bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Mice Model for Studying the Efficacy and IRAEs of Anti-CTLA4 Targeted Immunotherapy
Authors: Xu Shengchao , Yan Xi , Dai Gan , Luo Chengke
Published: June 2021

Background

Patient-derived orthotopic xenograft (PDOX) is a popular animal model for translational cancer research. Immunotherapy is a promising therapy against glioblastoma (GBM). However, the PDOX model is limited to evaluating immune-related events. Our study aims to establish GBM humanized PDOX (HPDOX) mice models to study the mechanism of anti-CTLA4 immunotherapy and immune-related adverse events (IRAEs).

Methods

HPDOX models were established by culturing GBM tissues and intracranially implanting them in NSG mice. Meanwhile, peripheral blood mononuclear cells (PBMCs) were separated from peripheral blood and of GBM patients and administrated in corresponding mice. The population of CD45+, CD3+, CD4+, CD8+, and regulatory T (Treg) cells was estimated in the peripheral blood or tumor.

Results

T cells derived from GBM patients were detected in HPDOX mice models. The application of anti-CTLA4 antibodies (ipilimumab and tremelimumab) significantly inhibited the growth of GBM xenografts in mice. Moreover, residual patient T cells were detected in the tumor microenvironment and peripheral blood of HPDOX mice and were significantly elevated by ipilimumab and tremelimumab. Additionally, Treg cells were decreased in mice with IRAEs. Lastly, the proportion of CD4+/CD8+ T cells dramatically increased after the administration of ipilimumab. And the degree of IRAEs may be related to CD56+ expression in HPDOX.

Conclusions

Our study established HPDOX mice models for investigating the mechanism and IRAEs of immunotherapies in GBM, which would offer a promising platform for evaluating the efficacy and IRAEs of novel therapies and exploring personalized therapeutic strategies.
Immunonutritive Scoring in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Prognostic Nutritional Index or Controlling Nutritional Status Score?
Authors: Müller Lukas , Hahn Felix , Mähringer-Kunz Aline , Stoehr Fabian , Gairing Simon J. , Foerster Friedrich , Weinmann Arndt , Galle Peter R. , Mittler Jens , Pinto dos Santos Daniel , Pitton Michael B. , Düber Christoph , Kloeckner Roman
Published: June 2021

Objectives

The Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) score are immunonutritive scoring systems with proven predictive ability in various cancer entities, including hepatocellular carcinoma (HCC). We performed the first evaluation of the CONUT score for patients undergoing transarterial chemoembolization (TACE) and compared CONUT and PNI in the ability to predict median overall survival (OS).

Methods

Between 2010 and 2020, we retrospectively identified 237 treatment-naïve patients with HCC who underwent initial TACE at our institution. Both scores include the albumin level and total lymphocyte count. The CONUT additionally includes the cholesterol level. Both scores were compared in univariate and multivariate regression analyses taking into account established risk factors. In a second step, a subgroup analysis was performed on BCLC stage B patients, for whom TACE is the recommended first-line treatment.

Results

A high CONUT score and low PNI were associated with impaired median OS (8.7 vs. 22.3 months, p<0.001 and 6.8 vs. 20.1 months, p<0.001, respectively). In multivariate analysis, only the PNI remained an independent prognostic predictor (p=0.003), whereas the CONUT score lost its predictive ability (p=0.201). In the subgroup of recommended TACE candidates, both CONUT and PNI were able to stratify patients according to their median OS (6.6 vs. 17.9 months, p<0.001 and 10.3 vs. 22.0 months, p<0.001, respectively). Again, in the multivariate analysis, only the PNI remained an independent prognostic factor (p=0.012).

Conclusion

Both scores were able to stratify patients according to their median OS, but only the PNI remained an independent prognostic factor. Therefore, PNI should be preferred when evaluating the nutritional status of patients undergoing TACE.
Microfluidic Assaying of Circulating Tumor Cells and Its Application in Risk Stratification of Urothelial Bladder Cancer
Authors: Fu Guanghou , Cheng Kok Suen , Chen Anqi , Xu Zhijie , Chen Xiaoyi , Tian Junjie , Xu Congcong , Sun Yukun , Neoh Kuang Hong , Dai Yun , Han Ray P. S. , Jin Baiye
Published: June 2021

Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.
Case Report: Cerebral Revascularization in a Child With Mucopolysaccharidosis Type I
Authors: Grant Nathan , Taylor J. Michael , Plummer Zach , Myers Kasiani , Burrow Thomas , Luchtman-Jones Lori , Byars Anna , Hammill Adrienne , Wusick Katie , Smith Edward , Leach James , Vadivelu Sudhakar
Published: June 2021

