bluuebunny/crossref_metadata_2025_split huggingface dataset:
FHL3 Contributes to EMT and Chemotherapy Resistance Through Up-Regulation of Slug and Activation of TGFβ/Smad-Independent Pathways in Gastric Cancer
Authors: Cao Guodong , Li Pengping , He Xiaobo , Jin Mengyao , Li Mengying , Chen Sihan , Xu Xin , Sun Qiang , Xiong Maoming , Chen Bo 
Published: June 2021

BackgroundGastric cancer presents high risk of metastasis and chemotherapy resistance. Hence, it is important to understand the mechanisms of gastric cancer distant metastasis and chemotherapeutic resistance. Our previous study has revealed Four and a Half LIM Domains 3 (FHL3) plays as a binding partner of Glycogen Synthase Kinase 3 Beta (GSK3β), promoted tumor metastasis in pancreatic cancer. However, the role of FHL3 in gastric cancer still remains unclear.MethodsTCGA database and clinical samples are used for exploring the role of FHL3 in disease progression and prognosis. Oxaliplatin (OHP) resistance cell lines were established to study the role of FHL3 in chemotherapy resistance. The experiments about cell proliferation, apoptosis, and metastasis were performed to measure the chemotherapy effects of sh-FHL3 on gastric cancer cell lines and in vivo. That FHL3 changed the EMT phenotype was verified by western blot. Finally, we explored the mechanism of FHL3-mediated EMT and chemotherapy resistance.ResultsmRNA and protein level of FHL3 were significantly up-regulated in gastric cancer tissues when compared with adjacent tissue. FHL3 higher expression is always accompanied with higher TNM stage and worse overall survival. FHL3 over-expressed could lead to OHP resistance. Knockdown of FHL3 slightly inhibited the cell growth, while it obviously sensitized the chemotherapy in vivo and in vitro. In addition, down-regulation of FHL3 increased the mesenchymal markers, such as Slug, Snail, Twist Family BHLH Transcription Factor 1 (Twist1), and Vimentin, while it decreased the epithelial marker E-cadherin. Cell and animal experiments also proved that down-regulation of FHL3 can decrease cancer cell metastasis. For mechanism study, FHL3 knockdown down-regulated the expression level of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Regulated Protein Kinase (ERK) pathway and Transforming Growth Factor-β (TGFβ)/Phosphatidylinositol 3-Kinase (PI3K)/protein kinase B(Akt)/GSK3β-(Ring Finger Protein 146) RNF146/ubiquitin pathway. FHL3 competitively bonded the ubiquitin complex (Slug/GSK3β/RNF146) with Slug and inhibited ubiquitination of Slug. Mesenchymal phenotype cells hold higher level of Multidrug Resistance Gene1 (MDR1), and the FHL3 knockdown reverts the MDR1 in this type cell.ConclusionFHL3 high expression contributed to EMT and chemotherapy resistance via MAPK, and PI3K pathways were activated. FHL3 competitively bonded the ubiquitin complex with Slug, resulting in the up-regulation of Slug and leading to metastasis of gastric cancer.
The Novel Methylation Biomarker SCARA5 Sensitizes Cancer Cells to DNA Damage Chemotherapy Drugs in NSCLC
Authors: Peng Qi , Liu Yan , Kong Xuehua , Xian Jie , Ye Lin , Yang Li , Guo Shuliang , Zhang Yan , Zhou Lan , Xiang Tingxiu 
Published: June 2021

