug Monitoring Programme for Challenging Childhood Cancer Patient Populations
Authors: Barnett Shelby , Holden Victoria , Campbell-Hewson Quentin , Veal Gareth J.
Published: January 2022

The utility of Therapeutic Drug Monitoring (TDM) in the setting of childhood cancer is a largely underused tool, despite the common use of cytotoxic chemotherapeutics. While it is encouraging that modern advances in chemotherapy have transformed outcomes for children diagnosed with cancer, this has come at the cost of an elevated risk of life-changing long-term morbidity and late effects. This concern can limit the intensity at which these drugs are used. Widely used chemotherapeutics exhibit marked inter-patient variability in drug exposures following standard dosing, with fine margins between exposures resulting in toxicity and those resulting in potentially suboptimal efficacy, thereby fulfilling criteria widely accepted as fundamental for TDM approaches. Over the past decade in the UK, the paediatric oncology community has increasingly embraced the potential benefits of utilising TDM for particularly challenging patient groups, including infants, anephric patients and those receiving high dose chemotherapy. This has been driven by a desire from paediatric oncologists to have access to clinical pharmacology information to support dosing decisions being made. This provides the potential to modify doses between treatment cycles based on a comprehensive set of clinical information, with individual patient drug exposures being used alongside clinical response and tolerability data to inform dosing for subsequent cycles. The current article provides an overview of recent experiences of conducting TDM in a childhood cancer setting, from the perspectives of the clinicians, scientists and pharmacists implementing TDM-based dosing recommendations. The ongoing programme of work has facilitated investigations into the validity of current approaches to dosing for some of the most challenging childhood cancer patient groups, with TDM approaches now being expanded from well-established cytotoxic drugs through to newer targeted treatments.
High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan
Authors: Lai Hong-Yue , Wu Li-Ching , Kong Po-Hsin , Tsai Hsin-Hwa , Chen Yen-Ta , Cheng Yuan-Tso , Luo Hao-Lun , Li Chien-Feng
Published: January 2022

Background

The unusual high dialysis prevalence and upper urinary tract urothelial carcinoma (UTUC) incidence in Taiwan may attribute to aristolochic acid (AA), which is nephrotoxic and carcinogenic, exposure. AA can cause a unique mutagenic pattern showing A:T to T:A transversions (mutational Signature 22) analyzed by whole exome sequencing (WES). However, a fast and cost-effective tool is still lacking for clinical practice. To address this issue, we developed an efficient and quantitative platform for the quantitation of AA and tried to link AA detection with clinical outcomes and decipher the genomic landscape of UTUC in Taiwan.

Patients and Methods

We recruited 61 patients with de novo onset of UTUC after kidney transplantation who underwent radical nephroureterectomy. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was developed for the quantitation of AA. Pearson’s chi-square test, Kaplan–Meier method, and Cox proportional hazard model were utilized to assess the correlations among AA detection, clinicopathological characteristics, and clinical outcomes. Seven tumors and seven paired normal tissues were sequenced using WES (approximately 800x sequencing depth) and analyzed by bioinformatic tool.

Results

We found that high level of 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AL-I) detected in paired normal tissues was significantly correlated with fast UTUC initiation times after renal transplantation (p = 0.035) and with no use of sirolimus (p = 0.046). Using WES analysis, we further observed that all tumor samples were featured by Signature 22 mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-associated gene mutations, p53 mutations, no fibroblast growth factor receptor 3 (FGFR3) mutation, and high tumor mutation burden (TMB). Especially, mammalian target of rapamycin (mTOR) activation predominated in dA-AL-I-detected samples compared with those without dA-AL-I detection and might be associated with UTUC initiation through cell proliferation and suppression of UTUC progression via autophagy inhibition.

Conclusion

Accordingly, dA-AL-I detection can provide more direct evidence to AA exposure and serve as a more specific predictive and prognostic biomarker for patients with de novo onset of UTUC after kidney transplantation.
The Need for Testing—The Exercise Challenge Test to Disentangle Causes of Childhood Exertional Dyspnea
Authors: Hengeveld Vera S. , van der Kamp Mattiènne R. , Thio Boony J. , Brannan John D.
Published: January 2022

