Postoperative RT is recommended after breast conserving surgery and mastectomy (with risk factors). Consideration of pros and cons including potential side effects demands for optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation - hypofractionation should be considered standard. For selected low risk situations PBI only or even the omission of RT might be appropriate. In contrast, tendencies in escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements the incorporation of molecular risk profiles but also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making if and how local and/or regional RT should be administered.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

This paper addresses the fate of extended space-time symmetries, in particular conformal symmetry and supersymmetry, in two-dimensional Rindler space-time appropriate to a uniformly accelerated non-inertial frame in flat 1+1-dimensional space-time. Generically, in addition to a conformal co-ordinate transformation, the transformation of fields from Minkowski to Rindler space is accompanied by local conformal and Lorentz transformations of the components, which also affect the Bogoliubov transformations between the associated Fock spaces. I construct these transformations for massless scalars and spinors, as well as for the ghost and super-ghost fields necessary in theories with local conformal and supersymmetries, as arising from coupling to 2-D gravity or supergravity. Cancellation of the anomalies in Minkowski and in Rindler space requires theories with the well-known critical spectrum of particles arising in string theory in the limit of infinite strings, and is relevant for the equivalence of Minkowski and Rindler frame theories.

The QCD Lagrangian is based on quark and gluonic fields -- not squarks nor gluinos. However, one can show that its hadronic eigensolutions conform to a representation of superconformal algebra, reflecting the underlying conformal symmetry of chiral QCD. The eigensolutions of superconformal algebra provide a unified Regge spectroscopy of meson, baryon, and tetraquarks of the same parity and twist as equal-mass members of the same 4-plet representation with a universal Regge slope. The predictions from light-front holography and superconformal algebra can also be extended to mesons, baryons, and tetraquarks with strange, charm and bottom quarks. % The pion $q \bar q$ eigenstate has zero mass for $m_q=0.$ % % A key tool is the remarkable observation of de Alfaro, Fubini, and Furlan (dAFF) which shows how a mass scale can appear in the Hamiltonian and the equations of motion while retaining the conformal symmetry of the action. When one applies the dAFF procedure to chiral QCD, a mass scale $\kappa$ appears which determines universal Regge slopes, hadron masses in the absence of the Higgs coupling. One also predicts the form of the nonperturbative QCD running coupling: $\alpha_s(Q^2) \propto e^{-{Q^2/4 \kappa^2}}$, in agreement with the effective charge determined from measurements of the Bjorken sum rule. One also obtains viable predictions for spacelike and timelike hadronic form factors, structure functions, distribution amplitudes, and transverse momentum distributions. % The combination of conformal symmetry, light-front dynamics, its holographic mapping to AdS$_5$ space, and the dAFF procedure thus provide new insights, not only into the physics underlying color confinement, but also the nonperturbative QCD coupling and the QCD mass scale.

We delve into the intricate dynamics governing anisotropic fluids within the cosmological paradigm, elucidating the nuanced influence of conformal anomalies upon the stress-energy tensor. Through the presentation of a sophisticated theoretical framework, we seamlessly intertwine unconventional fluidic properties with profound cosmological considerations, thereby augmenting and refining our comprehension of the primordial universe.

In the paper we consider conformal mappings of Riemannian spaces onto Ricci-2-symmetric Riemannian spaces and geodesic mappings of spaces with affine connections onto Ricci-2-symmetric spaces. The main equations for the mappings are obtained as a closed system of differential equations of Cauchy-type in covariant derivatives. We have found the number of essential parameters which the solution of the system depends on. Similar approach was applied for the case of conformal mappings of Riemannian spaces onto Ricci-m-symmetric Riemannian spaces and geodesic mappings of spaces with affine connections onto Ricci-m-symmetric spaces.

This review explores the nuanced decision-making surrounding postoperative radiotherapy for diffuse low-grade glioma (DLGG) patients, emphasizing the need for personalized treatment to balance the benefits of tumor control with the risks of long-term side effects. Radiotherapy is a cornerstone of DLGG treatment, offering significant improvements in progression-free survival, but its potential for cognitive decline and vascular lesions necessitates careful consideration of individual patient factors. The review delves into the complexities of radiotherapy timing, revealing that while early radiotherapy enhances progression-free survival, it does not significantly impact overall survival and may lead to earlier onset of cognitive decline. Conversely, delayed radiotherapy may mitigate cognitive decline but may result in shorter progression-free survival and the onset of neurological symptoms. The review advocates for a patient-centered approach, emphasizing the importance of weighing individual risks and benefits, and highlights the potential of artificial intelligence in predicting cognitive decline and the need to revisit previous research findings in light of the 2021 WHO (World Health Organization) classification update, underscoring the evolving nature of DLGG treatment and the ongoing quest for optimal therapeutic strategies.

The article is devoted to infinitesimal transformations. We have obtained that LCK-manifolds do not admit nontrivial infinitesimal projective transformations. Then we study infinitesimal conformal transformations of LCK-manifolds. We have found the expression for the Lie derivative of a Lee form. Also we have obtained the system of partial differential equations for the transformations, and explored its integrability conditions. Hence we have got the necessary and sufficient conditions in order that the an LCK-manifold admits a group of conformal motions. Also we have calculated the number of parameters which the group depends on. We have proved that a group of conformal motions admitted by an LCK-manifold is isomorphic to a homothetic group admitted by corresponding K\"{a}hlerian metric. We also established that an isometric group of an LCK-manifold is isomorphic to a some subgroup of homothetic group of the coresponding local K\"{a}hlerian metric.

Primate vision is an active process that constructs a stable internal representation of the 3D world based on 2D sensory inputs that are inherently unstable due to incessant eye movements. We present here a mathematical framework for processing visual information for a biologically-mediated active vision stereo system with asymmetric conformal cameras. This model utilizes the geometric analysis on the Riemann sphere developed in the group-theoretic framework of the conformal camera, thus far only applicable in modeling monocular vision. The asymmetric conformal camera model constructed here includes the fovea’s asymmetric displacement on the retina and the eye’s natural crystalline lens tilt and decentration, as observed in ophthalmological diagnostics. We extend the group-theoretic framework underlying the conformal camera to the stereo system with asymmetric conformal cameras. Our numerical simulation shows that the 1 theoretical horopter curves in this stereo system are conics that well approximate the empirical longitudinal horopters of the primate vision system.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

We demonstrated a new approach to the production of three-dimensional-coated patterns using liquid route. Metallic perovskite oxides were coated onto three-dimensional (3D) microstructured substrates with different aspect ratios. The success of the method relies on the solution viscosity monitored by adding viscous liquid. The process of oxide thin films consists in three steps: preparing the precursor solution, coating the solution by spin-coating process onto three-dimensional-Si substrates and post-annealing. The chemical solution 3D-coating is conformal.

We construct families of ground state representations of the U(1)-current net and of the Virasoro nets Vir_c with central charge c ≥ 1. We show that these representations are not covariant with respect to the original dilations, and those on the U(1)-current net are not solitonic. Furthermore, by going to the dual net of with respect to the ground state representations of Vir_c, one obtains possibly new family of Möbius covariant nets on S¹.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Reviewed are recent efforts leading to chemo-enzymatic syntheses of strongly fluorescent ribosides of nucleobase analogs, potentially applicable in analytical biochemistry and cell biology. Described are syntheses and properties of fluorescent purine, 8-azapurine and etheno-purine ribosides, obtained using various types of the purine nucleoside phosphorylase (PNP) as catalysts of ribosylation, and -ribose-1-phosphate (r1P) as a second substrate. In several instances, the ribosylation sites were different than the canonical purine N9. Some of the obtained ribosides show fluorescence yields close to 100%. Their main applications are assays of PNP, nucleoside hydrolases, and other enzyme activities both in vitro and, possibly, within the living cells, using fluorescence microscopy.

Conventional X-ray therapy (XRT) is commonly applied to suppress cancerous tumors, however it often inflicts collateral damage to nearby healthy tissue. In order to provide a better conformity of the dose distribution in the irradiated tumor, proton therapy (PT) is increasingly being used to treat solid tumors. Furthermore, radiosensitization with gold nanoparticles (GNPs) has been extensively studied to increase the therapeutic ratio. The mechanism of radiosensitization is assumed to be connected with an enhancement of the absorbed dose due to huge photoelectric cross-sections with gold. Nevertheless, numerous theoretical studies mostly based on Monte Carlo (MC) simulations did not provide consistent and thorough picture of dose enhancement and, therefore, radiosensitization effect. Radiosensitization by nanoparticles in PT is even less studied than in XRT. Therefore, we investigate physics picture of GNP-enhanced RT using MC simulation with Geant4 equipped with the most recent physics models, taking into account a wide range of physics processes relevant for realistic PT and XRT. Namely, we measured dose enhancement factors in the vicinity of GNP with diameters ranging from 10 nm to 80 nm. The dose enhancement in the vicinity of GNP reaches high values for XRT, while it is very modest for PT. The macroscopic dose enhancement factors for realistic therapeutic GNP concentrations are rather low for all RT scenarios, therefore other physicochemical and biological mechanisms should be additionally invoked for an explanation of the radiosensitization effect observed in many experiments.

