Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Current therapy results in poor prognosis for high-risk SHH/p53-mutated MB, emphasizing the importance of more effective therapeutic strategies. Here, we investigated potential radiosensitizing effects of checkpoint kinase inhibitors (Chk-i) prexasertib (Chk1/2) and SAR-020106 (Chk1) in human SHH/p53-mutated MB in vitro and in vivo. UW228 and DAOY cells were treated with Chk-i and irradiation (RT). Metabolic activity, proliferation, and apoptosis was determined at d3, long-term clonogenicity at d14. DNA damage was assessed after 1, 24, and 72 h. Patient-derived SHH/p53-mutated, luciferase-transfected MB cells were implanted orthotopically into NSG mice (d0). Fractionated therapy (daily, d7-11) was applied. Body weight (BW) was documented daily, tumor growth weekly, and proliferation at d42. In vitro, Chk-i exhibited dose-dependent reduction of metabolic activity, proliferation, and clonogenicity, and enhancement of apoptosis. Combination with RT showed additive antitumor effects and enhanced residual DNA damage. In vivo, tumor growth was delayed by Chk-i alone. Low-dose prexasertib enhanced RT-induced tumor growth inhibition (37-fold) and reduced proliferating cells, high-dose prexasertib and SAR-020106 showed opposite effects (n=3, n.s.). BW assessments revealed that the treatment was well tolerated. Our data indicate a benefit of Chk-i in combination with RT in SHH/p53-mutated MB. However, high-dose Chk-i may compromise the RT effect, possibly by its anti-proliferative activity. Furthermore, we demonstrate for the first time the antitumor activity of the Chk1-specific inhibitor SAR-020106 in the murine brain.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity < 80%, but both values > 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

This work presents the results regarding the synthesis of tungsten nanoparticles (W NPs) by magnetron sputtering combined with gas aggregation (MSGA) when H2 mixed with Ar is used as working gas, the amount of H2 being increased up to 82%. The results show that up to 40% H2 in discharge the synthesis rate increases over 60 times, rapidly decreasing for over 50% H2 in discharge. The W dust is still produced in H2 dominated discharge (82%), the deposition rate being small but not negligible (20 mg/hour). The obtained WNPs are isolated, with the diameter decreasing from 50 nm to 15 nm when the amount of H2 in discharge is smaller than 41%. Over this value, the particles tend to agglomerate, forming structures similar to film-like deposits. Also, the diameter of the deposited spots on substrates is dependent on the H2 content in discharge. This allows the efficient coating of substrates with dimensions up to 26 mm by translating them in front of the MSGA cluster source exit aperture. Supplementary, for 41% H2 in discharge, the influence of synthetic air leaks (0-5%) in discharge was investigated. The deposition rate decreases rapidly (ceasing for around 4% air in discharge) and the obtained nanoparticles tend to agglomerate (at 2% air content, the dust deposit has the aspect of a near continuous film). Chemical composition investigations show a pronounced tendency of oxidation, nitridation and oxynitride formation in the presence of air leaks.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

We investigate solutions of the classical Mathieu-Hill (MH) equation which characterizes the dynamics of trapped ions, based on the Floquet theory and starting from a well known analytical model. The analytical model we introduce demonstrates that the equations of motion are equivalent to those of the harmonic oscillator (HO). Two independent approaches are used, based on two classes of complex solutions of the MH equation. The paper addresses both the damped HO and parametric oscillator (PO) for an ion confined in an electrodynamic (Paul) trap. Stability and instability regions for the periodic orbits associated to the MH equation which describes a HO (PO) confined in an electrodynamic trap are also discussed, depending on the values of the Floquet exponent, for very small values of the $q$ parameter. The main objective of the paper is to identify stable and bounded solutions for the dynamics of a HO levitated in an electrodynamic trap. This paper represents a follow-up of a recently published article in Photonics, 11 (6) 551.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

FLASH-RT represents a novel therapeutic radiation modality that holds remarkable potential for mitigating radiation therapy’s adverse side effects. This cutting-edge technology allows for the sparing of healthy tissue while precisely targeting cancerous cells by administering an ultra-high dose-rates of typically between 10 and 30 Gy in less than a few hundred milliseconds. FLASH-RT has demonstrated impressive results in small-animal models, prompting scientists to adapt and advance existing technologies to make it a viable treatment option for humans. However, producing the ultra-high-dose-rate radiation required for the therapy remains a significant challenge. Several radiation sources, such as very high energy electrons (VHEEs), low energy electrons, x-rays, and protons, have been studied for their ability to deliver the necessary dose. Among them, FLASH-x-ray has gained the most attention owing to its capacity to penetrate deeply seated tumours. Despite the complexity of the process, the potential advantages of FLASH-RT make it an exciting area of research. To achieve the FLASH effect, high-frequency, pulsed irradiated accelerator technology can be employed. Sparing healthy tissue, it may allow for more aggressive and effective cancer treatments, leading to a better quality of life for patients. Ongoing research and development will be necessary to refine and optimize this approach to radiation therapy.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

The stability properties of the Hill equation are discussed, and especially those of the Mathieu equation that characterize ion motion in electrodynamic traps. The solutions of the Mathieu equation for a trapped ion are characterized by using the Floquet theory and Hill's Method solution, which yields an infinite system of linear and homogeneous equations whose coefficients are recursively determined. Stability is discussed for parameters $a$ and $q$ that are real. Characteristic curves are introduced naturally by the Sturm-Liouville problem for the well known even and odd Mathieu equations $ce_m(z,q)$ and $se_m(z,q)$. We illustrate the stability diagram for a combined (Paul and Penning) trap and represent the frontiers of the stability domains for axial and radial motion. In case of a Paul trap the stable solution corresponds to a superposition of harmonic motions. The problem of evaluating the maximum amplitudes of stable oscillations for the ideal conditions (taken into consideration) is also approached. Anharmonic corrections are discussed within the frame of the perturbation theory, while the frontiers of the modified stability domains are determined as a function of the chosen perturbation parameter. The results apply to 2D and 3D ion traps used for different applications in quantum engineering, among which optical clocks, quantum logic and quantum metrology, but not restricted only to these.