Exertional dyspnea is a common symptom in childhood which can induce avoidance of physical activity, aggravating the original symptom. Common causes of exertional dyspnea are exercise induced bronchoconstriction (EIB), dysfunctional breathing, physical deconditioning and the sensation of dyspnea when reaching the physiological limit. These causes frequently coexist, trigger one another and have overlapping symptoms, which can impede diagnoses and treatment. In the majority of children with exertional dyspnea, EIB is not the cause of symptoms, and in asthmatic children it is often not the only cause. An exercise challenge test (ECT) is a highly specific tool to diagnose EIB and asthma in children. Sensitivity can be increased by simulating real-life environmental circumstances where symptoms occur, such as environmental factors and exercise modality. An ECT reflects daily life symptoms and impairment, and can in an enjoyable way disentangle common causes of exertional dyspnea.
Serotherapy as Graft-Versus-Host Disease Prophylaxis in Haematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukaemia
Authors: Keogh Steven J. , Dalle Jean-Hugues , Admiraal Rick , Pulsipher Michael A.
Published: January 2022

Serotherapy comprising agents such as anti-thymocyte globulin, anti-T-lymphocyte globulin, and the anti-CD52 monoclonal antibody alemtuzumab is used widely to reduce the incidence of graft-versus-host disease (GvHD) after paediatric haematopoietic stem cell transplantation (HSCT). The outcome of transplants using matched unrelated donors now approaches that of matched sibling donors. This is likely due to better disease control in recipients, the use of donors more closely human-leukocyte antigen (HLA)-matched to recipients, and more effective graft-versus-host disease (GvHD) prophylaxis. The price paid for reduced GvHD is slower immune reconstitution of T cells and thus more infections. This has led to studies looking to optimise the amount of serotherapy used. The balance between prevention of GvHD on one side and prevention of infections and relapse on the other side is quite delicate. Serotherapy is given with chemotherapy-/radiotherapy-based conditioning prior to HSCT. Due to their long half-lives, agents used for serotherapy may be detectable in patients well after graft infusion. This exposes the graft-infused T cells to a lympholytic effect, impacting T-cell recovery. As such, excessive serotherapy dosing may lead to no GvHD but a higher incidence of infections and relapse of leukaemia, while under-dosing may result in a higher chance of serious GvHD as immunity recovers more quickly. Individualised dosing is being developed through studies including retrospective analyses of serotherapy exposure, population pharmacokinetic modelling, therapeutic drug monitoring in certain centres, and the development of dosing models reliant on factors including the patient's peripheral blood lymphocyte count. Early results of “optimal” dosing strategies for serotherapy and conditioning chemotherapy show promise of improved overall survival.
Opioids in COVID-19: Two Sides of a Coin
Authors: Palamim Camila Vantini Capasso , Boschiero Matheus Negri , Faria Aléthea Guimarães , Valencise Felipe Eduardo , Marson Fernando Augusto Lima
Published: January 2022

Introduction: The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics–possibly in higher doses than usual–which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: “Opioids”, “COVID-19,” “COVID-19 pandemic,” “SARS-CoV-2,” “Opioid use disorder,” “Opioid dependence” and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic.

Results: Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug.

Conclusion: The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.
Sources of Information on Medicinal Products Among Physicians – A Survey Conducted Among Primary Care Physicians in Poland
Authors: Zielińska Magdalena , Hermanowski Tomasz
Published: January 2022

Introduction: Primary care physicians need to have access to up-to-date knowledge in various fields of medicine and high-quality information sources, but little is known about the use and credibility of sources of information on medicinal products among Polish doctors. The main goal of this study was to analyze the sources of information on medicinal products among primary care physicians in Poland.

Methods: A survey was conducted among 316 primary care physicians in Poland. The following information was collected: demographic data of participants, type and frequency of using data sources on medicinal products, barriers to access credible information, assessment of the credibility of the sources used, impact of a given source and other factors on prescription decisions.

Results: The most frequently mentioned sources of information were medical representatives (79%), medical journals (78%) and congresses, conventions, conferences, and training (76%). The greatest difficulty in finding the latest information about medicinal products was the lack of time. The surveyed doctors considered clinical guidelines to be the most credible source of information, and this source also had the greatest impact on the choice of prescribed medicinal products.

Conclusion: The study showed that clinicians consider clinical guidelines as the most credible source of information with the greatest impact on prescribing medicinal products. However, it is not the source most often mentioned by doctors for obtaining knowledge about medicinal products. There is a need to develop strategies and tools to provide physicians with credible sources of information.
Caffeine Protects Against Retinal Inflammation
Authors: Conti Federica , Lazzara Francesca , Romano Giovanni Luca , Platania Chiara Bianca Maria , Drago Filippo , Bucolo Claudio
Published: January 2022