BUB1 is overexpressed in most human solid cancers including breast cancer. Higher BUB1 levels are associated with poor prognosis especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitor sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin and paclitaxel synergistically (combination index; CI

Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. Central to the issue are reported differences in response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low dose region of the dose response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.

Vitamin A, or retinol, is one of the most effective anti-ageing molecules, but it presents issues with photo-sensitivity and irritation. Retinol-like alternatives are emerging, but have so far been less effective. Here, we present a Silibum marianum extract (SME) as a retinol-like ingredient providing both safety and efficacy. SME was compared to the reference compound, retinol, and to the main alternative, bakuchiol. In ex vivo tests, skin explants from a 58-year-old donor were treated with pure retinol (0.1%), bakuchiol (0.2%) or SME (0.8%). After 5 days, collagen and hyaluronic acid levels were analysed. A placebo-controlled study involving 57 volunteers (ages 45-73 years) was also conducted, with products applied twice-daily for 56 days. Results were measured by AEVA-HE and VISA. Levels of collagen III were significantly increased by SME, by 23% and 16% compared to bakuchiol and retinol, respectively. Compared to bakuchiol, SME treatment increased hyaluronic acid production by 36%. In clinical tests, SME had a significantly stronger anti-wrinkle effect than bakuchiol – reducing the number of wrinkles on the forehead by 21%, and their circumference by 17% – producing effects similar to retinol, and better than bakuchiol. In the self-assessment, 43% of volunteers reported discomfort while using retinol, as compared to 0% for the SME formulation. By enhancing levels of collagen III – the youth collagen – and hyaluronic acid in the skin, SME paves the way for the maturation of collagen I fibrils and skin plumping. With its stronger efficacy compared to bakuchiol and enhanced safety profile compared to retinol, SME may be the next-generation of natural alternatives to retinoids.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

We study in detail the influence of different chemical potentials (baryon, charged, strange, and neutrino) on how and how fast a free gas of quarks in the zero-temperature limit reaches the conformal limit. We discuss the influence of non-zero masses, the inclusion of leptons, and different constraints, such as charge neutrality, zero-net strangeness, and fixed lepton fraction. We also investigate for the first time how the symmetry energy of the system under some of these conditions approaches the conformal limit. Finally, we briefly discuss what kind of corrections are expected from perturbative QCD as one goes away from the conformal limit.

The limitations of conventional sensors have made phased array antennas increasingly crucial for gathering information and communication applications in intelligent transportation systems. Compact cylindrical arrays, in particular, are favored for their ability to achieve azimuth angle scan. However, the substantial mutual coupling effect between elements on curved surfaces and its implication in these arrays remains unclear, which is a crucial factor to consider when such arrays are used for multibeam applications. This study investigated the effect of mutual coupling in a dual-slant-polarized cylindrical array. The results showed that mutual coupling is essential for achieving an ultra-wide bandwidth. Mutual coupling is predominantly observed among elements that are closely positioned. The study also analyzes the impact of mutual coupling on scan impedance and radiation characteristics for multibeam applications and reveals that these arrays exhibit robust multibeam capability, hence having great potential for use in intelligent transportation systems.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Flexible wearable pressure sensors offer numerous benefits, including superior sensing capabilities, a lightweight and compact design, and exceptional conformal properties, making them highly sought after in various applications including medical monitoring, human-computer interaction, and electronic skin. Because of their excellent characteristics, such as simple fabrication, low power consumption, and short response time, capacitive pressure sensors have received widespread attention. As a flexible polymer material, polydimethylsiloxane (PDMS) is widely used in the preparation of dielectric layers for capacitive pressure sensors. The Young's modulus of the flexible polymer can be effectively decreased through the synergistic application of sacrificial template and laser ablation techniques, thereby improving the functionality of capacitive pressure sensors. In this study, a novel sensor was developed through a series of processes including sacrificial template method using NaCl microparticles, CO₂ laser ablation, and sandwiching a porous PDMS dielectric layer between two flexible electrodes to create a capacitive pressure sensor. The sensor demonstrates a sensitivity of 0.694 kPa-1 within the pressure range of 0-1 kPa, and can effectively detect pressures ranging from 3 Pa to 200 kPa. The sensor demonstrates stability for up to 500 cycles, with a rapid response time of 96ms and a recovery time of 118ms, coupled with a low hysteresis of 6.8%. Furthermore, our testing indicates that the sensor possesses limitless potential for use in detecting human physiological activities and signaling emergencies.

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.

Conventional MRI sequences are standard methods to monitor patients with brain tumors but have significant limitations especially after irradiation. Currently, the role of FET-PET in radiotherapy of glioblastoma is emerging, starting from target definition, response assessment and in distinguishing progression from post-irradiation changes. Recently a PET RANO criteria have been published providing optimal strategy for treatment evaluation with amino-acid PET. Earlier, a PET/RANO group reported contribution of PET imaging to radiotherapy planning and monitoring in glioma patients. Also, increasing evidence have showed advantages of amino-acid PET vs. RANO MRI for prediction of overall survival. In this narrative review we aimed to summarize published data on FET-PET based treatment response assessment to radiotherapy and focused on details in protocols.

This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on healthy liver (HL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA-double strand breaks were investigated in irradiated and non-irradiated organotypic slice culture (OSC) and ex vivo samples by detection of Ki67 and γ-H2AX. OSC proved useful to determine dose-dependent effects on proliferation and DNA damage but appeared unsuited to test the chronotherapeutic approach. Irradiation of ex vivo samples was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on HL were minimal at ZT20. Ex vivo samples revealed disruption in daily variation and down-regulation of all investigated clock genes except Per1 in non-irradiated HCC as compared with HL. Irradiation affected rhythmic clock gene expression in HL and HCC at all ZTs except at ZT20. Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

After reviewing cancer theories, cancer treatment development histories, randomized clinical trial's performance, cancer treatment strategy, trial follow-up times, and conducting numerous simulations using existing data, the authors found: (1) medical treatments come with three to four lethal factors: treatment side-effects, emotional distress and chronic dress, lack of exercises or physical inactivity, and excessive nutrition in some cases; (2) clinical trial exaggerates the benefits of fast-acting treatments and underestimates the slow-delivering adverse side effects as a result of statistical averaging, interfering effects of personal lifestyle factors, and insufficient follow-up times; (3) the benefits of medical treatments are limited by chain comparison, where surgery sets up a negative standard relative to the best way for resolving cancer; (4) the strategy of destroying the tumor is unworkable; (5) medical treatments can turn natural cancer growth curve into approximately doubly exponential curve; (6) multiple factor non-medical measures are much more powerful than medical treatments in controlling cancer growth and metastasis rates; and (7) cancer early diagnosis and over treatments are bad strategies that have great adverse impacts on cancer patients. Based on huge increases in cancer growth rate constants, substantial of loss of organ functional capacity, and severe systemic aging-like cellular damages, the authors concluded that medical treatments promote cancer growth and metastasis rates and shorten patient lives in most cases, and the claimed benefits are caused by triple biases of clinical trials. The authors believe that the better strategy for ending the global cancer epidemic is abandoning clinical trails as the research model, changing caner treatment strategy from killing cancer cells to slowing down cancer growth rates by using multiple factors optimization approach in personalized medicine.

N6-methyladenosine (M6A) modification is the most abundant internal chemical modification on RNA molecules in eukaryotes and can affect mRNA metabolism and regulate RNA transcription, nuclear export, splicing, degradation, translation, ets, and has a significant impact on various aspects of physiology or pathobiology. Radiotherapy is the most common measure of tumor treatment, variety of cellular intrinsic mechanisms affect the responses of cells to ionizing radiation (IR) and effectiveness of cancer radiotherapy. In this review, we summarize and discuss the recent advances about the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage response, and outcomes of cancer radiotherapy. Insights into the RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy as well as radioprotection on normal tissues.