Mucopolysaccharidosis (MPS) type I is a rare lysosomal storage disorder caused by an accumulation of glycosaminoglycans (GAGs) resulting in multisystem disease. Neurological morbidity includes hydrocephalus, spinal cord compression, and cognitive decline. While many neurological symptoms have been described, stroke is not a widely-recognized manifestation of MPS I. Accordingly, patients with MPS I are not routinely evaluated for stroke, and there are no guidelines for managing stroke in patients with this disease. We report the case of a child diagnosed with MPS I who presented with overt stroke and repeated neurological symptoms with imaging findings for severe ventriculomegaly, infarction, and bilateral terminal carotid artery stenosis. Direct intracranial pressure evaluation proved negative for hydrocephalus. The patient was subsequently treated with cerebral revascularization and at a 3-year follow-up, the patient reported no further neurological events or new ischemia on cerebral imaging. Cerebral arteriopathy in patients with MPS I may be associated with GAG accumulation within the cerebrovascular system and may predispose patients to recurrent strokes. However, further studies are required to elucidate the etiology of cerebrovascular arteriopathy in the setting of MPS I. Although the natural history of steno-occlusive arteriopathy in patients with MPS I remains unclear, our findings suggest that cerebral revascularization is a safe treatment option that may mitigate the risk of future strokes and should be strongly considered within the overall management guidelines for patients with MPS I.
Multisystem Inflammatory Syndrome in Children (MIS-C)—A Case Series in December 2020 in Vienna, Austria
Authors: Kurz Herbert , Gombala Tomas
Published: June 2021

MIS-C is a novel clinical syndrome in children and adolescents, was first encountered in the spring of 2020 as a post COVID-19 multisystem inflammatory syndrome. The highest number of SARS-CoV-2 infections in Austria were registered in November 2020. In December 2020, eight patients with MIS-C were hospitalized at the pediatric department of Klinik Donaustadt, a large municipal hospital in Vienna. Six of the patients needed pediatric intensive care. As we lack any international consensus on the diagnosis and treatment of this severe complication, we used a multidisciplinary approach. The purpose was to establish an internal standard for maximizing the efficacy and safety of treatment, and standardizing the clinical management of this disease.
Clinical Characteristics of Paediatric Pancreatitis Caused by Pancreaticobiliary Malformation: A Single-Centre Retrospective Analysis
Authors: Guo Jing , Jia Qian-ru , Sun Mei
Published: June 2021

Background/Aims: To investigate the clinical profiles of children with pancreatitis caused by pancreaticobiliary malformation.

Methods: We retrospectively analysed the clinical data of children diagnosed with pancreatitis at our institute from June 2017 to January 2021.

Results: A total of 195 patients and 169 control subjects were included in this study. Twenty-six (13.3%) patients had pancreaticobiliary malformation-related pancreatitis. The average age of onset in the pancreaticobiliary malformation pancreatitis (PMP) group was lower than that in the non-PMP group, and the difference was statistically significant. The number of patients in the PMP group that had jaundice was significantly higher than that of the non-PMP group (P < 0.05). Logistic regression analysis showed that total bilirubin (TB) and γ-glutamyltransferase (GGT) (odds ratio = 1.096, P < 0.01) were independent predictors of pancreaticobiliary malformation-related pancreatitis in children. The positive detection rate of pancreaticobiliary malformation was 68% for abdominal ultrasound, 38.4% for abdominal enhanced computed tomography, and 91.3% for magnetic resonance cholangiopancreatography (MRCP). The recurrence rate (34.6%) in the PMP group was higher than that in the non-PMP group (15.4%, P < 0.05); surgical therapy had the lowest recurrence rate. Age at initial onset of pancreatitis was younger and the period to recurrence was shorter in the PMP group than in the non-PMP group (P < 0.05).

Conclusion: Pancreaticobiliary malformation is one of the major causes of paediatric pancreatitis. Elevated TB and GGT in patients with pancreatitis may be suggestive for underlying pancreaticobiliary malformation not solely to pancreatitis. MRCP should be used when pancreatitis due to pancreaticobiliary malformation is suspected. Surgery or endoscopic retrograde cholangiopancreatography-guided intervention may be helpful but further study is needed.
Severe Retinopathy of Prematurity Is Not Independently Associated With Worse Neurodevelopmental Outcomes in Preterm Neonates
Authors: Altendahl Marie , Sim Myung Shin , Kokhanov Artemiy , Gundlach Bradley , Tsui Irena , Chu Alison
Published: June 2021

Purpose: To evaluate the relationship between retinopathy of prematurity (ROP) severity and neurodevelopmental outcomes in premature neonates at 0–36 months corrected age.

Methods: A retrospective chart review was performed on 228 neonates screened for ROP at the UCLA Mattel Children's Hospital between 2011 and 2018. Demographic information, clinical outcomes, ROP severity (no ROP, type 1 ROP, type 2 ROP), and Bayley-III neurodevelopmental scores were collected. Infants were grouped into corrected age cohorts (0–12, 12–24, and 24–36 months) to assess neurodevelopmental outcomes with increasing age. Within each age cohort, ANOVA and Chi-Square testing were used to detect differences in birth characteristics and neurodevelopmental scores between infants with type 1 ROP, type 2 ROP, or no ROP. Univariable analyses assessed the relationship between ROP severity and neurodevelopmental outcomes within each age cohort. A multivariable analysis was then performed to determine if ROP severity remained significantly associated with worse neurodevelopmental scores after controlling for birth weight (BW), intraventricular hemorrhage grade (IVH), health insurance type, male sex, and age at Bayley testing.