Caffeine, one of the most consumed central nervous system (CNS) stimulants, is an antagonist of A1 and A2A adenosine receptors. In this study, we investigated the potential protective effects of this methylxanthine in the retinal tissue. We tested caffeine by using in vitro and in vivo paradigms of retinal inflammation. Human retinal pigment epithelial cells (ARPE-19) were exposed to lipopolysaccharide (LPS) with or without caffeine. This latter was able to reduce the inflammatory response in ARPE-19 cells exposed to LPS, attenuating the release of IL-1β, IL-6, and TNF-α and the nuclear translocation of p-NFκB. Additionally, caffeine treatment restored the integrity of the ARPE-19 monolayer assessed by transepithelial electrical resistance (TEER) and the sodium fluorescein permeability test. Finally, the ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to induce retinal inflammation and investigate the effects of caffeine treatment. Mouse eyes were treated topically with caffeine, and a pattern electroretinogram (PERG) was used to assess the retinal ganglion cell (RGC) function; furthermore, we evaluated the levels of IL-6 and BDNF in the retina. Retinal BDNF dropped significantly (p < 0.05) in the I/R group compared to the control group (normal mice); on the contrary, caffeine treatment maintained physiological levels of BDNF in the retina of I/R eyes. Caffeine was also able to reduce IL-6 mRNA levels in the retina of I/R eyes. In conclusion, these findings suggest that caffeine is a good candidate to counteract inflammation in retinal diseases.
High Hydrostatic Pressure–A Key Element to Investigate Molecular Dynamics in Biosystems
Authors: Peters Judith
Published: January 2022

Temperature variations are often used to investigate molecular dynamics through neutron scattering in biosystems, as the required techniques are well-known. Hydrostatic pressure is much less applied due to technological difficulties. However, within the last decade, a reliable and suitable equipment has been developed at the Institut Laue Langevin, Grenoble, France, which is now available on different instruments. Here, an overview on its application in relation with elastic incoherent neutron scattering to study, for instance, the impact of transitions on atomic mobility in biological samples, is presented, as well as the conclusions that can be drawn therefrom.
Myocardial Function in Offspring Aged 5 to 8 Years of Pregnancy Complicated by Severe Preeclampsia Measured by Two-Dimensional Speckle-Tracking Echocardiography
Authors: Chen Huiyun , Gong Yu , Sun Fangcan , Han Bing , Zhou Bingyuan , Fan Jiali , Gu Xinxian
Published: January 2022

Objective: This study aimed to quantitatively assess myocardial strain in preterm children aged 5 to 8 years of pregnancy complicated by severe preeclampsia (PE) by two-dimensional (2D) speckle tracking echocardiography.

Method: A cohort study of 23 preterm children delivered by severe PE pregnant women from 2010 to 2012 in the First Affiliated Hospital of Soochow University was carried out. 23 preterm children from uneventful pregnancies in the same period served as controls. Myocardial functions including left ventricular longitudinal strain, radial strain, circumferential strain, and right ventricular longitudinal strain were evaluated by conventional Doppler, tissue Doppler imaging, and 2D speckle-tracking echocardiography (2D STE). All examinations were performed by an experienced ultrasonographer using the VIVID E9 (GE Healthcare) machine, according to standard techniques.

Results: Children aged 5–8 years delivered from severe PE presented less weight (24.41 vs. 20.89 kg, P < 0.05), shorter height (124.1 vs 115.6 cm, P < 0.05) and faster heart rates (84 vs. 93 bpm, P < 0.05) compared to offspring of normotensive women. There were no significant differences in global left ventricular longitudinal strain, radial strain, circumferential strain, and right ventricular longitudinal strain between the children in the experimental group and the control group (P > 0.05).

Conclusion: Exposure to the intrauterine environment of severe PE during the fetal period did not have a significant impact on cardiac structure in premature children at 5–8 years old, but they had a higher resting heart rate which may be associated with cardiovascular disease in the long run.
Ten Years of Pediatric Lung Ultrasound: A Narrative Review
Authors: Musolino Anna Maria , Tomà Paolo , De Rose Cristina , Pitaro Eugenio , Boccuzzi Elena , De Santis Rita , Morello Rosa , Supino Maria Chiara , Villani Alberto , Valentini Piero , Buonsenso Danilo
Published: January 2022

Lung diseases are the most common conditions in newborns, infants, and children and are also the primary cause of death in children younger than 5 years old. Traditionally, the lung was not thought to be a target for an ultrasound due to its inability to penetrate the gas-filled anatomical structures. With the deepening of knowledge on ultrasound in recent years, it is now known that the affected lung produces ultrasound artifacts resulting from the abnormal tissue/gas/tissue interface when ultrasound sound waves penetrate lung tissue. Over the years, the application of lung ultrasound (LUS) has changed and its main indications in the pediatric population have expanded. This review analyzed the studies on lung ultrasound in pediatrics, published from 2010 to 2020, with the aim of highlighting the usefulness of LUS in pediatrics. It also described the normal and abnormal appearances of the pediatric lung on ultrasound as well as the benefits, limitations, and possible future challenges of this modality.
Mahonia vs. Berberis Unloaded: Generic Delimitation and Infrafamilial Classification of Berberidaceae Based on Plastid Phylogenomics
Authors: Hsieh Chia-Lun , Yu Chih-Chieh , Huang Yu-Lan , Chung Kuo-Fang
Published: January 2022