Titanium-based metal-matrix composites manufactured by additive manufacturing offer tremendous lightweighting opportunities. However, processing high reinforcement content remains challenging. This study reports an improved manufacturing process for Ti-TiC enabling high reinforcement content and significant fracture strain concurrently: mechanical blending, followed by laser powder bed fusion and a single heat treatment. As-built microstructure shows both un-melted TiC particles and sub-stoichiometric TiC dendrites resulting from a partial dissolution of TiC particles. The heat treatment is shown to fully convert TiC dendrites into equiaxed TiC grains. Reduction of the C/Ti ratio in TiC during the process results in an increase in the reinforcement content, from a nominal 12 vol% to an effective 21.5 vol%. Ti-TiC tensile samples reached fracture strains of up to 1.7%, Young’s moduli of up to 149 GPa and ultimate tensile strengths of up to 827 MPa. Lower TiC initial powder size distributions displayed the best mechanical performance.

Interest grows in designing silicon-on-insulator slot waveguides to trap optical fields in subwavelength-scale slots and developing their optofluidic devices. However, it is worth noting that the inherent limitations of the waveguide structures may result in high optical losses and short optical paths, which challenge the device performance in optofluidics. Incorporating the planar silicon-based slot waveguide concept into a silica-based hollow-core fiber can provide a perfect solution to realize an efficient optofluidic waveguide. Here we propose a subwavelength-scale liquid-core hybrid fiber (LCHF), where the core is filled with carbon disulfide and surrounded by a silicon ring in a silica background. The waveguide properties and the Stimulated Raman Scattering (SRS) effect in the LCHF are investigated. The fraction of power inside the core of 56.3% allows an improved sensitivity in optical sensing; while the modal Raman gain of 23.60 m-1·W-1 is 2 times larger than that generated around a nano fiber with the interaction between the evanescent optical field and the surrounding Raman media benzene-methanol, which enables a significant low-threshold SRS effect. Besides, this in-fiber structure features compactness, robustness, flexibility, ease of implementation in both trace sample consumption and reasonable liquid filling duration, as well as compatibility with optical fiber systems. The detailed analyses of the properties and utilizations of the LCHF suggest a promising in-fiber optofluidic platform, which provides a novel insight into optofluidic devices, optical sensing, nonlinear optics, etc.

A single mode waveguide grating coupler based on multiple Si-SiO₂ pairs onto Si substrate has been designed. Numerical analysis has been carried out to calculate optimum thickness of the layers of Si-SiO₂ that ensures the constructive interference between reflected waves and actual guided wave for high coupling efficiency. Based on the results, an optimal design is developed and modeled by using a 2-D finite difference time domain (2-D FDTD) simulator that dictates a coupling efficiency of as much as 78% (-1.07 dB) at the wavelength of 1550 nm, and a 1-dB bandwidth of 77 nm. The numerical method will be useful to calculate the optimum thicknesses of the layers for any reflector based grating coupler of different materials.

A novel means of applying radiotherapy in cancer treatment is the application of the radiation dose at a very high intensity for a very short time, FLASH radiotherapy (FLASH-RT). This technique involves exposure of tumors to >40 Gy/s, usually for less than one second. Studies conducted in cell and preclinical models suggest that FLASH-RT seems less damaging to normal tissues from adverse effects, relative to the same overall dose of radiation administered in conventional therapy (CONV-RT) which involves administration of lower levels of radiation repeated intermittently over a protracted period. In contrast, the susceptibility of tumor tissues to FLASH-RT is not diminished relative to CONV-RT. Within solid tumors both modes of dispensation of radiation produce an equivalent degree of cell damage. This differential between normal and malignant material has been found in isolated tissues, animal studies, and more recently in clinical trials. However, the classical radiation concept is that high energy linear transfer radiation (LET) is more damaging than the equivalent total dose of low LET. Thus, the susceptibility of cells should be greater to short-term exposure to high LET. This article discusses the potential reasons that may account for this discrepancy. While the relative protection given to untransformed tissues by FLASH-RT relative to tumor tissue is a major step forward in radiation therapy of cancer, the processes that lie behind this phenomenon are incompletely understood and are considered here.

Purpose Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20-50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Methods Patients (N=36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). Results Median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and 9 (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and 15(42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax, and 9 (25%) to the abdomen or pelvis. Total dose ranged from 18 to 42.5 Gy in 6-17 fractions/ 2.67-5 Gy per fraction. Median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86), and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. Two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort, and 100, 87 (95%CI: 56.4-96.5%) and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI:59.9-90.5%), and 100, 66.1 (95% CI: 36.4-84.4%) and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. Conclusion HFRT in HM provides excellent local control without any increase in toxicity.

The analysis of chemical warfare agents and their degradation products has become increasingly important for public and military safety in recent years. In the article, we drew attention to the possibilities of the HPLC-ICP-MS analytical technique, which has been relatively rarely used for identifying and quantitatively analyzing highly toxic and hazardous substances in environmental samples. This technique enables the identification and determination of minimal amounts (ppt range) of chemicals in various matrices. This fact is important for the analysis of chemical warfare agents and other highly harmful compounds, even small amounts of which can have serious consequences for living organisms. The article critically analyzes the results of scientific research on the identification and quantitative analysis of extremely toxic organophosphorus, organosulfur and organoarsenic substances, their derivatives and degradation products using high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS).

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Nowadays, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy and maculopathy and optic neuropathy are the most common. This article aims to summarize the current literature on the ocular complications after radiotherapy, their clinical features, risk factors and management strategies. A thorough understanding is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications.

Displacement mapping is a computer graphics technique that enables the design of components with regularly or randomly textured surfaces that can be quickly materialized on a three-dimensional (3D) printer when needed. This approach is in principle more flexible, faster and more economical compared to conventional texturing methods, but the accuracy of the texture depends heavily on the parameters used. The purpose of this study is to demonstrate how to produce a surface-textured part using polygonal (mesh) modeling software and a photopolymerizable resin, and to develop a universal methodology to predict the dimensional accuracy of the model file log combined with a resin 3D printer. The printed components were characterized on a scanning confocal microscope. In the setup used in this study, the mesh size had to be reduced to 10% of the smallest feature size and the textured layer had to be heavily (x4) overexposed to achieve the desired accuracy. As a practical application, two functional stamps with a regular (honeycomb) and a random texture, respectively, were successfully manufactured. The insights gained will be of great benefit in quickly and cost-effectively producing components with innovative patterns and textures for a variety of hobby, industrial and biomedical applications.

In a dynamic production processes, mechanical degradation poses a significant challenge, impacting product quality and process efficiency. This paper explores a novel approach for monitoring degradation in the context of viscose fiber production, a highly dynamic manufacturing process. Using causal discovery techniques, our method allows domain experts to incorporate background knowledge into the creation of causal graphs. Further, it enhances the interpretability and increases the ability to identify potential problems via changes in causal relations over time. The case study employs a comprehensive analysis of the viscose fiber production process within a prominent textile industry, emphasizing the advantages of causal discovery for monitoring degradation. The results are compared with state-of-the-art methods, which are not considered to be interpretable, specifically LSTM-based autoencoders, showcasing the alignment and validation of our approach. This paper provides valuable information on degradation monitoring strategies, demonstrating the efficacy of causal discovery in dynamic manufacturing environments. The findings contribute to the evolving landscape of process optimization and quality control.

Spectral characteristics of CDOM in water column are a key parameter for bio-optical modeling. Knowledge of CDOM optical properties and spatial discrepancy based on the relationship between water quality and spectral parameters in Yinma River watershed with in situ data collected highly-polluted waters are exhibited in this study. Seasonal field data sets collected over a period of 2 months in 2015 in Yinma River Watershed. Based on the comprehensive index method, the riverine waters showed serious contamination, especially the COD, Fe, Mn, Hg and DO were out of range contamination warning. Dissolved organic carbon (DOC) and total suspended matter (TSM) with prominent non-homogenizing were significantly high in the riverine waters, but chlorophyll-a (Chl-a) was opposite. Ternary phase diagram showed that non-algal paritcles absorption played an important role in total non-water light absorption (>50%) in most sampling locations, and mean contribution of CDOM were 13% and 22% in summer and autumn respectively. Analysis of ratio of absorption at 250-365 nm (E_250:365) and spectral slope (S_275-295) indicated that CDOM had higher aromaticity and molecular weight in autumn than in summer, is consistent with the results of water quality and relative contribution. Redundancy analysis (RDA) indicated that the environmental variables OSM had a strong correlation with CDOM absorption, followed by heavy metal, e.g., Mn, Hg and Cr⁶⁺. However, for the specific UV absorbance (SUVA₂₅₄), the seasonal values showed opposite results compared with the reported literature. The potential reasons were the more UDOM (uncolored Dissolved Organic Matter) from human source (wastewater effluent) existed in waters. Terrigenous inputs simultaneously are in relation to the a_CDOM(440)-DOC relationship with the correlation coefficient was 0.90 in summer (2-tailed, p<0.01), and 0.58 in autumn (2-tailed, p<0.05). Spatial distribution of CDOM parameters exhibited that the downstream regions focused on dry land have high CDOM molecular weight and aromatic hydrocarbon. Partial sampling locations around the cities or countries generally showed abnormal values due to terrigenous inputs. As a bio-optical model parameter, spectral characteristic of CDOM is helpful in adjusting the derived algorithms in highly-polluted environments. The study on organic carbon and pollutants in highly-polluted waters had an important contribution to global carbon balance estimation and water environment protection.

