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The social and health benefits that green areas and forests can provide are now recognized in the scientific community worldwide. There is a growing interest in and demand for forest care initiatives and nature-based therapy, also as a result of the impacts of Covid-19 pandemic. In Italy, the increasing interest in alternative and integrated solutions for care and healthcare promotion have laid the basis for the implementation of several projects and activities, particularly those known as Forest Therapy (FT). These initiatives provide a business opportunity for forestry and social sectors, for the development of rural areas, and they are a cost-saving opportunity for the National Health System because of the expected benefits (as assessed by several clinical studies confirming the therapeutic effectiveness of these activities). Despite the importance, in Italy there is not a specific legal basis and standardized procedures to determine the suitability of a FT site. As a result, FT initiatives have been carried out in different environments, whether in urban or extra-urban forest areas, with the implementation of activities deemed suitable in a "selfreferential" approach. Establishing a standard procedure for the recognition of FT suitable locations and related FT activities is a first step for the promotion of an important instrument that can meet several social needs. This work proposes (i) a standard procedure ("iter") for the validation of a Forest Therapy and Urban forest therapy (UFT) site by the competent authority to obtain the official "environmental recognition" of site suitability; (ii) the technical and objective criteria to assess the stationary and environmental parameters of a site in order to be qualified as a FT/UFT site, both in natural and urban contexts. The iter and criteria proposed take into account the relevant national regulations, the literature found on the subject, and the expertise of scientists and technicians. The procedure and criteria proposed can be used as basis of a regulation on FT in Italy, ensuring suitable sites officially recognised by public institutions and providing a high-quality service to society. Finally, a baseline regulation would also facilitate opportunities for dedicated funding, as well as the recognition of "green prescriptions" for the prevention and treatment of certain health problems. [ABSTRACT FROM AUTHOR]

Background: Quality assurance (QA) of patient‐specific treatment plans for intensity‐modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) necessitates prior validation. However, the standard methodology exhibits deficiencies and lacks sensitivity in the analysis of positional dose distribution data, leading to difficulties in accurately identifying reasons for plan verification failure. This issue complicates and impedes the efficiency of QA tasks. Purpose: The primary aim of this research is to utilize deep learning algorithms for the extraction of 3D dose distribution maps and the creation of a predictive model for error classification across multiple machine models, treatment methodologies, and tumor locations. Method: We devised five categories of validation plans (normal, gantry error, collimator error, couch error, and dose error), conforming to tolerance limits of different accuracy levels and employing 3D dose distribution data from a sample of 94 tumor patients. A CNN model was then constructed to predict the diverse error types, with predictions compared against the gamma pass rate (GPR) standard employing distinct thresholds (3%, 3 mm; 3%, 2 mm; 2%, 2 mm) to evaluate the model's performance. Furthermore, we appraised the model's robustness by assessing its functionality across diverse accelerators. Results: The accuracy, precision, recall, and F1 scores of CNN model performance were 0.907, 0.925, 0.907, and 0.908, respectively. Meanwhile, the performance on another device is 0.900, 0.918, 0.900, and 0.898. In addition, compared to the GPR method, the CNN model achieved better results in predicting different types of errors. Conclusion: When juxtaposed with the GPR methodology, the CNN model exhibits superior predictive capability for classification in the validation of the radiation therapy plan on different devices. By using this model, the plan validation failures can be detected more rapidly and efficiently, minimizing the time required for QA tasks and serving as a valuable adjunct to overcome the constraints of the GPR method. [ABSTRACT FROM AUTHOR]

In recent years, the application of positron emission tomography (PET) for the dose range verification of proton therapy has been proposed. However, the positron distribution is determined by the nuclear reaction cross section; hence, PET may not accurately reflect the dose range primarily influenced by ionization. Consequently, a proton dose range verification system based on scattered proton measurements has been suggested owing to the similarity in the reaction cross section between Rutherford scattering and ionization. While previous investigations have only verified the feasibility of dose range estimation through simple simulations, the objective of this study is to demonstrate this feasibility through experimental investigation. In this paper, we established an experimental framework for capturing scattered protons and introduced an algorithm that compares measured signal patterns with a reference database to estimate the dose range. A therapeutic beam was irradiated onto the abdominal region of a human phantom, and scattered protons were measured using scintillation detectors placed on the phantom surface. Consequently, the dose range was estimated with error margins of 4.22 ± 3.68 and 0.60 ± 1.03 mm along the beam axis and perpendicular directions to the Bragg peak, respectively. While providing the same level of Bragg peak positioning accuracy as conventional methods, our system features small size, cost-effectiveness, and system simplicity. One notable limitation of our method is the challenge in achieving precise detector positioning, which is crucial for accurate dose range estimation. Future research will focus on improving detector-position accuracy and exploring advanced algorithms for signal analysis to further refine dose range estimations. [ABSTRACT FROM AUTHOR]