The early-diverging eudicot family Berberidaceae is composed of a morphologically diverse assemblage of disjunctly distributed genera long praised for their great horticultural and medicinal values. However, despite century-long studies, generic delimitation of Berberidaceae remains controversial and its tribal classification has never been formally proposed under a rigorous phylogenetic context. Currently, the number of accepted genera in Berberidaceae ranges consecutively from 13 to 19, depending on whether to define Berberis, Jeffersonia, and Podophyllum broadly, or to segregate these three genera further and recognize Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Dysosma, Diphylleia, and Sinopodophyllum, respectively. To resolve Berberidaceae’s taxonomic disputes, we newly assembled 23 plastomes and, together with 85 plastomes from the GenBank, completed the generic sampling of the family. With 4 problematic and 14 redundant plastome sequences excluded, robust phylogenomic relationships were reconstructed based on 93 plastomes representing all 19 genera of Berberidaceae and three outgroups. Maximum likelihood phylogenomic relationships corroborated with divergence time estimation support the recognition of three subfamilies Berberidoideae, Nandinoideae, and Podophylloideae, with tribes Berberideae and Ranzanieae, Leonticeae and Nandineae, and Podophylleae, Achlydeae, Bongardieae tr. nov., Epimedieae, and Jeffersonieae tr. nov. in the former three subfamilies, respectively. By applying specifically stated criteria, our phylogenomic data also support the classification of 19 genera, recognizing Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Diphylleia, Dysosma, and Sinopodophyllum that are morphologically and evolutionarily distinct from Berberis, Jeffersonia, and Podophyllum, respectively. Comparison of plastome structures across Berberidaceae confirms inverted repeat expansion in the tribe Berberideae and reveals substantial length variation in accD gene caused by repeated sequences in Berberidoideae. Comparison of plastome tree with previous studies and nuclear ribosomal DNA (nrDNA) phylogeny also reveals considerable conflicts at different phylogenetic levels, suggesting that incomplete lineage sorting and/or hybridization had occurred throughout the evolutionary history of Berberidaceae and that Alloberberis and Moranothamnus could have resulted from reciprocal hybridization between Berberis and Mahonia in ancient times prior to the radiations of the latter two genera.
Series-Spatial Transcriptome Profiling of Leafy Head Reveals the Key Transition Leaves for Head Formation in Chinese Cabbage
Authors: Guo Xinlei , Liang Jianli , Lin Runmao , Zhang Lupeng , Wu Jian , Wang Xiaowu
Published: January 2022

Chinese cabbage is an important leaf heading vegetable crop. At the heading stage, its leaves across inner to outer show significant morphological differentiation. However, the genetic control of this complex leaf morphological differentiation remains unclear. Here, we reported the transcriptome profiling of Chinese cabbage plant at the heading stage using 24 spatially dissected tissues representing different regions of the inner to outer leaves. Genome-wide transcriptome analysis clearly separated the inner leaf tissues from the outer leaf tissues. In particular, we identified the key transition leaf by the spatial expression analysis of key genes for leaf development and sugar metabolism. We observed that the key transition leaves were the first inwardly curved ones. Surprisingly, most of the heading candidate genes identified by domestication selection analysis obviously showed a corresponding expression transition, supporting that key transition leaves are related to leafy head formation. The key transition leaves were controlled by a complex signal network, including not only internal hormones and protein kinases but also external light and other stimuli. Our findings provide new insights and the rich resource to unravel the genetic control of heading traits.
Polyketide Derivatives in the Resistance of Gerbera hybrida to Powdery Mildew
Authors: Mascellani Anna , Leiss Kirsten , Bac-Molenaar Johanna , Malanik Milan , Marsik Petr , Hernandez Olesinski Estuardo , Tauchen Jan , Kloucek Pavel , Smejkal Karel , Havlik Jaroslav
Published: January 2022

Powdery mildew is a common disease affecting the commercial production of gerbera flowers (Gerbera hybrida, Asteraceae). Some varieties show a certain degree of resistance to it. Our objective was to identify biomarkers of resistance to powdery mildew using an 1H nuclear magnetic resonance spectroscopy and chemometrics approach in a complex, fully factorial experiment to suggest a target for selection and breeding. Resistant varieties were found to differ from those that were susceptible in the metabolites of the polyketide pathway, such as gerberin, parasorboside, and gerberinside. A new compound probably involved in resistance, 5-hydroxyhexanoic acid 3-O-β-D-glucoside, was described for the first time. A decision tree model was built to distinguish resistant varieties, with an accuracy of 57.7%, sensitivity of 72%, and specificity of 44.44% in an independent test. Our results suggest the mechanism of resistance to powdery mildew in gerbera and provide a potential tool for resistance screening in breeding programs.
Risk Factors Associated With Quality of Life in Patients With Hepatitis B Virus Related Cirrhosis
Authors: Zhang Qi , Zhong Chunxiu , Cai Shaohang , Yu Tao , Xu Xuwen , Yin Junhua
Published: January 2022