Results: Without controlling for factors associated with prematurity, neonates with type 1 ROP had poorer cognition (p = 0.001) and motor (p = 0.006) scores at ages 0–12 months and poorer cognition (p = 0.01), language (p = 0.04) and motor (p = 0.04) scores at ages 12–24 months than infants without ROP, but no significant differences were detected at ages 24–36 months. After adjusting for BW, IVH, insurance type, male sex, and age at Bayley testing, ROP severity was no longer associated with worse neurodevelopmental scores in any domain.

Conclusion: This study emphasizes that poorer neurodevelopmental outcomes in preterm neonates are most likely related to lower birthweight, associated co-morbidities of prematurity, and socioeconomic factors such as health insurance, not severity of ROP itself.
Glycyrrhizic Acid for COVID-19: Findings of Targeting Pivotal Inflammatory Pathways Triggered by SARS-CoV-2
Authors: Zheng Wenjiang , Huang Xiufang , Lai Yanni , Liu Xiaohong , Jiang Yong , Zhan Shaofeng
Published: June 2021

Background: Coronavirus disease 2019 (COVID-19) is now a worldwide public health crisis. The causative pathogen is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Novel therapeutic agents are desperately needed. Because of the frequent mutations in the virus and its ability to cause cytokine storms, targeting the viral proteins has some drawbacks. Targeting cellular factors or pivotal inflammatory pathways triggered by SARS-CoV-2 may produce a broader range of therapies. Glycyrrhizic acid (GA) might be beneficial against SARS-CoV-2 because of its anti-inflammatory and antiviral characteristics and possible ability to regulate crucial host factors. However, the mechanism underlying how GA regulates host factors remains to be determined.

Methods: In our report, we conducted a bioinformatics analysis to identify possible GA targets, biological functions, protein-protein interactions, transcription-factor-gene interactions, transcription-factor-miRNA coregulatory networks, and the signaling pathways of GA against COVID-19.

Results: Protein-protein interactions and network analysis showed that ICAM1, MMP9, TLR2, and SOCS3 had higher degree values, which may be key targets of GA for COVID-19. GO analysis indicated that the response to reactive oxygen species was significantly enriched. Pathway enrichment analysis showed that the IL-17, IL-6, TNF-α, IFN signals, complement system, and growth factor receptor signaling are the main pathways. The interactions of TF genes and miRNA with common targets and the activity of TFs were also recognized.

Conclusions: GA may inhibit COVID-19 through its anti-oxidant, anti-viral, and anti-inflammatory effects, and its ability to activate the immune system, and targeted therapy for those pathways is a predominant strategy to inhibit the cytokine storms triggered by SARS-CoV-2 infection.
Chaihu Guizhi Ganjiang Decoction Ameliorates Pancreatic Fibrosis via JNK/mTOR Signaling Pathway
Authors: Cui Lihua , Li Caixia , Shang Ye , Li Dihua , Zhuo Yuzhen , Yang Lei , Cui Naiqiang , Li Yuhong , Zhang Shukun
Published: June 2021

Pancreatic fibrosis is a pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Chaihu Guizhi Ganjiang Decoction (CGGD) is a traditional Chinese medicine, which is widely used in the clinical treatment of digestive diseases. However, the potential anti-fibrosis mechanism of CGGD in treating CP remains unclear. Here, we conducted a series of experiments to examine the effect of CGGD on the CP rat model and primary isolated pancreatic stellate cells (PSCs). The results revealed that CGGD attenuated pancreatic damage, decreased collagen deposition, and inhibited PSC activation in the pancreas of CP rats. However, compared with the CP group, CGGD had no effect on body weight and serum amylase and lipase. In addition, CGGD suppressed autophagy by downregulating Atg5, Beclin-1, and LC3B and facilitated phosphorylation of mTOR and JNK in pancreatic tissues and PSCs. Moreover, the CGGD-containing serum also decreased LC3B or collagen I expression after rapamycin (mTOR inhibitor) or SP600125 (JNK inhibitor) treatment in PSCs. In conclusion, CGGD attenuated pancreatic fibrosis and PSC activation, possibly by suppressing autophagy of PSCs through the JNK/mTOR signaling pathway.
Nasal High Flow at 25 L/min or Expiratory Resistive Load Do Not Improve Regional Lung Function in Patients With COPD: A Functional CT Imaging Study
Authors: Cohen Julien G. , Broche Ludovic , Machichi Mohammed , Ferretti Gilbert R. , Tamisier Renaud , Pépin Jean-Louis , Bayat Sam
Published: June 2021

Background

Nasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery via a large-caliber nasal cannula of heated and humidified air at flow rates that exceed peak inspiratory flow. It is thought that positive airway pressure generated by NHF can help reduce gas trapping and improve regional lung ventilation. There are no data to confirm this hypothesis at flow rates applicable in stable chronic obstructive pulmonary disease (COPD) patients.