BackgroundScavenger Receptor Class A Member 5 (SCARA5), also known as TESR, is expressed in various tissues and organs and participates in host defense. Recent studies have found SCARA5 to produce an anti-tumor effect for multiple tumors, although the mechanistic basis for the effect is unknown.MethodsBioinformatics, methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR, and immunohistochemistry were used to assess promoter methylation and expression of SCARA5 in lung cancer tissues and cell lines. The biological effect of SCARA5 on lung cancer cells was confirmed by the CCK8 assay, colony formation assay, and flow cytometry. GSEA, Western blot, RNA sequencing, and luciferase-based gene reporter assay were used to explore the mechanistic basis for the anti-tumor effect of SCARA5. Chemosensitivity assays were used to evaluate the anti-tumor effect of SCARA5 in conjunction with chemotherapeutic drugs.ResultsWe found SCARA5 to be downregulated in lung cancer cell lines and tissues with SCARA5 levels negatively related to promoter methylation. Ectopic expression of SCARA5 suppressed proliferation of lung cancer both in vitro and in vivo through upregulation of HSPA5 expression, which inhibited FOXM1 expression resulting in G2/M arrest of the A549 cell line. SCARA5 also improved susceptibility of A549 cells to chemotherapeutic drugs that damage DNA.ConclusionSCARA5 was silenced in NSCLC due to promoter methylation and could be a potential tumor marker in NSCLC.
Patient-Reported Outcomes Assessing the Impact of Palliative Radiotherapy on Quality of Life and Symptom Burden in Head and Neck Cancer Patients: A Systematic Review
Authors: Fabian Alexander , Domschikowski Justus , Hoffmann Markus , Weiner Oliver , Schmalz Claudia , Dunst Jürgen , Krug David 
Published: June 2021

Incurable head and neck cancer has a poor prognosis and impairs a patient’s health-related quality of life. Palliative radiotherapy may improve or stabilize health-related quality of life and symptoms, best measured by patient-reported outcomes. There is no systematic analysis if palliative radiotherapy for head and neck cancer improves or stabilizes health-related quality of life or symptoms as validly measured by patient-reported outcomes. Therefore, the primary objective of this systematic review (PROSPERO-ID: CRD42020166434) was to assess the effect of palliative radiotherapy for head and neck cancer on patient-reported outcomes. The secondary objective was to assess the rate and quality of use of patient-reported outcomes in relevant studies claiming a “palliative effect” of radiotherapy. The databases MEDLINE/PubMed, EMBASE, Cochrane CENTRAL, “ClinicalTrials.gov” were searched. Concerning the primary objective, four studies were eligible to assess the effectiveness of palliative radiotherapy as measured by patient-reported outcomes. A narrative synthesis suggests a favorable impact of palliative radiotherapy on health-related quality of life and symptom burden. The risk of bias, however, is considerable and the overall quality of evidence low. Concerning the secondary objective, over 90% of studies claiming a “palliative effect” of palliative radiotherapy did either not use patient-reported outcomes or did so by limited quality. In conclusion, implementation of patient-reported outcomes in studies assessing palliative radiotherapy for head and neck cancer should be fostered. Palliative radiotherapy remains an option for head and neck cancer patients, although more studies focusing on patient-reported outcomes are needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020166434
Recurrent Wheezing and Asthma After Respiratory Syncytial Virus Bronchiolitis
Authors: Zhou Yunlian , Tong Lin , Li Mengyao , Wang Yingshuo , Li Lanxin , Yang Dehua , Zhang Yuanyuan , Chen Zhimin 
Published: June 2021

Background: Respiratory syncytial virus (RSV) is the most common pathogen of acute bronchiolitis in children, which sometimes triggers the development of recurrent wheezing and increases the risk of childhood asthma.Methods: We enrolled 425 children who were diagnosed with RSV-infected bronchiolitis at the department of pulmonology, Children's Hospital Zhejiang University School of Medicine in 2011. Long-term follow-up was performed to explore the consequence of bronchiolitis on subsequent recurrent wheezing and asthma.Results: Of 425 patients, 266 cases completed the entire follow-up, the mean age of onset was 4.9 (3.3) months, and the male-to-female ratio was 2.5. The mean birth weight of all patients was 3.22 (0.63) kg, and the number of patients who had a history of cesarean section was 148. According to the outcome of follow-up, 36 were in the recurrent wheezing (RW) group, 65 were in the asthma (AS) group, and the remaining 165 were in the completely recovered (CR) group. The age of onset was older and the birth weights were higher in the AS group than those in the CR group (P &lt; 0.05). And the higher proportion of cesarean sections was higher in the RW group than that in the CR group (P &lt; 0.05). Furthermore, we found a remarkable increasing of serum IgE in the AS groups than that in the CR group (P &lt; 0.01). Multiple logistic regression analysis showed that the cesarean section was the risk factor for the development of recurrent wheezing and the higher birth weight was the risk factor for the development of asthma.Conclusion: RSV bronchiolitis might increase the incidence of recurrent wheezing and asthma. Allergic constitution was an important prerequisite for the occurrence of asthma, and related risk factor such as cesarean section can only increase recurrent wheezing to a certain extent within a certain period of time. And we also find higher birth weight and older onset age for those who develop asthma, which should be verified in the future.
High Glucose Activates YAP Signaling to Promote Vascular Inflammation
Authors: Ortillon Jeremy , Le Bail Jean-Christophe , Villard Elise , Léger Bertrand , Poirier Bruno , Girardot Christine , Beeske Sandra , Ledein Laetitia , Blanchard Véronique , Brieu Patrice , Naimi Souâd , Janiak Philip , Guillot Etienne , Meloni Marco 
Published: June 2021

