bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Role of Tumor Mutational Burden in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Authors: Huang Taobi , Chen Xia , Zhang Huiyun , Liang Yuan , Li Longquan , Wei Hui , Sun Weiming , Wang Yuping 
Published: July 2021

PurposeImmunotherapy is regarded as the most promising treatment for cancer. However, immune checkpoint inhibitors (ICIs) are not effective for all patients. Herein, we conducted a systematic review and meta-analysis to explore whether tumor mutational burden (TMB) can be used as a potential prognostic biomarker for cancer patients treated with ICIs.MethodsWe systematically retrieved relevant literature published in the PubMed, Embase, Web of Science, and Cochrane databases up to December 28, 2020. All cohort studies and clinical trials that reported hazard ratios (HRs) for overall (OS) and progression-free survival (PFS), as well as the corresponding 95% confidence intervals (CIs) of high and low TMB patients, were included. All statistical analyses were performed using the R software.ResultsPooled results from a total of 32 studies with 6,131 participants showed significantly increased OS (HR: 0.61, 95% CI: 0.53–0.71; P &lt;0.01) and PFS (HR: 0.51, 95% CI: 0.44–0.60; P &lt;0.01) for the high TMB group receiving ICIs as compared to the low TMB group. Particularly, results were found to be more significant in studies with larger sample sizes (≥30), Western patients, higher TMB cutoff values (≥20 mut/Mb), anti–PD-1 therapy, and when the sample source was tissue and tumor type was either melanoma, small cell lung cancer, or gastric cancer.ConclusionTMB is a promising independent prognostic biomarker for cancer patients receiving ICIs, which could provide a new potential therapeutic strategy for high TMB patients who have failed traditional therapy. Furthermore, consistency in the key aspects of TMB assessment is expected in the future.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42021229016.
LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification
Authors: Yang Huiyun , Pan Yuliang , Zhang Jun , Jin Long , Zhang Xi 
Published: July 2021

BackgroundLong noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC.MethodsBioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays.ResultsFOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown.ConclusionLncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.
Erythema Multiforme Major Associated With Community-Acquired Pneumonia: Lessons From a Case Report
Authors: Fan Xiaomei , Luo Yong , Lu Jieluan , Xu Jinji , Chen Qing , Guo Huijuan , Jin Ping 
Published: July 2021

Background:Erythema multiforme (EM) is an acute immune-mediated inflammatory mucinous skin disorder. The etiology of pediatric EM involves infections, medications, autoimmune diseases, and genetic factors.Case Report:An 8-year-old girl withMycoplasma pneumoniae(MP) associated community-acquired pneumonia developed erythema target-like symptoms 1 week after azithromycin administration. The erythema quickly spread throughout the body involving the oral and ocular mucous membranes, the trunk, and the extremities, and eventually developed into erythema multiform major (EMM). Through drug withdrawal and specific treatment including systemic corticosteroids and supportive care, her clinical symptoms were improved. After 31 days, most of the mucocutaneous symptoms were relieved, except pigmentation. Human leukocyte antigen (HLA) gene sequencing was performed and 20 HLA genotypes were identified. The patient follow-up lasted for 18 months. Rashes appeared on her trunk when receiving azithromycin orally after discharge and then disappeared after azithromycin withdrawal.Conclusions:Pediatric EM is a rare disease and recognition of its etiology is important for EM management. In this case, azithromycin andHLA-DQB1*03:01genotype may contribute to EMM.Lesson:For drug-induced EM, rapid identification and withdrawal of the causative drugs is critical. Re-exposure to the same drug or exposure to drugs with similar chemical structures should also be avoided. Patient education and rational use of medicines are essential for pediatric patients.
Early Identification of Prolonged QT Interval for Prevention of Sudden Infant Death
Authors: Sarquella-Brugada Georgia , García-Algar Oscar , Zambrano María Dolores , Fernández-Falgueres Anna , Sailer Sebastian , Cesar Sergi , Sebastiani Giorgia , Martí-Almor Julio , Aurensanz Esther , Cruzalegui Jose Carlos , Merchan Erika Fernanda , Coll Mónica , Pérez-Serra Alexandra , Olmo Bernat del , Fiol Victoria , Iglesias Anna , Ferrer-Costa Carles , Puigmulé Marta , Lopez Laura , Pico Ferran , Arbelo Elena , Jordà Paloma , Brugada Josep , Brugada Ramon , Campuzano Oscar 
Published: July 2021