Objective: Subclinical left ventricular disfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). Many patients with diabetes have an impaired diastolic and systolic function. With preserved ejection fraction LV (EFLV), the latter is defined as reduced global longitudinal strain (GLS), detected using the speckle-tracking echocardiography. This study is aimed to define the long-term structural and functional disorders of the LV myocardium in patients with T2D without CVD. Methods: Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11±7.9 years), included in the study in 2012-2013, only 57 responded to the follow-up study. The patients were divided into two groups: one with T2D (n=29), the other without it, control (n=28). All patients underwent transthoracic two-dimensional echocardiography with assessment of standard indicators of systolic and diastolic cardiac function, as well as GLS. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. Results: During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) in the type 2 diabetes group was found from 53% to 61% (p = 0.004); no significant dynamics were noted in the control group (p = 0.48). The presence of T2D significantly increases the risk of developing DD (p=0.04). The presence of T2D, increased fasting glucose levels, and an increased HOMA index were independent predictors of the development of DD. Impairment of LVEF was not observed in both groups. At the same time, the proportion of patients with reduced GLS (< -18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on T2D was demonstrated. The presence of obesity, an increase in the HOMA index and an increase in CRP levels are independent predictors of impaired GLS. Conclusions: T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up. Diastolic dysfunction is represented by delayed relaxation of the LV myocardium; with preserved LVEF, reduced 2D GLS identifies systolic dysfunction. The tight control of glycemia, lipidemia, blood pressure and body weight is associated with the absence of poor clinical outcomes.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Adeno-associated viruses (AAV) are widely used as viral vectors for gene delivery in mammalian cells. We focused on the efficacy of transduction of AAV 2/5, 2/6, 2/8 and 2/9 expressing GFP in 3T3-L1 murine preadipocyte cells by live imaging microscopy using IncuCyte S3 and flow cytom-etry. Three transduction modes were assessed: AAV transduction in 3T3-L1 preadipocyte cells with or without further differentiation into mature adipocyte-like cells and injection of AAVs in differ-entiated adipocyte-like cells. AAV2/6 demonstrated the highest transduction efficiency in 3T3-L1 preadipocytes, as it was 1.5–2-fold more effective than AAV2/5, and AAV2/8 in the range of viral concentrations from 2×104 to 1,6×105 VG/cell. AAV2/5 and AAV2/8 showed transduction effi-ciencies similar to each other. The expression of GFP under the CMV promoter remained stable for up to 20 days. The induction of 3T3-L1 differentiation in three days after AAV transduction did not alter the GFP expression level, and AAV2/6 showed the best transduction efficiency. AAV2/6 demonstrated the ability to transduce mature adipocytes. These results were confirmed by in vivo studies on C57BL6 mice AAV2/6 had the highest transducing activity on both inguinal and inter-scapular adipose tissue. Thus, AAV2/6 has demonstrated higher transduction efficacy compared to AAV2/5, AAV2/8 and AAV2/9 both in 3T3-L1 adipocytes and adipose tissue in vivo, which proves its usability along with AAV8 and AAV9 for gene delivery to adipocytes.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

The isotopic and nuclear techniques discussed, namely: Fallout Radionuclide, Fingerprint, and Isotope Hydrology, are linked to the evaluation of soil and water degradation processes. A traditional literature review was conducted to gain the most comprehensive understanding of both the current state of the art and the subject matter, with the aim of proposing a hypothesis that integrates the synergistic convergence of these techniques in order to offer results that are more reliable. A case study is presented as a synthesis of the preceding discussion.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P&lt;0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P&lt;0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg PE, DSPC, cholesterol, and DSPE-PEG-2000, and the mean size of the RTL was in the range of 114 to 133 nm, as measured by NTA. The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three i.v. injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

The theory of water transport in trees, according to which the main driving force of water movement is the suction created by the evaporation of water by the meniscus (the curved surface of the capillary liquid column) on the evaporating elements, supported from below by root pressure, is flawed. The capillary effect in nature is around one meter. In the case of open-air gaps, the leaf cannot suck in the water against gravity because, in this case, the plant would not be sucking in water, but air through the open-air gap. If not, how do trees transport water? When evaporation occurs, there is no suction towards the canopy, but pressure is due to a reduction in the cross-section of the water pipe caused by heat loss through evaporation. At night, when evaporation stops, a thermal equilibration process is triggered, which restores the original cross-section of the pipe. This generates suction and draws water from the soil. As the hydrostatic pressure in the pipe is high for tall trees, the pipe is cut off. To prove my theory, I have given several examples. Water transport is not based on physical mechanical laws alone. There may be complex physiological, biochemical, and biophysical processes behind the operation of the pipe system.

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (¹⁰B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of ¹⁰B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of ¹⁰B in a specific tissue in real-time using noninvasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. Moreover, functional imaging technologies such as PET can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Anyway, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.

With an aging population, the prevalence of geriatric diseases is increasing, especially among older individuals who live alone. This study investigates the potential of using TV viewing patterns to detect these diseases by analyzing variables such as daily average viewing time, peak viewing hours, and channel-switching behaviors. Significant correlations between TV viewing patterns and early indicators of geriatric diseases (depression, activities of daily living (ADL) performance, and cognitive function) were found. The correlations between the Korean form of the Geriatric Depression Scale (KGDS) and daily average viewing time and excessive channel switching were 0.320 and 0.308, respectively. The Korean version of the Modified Barthel Index (KMBI) showed correlations of -0.313 with daily average viewing time and -0.352 with excessive channel switching. Participants were divided into groups based on scores, and significant differences in peak viewing hours were observed among the different groups. The Korean version of the Mini-Mental State Examination (MMSE-K) groups showed significant differences at 3, 4, and 5 PM. The KGDS and KMBI groups showed significant differences at 8 PM and midnight and 1 AM and 2 AM, respectively. These findings suggest that TV viewing patterns can serve as effective early diagnostic indicators for geriatric diseases.

