Publications by authors named "Luigi Grassi"

213 Publications

Insomnia and circadian sleep disorders in ovarian cancer: Evaluation and management of underestimated modifiable factors potentially contributing to morbidity.

J Sleep Res 2021 Oct 29:e13510. Epub 2021 Oct 29.

Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Ovarian cancer is the leading cause of gynaecological cancer deaths and the seventh most commonly diagnosed cancer among women worldwide, so that, as it is related to substantial and increasing disease burden, the management of ovarian cancer survivors should be a priority. Such issues involve prevention and management of emotional distress, anxiety/depressive symptoms, and maintenance of quality of life from initial diagnosis to post-treatment. Within this framework, sleep disturbances, in particular insomnia, are emerging as modifiable determinants of mental health, also contributing to substantial morbidity among cancer, including ovarian cancer. To this aim we conducted a systematic review according to PRISMA guidelines on prevalence and management of insomnia and circadian sleep disorders in ovarian cancer, while selecting 22 papers. Insomnia was evaluated in ovarian cancer and, while circadian sleep disturbances were poorly assessed in ovarian cancer, insomnia increased from 14% to 60% of patients. Insomnia was associated with cancer-related comorbid conditions such as emotional distress, anxiety/depressive symptoms and low quality of life. Despite this evidence, no studies have been conducted about insomnia treatment in ovarian cancer. The burden of insomnia and circadian sleep disorders in patients with ovarian cancer still needs to be addressed, and requires a call to action for the evaluation and management of these potential modifiable factors that might contribute to ovarian cancer morbidity.
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http://dx.doi.org/10.1111/jsr.13510DOI Listing
October 2021

Exploring the Level of Post Traumatic Growth in Kidney Transplant Recipients via Network Analysis.

J Clin Med 2021 Oct 16;10(20). Epub 2021 Oct 16.

Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, 44124 Ferrara, Italy.

Although kidney transplant can lead to psychiatric disorders, psychosocial syndromes and demoralization, a positive post-traumatic growth (PTG) can occur in kidney transplant recipients (KTRs). However, the PTG-Inventory (PTGI), a reliable tool to measure PTG is scarcely used to explore the effect of this stressful event in KTRs. Thus, the purpose of our study was to assess the level of PTG and its correlation with demoralization, physical and emotional symptoms or problems via network analysis in KTRs. Additionally, we aimed at exploring the association of PTG with psychiatric diagnoses, Diagnostic Criteria for Psychosomatic Research (DCPR) conditions, and medical variables. A total of 134 KTRs were tested using MINI International Neuropsychiatric Interview 6.0 (MINI 6.0), DCPR interview, PTGI, Edmonton Symptom Assessment System (ESAS), Canadian Problem Checklist (CPC) and Demoralization scale (DS-IT). PTGI was used to investigate the positive psychological experience of patients after KT. It consists of 21 items divided in five factors. Routine biochemistry, immunosuppressive agents, socio-demographic and clinical data were collected. A symptom network analysis was conducted among PTGI, ESAS and DS-IT. Mean score of PTGI total of sample was 52.81 ± 19.81 with higher scores in women (58.53 ± 21.57) than in men (50.04 ± 18.39) ( < 0.05). PTGI-Relating to Others (16.50 ± 7.99) sub-score was markedly higher than other PTGI factor sub-scores. KTRs with DCPR-alexithymia or International Classification of Diseases, tenth revision (ICD-10) anxiety disorders diagnosis had lower PTGI total score and higher PTGI-Personal Strength sub-score, respectively ( < 0.05). The network analysis identified two communities: PTGI and ESAS with DS-IT. DS-IT Disheartenment, DS-IT Hopelessness and PTGI Relating to Others were the most central items in the network. After 1000 bootstrap procedures, the Exploratory graph analysis revealed the presence of a median of two communities in the network in 97.5% of the bootstrap iterations. A more extensive use of PTGI should be encouraged to identify and enhance the positive psychological changes after KT.
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http://dx.doi.org/10.3390/jcm10204747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540707PMC
October 2021

Depressive symptom complexes of community-dwelling older adults: a latent network model.

Mol Psychiatry 2021 Oct 12. Epub 2021 Oct 12.

Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medicine, White Plains, NY, USA.

