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Keywords = high-involvement HR practices

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19 pages, 1087 KB  
Article
Exploring Sarcopenic Obesity in the Cancer Setting: Insights from the National Health and Nutrition Examination Survey on Prognosis and Predictors Using Machine Learning
by Yinuo Jiang, Wenjie Jiang, Qun Wang, Ting Wei and Lawrence Wing Chi Chan
Bioengineering 2025, 12(9), 921; https://doi.org/10.3390/bioengineering12090921 - 27 Aug 2025
Viewed by 488
Abstract
Objective: Sarcopenic obesity (SO) is a combination of depleted skeletal muscle mass and obesity, with a high prevalence, undetected onset, challenging diagnosis, and poor prognosis. However, studies on SO in cancer settings are limited. We aimed to explore the association between SO [...] Read more.
Objective: Sarcopenic obesity (SO) is a combination of depleted skeletal muscle mass and obesity, with a high prevalence, undetected onset, challenging diagnosis, and poor prognosis. However, studies on SO in cancer settings are limited. We aimed to explore the association between SO and mortality and to investigate potential predictors involved in the development of SO, with a further objective of constructing a model to detect its occurrence in cancer patients. Methods: The data of 1432 cancer patients from the National Health and Nutrition Examination Survey (NHANES) from the years 1999 to 2006 and 2011 to 2016 were included. For survival analysis, univariable and multivariable Cox proportional hazard models were used to examine the associations of SO with overall survival, adjusting for potential confounders. For machine learning, six algorithms, including logistic regression, stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost), were utilized to build models to predict the presence of SO. The predictive performances of each model were evaluated. Results: From six machine learning algorithms, cancer patients with SO were significantly associated with a higher risk of all-cause mortality (adjusted HR 1.368, 95%CI 1.107–1.690) compared with individuals without SO. Among the six machine learning algorithms, the optimal LASSO model achieved the highest area under the curve (AUC) of 0.891 on the training set and 0.873 on the test set, outperforming the other five machine learning algorithms. Conclusions: SO is a significant risk factor for the prognosis of cancer patients. Our constructed LASSO model to predict the presence of SO is an effective tool for clinical practice. This study is the first to utilize machine learning to explore the predictors of SO among cancer populations, providing valuable insights for future research. Full article
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20 pages, 2544 KB  
Article
TTF-1 Negativity Predicts Poor Outcomes in Advanced Non-Squamous NSCLC Also in the Immunotherapy Era: A Multicenter Cohort Study and Meta-Analysis
by Leonardo Brunetti, Valentina Santo, Alessandro Galletti, Alain Gelibter, Antonio Lugini, Gian Paolo Spinelli, Daniele Santini, Alessio Cortellini, Alessia Vendittelli, Giuseppina Rita Di Fazio, Fabrizio Citarella, Giulia La Cava, Emanuele Claudio Mingo, Matteo Fiorenti, Leonardo Cristofani, Sabrina Mariotti, Serena Ricciardi, Francesco Pantano, Bruno Vincenzi, Giuseppe Tonini and Marco Russanoadd Show full author list remove Hide full author list
Cancers 2025, 17(13), 2188; https://doi.org/10.3390/cancers17132188 - 28 Jun 2025
Viewed by 702
Abstract
Background/Objectives: Despite advances in immunotherapy, reliable biomarkers beyond PD-L1 expression are urgently needed to optimize treatment decisions in advanced non-squamous NSCLC. Thyroid Transcription Factor-1 (TTF-1), a biomarker associated with favorable prognosis in chemotherapy-treated patients, has unclear prognostic implications in the immunotherapy era. Methods [...] Read more.