Purpose: To report the early clinical outcomes of combining intensity‐modulated radiation therapy (IMRT) and intensity‐modulated proton therapy (IMPT) in comparison with IMRT alone in treating the oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients were retrospectively reviewed, who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity‐score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow‐up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, IMRT/IMPT combination group experienced grade ≥3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p<0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p=0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p=0.021); and AQA in 47.4% and 21.1% (p=0.016), respectively. In multivariate logistic regression, grade ≥3 mucositis was significantly less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.027 and 0.024, respectively). AQA score ≥3 was also less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

This study investigates job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesia and intensive care medicine in Germany, comparing them to their native German counterparts. Utilizing a cross-sectional survey design, the study collected data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the German version of the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Notably, migrant physicians reported higher difficulty and frustration in working with patients. Well-being ratings indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. The findings underscore the unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumour cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83+-20 nm and 49+-12 nm, respectively. For RT alone, a reduction in cell viability of up to 33+-12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 μM showed a reduction in cell viability of 20+-4% and 35+-4%, respectively, while for BBN-AuNPs, at 50 and 200 μM, a reduction in cell viability of 25+-3% and 37+-3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26+-3% and 22+-2% between RT+HAOA-AuNPs at 400 μM and RT+BBN-AuNPs at 50 μM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.

Background: The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assesses circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. Aim: Evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes. Identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities related to social determinants of health (SDoH). Design: IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon. Survival analyses utilized Kaplan–Meier curves. Setting/Participants: Single-institution study involving patients receiving whole-brain radiotherapy. Collected demographic, disease, and socioeconomic parameters from electronic medical records. Results: Morning treatment (n=158) showed a trend towards improved overall survival vs. afternoon (n=79), median survival 158 vs. 79 days (p=0.20, HR=0.84, CI95% 0.84–0.91). Subgroup benefits for morning treatment in females (p=0.04) and trends in controlled primary disease (p=0.11) and breast cancer metastases (p=0.08). SDoH-based disparities observed, with Black and lower-income patients exhibiting diminished circadian influence. Conclusions: Emphasizes chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlates with improved survival, particularly in specific subgroups. Identifies potential circadian influence disparities based on SDoH, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

Stress can reduce the accuracy of radiation therapy owing to muscle contraction and changes in breathing patterns. This study aimed to predict stress in patients before each treatment session using artificial intelligence (AI) from biological signals to enhance treatment accuracy. We measured 123 stress cases in 41 patients and calculated stress scores by analyzing seven stress-related features derived from heart rate variability obtained from photoplethysmography. The study analyzed stress score distribution and observed its trend changes throughout the treatment. Before-treatment information was used to predict changes in stress features during treatment. AI models included both non-pre-trained (Decision Tree, Random Forest, Support Vector Machine, Long Short-Term Memory (LSTM), Transformer) and pre-trained (ChatGPT) models. The performance was evaluated using 10-fold cross-validation, exact match ratio, accuracy, recall, precision, and F1 score. More than 90% of the patients experienced stress during radiation therapy. From all the classifications, LSTM and prompt engineering GPT4.0 had the highest accuracy (feature classification, LSTM: 0.703, GPT4.0: 0.659, stress classification: LSTM: 0.846, GPT4.0: 0.769). Our research pioneers the use of AI and biological signals for stress prediction in radiation therapy, potentially identifying patients needing psychological support, and suggesting methods to improve radiotherapy effectiveness through stress management.

Abstract: A recent approach to radiotherapy for prostate cancer is the administration of high doses of radiation to the prostate while minimizing the risk of side effects. Thus, image-guided radiotherapy utilizes advanced imaging techniques and is a feasible strategy for increasing the radiation dose. New radioactive particles are another approach to achieving high doses and safe procedures. Prostate brachytherapy is currently considered as a combination therapy. Spacers are useful to protect adjacent organs, specifically the rectum, from excessive radiation exposure.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Background: Boron Neutron Capture Therapy (BNCT) is an emerging radiotherapy. There are ongoing efforts to develop a Canadian accelerator-based BNCT center. However, it remains unclear how Canadian radiation oncologists (RO), medical physicists (MP), and their trainees perceive BNCT and its impact on radiation oncology as a discipline. Methods: A survey was created to explore knowledge of BNCT, its clinical role, and support for Canadian research. It was distributed through the Canadian Association of Radiation Oncology (CARO) and Canadian Organization of Medical Physicists (COMP). Results: We received 118 valid responses from all 10 provinces, from 70 RO (59.3%) and 48 MP (40.7%), including 9 residents. Most knew of BNCT and its indications (60.2%). Although many were unaware of reasons behind early failures (44.1%), common reasons were lack of clinical trials and inaccessibility of neutron sources (42.4%) and reactor unsuitability (34.7%). Additionally, 90.6% showed definite (66.9%) or possible (23.7%) support for Canadian BNCT research, while 89% indicated definite (56.8%) or possible (32.2%) willingness for BNCT referrals. Conclusions: Most RO and MP supported Canadian BNCT research and would refer patients. However, limited awareness and lack of experiences remain a challenge. Educational sessions are needed to realize this innovative cancer treatment in Canada.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor with sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as alternative to brachytherapy boost after external beam RT. It also used as a primary treatment option for elderly or medically unfit patients. More recently, SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

Up to now in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) precedes adjuvant radiotherapy (A-RT). It’s beyond question that A-RT improves local control while A-CT improves the Disease Free Survival (DFS) due to the reduction of metastatic distant recurrences. Taken togheter these two approaches impact favourably on the reduction of breast cancer mortality. In the last twenty years, the adjuvant treatment of BC has evolved quickly due to a better knowledge of its molecular biology , genetic prohile and its α/β ratio 3 / 4 Gy for the tumor and normal tissues radiosensitivity. Thus new schedules with hypofractionated radiotherapy have been tested and third generation of A-CT have been introduced leading to a better survival rate but a further delay in A-RT starting, raising the question to rethink the sequencing between these two approaches. However the sequencing timing between these two approaches still remains unchanged with A-CT before A-RT as the standard of care. Many attempts have been provided in order to optimize this sequencing. This comprehensive review is a journey among randomised, retrospective and prospective studies which highlights the past, the current and the novelties on timing sequencing proposals between these two modalities to assess the state of art. Sequential, concomitant and sandwitch modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies will be analysed in this review.