Aim: To evaluate health-related quality of life (HRQoL) of chronic hepatitis B (CHB) and hepatitis B virus (HBV) related cirrhosis patients and analyzed specific differences in all dimensions of HRQoL.

Methods: A total of 349 patients met selection criteria were enrolled. The 36-Item Short-Form Health Survey was adopted.

Results: Results showed that the physiological HRQoL of the cirrhotic group was significantly lower than that of the non-cirrhotic group (P = 0.003), the psychological HRQoL was also lower (P = 0.006). HRQoL was significantly negatively correlated with liver stiffness (P = 0.001). We further evaluated the risk factors associated with poor HRQoL in HBV-related cirrhosis patients. Results showed that positive HBV DNA viral load (OR = 6.296, P = 0.041) and HCC family history (OR = 36.211, P = 0.001) were independent factors associated with HRQoL in HBV-related cirrhosis. For better risk stratification of patients, multivariable analyses were conducted to explore the independent factors that affected specific physiological and psychological HRQoL. In specific physiological HRQoL, results show that marital status (OR = 9.971, P = 0.034), positive HBV DNA viral load (OR = 6.202, P = 0.042) and antiviral drugs (OR = 0.45, P = 0.031) were independent factors associated with physiological HRQoL in cirrhosis patients. In psychological HRQoL, only HCC family history was independent risk factors associated with psychological HRQoL (OR = 42.684, P = 0.002).

Conclusion: We found that the impaired HRQoL dimensions of HBV related cirrhosis patients differ between the various subpopulations. According to our results, risk stratification, medical decision making and personalizing interventions could be made.
Serial Recall Order of Category Fluency Words: Exploring Its Neural Underpinnings
Authors: De Marco Matteo , Venneri Annalena
Published: January 2022

Background: Although performance on the category fluency test (CFT) is influenced by many cognitive functions (i.e., including language, executive functioning and speed of processing), item-level scoring methods of CFT performance might be a promising way to capture aspects of semantic memory that are less influenced by intervenient abilities. One such approach is based on the calculation of correlation coefficients that quantify the association between item-level features and the serial order with which words are recalled (SRO).

Methods: We explored the neural underpinnings of 10 of these correlational indices in a sample of 40 healthy adults who completed a classic 1-min CFT and an MRI protocol inclusive of T1-weighted (analysed with voxel-based morphometry) and resting-state fMRI sequences for the evaluation of the default-mode network (DMN). Two sets of linear models were defined to test the association between neural maps and each correlational index: a first set in which major demographic and clinical descriptors were controlled for and a second set in which, additionally, all other 9 correlational indices were regressed out.

Results: In the analysis of the DMN, ‘SRO-frequency’, ‘SRO-dominance’ and ‘SRO-body-object interaction’ correlational indices were all negatively associated with the anterior portion of the right temporoparietal junction. The ‘SRO-frequency’ correlational index was also negatively associated with the right dorsal anterior cingulate and the ‘SRO-dominance’ correlational index with the right lateral prefrontal cortex. From the second set of models, the ‘SRO-typicality’ correlational index was positively associated with the left entorhinal cortex. No association was found in relation to grey matter maps.

Conclusion: The ability to retrieve more difficult words during CFT performance as measured by the correlational indices between SRO and item-level descriptors is associated with DMN expression in regions deputed to attentional reorienting and processing of salience of infrequent stimuli and dominance status. Of all item-level features, typicality appears to be that most closely linked with entorhinal functioning and may thus play a relevant role in assessing its value in testing procedures for early detection of subtle cognitive difficulties in people with suspected Alzheimer’s degeneration. Although exploratory, these findings warrant further investigations in larger cohorts.
Psychosocial Intervention for Youth With High Externalizing Behaviors and Aggression Is Associated With Improvement in Impulsivity and Brain Gray Matter Volume Changes
Authors: Kolla Nathan J. , Smaragdi Areti , Gainham George , Karas Karolina H. , Hawco Colin , Haas Justin , Skilling Tracey A. , Walsh Margaret , Augimeri Leena
Published: January 2022

Background: Stop, Now And Plan (SNAP) is a cognitive behavioral-based psychosocial intervention that has a strong evidence base for treating youth with high aggression and externalizing behaviors, many of whom have disruptive behavior disorders. In a pre-post design, we tested whether SNAP could improve externalizing behaviors, assessed by the parent-rated Child Behavior Checklist (CBCL) and also improve behavioral measures of impulsivity in children with high aggression and impulsivity. We then investigated whether any improvement in externalizing behavior or impulsivity was associated with gray matter volume (GMV) changes assessed using structural magnetic resonance imaging (sMRI). We also recruited typically developing youth who were assessed twice without undergoing the SNAP intervention.

