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Article ; Online: Metabolic reprogramming associated with aggressiveness occurs in the G-CIMP-high molecular subtypes of IDH1mut lower grade gliomas.

2019 Volume 22, Issue 4, Page(s) 480–492

Abstract: ... phenotype occurs at the glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP)-high ...

Abstract	Background: Early detection of increased aggressiveness of brain tumors is a major challenge in the field of neuro-oncology because of the inability of traditional imaging to uncover it. Isocitrate dehydrogenase (IDH)-mutant gliomas represent an ideal model system to study the molecular mechanisms associated with tumorigenicity because they appear indolent and non-glycolytic initially, but eventually a subset progresses toward secondary glioblastoma with a Warburg-like phenotype. The mechanisms and molecular features associated with this transformation are poorly understood. Methods: We employed model systems for IDH1 mutant (IDH1mut) gliomas with different growth and proliferation rates in vivo and in vitro. We described the metabolome, transcriptome, and epigenome of these models in order to understand the link between their metabolism and the tumor biology. To verify whether this metabolic reprogramming occurs in the clinic, we analyzed data from The Cancer Genome Atlas. Results: We reveal that the aggressive glioma models have lost DNA methylation in the promoters of glycolytic enzymes, especially lactate dehydrogenase A (LDHA), and have increased mRNA and metabolite levels compared with the indolent model. We find that the acquisition of the high glycolytic phenotype occurs at the glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP)-high molecular subtype in patients and is associated with the worst outcome. Conclusion: We propose very early monitoring of lactate levels as a biomarker of metabolic reprogramming and tumor aggressiveness.
MeSH term(s)	Brain Neoplasms/genetics ; DNA Methylation ; Glioma/genetics ; Guanine ; Humans ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/metabolism ; Mutation ; Phenotype
Chemical Substances	Guanine (5Z93L87A1R) ; Isocitrate Dehydrogenase (EC 1.1.1.41)
Language	English
Publishing date	2019-12-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noz207
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Article ; Online: Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications.

Malta, Tathiane M / de Souza, Camila F / Sabedot, Thais S / Silva, Tiago C / Mosella, Maritza S / Kalkanis, Steven N / Snyder, James / Castro, Ana Valeria B / Noushmehr, Houtan

Neuro-oncology

2017 Volume 20, Issue 5, Page(s) 608–620

Abstract: ... in gliomas. IDH-mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator phenotype (G ... CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high ... and G-CIMP-low) provides a further refinement in glioma classification that is independent of grade ...

Abstract	Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties. Despite advances in surgical techniques and clinical regimens, treatment of high-grade glioma remains challenging and carries dismal rates of therapeutic success and overall survival. Challenges include the molecular complexity of gliomas, as well as inconsistencies in histopathological grading, resulting in an inaccurate prediction of disease progression and failure in the use of standard therapy. The updated 2016 World Health Organization (WHO) classification of tumors of the central nervous system reflects a refinement of tumor diagnostics by integrating the genotypic and phenotypic features, thereby narrowing the defined subgroups. The new classification recommends molecular diagnosis of isocitrate dehydrogenase (IDH) mutational status in gliomas. IDH-mutant gliomas manifest the cytosine-phosphate-guanine (CpG) island methylator phenotype (G-CIMP). Notably, the recent identification of clinically relevant subsets of G-CIMP tumors (G-CIMP-high and G-CIMP-low) provides a further refinement in glioma classification that is independent of grade and histology. This scheme may be useful for predicting patient outcome and may be translated into effective therapeutic strategies tailored to each patient. In this review, we highlight the evolution of our understanding of the G-CIMP subsets and how recent advances in characterizing the genome and epigenome of gliomas may influence future basic and translational research.
MeSH term(s)	CpG Islands ; DNA Methylation ; Epigenomics ; Genome, Human ; Glioma/genetics ; Glioma/pathology ; Humans ; Mutation ; Phenotype
Language	English
Publishing date	2017-11-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/nox183
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Article ; Online: Acenaphthylene-Based Chromophores for Dye-Sensitized Solar Cells: Synthesis, Spectroscopic Properties, and Theoretical Calculations.