Silver nanoparticles (AgNPs) have arisen as promising specialists in malignant growth treatment, especially in further developing radiotherapy results. In vitro examinations feature AgNPs' capacity to increment radiosensitivity in disease cell lines, prompting uplifted cell demise and decreased clonogenic endurance. Outstandingly, AgNPs display insignificant poisonousness to ordinary cells, recommending potential for specific focusing of disease cells during radiotherapy. The blend of AgNPs with cisplatin shows huge cytotoxicity and oxidative pressure, particularly in tumoral cells, underscoring the requirement for additional investigation of this therapeutic methodology. AgNPs likewise show guarantee in prompting oxidative pressure in pancreatic disease cells, recommending an expected application in pancreatic malignant growth treatment. In co-openness situations, AgNPs, when joined with cadmium, prompt metabolic variation, showing compromised cell safeguard systems. Moreover, AgNPs display potential in tweaking ABC carrier action, offering a procedure to defeat multidrug obstruction in disease cells. While featuring the significant capability of AgNPs in disease treatment, the rundown highlights the need for continuous exploration to clarify their components, well-being profiles, and clinical applications. Combining AgNPs with radiotherapy presents a promising road, tending to limits in ordinary disease therapies and underlining their multifunctionality in forming the eventual fate of malignant growth therapeutics.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

The evolution of the H5 highly pathogenic avian influenza (HPAI) viruses has led to the emergence of distinct groups with genetically similar clusters of hemagglutinin (HA) sequences. In this study, a consensus H5 HA sequence was cloned into the baculovirus expression system. The HA protein was expressed in baculovirus-infected insect cells and utilized as the antigen for the production of an oil emulsion-based H5 avian influenza vaccine (rBacH5Con5Mut). 21-day old SPF chickens were immunized with this vaccine and then challenged at 21 days post-vaccination (dpv) with clade 2.3.2.1, clade 2.3.4.4 and clade 7.2 of H5 HPAI virus, respectively. The chicken sera of vaccinated chickens exhibited high hemagglutination inhibition (HI) titers against the rBacH5 vaccine antigen, while lower HI titers were observed against the different challenge virus H5 hemagglutinins. Furthermore, the rBacH5Con5Mut vaccine provided 100% protection from mortality and clinical signs. Virus isolation results showed that oropharyngeal and cloacal shedding was prevented in 100% of the vaccinated chickens when challenged with clade 2.3.2.1 and clade 2.3.4.4 H5 viruses. When the rBacH5Con5Mut vaccine candidate was administrated at one day of age, 100% protection was demonstrated against challenge of clade 2.3.4.4 virus at 3 weeks of age, indicating the potential of this vaccine for hatchery vaccination. Overall, the rBacH5Con5Mut vaccine candidate with a consensus HA antigen and a single dose can protect chickens against different clades of H5 HPAI viruses throughout the rearing period of broiler chickens without a boost, thus fulfilling the criteria for an efficacious broad-spectrum H5 avian influenza vaccine.

This study introduces a novel method that combines Generative Adversarial Networks (GANs) with conformal prediction to revolutionize the domain of stock ticker forecasting. Our approach enhances prediction accuracy and offers dependable prediction intervals to gauge uncertainty, surpassing current GAN-based techniques in unpredictable market scenarios. We made a validation using AAPL stock data, showing the ability of our model to generate accurate forecasts and reliable assessments of prediction uncertainty. The prediction intervals generated provide investors and risk managers with a powerful tool to make informed decisions. Our approach represents a notable advancement in financial prediction as it improves the clarity and reliability of forecasts. By incorporating conformal prediction into the GAN framework, the reliability of forecasts is improved, providing a thorough evaluation of uncertainty that is crucial for successful risk management. This framework has the potential to transform the field of predictive analytics in finance. It shows a solution that balances accuracy and uncertainty quantification. The results clearly show the effectiveness of this method, paving the way for its potential application in a wide range of financial prediction scenarios.

The G2 gas cloud motion data and the scarcity of observations on the event horizon-scale distances have challenged the comprehensiveness of the central supermassive black hole model. In addition, the Planck Legacy 2018 release has preferred a positively curved early Universe with a confidence level higher than 99%. This study investigates the impact of the background curvature and its evolution over the conformal time on the formation and morphological evolution of central compact objects and the consequent effect on their host galaxies. The formation of a galaxy from the collapse of a supermassive gas cloud in the early Universe is modeled based on interaction field equations as a 4D relativistic cloud-world that flows and spins through a 4D conformal bulk of a primordial positive curvature considering the preference of the Planck release. Owing to the curved background, this scenario of galaxy formation reveals that the core of the galaxy undergoes a forced vortex formation with a central event horizon leading to opposite vortices (traversable wormholes) that spatially shrink while evolving in the conformal time. It indicates that the galaxy and its core are formed in the same process whereas the surrounding gas clouds form the spiral arms due to the frame-dragging induced by the fast-rotating core. It demonstrates that the accretion flow onto the central supermassive compact object only occurs at the central event horizon of the two opposite vortices while their other ends eject the relativistic jets. This can elucidate the relativistic jet formation and explain the G2 gas cloud motion if its orbit is around one of the vortices but at a distance from the central event horizon. The gravitational potential of the early curved bulk could contribute to galaxy formation while the present spatial flatness deprives the potential of bulk which could lead to galaxy quenching. The formation of a galaxy and its core simultaneously could explain the growth of the supermassive compact galaxy core to a mass of ~10⁹ M_⊙ at just 6% of the current Universe age.

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.

The most important prognostic factors in curatively treated prostate cancer at the initial diagnosis are T and N stage, histological subtype, Gleason score, initial PSA, PSA density and percentage of core biopsy positivity. Newer, but non-standard prognostic factors are urine PCA3 and genetic markers of prostate cancer. A simple, but seemingly underestimated standard test is serum Calcium (Ca) level, which has been shown by a previous study group to be a good predictor of lethal prostate cancer, but there is scarce evidence regarding the prognostic value of calcium levels at diagnosis. We aimed to determine whether a Ca level in the upper part of normal values has a prognostic value in curatively treated prostate cancer. We have retrospectively included 84 consecutive patients with prostate cancer, who underwent curative radiotherapy (primary or adjuvant; external beam RT with or without brachytherapy). We have performed statistical analysis of available prognostic factors. Ca level at diagnosis was found to be a statistically significant predictor of disease-free survival.

In recent years, the field of radiotherapy has witnessed remarkable advancements with the integration of artificial intelligence (AI) technologies into clinical practice. Traditionally, radiotherapy treatment planning has been a labor-intensive process, requiring meticulous manual segmentation and optimization. With the advent of AI, particularly deep learning algorithms, the accuracy and efficiency of target delineation and organ-at-risk segmentation have significantly improved. AI-driven algorithms analyze voluminous medical imaging data, enabling rapid and precise contouring, thus expediting the planning phase and reducing inter-observer variability. Furthermore, AI's role extends to treatment plan optimization, where it intelligently explores vast parameter spaces to generate optimal plans tailored to individual patients. This not only saves dosimetrists' time but also enhances plan quality by accounting for complex anatomical variations and personalized clinical goals. In the realm of treatment delivery, AI-powered real-time image guidance enhances the accuracy of patient positioning, ensuring precise radiation targeting. Adaptive radiotherapy, enabled by AI, allows on-the-fly plan modifications in response to anatomical changes, significantly improving treatment accuracy in scenarios like tumor shrinkage or weight loss. Beyond planning and delivery, AI algorithms contribute to outcome prediction by analyzing historical patient data and treatment responses. This predictive capability aids clinicians in making informed decisions and refining treatment strategies for better prognoses. Despite the revolutionary potential, challenges remain in seamlessly integrating AI into clinical workflows. Ethical considerations, data privacy, and algorithm interpretability necessitate cautious implementation. Additionally, fostering interdisciplinary collaboration between AI experts and radiation oncologists is imperative to harness the technology's full potential. This paper explores the impact of AI in four key areas of radiotherapy: automated segmentation, dosimetric and machine quality assurance, adaptive radiation therapy, and clinical outcome prediction.