Late-life depression has multiple, heterogeneous clinical presentations. The aim of the study was to identify higher-order homogeneous clinical features (symptom complexes), while accounting for their potential causal interactions within the network approach to psychopathology. We analyzed cross-sectional data from community-dwelling adults aged 65-85 years recruited by the European MentDis_ICF65+ study (n = 2623, mean age 74, 49% females). The severity of 33 depressive symptoms was derived from the age-adapted Composite International Diagnostic Interview. Symptom complexes were identified using multiple detection algorithms for symptom networks, and their fit to data was assessed with latent network models (LNMs) in exploratory and confirmatory analyses. Sensitivity analyses included the Partial Correlation Likelihood Test (PCLT) to investigate the data-generating structure. Depressive symptoms were organized by the Walktrap algorithm into eight symptom complexes, namely sadness/hopelessness, anhedonia/lack of energy, anxiety/irritability, self-reproach, disturbed sleep, agitation/increased appetite, concentration/decision making, and thoughts of death. An LNM adequately fit the distribution of individual symptoms' data in the population. The model suggested the presence of reciprocal interactions between the symptom complexes of sadness and anxiety, concentration and self-reproach and between self-reproach and thoughts of death. Results of the PCLT confirmed that symptom complex data were more likely generated by a network, rather than a latent-variable structure. In conclusion, late-life depressive symptoms are organized into eight interacting symptom complexes. Identification of the symptom complexes of late-life depression may streamline clinical assessment, provide targets for personalization of treatment, and aid the search for biomarkers and for predictors of outcomes of late-life depression.
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http://dx.doi.org/10.1038/s41380-021-01310-yDOI Listing
October 2021

Knowledge about risk factors for cancer and cancer risk behavior among patients with severe mental illness.

Psychooncology 2021 Sep 21. Epub 2021 Sep 21.

Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, Ferrara, Italy.

Objective: To examine knowledge about, perception of and current risk factors for cancer, among patients with severe mental illness (SMI) and to compare these variables with patients without SMI.

Methods: A series of patients affected by SMI (i.e., schizophrenia spectrum disorders, bipolar disorders and severe personality disorders) and a matched (gender, age) control group of primary care attenders were assessed, by using an ad hoc semi-structured interview and a short true/false 17-item questionnaire, about family history of cancer, cancer risk-related lifestyles, personal perception and knowledge of risk for cancer.

Results: Patients with SMI (n = 185, mainly schizophrenia spectrum disorders, 48%, and mood disorders, 33%) significantly differed from primary care attenders (n = 173) for: lower participation to occult stool blood screening test, Pap smear test and mammography; higher prevalence of current and past smoking habits; lower awareness towards their own physical symptoms and their perception of risks for cancer; lower physical exercise practicing; lower knowledge about risk factors for cancer (e.g. familiarity for cancer, smoke-habits, breast and uterine cancer).

Conclusions: Patients suffering from SMI had higher at-risk behavior for cancer and showed fewer concerns and less knowledge about risk for cancer than primary care attendees. These findings can guide to implement screening for cancer (e.g., Pap test, blood) and to design evidence-based interventions to reduce cancer risk (e.g., educational and behavioral change for smoking cessation, dietary habits) among patients with SMI.
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http://dx.doi.org/10.1002/pon.5822DOI Listing
September 2021

Psychiatric care in oncology and palliative medicine: new challenges and future perspectives.

World Psychiatry 2021 Oct;20(3):452-453

Department of Psychiatry and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.

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http://dx.doi.org/10.1002/wps.20836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429337PMC
October 2021

Mortality from cancer in people with severe mental disorders in Emilia Romagna Region, Italy.

Psychooncology 2021 Sep 9. Epub 2021 Sep 9.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Objective: To examine cancer-related mortality in patients with severe mental disorders (SMI) in the Emilia Romagna (ER) Region, Northern Italy, during the period 2008-2017 and compare it with the regional population.

Methods: We used the ER Regional Mental Health Registry identifying all patients aged ≥18 years who had received an ICD-9CM system diagnosis of SMI (i.e., schizophrenia or other functional psychosis, mania, or bipolar affective disorders) during a 10-year period (2008-2017). Information on deaths (date and causes of death) were retrieved through the Regional Cause of Death Registry. Comparisons were made with the deaths and cause of deaths of the regional population over the same period.

Results: Amongst 12,385 patients suffering from SMI (64.1% schizophrenia spectrum and 36.9% bipolar spectrum disorders), 24% (range 21%-29%) died of cancer. In comparison with the general regional population, the mortality for cancer was about 50% higher among patients with SMI, irrespective if affected by schizophrenia or bipolar disorders. As for the site-specific cancers, significant excesses were reported for stomach, central nervous system, respiratory, and pancreas cancer with a variability according to psychiatric diagnosis and gender.

Conclusions: Patients suffering from SMI had higher mortality risk than the regional population with some differences according to cancer type, gender, and psychiatric diagnosis. Proper cancer preventive and treatment interventions, including more effective risk modification strategies (e.g., smoking cessation, dietary habits) and screening for cancer, should be part of the agenda of all mental health departments in conjunction with other health care organizations, including psycho-oncology.
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http://dx.doi.org/10.1002/pon.5805DOI Listing
September 2021

From Distress Screening to Uptake: An Italian Multicenter Study of Cancer Patients.

Cancers (Basel) 2021 Jul 27;13(15). Epub 2021 Jul 27.

Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, 44121 Ferrara, Italy.

Introduction: Little consideration is given to the referral and uptake of available supportive services after distress screening. However, identifying the reasons for accepting or refusing help is mandatory for implementing a screening policy. The present study explored the practical usefulness of and potential barriers to the application of distress management.

