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PTEN restoration and CXCR2 depletion synergistically enhance the effect of enzalutamide and inhibit bone metastatic CRPC
No full textRationale: Enzalutamide (Enz) is the first-line therapy for castration-resistant prostate cancer (CRPC). However, drug resistance has hindered its further application. Moreover, CRPC is frequently prone to metastasis, particularly to bone (BmCRPC). Methods: To investigate the involvement of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deletion and C-X-C motif chemokine receptor 2 (CXCR2) overexpression in Enz-resistant CRPC and BmCRPC, we constructed a bisphosphonate (BP) lipid-like material with high bone affinity (GB4-BPL) for the codelivery of a PTEN plasmid (pPTEN) and CXCR2 siRNA (siCXCR2) to BmCRPC. Results: GB4-BPL demonstrated twice the bone metastasis-targeting ability of GB4-lipo (which lacks bisphosphonate modification) while maintaining a gene transfection efficiency comparable to that of Lipo8000 and exhibiting significantly lower cytotoxicity. Moreover, siCXCR2 and pPTEN loaded in GB4-BPL (GB4-BPL@siCXCR2/pPTEN) synergistically inhibited tumor growth and metastasis, highly enhancing the effect of Enz by 69.45% in the Enz-resistant model. Furthermore, GB4-BPL@siCXCR2/pPTEN significantly reduced the numbers of MDSCs, Tregs, and M2-like TAMs by 55.01%, 64.75%, and 52.53%, respectively, while increasing the proportions of M1 macrophages, NK cells, and CD8+ T cells by 1.65-, 1.40-, and 4.60-fold, respectively. In addition, this nanosystem reduced skeletal-related events. Conclusions: Our studies demonstrated the potential of GB4-BPL for delivering siCXCR2/pPTEN to tumor and bone metastatic sites. GB4-BPL@siCXCR2/pPTEN alone or in combination with Enz could provide a new strategy for the treatment of drug-resistant BmCRPC.Peer reviewe
The Utility of Infrared Thermography and Hyperspectral Imaging in Peripheral Artery Disease: A Systematic Review
No full textBackground: Peripheral artery disease (PAD) is a prevalent vascular disorder that reduces blood flow and tissue oxygenation. Early detection is crucial to optimise treatment outcomes and minimise ulceration or gangrene and possible subsequent amputations. This systematic review evaluated the diagnostic significance and clinical utility of infrared thermography (IRT) and hyperspectral imaging (HSI) as non-invasive, contactless techniques for PAD and chronic limb-threatening ischaemia assessment. Infrared thermography assesses blood perfusion by detecting temperature changes in limbs and HSI can be utilised to evaluate oxygen saturation, and deoxyhaemoglobin and oxyhaemoglobin concentrations in superficial tissue. Methods: After a comprehensive PubMed literature search, a total of 15 articles were included in the final analysis: eight studies utilising IRT for circulation assessment, six studies employing HSI, and one study combining the two. A total 607 participants with PAD were included. Results: In the IRT studies, varying levels of correlations were found between established assessment modalities and temperature changes. Significant, but mostly modest, correlations were discovered in the HSI studies—particularly with deoxyhaemoglobin, oxyhaemoglobin, and the ankle–brachial index—making the clinical significance of the results unclear, but still suggesting that HSI has potential for assessing and screening PAD. Head-to-head, HSI accurately detected immediate perfusion changes after PAD treatment, while IRT did not, suggesting that HSI-derived parameters may be more precise for perfusion assessment. Conclusions: The results indicate that both IRT and HSI hold promise for assessing circulation, oxygenation, and perfusion in participants with vascular deficiency. Further research with larger sample sizes and standardised measurement protocols is needed to validate the clinical utility of IRT and HSI.Peer reviewe
Paikallisen eturauhassyövän vaikutus elämänlaatuun EPIC-26-kyselyllä arvioituna
Full text linkEturauhassyöpä on maailmanlaajuisesti miesten toiseksi yleisin syöpä ja Suomessa miesten yleisin syöpä. Paikallisen eturauhassyövän hyvän ennusteen ja hoitomenetelmästä riippumattoman matalan kuolleisuuden johdosta taudin ja sen hoitojen vaikutukset elämänlaatuun korostuvat. Paikallinen eturauhassyöpä ja sen hoidot usein aiheuttavat tyypillisen oirekuvan potilaille, mahdollisesti vaikuttaen vielä pitkään taudin jälkeen. Tämän tutkimuksen tavoitteena on raportoida paikallista eturauhassyöpää sairastavien potilaiden elämänlaatua EPIC-26-kyselyn avulla.
Aineisto koostuu 170 potilaasta, jotka saivat sädehoitoa paikalliseen eturauhassyöpään Tampereen yliopistollisessa sairaalassa vuosina 2020–2022. Potilaat vastasivat EPIC-26-kyselyyn, joka on tarkoitettu mittaamaan eturauhassyöpää sairastavien elämänlaatua ja oirekuvaa. Potilaista 31 vastasi kyselyyn kahdesti tai kolmesti ja yhteensä vastauksia saatiin 205.
Tutkimuksen perusteella paikallisen eturauhassyövän oireet painottuivat tietyille osa-alueille. Eniten ongelmia koettiin virtsaamistoiminnoissa, joista suurin osa potilaista koki ongelmallisena virtsaamiskyvyn heikentymisen ja tiheän virtsaamistarpeen. Virtsaamistoimintojen lisäksi erityisen heikkona osa-alueena koettiin seksuaalinen toimintakyky ja siihen liittyvät häiriöt erektion saamisessa.