Malta, Gabriela / Pina, João / Lima, J Carlos / Parola, A Jorge / Branco, Paula S

ACS omega

2024 Volume 9, Issue 12, Page(s) 14627–14637

Abstract: A set of acenaphthylene dyes with arylethynyl π-bridges was tested for dye-sensitized solar cells (DSSCs). Crucial steps for the extension of the conjugated system from the acenaphylene core involved Sonogashira coupling reactions. Phenyl, thiophene, ... ...

Abstract	A set of acenaphthylene dyes with arylethynyl π-bridges was tested for dye-sensitized solar cells (DSSCs). Crucial steps for the extension of the conjugated system from the acenaphylene core involved Sonogashira coupling reactions. Phenyl, thiophene, benzotriazole, and thieno-[3,2-
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.4c01201
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Article ; Online: Correlation among job-induced stress, overall well-being, and cardiovascular risk in Italian workers of logistics and distribution.

Fruscione, Santo / Malta, Ginevra / Verso, Maria Gabriella / Calascibetta, Anna / Martorana, Daniela / Cannizzaro, Emanuele

Frontiers in public health

2024 Volume 12, Page(s) 1358212

Abstract: Introduction: Work-related stress is an occupational risk that has been linked to the development of cardiovascular disease (CVD). While previous studies have explored this association in various work contexts, none have focused specifically on ... ...

Abstract	Introduction: Work-related stress is an occupational risk that has been linked to the development of cardiovascular disease (CVD). While previous studies have explored this association in various work contexts, none have focused specifically on logistics and distribution personnel. These workers may be exposed to significant job stress, which potentially increases the risk of CVD. Methods: In this study, we aimed to examine the relationship between work-related stress and cardiovascular risk in a sample of 413 healthy workers of a logistics and distribution company. To assess work-related stress and cardiovascular risk, we used the organisational well-being questionnaire proposed by the Italian National Anti-Corruption Authority, the Framingham Heart Study General Cardiovascular Disease (CVD) Risk Prediction Score and the WHO General Wellbeing Index (WHO-5). Results: Our results revealed that individuals with low job support had a significantly higher CVD risk score and lower well-being index than those reporting high job support. Furthermore, workers with high-stress tasks showed higher well-being index scores than those with passive tasks. Approximately 58% of the subjects were classified as low CVD risk (CVD risk <10%), approximately 31% were classified as moderate risk (CVD risk between 10 and 20%) and 11% were considered high risk (CVD risk >20%). The overall median CVD risk for the population was moderate (6.9%), with individual scores ranging from 1 to 58%. Discussion: Further analyses confirmed the protective effect of work support, also identifying physical inactivity, regular alcohol consumption and low educational level as factors contributing to an increased risk of CVD. Interestingly, factors such as job control and work support demonstrated a positive impact on psychological well-being. These results emphasise the importance of intervention strategies aimed at promoting health in the workplace. By addressing these combined factors, organisations can effectively reduce the risk of CVD and improve the general well-being of their workforce.
MeSH term(s)	Humans ; Italy/epidemiology ; Male ; Female ; Cardiovascular Diseases/epidemiology ; Adult ; Middle Aged ; Surveys and Questionnaires ; Occupational Stress/epidemiology ; Occupational Stress/psychology ; Risk Factors ; Heart Disease Risk Factors ; Stress, Psychological/psychology
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2024.1358212
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Article ; Online: How to support the sexual wellbeing of older patients.

Hinchliff, Sharron / Mawson, Rebecca L / Malta, Sue / Cliff, Gilli

BMJ (Clinical research ed.)

2023 Volume 380, Page(s) e072388

MeSH term(s)	Humans ; Sexual Behavior ; Sexuality
Language	English
Publishing date	2023-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj-2022-072388
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Article ; Online: Extended validation of the Relational Depth Frequency Scale: Retest reliability, divergent validity, criterion validity with psychotherapy satisfaction, and measurement invariance in UK- and US-stratified samples.

Di Malta, Gina / She, Zhuang / Raymond-Barker, Brett / Cooper, Mick

Journal of clinical psychology

2023 Volume 79, Issue 9, Page(s) 2040–2052

Abstract: Background: The Relational Depth Frequency Scale (RDFS) assesses moments of profound connection in psychotherapy, associated with therapeutic benefit. To date, the RDFS has not been tested for its retest reliability, divergent and criterion validity, ... ...