Background/Objectives: Despite advances in immunotherapy, reliable biomarkers beyond PD-L1 expression are urgently needed to optimize treatment decisions in advanced non-squamous NSCLC. Thyroid Transcription Factor-1 (TTF-1), a biomarker associated with favorable prognosis in chemotherapy-treated patients, has unclear prognostic implications in the immunotherapy era. Methods: We conducted a multicenter retrospective study involving 163 advanced non-squamous NSCLC patients treated with first-line immunotherapy or chemo-immunotherapy and an additional historical chemotherapy-only cohort (n = 37). We evaluated the prognostic significance of TTF-1 expression for progression-free survival (PFS) and overall survival (OS). A systematic review and meta-analysis, performed following PRISMA guidelines, integrated our findings with existing evidence. Hazard ratios (HRs) were calculated using Cox proportional hazards models. Results: TTF-1 negativity was associated with significantly worse median PFS (6.7 vs. 16 months; HR 2.22, 95% CI 1.59–3.13; p < 0.001) and OS (11.5 vs. 26.4 months; HR 2.33, 95% CI 1.64–3.45; p < 0.001) compared to TTF-1 positivity. The prognostic value of TTF-1 was independent of PD-L1 status, with limited predictive relevance of PD-L1 expression observed within TTF-1-negative tumors. Meta-analysis (9 studies, 14 cohorts, n = 2019 patients) confirmed significantly inferior outcomes for TTF-1-negative patients across multiple immunotherapy-based regimens (pooled HR for PFS: 1.75, 95% CI 1.50–2.04; OS: 1.76, 95% CI 1.45–2.14). Conclusions: TTF-1 negativity independently predicts poor prognosis in advanced non-squamous NSCLC treated with immunotherapy-based regimens, identifying patients with limited benefit despite high PD-L1 expression. Integrating TTF-1 status into clinical practice may guide personalized treatment strategies, highlighting the need for prospective validation. Full article
(This article belongs to the Special Issue Immunotherapy in Non-Small Cell Lung Cancers)
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11 pages, 482 KB  
Article
Immunological Markers of Cardiovascular Pathology in Older Patients
by Akbota Bugibayeva, Almagul Kurmanova, Kuat Abzaliyev, Symbat Abzaliyeva, Gaukhar Kurmanova, Diana Sundetova, Merei Abdykassymova, Raushan Bitemirova, Ulzas Sagalbayeva, Karashash Absatarova and Madina Suleimenova
Biomedicines 2025, 13(6), 1392; https://doi.org/10.3390/biomedicines13061392 - 6 Jun 2025
Cited by 1 | Viewed by 735
Abstract
Background: The aging process is accompanied by changes in the immunological status of a person. Immunosenescence is considered a significant cause of the development of cardiovascular diseases (CVD) in elderly people. However, to date, the relationship between immune/inflammatory processes and diseases associated with [...] Read more.
Background: The aging process is accompanied by changes in the immunological status of a person. Immunosenescence is considered a significant cause of the development of cardiovascular diseases (CVD) in elderly people. However, to date, the relationship between immune/inflammatory processes and diseases associated with age is considered quite complex and is not fully understood. Immunophenotyping and the intracellular production of cytokines involved in the processes of inflammatory aging will allow us to identify biomarkers that are associated with cardiovascular diseases in the elderly. Objectives: To identify immunological markers associated with the process of inflammatory aging in older individuals with cardiovascular diseases. Methods: CD-phenotyping and intracellular cytokine analysis of peripheral blood using the flow cytometry method were conducted in 52 people over 60 years of age (group 1 had CVD and group 2 did not). Blood samples were stained with monoclonal antibodies (mAb) using Becton Dickinson (BD) reagents for the staining and binding of surface receptors CD4+, CD8+, CD14+, CD19+, CD16+, CD56+, CD59+, CD95+, and HLA DR+ and intracellular receptors TNF, IL-10, GM-CSF, VEGFR-2, IGF, and perforin. In addition, the following parameters were studied: questionnaire data (gender, age, alcohol consumption, smoking, physical activity, and marital status), clinical data (blood pressure (BP), heart rate (HR), body mass index (BMI)), comorbid conditions, and cardiovascular diseases (coronary heart disease (CHD), chronic heart failure (CHF), arterial hypertension (AH), previous myocardial infarction (PICS), diabetes mellitus (DM), atrial fibrillation (AF), and stroke). Results: The older patients with cardiovascular pathology had high levels of monocytes CD14+ (p = 0.014), low levels of CD8+ lymphocytes (p = 0.046), and low intracellular production of GM-CSF (p = 0.013) compared to the older people without CVD. Conclusions: The revealed differences in the expression of CD14+ monocytes indicate their role in the development of cardiovascular pathology associated with age-related changes. A decrease in cytotoxic CD8+ lymphocytes and intracellular GM-CSF production leads to an increased risk of developing cardiovascular diseases in older individuals. These observed changes with age will not only expand existing knowledge about the aging of the regulatory link of the immune system but also help to obtain data to predict CVD in older people. Thus, the obtained results support the use of these immunological markers to identify the risk of circulatory disease and a personalized approach in geriatric practice. Full article
(This article belongs to the Special Issue Inflammaging and Immunosenescence: Mechanisms and Link)
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24 pages, 2654 KB  
Article
Short-Term Beetroot Juice Supplementation Enhances Strength, Reduces Fatigue, and Promotes Recovery in Physically Active Individuals: A Randomized, Double-Blind, Crossover Trial
by Atef Salem, Achraf Ammar, Mohamed Kerkeni, Mohamed Ali Boujelbane, Ayse Merve Uyar, Leonard Moritz Köbel, Saranya Selvaraj, Reza Zare, Katie M. Heinrich, Haitham Jahrami, Slim Tounsi, Piotr Zmijewski, Wolfgang I. Schöllhorn, Khaled Trabelsi and Hamdi Chtourou
Nutrients 2025, 17(10), 1720; https://doi.org/10.3390/nu17101720 - 19 May 2025
Cited by 2 | Viewed by 5584
Abstract
Background/Objectives: Beetroot juice (BJ), a natural source of dietary nitrate, has gained increasing attention for its potential to improve exercise performance and cardiovascular function. While its benefits are well documented in endurance contexts, less is known about its short-term effects on resistance training [...] Read more.
Background/Objectives: Beetroot juice (BJ), a natural source of dietary nitrate, has gained increasing attention for its potential to improve exercise performance and cardiovascular function. While its benefits are well documented in endurance contexts, less is known about its short-term effects on resistance training performance and recovery. Thus, this study investigated the effects of short-term BJ supplementation on strength performance, cardiovascular responses, muscle oxygenation, and post-exercise recovery in resistance-trained males. Methods: Twelve healthy men (age: 21.3 ± 1.9 years; body mass index: 21.42 ± 2.36 kg/m2) completed two supplementation protocols involving BJ, providing 450 mg of nitrate per day, and a nitrate-free placebo (PLA). Each protocol consisted of two laboratory visits, one to assess the acute ergogenic effects and another to evaluate recovery after 72 h, resulting in a total of four sessions over a two-week period. During the three consecutive days of supplementation, participants ingested a single 900 mL dose (15 g BJ powder/PLA) 2 h before the first session, followed by three daily 300 mL doses (5 g BJ each/PLA) over the next two days, and a final dose (15 g BJ powder/PLA) taken 2 h before the second session (72 h post-first session). Each testing session involved incremental back squat (BS) and bench press (BP) exercises at 60%, 70%, and 80% of the one-repetition maximum (1RM) performed to failure, with three-minute rest intervals between sets. Repetition to failure, movement velocity, peak power, peak heart rate (HR), and muscle oxygenation (SmO2) were recorded during BP and BS exercises. Heart rate variability (HRV) and blood lactate were assessed before and after each training session. Lower-limb strength (CMJ and SJ) and delayed-onset muscle soreness (DOMS) were assessed daily during the 3-day supplementation period. Results: BJ significantly increased repetitions completed at 80% 1RM during BP and BS (p < 0.05) compared to the PLA. Peak movement velocity improved across all intensities using BJ with higher values compared to the PLA at 60–80% 1RM (p < 0.05). SmO2 was higher in BJ at 70–80% 1RM) and further improved after 72 h of BJ supplementation (p < 0.05). Cardiovascular strain was reduced in BJ, evidenced by lower peak HRs and smaller post-exercise declines in HRV indices (p < 0.05). Post-exercise recovery favored BJ, with faster recovery in jump performance at 24 h and reduced upper-limb DOMS at 24–48 h (p < 0.05). Conclusions: Short-term BJ supplementation enhances high-intensity resistance performance, improves muscle oxygenation, attenuates cardiovascular strain, and accelerates neuromuscular recovery. These benefits highlight its potential as a practical strategy for athletes seeking to optimize training performance and recovery during periods of intense resistance training. Full article