Background and AimsThe YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known.MethodsThe effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice.ResultsIn vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased.ConclusionWith the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications.
Paternal Leave and Father-Infant Bonding: Findings From the Population-Based Cohort Study DREAM
Authors: Schaber Ronja , Kopp Marie , Zähringer Anna , Mack Judith T. , Kress Victoria , Garthus-Niegel Susan 
Published: June 2021

Background: Father-infant bonding is important for child development. Yet, in contrast to mother-infant bonding, little is known about factors that might facilitate father-infant bonding. With new generations of fathers being more involved in childcare, this study aims to examine the impact of paternal leave duration on father-infant bonding, and whether this relation is mediated by the amount of time fathers actively spend on childcare.Methods: Data of n = 637 fathers were derived from the German population-based cohort study “Dresden Study on Parenting, Work, and Mental Health” (DREAM). Mediation analyses were conducted. Duration of paternal leave (predictor), weekly hours spent on childcare (mediator), and father-infant bonding (outcome) were measured at 14 months postpartum. The potential confounders current status of paternal leave, part-time work during paternal leave, duration of solo paternal leave, age, education, and partnership satisfaction were included in a second mediation analysis.Results: Without considering confounders, duration of paternal leave positively predicted father-infant bonding through weekly hours spent on childcare. When adding confounders to the model, this indirect path did not stay significant. Moreover, in the adjusted model and on the direct path duration of paternal leave negatively predicted father-infant bonding. Additionally, partnership satisfaction positively predicted father-infant bonding. Some study variables were significantly associated with the mediator. Longer duration of paternal leave, currently being on paternal leave, younger age, and lower educational level predicted more weekly hours spent on childcare.Conclusions: Duration of paternal leave not being a stable predictor for father-infant bonding suggests that fathers, who do not have the opportunity to take long periods of paternal leave, can still form strong bonds with their infants. Other factors, for example partnership satisfaction, which might represent fathers' underlying capacity to bond, might be more crucial for father-infant bonding. At the same time, results should not be interpreted in a way that father involvement (e.g., paternal leave/time spent) does not matter for children's development. The finding that longer duration of paternal leave increases weekly hours spent on childcare supports the idea that facilitating father involvement can be achieved by paternal leave incentives such as non-transferable father months.
Diagnostic Accuracy of the Drug Use Disorder Identification Test and Its Short Form, the DUDIT-C, in German Adolescent Psychiatric Patients
Authors: Basedow Lukas A. , Kuitunen-Paul Sören , Eichler Anna , Roessner Veit , Golub Yulia 
Published: June 2021

BackgroundA common screening instrument for substance use disorders (SUDs) is the Drug Use Disorders Identification Test (DUDIT) which includes a short form regarding only drug consumption (DUDIT-C). We aim to assess if a German version of the DUDIT, adapted for adolescents, is a suitable screening instrument in a sample of adolescent psychiatric patients.MethodsN = 124 (54 female) German adolescent (M = 15.6 + 1.5 years) psychiatric patients completed the DUDIT and received a diagnostic interview (MINI-KID) assessing DSM-5 SUD criteria. A confirmatory factor analysis (CFA), receiver operating characteristic (ROC) curves, the area under the curve (AUC), and Youden’s Index were calculated.ResultsA two-factor model of the DUDIT shows the best model fit (CFI = 0.995, SRMR = 0.055, RMSEA = 0.059, WRMR = 0.603). The DUDIT as well as the DUDIT-C show high diagnostic accuracy, with AUC = 0.95 and AUC = 0.88, respectively. For the DUDIT a cut-off value of 8.5 was optimal (sensitivity = 0.93, specificity = 0.91, J = 0.84), while for the DUDIT-C the optimal cut-off value was at 1.5 (sensitivity = 0.86, specificity = 0.84, J = 0.70).ConclusionThis is the first psychometric evaluation of the DUDIT in German, adolescent psychiatric outpatients, using the DSM-5 diagnostic criteria. The DUDIT as well as the DUDIT-C are well suited for use in this population. Since in our sample only few patients presented with a mild or moderate SUD, our results need to be replicated in a sample of adolescents with mild SUD.
Psychiatrization of Society: A Conceptual Framework and Call for Transdisciplinary Research
Authors: Beeker Timo , Mills China , Bhugra Dinesh , te Meerman Sanne , Thoma Samuel , Heinze Martin , von Peter Sebastian 
Published: June 2021