Abstract: Spinal disorders are some of the most prevalent health concerns, especially among stu-dents. Based on student demographics, this cross-sectional study evaluated the correlation be-tween functional tests (FT) and spinal range of motion (ROM). This study included 206 students from Vasile Alecsandri University of Bacău. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using Spearman correlation coefficient analysis. The results indicated a very strong re-lationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM of physical education department students compared to students from other de-partments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation be-tween FT and spinal ROM based on age (p > 0.05). The study results provide evidence of the pri-mary risk factors that predispose students to postural deviations. Practitioners and physiothera-pists can utilize these values as a reference for potential therapeutic interventions.

There are various types of charged particles in the space environment, which can cause different types of radiation damage to materials and devices, leading to on-orbit failures and even accidents of spacecraft. Developing lightweight and efficient radiation shielding materials is an effective approach to improve the inherent protection of spacecraft. The protective performance of different materials against proton and electron spectra in the Earth’s radiation belts is evaluated by Geant4 simulation. Based on the simulation results, suitable hardening components are selected to design composite materials, and B4C/PEEK composites with different B4C content were successfully prepared. Experimental results demonstrate that the simulated and experimental results for the electron, proton and neutron shielding performance of B4C/PEEK composites are consistent. These composites exhibit excellent radiation shielding capabilities against electrons, protons and neutrons, and the radiation protection performance improves with increasing B4C content in the B4C/PEEK composite materials.

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a ``natural selection'' of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the ``thermodynamic dissipation theory for the origin of life'' argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic ``design goals'' of microscopic dissipative structuring of organic UV-C pigments, today known as the ``fundamental molecules of life'', from common precursors under this light. This ``UV-C Pigment World'' evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons, up to wavelengths of the ``red-edge''. The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide and a major global health burden. The treatment of HCC has experienced a paradigm shift in the last few years, following the discovery of immunotherapy. However, despite the profound success of immunotherapy in other cancer types, their response in HCC remains unsatisfactory. Some of the reasons that can explain this poor response include the immunosuppressive microenvironment of HCC, the absence of reliable biomarkers for response, and drug resistance. Previous preclinical and clinical studies have highlighted the role of combination therapy in overcoming some of these hurdles. In this article, we discuss the benefit of combining immune checkpoint inhibitors (ICIs) with stereotactic body radiation therapy (SBRT) in HCC and shed light on promising clinical trials.

Introduction: To compare the results of patient-specific absolute dosimetry using homogeneous slab phantom and anthropomorphic heterogeneous female pelvic phantom in cervical cancer patients. Materials and method: Thirty RapidArc plans already planned on treatment planning system (TPS) for cervical cancer patients were exported on both the phantoms viz. RW3 slab phantom and AHFP and dose were calculated using an anisotropic analytic algorithm (AAA). All the plans were delivered by linear accelerator (LA) and the dose for each plan was measured by a 0.6cc ion chamber. The percentage (%) variation between planned and measured doses were calculated and analyzed.Results: In the case of slab phantom, the mean percentage variations between planned and measured doses of all rapid arc QA plans were as 1.4299 and standard deviation 0.768 (t=0.00508, ρ= 0.497982) The result is not significant at p < .05. For the AHFP phantom, the mean percentage variations between planned and measured doses of all rapid arc QA plans were as 6.890 and standard deviation 2.565 (t= 3.21604, ρ= 0.001063 <0.05), the outcome is significant. Discussion: In the case of homogenous slab phantom, there is less than a 3% difference in percentage between planned and measured doses with a standard deviation of 0.7682 (t=0.00508, p= .497982. The result is not significant at p< 0.05). The deviations of planned and measured value of dose in the AHFP phantom were found as 10.67% (maximum value), 2.31% (minimum value) and 6.89% (average value) with standard deviation 2.565 (t=3.21604, p=0.001063. The result is significant at p<0.05). Also, the percentage of variation between homogeneous slab phantoms with AHFP phantom, the t-value is -11.17016. The p-value is < .00001. The result is significant at p<0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media.Conclusion: AHFP phantom results showed more dose variability than slab homogenous phantom outcomes. Therefore, patient-specific absolute dosimetry should be performed using a heterogeneous phantom that closely resembles the actual human body in terms of both density and design.

Background: In high-risk breast cancer patients with skin infiltration the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential standard bolus’ inadequate dose distribution due to air gaps between the bolus and the skin. In this pilot study, we introduced in clinical practice the use of a personalized 3D printed bolus filled with ultrasound transmission gel. Methods: Seven patients undergoing radiotherapy after mastectomy were selected. 3D printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and subsequently on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control was assessed. Results: Overall, for the clinical cases the percentage median difference between measured and calculated doses was -2.7% (-7.0%÷4.9%). Median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. Conclusions: Personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus’ consistency providing an accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study and further investigations are needed.