Whole cell biosensors could serve as eco-friendly and cost-effective alternatives for detecting potentially toxic bioavailable heavy metals in aquatic environments. However, they often fail to meet practical requirements due to an insufficient limit of detection (LOD) and high background noise. In this study, we designed a synthetic genetic circuit specifically tailored for detecting ionic mercury, which we applied to environmental samples collected from artisanal gold mining sites in Peru. We developed two distinct versions of the biosensor, each utilizing a different reporter protein: a fluorescent biosensor (Mer-RFP) and a colorimetric biosensor (Mer-Blue). Mer-RFP enabled real-time monitoring of the culture’s response to mercury samples using a plate reader, whereas Mer-Blue was analysed for colour accumulation at the endpoint using a specially designed, low-cost camera set up for harvested cell pellets. Both biosensors exhibited negligible baseline expression of their respective reporter proteins and responded specifically to HgBr2 in pure water. Mer-RFP demonstrated a linear detection range from 1 nM to 1 μM, whereas Mer-Blue showed a linear range from 2 nM to 125 nM. Our biosensors successfully detected a high concentration of ionic mercury in the reaction bucket where artisanal miners produce a mercury-gold amalgam. However, they did not detect ionic mercury in the water from active mining ponds, indicating a concentration lower than 3.2 nM Hg2+ -a result consistent with chemical analysis quantitation. Furthermore, we discuss the potential of Mer-Blue as a practical and affordable monitoring tool, highlighting its stability, reliance on simple visual colorimetry, and the possibility of sensitivity expansion to organic mercury.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

In recent years, the demand for natural and synthetic zeolites has surged due to their distinctive properties and myriad industrial applications. This research aims to synthesise crystalline zeolites by co-recycling two industrial wastes: salt slag (SS) and rice husk ash (RHA). Salt slag, a problem-atic by-product of secondary aluminium smelting, is classified as hazardous waste due to its reac-tive and leachable nature, though it is rich in aluminium. Conversely, RHA, an abundant and cost-effective by-product of the agro-food sector, boasts a high silicon content. These wastes were utilised as aluminium and silicon sources for synthesising various zeolites. The study examined the effects of temperature, ageing time, and sodium concentration on the formation of different zeolite phases and their crystallinity. Results indicated that increased Na+ concentration favoured SOD zeolite formation, whereas LTA-type zeolite formation was promoted at higher temperatures and extended ageing times. The formation range of the different zeolites was defined and supported by a crystallographic, microstructural, and morphological analysis. Additionally, the thermal be-haviour of the zeolites was investigated. This work underscores the potential to transform indus-trial waste, including hazardous materials like salt slag, into sustainable, high-value materials, fostering efficient waste co-recycling and promoting clean, sustainable industrial production through cross-sectoral industrial symbiosis.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with 4 or more positive lymph nodes or extracapsular extension regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than 3 positive lymph nodes should be treated with radiotherapy, there is a controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in case of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

Background: Optimal hypofractionated schedule of post-prostatectomy radiotherapy remains to be established. We evaluated treatment outcomes and toxicity of the moderately hypofractionated post-prostatectomy radiotherapy in 16 daily fractions delivered with IMRT/VMAT. The treatment schedule selection was motivated by limited technology resources. Methods: One hundred consecutive M0 patients with post-prostatectomy radiotherapy were evaluated. Radiotherapy indication was adjuvant (ART) in 19%, early salvage (eSRT) in 46% and salvage (SRT) in 35%. The dose prescription for prostate bed PTV was 52.8 Gy in 16 fractions of 3.3 Gy. The Common Terminology Criteria v.4 for Adverse Events scale was used for toxicity grading. Results: The median follow-up was 61 months. Five-year biochemical recurrence-free survival (bRFS) was 78.6%, distant metastases-free survival was 95.7% and overall survival was 98.8%. Treatment indication was the only significant factor for 5-year bRFS in multivariate analysis which was 84.6% vs. 67.6% for ART or eSRT vs. SRT respectively (HR 0.15, 95% CI 0.05–0.47, p=0.001). Acute GI toxicity grade 2 was recorded in 24%, grade 3 in 2% and acute GU toxicity grade 2 in 10% and no grade 3. Cumulative rate of late GI toxicity grade ≥2 was observed in 9% and late GU toxicity grade ≥2 in 16%. Conclusion: Observed results confirmed efficacy and acceptable toxicity of post-prostatectomy hypofractionated radiotherapy in 16 daily fractions.

This review highlights normal and tumor tissue vasculature, immunological changes, and phenotypic alterations (VIP model) as fundamental in abscopal interaction. In the stereotactic body radiotherapy (SBRT) and immunotherapy era, we are moving toward “immunological radiation planning,” i.e., radiation scheduling with abscopal effect as a vital endpoint as well. Towards this end, this manuscript presents specific diagrammatic tumor models to optimize the outcome of abscopal response in SBRT, based on the principle of the four R’s - Repair, Redistribution, Repopulation, and Reoxygenation of radiotherapy. The article highlights the importance of restricting the dose of SBRT to < 10 Gy per fraction, appropriate use of dose painting, and concomitant/delayed SBRT boost potential. Current literature indicates that immunotherapy should not precede but follow SBRT within seven days. Included is the review of integrating “cyclical” antiangiogenics, immune adjuvants/immune-metabolites as abscopal effect enhancers with SBRT. The importance of proton, carbon-ion SBRT is dealt with briefly. Proposed six fundamental requirements for augmentation of the abscopal cascade are listed. The existing exploratory results need to develop a definitive strategy amidst complex interactions in SBRT, immunotherapy, immune-adjuvants, & abscopal effects. We now have enough literature evidence to convert “abscopal by chance” to “abscopal by design” by harmonized combinatorial approach.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

As an important follow-up report on the latest study of the first author (H.S.) on an off-shell quantum field causing a dressed photon and dark energy, we further discuss a couple of intriguing subjects based on our new theory. One is the dressed photon constant. If we use it, in addition to h¯ and c, as the third component of natural units, then it is defined as the geometric mean of the smallest and the largest lengths: Planck length and that relating to the cosmological constant. Interestingly, this length (≈ 50 nanometers) seems to give a rough measure of the Heisenberg cut for electromagnetic phenomena. The other is a new perspective on cosmology that combines two original notions, i.e., twin universes and conformal cyclic cosmology, proposed respectively by Petit and Penrose, into one novel picture where universes expand self-similarly. We show the possibility that twin universes having a dual structure of [matter with (dark energy &amp; matter)] vs. corresponding anti-entities, separated by an event horizon embedded in the geometric structure of de Sitter space, undergo endless cyclic processes of birth and death, as in the case of the pair creation and annihilation of elementary particles through the intervention of a conformal light field.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Hot stamping dies include cooling channels to treat the formed sheet. The optimum cooling channels of dies & molds should adapt to the shape and surface of the dies, so that a homogeneous temperature distribution and cooling are guaranteed. Nevertheless, cooling ducts are conventionally manufactured by deep drilling, attaining straight channels unable to follow the geometry of the tool. Laser Metal Deposition (LMD) is an additive manufacturing technique capable to fabricate nearly free-form integrated cooling channels and therefore shape the so-called conformal cooling. The present work investigates the design and manufacturing of conformal cooling ducts, which are additively built up on hot work steel and then milled in order to attain the final part. Their mechanical performance and heat transfer capability has been evaluated, both experimentally and by means of thermal simulation. Finally, conformal cooling conduits are evaluated and compared to traditional straight channels. The results show that LMD is a proper technology for the generation of cooling ducts, opening the possibility to produce new geometries on dies & molds and, therefore, new products.