Introduction: Long QT syndrome is the main arrhythmogenic disease responsible for sudden death in infants, especially in the first days of life. Performing an electrocardiogram in newborns could enable early diagnosis and adoption of therapeutic measures focused on preventing lethal arrhythmogenic events. However, the inclusion of an electrocardiogram in neonatal screening protocols still remains a matter of discussion. To comprehensively analyse the potential clinical value of performing an electrocardiogram and subsequent follow-up in a cohort of newborns.Methods: Electrocardiograms were performed in 685 neonates within the first week of life. One year follow-up was performed if QTc &gt; 450 ms identified. Comprehensive genetic analysis using massive sequencing was performed in all cases with QTc &gt; 470 ms.Results: We identified 54 neonates with QTc &gt; 450 ms/ &lt;470 ms; all normalized QTc values within 6 months. Eight cases had QTc &gt; 480 ms at birth and, if persistent, pharmacological treatment was administrated during follow-up. A rare variant was identified as the potential cause of long QT syndrome in five cases. Three cases showed a family history of sudden arrhythmogenic death.Conclusions: Our prospective study identifies 0.14% of cases with a definite long QT, supporting implementation of electrocardiograms in routine pediatric protocols. It is an effective, simple and non-invasive approach that can help prevent sudden death in neonates and their relatives. Genetic analyses help to unravel the cause of arrhythmogenic disease in diagnosing neonates. Further, clinical assessment and genetic analysis of relatives allowed early identification of family members at risk of arrhythmias helping to adopt preventive personalized measures.
Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats
Authors: Delgado Nathalie Tristão Banhos , Rouver Wender do Nascimento , Freitas-Lima Leandro Ceotto , Vieira-Alves Ildernandes , Lemos Virgínia Soares , Santos Roger Lyrio dos 
Published: July 2021

BackgroundThe protective effect of estrogen on the vasculature cannot be explained only by its action through the receptors ERα and ERβ. G protein-coupled estrogen receptors (GPER)—which are widely distributed throughout the cardiovascular system—may also be involved in this response. However, little is known about GPER actions in hypertension. Therefore, in this study we evaluated the vascular response mediated by GPER using a specific agonist, G-1, in spontaneously hypertensive rats (SHR). We hypothesized that G-1 would induce a relaxing response in resistance mesenteric arteries from SHR of both sexes.MethodsG-1 concentration-response curves (1 nM-10 μM) were performed in mesenteric arteries from SHR of both sexes (10–12-weeks-old, weighing 180–250 g). The effects of G-1 were evaluated before and after endothelial removal and incubation for 30 min with the inhibitors L-NAME (300 μM) and indomethacin (10 μM) alone or combined with clotrimazole (0.75 μM) or catalase (1,000 units/mL). GPER immunolocalization was also investigated, and vascular hydrogen peroxide (H2O2) and ROS were evaluated using dichlorofluorescein (DCF) and dihydroethidium (DHE) staining, respectively.ResultsGPER activation promoted a similar relaxing response in resistance mesenteric arteries of female and male hypertensive rats, but with the participation of different endothelial mediators. Males appear to be more dependent on the NO pathway, followed by the H2O2 pathway, and females on the endothelium and H2O2 pathway.ConclusionThese findings show that the GPER agonist G-1 can induce a relaxing response in mesenteric arteries from hypertensive rats of both sexes in a similar way, albeit with differential participation of endothelial mediators. These results contribute to the understanding of GPER activation on resistance mesenteric arteries in essential hypertension.
Can Reactivity of Heart Rate Variability Be a Potential Biomarker and Monitoring Tool to Promote Healthy Aging? A Systematic Review With Meta-Analyses
Authors: Manser Patrick , Thalmann Melanie , Adcock Manuela , Knols Ruud H. , de Bruin Eling D. 
Published: July 2021