Background: To carry out a validation questionnaire that assesses beliefs about inhaled treatments in patients with chronic obstructive pulmonary disease (COPD), as knowing patients' beliefs could help to improve medication adherence and health outcomes. Methods: We evaluated data from 260 COPD patients from electronic medical record databases from five primary healthcare centers, in a descriptive, cross-sectional study with a sample size calculated for a 10-item questionnaire, with an estimated Cronbach's alpha of 0.70 and a 95% confidence level. Study participants were selected via systematic random sampling. Variables: Ten-item Inhaled Therapy Beliefs Questionnaire, CCTI-Questionnaire v.2.0, time for completion, age, sex, educational level, spirometry severity (GOLD criteria), exacerbations (previous year), characteristics of inhaled treatment, and smoking habit. A two-year follow-up in a subsample of 77 patients from one health center was utilized. The Morisky–Green test, pharmacy dispensing data, test–retest (kappa coefficient), and an exploratory analysis of the adherence–belief relationship (ji-squared) were measured. Results: The 10-item questionnaire showed good viability (3 min completion time) when performed face-to-face or telephonically; its psychometric properties were acceptable, with an internal consistency (Cronbach's alpha) score of 0.613. Three factors explained 47.58% of the total variance (p < 0.0001): use (factor 1), effects (factor 2), and objectives (factor 3) of inhalers. The two-year follow-up ultimately considered 58 out of the 77 patients (10 deceased, 4 unlocated, 2 mistakes, 2 no inhaled treatment, and 1 withdrawal). Non-adherence was 48.3% in terms of the Morisky–Green test; 31% in terms of pharmacy dispensing data; and 40.4% considering both methods. There was low test–retest reliability, indicated by items 4, 8, and 9 of the CCTI-Questionnaire (Kappa = 0.4, 0.26, and 0.34; p-value < 0.0001, 0.008, and 0.001, respectively). There was mild correlation between beliefs and adherence. Conclusions: The ten-item CCTI-Questionnaire v.2.0 demonstrated acceptable psychometric properties regarding feasibility, reliability, and content validity. [ABSTRACT FROM AUTHOR]

Objectives: To assess the therapeutic response of HCC to antiangiogenic therapy plus immunotherapy by integrating RECIST 1.1 and alpha-fetoprotein (AFP) response at the 6th week to predict overall survival (OS). Methods: This retrospective study included 150 and 214 patients with HCC who received combination therapy in training and validation cohorts. The medical images and AFP levels obtained at baseline and 6th week were collected. AFP response stratification: partial response (PR): AFP% ≥ 75% decline; stable disease (SD): AFP% < 75% decline and ≤ 10% elevation; progressive disease (PD): AFP% > 10% elevation. The alpha-RECIST was: PR: RECIST 1.1-PR or AFP-PR; PD: AFP-PD or RECIST 1.1-PD and does not satisfy AFP-PR; SD: neither PR nor PD. OS was compared using Kaplan–Meier curves. The predictive ability of various criteria was evaluated using the concordance index and time-dependent area under the receiver-operating characteristic curve. Results: RECIST 1.1 achieved significant OS stratification (p = 0.020) for AFP < 20 ng/mL. For AFP ≥ 20 ng/mL, alpha-RECIST showed better performance than RECIST 1.1, mRECIST, and AFP response according to C-index (0.73 vs 0.66 vs 0.68 vs 0.69). The National Cancer Center (NCC) strategy utilized RECIST 1.1 for AFP < 20 ng/mL and alpha-RECIST for AFP ≥ 20 ng/mL and showed better performance than RECIST 1.1, mRECIST and AFP response according to C-index (0.73 vs 0.67 vs 0.69 vs 0.64). The performances of alpha-RECIST and NCC Strategy were confirmed in the validation cohort (C-index = 0.77 and 0.74). Conclusions: The alpha-RECIST and NCC Strategy achieved better survival stratification in patients with HCC under combination therapy in the AFP ≥ 20 ng/mL group and the whole cohort compared to the RECIST 1.1, mRECIST, and AFP response. Clinical translational relevance: The alpha-RECIST and National Cancer Center strategy are optimal methods for determining therapeutic response to a combination of anti-angiogenic therapy plus immunotherapy and facilitating accurate prognostic stratification for HCC in the AFP ≥ 20 ng/mL group and the whole cohort, which may help oncologists for early identification of responders and progression at 6 weeks and clinical decision-making. Key Points: • RECIST 1.1 is indicated for patients with baseline alpha-fetoprotein (AFP) < 20 ng/mL. • For patients with baseline AFP ≥ 20 ng/mL, integrating RECIST 1.1 and AFP response (alpha-RECIST) may aid in the early identification of survival benefits and progression definition prior to the administration of additional efficacious drugs. • The National Cancer Center strategy is an optimal stratified strategy for determining therapeutic response to a combination of anti-angiogenic therapy and immunotherapy for HCC based on baseline AFP levels. [ABSTRACT FROM AUTHOR]

Background: Former studies demonstrated that negative outcome expectations (OE) toward psychotherapy predict unfavorable psychotherapy outcomes. Critically, the measurement of OE is limited to direct measures that could be subject to self-presentational distortions. This study aimed to validate an online single category implicit association test (SC-IAT) to measure OE toward psychotherapy indirectly. Methods: We conducted three direct measures of OE, the Therapy SC-IAT, and a (control) Flower SC-IAT in a large sample (N = 705). Results: The Therapy SC-IAT correlated with most direct measures of OE (convergent validity) but not with measures of flower associations (discriminant validity). In exploratory analyses, we found that direct and indirect measurements of OE were related to prior experiences with psychotherapy. Conclusion: We discuss ways to improve the indirect-direct correlations and suggest that our newly developed indirect measure could complement the assessment of expectations in research and clinical practice. [ABSTRACT FROM AUTHOR]