Abstract	Background: The Relational Depth Frequency Scale (RDFS) assesses moments of profound connection in psychotherapy, associated with therapeutic benefit. To date, the RDFS has not been tested for its retest reliability, divergent and criterion validity, and measurement invariance, nor has it been tested in stratified samples of psychotherapy patients. Methods: Two stratified online samples of United Kingdom (n = 514) and United States (n = 402) psychotherapy patients filled out the RDFS, the Brief Social Desirability Scale (BSDS); and the Satisfaction with Therapy and Therapist Scale-revised (STTS-R). Two subsamples of patients (United Kingdom: n = 50 and United States: n = 203) filled out the RDFS again after 1 month. Results: Reliability for the six-item RDFS were excellent in United Kingdom and United States samples (Cronbach's α = 0.91 and 0.92; retest r = 0.73 and r = 0.76). Divergent (r = 0.10 and r = 0.12) and criterion validity (r = 0.69; and r = 0.70) were good. Full scalar invariance was established across countries, genders, and time. Conclusion: This contributes important evidence to the validity of the RDFS. Future research should assess predictive validity against psychotherapy outcomes and replicate these analyses in diverse samples.
MeSH term(s)	Humans ; Male ; Female ; Reproducibility of Results ; Surveys and Questionnaires ; Psychometrics ; Personal Satisfaction ; United Kingdom ; Psychotherapy
Language	English
Publishing date	2023-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219160-x
ISSN	1097-4679 ; 0021-9762
ISSN (online)	1097-4679
ISSN	0021-9762
DOI	10.1002/jclp.23525
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Article ; Online: Non-canonical mTORC1 signaling at the lysosome.

Napolitano, Gennaro / Di Malta, Chiara / Ballabio, Andrea

Trends in cell biology

2022 Volume 32, Issue 11, Page(s) 920–931

Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) signaling hub integrates multiple environmental cues to modulate cell growth and metabolism. Over the past decade considerable knowledge has been gained on the mechanisms modulating mTORC1 lysosomal ... ...

Abstract	The mechanistic target of rapamycin complex 1 (mTORC1) signaling hub integrates multiple environmental cues to modulate cell growth and metabolism. Over the past decade considerable knowledge has been gained on the mechanisms modulating mTORC1 lysosomal recruitment and activation. However, whether and how mTORC1 is able to elicit selective responses to diverse signals has remained elusive until recently. We discuss emerging evidence for a 'non-canonical' mTORC1 signaling pathway that controls the function of microphthalmia/transcription factor E (MiT-TFE) transcription factors, key regulators of cell metabolism. This signaling pathway is mediated by a specific mechanism of substrate recruitment, and responds to stimuli that appear to converge on the lysosomal surface. We discuss the relevance of this pathway in physiological and disease conditions.
MeSH term(s)	Humans ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Signal Transduction ; Transcription Factors/metabolism
Chemical Substances	Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Transcription Factors
Language	English
Publishing date	2022-05-30
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	30122-x
ISSN	1879-3088 ; 0962-8924
ISSN (online)	1879-3088
ISSN	0962-8924
DOI	10.1016/j.tcb.2022.04.012
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Zs.A 3410: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Machine learning determines stemness associated with simple and basal-like canine mammary carcinomas.

Xavier, Pedro L P / Marção, Maycon / Simões, Renan L S / Job, Maria Eduarda G / de Francisco Strefezzi, Ricardo / Fukumasu, Heidge / Malta, Tathiane M

Heliyon

2024 Volume 10, Issue 5, Page(s) e26714

Abstract: Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation, malignancy, and ... ...