Work disparities experienced by nurses in long-term care (LTC) can impact the retention, well-being, and health of this workforce. Despite the significant impact disparities experienced by nurses have on the workforce and LTC sector, a review of the available literature on work disparities has not been conducted on work disparities experienced by nurses in LTC. Consequently, this scoping review aimed to explore the nature and extent of research on meso-level work disparities experienced by nurses in LTC and how such disparities are linked with nurse health and well-being. Five databases were searched: MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO host). Of the 5,652 articles retrieved, 16 studies published between 1997 and 2024 met the inclusion criteria. The average number of work disparities within each study was 3.06 (minimum = 1, maximum = 6, SD = 1.62). Types of work disparities across the 16 studies were work opportunities (n = 19), work treatment (n = 18), job security (n = 8), and work compensation (n = 8). Only four articles investigated the association of a work disparity with a variable of health and well-being. Future research on how macro-level disparities intersect with meso-level work disparities may inform a contextual understanding of how disparities transpire in the work of nurses in LTC. Studies are required to address the gaps in knowledge regarding how work disparities negatively influence the health of nurses to inform better retention, well-being, and health of nurses in LTC.

Recombinant α1-microglobulin (A1M) is proposed as protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but, the radioprotecting action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation induced protein expression early after exposure, and late effects should be further studied.

The study of localized surface plasmons (LSPs) in nanoscale structures is an essential step towards identifying optimal plasmonic modes that can facilitate robust optomechanical coupling and deepen our understanding of light-matter interactions at the nanoscale. This paper investigates numerically, using the finite element method, LSPs modes in a design comprising two coupled nano-ridges deposited on a gold layer, with an interposing polymer spacer layer. Such a structure, usually referred to as particles-on-mirror, shows exquisite optical properties at the nanoscale. We first examine the LSPs modes of a single nano-ridge through the analysis of its scattering cross-section in the visible and infrared range. To enhance the plasmonic response, a thin polymer layer is placed at the middle of the ridge, which introduces additional LSPs modes confined within the former. Then, we extend the analysis to the dimer configuration, which exhibits more complex and enhanced plasmonic behavior compared to a single nano-ridge. In particular, the dimer configuration yields LSPs resonances with a quality factor enhancement of approximately threefold relative to single nano-ridge. Furthermore, the presence of the polymer layer within the ridges significantly improves plasmon field localization and quality factor. These findings underscore the potential of nano-ridge-based structures in advancing optomechanical coupling and plasmon-phonon interaction studies, offering valuable insights for the development of high-performance acousto-plasmonic devices. In particular, the proposed device could help significantly improve the design of nano-acousto-optic modulators operating in the visible or in the near infrared, that require enhanced light-photon coupling rate.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

During the high-speed flight of a vehicle in the atmosphere, surface friction with the air generates aerodynamic heating. The aerodynamic heating phenomenon can create extremely high temperatures near the surface. These high temperatures impact material properties and the structure of the aircraft, so thermal deformation measurement is essential in aerospace engineering. This paper revisits high-temperature deformation measurement using the digital image correlation (DIC) technique under high-intensity blackbody radiation with a precise speckle pattern fabrication and a heat haze reduction method. The effect of speckle pattern on the DIC measurement has been thoroughly studied at room temperature, but high-temperature measurement studies have not reported such effects so far. We found that the commonly used methods to reduce the heat haze effect could produce incorrect results. Hence, we propose a new method to mitigate heat haze effects. An infrared radiation heater was employed to make an experimental setup that could heat a specimen up to 950 ℃. First, we mitigated image saturation using a short-wavelength bandpass filter with blue light illumination, a standard procedure for high-temperature DIC deformation measurement. Second, we studied how to determine the proper size of the speckle pattern under a high-temperature environment. Third, we devised a reduction method for the heat haze effect. As proof of the effectiveness of our developed experimental method, we successfully measured the deformation of stainless steel 304 specimens from 25 ℃ to 800 ℃. The results confirmed that this method can be applied to the research and development of thermal protection systems in the aerospace field.

The variation of aerosols, especially dust aerosol, in time and space plays an important role in climate forcing studies. Aerosols can effectively reduce land surface longwave emission and re-emit energy at a colder temperature, making estimation of downwelling surface longwave radiation (DSLR) with satellite data difficult. Using the latest atmospheric radiative transfer code (MODTRAN 5.0), we simulate the outgoing longwave radiation (OLR) and DSLR under different land surface and atmospheric profile conditions. The results show that dust aerosol has an obvious “warming” effect to longwave radiation compared with other aerosols, that aerosol longwave radiative forcing (ALRF) increased with increasing aerosol optical depth (AOD), and that the atmospheric water vapor content (WVC) is critical to the understanding of ALRF. A method is proposed to improve the accuracy of DSLR estimation from satellite data for the skies under heavy dust aerosols. The AOD and atmospheric WVC under cloud-free conditions with a relatively simple satellite-based radiation model that yields the high accurate DSLR under heavy dust aerosol are used explicitly as model input to reduce the effects of dust aerosol on the estimation of DSLR. Validations of the proposed model with satellites data and field measurements show that it estimates the DSLR accurately under heavy dust aerosol skies. The root mean square errors (RMSEs) are 20.4 W/M² and 24.2 W/M² for Terra and Aqua satellites, respectively, at the Yingke site, and the biases are 2.7 W/M² and 9.6 W/M², respectively. For the Arvaikheer site, the RMSEs are 23.2 W/M² and 19.8 W/M² for Terra and Aqua, respectively, and the biases are 7.8 W/M² and 10.5 W/M², respectively. The proposed method is especially applicable to acquire relatively high accurate DSLR under heavy dust aerosol using MODIS data with available WVC and AOD data.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.