Background: Monitoring phasic responses of heart rate variability (HRV) in terms of HRV reactivity [i. e., the absolute change from resting state to on-task (i.e., absolute values of HRV measured during exercise)] might provide useful insights into the individual psychophysiological responses of healthy middle-aged to older adults (HOA) to cognitive and physical exercises.Objectives: To summarize the evidence of phasic HRV responses to cognitive and physical exercises, and to evaluate key moderating factors influencing these responses.Methods: A systematic review with meta-analyses was performed. Publications up to May 2020 of the databases Medline (EBSCO), Embase, Cochrane Library, CINAHL, Psycinfo, Web of Science, Scopus, and Pedro were considered. Controlled clinical trials and observational studies measuring phasic HRV responses to cognitive and/or physical exercises in HOA (≥50 years) were included.Results: The initial search identified 6,828 articles, of which 43 were included into the systematic review. Compared to resting state, vagally-mediated HRV indices were significantly reduced during all types of exercises [Hedge's g = −0.608, 95 % CI (−0.999 to −0.218), p = 0.002] indicating a significant parasympathetic withdrawal compared to rest. The key moderating variables of these responses identified included exercise intensity for physical exercises, and participant characteristics (i.e., level of cognitive functioning, physical fitness), task demands (i.e., task complexity and modality) and the individual responses to these cognitive challenges for cognitive exercises. In particular, higher task demands (task complexity and physical exercise intensity) were related to larger HRV reactivities. Better physical fitness and cognition were associated with lower HRV reactivities. Additionally, HRV reactivity appeared to be sensitive to training-induced cognitive and neural changes.Conclusion: HRV reactivity seems to be a promising biomarker for monitoring internal training load and evaluating neurobiological effects of training interventions. Further research is warranted to evaluate the potential of HRV reactivity as a monitoring parameter to guide cognitive-motor training interventions and/or as a biomarker for cognitive impairment. This may facilitate the early detection of cognitive impairment as well as allow individualized training adaptations that, in turn, support the healthy aging process by optimizing individual exercise dose and progression of cognitive-motor training.
Long-Term Narrowband Lighting Influences Activity but Not Intrinsically Photosensitive Retinal Ganglion Cell-Driven Pupil Responses
Authors: Lou Linjiang , Arumugam Baskar , Hung Li-Fang , She Zhihui , Beach Krista M. , Smith Earl L. , Ostrin Lisa A. 
Published: July 2021