Purpose:Worldwide, there have been consistently high or even rising incidences of diagnosed mental disorders and increasing mental healthcare service utilization over the last decades, causing a growing burden for healthcare systems and societies. While more individuals than ever are being diagnosed and treated as mentally ill, psychiatric knowledge, and practices affect the lives of a rising number of people, gain importance in society as a whole and shape more and more areas of life. This process can be described as the progressing psychiatrization of society.Methods:This article is a conceptual paper, focusing on theoretical considerations and theory development. As a starting point for further research, we suggest a basic model of psychiatrization, taking into account its main sub-processes as well as its major top-down and bottom-up drivers.Results:Psychiatrization is highly complex, diverse, and global. It involves various protagonists and its effects are potentially harmful to individuals, to societies and to public healthcare. To better understand, prevent or manage its negative aspects, there is a need for transdisciplinary research, that empirically assesses causes, mechanisms, and effects of psychiatrization.Conclusion:Although psychiatrization has highly ambivalent effects, its relevance mainly derives from its risks: While individuals with minor disturbances of well-being might be subjected to overdiagnosis and overtreatment, psychiatrization could also result in undermining mental healthcare provision for the most severely ill by promoting the adaption of services to the needs and desires of the rather mild cases. On a societal level, psychiatrization might boost medical interventions which incite individual coping with social problems, instead of encouraging long-term political solutions.
Platelet-Rich Plasma Combined With Autologous Grafting in the Treatment of Long Bone Delayed Union or Non-union: A Meta-Analysis
Authors: An Weijun , Ye Peng , Zhu Tao , Li Zhizhong , Sun Jianbin 
Published: June 2021

Background: Platelet-rich plasma (PRP) has been suggested as an emerging treatment for bone defects. However, whether PRP could enhance the therapeutic efficacy of autologous bone grafting for long bone delayed union or non-union remains unknown. A meta-analysis of randomized and non-randomized controlled trials (RCT and NRCT) was performed to summarize current evidence.Methods: Relevant RCTs and NRCTs comparing the influences of autologous bone grafting on healing of long bone delayed union or non-union with and without PRP were obtained by searching PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure, and WanFang databases from inception to September 10, 2020. A random-effect model was applied to pool the results with the incorporation of the potential heterogeneity. Subgroup analysis according to study design was also performed.Results: Six RCTs and two NRCTs with 420 patients were included. Compared to patients allocated to autologous bone grafting alone, those allocated to combined treatment with PRP and autologous bone grafting were not associated with higher rates of radiographic bone healing [risk ratio (RR): 1.06, 95% confidence interval (CI): 0.99–1.13, P = 0.09; I2 = 24%] or excellent/good posttreatment limb function (RR: 1.14, 95% CI: 0.95–1.37, P = 0.37; I2 = 0%) but was associated with a shorter healing time (mean difference: −1.35 months, 95% CI: −1.86 to −0.84, P &lt; 0.001; I2 = 58%). Subgroup analysis according to study design showed similar results for the above outcomes (P-values for subgroup difference all &gt;0.10).Conclusions: Combined treatment with PRP and autologous bone grafting may be effective to accelerate the healing of long bone delayed union or non-union compared to autologous bone grafting alone.
Lessons Learned in 11 Years of Experience With Open Abdomen Treatment With Negative-Pressure Therapy for Various Abdominal Emergencies
Authors: Gasser Elisabeth , Rezaie Daniel , Gius Johanna , Lorenz Andreas , Gehwolf Philipp , Perathoner Alexander , Öfner Dietmar , Kafka-Ritsch Reinhold 
Published: June 2021