Methods: 406 cancer patients were consecutively selected and asked to complete the Distress Thermometer (DT) and Problem Check List (PL). All patients with a DT score ≥6 were invited for a post-DT telephone interview with a trained psychologist.

Results: The 112 patients who refused to take part were more often older, retired, at a more advanced stage of illness, and with no previous experience of psychological intervention with respect to those who accepted. Of the 78 patients with a score ≥6 who were referred to the Psycho-Oncology Service, 65.4% accepted the telephone interview. Twenty-two patients rejected the initial invitation immediately for various reasons including logistic difficulties, physical problems, and feeling embarrassed about opening up to a psychologist.

Conclusions: Our study confirms that screening is insufficient to deal with the problem of distress and that more emphasis should be placed on implementing referral and treatment.
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http://dx.doi.org/10.3390/cancers13153761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345103PMC
July 2021

Veno-venous extracorporeal blood phototherapy increases the rate of carbon monoxide (CO) elimination in CO-poisoned pigs.

Lasers Surg Med 2021 Aug 5. Epub 2021 Aug 5.

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background And Objectives: Carbon monoxide (CO) inhalation is the leading cause of poison-related deaths in the United States. CO binds to hemoglobin (Hb), displaces oxygen, and reduces oxygen delivery to tissues. The optimal treatment for CO poisoning in patients with normal lung function is the administration of hyperbaric oxygen (HBO). However, hyperbaric chambers are only available in medical centers with specialized equipment, resulting in delayed therapy. Visible light dissociates CO from Hb with minimal effect on oxygen binding. In a previous study, we combined a membrane oxygenator with phototherapy at 623 nm to produce a "mini" photo-ECMO (extracorporeal membrane oxygenation) device, which improved CO elimination and survival in CO-poisoned rats. The objective of this study was to develop a larger photo-ECMO device ("maxi" photo-ECMO) and to test its ability to remove CO from a porcine model of CO poisoning.

Study Design/materials And Methods: The "maxi" photo-ECMO device and the photo-ECMO system (six maxi photo-ECMO devices assembled in parallel), were tested in an in vitro circuit of CO poisoning. To assess the ability of the photo-ECMO device and the photo-ECMO system to remove CO from CO-poisoned blood in vitro, the half-life of COHb (COHb-t ), as well as the percent COHb reduction in a single blood pass through the device, were assessed. In the in vivo studies, we assessed the COHb-t in a CO-poisoned pig under three conditions: (1) While the pig breathed 100% oxygen through the endotracheal tube; (2) while the pig was connected to the photo-ECMO system with no light exposure; and (3) while the pig was connected to the photo-ECMO system, which was exposed to red light.

Results: The photo-ECMO device was able to fully oxygenate the blood after a single pass through the device. Compared to ventilation with 100% oxygen alone, illumination with red light together with 100% oxygen was twice as efficient in removing CO from blood. Changes in gas flow rates did not alter CO elimination in one pass through the device. Increases in irradiance up to 214 mW/cm were associated with an increased rate of CO elimination. The photo-ECMO device was effective over a range of blood flow rates and with higher blood flow rates, more CO was eliminated. A photo-ECMO system composed of six photo-ECMO devices removed CO faster from CO-poisoned blood than a single photo-ECMO device. In a CO-poisoned pig, the photo-ECMO system increased the rate of CO elimination without significantly increasing the animal's body temperature or causing hemodynamic instability.

Conclusion: In this study, we developed a photo-ECMO system and demonstrated its ability to remove CO from CO-poisoned 45-kg pigs. Technical modifications of the photo-ECMO system, including the development of a compact, portable device, will permit treatment of patients with CO poisoning at the scene of their poisoning, during transit to a local emergency room, and in hospitals that lack HBO facilities.
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http://dx.doi.org/10.1002/lsm.23462DOI Listing
August 2021

Reflecting on meaning in an existential-reorientation group psychotherapy approach for cancer patients: A qualitative thematic analysis.

Palliat Support Care 2021 Jul 19:1-8. Epub 2021 Jul 19.

Department of Philosophy, Sociology, Education and Applied Psychology (FISPPA), University of Padova, Padova, Italy.

Objective: The objectives of this study were to evaluate, in the Italian cultural context, breast cancer patients' main meaning themes related to the experience of the disease, on the one side, and to be part of an existentially oriented group intervention, on the other.

Method: A short reorientation-existential (RET) group intervention, structured by using some tools and background from cognitive analytic therapy (CAT) and based on the meaning-centered psychotherapy (MCP) existential framework, was delivered to 29 breast cancer patients. The sessions were audio-recorded and transcribed verbatim, with the narratives from reflective exercises (meaning of the journey cancer, meaning of the journey of intervention) uploaded to computer software NVivo 11. Analysis of the transcripts emerged from reflective exercises on the personal meaning of cancer and the letters of meaning (goodbye letter) written by the patients to express the meaning of their experience in the group was conducted through the interpretative phenomenological analysis (IPA) framework.