Purpose:Light affects a variety of non-image forming processes, such as circadian rhythm entrainment and the pupillary light reflex, which are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The purpose of this study was to assess the effects of long- and short-wavelength ambient lighting on activity patterns and pupil responses in rhesus monkeys.Methods:Infant rhesus monkeys were reared under either broadband “white” light (n= 14), long-wavelength “red” light (n= 20; 630 nm), or short-wavelength “blue” light (n= 21; 465 nm) on a 12-h light/dark cycle starting at 24.1 ± 2.6 days of age. Activity was measured for the first 4 months of the experimental period using a Fitbit activity tracking device and quantified as average step counts during the daytime (lights-on) and nighttime (lights-off) periods. Pupil responses to 1 s red (651 nm) and blue (456 nm) stimuli were measured after approximately 8 months. Pupil metrics included maximum constriction and the 6 s post-illumination pupil response (PIPR).Results:Activity during the lights-on period increased with age during the first 10 weeks (p&lt; 0.001 for all) and was not significantly different for monkeys reared in white, red, or blue light (p= 0.07). Activity during the 12-h lights-off period was significantly greater for monkeys reared in blue light compared to those in white light (p= 0.02), but not compared to those in red light (p= 0.08). However, blue light reared monkeys exhibited significantly lower activity compared to both white and red light reared monkeys during the first hour of the lights-off period (p= 0.01 for both) and greater activity during the final hour of the lights-off period (p&lt; 0.001 for both). Maximum pupil constriction and the 6 s PIPR to 1 s red and blue stimuli were not significantly different between groups (p&gt; 0.05 for all).Conclusion:Findings suggest that long-term exposure to 12-h narrowband blue light results in greater disruption in nighttime behavioral patterns compared to narrowband red light. Normal pupil responses measured later in the rearing period suggest that ipRGCs adapt after long-term exposure to narrowband lighting.
Attributed Contribution of Therapist’s Emotional Variables to Psychotherapeutic Effectiveness: A Preliminary Study
Authors: Romero-Moreno Antonio , Paramio Alberto , Cruces-Montes Serafín , Zayas Antonio , Guil Rocío 
Published: July 2021

BackgroundThe aim of this manuscript is to analyze the degrees of responsibility for healing that psychotherapists attribute to a set of emotional variables of the therapist involved in the therapeutic process. Such variables, framed within the well-known common factors in psychotherapy, have been proven to be essential in making the therapeutic process effective, as has been shown by research in psychotherapy in recent decades.Materials and MethodsBased on an extensive literature review, the responses from a sample of 69 psychotherapists to a tool createdad hocare analyzed to verify whether their attributions are in line with the results of said review.ResultsThe therapists have doubts about the factors responsible for psychotherapeutic effectiveness, as well as about the value of common variables, including those of an emotional nature, not valuing them above those of a specific type. They also argue against the similar effectiveness of different psychotherapeutic models.ConclusionDiscrepancies have thus been found between the conclusions reached by research on therapeutic processes and the statements made by the therapists studied, which could indicate an insufficient impact of psychotherapeutic research on clinical practice. We also propose courses of action such as establishing training programs for the acquisition and development of emotional skills for therapists that could increase the effectiveness of their interventions.
Using Generalizability Theory and Many-Facet Rasch Model to Evaluate In-Basket Tests for Managerial Positions
Authors: Li Guangming , Pan Yuxi , Wang Weijun 
Published: July 2021

Purpose: This study aimed to analyze interview data collected from a series of in-basket tests during managerial personnel recruitment in a local Chinese company, taking advantage of the use of combination of Generalizability theory (GT) and Many-facet Rasch Model (MFRM), rather than the Classical Test Theory (CTT).Design/Methodology/Approach: Participants included 78 candidates (Mage = 37.76, SD = 6.36; 35.9% female) interviewed for eight managerial positions in a local Chinese company. Data were collected based on a series of 10 in-basket interview tests, and a 20-item rating scale (the in-basket test rating scale; IBTRS) was developed and piloted, and five expert raters rated the participants on their performance in five aspects (planning, communication and coordination, capital operations and management, analysis and problem solving, and empowerment and controlling). The data were analyzed using a crossed design of p × i × r, where p represents person, i represents item, and r represents rater. Effects of candidate (person), test item, rater, and the interaction of item and rater were examined.Findings: The use of the combination of GT and MFRM was able to provide accurate, comprehensive information over the process of in-basket interview tests. Specifically, GT analysis showed good generalization coefficient and reliability index (0.893 and 0.871, respectively), and the variation of candidates explained most of the total variance (53.22%). The candidates scored high in the dimension of empowerment and controlling. There were differences in the severity of raters. Three raters should be sufficient to ensure good scoring stability.Originality/Value: This study used the combination of GT and MFRM to assess the interview data instead of using a CTT approach.
Patterns of Lifetime Criminality in Mentally Disordered Offenders – Findings From a Nationally Representative Cohort
Authors: Krona Hedvig , Anckarsäter Henrik , Nilsson Thomas , Hofvander Björn 
Published: July 2021