Introduction: During the COVID-19 pandemic, many countries implemented restrictions, social distancing measures, and lockdowns to limit the spread of the disease. The lockdowns have affected children’s screen time (ST), pain, and physical activity (PA) levels. The present study aimed to explore the relationships between several personal factors during the COVID-19 pandemic. Methods: The caregivers of 329 children (median age=8 years) filled out an online self-reported survey about the children’s PA, ST, and pain before, during, and after the COVID-19 curfew. Spearman’s rank correlation coefficient was used to explore the associations between these variables. Results: After the curfew, pain that existed before the pandemic had a weak negative relationship with PA intensity (-0.11, p=0.04) and a weak positive relationship with ST (r=+0.12, p=0.04). There was a strong positive relationship between ST in all time periods (p&gt;0.01). PA and ST had a weak negative relationship (p&gt;0.05) during the curfew and after the curfew but not before the COVID-19 pandemic. Age had a weak positive correlation with ST in all time periods (p&gt;0.01). In addition, ST was affected by the curfew. Conclusion: The study findings indicated that young children had longer ST during the curfew and after the curfew compared with before the curfew. Increasing PA could lessen children’s ST, which could, in turn, increase the probability that their general pain would decrease.

Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitates the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. Increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID downregulated and HRK upregulated on days 2 and 7, respectively. The data suggests that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide.

This paper presents a wideband dual-polarized dipole antenna structure operating at 1.7-3.8 GHz (76.4%). For a traditional 4G dipole antenna which covers the band 1.71 GHz- 2.69 GHz, it’s difficult to maintain the satisfactory impedance matching and normal stable radiation patterns within the 5G sub-6 GHz band 3.3-3.8 GHz, which mainly due to the fixed antenna height is no longer a quarter-wavelength. To solve this, a connected-ring-shaped metasurface structure is proposed and deployed to operate as an artificial magnetic conductor (AMC). As a result, stable antenna radiation patterns are obtained within the whole band 1.7-3.8 GHz. For verification, this wideband dipole antenna using AMC is implemented and tested. The measured results show that the proposed antenna has an impedance bandwidth of 80.7% (1.7-4.0 GHz). It has an average measured in-band realized gain of 7.0±1.0 dBi and a stable 70∘±5∘ half power beam width (HPBW) within the 4G/5G-sub 6GHz bands 1710-2690 MHz and 3300-3800 MHz.

Spectral photon counting cone-beam CT imaging is challenged by individual pixel response behaviour, which leads to noisy projection images and subsequent image artefacts like rings. Existing methods to correct for this either use calibration measurements, like signal-to-thickness calibration (STC), or perform post-processing ring artefact correction of sinogram data or scan reconstructions, without taking the pixel response explicitly into account. Here we present a novel post-processing method (DAC-shifting), which explicitly measures the current pixel response using flat field images, and subsequently corrects the projection data. The DAC-shifting method was evaluated with a repeat series of spectral photon counting imaging (Medipix3) of a phantom with different density inserts, and in iodine K-edge imaging. The method was also compared against PMMA based STC. The DAC-shifting method was shown to be effective in correcting individual pixel response, and was robust against detector instability. On the contrary, STC correction showed varying results, which was almost as good as DAC-shifting when data was acquired just after STC calibration, but worse with larger time differences. In K-edge imaging, DAC-shifting provides a sharper attenuation peak, and more uniform CT values, which is expected to benefit iodine concentration quantification.

High-energy small electron beams generated by linear accelerators are used for radiotherapy of localized superficial tumors. The aim of the present study is to assess the dosimetric performance under small radiation therapy electron beams of the novel PTW microSilicon detector by comparison with commercially available dosimeters. Relative dose measurements of circular fields with 20, 30, 40 and 50 mm aperture diameters were performed for 4 to 12 MeV energy range of electron beams generated by an Elekta Synergy linac. Percentage depth dose, transverse profiles and output factors normalized to the 10 × 10 cm2 reference field were measured. All dosimetric data were collected in a PTW MP3 motorized water phantom at SSD of 100cm by using the novel PTW microSilicon detector. The PTW diode E and the PTW microDiamond were also used in all beam aperture for benchmarking. Data for the biggest field size were also measured by the PTW Advanced Markus ionization chamber.Measurements performed by the microSilicon are in good agreement with the reference values for all the tubular applicators and beam energies, within the stated uncertainties. This confirms the reliability of the microSilicon detector for relative dosimetry of small radiation therapy electron beams collimated by tubular applicators.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Background and Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised 8 pediatric patients (ages 3-18) and 2 adult patients (ages 19-75). Median age at the time of SRS was 13 years, median tumor volume accounted for 1.9 cc, median biologically equivalent dose (BED) was 126 Gy, and single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusion: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (ARE) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

The utilization of optical antennas for active control of far-field radiation at the subwavelength scale is crucial in various scientific and technological applications. We propose a thermally tunable disk design of indium tin oxide (ITO) and aluminum gallium nitride (Al0.18Ga0.82As), enabling a switch between absorption and scattering. Furthermore, the control of far-field radiation pattern can be easily realized by combining ITO and Al0.18Ga0.82As to enhance or suppress emission. Our results demonstrate that hybrid structure can be dynamically tuned with temperature variations. In the proposed design, a frequency is achieved at the epsilon-near-zero wavelength of 1240 nm. The thermal tunability of hybrid structure introduces new multifunctional possibilities for light manipulation, thereby enhancing the potential applications of new devices in the near-infrared range.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

Electromagnetic interference (EMI) generated by switching operations within high voltage DC (HVDC) converter stations is an issue that has been addressed by CIGRE and methods to manage EMI should be considered in the design phase using electromagnetic modeling techniques. It is shown that method of moments-based techniques that have been used in many previous studies may not be sufficient. Here, the finite-difference time-domain method is used to study the properties of single switching events using a realistic model of an HVDC converter station with special emphasis on determining the impact of the valve hall on shielding EMI. It is shown that the valve hall does not confine high frequency electromagnetic fields to the valve hall; rather it delays them from exiting through bushings in the wall. Further, it is shown that incorporating electromagnetic absorbing material into the valve hall design can significantly reduce EMI outside the converter station.