Methods: Ten children who were participating in SNAP treatment completed the entire study protocol. CBCL measures, behavioral measures of impulsivity, and sMRI scanning was conducted pre-SNAP and then 13 weeks later post-SNAP. Twelve healthy controls also completed the study; they were rated on the CBCL, performed the same behavioral measure of impulsivity, and underwent sMRI twice, separated by 13 weeks. They did not receive the SNAP intervention.

Result: At baseline, SNAP participants had higher CBCL scores and performed worse on the impulsivity task compared with the healthy controls. At the second visit, SNAP participants still had higher scores on the CBCL compared with normally-developing controls, but their performance on the impulsivity task had improved to the point where their results were indistinguishable from the healthy controls. Structural magnetic resonance imaging in the SNAP participants further revealed that improvements in impulsivity were associated with GMV changes in the frontotemporal region.

Conclusion: These results suggest that SNAP led to improvement in behavioral measures of impulsivity in a cohort of boys with high externalizing behavior. Improvement in impulsivity was also associated with increased GMV changes. The mechanism behind these brain changes is unknown but could relate to cognitive behavioral therapy and contingency management interventions, important components of SNAP, that target frontotemporal brain regions. Clinically, this study offers new evidence for the potential targeting of brain regions by non-invasive modalities, such as repetitive transcranial magnetic stimulation, to improve externalizing behavior and impulsivity.
Demographic Factors and Job Characteristics Associated With Burnout in Chinese Female Nurses During Controlled COVID-19 Period: A Cross-Sectional Study
Authors: Zhou Li-Li , Zhang Shu-E , Liu Jiao , Wang Hong-Ni , Liu Li , Zhou Jing-Jing , Bu Zhi-Hua , Gao Yu-Fang , Sun Tao , Liu Bei
Published: January 2022

Background: To investigate the prevalence of burnout syndrome among Chinese female nurses during the controlled coronavirus disease 2019 (COVID-19) period and explore its associated socio-demographic factors and job characteristics.

Methods: With the multistage, stratified sampling method, a cross-sectional online survey was conducted from September to October 2020 in China. The survey tool included revised Maslach Burnout Inventory (MBI) with 15 items, socio-demographic and job characteristics. Univariate logistic regression analysis and multivariate factor logistic regression analysis were used to identify the risk factors for burnout of female nurses.

Results: During controlled COVID-19 period in China, the overall prevalence of burnout symptoms among Chinese female nurses was 60.2% with a breakdown in severity as follows: 451 (39.8 %) mild, 163 (14.4%) moderate, and 68 (6.0%) severe burnout. Little variance was reported for burnout symptoms according to job tenure (Waldχ2 = 14.828, P < 0.05,odds ratio [OR] <1), monthly salary income (Waldχ2 = 12.460, P < 0.05, OR <1), and night shift (Waldχ2 = 3.821, P < 0.05, OR > 1).

Conclusion: Burnout symptoms among Chinese female nurses were prevalent and associated with job tenure, monthly salary income, and night shift. Female nurses who were with shorter job tenure, worked at night shifts, and had lower monthly salaries tended to exhibit increasing high-level burnout than their counterparts. This study serves as an implication for administrators and policy-makers to improve the work conditions of nurses for promoting overall healthcare service quality.
S3 and Recovery and Resilience Funds: A Case Study Built on the Experience of 10 Spanish Regions
Authors: Gañán de Molina Cecilia , Guerrero Ginel José Emilio , Sillero Illanes Carmen
Published: January 2022