The three dimensional conformable time fractional Kadomtsev-Petviashvili and the conformable time fractional modified Kawahara equations are solved by implementing the Kudryashov's procedure. The corresponding wave transformation reduces both equations to some ODEs. Balancing the nonlinear and the highest order derivative terms gives the structure of the solutions in the finite series form. The useful symbolic tools are used to solve the resultant algebraic systems. The solutions are expressed in explicit forms.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Background: Emerging data indicate that radiotherapy can modulate antitumour immune responses. Regulatory T cells (Tregs) are a key immunosuppressive subpopulation of interest. We aimed to evaluate the impact of conventional fractionated radiotherapy on circulating Treg levels in melanoma patients and to determine the correlation between these changes and survival. Understanding radiotherapy–immunity interactions may facilitate personalized combination therapies. Methods: Peripheral blood samples from 32 melanoma patients were analysed to quantify Tregs before and 1-3 months after regional lymph node radiotherapy using flow cytometry. Tregs were characterized as CD4+/CD25+/CD127-. Total CD4+ T cells were also evaluated. Changes were compared to those in a control group of 30 tumor-free patients. Overall survival was correlated with T-cell subset dynamics induced by radiotherapy. Results: At baseline, the median percentage of Tregs was not significantly lower in melanoma patients than in controls (7.4% vs 8.32%, p=0.17). Radiotherapy markedly increased the median Treg count to 10.01% (p=0.0008), with a concomitant increase in total CD4+ cells (to 11.71%, p=0.001), indicating systemic expansion. Patients exhibiting coordinated increases in Treg and CD4+ T cells after treatment had a significantly improved prognosis compared with nonresponders (median OS 27.8 vs 13.1 months, p=0.001). Conclusions: Our study demonstrated the significant effects of standard fractionated radiotherapy on systemic Treg levels in melanoma patients. Radiation-induced changes in T-cell subset proportions hold prognostic value. Monitoring of circulating lymphocyte subsets could facilitate personalized combination therapies.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine the impact on survival of adjuvant RT according to the Sedlis criteria. Patients with early-stage cervical cancer who underwent radical hysterectomy between 2005 and 2022 at a single tertiary institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analyzed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. In this retrospective study 121 patients were included of whom 48(39.7%) received adjuvant RT due to the presence of unfavorable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p=0.584) or disease-free survival (DFS) (p=0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate-risk factors.

Introduction The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 Gy is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the presented study to assess the safety of dose escalation up to 84 Gy. Patients and methods In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity. Results A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients had received 84 Gy (35 without pelvis- and 27 with pelvis-radiotherapy). Regarding acute toxicities, no adverse events > grade 2 occurred. 12.5% of patients treated with 80Gy, in 25.7% of patients treated with 84 Gy excluding pelvis, and in 51.9% of patients treated with 84Gy including pelvis suffered from Grade 2 GU acute toxicity (80 Gy versus 84 Gy: p=0.186; with pelvis versus without pelvis: p=0.032). Grade 2 GI toxicity occurred in 12.5% of patients irradiated with 80Gy, in 14.3% of patients treated with 84 Gy excluding pelvis, and in 12.9% of patients treated with 84Gy including pelvis (80 Gy versus 84 Gy: p=0.582; with pelvis versus without pelvis: p=0.510).GU late toxicity of grade ≥ 2 occurred in 4.2% of patients treated with 80 Gy, in 7.1% of patients treated with 84 Gy excluding pelvic RT, and in 18.2% of patients treated with 84 Gy including pelvic RT (logrank-test p=0.237). 8.3% of patients treated with 80 Gy, in 3.6% of patients treated with Gy excluding pelvic RT, and in 0% of patients treated with 84 Gy including pelvic RT suffered from GI late toxicity of grade ≥ 2(logrank-test p=0.358). Conclusion We were able to show that dose-escalated RT in PCA up to 84 Gy is feasible and safe without asubstantial increase in toxicity. Further follow up is needed to assess survival.

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

Dispersion of antibiotic in livestock farming represents a health concern worldwide, contributing to the spread of antimicrobial resistant bacteria through animals, the environment, and humans. Phenolic compounds could be alternatives to antibiotics, once drawbacks such as low water solubility, bioavailability, and reduced stability are overcome. Although nano- or microsized formulations could respond to these shortcomings they do not represent cost-effective options. Here, three phenolic compounds, obtained from wood processing manufacturers, were characterized, revealing suitable features such as antioxidant activity, size, and chemical and colloidal stability for in-field applications. The Minimum Inhibitory Concentration (MIC) of these colloidal suspensions was measured against six bacterial strains isolated from livestock. These particles showed different inhibition behaviors: Colloidal chestnut was effective against one of the most threatening antibiotic resistant pathogens such as S. aureus but was ineffective toward E. coli. On the other hand, colloidal pine showed a weak effect on S. aureus but specificity toward E. coli. The present proof-of-concept points at colloidal polyphenols as valuable alternatives for antimicrobial substitutes in the livestock context.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TNM-stages. Locoregional control rates have been impressive even from the 2D-radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there had been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally-advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

Inland waters pose a unique challenge for water quality monitoring by remote sensing techniques due to their complicated spectral features and small-scale variability. At the same time, collecting the high-quality reference data needed to calibrate remote sensing data products is both time consuming and expensive. In this study, we present the further development of a robotic team composed of an uncrewed surface vessel (USV) providing in situ reference measurements and an unmanned aerial vehicle (UAV) equipped with a hyperspectral imager. Together, this team is able to address the limitations of existing approaches by enabling the simultaneous collection of comprehensive in situ data together with high-resolution hyperspectral imagery. We showcase the capabilities of this team using data collected in a north Texas pond during three collections in the fall of 2020. Machine learning models for 13 variables are trained using the data set of paired in situ measurements and coincident reflectance spectra. These models can successfully estimate physical variables, including temperature, conductivity, pH, and turbidity, as well as the concentrations of blue-green algae, colored dissolved organic matter (CDOM), chlorophyll-a, crude oil, optical brighteners and the ions Ca2+, Cl−, and Na+. We extend the training procedure to utilize conformal prediction to estimate 90% confidence intervals for the output of each trained model. The maps generated by applying each trained model to the collected images reveal the small-scale spatial variability within the pond. Additionally, the permutation importance computed for each feature of the trained models highlights the spectral features relevant to each water quality variable.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

It is a challenging and meaningful task to carry out drone-based livestock monitoring in high-altitude and cold regions. The purpose of AI is to execute automated tasks and to solve practical problems in actual applications by combining the software technology with the hardware carrier to create integrated advanced devices. Only in this way, the maximum value of AI could be realized. In this paper, a real-time tracking system with dynamic target tracking ability is proposed. It is developed based on the tracking-by-detection architecture using YOLOv7 and DeepSORT algorithms for target detection and tracking, respectively. To address the existing problems of the DeepSORT algorithm, the following two optimizations are made: (1) Optical flow is used to compensate the Kalman filter for improvement of the prediction accuracy; (2) A low-confidence trajectory filtering method is adopted to reduce the influence of unreliable detection on target tracking. In addition, an visual servo controller for the UAV is designed to enable the automated tracking task. Finally, the system is tested using the Tibetan yaks living in the Tibetan Plateau as the tracking targets, and the results reveal the real-time multiple tracking ability and the ideal visual servo effect of the proposed system.

Highly macroporous thin films of WO₃ were fabricated on transparent conductive substrates by application of a polymeric organic paste loaded with an amine/tungstate complex. After spin-coating and annealing at 550^oC, the resulting yellow films are found to be comprised of channeled array of clustered nanoparticles. These channels are confirmed by scanning electron microscopy to extend through the entire length of the coating. The high porosity of the material enables the insertion of a co-catalyst into the internal structure of the film. These internally functionalized composites demonstrate good photosensitivity and stability in neutral electrolyte.

Genetically diverse influenza A viruses (IAV) circulates in wild aquatic birds with relatively frequent spillover (cases of single infections) to other mammals, but only a small proportion of outbreaks. The spillover of IAV to marine mammals such as seals have been reported throughout the last 45 years. Majority of these viruses when reached seals population cased pneumonia and death of infected animals. Until 2016, all avian influenza viruses found in seals were of low pathotype (LP) IAV. The H5Nx clade 2.4.4.4b highly pathogenic avian influenza viruses (HPAIV) were found in seals for the first time in 2016/2017. Our review highlights 45 years of AIV history in seals population, showing interesting features of different AIV subtypes and emphasis on avian-to-mammals transmission. Furthermore, we also included phylogenetic characterisation of the representative seal isolates.

In this work we introduce an end-to-end multi-modal neural network to segment the Gross Tumor Volume (GTV) from 3D-CBCT’s during radiotherapy. We improve the tumor segmentation by using a U-net which takes additional information such as the tumor mask generated at the planning phase along with the CBCT volume. The mask contains relevant information about the tumor’s location and can guide the model to use this knowledge appropriately to give a better prediction. This technique could become an alternative to produce segmentation masks of GTV in CBCT automatically during radiotherapy as in the traditional RT-pipeline, they are not segmented. We have evaluated our model on a dataset of 82 patients who have undergone radiotherapy. We compare the results of registered target volumes from planning CT as mask seed with 2 different types of multi-modal architectures. Our model shows a DSC of 0.706±0.002 with Late Fusion and 0.702±0.015 with Early Fusion using the GTV Mask. The performance of the two models on this mask is similar, so we perform further experiments with different types of masks which suggest that Late Fusion model produces a better segmentation of the tumor than the Early Fusion model. We also provide an ablation study consisting of a single modality U-net and a metric based on the Planning CT mask registration. It indicates a clear advantage of using our model to produce segmentation for this type of imaging.