Methods

In this study, we used non-rigid registration of computed tomography (CT) images acquired at maximal expiration and inspiration to compute regional lung attenuation changes (ΔHU), and lung displacement (LD), indices of regional lung ventilation. Parametric response maps (Galban et al., 2012) were also computed in each experimental condition. Eight COPD patients were assessed at baseline (BL) and after 5 min of NHF and expiratory resistive loading (ERL).

Results

ΔHU was: BL (median, IQR): 85 (67.2, 102.8); NHF: 90.7 (57.4, 97.6); ERL: 74.6 (46.4, 89.6) HU (p = 0.531); and LD: 27.8 (22.3, 39.3); 17.6 (15.4, 27.9); and 20.4 (16.6, 23.6) mm (p = 0.120) in the 3 conditions, respectively. No significant difference in trapping was observed. Respiratory rate significantly decreased with both treatments [BL: 17.3 (16.4, 18.9); NHF: 13.7; ERL: 11.4 (9.6, 13.2) bpm; and p < 0.001].

Conclusion

Neither NHF at 25 L/min nor ERL significantly improved the regional lung ventilation of stable COPD patients with gas trapping, based on functional lung CT imaging. Further study including more subjects is needed to assess the potential effect of NHF on regional lung function at higher flow rates.

Clinical Trial Registration

www.clinicaltrials.gov/under, identifier NCT03821311.
Alternative Splicing of the Basic Helix–Loop–Helix Transcription Factor Gene CmbHLH2 Affects Anthocyanin Biosynthesis in Ray Florets of Chrysanthemum (Chrysanthemum morifolium)
Authors: Lim Sun-Hyung , Kim Da-Hye , Jung Jae-A. , Lee Jong-Yeol
Published: June 2021

Chrysanthemum is an important ornamental crop worldwide. Some white-flowered chrysanthemum cultivars produce red ray florets under natural cultivation conditions, but little is known about how this occurs. We compared the expression of anthocyanin biosynthetic and transcription factor genes between white ray florets and those that turned red based on cultivation conditions to comprehend the underlying mechanism. Significant differences in the expression of CmbHLH2 were detected between the florets of different colors. CmbHLH2 generated two alternatively spliced transcripts, designated CmbHLH2Full and CmbHLH2Short. Compared with CmbHLH2Full, CmbHLH2Short encoded a truncated protein with only a partial MYB-interaction region and no other domains normally present in the full-length protein. Unlike the full-length form, the splicing variant protein CmbHLH2Short localized to the cytoplasm and the nucleus and could not interact with CmMYB6. Additionally, CmbHLH2Short failed to activate anthocyanin biosynthetic genes and induce pigment accumulation in transiently transfected tobacco leaves, whereas CmbHLH2Full promoted both processes when simultaneously expressed with CmMYB6. Co-expressing CmbHLH2Full and CmMYB6 also enhanced the promoter activities of CmCHS and CmDFR. Notably, the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, could be complemented by the heterologous expression of CmbHLH2Full, which restored red pigmentation and resulted in red pigmentation in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively, whereas expression of CmbHLH2Short did not. Together, these results indicate that CmbHLH2 and CmMYB6 interaction plays a key role in the anthocyanin pigmentation changes of ray florets in chrysanthemum. Our findings highlight alternative splicing as a potential approach to modulate anthocyanin biosynthesis in specific tissues.
Identification of DNA Methylation and Transcriptomic Profiles Associated With Fruit Mealiness in Prunus persica (L.) Batsch
Authors: Rothkegel Karin , Espinoza Alonso , Sanhueza Dayan , Lillo-Carmona Victoria , Riveros Aníbal , Campos-Vargas Reinaldo , Meneses Claudio
Published: June 2021

Peach (Prunus persica) fruits have a fast ripening process and a shelf-life of days, presenting a challenge for long-distance consuming markets. To prolong shelf-life, peach fruits are stored at low temperatures (0 to 7 °C) for at least two weeks, which can lead to the development of mealiness, a physiological disorder that reduces fruit quality and decreases consumer acceptance. Several studies have been made to understand this disorder, however, the molecular mechanisms underlying mealiness are not fully understood. Epigenetic factors, such as DNA methylation, modulate gene expression according to the genetic background and environmental conditions. In this sense, the aim of this work was to identify differentially methylated regions (DMRs) that could affect gene expression in contrasting individuals for mealiness. Peach flesh was studied at harvest time (E1 stage) and after cold storage (E3 stage) for 30 days. The distribution of DNA methylations within the eight chromosomes of P. persica showed higher methylation levels in pericentromeric regions and most differences between mealy and normal fruits were at Chr1, Chr4, and Chr8. Notably, differences in Chr4 co-localized with previous QTLs associated with mealiness. Additionally, the number of DMRs was higher in CHH cytosines of normal and mealy fruits at E3; however, most DMRs were attributed to mealy fruits from E1, increasing at E3. From RNA-Seq data, we observed that differentially expressed genes (DEGs) between normal and mealy fruits were associated with ethylene signaling, cell wall modification, lipid metabolism, oxidative stress and iron homeostasis. When integrating the annotation of DMRs and DEGs, we identified a CYP450 82A and an UDP-ARABINOSE 4 EPIMERASE 1 gene that were downregulated and hypermethylated in mealy fruits, coinciding with the co-localization of a transposable element (TE). Altogether, this study indicates that genetic differences between tolerant and susceptible individuals is predominantly affecting epigenetic regulation over gene expression, which could contribute to a metabolic alteration from earlier stages of development, resulting in mealiness at later stages. Finally, this epigenetic mark should be further studied for the development of new molecular tools in support of breeding programs.
Perspective From a Youth Environmental Activist: Why Adults Will Listen to Youth in Politics
Authors: Hartley Jenna M. , Higgins Katelyn M. , Peterson M. Nils , Stevenson Kathryn T. , Jackson Megan W.
Published: June 2021