Despite great technical capabilities, the theory of non-contact temperature measurement is usually not fully applicable to the use of measuring instruments in practice. While black body calibrations are in practice well established and easy to accomplish, this calibration protocol is never fully applicable to measurements of real objects under real conditions. Currently, the best approximation to real world radiation thermometry is grey body radiation thermometry, which is supported by most measuring instruments to date. Nevertheless, the metrological requirements necessitate traceability, therefore real body radiation thermometry is required for temperature measurements of real bodies. This article documents the current state of temperature calculation algorithms for radiation-thermometers and the creation of a traceable model for radiation thermometry of real bodies that uses a digital twin model of the system of measurement to compensate for the loss of data, caused by spectral integration, which occurs when thermal radiation is absorbed on the active surface of the sensor. To solve this problem, a hybrid model with variable scalar inputs is proposed, in which the scalar input parameters are calculated to correspond to the system of measurement. The method for calculating the effective parameters is proposed and verified with the theoretical model of non-contact thermometry. The sum of effective instrumental parameters is presented for different temperatures to show that the rule of radiation thermometry of grey bodies, according to which the sum of instrumental emissivity and instrumental reflectivity equals to 1, does not hold in radiation thermometry for real bodies. Using the derived models of radiation thermometry, the uncertainty of radiation thermometry due to the uncertainty of spectral emissivity is analysed by simulated measurements along the temperature ranges of various radiation thermometers, enabling traceable non-contact temperature measurements with known measurement uncertainty under any known conditions.

Introduction Image Guided Superficial Radiation Therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state of the art operating principles in US dermatologic practices. Materials and Methods A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors’ published and unpublished documents, procedures and clinical experience with IGSRT were synthesized for this paper. Results Studies have demonstrated IGSRT consistently delivers high cure rates( >99%) with low complications for early stage (stage 0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs Micrographic Surgery(MMS). This improvement is attributed to in-vivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand. Conclusion While the safety and cosmetic benefits of SRT/XRT has been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in-vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis and ability to treat multiple lesions per session using IGSRT is establishing this modality as a standard first line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.

Art therapy fosters emotional healing and growth. This process can offer healthcare professionals (HCPs) novel insights into patients’ medication experiences. We developed a Metaverse Art Gal-lery of Image Chronicles (MAGIC), which depicted patients’ medication experiences symbolically as hero-villain portrayals. This gallery aimed to enhance healthcare students’ learning through re-latable insights into patients’ medication therapies. A character sheet was used to craft patients’ personifications of their medication experiences. ChatGPT, NightCafe, Canva, HeyGen and Cam-tasia were used to generate hero-villain portraits based on the character traits and mounted in MAGIC, which consisted of three virtual realms, each with a unique theme. Alpha-testing among sixteen Generation Z healthcare learners indicated that the content in MAGIC enabled them to understand the concepts of medication adherence (93.7%), art therapy (87.5%) and how patients related to their medications (81.3%). Perceived playfulness (rs=0.925, p

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

Background/Objectives: interpretation of evidence on de-escalation of triple therapy with with-drawal of inhaled corticosteroids (ICS) to dual bronchodilator therapy with a long-acting musca-rinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstruc-tive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discon-tinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: we searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov and CENTRAL for RCTs and observational studies from inception to March 22, 2024, investigating the effect of triple therapy de-escalation with withdrawal of ICS to dual therapy on the risk of COPD exacerbation, pneumonia and lung function. This study was registered with PROSPERO, CRD42024527942. Results: 3335 studies were screened; three RCTs and three real-world non-interventional studies were ultimately identified as eligible. Analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80 to 1.15; I²=77%) for ICS withdrawal compared with triple therapy continuation. Analysis according eosinophil levels showed that COPD subjects with ≥300 eosino-phils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated from ICS/LABA/LAMA to LABA/LAMA (pooled HR: 1.35, 95% CI 1.00-1.82; I2: 56%). The ICS withdrawal in favour of LABA/LAMA did not significantly affect the risk of mortality and pneumonia. Conclusions: the main findings of this meta-analysis are consistent with current recommendations and suggest that the use of eosinophil counts may be of help in guiding maintenance therapy. However, methodological heterogeneity between the included studies is evident.

Transcatheter Aortic Valve Implantation (TAVI) now represents the mainstay in the treatment of severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as a cornerstone. Leveraging data from multiple randomized controlled trials, current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without, or with atrial fibrillation respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual-patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Pretreatment of cells with proteolysis inhibitors diminished intensity and changed shape of DNICs specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

The month of May 2024 was characterized by solar energetic particles events directed towards the Earth, especially the big event causing a strong terrestrial geomagnetic storm during the night from 10 to 11 May 2024, with auroras observed everywhere in Europe. This was the strongest storm for the last 20 years with a Dst < -400 nT. In the present work, we show with observations of GOES, PROBA-V/EPT and MetOP/MEPED that this exceptional event was associated with the injection of energetic protons in the proton radiation belt, with important consequences for the South part of the South Atlantic Anomaly (SAA). In addition, the geomagnetic storm caused by the solar eruption has had tremendous impacts on the electron radiation belts. Indeed, we show that for 0.3 to 1 MeV electrons, the storm led to a long lasting four belts configuration which was not observed before with EPT launched in 2013, until a smaller geomagnetic storm on June 15 took place. Moreover, for the first time since its launch, observations of the EPT show that ultra-relativistic electrons with E>2 MeV have been injected into the inner belt until L=2.4, violating the impenetrable barrier previously estimated to be located at L=2.8.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

Background: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different chest wall (CW) delineation according to ESTRO ACROP guideline for patients underwent implant-based reconstruction. Methods: We conducted a retrospective review of breast cancer patients who underwent mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. Results: The study included 26 patients, 15 in prepectoral group and 11 in whole expander group. No significant differences were observed in normal organs exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p=0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. Conclusions: For patients undergoing two-stage expander-implant retropectoral breast reconstruction and PMRT, our data have provided comparable outcomes and normal organs exposure for those omitting the deep lymphatic plexus.