Introduction: Open abdomen (OA) treatment with negative-pressure therapy (NPT) was initiated for perforated diverticulitis and subsequently extended to other abdominal emergencies. The aim of this retrospective study was to analyze the indications, procedures, duration of NPT, and the outcomes of all our patients.Methods: All consecutive patients treated with intra-abdominal NPT from January 1, 2008 to December 31, 2018 were retrospectively analyzed.Results: A total of 438 patients (44% females) with a median (range) age of 66 (12–94) years, BMI of 25 (14–48) kg/m2, and ASA class I, II, III, and IV scores of 36 (13%), 239 (55%), 95 (22%), and 3(1%), respectively, were treated with NPT. The indication for surgery was primary bowel perforation in 163 (37%), mesenteric ischemia in 53 (12%), anastomotic leakage in 53 (12%), ileus in 53 (12%), postoperative bowel perforation/leakage in 32 (7%), abdominal compartment in 15 (3%), pancreatic fistula in 13 (3%), gastric perforation in 13 (3%), secondary peritonitis in 11 (3%), burst abdomen in nine (2%), biliary leakage in eight (2%), and other in 15 (3%) patients. A damage control operation without reconstruction in the initial procedure was performed in 164 (37%) patients. The duration of hospital and intensive care stay were, median (range), 28 (0–278) and 4 (0–214) days. The median (range) duration of operation was 109 (22–433) min and of NPT was 3(0–33) days. A trend to shorter duration of NPT was observed over time and in the colonic perforation group. The mean operating time was shorter when only blind ends were left in situ, namely 110 vs. 133 min (p = 0.006). The mortality rates were 14% at 30 days, 21% at 90 days, and 31% at 1 year. An entero-atmospheric fistula was observed in five (1%) cases, most recently in 2014. Direct fascia closure was possible in 417 (95%) patients at the end of NPT, but least often (67%, p = 0.00) in patients with burst abdomen. During follow-up, hernia repair was observed in 52 (24%) of the surviving patients.Conclusion: Open abdomen treatment with NPT is a promising concept for various abdominal emergencies, especially when treated outside normal working hours. A low rate of entero-atmospheric fistula formation and a high rate of direct fascia closure were achieved with dynamic approximation of the fascia edges. The authors recommend an early-in and early-out strategy as the prolongation of NPT by more than 1 week ends up in a frozen abdomen and does not improve abdominal sepsis.
First Detection of Human ST131-CTX-M-15-O25-B2 Clone and High-Risk Clonal Lineages of ESBL/pAmpC-Producing E. coli Isolates from Diarrheic Poultry in Tunisia
Authors: Jouini Ahlem , Klibi Amira , Elarbi Imen , Chaabene Meriem Ben , Hamrouni Safa , Souiai Oussema , Hanachi Mariem , Ghram Abdeljelil , Maaroufi Abderrazak 
Published: June 2021

Circulation of a multi-resistance clone of bacteria associated with genetic elements in diseased animals constitutes a global public health problem. Our study focused on the characterization of the support of ESBL in cefotaxime resistant E. coli (CTXR) isolates recovered from poultry with diarrhea, analysis of their clonal lineage, and virulence-associated genes. The study was carried out on 130 samples of chickens with diarrhea, collected in 2015 from poultry farms in Tunisia. Isolates of 20 CTXR E. coli strains were identified as ESBL and AmpC β- lactamase producers. The following β-lactamase genes (number of isolates) were detected: blaCTX-M-15+ blaOXA1 (4), blaCTX-M-15 + blaOXA1 + blaTEM-1b (2), blaCTX-M-1 + blaTEM-1b (9), blaCTX-M-1 (2), blaCMY2 + blaTEM-1b (3). Six E. coli harboring blaCTXM-15 were allocated to ST131-B2-O25b-; six and three blaCTX-M-1 were grouped in ST155, ST10, and ST58, respectively, related to the phylogroup D and A. The qnrB gene, the variant aac(6′)-Ib-cr, and the class 1 integrons with different gene cassettes, were detected amongst our 20 isolated strains, which were classified as ExPEC and aEPEC. Our findings highlighted the emergence of the human pandemic ST131-CTX-M-15-O25-B2 clone and the high risk of such clonal lineage strains in diarrheic poultry, in Tunisia, which could constitute a risk of their transfer to healthy animals and humans.