Paikallinen eturauhassyöpä aiheuttaa elämänlaatua merkittävästi heikentäviä haittavaikutuksia. Tutkimuksen tuloksia voidaan hyödyntää potilaan kokonaisvaltaisen hoidon suunnittelussa ja elämänlaadun tukemisessa taudin alkuvaiheissa
Enacted utopias: Learning from insurgent spatial practices
No full textThis chapter argues that engagement with insurgent spatial practices opens avenues for politically progressive architectural thinking that is better capable of recognising context specific sustainability with the potential to address the climate emergency. It offers one perspective on sustainable spatial production and draws on Lefebvre’s concepts of abstract and differential space, depicting dominant forms of spatial production and delving into practices that challenge them. The concept of insurgent spatial practices is built on, by which we mean the forms of spatial production that occur outside of profit-driven urbanisation and official urban development. Through multiple cases, we demonstrate concrete ways how architectural thinking is situated and experiential knowledge is produced and mobilised for sustainability.Peer reviewe
3D printed glass-based biophotonic scaffolds for in situ activation of photoswitchable drugs
No full textThe fabrication of porous biophotonic scaffold using a robocasting is reported here. Such material could be used for in-situ activation of photoswitchable drugs, which is essential for improving therapeutic efficacy while minimizing side effects. The scaffold is made of a phosphate glass mixed with CaWO₄:Yb³ ⁺,Tm³ ⁺ crystals and SrAl₂O₄:Eu²⁺,Dy³ ⁺ phosphors. Upon 980 nm irradiation, the scaffold emits blue light and green afterglow, enabling in-situ activation post-implantation as NIR light penetrates tissue. The challenges related to the sintering process and its effect on the spectroscopic properties of the scaffold are discussed. The as-3D printed scaffold successfully enables one to activate the muscarinic photoswitchable drug Phthal Azobenzene Iperoxo (PAI) upon NIR excitation, confirming the potential for in-situ phototriggered delivery of drug action using tissue-permeable light stimulus.Peer reviewe
Tensorial continuum damage model for concrete
No full textA tensorial continuum damage model for concrete which can correctly predict the failure stress states and failure modes in general multiaxial stress states is presented. The model is thermo-dynamically consistent and is based on proper expressions for the specific Gibbs free energy and the complementary form of the dissipation potential. Damaging of the material is described by a symmetric positive definite second order damage tensor. Invariant theory is used in construction of the potential functions which guarantees that the proper symmetry behaviour is satisfied and no artificial symmetrization operations need not to be done. The failure surface is formulated in a way that it mimics the behaviour of the well-known Ottosen’s four parameter failure surface. The predictions of the proposed model are compared to the Concrete Damaged Plasticity (CDP) model available in the commercial finite element software Abaqus in uniaxial and equibiaxial cases. The CDP model is calibrated against the uniaxial test results. However, for the CDP model the strain in the loading direction in the biaxial case starts to deviate from the experimental results already before the peak stress, while the present model yields accurate prediction. The constitutive model is implemented as an UMAT subroutine to be used in Abaqus.Peer reviewe
Combining Deep Reinforcement Learning with a Jerk-Bounded Trajectory Generator for Kinematically Constrained Motion Planning
No full textDeep reinforcement learning (DRL) is emerging as a promising method for adaptive robotic motion and complex task automation, effectively addressing the limitations of traditional control methods. However, ensuring safety throughout both the learning process and policy deployment remains a key challenge due to the risky exploration inherent in DRL, as well as the discrete nature of actions taken at intervals. These discontinuities, despite being part of a continuous action space, can lead to abrupt changes between successive actions, causing instability and unsafe intermediate states. To address these challenges, this paper proposes an integrated framework that combines DRL with a jerk-bounded trajectory generator (JBTG) and a robust low-level control strategy, significantly enhancing the safety, stability, and reliability of robotic manipulators. The low-level controller ensures the precise execution of DRL-generated commands, while the JBTG refines these motions to produce smooth, continuous trajectories that prevent abrupt or unsafe actions. The framework also includes pre-calculated safe velocity zones for smooth braking, preventing joint limit violations and ensuring compliance with kinematic constraints. This approach not only guarantees the robustness and safety of the robotic system but also optimizes motion control, making it suitable for practical applications. The effectiveness of the proposed framework is demonstrated through its application to a highly complex heavy-duty manipulator.Peer reviewe
Low parental stress and positive well-being in Finnish children and adolescents with type 1 diabetes
No full textINTRODUCTION: Given the limited knowledge about family dynamics and well-being among pediatric patients with type 1 diabetes (T1D) in Finland, this study aimed to assess parental stress, patient well-being, and their potential associations with glycemic control at a Finnish diabetes clinic.RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted with 199 children (aged 1-16 years) using a background information questionnaire, the Parenting Stress Index Short Form (PSI-4-SF), and the WHO-5 Well-Being Index (WHO-5) questionnaire.RESULTS: The mean glycated hemoglobin (HbA1c) level was 7.7% (61 mmol/mol), and the time in range (TIR) was 55.4%. Parents reported low stress levels (PSI total stress: median=31, IQR=12-55, n=133), with no significant correlation between parental stress and children's glycemic control. However, parents of children aged <7 years reported higher stress levels, which correlated with better metabolic control in children (HbA1c: rho=-0.86; TIR: rho=0.78; n=9). The mean WHO-5 score for all children was good (70; IQR=64-80, n=180). Their WHO-5 did not correlate with HbA1c (rho=-0.08, n=180) but correlated positively with TIR (rho=0.17, p=0.038, n=156).CONCLUSIONS: Better glycemic stability in children, as measured by TIR, correlated with well-being. Additionally, higher parental stress in young children was linked to better metabolic control in their children. These findings emphasize the importance of integrating psychosocial aspects into the care of pediatric patients with T1D.Peer reviewe