Results: Four superordinate themes were identified in the exercise meaning of the experience of cancer, namely "sense of stigma and loneliness (the foreigner)," "guilt (unjust guilt and anticipatory guilt)," "reconsidering one's own life and nostalgia," and "rebirth (a new life, life after life)." Three superordinate themes were found in the meaning of the group experience in the letters, namely "togetherness and gratitude," "legacy," and "acceptance."

Significance Of Results: The study confirmed that a short group intervention, based on the existentially oriented framework and delivered in a public clinical healthcare setting, was enriched by focusing on the personal meaning of cancer. Some themes, such as loneliness, nostalgia, and rebirth, emerged during reflection giving, in written letters to participants, the sense of the group therapeutic experience.
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http://dx.doi.org/10.1017/S1478951521000936DOI Listing
July 2021

Impact of COVID-19 outbreak on Italian healthcare workers versus general population: Results from an online survey.

Clin Psychol Psychother 2021 Jul 13. Epub 2021 Jul 13.

Department of Health Sciences, University of Florence, Florence, Italy.

Objective: COVID-19 pandemic has been a stressful condition. We explored life changes and health-related consequences of COVID-19 outbreak in Italian healthcare workers in comparison to the general population.

Methods: A total of 593 subjects participated to the online CoRonavIruS Health Impact Survey. Life events and changes, physical health and worries were evaluated referring to 2 weeks prior to the survey. Mood states and daily behaviour were retrospectively evaluated referring to 3 months before COVID-19 (T1) and 2 weeks prior to the survey (T2). Student t test, Mann-Whitney test and multivariate logistic regression analyses were run.

Results: Five hundred and twenty-one subjects were analysed (healthcare workers: n = 163, 31.84%; general population: n = 349, 68.16%). Healthcare workers were more likely to report fatigue and have spent more time outside home during the 2 weeks prior to the survey than the general population (χ  = 266.0 , p < 0.001, R  = 0.57). From T1 to T2, healthcare workers had a significant increase in negative mood, worry, restlessness, loneliness and a decrease in happiness, while subjects from the general population had a statistically significant increase in negative mood, worry, attention, concentration difficulties and a decrease in happiness, pleasure related to daily activities, time spent outdoors and alcohol use.

Conclusion: In the framework of a growing literature on healthcare workers' status during the COVID-19 pandemic, the present study allowed to identify fatigue and loneliness as psychosomatic modifiable variables in need of being monitored and, possibly managed, to ameliorate the health status of healthcare workers.
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http://dx.doi.org/10.1002/cpp.2644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426916PMC
July 2021

Incidence and risk factors of mental disorders in the elderly: The European MentDis_ICF65+ study.

Aust N Z J Psychiatry 2021 Jul 10:48674211025711. Epub 2021 Jul 10.

Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objective: While incidence rates of depression and anxiety disorders in the elderly have been comprehensively investigated, the incidence rates of other mental disorders have rarely been researched. The incidence rate and predictors of various mental disorders in the elderly were evaluated in different European and associated countries.

Methods: A cross-sectional and longitudinal multi-centre survey of (4th ed.) diagnoses was conducted in different European and associated countries (Germany, Italy, Spain, Switzerland, the United Kingdom and Israel) to collect data on the prevalence and incidence of mental disorders in the elderly. The sample size of the longitudinal wave was  = 2592 elderly.

Results: The overall 1-year incidence rate for any mental disorder in the elderly is 8.65%. At 5.18%, any anxiety disorder had the highest incidence rate across all diagnostic groups. The incidence rate for any affective disorder was 2.97%. The lowest incidence rates were found for agoraphobia (1.37%) and panic disorder (1.30%). Risk factors for the development of any mental disorder were never having been married, no religious affiliation, a higher number of physical illnesses and a lower quality of life.

Conclusion: In comparison to other studies, lower incidence rates for any affective disorder and middle-range incidence for any anxiety disorder were found. To the authors' knowledge, no prior studies have reported 1-year incidence rates for somatoform disorder, bipolar disorder and substance misuse in community-dwelling elderly. These findings indicate the need to raise awareness of psychosocial problems in the elderly and to ensure adequate availability of mental health services.
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http://dx.doi.org/10.1177/00048674211025711DOI Listing
July 2021

Individualized Multimodal Physiologic Approach to Mechanical Ventilation in Patients With Obesity and Severe Acute Respiratory Distress Syndrome Reduced Venovenous Extracorporeal Membrane Oxygenation Utilization.

Crit Care Explor 2021 Jul 29;3(7):e0461. Epub 2021 Jun 29.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Objective: To investigate whether individualized optimization of mechanical ventilation through the implementation of a lung rescue team could reduce the need for venovenous extracorporeal membrane oxygenation in patients with obesity and acute respiratory distress syndrome and decrease ICU and hospital length of stay and mortality.

Design: Single-center, retrospective study at the Massachusetts General Hospital from June 2015 to June 2019.