Through the application of a discovery‐oriented task analysis, this research delineated specific therapist behaviors that resulted in a successful caregiver openness event in emotionally focused family therapy (EFFT). EFFT experts were recruited via email and asked to submit family therapy recordings where they believed a caregiver openness event occurred. Ten family therapy recordings were submitted by three experts. Within these recordings, 12 caregiver openness events were discovered and critically analyzed. Nine themes were identified and interventions therapists applied to accomplish these themes were delineated using the emotionally focused therapy‐coding scheme (EFT‐CS). These themes included: (1) validating and reframing the child's protected stance, (2) processing the impact of the child's unmet attachment longings, (3) validating the caregiver's blocked relational stance, (4) expanding caregiving intentions, (5) enacting the caregiver's intentions to meet the child's attachment longings, (6) processing the enactment, (7) processing and promoting caregiver accessibility to the child's response, (8) heightening the caregiver's accessible stance, and (9) enhancing shifting family dynamics. Additional findings, implications for clinical practice, training, and future research are discussed. [ABSTRACT FROM AUTHOR]

In this article, I explore play in dementia care settings, specifically two types: creative play (play that engages creativity and imagination) and 'playing along'. Acknowledging debates on truth-telling in dementia care, I consider how engagement-focused approaches in dementia contexts employ play to encourage connection, communication and care. To do so, I explore the work of researchers and applied theatre creatives in two projects, the Playful Engagement and Dementia Project and TimeSlips, alongside the communication strategy validation therapy. Considering the relational qualities and use of play in all three, I ask whether, in dementia care settings, embracing the flexible way in which play deals with the divide between fiction and reality can, without harm, address the needs of individuals living with dementia. [ABSTRACT FROM AUTHOR]

In a vehicle, the operation of mechanical systems generates undesirable vibrations and noise, and their reduction requires the study of three parts: vibrating systems, receiving structures, and connecting interfaces. The study presented in this paper concerns the connecting interfaces between subsystems. In particular, the in situ characterization of the isolation interface between two substructures by measuring dynamic transfer stiffness. In contrast to current methods, which require the disassembly of the vibration isolator from its original assembly, in situ methods have been studied and validated. This study sheds light on the strengths and limitations of each approach. These are known as the direct in situ method (D-IS) and round trip in situ method (RT-IS). Experimental validation has been carried out by comparing the D-IS method to the resonance method on a simple system. Good agreement is obtained between the two methods, making it possible to validate the method at low frequencies. Then, a comparison between the two methods D-IS and RT-IS is carried out on a more resonant test bench. The obtained stiffnesses were further validated using transfer path analysis (TPA) techniques to verify the performance of the proposed methods, and it was used to predict the response of another system, showing thus the independent nature of the identified dynamic stiffness. [ABSTRACT FROM AUTHOR]

Thrombus is an extremely dangerous factor in the human body that can block the blood vessel. Once thrombosis happens in venous of lower limbs, local blood flow is impeded. This leads to venous thromboembolism (VTE) and even pulmonary embolism. In recent years, venous thromboembolism has frequently occurred in a variety of people, and there is no effective treatment for patients with different venous structures. For the patients with venous isomer with single valve structure, we establish a coupled computational model to simulate the process of thrombolysis with multi‐dose treatment schemes by considering the blood as non‐Newtonian fluid. Then, the corresponding in vitro experimental platform is built to verify the performance of the developed mathematical model. At last, the effects of different fluid models, valve structures and drug doses on thrombolysis are comprehensively studied through numerical and experimental observations. Comparing with the experimental results, the relative error of blood boosting index (BBI) obtained from non‐Newtonian fluid model is 11% smaller than Newtonian fluid. In addition, the BBI from venous isomer is 1300% times stronger than patient with normal venous valve while the valve displacement is 500% times smaller. As consequence, low eddy current and strong molecular diffusion near the thrombus in case of isomer promote thrombolysis rate up to 18%. Furthermore, the 80 μM dosage of thrombolytic drugs gets the maximum thrombus dissolution rate 18% while the scheme of 50 μM doses obtains a thrombolysis rate of 14% in case of venous isomer. Under the two administration schemes for isomer patients, the rates from experiments are around 19.1% and 14.9%, respectively. It suggests that the proposed computational model and the designed experiment platform can potentially help different patients with venous thromboembolism to carry out clinical medication prediction. [ABSTRACT FROM AUTHOR]

The management of osteosarcoma (OS) patients presents a significant clinical challenge. Despite progress in conventional and targeted therapies, the survival rate of OS patients remains limited largely due to therapy resistance and the high metastatic potential of the disease. OS models that accurately reflect the fundamental characteristics are vital to the innovation and validation of effective therapies. This review provides an insight into the advances and challenges in OS drug development, focusing on various preclinical models, including cell lines, 3D culture models, murine models, and canine models. The relevance, strengths, and limitations of each model in OS research are explored. In particular, we highlight a range of potential therapeutics identified through these models. These instances of successful drug development represent promising pathways for personalized OS treatment. [ABSTRACT FROM AUTHOR]