Immunotherapy with stereotactic body radiotherapy (SBRT), low-dose antiangiogenics, immune adjuvants, nanomedicine, or other combinations will likely play a lead role in managing malignancies soon. Presently, its benefit extends to about 12% to 20% of patients, in the background of possible recurrence eventually and the toxicities, including in non-responders. Stereotactic body radiotherapy (SBRT) not only eliminates the indexed lesions, but recently, the evidence is accumulating about its systemic abscopal effects. It needs to be evolved to a dependable in situ therapeutic vaccine production and to activate short- and long-term memory immune lymphocytes. The in-situ immune cascade happens with the ability of SBRT to generate Tumor-specific neoantigens and neoepitopes, which enhance the activation of antigen-presenting cells, invoke and restore the competence of Tumor-infiltrating lymphocytes, resulting in cancer cell lysis. This cell lysis, in turn, can generate further neoantigens and epitopes, imparting a virtuous cycle that is the hallmark of effective vaccines. Additionally, SBRT can synergistically enhance the other in situ vaccination strategies, concurrent in vitro vaccines or nanomedicines, making it a primary tool for sensitizing even the “cold” tumors for immunotherapy. The present proposed hypotheses, primarily based on a preclinical literature review, focus on the critical aspects of the in-situ vaccination generation capability of SBRT when used in pulsed, cyclical, or intermittent endothelial-sparing single dose schedules along with immunotherapy and other supportive measures. This schedule is categorized as in situ vaccine dose (ISVD) radiotherapy (RT) (distinguishable from the standard therapeutic SBRT schedule) in metastatic cancer settings after standard /first-line therapies.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuiviruses, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and researches on phenuiviruses have made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and very important virus family.

Physicians often label anatomical structure sets in Digital Imaging and Communications in Medicine (DICOM) images with nonstandard names. As these names vary widely, the standardization of the nonstandard names in the Organs at Risk (OARs), Planning Target Volumes (PTVs), and 'Other' organs inside the area of interest is a vital problem. Prior works considered traditional machine learning approaches on structure sets with moderate success. This paper presents integrated deep learning methods applied to structure sets by integrating the multimodal data compiled from the radiotherapy centers administered by the US Veterans Health Administration (VHA) and the Department of Radiation Oncology at Virginia Commonwealth University (VCU). The de-identified radiation oncology data collected from VHA and VCU radiotherapy centers have 16,290 prostate structures. Our method integrates the heterogeneous (textual and imaging) multimodal data with Convolutional Neural Network (CNN)-based deep learning approaches like CNN, Visual Geometry Group (VGG) network, and Residual Network (ResNet). Our model presents improved results in prostate (RT) structure name standardization. Evaluation of our methods with macro-averaged F1 Score shows that our deep learning model with single-modal textual data usually performs better than the previous studies. We also experimented with various combinations of multimodal data (masked images, masked dose) besides textual data. The models perform well on the textual data alone, while the addition of imaging data shows that deep neural networks can achieve improved performance using information present in the other modalities. Additionally, using masked images and masked doses along with text leads to an overall performance improvement with the various CNN-based architectures than using all the modalities together. Undersampling the majority class leads to further performance enhancement. The VGG network on the masked image-dose data combined with CNNs on the text data performs the best and establishes the state-of-the-art in this domain.

Background: We aimed to assess the risk of chemotherapy- and radiotherapy-related cognitive impairment in colorectal cancer patients. Methods: We randomly selected 40% of colorectal cancer patients from Korean National Health Insurance Database (NHID), 2004-2018 (N=148,848). Patients with one or more ICD-10 diagnostic codes for dementia or mild cognitive impairment was defined as cognitive impairment cases. Patients who were aged 18 or younger, diagnosed with cognitive impairment before colorectal cancer (N=8,225) and did not receive primary resection (N=45,320) were excluded. The effects of each chemotherapy agent on cognitive impairment were estimated. We additionally estimated the effect of radiotherapy in rectal cancer patients. Time-dependent competing risk Cox regression was conducted to estimate overall and age-specific hazard ratios (HR) separately for colon and rectal cancer. Results: In colon cancer, capecitabine and irinotecan was associated with higher cognitive im-pairment, while 5-fluorouracil was not. In rectal cancer, no chemotherapy agents increased the risk of cognitive impairment, nor did radiotherapy. Hazardous association of irinotecan was estimated larger in elderly patients compared with younger counterparts. Conclusion: Heterogeneous associations between various chemotherapy agents and cognitive impairment were observed. Elderly patients were more vulnerable to possible adverse cognitive effects. Radiotherapy did not increase the risk of cognitive impairment.

Background: Radiotherapy plays an important role in the management and survival of patients with breast cancer. The aim of this study was to examine the association between age, comorbidities and use of radiotherapy in this population. Methods: Patients diagnosed with breast cancer from 2004–2013 were identified from the American College of Surgeons National Cancer Database (NCDB). Follow-up time was measured from the date of diagnosis (baseline) to the date of death or censoring. Adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) were used as the measure of association. Results: Independently of comorbidities and other important outcome-related factors, patients >65 years of age who received radiotherapy survived significantly longer than those who did not receive radiotherapy (aHR = 0.53, 95%CI = 0.52–0.54). However, as women aged, those with comorbidities were less likely to receive RT (adjusted P-trend by age <0.0001). Conclusions: The development of decision-making tools to assist clinicians, and older women with breast cancer and comorbidities, are needed to facilitate personalized treatment plans regarding RT. This is particularly relevant as the population ages and the number of women with breast cancer is expected to increase in the near future.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

Image-guided radiotherapy supported by surface guidance can help track lower lung lesion respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how skin respiratory motion magnitudes and correlations with lung lesion respiratory motion vary between different skin regions of interest (ROI). Four-dimensional Computed Tomography (4DCT) images provide information on both skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. Analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing lower lung lobe lesion, as well as respiratory motion correlations between nine ROIs and TS. The effects of gender and adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between ROIs in both respiratory motion magnitudes and correlations to TS have been detected. An overall negative correlation between ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. Respiratory magnitudes in regions without rib support tended to be larger for men than for women, but no differences in ROI-to-TS correlation between sexes have been detected. Described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

This review explores the unique structural and functional characteristics of natural products featuring highly oxygenated cyclobutane rings, with a specific focus on oxetane and 1,2-dioxetane motifs. It presents the structures and biological activities of compounds containing these rings, highlighting their contribution to molecular stability and pharmacological potency. Through detailed case studies and recent research findings, it has been demonstrated that these oxygen-rich rings enhance the molecular diversity and biological efficacy of natural products, potentially offering new avenues for drug development. Notably, these compounds are predominantly synthesized by microorganisms and can also be found in extracts from fungi, plants, and certain marine invertebrates. Compounds with oxetane and 1,2-dioxetane rings are primarily noted for their strong antineoplastic properties, among other biological activities. In contrast, most 1,2-dioxetanes exhibit potent antiprotozoal effects. It is important to note that 1,2-dioxetanes often serve as intermediate products in oxidation reactions, characterized by their instability and propensity to decompose into new compounds.

A highly efficient deep red (DR) emitting organic solid based on a dicyano-phenylenevinylene derivative was reported. The structural and spectroscopic properties of the solid have been described in terms of crystallographic data and time dependent DFT analysis. A noteworthy fluorescence quantum yield of 53% was observed for the brightest emitter cast into solid films. This result can be explained in terms of aggregation-induced emission (AIE) effect.