This perspective article is divided between the account of an emerging youth political activist, Katelyn Higgins, and the subsequent collaborative research project she coordinated. After 10 years of experience in youth political action, Higgins worked with co-authors to develop a qualitative study to explore the processes underlying youth influence over local environmental policymaking. We present findings from that study to supplement her perspective. The study supported fourth and fifth grade teachers by offering a marine debris curriculum which encouraged students to share their knowledge with local community members through environmental activism events. At the first event, students aged 8–10 presented at a town hall meeting; we interviewed 16 adults in attendance. The second “event” was a series of video PSAs (Public Service Announcements) in which students from across the state of North Carolina, United States, explained the harms of marine debris. Those PSAs were emailed to local officials; we conducted follow-up interviews with two officials. Four themes emerged to characterize how adults responded to youth environmental activism: young people were inspiring; adults want to support young people; and adults view young people as able to provide leadership for local action and challenge the establishment. Youth leaders and those looking to support them should be encouraged by these results, as they suggest adults, including local public officials, consider youth voices valuable and uniquely situated to foster productive political processes for addressing marine debris. Future research should continue to explore the degree to which positive feelings expressed by adults translate to action.
Reality Meets Belief: A Mixed Methods Study on Character Strengths and Well-Being of Hospital Physicians
Authors: Kachel Timo , Huber Alexandra , Strecker Cornelia , Höge Thomas , Höfer Stefan
Published: June 2021

Positive psychology deals with factors that make life most worth living and focuses on enhancing individual potentials. Particularly, character strengths can positively contribute to well-being and work-related health, bearing a promising potential for professions, such as physicians, who are at risk for burnout or mental illnesses. This study aims to identify beneficial character strengths by examining the quantitative and qualitative data. In a cross-sectional multi-method study, 218 hospital physicians completed an online survey assessing their character strengths and their general and work-related well-being, comprising thriving, work engagement, and burnout dimensions (outcome variables). Quantitative data were analyzed for the total sample and by tertiary split. Additionally, interview-gathered opinions of four resident physicians and four medical specialist educators were collected to expand the perspective on which character strengths might be beneficial for the well-being of the resident physicians. The highest significant correlations between character strengths and outcome variables were found forhopeand thriving (r= 0.67),zest, and work engagement (r= 0.67) as well as emotional exhaustion (r= −0.47),perseverance/leadershipand depersonalization (r= −0.27),bravery, and reduced personal accomplishment (r= −0.39). Tertiary splits revealed that some correlations were not consistent across the entire scale continuum, for example,creativitywas only significantly correlated with comparatively high levels of thriving (r= 0.28) orforgivenesswith comparatively high levels of depersonalization (r= −0.34).Humility, social intelligence, andteamworkshowed predominantly low correlations with all outcome variables (r= −0.17 − 0.34), althoughhumilitywas stated by all interviewed medical specialist educators to be the most relevant for the well-being at work, and the latter two by three resident physicians, respectively. Different perspectives resulting from quantitative and qualitative data in terms of beneficial character strengths for work-related well-being may be driven by different work experiences, professional understandings, generational beliefs, or social expectations. Some significant correlations between character strengths and well-being outcomes varied depending on low, medium, or high outcomes. This raises questions about suitable work-related well-being interventions, as simple single intervention approaches (one intervention fits all) may not work for the respective outcome levels. These new findings warrant further research on how to foster the well-being of resident physicians at work.
Psychometric Properties of the Spanish Version of Psychosocial Impact of Assistive Devices Scale in a Large Sample of People With Neuromuscular, Neurological, or Hearing Disabilities
Authors: Díez Emiliano , Jiménez-Arberas Estíbaliz , Pousada Thais
Published: June 2021