Objective. Respiration negatively affects the outcome of a radiation therapy treatment, with potentially severe effects especially in particle therapy (PT). If compensation strategies are not applied, accuracy cannot be achieved. To support the clinical practice based on 4D computed tomography (CT), 4D magnetic resonance imaging (MRI) acquisitions can be exploited. The purpose of this study was to validate a method for virtual 4DCT generation from 4DMRI data for lung cancers on a porcine lung phantom, and to apply it to lung cancer patients in PT. Approach. Deformable image registration was used to register each respiratory phase of the 4DMRI to a reference phase. Then, a static 3DCT was registered to this reference MR image set, and the virtual 4DCT was generated by warping the registered CT according to previously obtained deformation fields. The method was validated on a physical phantom for which a ground truth 4DCT was available and tested on lung tumor patients, treated with gated PT at end-exhale, by comparing the virtual 4DCT with a re-evaluation 4DCT. The geometric and dosimetric evaluation was performed for both proton and carbon ion treatment plans. Main results. The phantom validation exhibited a geometrical accuracy within the maximum resolution of the MRI and mean dose deviations, with respect to the prescription dose, up to 3.2% for target D 95%, with a mean gamma pass rate of 98%. For patients, the virtual and re-evaluation 4DCTs showed good correspondence, with errors on target D 95% up to 2% within the gating window. For one patient, dose variations up to 10% at end-exhale were observed due to relevant inter-fraction anatomo-pathological changes that occurred between the planning and re-evaluation CTs. Significance. Results obtained on phantom data showed that the virtual 4DCT method was accurate, allowing its application on patient data for testing within a clinical scenario. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) melanoma culture is a personalized in vitro model that can be used for high-fidelity pre-clinical testing and validation of novel therapies. However, whether the genomic landscape of 3D cultures faithfully reflects the original primary tumor which remains unknown. The purpose of our study was to compare the genomic landscapes of 3D culture models with those of the original tumors. Patient-derived xenograft (PDX) tumors were established by engrafting fresh melanoma tissue from each patient. Then, a 3D culture model was generated using cryopreserved PDX tumors embedded in pre-gelled porcine skin decellularized extracellular matrix with normal human dermal fibroblasts. Using whole-exome sequencing, the genomic landscapes of 3D cultures, PDX tumors, and the original tumor were compared. We found that 91.4% of single-nucleotide variants in the original tumor were detected in the 3D culture and PDX samples. Putative melanoma driver mutations (BRAF p.V600E, CDKN2A p.R7*, ADAMTS1 p.Q572*) were consistently identified in both the original tumor and 3D culture samples. Genome-wide copy number alteration profiles were almost identical between the original tumor and 3D culture samples, including the driver events of ARID1B loss, BRAF gain, and CCND1 gain. In conclusion, our study revealed that the genomic profiles of the original tumor and our 3D culture model showed high concordance, indicating the reliability of our 3D culture model in reflecting the original characteristics of the tumor. [ABSTRACT FROM AUTHOR]

The outcome of chronic myeloid leukemia (CML) patients improved in the last decade. Clinical prognostic scoring systems aim to provide information about survival in the long-term, without determining from baseline the subset of patients who require a strictly monitoring because at increased risk of failure. Imatinib, the first-generation tyrosine kinase inhibitor (TKI), is still widely used as frontline treatment: recently, the imatinib therapy failure (IMTF) score was proposed to identify the failure free survival. Aim of our study was to validate this index in a large cohort of patients treated with imatinib. [ABSTRACT FROM AUTHOR]

Background: To develop and validate a predictive nomogram for tumor residue 3–6 months after treatment based on postradiotherapy plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II–IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods: In this retrospective study, 1050 eligible patients with stage II–IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3–6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). Results: Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P<0.001). A prediction nomogram based on postradiotherapy plasma EBV DNA level (0 vs. 1–499 vs. ≥500 copies/ml), clinical stage (II vs. III vs. IVA), and RT dose (68.00–69.96 vs. 70.00–74.00 Gy) estimated the probability of residue development. The nomogram showed better discrimination (area under the curve (AUC): 0.752) than either the clinical stage (0.659) or postradiotherapy EBV DNA level (0.627) alone in the development and validation cohorts (AUC: 0.728). Conclusions: We developed and validated a nomogram model integrating clinical characteristics at the end of IMRT for predicting whether tumor will residue or not after 3–6 months. Thus, high-risk NPC patients who might benefit from immediate additional intervention could be identified by the model, and the probability of residue can be reduced in the future. [ABSTRACT FROM AUTHOR]