Patients: All patients with obesity and acute respiratory distress syndrome who were referred for venovenous extracorporeal membrane oxygenation evaluation due to hypoxemic respiratory failure.

Intervention: Evaluation and individualized optimization of mechanical ventilation by the lung rescue team before the decision to proceed with venovenous extracorporeal membrane oxygenation. The control group was those patients managed according to hospital standard of care without lung rescue team evaluation.

Measurement And Main Results: All 20 patients (100%) allocated in the control group received venovenous extracorporeal membrane oxygenation, whereas 10 of 13 patients (77%) evaluated by the lung rescue team did not receive venovenous extracorporeal membrane oxygenation. Patients who underwent lung rescue team evaluation had a shorter duration of mechanical ventilation ( = 0.03) and shorter ICU length of stay ( = 0.03). There were no differences between groups in in-hospital, 30-day, or 1-year mortality.

Conclusions: In this hypothesis-generating study, individualized optimization of mechanical ventilation of patients with acute respiratory distress syndrome and obesity by a lung rescue team was associated with a decrease in the utilization of venovenous extracorporeal membrane oxygenation, duration of mechanical ventilation, and ICU length of stay. Mortality was not modified by the lung rescue team intervention.
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http://dx.doi.org/10.1097/CCE.0000000000000461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245114PMC
July 2021

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders.

Front Psychiatry 2021 10;12:688890. Epub 2021 Jun 10.

Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, Paris, France.

Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders. To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method. We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders. The administration of prolonged release melatonin at 2-10 mg, 1-2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders.
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http://dx.doi.org/10.3389/fpsyt.2021.688890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222620PMC
June 2021

Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions.

Sci Rep 2021 06 11;11(1):12358. Epub 2021 Jun 11.

Department of Biochemistry, CARIM, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome-wide transcriptomes (57.8 k mRNAs). For 14.8 k protein-coding transcripts, we assigned the proteins to 21 UniProt-based classes, based on their preferential intracellular localization and presumed function. This classified transcriptome-proteome profile of platelets revealed: (i) Absence of 37.2 k genome-wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein-coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43-0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identified proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma-derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identified proteome of nuclear-related, membrane and signaling proteins, as well proteins with low-level transcripts. We then constructed a prediction model, based on protein function, transcript level and (peri)nuclear localization, and calculated the achievable proteome at ~ 10 k proteins. Model validation identified 1.0 k additional proteins in the predicted classes. Network and database analysis revealed the presence of 2.4 k proteins with a possible role in thrombosis and hemostasis, and 138 proteins linked to platelet-related disorders. This genome-wide platelet transcriptome and (non)identified proteome database thus provides a scaffold for discovering the roles of unknown platelet proteins in health and disease.
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http://dx.doi.org/10.1038/s41598-021-91661-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196183PMC
June 2021

Post-traumatic stress symptoms in long-term disease-free cancer survivors and their family caregivers.

Cancer Med 2021 06 1;10(12):3974-3985. Epub 2021 Jun 1.

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Background: The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post-Traumatic Stress Symptoms (PTSS) in long-term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term.

Methods: In this cross-sectional study 212 survivor-family caregiver dyads completed measures of post-traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects.

Results: Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post-traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p < 0.001), whereas among caregivers it was associated with depression and having a closer relationship with patients (p < 0.001). Patients' depression was associated with caregivers' intrusion symptoms.

Conclusions: High levels of cancer-related PTSS were still present several years after treatment in both survivors and caregivers. Psychopathology may derive from complex interactions among coping, previous disorders and between-person dynamics.
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http://dx.doi.org/10.1002/cam4.3961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209622PMC
June 2021

DetectIS: a pipeline to rapidly detect exogenous DNA integration sites using DNA or RNA paired-end sequencing data.

Bioinformatics 2021 May 12. Epub 2021 May 12.

Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZenec, Cambridge, UK a.

Motivation: Recombinant DNA technology is widely used for different applications in biology, medicine and bio-technology. Viral transduction and plasmid transfection are among the most frequently used techniques to generate recombinant cell lines. Many of these methods result in the random integration of the plasmid into the host genome. Rapid identification of the integration sites is highly desirable in order to characterize these engineered cell lines.

Results: We developed detectIS: a pipeline specifically designed to identify genomic integration sites of exogenous DNA, either a plasmid containing one or more transgenes or a virus. The pipeline is based on a Nextflow workflow combined with a Singularity image containing all the necessary software, ensuring high reproducibility and scalability of the analysis. We tested it on simulated datasets and RNA-seq data from a human sample infected with Hepatitis B virus. Comparisons with other state of the art tools show that our method can identify the integration site in different recombinant cell lines, with accurate results, lower computational demand and shorter execution times.

Availability: The Nextflow workflow, the Singularity image and a test dataset are available at https://github.com/AstraZeneca/detectIS.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab366DOI Listing
May 2021

Post-traumatic Stress Symptoms and Serotonin Transporter (5-HTTLPR) Polymorphism in Breast Cancer Patients.