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10 pages, 502 KB  
Article
New Therapeutic Scenarios in the Context of Adjuvant Treatment for HR+/HER2−Breast Cancer: The Possible Role of Ribociclib in Treatment Algorithms for Stage II and III
by Nicola Battelli, Carmela Mocerino, Michele Montedoro, Mirco Pistelli, Ilaria Portarena, Mario Rosanova, Tina Sidoni and Patrizia Vici
Curr. Oncol. 2025, 32(4), 192; https://doi.org/10.3390/curroncol32040192 - 25 Mar 2025
Viewed by 1343
Abstract
Early breast cancer (EBC) treatment has evolved from radical surgery to a multidisciplinary approach, integrating radiotherapy, chemotherapy, targeted therapy, and hormone therapy with surgery to ensure the best possible outcome. Despite these advancements, hormone receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2-Negative (HER2−) EBC [...] Read more.
Early breast cancer (EBC) treatment has evolved from radical surgery to a multidisciplinary approach, integrating radiotherapy, chemotherapy, targeted therapy, and hormone therapy with surgery to ensure the best possible outcome. Despite these advancements, hormone receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2-Negative (HER2−) EBC still faces high recurrence rates after endocrine therapy. A panel of oncologists from Central-Southern Italy discussed the profile of ribociclib as an adjuvant therapy, based on the results of the NATALEE study, focusing on efficacy, safety, patient profiles, and regional challenges in treatment access. The experts identified ribociclib as suitable adjuvant treatment for stage II and III HR+/HER2− EBC patients, including those without lymph node involvement but with biologically aggressive disease. In their view, ribociclib could be an interesting option for patients not eligible for chemotherapy due to contraindications. Key challenges in translating the evidence on ribociclib in EBC into clinical practice include treatment duration, patient follow-up, and adverse events management. Strategies to address these challenges range from telemedicine and support from local clinics to tailored communication to improve adherence. Ribociclib is expected to significantly impact adjuvant treatment for HR+/HER2− EBC by addressing broader patient needs and potentially improving long-term outcomes through enhanced adherence and personalized management strategies. Full article
(This article belongs to the Section Breast Cancer)
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18 pages, 2749 KB  
Article
Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022
by Raffaele Del Prete, Daniela Nesta, Francesco Triggiano, Mara Lorusso, Stefania Garzone, Lorenzo Vitulano, Sofia Denicolò, Francesca Indraccolo, Michele Mastria, Luigi Ronga, Francesco Inchingolo, Sergey K. Aityan, Kieu C. D. Nguyen, Toai Cong Tran, Ciro Gargiulo Isacco and Luigi Santacroce
Diagnostics 2024, 14(9), 968; https://doi.org/10.3390/diagnostics14090968 - 6 May 2024
Cited by 2 | Viewed by 2264
Abstract
Background: The current manuscript’s aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed [...] Read more.
Background: The current manuscript’s aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV’s molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41–50 and 51–60 years old, and finally, 44% of subjects were >60 years old. Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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24 pages, 3590 KB  
Review
Novel Role of Molecular Hydrogen: The End of Ophthalmic Diseases?
by Si-Yu Li, Rong-Yue Xue, Hao Wu, Ning Pu, Dong Wei, Na Zhao, Zong-Ming Song and Ye Tao
Pharmaceuticals 2023, 16(11), 1567; https://doi.org/10.3390/ph16111567 - 7 Nov 2023
Cited by 8 | Viewed by 10662
Abstract
Molecular hydrogen (H2) is a colorless, odorless, and tasteless gas which displays non-toxic features at high concentrations. H2 can alleviate oxidative damage, reduce inflammatory reactions and inhibit apoptosis cascades, thereby inducing protective and repairing effects on cells. H2 can [...] Read more.