Purpose: People living with chronic illness face significant challenges with employment. This study explores the impact of participating in the Career Construction Interview (CCI) on the career exploration of individuals facing a forced career transition due to the onset or exacerbation of a chronic illness. Method: An instrumental multiple case study design was used in this qualitative study. A purposeful, homogeneous sample of three female adults was used to gain multiple perspective of forced career transitions. The participants were within 2 years of their diagnosis or exacerbation of one or more chronic health conditions and had to change their career because of the impact of their condition(s). Results: Eight open codes and five axial codes were discovered through the process of constant comparative analysis. For this study one open code (CCI experience) and five axial codes will be discussed. Conclusions: This study found patterns related to chronic illness and career and that the Career Construction Interview was helpful to the participants in assisting them with making decisions about potential careers and options for employment. Implications for rehabilitation counseling practice and suggestions for future research. [ABSTRACT FROM AUTHOR]

Due to the concerning rise in the number of multiple- and prolonged-drug-resistant (MDR and XDR) Mycobacterium tuberculosis (Mtb) strains, unprecedented demand has been created to design and develop novel therapeutic drugs with higher efficacy and safety. In this study, with a focused view on implementing an in silico drug design pipeline, a diverse set of glycosylated flavonoids were screened against the Mtb cytochrome-P450 enzyme 121 (CYP121), which is established as an approved drug target for the treatment of Mtb infection. A total of 148 glycosylated flavonoids were screened using structure-based virtual screening against the crystallized ligand, i.e., the L44 inhibitor, binding pocket in the Mtb CYP121 protein. Following this, only the top six compounds with the highest binding scores (kcal/mol) were considered for further intermolecular interaction and dynamic stability using 100 ns classical molecular dynamics simulation. These results suggested a considerable number of hydrogen and hydrophobic interactions and thermodynamic stability in comparison to the reference complex, i.e., the CYP121-L44 inhibitor. Furthermore, binding free energy via the MMGBSA method conducted on the last 10 ns interval of MD simulation trajectories revealed the substantial affinity of glycosylated compounds with Mtb CYP121 protein against reference complex. Notably, both the docked poses and residual energy decomposition via the MMGBSA method demonstrated the essential role of active residues in the interactions with glycosylated compounds by comparison with the reference complex. Collectively, this study demonstrates the viability of these screened glycosylated flavonoids as potential inhibitors of Mtb CYP121 for further experimental validation to develop a therapy for the treatment of drug-resistant Mtb strains. [ABSTRACT FROM AUTHOR]

• A sensitive method for quantifying decitabine in mouse plasma was developed and validated. • Robust, accurate, and precise results were demonstrated, with a lower limit of quantitation of 0.4 ng/mL. • Decitabine was determined in microvolumes of mouse plasma. • Increased oral bioavailability of decitabine was observed when given with cedazuridine. • The mouse model was found useful for evaluating pharmacokinetic drug-drug interactions with decitabine. Decitabine is a DNA methyltransferase inhibitor used in the treatment of acute myeloid leukemia and myelodysplastic syndrome. The notion that ongoing trials are presently exploring the combined use of decitabine, with or without the cytidine deaminase inhibitor cedazuridine, and other antileukemic drugs necessitates a comprehensive understanding of pharmacokinetic properties and an evaluation of drug-drug interaction liabilities. We report here the development and validation of a sensitive UHPLC-MS/MS method for quantifying decitabine in mouse plasma, which should be useful for such studies. The method involved a one-step protein precipitation extraction, and chromatographic separation on an XBridge HILIC column using gradient elution. The method was found to be robust, accurate, precise, and sufficiently sensitive (lower limit of quantitation, 0.4 ng/mL) to determine decitabine concentrations in microvolumes of plasma from mice receiving the agent orally or intravenously in the presence or absence of cedazuridine. [ABSTRACT FROM AUTHOR]

Objective. In this study, a prognostic model for the respiratory function was constructed based on the treatment methods of patients with nonsevere pulmonary infection, aiming to provide a reference for clinical decision-making. Method. A total of 500 patients with nonsevere pulmonary infection were included in this study. The patients were randomized into training set (n = 350) and validation set (n = 150), and the baseline characteristics were collected. All patients received breathing exercises or breathing exercises combined with acupuncture therapy for 3 months, and then the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was assessed. Next, an ordinal multinomial logistic regression model was used to analyze prognostic factors affecting respiratory function of patients with nonsevere pulmonary infection. The Test of Parallel Lines was used to determine the accuracy (ACC) of the model and screen the influencing factors. The confusion matrix was drawn, and the ACC and harmonic mean (F1 score) were calculated to evaluate the feasibility of the model results. Results. Results of the ordinal multinomial logistic regression model showed that age (P = 0.000), treatment method (P = 0.000), underlying diseases (P < 0.001), and sex (P = 0.389) were independent factors affecting the respiratory function of patients in the training set. The ACC value of the training set was 88.86%, and that of the validation set was 91.33%, indicating a high accuracy and favorable predictive ability of the model. Besides, the F1 score was 62.38%, indicating a high reliability of the model. Conclusion. The prognostic model for respiratory function of patients with nonsevere pulmonary infection constructed in this study had favorable predictive performance, which is of great significance in the clinical nursing and treatment of patients with pulmonary infection. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the psychometric properties of the Nurse Professional Competence Scale in Croatia in order to use it as a valid and reliable instrument for assessing nurses' competence. Methodological study. Content and construct validity as well as internal consistency and confirmatory factor analysis (CFA) was conducted. The six-factor structure of the Nurse Professional Competence Scale in the Republic of Croatia was confirmed by CFA. The six-factor model showed a satisfactory fit to the data (RMSEA = 0.085, CFI = 0.84). All factor loadings were significant at p < 0.05. Cronbach's alpha for each scale ranged from 0.76 to 0.92. The psychometric properties of the Nurse Professional Competence Scale in the Republic of Croatia show that the scale is a reliable and valid measurement tool and as such can be used in research to assess the quality of professional competencies of nurses. The Scale consists of 35 items distributed in six competence areas. [ABSTRACT FROM AUTHOR]

