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  • 1
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 10, No. 8 ( 2015-8-12), p. e0135863-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2015
    detail.hit.zdb_id: 2267670-3
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  • 2
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 10, No. 4 ( 2015-4-9), p. e0123522-
    Type of Medium: Online Resource
    ISSN: 1932-6203
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2015
    detail.hit.zdb_id: 2267670-3
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  The FEBS Journal Vol. 288, No. 21 ( 2021-11), p. 6087-6094
    In: The FEBS Journal, Wiley, Vol. 288, No. 21 ( 2021-11), p. 6087-6094
    Abstract: Anthony Letai is Professor in Medicine at Harvard Medical School and Dana Farber Cancer Institute, and President of The Society for Functional Precision Medicine. Among Tony’s scientific achievements, work from his lab contributed toward the FDA approval of Venetoclax combination treatment for adult acute myeloid leukemia (AML) patients. Moreover, his studies on cancer cell death have led to the development of BH3 profiling, an assay that allows for the definition of how close a cell is to the threshold required to commit to apoptosis, which can be used to improve clinical outcomes for cancer patients. In this interview, Tony relays the story behind some of his scientific breakthroughs, discusses the importance of function when designing targeted cancer therapies, gives an overview of BH3 profiling and its application to cancer therapy, and recalls the key events and collaborations that drove his successful research career.
    Type of Medium: Online Resource
    ISSN: 1742-464X , 1742-4658
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2172518-4
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Hellenic Psychiatric Association ; 2023
    In:  Psychiatriki ( 2023-7)
    In: Psychiatriki, Hellenic Psychiatric Association, ( 2023-7)
    Abstract: Since the COVID-19 pandemic outburst, numerous studies have reported on the holistic approach of the disease, which has negative consequences on physical and mental health as well as short- and long-term effects on cognition, independently of age. The context of the pandemic brought significant demands on public health systems, leading to restrictive measures against coronavirus expansion (quarantines, physical distancing policies, etc.). Such measures are reported to increase perceived loneliness and helplessness and may exacerbate feelings of emotional distress.1 Elderly diagnosed with neurocognitive disorders, i.e., mild cognitive impairment (MCI) or dementia, may present multifaceted cognitive deficits accompanied by neuropsychiatric symptoms, medical comorbidities, and high mortality rates. Furthermore, elderly with MCI/dementia are more vulnerable to SARS-COV-2 infection and disease complications due to decreased compliance with protective measures and multimorbidity. Simultaneously, limited access to health care services, distancing from their loved ones, abrupt changes in their daily routines or cancellation of daycare programs may make them more susceptible to pandemic secondary effects. According to the World Health Organization about 55 million people live with dementia globally. Dementia diagnosis was reported as an independent risk factor for increased mortality rate among the elderly infected with SARS-COV-2.2 Cross-sectional studies conducted all over Europe reported increased cognitive deterioration rate in patients with MCI and dementia during lockdown compared to the pre-lockdown period, as well as among dementia patients infected with COVID-19 compared to those not infected.3 Exacerbation of pre-existing sleep/appetite dysregulation and aberrant motor behavior, worsened symptoms of apathy, depression, and agitation, a rise in delirium episodes and disease-related falls and onset of behavioral symptoms during quarantine occurred.4 Also, patients living alone expressed excessive worrying and an overall decline in well-being. However, results from a large cohort study conducted in England failed to distinguish COVID-19 effects on dementia patients’ psychological state between 2018 and 2020, possibly due to the small number of dementia patients recruited and disease severity.5 Among the Greek elderly, dementia prevalence rates range between 5-10.8% and 32.4% for MCI incidence.6,7 Only a few studies have investigated the impact of COVID-19 quarantine on mental and psychological health of the Greek elderly diagnosed with cognitive disorders. A longitudinal study was conducted between 2018 and 2020 including a rather large number of elderly people with MCI or Alzheimer’s disease (AD). The authors compared the objectively assessed deterioration difference pre- and during the quarantine in terms of cognition, behavior and function level. They concluded that no significant quarantine-related changes were detected in cognition between the three time points, although the possibility that behavioral and psychological deterioration indirectly affected cognitive and functional decline among AD patients cannot be excluded.8 In a cross-sectional study conducted during the first quarantine period (i.e., February to May 2020), critical aspects of everyday life (mood, physical health, communication) as well as compliance with confinement policies were examined based on subjective information provided by caregivers of elderly with MCI or dementia. Based on their findings, the authors report that MCI and dementia patients exhibited a significant overall decline, whereas those with dementia were more likely to deteriorate in terms of neuropsychiatric symptoms (apathy, mood changes, psychomotor anxiety), excessive worrying, and limited compliance with measures against COVID-19 expansion.9 In an effort to minimize possible deleterious effects of the pandemic-related quarantine on the elderly with neurocognitive disorders, telemedicine was implemented instead. Neuropsychological online testing, systematic monitoring of clinical outcome (compliance with pharmacotherapy) and motivational interventions such as physical activity programs were accommodated using user-friendly applications and telephone consultations.10 Nevertheless, limited access to and familiarization with technology, severity of cognitive deficits, and demographic factors (i.e., low educational and socioeconomic status), may have limited positive outcomes in the current population. In conclusion, the combined effect of neurocognitive disorders and the pandemic exceeds the healthcare system’s demands, posing in some cases insurmountable challenges. To minimize the negative effect of future similar conditions, focus should be given on the following directions: Patient-oriented, holistic protocols for systematic monitoring of clinical course, future cognitive decline, and timely psychiatric/neuropsychological interventions when necessary. Specialized training for caregivers’ and nursing staff focusing on the inclusion of self-hygiene measures in patients’ daily routine. Patients’ familiarization with online tools both for cognitive enhancement programs and for diagnostic/ monitoring purposes.