Background: Painful spinal bone metastases (PSBMs) patients regularly receive palliative radiation therapy (RT) with response rates in about 2 of 3 patients. In this exploratory study, we evaluated the value of machine learning (ML) models based on radiomic, semantic and clinical features to predict complete pain response. Methods: Gross tumour volumes (GTV) and clinical target volumes (CTV) of 261 PSBMs were segmented on planning computed tomography (CT) scans. Radiomic, semantic and clinical features were collected for all patients. Random forest (RFC) and support vector machine (SVM) classifiers were compared using repeated nested cross-validation.Results: The best radiomic classifier was trained on CTV with an area under the receiver-operator curve (AUROC) of 0.62 ± 0.01 (RFC; 95% confidence interval). The semantic model achieved a comparable AUROC of 0.63 ± 0.01 (RFC), significantly below the clinical model (SVM, AUROC: 0.80 ± 0.01); and slightly lower than the spinal instability neoplastic score (SINS; LR, AUROC: 0.65 ± 0.01). A combined model did not improve performance (AUROC: 0,74 ± 0,01).Conclusions: We could demonstrate that radiomic and semantic analyses of planning CTs allowed for limited prediction of therapy response to palliative RT. ML predictions based on established clinical parameters achieved the best results.

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

For the first time, the effect of a significant change in the resistance of the aquatic environment of a population of protozoan microorganisms under the influence of radiofrequency electromagnetic radiation from cell phones has been experimentally studied. The results of the experiment demonstrate the biological nature of the changes occurring in the “water population of protozoa” system, which indicates that the impact of radiation directly affects the cell. This conclusion is confirmed by the same order of magnitude time of information exchange between individual individuals of the population in the calculation and in the experiment. An extremely low concentration of protozoa in the experiment was established, equal to 1000 pcs./liter, at which the indicated effect is observed.An unambiguous dependence of the biological effect in the “water – amoeba population” system on the average power of electromagnetic radiation of cell phones, both in standby mode and in talk mode, has been established. It is concluded that the presented method of changing the physical properties of the aquatic environment of a population of protozoa under the influence of electromagnetic fields can be a model experiment in identifying the mechanisms of interaction of biological systems with electromagnetic radiation, determining the response time of biological systems to external electromagnetic influence, and establishing the degree of influence of radiation in the 4G, 5G ranges.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

The article presents the results of the γ-ray and fast neutrons impact on various rice species, in order to obtain mutant forms resistant to salinity (NaCl) and drought factors (sorbite). They are going to be used as initial forms in synthetic selection when creating varieties, adapted to the stressful conditions of, both, soil and climate in the Kazakhstan Aral Sea. The average lethal doses (LD50) of γ-rays and fast neutrons, as well as, the average NaCl and sorbite lethal concentrations were established. A distinct dependence on the effect of ionizing radiation and stress factors on the number of induced resistant mutant forms has been related to the initial rice variety. The largest number of mutant forms was obtained from the local variety Syr Suluy, followed by Leader and Aikerim varieties. Out of all varieties, only 1% of the initially irradiated by γ-rays seeds survived, while after fast neutron irradiation – 4,3%. M1 mutant plants significantly differ from the initial forms in terms of morphological features – plant height, panicle length, and grain size. They are tolerant to lodging, and have short and highly sterile panicles, indicating that they are mutants.

This review summarizes studies dedicated to the assessment of microvascular function based on microcirculatory oscillations monitored by the FMSF technique. Two approaches are presented. The first approach uses oscillatory parameters measured under normoxia conditions, expressed as flowmotion (FM), vasomotion (VM), and the normoxia oscillatory index (NOI). These parameters have been used for identification of impaired microcirculatory oscillations associated with intense physical exercise, post-COVID syndrome, psychological stress, and erectile dysfunction. The second approach involves characterization of the microcirculatory response to hypoxia based on the measurement of hypoxia sensitivity (HS). The HS parameter is used to characterize microvascular complications in diabetes, such as diabetic kidney disease and diabetic foot ulcers. Based on research conducted by the authors of this review, the FMSF parameter ranges characterizing microvascular function are presented. The diagnostic approach to assessing microvascular function based on flowmotion monitored by the FMSF technique has a wide range of applications and potential to be integrated into widespread medical practice.

A high step-up DC-to-DC converter that integrates an isolated transformer and a switched-clamp capacitor is presented in this study. The voltage stress of the main power switch should be clamped to 1/4 V by using the turn ratio and switched-clamp capacitor of an isolated transformer to achieve a high voltage gain. In addition, a passive clamp circuit is employed reduce voltage stress on the main power switch. The energy of the leakage inductor can be recycled by the clamp capacitor because of the passive clamp circuit, thereby improving the power converter efficiency. The converter consists of one isolated transformer, one main switch, three capacitors, and four diodes. Operating principle and steady-state analyses are also discussed. Finally, a 24-V-input voltage to 200-V-output voltage and a 150 W output power prototype converter are fabricated in the laboratory. The maximum efficiency of the converter is 95.1 at 60 W.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

Conventional radiation therapy uses white X-rays that consist of a mixture of X-ray waves with various energy levels. In contrast, a monochromatic X-ray (monoenergetic X-ray) has a single energy level. Irradiation of high Z elements with a synchrotron generated monochromatic X-ray with the energy at or higher than the K-edge energy of the element results in the production of the Auger electrons that cause DNA damage leading to cell killing. Delivery of high Z elements into cancer cells and tumor mass can be facilitated by the use of nanoparticles. Mesoporous silica nanoparticles (MSNs) have been shown to be effective in delivering high Z elements to cancer cells. A proof of principle experiment was reported that demonstrated the feasibility of this approach. This opens up a possibility to pursue the Auger cancer therapy by the combined use of MSNs loaded with high Z elements and monochromatic X-rays. Similar cancer therapies using other types of quantum beams such as neutron, proton and carbon ion beams can be envisioned.