Schwannomas are slow-growing benign neoplasms that develop throughout the body causing pain, sensory/motor dysfunction, and death. Because bacterial immunotherapy has been used in the treatment of some malignant neoplasms, we evaluated attenuated Salmonella typhimurium strains as immunotherapies for benign murine schwannomas. Several bacterial strains were tested, including VNP20009, a highly attenuated strain that was previously shown to be safe in human subjects with advanced malignant neoplasms, and a VNP20009 mutant that was altered in motility and other properties that included adherence and invasion of cultured mammalian cells. VNP20009 controlled tumor growth in two murine schwannoma models and induced changes in cytokine and immune effector cell profiles that were consistent with induction of enhanced innate and adaptive host immune responses compared with controls. Intratumoral (i.t.) injection of S. typhimurium led to tumor cell apoptosis, decreased tumor angiogenesis, and lower growth of the injected schwannoma tumors. Invasive VNP20009 was significantly more efficacious than was a noninvasive derivative in controlling the growth of injected tumors. Bacterial treatment apparently induced systemic antitumor immunity in that the growth of rechallenge schwannomas implanted following primary bacterial treatment was also reduced. Checkpoint programmed death-1 (PD-1) blockade induced by systemic administration of anti-PD-1 antibodies controlled tumor growth to the same degree as i.t. injection of S. typhimurium, and together, these two therapies had an additive effect on suppressing schwannoma growth. These experiments represent validation of a bacterial therapy for a benign neoplasm and support development of S. typhimurium VNP20009, potentially in combination with PD-1 inhibition, as a schwannoma immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Dementia is a very common disorder that affects people over 65 years old all over the world. Apart from the cognitive decline, Behavioral and Psychological Symptoms of Dementia (BPSD) are a crucial matter in dementia, because they affect up to 90% of the patients during the course of their illness. Irritability has been found to be a common BPSD and one of the most distressing behaviors for the caregivers. The aim of the current study was to explore the efficacy of a combination of non-pharmacological interventions to treat irritability. Methods: Sixty patients with different types and stages of dementia with irritability were participated in a cross-over RCT. Three non-pharmacological interventions were used; (a) Validation Therapy (VT)/Psycho-educational program, (b) Aromatherapy/massage and (c) Music Therapy (MT). The study assessed the three non-pharmacological interventions in order to find the most effective combination of the interventions. This study did not compare pharmacological and non-pharmacological treatments. The interventions lasted for five days. There was no drop-out rate. All patients were assessed at baseline using Mini Mental State of Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for symptoms in dementia (FRSSD), and Neuropsychiatric Inventory (NPI) (sub questions for irritability). Only NPI used for the assessment after each intervention. The analyses used categorical variables, Wilcoxon signed-rank test, Chi-square test and z value score. Results: The most effective combination of non-pharmacological interventions was Aromatherapy/massage (p = 0.003)-VT plus Psycho-educational program (p = 0.014) plus MT (p = 0.018). The same combination was the most effective for the caregivers' burden, too (p = 0.026). Conclusions: The above combination of non-pharmacological interventions can reduce irritability in patients with dementia and caregivers' burden. [ABSTRACT FROM AUTHOR]

Objectives: Survival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.Methods: Three different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.Results: Standard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).Conclusions: Where a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas. [ABSTRACT FROM AUTHOR]

The registry project led by the Japanese Society for Clinical Transcranial Magnetic Stimulation (TMS) Research aims to establish a centralized database of epidemiological, clinical, and biological data on TMS therapy for refractory psychiatric disorders, including treatment-resistant depression, as well as to contribute to the elucidation of the therapeutic mechanism of TMS therapy and to the validation of its efficacy by analyzing and evaluating these data in a systematic approach. The objective of this registry project is to collect a wide range of complex data linked to patients with various neuropsychiatric disorders who received TMS therapy throughout Japan, and to make effective use of these data to promote cross-sectional and longitudinal exploratory observational studies. Research utilizing this registry project will be conducted in a multicenter, non-invasive, retrospective, and prospective observational research study design, regardless of the framework of insurance medical care, private practice, or clinical research. Through the establishment of the registry, which aims to make use of data, we will advance the elucidation of treatment mechanisms and identification of predictors of therapeutic response to TMS therapy for refractory psychiatric disorders on a more real-world research basis. Furthermore, as a future vision, we aim to develop novel neuromodulation medical devices, algorithms for predicting treatment efficacy, and digital therapeutics based on the knowledge generated from this TMS registry database. [ABSTRACT FROM AUTHOR]