    Type of Medium: Online Resource
    ISSN: 1105-2333 , 1105-2333
    Language: Unknown
    Publisher: Hellenic Psychiatric Association
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    Begell House ; 2017
    In:  Critical Reviews™ in Oncogenesis Vol. 22, No. 3-4 ( 2017), p. 303-311
    In: Critical Reviews™ in Oncogenesis, Begell House, Vol. 22, No. 3-4 ( 2017), p. 303-311
    Type of Medium: Online Resource
    ISSN: 0893-9675
    URL: Issue
    Language: English
    Publisher: Begell House
    Publication Date: 2017
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  • 6
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4675-4675
    Abstract: Resistance to chemotherapy is a major clinical challenge in breast cancer (BC), and patients developing resistance need treatment alternatives. In this project we utilize patient-derived xenografts (PDXs) from triple negative BC (TNBC), as these models better reflect the human tumor complexity and heterogeneity, compared to cell line-based- and transgene animal models. An in-house established orthotopically growing PDX, MAS98.12, has gained resistance to chemotherapy due to prolonged exposure to paclitaxel (MAS98.12-PR), a microtubule-targeting chemotherapeutic agent. As the resistance was obtained in animals, we also have the paclitaxel sensitive equivalent (MAS98.12-PS). By utilizing the pair of sensitive and resistant tumors we can study the corresponding mechanism evolving in patients who initially respond to chemotherapy before resistance and disease progression. This model will aid in identifying key mechanisms of survival in the resistant tumors, and eventually in identifying targets for use as novel therapeutic opportunities in TNBC patients resistant to standard therapy. Finally, we have samples collected early and late after resistance development, allowing us to characterize mechanisms involved in stepwise progression of paclitaxel resistance. We are currently performing molecular profiling to reveal the mechanisms involved in development of resistance. Data from bulk RNAseq, immune profiling of myeloid cells, exome sequencing, secretome profiling and reverse-phase protein array (RPPA) allow for characterizing the isogenic pair of tumors on multiple levels. Preliminary observations include aberrant expression of ABCB1/MDR1, normally involved in translocating drugs across membranes, and previously described as a mechanism involved in pertaining resistance in tumor cells. As multiple attempts to target MDR1 itself has failed, we hypothesize that our PS and PR pair will identify vulnerable/targetable signaling axis in the resistant tumors. Additionally, both PDX models have been assessed for their sensitivity to various chemo-/targeted-drugs and their combinations, revealing alternative means of treating the resistant tumors. Altogether, the molecular profiles and the sensitivity data will give novel knowledge and treatment options for patients failing to respond to standard chemotherapy. Citation Format: Eivind Valen Egeland, Kotryna Seip, Geir Frode Øy, Eleni Skourti, Solveig J Pettersen, Siri Juell, Mads Haugland Haugen, Olav Engebraaten, Lina Prasmickaite, Gunhild M Maelandsmo. Chemoresistant patient-derived xenografts to identify treatment options in breast cancer patients not responding to standard chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4675.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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    detail.hit.zdb_id: 410466-3
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  • 8
    In: Cells, MDPI AG, Vol. 10, No. 8 ( 2021-07-30), p. 1942-
    Abstract: The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 9
    In: Sleep, Oxford University Press (OUP), Vol. 45, No. Supplement_1 ( 2022-05-25), p. A279-A280
    Abstract: Sleep disturbances have been linked with cognitive decline and previous cross-sectional have shown that long sleep duration is a marker of disease severity in patients Mild Cognitive Impairment (MCI) and Dementia.Our aim was to examine the longitudinal associations between sleep quantity and quality indices and cognitive progression in non-demented community-dwelling elderly. Methods A sub-sample of 62 participants (72.6% females) were recruited from a large population-based cohort in the island of Crete, Greece of 3,140 older adults ( & gt;60yrs). Participants were followed-up 8 years later (phase III). All participants underwent neuropsychiatric/neuropsychological evaluation (phases II & III) and a 3-day 24h actigraphy (phase II).Participants were diagnosed as CNI(N=38) and MCI(N=24) during phase II, and CNI (N=22), MCI (N=27) and Dementia (N=13) during phase III. On follow-up, 28 participants progressed to a cognitively declined diagnosis compared to phase II (deteriorated group), while 34 did not (non-deteriorated group). Objective sleep variables at phase II were compared between the deteriotated/non-deteriorated groups using ANCOVA controlling for confounders. Also, differences in neuropsychological testing scores (phase II- phase III) were calculated and associations of differences with sleep variables were examined using partial correlation models controlling for confounders. Results The deteriorated group compared to non-deteriorated had significantly longer night total sleep time (TST) (442±72.6min vs. 407±53.6min, p=0.033), 24h-TST (484±8.9min vs. 434±66.4min, p=0.008), night time in bed (TMB) (537±78.7min vs. 497±62.7min, p=0.03), and 24h-TMB (603±85min vs. 539±85min, p=0.005). Episodic memory worsening was moderately correlated with night TST (r=.316), night and 24h-TMB (r=.526, and r= .442 respectively), wake time after sleep onset (r=.351), and average duration of night awakenings (r=.405). Immediate episodic memory recall decline was positively correlated with night TMB (r=.338). Conclusion Preliminary results from the Cretan aging cohort indicate that almost half of the participants deteriorated cognitively in 8 years and this decline was predicted by objective sleep duration at baseline. Long sleep at baseline may predict deterioration of clinical cognitive status in non-demented elderly at follow-up. It appears that prolonged objective sleep duration and time in bed are novel and clinically useful prognostic factors of cognitive deterioration in elderly with or without cognitive deficits. Support (If Any) National Strategic Reference Framework (NSRF) - Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2056761-3
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  • 10
    In: SLEEP, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2023-05-29), p. A393-A394
    Abstract: We have previously shown that although sleep duration is similar between cognitively non-impaired (CNI) elders and patients with Mild Cognitive Impairment (MCI), long sleep duration is associated with disease severity in patients with multi-domain MCI and Dementia. Our aim was to examine the associations between sleep duration and cognitive status in subjects with CNI and MCI followed 8 years later. Methods A sub-sample of 110 participants (77.3% females) were recruited from a large population-based cohort in Crete, Greece of 3,140 older adults ( & gt;60 years). Participants with an initial diagnosis of CNI (n=57) and MCI (n=53) (mean age at baseline=72.7 years [SD=6.8]) were followed-up 8 years later (mean age at follow up=80.5 years [SD=6.7] ). All participants underwent neuropsychiatric/neuropsychological evaluation (baseline & follow-up) and a 7-day 24h actigraphy (follow-up). Sleep duration measured as night Total Sleep Time (TST) at follow-up was compared between the diagnostic groups using ANCOVA controlling for age, gender, depression symptom severity, psychotropic medication. Long sleep duration was defined by values & gt;75% percentile of the total sample distribution on each sleep index. Results At follow up 62.7% of participants have deteriorated cognitively with 29 being diagnosed with CNI, 49 with MCI and 32 with dementia. Patients with dementia had significantly longer night TST (mean=493, SD=106 min) than persons with MCI (mean=453, SD=68 min, p=0.05) who in turn had longer night TST than CNI participants (mean=409, SD=58 min, p=0.02). Also, long night sleep duration was significantly more prevalent among dementia patients and MCI compared to CNI individuals [67.7% vs. 36.7% vs. 10.3%, respectively; all p & lt; 0.02)]. Conclusion Our study confirms and expands previous findings that objective long sleep duration is a marker of worse cognitive status in elderly with MCI or Dementia and that this association is even stronger in old-old individuals. Support (if any) National Strategic Reference Framework (NSRF)-Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299 HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397
    Type of Medium: Online Resource
    ISSN: 0161-8105 , 1550-9109
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2056761-3
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