Abstract	Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation, malignancy, and therapeutic resistance, but is still few elucidated in canine mammary tumor subtypes. Here, we first validated, using CMT samples, a previously published canine one-class logistic regression machine learning algorithm (OCLR) to predict stemness (mRNAsi) in canine cancer cells. Then, using the canine mRNAsi, we observed that simple carcinomas exhibit higher stemness than complex carcinomas and other histological subtypes. Also, we confirmed that stemness is higher and associated with basal-like CMTs and with NMF2 metagene signature, a tumor-specific DNA-repair metagene signature. Using correlation analysis, we selected the top 50 genes correlated with higher stemness, and the top 50 genes correlated with lower stemness and further performed a gene set enrichment analysis to observe the biological processes enriched for these genes. Finally, we suggested two promise stemness-associated targets in CMTs,
Language	English
Publishing date	2024-02-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e26714
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Article ; Online: Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

Martins, J-O / Borges, M-M / Malta, C-E / Guerra, J-M / Crispim, A-A / Coelho, B-C / Silva, L-F / Silva, P-G

Medicina oral, patologia oral y cirugia bucal

2024 Volume 29, Issue 2, Page(s) e248–e254

Abstract: Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment.: Material and methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. ...

Abstract	Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. Material and methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). Results: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. Conclusions: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.
MeSH term(s)	Humans ; Female ; Aged ; Male ; Cetuximab/adverse effects ; Retrospective Studies ; Cross-Sectional Studies ; Undertreatment ; Carcinoma, Squamous Cell/pathology ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/complications ; Stomatitis/chemically induced ; Risk Factors
Chemical Substances	Cetuximab (PQX0D8J21J)
Language	English
Publishing date	2024-03-01
Publishing country	Spain
Document type	Journal Article
ZDB-ID	2171573-7
ISSN	1698-6946 ; 1698-4447
ISSN (online)	1698-6946
ISSN	1698-4447
DOI	10.4317/medoral.26237
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Article ; Online: Comparison of a daily and alternate-day photobiomodulation protocol in the prevention of oral mucositis in patients undergoing radiochemotherapy for oral cancer: a triple-blind, controlled clinical trial.

Oliveira, F-M / Borges, M-M / Malta, C-E / Moura, J-F / Forte, C-P / Barbosa, J-V / Silva, P-G / Dantas, T-S

Medicina oral, patologia oral y cirugia bucal

2024

Abstract: Background: Preventive Photobiomodulation Therapy (PBMT) significantly reduces oral mucositis (OM) severity in patients undergoing Radiochemotherapy (RCT) for the treatment of oral cancer, but daily applications generate cost, overload the dental team, ... ...

Abstract	Background: Preventive Photobiomodulation Therapy (PBMT) significantly reduces oral mucositis (OM) severity in patients undergoing Radiochemotherapy (RCT) for the treatment of oral cancer, but daily applications generate cost, overload the dental team, and reduce the number of patients assisted.To evaluate the effectiveness of two PBMT protocols in preventing OM in patients undergoing RCT for oral cancer. Material and methods: 16 patients diagnosed with oral cancer undergoing RCT were included, equally divided into two groups: a group treated daily with PBMT, and another group also submitted to daily treatment, however, performing the application of PBMT every three days, interspersed with a simulation of PBMT (placebo). A red laser was used (~660 nm), 0.1W power, 1J of energy applied per point, 9 points per area (labial mucosa, buccal mucosa, lateral borders of the tongue, body of the tongue, and floor of the mouth) from the beginning of RCT until the end of the oncological treatment. Daily assessments were performed regarding OM scores, the World Health Organization (WHO) pain scale, and the visual analog scale (VAS). Weight, salivary flow (SGAPP), OHIP-14, and DMFT were evaluated on the initial and final days of RT. OM incidence and clinical data were compared by Pearson's chi-square test or Fisher's exact test. Pain and other scale scores were compared using the Mann-Whitney and Friedman/Dunn tests (SPSS v20.0 p<0.05). Results: In the group with PBMT on alternate days, there was an increase in the frequency of grade 2 and grade 3 oral mucositis and an increased risk of grade 2 oral mucositis, in addition to higher mean pain scores and greater reduction in salivary flow. Conclusions: The daily PBMT protocol proved more effective in controlling the frequency and severity of OM, pain, and salivary flow.
Language	English
Publishing date	2024-04-14
Publishing country	Spain
Document type	Journal Article
ZDB-ID	2171573-7
ISSN	1698-6946 ; 1698-4447
ISSN (online)	1698-6946
ISSN	1698-4447
DOI	10.4317/medoral.26436
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