Assistive technology (AT) is any device, software, or equipment designed for and used by individuals with disabilities to engage in everyday activities and achieve independence. However, the usefulness of those technology-based or supported treatments is a complex issue that has led to the development of various conceptual models for assistive technology outcomes research and practice as well as different assessment tools that help to explore the effect of technology on people's lives. One of those instruments is the Psychosocial Impact of Assistive Device Scale (PIADS), a 26-item questionnaire that measures the psychosocial impact of interventions, using assistive devices in three quality-of-life domains: competence, adaptability, and self-esteem. PIADS scale has been translated and adapted to several languages, and it has been successfully used to measure AT outcomes in different disability profiles to predict abandonment or even as a relevant determinant of future adoption of eHealth. Quinteiro (2010) adapted PIADS to Spanish for the first time, although no studies have yet been published to systematically study its psychometric properties. Therefore, the purpose of this study was to evaluate measurement properties of the Spanish version of PIADS scale by means of a dataset obtained from its application to a large sample (n = 417) of people with neuromuscular, neurological, or hearing disabilities that used different assistive devices. The results will provide valuable indicators about the measurement quality of the Spanish PIADS scale and will help to promote the use of reliable and valid AT outcome assessment tools for research and clinical purposes.
Identifying Resilience Factors of Distress and Paranoia During the COVID-19 Outbreak in Five Countries
Authors: Mækelæ Martin Jensen , Reggev Niv , Defelipe Renata P. , Dutra Natalia , Tamayo Ricardo M. , Klevjer Kristoffer , Pfuhl Gerit
Published: June 2021

The ongoing COVID-19 pandemic outbreak has affected all countries with more than 100 million confirmed cases and over 2.1 million casualties by the end of January 2021 worldwide. A prolonged pandemic can harm global levels of optimism, regularity, and sense of meaning and belonging, yielding adverse effects on individuals' mental health as represented by worry, paranoia, and distress. Here we studied resilience, a successful adaptation despite risk and adversity, in five countries: Brazil, Colombia, Germany, Israel, and Norway. In April 2020, over 2,500 participants were recruited for an observational study measuring protective and obstructive factors for distress and paranoia. More than 800 of these participants also completed a follow-up study in July. We found that thriving, keeping a regular schedule, engaging in physical exercise and less procrastination served as factors protecting against distress and paranoia. Risk factors were financial worries and a negative mindset, e.g., feeling a lack of control. Longitudinally, we found no increase in distress or paranoia despite an increase in expectation of how long the outbreak and the restrictions will last, suggesting respondents engaged in healthy coping and adapting their lives to the new circumstances. Altogether, our data suggest that humans adapt even to prolonged stressful events. Our data further highlight several protective factors that policymakers should leverage when considering stress-reducing policies.
Personality Development in Emerging Adulthood—How the Perception of Life Events and Mindset Affect Personality Trait Change
Authors: De Vries Jantje Hinrika , Spengler Maik , Frintrup Andreas , Mussel Patrick
Published: June 2021

Personality changes throughout the life course and change is often caused by environmental influences, such as critical life events. In the present study, we investigate personality trait development in emerging adulthood as a result of experiencing two major life events: graduating from school and moving away from home. Thereby, we examined the occurrence of the two life events per se and the subjective perception of the critical life event in terms of valence. In addition, we postulate a moderation effect of the construct of mindset, which emphasizes that beliefs over the malleability of global attributes can be seen as predictors of resilience to challenges. This suggests that mindset acts as a buffer for these two distinct events. In a large longitudinal sample of 1,243 people entering adulthood, we applied latent structural equation modeling to assess mean-level changes in the Big Five, the influence of life events per se, the subjective perception of life events, and a moderating role of mindset. In line with maturity processes, results showed significant mean-level changes in all Big Five traits. While no changes in the Big Five dimensions were noted when the mere occurrence of an event is assessed, results indicated a greater increase in extraversion and diminished increase in emotional stability when we accounted for the individual's (positive/negative) perception of the critical life event. In case of extraversion, this also holds true for the moderator mindset. Our findings contribute valuable insights into the relevance of subjective appraisals to life events and the importance of underlying processes to these events.
Cannabis and Cognitive Functioning: From Acute to Residual Effects, From Randomized Controlled Trials to Prospective Designs
Authors: Bourque Josiane , Potvin Stéphane
Published: June 2021

In recent years, several jurisdictions have revised their regulation policy toward both medical and recreational use of cannabis. These changes have elicited concerns regarding how legalization impacts academic achievement and work performance. This review evaluates the acute and long-term (residual) association between cannabis use and cognitive functioning that underlies poor academic and work performance. Relative to other reviews, this article focuses on cross-over randomized controlled trials and prospective designs given that they allow to test the impairing effects of cannabis exposure at the within-subject level. Acute cannabis cognitive effects are discussed separately for known confounding factors such as levels of delta-9-tetrahydrocannabinol (Δ9-THC), Δ9-THC:cannabidiol ratio, previous cannabis use and, comorbidity with psychosis-spectrum disorders. The cognitive residual effects of cannabis are detailed in relation to duration of abstinence, frequency of use, comorbidity with psychosis-spectrum disorders, types of cognitive domains assessed, and age of cannabis use initiation. Moreover, considering the fact that adequate longitudinal studies can make inferences about causality between cannabis use and impaired cognitive functioning when disentangling between-subject from within-subject variation, proofs for the three main non-mutually exclusive hypotheses about this relationship will be presented: i) the cognitive vulnerability hypothesis as part of the more general common antecedent hypothesis, ii) the concurrent cannabis impairing hypothesis, and iii) the neurotoxic hypothesis of cannabis. Current research provides evidence for mild to moderate acute cannabis effects on episodic and working memory, processing speed, and executive functions. Mild residual impairing effects were also observed in these exact same cognitive domains, suggesting that adverse effects following cannabis intoxication persist at least days or weeks following cannabis abstinence. Relative to adult-onset, adolescent-onset cannabis use seems to explain the dose-response relationship and is associated with longer lasting residual effects even in mild users (<weekly). The association between cannabis and cognition is likely explained by common antecedents, such that genetic and shared environment factors predispose individuals to both cannabis use and cognitive deficits, and to a lesser degree, neurotoxic effects.
Multifamily Therapy for Adolescents With School Refusal: Perspectives of the Adolescents and Their Parents
Authors: Roué Aurélie , Harf Aurélie , Benoit Laelia , Sibeoni Jordan , Moro Marie Rose
Published: June 2021