Molecular hydrogen (H2) is a colorless, odorless, and tasteless gas which displays non-toxic features at high concentrations. H2 can alleviate oxidative damage, reduce inflammatory reactions and inhibit apoptosis cascades, thereby inducing protective and repairing effects on cells. H2 can be transported into the body in the form of H2 gas, hydrogen-rich water (HRW), hydrogen-rich saline (HRS) or H2 produced by intestinal bacteria. Accumulating evidence suggest that H2 is protective against multiple ophthalmic diseases, including cataracts, dry eye disease, diabetic retinopathy (DR) and other fields. In particular, H2 has been tested in the treatment of dry eye disease and corneal endothelial injury in clinical practice. This medical gas has brought hope to patients suffering from blindness. Although H2 has demonstrated promising therapeutic potentials and broad application prospects, further large-scale studies involving more patients are still needed to determine its optimal application mode and dosage. In this paper, we have reviewed the basic characteristics of H2, and its therapeutic effects in ophthalmic diseases. We also focus on the latest progress in the administration approaches and mechanisms underlying these benefits. Full article
(This article belongs to the Special Issue Therapeutic Potential of Molecular Hydrogen)
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18 pages, 10674 KB  
Article
Correlation Matrix-Based Fusion of Hyperspectral and Multispectral Images
by Hong Lin, Jun Li, Yuanxi Peng, Tong Zhou, Jian Long and Jialin Gui
Remote Sens. 2023, 15(14), 3643; https://doi.org/10.3390/rs15143643 - 21 Jul 2023
Viewed by 2441
Abstract
The fusion of the hyperspectral image (HSI) and the multispectral image (MSI) is commonly employed to obtain a high spatial resolution hyperspectral image (HR-HSI); however, existing methods often involve complex feature extraction and optimization steps, resulting in time-consuming fusion processes. Additionally, these methods [...] Read more.
The fusion of the hyperspectral image (HSI) and the multispectral image (MSI) is commonly employed to obtain a high spatial resolution hyperspectral image (HR-HSI); however, existing methods often involve complex feature extraction and optimization steps, resulting in time-consuming fusion processes. Additionally, these methods typically require parameter adjustments for different datasets. Still, reliable references for parameter adjustment are often unavailable in practical scenarios, leading to subpar fusion results compared to simulated scenarios. To address these challenges, this paper proposes a fusion method based on a correlation matrix. Firstly, we assume the existence of a correlation matrix that effectively correlates the spectral and spatial information of HSI and MSI, enabling fast fusion. Subsequently, we derive a correlation matrix that satisfies the given assumption by deducing the generative relationship among HR-HSI, HSI, and MSI. Finally, we optimize the fused result using the Sylvester equation. We tested our proposed method on two simulated datasets and one real dataset. Experimental results demonstrate that our method outperforms existing state-of-the-art methods. Particularly, in terms of fusion time, our method achieves fusion in less than 0.1 seconds in some cases. This method provides a practical and feasible solution for the fusion of hyperspectral and multispectral images, overcoming the challenges of complex fusion processes and parameter adjustment while ensuring a quick fusion process. Full article
(This article belongs to the Section Remote Sensing Image Processing)
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23 pages, 6706 KB  
Article
Channel Intensity and Edge-Based Estimation of Heart Rate via Smartphone Recordings
by Anusha Krishnamoorthy, G. Muralidhar Bairy, Nandish Siddeshappa, Hilda Mayrose, Niranjana Sampathila and Krishnaraj Chadaga
Computers 2023, 12(2), 43; https://doi.org/10.3390/computers12020043 - 17 Feb 2023
Cited by 4 | Viewed by 2177
Abstract
Smartphones, today, come equipped with a wide variety of sensors and high-speed processors that can capture, process, store, and communicate different types of data. Coupled with their ubiquity in recent years, these devices show potential as practical and portable healthcare monitors that are [...] Read more.