Background: Treatment of mentally disordered offenders (MDOs) is challenging as their behavior and clinical conditions can be traced to a complex constellation of major mental disorders, substance use and antisocial lifestyle. Finding subgroups of these offenders, which could guide treatment and risk assessment, is desirable. There are few long-term, prospective studies of risk factors for persistent criminal behavior among MDOs.Aims: The aims are (1) to provide a map of lifetime criminality in MDOs, (2) to identify subgroups of offenders, and (3), if such clusters exist, to test whether they differ in lifetime criminality and patterns of negative events during in-patient treatment.Methods: Background data on all offenders from the Malmö University Hospital catchment area sentenced to forensic psychiatric in-patient treatment 1999–2005 (n = 125) was collected. Data on negative events during treatment (violence, threats, absconding and substance use) from date of admittance until discharge or until June 30, 2008 was gathered. Court decisions for 118 of the cohort-individuals were collected from the 1st of January 1973 until December 31, 2013. We used hierarchical cluster analysis to identify subgroups and MANOVA-analysis to examine differences between these clusters on lifetime criminality variables and negative events. A MANCOVA was used to control for time in treatment.Results: The cohort was sentenced to a total of 3,380 crimes (944 violent) during the study period. Median age at first crime was 20 years (range 15–72), and at first violent crime 27 years (range 15–72). A subgroup (n = 26) was characterized by childhood adversities, neurodevelopmental disorders and later substance use disorders and was more often associated with substance-related crimes, financial crimes and lower age at first crime. During treatment, this cluster showed higher rates of substance use and threats. When controlling for treatment time, no differences in negative events were found.Conclusions: This study replicated findings from prison populations of the existence of a more criminally persistent phenotype characterized by early-onset neurodevelopmental and behavior disorders, childhood adversities and later substance use disorders. We did not find this cluster of variables to be related to negative events during inpatient treatment when controlling for length of stay.
Systematic Review of Integration and Radicalization Prevention Programs for Migrants in the US, Canada, and Europe
Authors: Del Pino-Brunet Natalia , Hombrados-Mendieta Isabel , Gómez-Jacinto Luis , García-Cid Alba , Millán-Franco Mario 
Published: July 2021

Background: International migration processes are some of the most important events of our time. Migrating implies a broad range of factors that affect integration, and which may be linked to radicalization. Host countries use different methods for the integration of migrants. The aim of this systematic review is to analyze intervention programs that aim at promoting social integration and preventing the radicalization of migrants, with the objective of studying actions carried out in the US, Canada, and Europe to this effect.Method: Worldwide known bibliographic databases (PsyCINFO, Sociological Abstracts, Psycarticles, Psychology Database, Medline, SCOPUS, and Google Scholar) were used to search studies published before January 2019 and which analyzed integration or radicalization prevention programs with migrants.Results: A total of 601 studies were screened, from which 18 met the inclusion criteria. The analysis of programs addressed to migrant women points to a decrease in loneliness and depression and an increase of migrants' perception of social support and self-esteem. Programs carried out in schools and families improve children's knowledge of their culture and that of others, increase their feelings of inclusion, and reduce their aggressiveness, stress, and anxiety. Language programs promote communication and employment search, as well as improve migrants' quality of life. One of the most effective activities included in these programs is to connect recently arrived migrants with local population and/or long-term residents. The latter act as mentors and teachers, helping recently arrived migrants understand resources and to be more integrated in the new country, as well as reducing discrimination from the local population.Conclusions: The review concluded the importance of intervention programs for integration, migrants' quality of life, prevention of extreme behaviors, and intercultural cohabitation. Future programs must be more detailed regarding participants' information and carry out more comprehensive assessments.