Front Psychiatry 2021 21;12:632596. Epub 2021 Apr 21.

Department of Biomedical and Specialty Surgical Sciences, Institute of Psychiatry, University of Ferrara, Ferrara, Italy.

Post-traumatic Symptoms (PTSS) and Post-traumatic Stress Disorder (PTSD) have been reported to affect a quite significant proportion of cancer patients. No study has examined the relationship between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cancer, including Gene-Environment interactions between this polymorphism and specific causes of distress, such as cancer related problems (CRP) or life stressful events (SLE). One hundred and forty five breast cancer outpatients participated in the study and were assessed using the Impact of Event Scale (IES), the Problem List (PL) developed by the National Comprehensive Cancer Network (NCCN) Distress Management Guidelines and the Paykel's Life Events Interview to evaluate the exposure to SLE during the year before the cancer diagnosis. Each patient was genotyped for 5-HTTLPR polymorphism by analyzing genomic DNA obtained from whole blood cells. Gene-Environment interactions were tested through moderation analysis. Twenty-six patients (17.7%) were classified as PTSS cases using the IES. Genotype and phenotype distributions did not differ across individuals with/without PTSS (genotype: χ = 1.5; df = 2; = 0.3; phenotype χ = 0.9; df = 1; = 0.2). For both the genotype and phenotype model, using CRP as a predictor showed significant gene-environment interactions with IES total score ( = 0.020 and = 0.004, respectively), with individuals carrying the allele showing a greater probability of experiencing PTSS. No interaction was found in relationship to SLE ( = 0.750). This study showed a significant GEI between CRP and PTSS in breast cancer patients, with carriers of the allele showing indicators consistent with greater sensitivity to stress.
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http://dx.doi.org/10.3389/fpsyt.2021.632596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097040PMC
April 2021

Aggressive Behavior and Psychiatric Inpatients: a Narrative Review of the Literature with a Focus on the European Experience.

Curr Psychiatry Rep 2021 04 7;23(5):29. Epub 2021 Apr 7.

Institute of Psychiatry, Department of Neurosciences and Rehabilitation, University of Ferrara, Ferrara, Italy.

Purpose Of Review: We summarized peer-reviewed literature on aggressive episodes perpetrated by adult patients admitted to general hospital units, especially psychiatry or emergency services. We examined the main factors associated with aggressive behaviors in the hospital setting, with a special focus on the European experience.

Recent Findings: A number of variables, including individual, historical, and contextual variables, are significant risk factors for aggression among hospitalized people. Drug abuse can be considered a trans-dimensional variable which deserves particular attention. Although mental health disorders represent a significant component in the risk of aggression, there are many factors including drug abuse, past history of physically aggressive behavior, childhood abuse, social and cultural patterns, relational factors, and contextual variables that can increase the risk of overt aggressive behavior in the general hospital. This review highlights the need to undertake initiatives aimed to enhance understanding, prevention, and management of violence in general hospital settings across Europe.
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http://dx.doi.org/10.1007/s11920-021-01233-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026454PMC
April 2021

The Relationship Between Cognitive Abilities and Trait Clinical Features in Patients With Borderline Personality Disorder.

J Pers Disord 2021 10 14;35(5):730-749. Epub 2020 Dec 14.

Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy.

Very few studies have focused on the relationship between cognitive functions and clinical features in borderline personality disorder (BPD). Subjects with BPD and healthy controls were administered the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Test A and B, and the Wisconsin Card Sorting Test. The Brief Symptom Inventory (BSI-53) was used to assess the severity of current symptoms. Attachment style was assessed with the Experiences in Close Relationship Questionnaire, identity integration with the Personality Structure Questionnaire, and other domains of personality dysfunction with the RUDE Scale for Personality Dysfunction. Patients with BPD performed significantly worse than healthy controls in all cognitive domains. Cognitive functions, particularly delayed memory and visuospatial abilities, displayed meaningful associations with trait-like clinical features, above the effect of global cognition and state psychopathology. These findings highlight the need to evaluate effects of cognitive rehabilitation on trait features among individuals with BPD.
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http://dx.doi.org/10.1521/pedi_2020_34_497DOI Listing
October 2021

Author Correction: Evolution from adherent to suspension: systems biology of HEK293 cell line development.

Sci Rep 2021 Mar 2;11(1):5407. Epub 2021 Mar 2.

KTH ‑ School of Engineering Sciences in Chemistry, Biotechnology, and Health, Dept. of Protein Science, Royal Institute of Technology, 106 91, Stockholm, Sweden.

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http://dx.doi.org/10.1038/s41598-021-85105-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925574PMC
March 2021

Between China and Italy: A case report of first-episode schizophrenia in the Covid-19 era.

Psychiatry Res 2021 04 11;298:113804. Epub 2021 Feb 11.

Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Italy; Integrated Department of Mental Health and Pathological Addictions, Ferrara, Italy.

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http://dx.doi.org/10.1016/j.psychres.2021.113804DOI Listing
April 2021

Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress.