Smartphones, today, come equipped with a wide variety of sensors and high-speed processors that can capture, process, store, and communicate different types of data. Coupled with their ubiquity in recent years, these devices show potential as practical and portable healthcare monitors that are both cost-effective and accessible. To this end, this study focuses on examining the feasibility of smartphones in estimating the heart rate (HR), using video recordings of the users’ fingerprints. The proposed methodology involves two-stage processing that combines channel-intensity-based approaches (Channel-Intensity mode/Counter method) and a novel technique that relies on the spatial and temporal position of the recorded fingerprint edges (Edge-Detection mode). The dataset used here included 32 fingerprint video recordings taken from 6 subjects, using the rear camera of 2 smartphone models. Each video clip was first validated to determine whether it was suitable for Channel-Intensity mode or Edge-Detection mode, followed by further processing and heart rate estimation in the selected mode. The relative accuracy for recordings via the Edge-Detection mode was 93.04%, with a standard error of estimates (SEE) of 6.55 and Pearson’s correlation r > 0.91, while the Channel-Intensity mode showed a relative accuracy of 92.75%, with an SEE of 5.95 and a Pearson’s correlation r > 0.95. Further statistical analysis was also carried out using Pearson’s correlation test and the Bland–Altman method to verify the statistical significance of the results. The results thus show that the proposed methodology, through smartphones, is a potential alternative to existing technologies for monitoring a person’s heart rate. Full article
(This article belongs to the Special Issue Machine and Deep Learning in the Health Domain)
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22 pages, 2215 KB  
Article
How Long Is Long Enough? Controlling for Acute Caffeine Intake in Cardiovascular Research
by Shara S. Grant, Kye Kim and Bruce H. Friedman
Brain Sci. 2023, 13(2), 224; https://doi.org/10.3390/brainsci13020224 - 29 Jan 2023
Cited by 10 | Viewed by 5895
Abstract
Caffeine substantially affects cardiovascular functioning, yet wide variability exists in caffeine control procedures in cardiovascular reactivity research. This study was conducted in order to identify a minimal abstention duration in habitual coffee consumers whereby cardiovascular reactivity is unconfounded by caffeine; Six hours (caffeine’s [...] Read more.
Caffeine substantially affects cardiovascular functioning, yet wide variability exists in caffeine control procedures in cardiovascular reactivity research. This study was conducted in order to identify a minimal abstention duration in habitual coffee consumers whereby cardiovascular reactivity is unconfounded by caffeine; Six hours (caffeine’s average half-life) was hypothesized. Thirty-nine subjects (mean age: 20.9; 20 women) completed a repeated measures study involving hand cold pressor (CP) and memory tasks. Caffeinated and decaffeinated coffee were administered. The following cardiovascular indices were acquired during pre-task, task, and post-task epochs prior to coffee intake, 30 min-, and six hours post-intake: Heart rate (HR), high-frequency heart rate variability (HF-HRV), root mean squared successive differences (RMSSD), systolic and diastolic blood pressures (SBP, DBP), mean arterial pressure (MAP), pre-ejection period (PEP), left ventricular ejection time (LVET), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI). Results support the adequacy of a six-hour abstention in controlling for caffeine-elicited cardiovascular changes. The current study offers a suggested guideline for caffeine abstention duration in cardiovascular research in psychophysiology. Consistent practice in caffeine abstention protocols would promote validity and reliability across such studies. Full article
(This article belongs to the Section Sensory and Motor Neuroscience)
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11 pages, 532 KB  
Article
Redox Genetic Risk Score and the Incidence of End-Stage Kidney Disease in People with Type 1 Diabetes
by Kamel Mohammedi, Michel Marre, Samy Hadjadj, Louis Potier and Gilberto Velho
Cells 2022, 11(24), 4131; https://doi.org/10.3390/cells11244131 - 19 Dec 2022
Cited by 2 | Viewed by 1860
Abstract
End-stage kidney disease (ESKD) is a multifactorial condition influenced by genetic background, but the extent to which a genetic risk score (GRS) improves ESKD prediction is unknown. We built a redox GRS on the base of previous association studies (six polymorphisms from six [...] Read more.