In this paper, new insights in the near infrared imaging process used in finger‐vein recognition by developing a physical model are presented. A realistic phantom finger that mimics the living human finger and also includes veins has been developed to validate this model. NIR phantom finger images show that the phantom can emulate the optical properties of a living human finger and can provide ground truth for the locations of the veins. Through physical modeling, it is particularly learned that—besides blood and soft tissue—bone also plays an important role in generating reliable NIR finger‐vein images. [ABSTRACT FROM AUTHOR]

In this contribution, we examine three stories of beneficent deception in medicine: the placebo machine invites children with treatment-resistant disorders to enter a high-tech machine and let their brains heal themselves; dementia villages extend validation therapy to the lived environment of geriatric care, supporting the illusion of living in the past through architecture; provocative testing relies on tricking patients suspected of fakery into experiencing seizures so that they can receive an expedited diagnosis. Enlisting the concept of misdirection from the realm of magic and theoretical contributions related to 'stories' and 'storying practices' from Feminist Science and Technologies Studies, we ask of each: Who is being deceived? Which 'characters' are given voice when these stories are told? How is deception justified? Following this, we question the onto-epistemological assumptions of reality and causation underlying each story and offer concluding thoughts on how 'magic' could be embraced within medical practice and research. [ABSTRACT FROM AUTHOR]

• Incidence of radiation-induced alopecia (RIA) in brain tumours patients treated with Proton Therapy is reported. • We independently validate previously published NTCP models for grade 2 RIA. • External validity of models was assessed in terms of discrimination and calibration. • Differences in reporting RIA outcomes could undermine the validation of NTCP models and impede their use in clinical settings. Radiation-induced alopecia (RIA) is one of the most frequent and upsetting cosmetic side effects after radiotherapy (RT) for brain cancer. We report the incidence of RIA in a cohort of brain tumours patients treated with Proton Therapy (PT) and externally validate published NTCP models of grade 2 (G2) RIA for their implementation in clinical practice. Data for patients treated for brain tumours with scanning beam PT between 2018 and 2022 were extracted. Acute, late and permanent RIA events were evaluated according to CTCAE 5.0. Lyman-Kutcher-Burman (LKB) and multivariable logistic regression (MLR) published models were computed from the relative dose-surface histogram of the scalp. External validity of models was assessed in terms of discrimination and calibration. In the 264 patients analysed, rates of any grade acute (≤90 days after PT completion), late (>90 days) and permanent RIA (persisting for> 12 months) were 61.8 %, 24.7 % and 14.4 %, respectively. In our independent cohort, LKB- and MLR-NTCP showed a good discrimination for G2 RIA (0.71≤ROC-AUC≤0.83) while model calibration was unsatisfactory possibly due to a different outcome evaluation between training and validation cohorts, as well as differences in clinical and treatment related variables between the two groups. Despite the reasonable sensitivity and specificity of the NTCP models for RIA in the validation cohort, our study emphasizes the significance of differences between the cohorts utilized for model development and validation. Specifically, variations in the reporting of clinical outcomes inevitably jeopardize the validation of NTCP models. A standardize and objective RIA scoring system is essential. [ABSTRACT FROM AUTHOR]

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Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia are a major reason for institutionalization, and high demanding for staff in Residential Care Facilities. This article reports the design, implementation, and evaluation of a Validation Therapy pilot-training program (VALIDA) for staff members of a residential care facility in Aveiro, Portugal. This pilot study involved 22 members of the staff, including qualified professionals and nonqualified direct care workers, who were involved in the design. The pilot-training program comprises two components: training sessions in group and individual monitoring between those sessions. The evaluation indicates that the structure of the pilot-program was well accepted, and participants reported positive impacts in professional (better skilled to deal with residents with dementia) and personal (better trained to deal with elderly relatives) lives. This pilot-training program shows potential to be used in residential care facilities and needs to be replicated. [ABSTRACT FROM AUTHOR]

The article examines that machine-compatible production processes, coupled with suitable CAD/CAM consumables are the focus of the Imes-icore group with Pritidenta and specially selected CAD\CAM materials go through a validation process. Topics include considered that CORiTEC label directly in product name, as is the case with the products presented for example with CORiTEC splint comfort.

Background: Motivational factors are generally regarded as an important ingredient for change in therapy. However, there is currently a lack of available instruments that can measure clients' readiness for change in therapy. Aim: The objective of this paper was to create an instrument, the Readiness for Therapy Questionnaire (RTQ), which could measure clients' readiness for change. Method: The RTQ was created by researchers following analysis of themes drawn from a review of the literature and interviews with patients at the end of therapy. This included both people who completed therapy and those who dropped out. As part of the standard assessment process, the RTQ was administered to 349 participants (69.6% female and 30.4% male; mean age 37.1 years; 90.5% Caucasian) who were patients at a psychological therapy service for common mental health difficulties. Result: An initial 12-item scale was reduced to 6 items. This scale significantly correlated with post-therapy PHQ-9 and GAD-7 scores and changes in these scores across therapy. After controlling for baseline scores and demographic variables, a logistic regression showed that scores on this 6-item measure pre-therapy significantly predicted three outcome variables: completing therapy, being recovered on both PHQ-9 and GAD-7 post-therapy, and having a reliable change in both the PHQ-9 and GAD-7 post-therapy. However, receiver operating characteristic (ROC) curve analysis showed the measure had poor sensitivity and specificity. Symptom severity did not have a significant impact on motivation to change. Conclusion: The RTQ is potentially a valid measure with useful clinical applications in treatment of common mental health difficulties. [ABSTRACT FROM AUTHOR]