Introduction:School refusal is an important public health concern in adolescent psychiatry increasing over the past several years (5% of child and adolescent psychiatry consultations in France). Multifamily therapy has developed over 30 years. Its efficacy is validated in adult, child and adolescent psychiatry, including for children at risk of school exclusion. In this study, we aimed to explore the adolescents and their parent's experience of a multifamily therapy treatment of school refusal with a qualitative method.

Materials and Methods:This qualitative study is based on an Interpretative Phenomenological Analysis approach. We conducted 15 semi-structured interviews, participants were adolescents (n= 6) and their parents (n= 9) who experienced multifamily therapy in an adolescent department in Paris. Data analysis was performed independently by two researchers.

Results:For the six families, school was a source of suffering, system paralysis and social exclusion. Families reported painful emotions and separation anxiety. For teenagers, multifamily therapy increased self-confidence and allowed group experience. For parents, it gave support and relieved from feelings of stigmatization and guilt. Parents became more aware of their adolescent's suffering and their insight. They all considered that multifamily therapy improved intra-family communication and expression of emotion. Participants highlighted the benefits of intergenerational interactions, activities, group and guidance from therapists.

Discussion:Multifamily therapy uses therapeutic tools from both family therapy (joining, resonance, family competence, and metacommunication) and group therapy (use of media, identity device, and mirror reactions). Parents expect school solutions from multifamily therapy and question how psychiatric treatment can deal with school, school refusal being therefore understood as a social functioning disorder.
Co-development of a Best Practice Checklist for Mental Health Data Science: A Delphi Study
Authors: Kirkham Elizabeth J. , Crompton Catherine J. , Iveson Matthew H. , Beange Iona , McIntosh Andrew M. , Fletcher-Watson Sue
Published: June 2021

Background: Mental health research is commonly affected by difficulties in recruiting and retaining participants, resulting in findings which are based on a sub-sample of those actually living with mental illness. Increasing the use of Big Data for mental health research, especially routinely-collected data, could improve this situation. However, steps to facilitate this must be enacted in collaboration with those who would provide the data - people with mental health conditions.

Methods: We used the Delphi method to create a best practice checklist for mental health data science. Twenty participants with both expertise in data science and personal experience of mental illness worked together over three phases. In Phase 1, participants rated a list of 63 statements and added any statements or topics that were missing. Statements receiving a mean score of 5 or more (out of 7) were retained. These were then combined with the results of a rapid thematic analysis of participants' comments to produce a 14-item draft checklist, with each item split into two components: best practice now and best practice in the future. In Phase 2, participants indicated whether or not each item should remain in the checklist, and items that scored more than 50% endorsement were retained. In Phase 3 participants rated their satisfaction with the final checklist.

Results: The final checklist was made up of 14 “best practice” items, with each item covering best practice now and best practice in the future. At the end of the three phases, 85% of participants were (very) satisfied with the two best practice checklists, with no participants expressing dissatisfaction.

Conclusions: Increased stakeholder involvement is essential at every stage of mental health data science. The checklist produced through this work represents the views of people with experience of mental illness, and it is hoped that it will be used to facilitate trustworthy and innovative research which is inclusive of a wider range of individuals.
Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts
Authors: Yamashita Ayumu , Sakai Yuki , Yamada Takashi , Yahata Noriaki , Kunimatsu Akira , Okada Naohiro , Itahashi Takashi , Hashimoto Ryuichiro , Mizuta Hiroto , Ichikawa Naho , Takamura Masahiro , Okada Go , Yamagata Hirotaka , Harada Kenichiro , Matsuo Koji , Tanaka Saori C. , Kawato Mitsuo , Kasai Kiyoto , Kato Nobumasa , Takahashi Hidehiko , Okamoto Yasumasa , Yamashita Okito , Imamizu Hiroshi
Published: June 2021