End-stage kidney disease (ESKD) is a multifactorial condition influenced by genetic background, but the extent to which a genetic risk score (GRS) improves ESKD prediction is unknown. We built a redox GRS on the base of previous association studies (six polymorphisms from six redox genes) and tested its relationship with ESKD in three cohorts of people with type 1 diabetes. Among 1012 participants, ESKD (hemodialysis requirement, kidney transplantation, eGFR < 15 mL/min/1.73 m2) occurred in 105 (10.4%) during a 14-year follow-up. High redox GRS was associated with increased ESKD risk (adjusted HR for the upper versus the lowest GRS tertile: 2.60 (95% CI, 1.51–4.48), p = 0.001). Each additional risk-allele was associated with a 20% increased risk of ESKD (95% CI, 8–33, p < 0.0001). High GRS yielded a relevant population attributable fraction (30%), but only a marginal enhancement in c-statistics index (0.928 [0.903–0.954]) over clinical factors 0.921 (0.892–0.950), p = 0.04). This is the first report of an independent association between redox GRS and increased risk of ESKD in type 1 diabetes. Our results do not support the use of this GRS in clinical practice but provide new insights into the involvement of oxidative stress genetic factors in ESKD risk in type 1 diabetes. Full article
(This article belongs to the Special Issue Recent Advances of Oxidative Stress and Inflammation in Diabetes)
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17 pages, 3522 KB  
Article
Employable until Retirement: How Inclusive Leadership and HR Practices Can Foster Sustainable Employability through Strengths Use
by Sait Gürbüz, Marianne van Woerkom, Dorien T. A. M. Kooij, Evangelia Demerouti, Jac J. L. van der Klink and Evelien P. M. Brouwers
Sustainability 2022, 14(19), 12195; https://doi.org/10.3390/su141912195 - 26 Sep 2022
Cited by 14 | Viewed by 3977
Abstract
Background: Although the new model of sustainable employability (SE), which builds on the capability approach, has received growing attention, research on how to enhance workers’ SE is scarce. In this study, we aimed to investigate whether (1) inclusive leadership and high-involvement HR practices [...] Read more.
Background: Although the new model of sustainable employability (SE), which builds on the capability approach, has received growing attention, research on how to enhance workers’ SE is scarce. In this study, we aimed to investigate whether (1) inclusive leadership and high-involvement HR practices are positively associated with SE and whether (2) strengths use mediates these associations. To test our research hypotheses, we surveyed Dutch employees (N = 364), selected with random sampling. The results of structural equation modeling showed that inclusive leadership and high-involvement HR practices were positively associated with workers’ SE. Moreover, we discovered that strengths use mediated these relationships. These results contribute to the SE literature by providing initial evidence that inclusive leadership and high-involvement HR practices are directly and indirectly (through strengths use) related to workers’ SE. Full article
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11 pages, 445 KB  
Review
Autologous Stem-Cell Transplantation for High-Risk Neuroblastoma: Historical and Critical Review
by Jaume Mora
Cancers 2022, 14(11), 2572; https://doi.org/10.3390/cancers14112572 - 24 May 2022
Cited by 9 | Viewed by 4362
Abstract
Curing high-risk neuroblastoma (HR-NB) is a challenging endeavor, which involves the optimal application of several therapeutic modalities. Treatment intensity for cancer became highly appealing in the 1990s. Investigative trials assumed that tumor response correlated with the dosage or intensity of drug(s) administered, and [...] Read more.