The EU's response to the COVID-19 crisis, namely the approval of the Next Generation package, provides an opportunity to explore to what extent the existing Smart Specialisation regional strategies and related ecosystems have been taken into account in the highly relevant territorial context in which the national Recovery Plans have been designed. According to our results the potential of the Smart Specialisation approach (S3) in relation with its place-based strategic prioritisation may have been overlooked in the process. The research is based on a desk review of relevant documents and recent literature in this field; followed by semi-structured interviews with regional planners and practitioners from 10 Spanish regions (autonomous communities); complemented, in a second phase, by the organisation of a focus group to validate the initial results. During our research we identified the main contributions that the Smart Specialisation approach has so far made to the regions (mainly in terms of participative governance and creation of regional ecosystems); and the unanimous perception shared by all the practitioners interviewed that the S3 approach has led to a change of vision in public intervention. However, all of the interviewed regions have confirmed that the drafting of the national recovery and resilience plan lacked an ex-ante alignment with the regional S3 strategies, and failed to consider the existing regional S3 ecosystems. The separation of the recovery logic (based on the operation of public consultations at national level to identify strategic projects) from the S3 logic (based on a strategic prioritisation exercise conducted by each regional ecosystem) confirms that an opportunity may have been missed in the recovery planning process to consolidate the multi-actor, multilevel and place-based S3 approach. Although there is a certain degree of disappointment among regional practitioners as a result of this misalignment, the majority of them believe in the possibility of an ex-post alignment between the two processes, that can protect existing regional shared visions. However, without clear recognition of the S3 ecosystems and the S3 managing bodies, the significant role that Smart Specialisation could play in the recovery process may be at risk.
Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
Authors: Kirkwood Phoebe M. , Shaw Isaac W. , Saunders Philippa T. K.
Published: January 2022

The human endometrium is a remarkable tissue which may experience up to 400 cycles of hormone-driven proliferation, differentiation and breakdown during a woman's reproductive lifetime. During menstruation, when the luminal portion of tissue breaks down, it resembles a bloody wound with piecemeal shedding, exposure of underlying stroma and a strong inflammatory reaction. In the absence of pathology within a few days the integrity of the tissue is restored without formation of a scar and the endometrium is able to respond appropriately to subsequent endocrine signals in preparation for establishment of pregnancy if fertilization occurs. Understanding mechanisms regulating scarless repair of the endometrium is important both for design of therapies which can treat conditions where this is aberrant (heavy menstrual bleeding, fibroids, endometriosis, Asherman's syndrome) as well as to provide new information that might allow us to reduce fibrosis and scar formation in other tissues. Menstruation only occurs naturally in species that exhibit spontaneous stromal cell decidualization during the fertile cycle such as primates (including women) and the Spiny mouse. To take advantage of genetic models and detailed time course analysis, mouse models of endometrial shedding/repair involving hormonal manipulation, artificial induction of decidualization and hormone withdrawal have been developed and refined. These models are useful in modeling dynamic changes across the time course of repair and have recapitulated key features of endometrial repair in women including local hypoxia and immune cell recruitment. In this review we will consider the evidence that scarless repair of endometrial tissue involves changes in stromal cell function including mesenchyme to epithelial transition, epithelial cell proliferation and multiple populations of immune cells. Processes contributing to endometrial fibrosis (Asherman's syndrome) as well as scarless repair of other tissues including skin and oral mucosa are compared to that of menstrual repair.
Impact of Virtual Reality Technology on Pain and Anxiety in Pediatric Burn Patients: A Systematic Review and Meta-Analysis
Authors: Smith Kathryn L. , Wang Yang , Colloca Luana
Published: January 2022

Introduction: Virtual reality (VR) has the potential to lessen pain and anxiety experienced by pediatric patients undergoing burn wound care procedures. Population-specific variables require novel technological application and thus, a systematic review among studies on its impact is warranted.

Objective: The objective of this review was to evaluate the effectiveness of VR on pain in children with burn injuries undergoing wound care procedures.

Methods: A systematic literature review was performed using PubMed and CINAHL databases from January 2010 to July 2021 with the keywords “pediatric,” “burn,” “virtual reality,” and “pain.” We included experimental studies of between- and within-subjects designs in which pediatric patients’ exposure to virtual reality technology during burn wound care functioned as the intervention of interest. Two researchers independently performed the literature search, made judgements of inclusion/exclusion based on agreed-upon criteria, abstracted data, and assessed quality of evidence using a standardized appraisal tool. A meta-analysis was conducted to evaluate the effectiveness of the VR on burning procedural pain in pediatric population. Standardized mean difference (SMD) was used as an index of combined effect size, and a random effect model was used for meta-analysis.

Results: Ten articles published between January 2010 and July 2021 passed the selection criteria: six randomized controlled trials and four randomized repeated-measures studies. Consistent results among the studies provided support for VR as effective in reducing pain and potentially pain related anxiety in children undergoing burn wound care through preprocedural preparation (n = 2) and procedural intervention (n = 8). A random effects meta-analysis model indicated a moderate and significant combined effect size (SMD = 0.60, 95% CI = 0.28–0.93, p = 0.0031) of VR effects on pain intensity ratings with no significant heterogeneity of VR intervention effects between studies. Only one study reported direct influence of VR intervention on pre-procedural situational anxiety with a moderate effect size (Cohen’s d = 0.575, 95%CI = 0.11–1.04).