Large-scale neuroimaging data acquired and shared by multiple institutions are essential to advance neuroscientific understanding of pathophysiological mechanisms in psychiatric disorders, such as major depressive disorder (MDD). About 75% of studies that have applied machine learning technique to neuroimaging have been based on diagnoses by clinicians. However, an increasing number of studies have highlighted the difficulty in finding a clear association between existing clinical diagnostic categories and neurobiological abnormalities. Here, using resting-state functional magnetic resonance imaging, we determined and validated resting-state functional connectivity related to depression symptoms that were thought to be directly related to neurobiological abnormalities. We then compared the resting-state functional connectivity related to depression symptoms with that related to depression diagnosis that we recently identified. In particular, for the discovery dataset with 477 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a brain network prediction model of depression symptoms (Beck Depression Inventory-II [BDI] score). The prediction model significantly predicted BDI score for an independent validation dataset with 439 participants from 4 different imaging sites. Finally, we found 3 common functional connections between those related to depression symptoms and those related to MDD diagnosis. These findings contribute to a deeper understanding of the neural circuitry of depressive symptoms in MDD, a hetero-symptomatic population, revealing the neural basis of MDD.
The Role of Whole Genome Sequencing in the Surveillance of Antimicrobial Resistant Enterococcus spp.: A Scoping Review
Authors: Rogers Lindsay A. , Strong Kayla , Cork Susan C. , McAllister Tim A. , Liljebjelke Karen , Zaheer Rahat , Checkley Sylvia L.
Published: June 2021

Enterococcus spp. have arisen as important nosocomial pathogens and are ubiquitous in the gastrointestinal tracts of animals and the environment. They carry many intrinsic and acquired antimicrobial resistance genes. Because of this, surveillance of Enterococcus spp. has become important with whole genome sequencing emerging as the preferred method for the characterization of enterococci. A scoping review was designed to determine how the use of whole genome sequencing in the surveillance of Enterococcus spp. adds to our knowledge of antimicrobial resistance in Enterococcus spp. Scoping review design was guided by the PRISMA extension and checklist and JBI Reviewer's Guide for scoping reviews. A total of 72 articles were included in the review. Of the 72 articles included, 48.6% did not state an association with a surveillance program and 87.5% of articles identified Enterococcus faecium. The majority of articles included isolates from human clinical or screening samples. Significant findings from the articles included novel sequence types, the increasing prevalence of vancomycin-resistant enterococci in hospitals, and the importance of surveillance or screening for enterococci. The ability of enterococci to adapt and persist within a wide range of environments was also a key finding. These studies emphasize the importance of ongoing surveillance of enterococci from a One Health perspective. More studies are needed to compare the whole genome sequences of human enterococcal isolates to those from food animals, food products, the environment, and companion animals.
From Modern Planetary Health to Decolonial Promotion of One Health of Peripheries
Authors: Baquero Oswaldo Santos , Benavidez Fernández Mario Nestor , Acero Aguilar Myriam
Published: June 2021

The concept of Planetary Health has recently emerged in the global North as a concern with the global effects of degraded natural systems on human health. It calls for urgent and transformative actions. However, the problem and the call to solve it are far from new. Planetary health is a colonial approach that disregards alternative knowledge that over millennia have accumulated experiences of sustainable and holistic lifestyles. It reinforces the monolog of modernity without realizing that threats to “planetary health” reside precisely in its very approach. It insists on imposing its recipes on political, epistemological, and ontological peripheries created and maintained through coloniality. The Latin American decolonial turn has a long tradition in what could be called a “transformative action,” going beyond political and economic crises to face a more fundamental crisis of civilization. It deconstructs, with other decolonial movements, the fallacy of a dual world in which the global North produces epistemologies, while the rest only benefit from and apply those epistemologies. One Health of Peripheries is a field of praxis in which the health of multispecies collectives and the environment they comprise is experienced, understood, and transformed within symbolic and geographic peripheries, ensuing from marginalizing apparatuses. In the present article, we show how the decolonial promotion of One Health of Peripheries contributes to think and advance decentralized and plural practices to attend to glocal realities. We propose seven actions for such promotion.
Deep Learning Assisted Neonatal Cry Classification via Support Vector Machine Models
Authors: K Ashwini , Vincent P. M. Durai Raj , Srinivasan Kathiravan , Chang Chuan-Yu
Published: June 2021

Neonatal infants communicate with us through cries. The infant cry signals have distinct patterns depending on the purpose of the cries. Preprocessing, feature extraction, and feature selection need expert attention and take much effort in audio signals in recent days. In deep learning techniques, it automatically extracts and selects the most important features. For this, it requires an enormous amount of data for effective classification. This work mainly discriminates the neonatal cries into pain, hunger, and sleepiness. The neonatal cry auditory signals are transformed into a spectrogram image by utilizing the short-time Fourier transform (STFT) technique. The deep convolutional neural network (DCNN) technique takes the spectrogram images for input. The features are obtained from the convolutional neural network and are passed to the support vector machine (SVM) classifier. Machine learning technique classifies neonatal cries. This work combines the advantages of machine learning and deep learning techniques to get the best results even with a moderate number of data samples. The experimental result shows that CNN-based feature extraction and SVM classifier provides promising results. While comparing the SVM-based kernel techniques, namely radial basis function (RBF), linear and polynomial, it is found that SVM-RBF provides the highest accuracy of kernel-based infant cry classification system provides 88.89% accuracy.