Front Oncol 2020 15;10:564346. Epub 2021 Jan 15.

Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.
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http://dx.doi.org/10.3389/fonc.2020.564346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844142PMC
January 2021

A Personalized Patient-Centered Intervention to Empower through Physical Activity the Patient in the Dialysis Center: Study Protocol for a Pragmatic Nonrandomized Clinical Trial.

Methods Protoc 2020 Dec 6;3(4). Epub 2020 Dec 6.

Unit of Nephrology and Dialysis, University Hospital of Ferrara, Via Aldo Moro 8, 44124 Ferrara, Italy.

Sedentariness of patients affected by end-stage kidney disease (ESKD) expose them to high risk of unfavorable clinical outcomes. Exercise training is effective in improving physical function, quality of life (QoL) and long-term outcomes. However, the existing barriers related to patients, programs and dialysis staff limit patient participation and call for new strategies. This pragmatic nonrandomized trial will test the impact on ESKD population of an intervention proposed by an exercise facilitator regularly present in a dialysis center. The patient will be free to choose among three-month walking and/or resistance low-intensity training programs: (a) guided physical activity increase; (b) home-based exercise; (c) in-hospital (pre/post dialysis) supervised exercise; (d) performance assessment only. The first phase will define feasibility and the characteristics and preference of responders. The second phase will evaluate safety and patients' adherence. Outcome measures will be collected at baseline, after three-month and at six-month follow-up. They will include: aerobic capacity, QoL, gait speed, strength, depression and long-term clinical outcomes (hospitalization and mortality). The trial was approved by the Area-Vasta Emilia-Romagna Centro Ethics Committee with approval number 48/2019. Written informed consent will be obtained from all participants. The results of the study will be presented in international congresses, published in peer-reviewed journals and communicated to the patient community. Registration details: Clinicaltrials.gov NCT04282616 [Registered:24/02/2020].
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http://dx.doi.org/10.3390/mps3040083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768449PMC
December 2020

[Evaluation and management of insomnia in clinical practice and in the time of CoViD-19 in Italy: expert consensus and task-force recommendations from five scientific societies].

Riv Psichiatr 2020 Nov-Dec;55(6):337-341

Dipartimento di Scienze della Vita e dell'Ambiente, Università di Cagliari; Società Italiana di Neuropsicofarmacologia (SINF).

Insomnia symptoms might affect about 60% of the Italian population. Insomnia is a "24 hours syndrome" and a risk factor for medical and mental disorders. It should always be assessed and treated in the clinical practice. Cognitive Behavioral Therapy for Insomnia is the first line treatment but its availability in Italy is scarce. Pharmacological options in Italy are: melatonin 2 mg prolonged release that should be the first choice in subjects ≥55 years old and used until 13 weeks; and for a short term use (≤4 weeks) Z-drugs or short-acting benzodiazepines (in subjects <65 years old) or a sedating antidepressant.
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http://dx.doi.org/10.1708/3503.34891DOI Listing
December 2020

First-episode psychosis in the Ferrara Mental Health Department: Incidence and clinical course within the first 2 years.

Early Interv Psychiatry 2021 Dec 2;15(6):1738-1748. Epub 2020 Dec 2.

Department of Biomedical and Specialty Surgical Sciences, Institute of Psychiatry, University of Ferrara, Ferrara, Italy.

Aim: To examine the incidence of with first-episode psychosis (FEP) in the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, and to examine the association between the Duration of Untreated Psychosis (DUP) and the clinical course.

Methods: Participants recruited in 2013-2019 were assessed with the Health of the Nation Outcome Scale (HoNOS) every 6 months for 24 months. Hierarchical growth models analysed changes of global severity (HoNOS total scores) and symptom dimensions. Regression modelled factors associated with remission (HoNOS < 8) and clinical improvement (<12).

Results: The incidence of FEP was 21.5 (95%CI: 21.2-21.9) cases per 100 000 person year. Among participants (n = 86, mean age 23, 76% males), baseline HoNOS scores were higher for those with a longer DUP. More than half subjects reached clinical remission (61.6%) or improvement (82.6%), while very few (2.3%) were re-hospitalized. HoNOS total scores decayed with a mixed linear/quadratic trend, with a slower decay among migrants. A longer DUP was associated with reduced improvements of positive symptoms and lower likelihood of clinical improvement (OR: 0.84; 95%CI: 0.73-0.96).

Conclusions: Patients from the FEP program of Ferrara reached good clinical outcomes. Nonetheless, individuals with a longer DUP may need additional clinical attention. Systematic monitoring of clinical outcomes may be an optimal strategy to improve the outcomes of FEP in the real world.
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http://dx.doi.org/10.1111/eip.13095DOI Listing
December 2021

Improving Dignity of Care in Community-Dwelling Elderly Patients with Cognitive Decline and Their Caregivers. The Role of Dignity Therapy.

Behav Sci (Basel) 2020 Nov 24;10(12). Epub 2020 Nov 24.