Conclusion: Children’s exposure to VR during burn care procedures was associated with lower levels of pain and pain related anxiety. Moderate to large effect sizes support the integration of VR into traditional pediatric burn pain protocols irrespective of innovative delivery methods and content required for use in burned pediatric patients.
The Ixodes scapularis Symbiont Rickettsia buchneri Inhibits Growth of Pathogenic Rickettsiaceae in Tick Cells: Implications for Vector Competence
Authors: Cull Benjamin , Burkhardt Nicole Y. , Wang Xin-Ru , Thorpe Cody J. , Oliver Jonathan D. , Kurtti Timothy J. , Munderloh Ulrike G.
Published: January 2022

Ixodes scapularis is the primary vector of tick-borne pathogens in North America but notably does not transmit pathogenic Rickettsia species. This tick harbors the transovarially transmitted endosymbiont Rickettsia buchneri, which is widespread in I. scapularis populations, suggesting that it confers a selective advantage for tick survival such as providing essential nutrients. The R. buchneri genome includes genes with similarity to those involved in antibiotic synthesis. There are two gene clusters not found in other Rickettsiaceae, raising the possibility that these may be involved in excluding pathogenic bacteria from the tick. This study explored whether the R. buchneri antibiotic genes might exert antibiotic effects on pathogens associated with I. scapularis. Markedly reduced infectivity and replication of the tick-borne pathogens Anaplasma phagocytophilum, R. monacensis, and R. parkeri were observed in IRE11 tick cells hosting R. buchneri. Using a fluorescent plate reader assay to follow infection dynamics revealed that the presence of R. buchneri in tick cells, even at low infection rates, inhibited the growth of R. parkeri by 86–100% relative to R. buchneri-free cells. In contrast, presence of the low-pathogenic species R. amblyommatis or the endosymbiont R. peacockii only partially reduced the infection and replication of R. parkeri. Addition of host-cell free R. buchneri, cell lysate of R. buchneri-infected IRE11, or supernatant from R. buchneri-infected IRE11 cultures had no effect on R. parkeri infection and replication in IRE11, nor did these treatments show any antibiotic effect against non-obligate intracellular bacteria E. coli and S. aureus. However, lysate from R. buchneri-infected IRE11 challenged with R. parkeri showed some inhibitory effect on R. parkeri infection of treated IRE11, suggesting that challenge by pathogenic rickettsiae may induce the antibiotic effect of R. buchneri. This research suggests a potential role of the endosymbiont in preventing other rickettsiae from colonizing I. scapularis and/or being transmitted transovarially. The confirmation that the observed inhibition is linked to R. buchneri's antibiotic clusters requires further investigation but could have important implications for our understanding of rickettsial competition and vector competence of I. scapularis for rickettsiae.
Function Identification of Bovine ACSF3 Gene and Its Association With Lipid Metabolism Traits in Beef Cattle
Authors: He Wei , Fang Xibi , Lu Xin , Liu Yue , Li Guanghui , Zhao Zhihui , Li Junya , Yang Runjun
Published: January 2022

Acyl-CoA synthetase family member 3 (ACSF3) carries out the first step of mitochondrial fatty acid synthesis II, which is the linkage of malonate and, to a lesser extent, methylmalonate onto CoA. Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry that is generated and utilized in the cytoplasm. In this research, we verified the relationship between expression of the ACSF3 and the production of triglycerides (TGs) at the cellular level by silencing and over-expressing ACSF3. Subsequently, through Sanger sequencing, five polymorphisms were found in the functional domain of the bovine ACSF3, and the relationship between ACSF3 polymorphism and the economic traits and fatty acid composition of Chinese Simmental cattle was analyzed by a means of variance analysis and multiple comparison. The results illustrated that the expression of ACSF3 promoted triglyceride synthesis in bovine mammary epithelial cells and bovine fetal fibroblast cells. Further association analysis also indicated that individuals with the AG genotype (g.14211090 G > A) of ACSF3 were significantly associated with the fatty acid composition of intramuscular fat (higher content of linoleic acid, α-linolenic acid, and arachidonic acid), and that CTCAG haplotype individuals were significantly related to the fatty acid composition of intramuscular fat (higher linoleic acid content). Individuals with the AA genotypes of g.14211055 A > G and g.14211090 G > A were substantially associated with a larger eye muscle area in the Chinese Simmental cattle population. ACSF3 played a pivotal role in the regulation of cellular triacylglycerol and long-chain polyunsaturated fatty acid levels, and polymorphism could serve as a useful molecular marker for future marker-assisted selection in the breeding of intramuscular fat deposition traits in beef cattle.