Several studies support group therapy effectiveness due to the activation in patients of unique psychological mechanisms defined as non-specific therapeutic factors (Therapeutic Factors-TFs), which shape the setting and, at the same time, enhance the specific group therapeutic factors. The objectives of this study were to preliminarly validate Therapeutic Factors Inventory-8 (TFI-8) Italian version and identify group therapeutic factors. In a psychiatric residential facility, a weekly psychotherapeutic group was evaluated during 1 year. One scale on group process (TFI-8, Ferrara-Group Experience Scale) and three clinical scales (Brief Symptom Inventory-53, Sheehan Disability Scale, WHO Quality of Life-Bref) were administered to participating patients. Internal consistency, Exploratory Factor Analysis (EFA), convergent validity of TFI-8 were assessed. Correlations between TFI-8 and other scale scores and selected variables were pwerformed. Our sample consisted of 64 participants. TFI-8 showed good internal consistency (Chronbach's alpha = 0.84), concurrent validity with Fe-GES (Rho = 0.42, p = 0.0008). EFA highlighted a single Factor, accounting for 92% of variance. TFI-8 was not significantly related to clinical scale scores. TFI-8 Italian version proved to be a valid and reliable tool which allowed us to identify one therapeutic factor indicating relational attraction in group therapy, composed of three dimensions: infusion of hope, cohesion and social learning. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC.Methods: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.Results: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.Conclusions: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation. [ABSTRACT FROM AUTHOR]

Drug development in oncology commonly exploits the tools of molecular biology to gain therapeutic benefit through reprograming of cellular responses. In immuno‐oncology (IO) the aim is to direct the patient's own immune system to fight cancer. After remarkable successes of antibodies targeting PD1/PD‐L1 and CTLA4 receptors in targeted patient populations, the focus of further development has shifted toward combination therapies. However, the current drug‐development approach of exploiting a vast number of possible combination targets and dosing regimens has proven to be challenging and is arguably inefficient. In particular, the unprecedented number of clinical trials testing different combinations may no longer be sustainable by the population of available patients. Further development in IO requires a step change in selection and validation of candidate therapies to decrease development attrition rate and limit the number of clinical trials. Quantitative systems pharmacology (QSP) proposes to tackle this challenge through mechanistic modeling and simulation. Compounds' pharmacokinetics, target binding, and mechanisms of action as well as existing knowledge on the underlying tumor and immune system biology are described by quantitative, dynamic models aiming to predict clinical results for novel combinations. Here, we review the current QSP approaches, the legacy of mathematical models available to quantitative clinical pharmacologists describing interaction between tumor and immune system, and the recent development of IO QSP platform models. We argue that QSP and virtual patients can be integrated as a new tool in existing IO drug development approaches to increase the efficiency and effectiveness of the search for novel combination therapies. [ABSTRACT FROM AUTHOR]

Despite the vastly increased dissemination of the low-intensity (LI) version of cognitive behavior therapy (CBT) for the treatment of anxiety and depression, no valid and reliable indices of the LI-CBT clinical competencies currently exist. This research therefore sought to develop and evaluate two measures: the low-intensity assessment competency scale (LIAC) and the low-intensity treatment competency scale (LITC). Inductive and deductive methods were used to construct the competency scales and detailed rating manuals were prepared. Two studies were then completed. The first study used a quantitative, fully-crossed design and the second a multi-center, quantitative longitudinal design. In study one, novice, qualified, and expert LI-CBT practitioners rated an LI-CBT assessment session (using the LIAC) and an LI-CBT treatment session (using the LITC). Study two used the LIAC and LITC across four training sites to analyze the competencies of LI-CBT practitioners over time, across raters, and in relation to the actor/patients' feedback concerning helpfulness, the alliance, and willingness to return. Both the LIAC and LITC were found to be single factor scales with good internal, test-retest reliability and reasonable inter-rater reliability. Both measures were sensitive to measuring change in clinical competence. The LIAC had good concurrent, criterion, discriminant, and predictive validity, while the LITC had good concurrent, criterion, and predictive validity, but limited discriminant validity. A score of 18 accurately delineated a minimum level of competence in LI-CBT assessment and treatment practice, with incompetent practice associated with patient disengagement. These observational ratings scales can contribute to the clinical governance of the burgeoning use of LI-CBT interventions for anxiety and depression in routine services and also in the methods of controlled studies. [ABSTRACT FROM AUTHOR]

Agitation is a symptom of many medical and psychiatric disorders that can manifest along a spectrum of severity. Agitation often delays treatment onset, potentially impacting morbidity and mortality, and may require emergency interventions. Management of acute agitation centers around three main goals: early recognition and treatment of the underlying etiology, rapid control of the behavior, and prevention of harm to the patient and personnel. Nurses should increase use of validated techniques, including frequent and sufficient reality orientation, validation therapy, and strategies that improve the individual's quality of life. [ABSTRACT FROM AUTHOR]