Institute of Psychiatry, Department of Neurosciences and Rehabilitation (formerly Department Biomedical and Specialty Surgical Sciences), University of Ferrara, 44121 Ferrara, Italy.

Demographic changes have placed age-related mental health disorders at the forefront of public health challenges over the next three decades worldwide. Within the context of cognitive impairment and neurocognitive disorders among elderly people, the fragmentation of the self is associated with existential suffering, loss of meaning and dignity for the patient, as well as with a significant burden for the caregiver. Psychosocial interventions are part of a person-centered approach to cognitive impairment (including early stage dementia and dementia). Dignity therapy (DT) is a therapeutic intervention that has been shown to be effective in reducing existential distress, mood, and anxiety symptoms and improving dignity in persons with cancer and other terminal conditions in palliative care settings. The aims of this paper were: (i) To briefly summarize key issues and challenges related to care in gerontology considering specifically frail elderly/elderly with cognitive decline and their caregivers; and (ii) to provide a narrative review of the recent knowledge and evidence on DT in the elderly population with cognitive impairment. We searched the electronic data base (CINAHL, SCOPUS, PSycInfo, and PubMed studies) for studies regarding the application of DT in the elderly. Additionally, given the caregiver's role as a custodian of diachronic unity of the cared-for and the need to help caregivers to cope with their own existential distress and anticipatory grief, we also propose a DT-dyadic approach addressing the needs of the family as a whole.
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http://dx.doi.org/10.3390/bs10120178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759823PMC
November 2020

The Sense of Dignity at the End of Life: Reflections on Lifetime Values through the Family Photo Album.

Behav Sci (Basel) 2020 Nov 23;10(11). Epub 2020 Nov 23.

Institute of Psychiatry, Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.

This study focuses on the dimensions of dignity, linking Chochinov's Dignity Therapy to Schwartz's Theory of Values. The use of family photo albums has enriched the application of dignity therapy. Seven terminal patients in home-based palliative care participated in the therapeutic intervention. To measure the effects of the intervention, we administered the Edmonton Symptom Assessment Scale and the Patient Dignity Inventory, then, at the end of the meetings, collected the opinions of participants, available nurses, and relatives who attended the sessions. The resulting generativity documents were then analyzed through thematic analysis, which revealed three main themes linked to both fundamental values and the dimensions of dignity: The relationship between continuity of self and myriad values in the context of family relationships; personal dignity as characterized by the values of personal success, hope, and wisdom; and hope and generativity. The fourth theme reflected the participants' final judgements on the intervention, which were highly positive and greatly encouraged further use of photographs in similar therapeutic interventions. The assessment protocol highlighted a significant decrease in tiredness amongst the participants and a trend towards a significant decrease in drowsiness after the intervention.
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http://dx.doi.org/10.3390/bs10110177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700553PMC
November 2020

Hostility in cancer patients as an underexplored facet of distress.

Psychooncology 2021 04 7;30(4):493-503. Epub 2020 Dec 7.

Department of Neuroscience and Rehabilitation, Institute of Psychiatry, University of Ferrara, Ferrara, Italy.

Objective: In the present study, we aimed to assess hostility and to examine its association with formal psychiatric diagnosis, coping, cancer worries, and quality of life in cancer patients.

Methods: The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to make an ICD-10 (International Classification of Disease) psychiatric diagnosis was applied to 516 cancer outpatients. The patients also completed the Brief Symptom Inventory-53 to assess hostility (BSI-HOS), and the Mini-Mental Adjustment to cancer scale (Mini-MAC). A subset of patients completed the Cancer Worries Inventory (CWI), the Openness Scale, and the Quality of Life Index.

Results: By analyzing the distribution of the responses 25% of the patients had moderate and 11% high levels of hostility, with about 20% being BSI-HOS "cases." Hostility was higher in patients with a formal ICD-10 psychiatric diagnosis (mainly major depression, other depressive disorders, anxiety disorders) than patients without ICD-10 diagnosis. However, about 25% of ICD-10-non cases also had moderate-to-high hostility levels. Hostility was associated with Mini-MAC hopelessness and anxious preoccupation, poorer quality of life, worries (mainly problems sin interpersonal relationships), and inability to openly discuss these problems within the family.

Conclusions: Hostility and its components should be considered as dimensions to be more carefully explored in screening for distress in cancer clinical settings for its implications in negatively impacting on quality of life, coping and relationships with the family, and possibly the health care system.
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http://dx.doi.org/10.1002/pon.5594DOI Listing
April 2021

Evolution from adherent to suspension: systems biology of HEK293 cell line development.

Sci Rep 2020 11 4;10(1):18996. Epub 2020 Nov 4.

KTH - School of Engineering Sciences in Chemistry, Biotechnology, and Health, Dept. of Protein Science, Royal Institute of Technology, 106 91, Stockholm, Sweden.

The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.
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http://dx.doi.org/10.1038/s41598-020-76137-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642379PMC
November 2020
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