Curing high-risk neuroblastoma (HR-NB) is a challenging endeavor, which involves the optimal application of several therapeutic modalities. Treatment intensity for cancer became highly appealing in the 1990s. Investigative trials assumed that tumor response correlated with the dosage or intensity of drug(s) administered, and that this response would translate into improved survival. It was postulated that, if myelotoxicity could be reversed by stem-cell rescue, cure might be possible by increasing the dose intensity of treatment. The principle supported autologous stem-cell transplant (ASCT) strategies. High-dose therapy transformed clinical practice, legislation, and public health policy, and it drove a two-decade period of entrepreneurial oncology. However, today, no ASCT strategies remain for any solid tumor indication in adults. As with most solid malignancies, higher dosing of cytotoxic agents has not resulted in a clear benefit in survival for HR-NB patients, whereas the long-term toxicity has been well defined. Fortunately, novel approaches such as anti-GD2 immunotherapy have demonstrated a significant survival benefit with a much less adverse impact on the patient’s wellbeing. On the basis of extensive experience, persisting with administering myeloablative chemotherapy as the standard to treat children with HR-NB is not consistent with the overall aim in pediatric oncology of curing with as little toxicity as possible. Full article
(This article belongs to the Section Pediatric Oncology)
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17 pages, 1100 KB  
Review
Recent Advances in Enhancing the Therapeutic Index of PARP Inhibitors in Breast Cancer
by Camille Franchet, Jean-Sébastien Hoffmann and Florence Dalenc
Cancers 2021, 13(16), 4132; https://doi.org/10.3390/cancers13164132 - 17 Aug 2021
Cited by 5 | Viewed by 3316
Abstract
As poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with the deficiency of DNA double-strand (DSB) break repair by homologous recombination (HR), PARP inhibitors (PARPi) are currently used to treat breast cancers with mutated BRCA1/2 HR factors. Unfortunately, the increasingly high rate of [...] Read more.
As poly-(ADP)-ribose polymerase (PARP) inhibition is synthetic lethal with the deficiency of DNA double-strand (DSB) break repair by homologous recombination (HR), PARP inhibitors (PARPi) are currently used to treat breast cancers with mutated BRCA1/2 HR factors. Unfortunately, the increasingly high rate of PARPi resistance in clinical practice has dented initial hopes. Multiple resistance mechanisms and acquired vulnerabilities revealed in vitro might explain this setback. We describe the mechanisms and vulnerabilities involved, including newly identified modes of regulation of DSB repair that are now being tested in large cohorts of patients and discuss how they could lead to novel treatment strategies to improve the therapeutic index of PARPi. Full article
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18 pages, 289 KB  
Review
Translational Research Opportunities Regarding Homologous Recombination in Ovarian Cancer
by Margarita Romeo, Juan Carlos Pardo, Anna Martínez-Cardús, Eva Martínez-Balibrea, Vanesa Quiroga, Sergio Martínez-Román, Francesc Solé, Mireia Margelí and Ricard Mesía
Int. J. Mol. Sci. 2018, 19(10), 3249; https://doi.org/10.3390/ijms19103249 - 19 Oct 2018
Cited by 6 | Viewed by 4292
Abstract
Homologous recombination (HR) is a DNA repair pathway that is deficient in 50% of high-grade serous ovarian carcinomas (HGSOC). Deficient HR (DHR) constitutes a therapeutic opportunity for these patients, thanks to poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi; olaparib, niraparib, and rucaparib are already [...] Read more.
Homologous recombination (HR) is a DNA repair pathway that is deficient in 50% of high-grade serous ovarian carcinomas (HGSOC). Deficient HR (DHR) constitutes a therapeutic opportunity for these patients, thanks to poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi; olaparib, niraparib, and rucaparib are already commercialized). Although initially, PARPi were developed for patients with BRCA1/2 mutations, robust clinical data have shown their benefit in a broader population without DHR. This breakthrough in daily practice has raised several questions that necessitate further research: How can populations that will most benefit from PARPi be selected? At which stage of ovarian cancer should PARPi be used? Which strategies are reasonable to overcome PARPi resistance? In this paper, we present a summary of the literature and discuss the present clinical research involving PARPi (after reviewing ClinicalTrials.gov) from a translational perspective. Research into the functional biomarkers of DHR and clinical trials testing PARPi benefits as first-line setting or rechallenge are currently ongoing. Additionally, in the clinical setting, only secondary restoring mutations of BRCA1/2 have been identified as events inducing resistance to PARPi. The clinical frequency of this and other mechanisms that have been described in preclinics is unknown. It is of great importance to study mechanisms of resistance to PARPi to guide the clinical development of drug combinations. Full article
(This article belongs to the Special Issue Ovarian Cancer: Pathogenesis, Diagnosis, and Treatment)
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