Backround: The purpose of this study was to evaluate the outcomes of different radiotherapy techniques used in routine clinical practice for the radical treatment of hypopharyngeal cancer and to assess improvements over the last few decades. Methods: We compared the outcomes of patients with hypopharyngeal squamous cell carcinoma treated with curative radiotherapy (RT) or chemoradiotherapy between January 1992 and December 2020, using 2D-RT, 3D-CRT/IMRT, and VMAT techniques. A retrospective analysis was conducted on eighty-one patients with hypopharyngeal cancer. Results: The median follow-up time was 26 months (range: 6-290). In multivariate analysis, radiotherapy technique, Karnofsky Performance Status (KPS), nodal stage, and clinical stage were identified as statistically significant factors affecting overall survival and local-regional relapse-free survival. Grade 2-4 early and late side effects were significantly more frequent in Group I patients (treated with 2D Conventional Radiotherapy) (20.3%) compared to Group II patients (treated with 3DCRT/IMRT and VMAT techniques) (3.1%) Conclusion: KPS, stage, and advanced RT techniques independently significantly affected outcomes. Moreover, advanced RT techniques were associated with a significant reduction in side effects.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

Recognizing highly occluded objects is believed to arises from the interaction between the brain's vision and cognition controlling areas, although supporting neuroimaging data is currently limited. To explore the neural mechanism during this activity, we conducted an occlusion object recognition experiment using functional magnetic resonance imaging (fMRI). During magnet resonance examinations, 66 subjects engaged in object recognition tasks with three different occlusion degrees. Generalized linear model (GLM) analysis showed that the activation degree of occipital lobe (inferior occipital gyrus, middle occipital gyrus, and occipital fusiform gyrus) and dorsal anterior cingulate cortex (dACC) was related to the occlusion degree of the objects. Multivariate pattern analysis (MVPA) further unearthed a considerable surge in classification precision when dACC activation was incorporated as a feature. This suggested the combined role of dACC and occipital lobe in occluded object recognition tasks. Moreover, psychophysiological interaction (PPI) analysis disclosed that functional connectivity (FC) between the dACC and the occipital lobe was enhanced with increased occlusion, highlighting the necessity of FC between these two brain regions in effectively identifying exceedingly occluded objects. In conclusion, these findings contribute to understanding the neural mechanisms of highly occluded objects recognition, augmenting our appreciation of how the brain manages incomplete visual data.

A microwave assisted method for synthesis of 2-substituted benzimidazoles has been developed. The combination of molar ratio N-phenyl-o-phenylenediamine:benzaldehyde (1:1) using microwave irradiation and only 1% mol of Er(OTf)3 provide an efficient, environmental and mild access to a diversity of benzimidazoles under solvent-free conditions.

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles, five-membered aromatic rings, emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazoles-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

We performed electronic research for articles published in PubMed, MEDLINE, and ScienceDirect databases from January 2004 to January 2023. The systematic review of twenty (20) peer-reviewed articles about dosimetric parameters and eight (8) articles about clinical outcomes confirmed the dosimetric advantages of ART through better target coverage and Organs at Risk (OARs) sparing, with subsequent benefits on decreased toxicity and improved clinical outcome, specifically local control of the disease. ART replanning is a sustainable strategy for minimizing toxicity by improving normal tissue sparing. Furthermore, it enhances target volume coverage by correctly determining the specific amount of dose to be delivered to the tumor. In conclusion, this review confirms that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Aiming at the problem of small size of some spots on apple leaves and the difficulty of accurate detection of spot targets brought by the complex background of the orchard, this paper takes the alternaria leaf spot, rust, brown spot, grey spot and frog eye leaf spot on apple leaves as the research object, and proposes a high-accuracy detection model YOLOv5-Res and lightweight detection model YOLOv5-Res4 are proposed. Firstly, a multiscale feature extraction module ResBlock is designed by combining the Inception multi-branch structure and ResNet residual idea. Secondly, a lightweight feature fusion module C4 is designed to reduce the number of model parameters while improving the detection ability of small targets. Finally, a parameter streamlining strategy based on optimized model architecture is proposed. The experimental results show that the performance of YOLOv5-Res model and YOLOv5-Res4 model is significantly improved, the [email protected] value is improved by 2.8% and 2.2% compared with YOLOv5s model and YOLOv5n model, respectively, and the size of YOLOv5-Res model and YOLOv5-Res4 model is only 10.8MB and 2.4MB, and the number of model parameters is reduced compared with YOLOv5s model and YOLOv5n model. counts are reduced by 22% and 38.3% compared to the YOLOv5s model and YOLOv5n model.

Abstract: Calcium-based catalysts are of a high interest for glycerol polymerization due to their high catalytic activity and large availability. However, their poor stability under reaction conditions is an issue. In the present study, we investigated the stability and catalytic activity of Ca-hydroxyapatites (HAps) as one of the most abundant Ca-source in nature. A stochiometric, a Ca-deficient and a Ca-rich HAps have been synthetized and tested as catalysts in the glycerol polymerization reaction. Deficient and stochiometric HAps exhibited a remarkable 100% selectivity to triglycerol at 15 % of glycerol conversion at 245 °C after 8 h of reaction in the presence 0.5 mol.% of catalyst. Moreover, under the same reaction conditions, Ca-rich HAp showed a high selectivity (88 %) to di- and triglycerol at a glycerol conversion of 27 %. Most importantly, these catalysts were unexpectedly stable towards leaching under the reaction conditions based on the ICP-OES results. However, based on the catalytic tests and characterization analysis performed by XRD, XPS, IR, TGA-DSC and ICP-OES, we found that HAps can be deactivated by the presence of the reaction products themselves, i.e., water and polymers.

The copper deposition on the platinum and palladium nanoelectrode has been studied using cyclic voltammetry. The use of nanoelectrode platinum and palladium are defined in the study of heavy metals. The noble nanoelectrode of metal has a typical silicone processing structure. In comparison to the nanoelectrodes, the geometry of the electrode series is complex and balanced. Nanoelectrodes of platinum are found effective in detecting heavy metal. There was regular analysis of the use of the sensors. The identification constraints down to the ng /L level was accomplished by refined electrode geometry and the stripping procedures. The process was used for the study of water sample determination. Another heavy metal ion attack voltammetric reaction was studied. The SEM picture clearly observed and characterized the nanoparticle electrode by X-ray diffraction and cyclic voltammetry.

More than 50% of patients with non-small cell lung cancer (NSCLC) are treated with radiotherapy (RT) during different phases of treatment. However, radiation pneu-monitis (RP) and resistance often lead to RT failure in NSCLC patients. JWA, a tumor suppressor gene, is known to enhance DNA damage in gastric cancer cells while protect normal cells from DNA damage induced by cisplatin. Recently, we have re-ported that JWA agonist compound 4 (JAC4) effectively protects intestinal epithelium from RT triggered damage in mice. However, the potential synergistic and attenuated effects of JAC4 in chest RT of lung cancer are not been illuminated. The aim of this study was to investigate the effects of JAC4 on the radiotoxicities of both NSCLC and normal lung tissue. CCK-8 and colony formation assays showed that JAC4 played a bidirectional role in radiation-treated SPCA-1 and BEAS-2B cells. Western blotting and immunofluorescence assays showed that JAC4 in combination with RT increased DNA damage and apoptosis in SPCA-1 cells, while the opposite effect was observed in BEAS-2B cells. Mechanistically, JAC4 inhibited homologous recombination repair (HR) and non-homologous end joining (NHEJ) in SPCA-1 cells, but not in normal cells. JAC4 increased antioxidant capacity, and reduced oxidative stress and inhibited nu-clear factor Kappa-B (NF-κB, P65) translocation to the nucleus in BEAS-2B cells. Im-portantly, the bidirectional roles of JAC4 on RT were reversed by siJWA in both SPCA-1 and BEAS-2B cells. Finally, the bidirectional effects of JAC4 in combination with RT were further validated in NSCLC xenograft model mice. In conclusion, JAC4 enhanced effect of RT on tumor growth while alleviated RP and lung injury. Our re-sults may provide new strategy for optimizing RT regimen for NSCLC.

Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient’s quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ at risk (OAR) avoidance structure, provider and patient reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p=0.0082) and hospitalization (p=0.0356) during and within 30 days of completing RT. Conclusion: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

The generalized dual-kinetic-balance approach for axially symmetric systems is employed to solve the two-center Dirac problem. The spectra of one-electron homonuclear quasimolecules are calculated and compared with the previous calculations. The analysis of the monopole approximation with two different choices of the origin is performed. Special attention is paid to the lead and xenon dimers, Pb82+–Pb82+–e− and Xe54+–Xe54+–e−, where the energies of the ground and several excited σ-states are presented in the wide range of internuclear distances. The developed method provides the quasicomplete finite basis set and allows for construction of the perturbation theory, including within the bound-state QED.

The interest in dry EEG electrodes has increased in recent years and especially as everyday suitability earplugs for measuring drowsiness or focus of auditory attention. However, the challenge is still the need for a good electrode material, which is reliable and can be easily processed for highly personalized applications. Laser processing as used here is a fast and very precise method to produce personalized electrode configurations that meet the high requirements of in-ear EEG electrodes, for example. The arrangement of the electrodes on the very flexible and compressible mats allows an exact alignment of the electrodes to the ear mold and contributes to a high wearing comfort, as no edges or metal protrusions are present. For better transmission properties, an adapted coating process for surface enlargement of platinum electrodes is used, which allows easy control of the thickness and growth form of the porous layer. The porous platinum-copper alloy is chemically very stable, shows no exposed copper residues and enlarges the effective surface area by 40. In a proof-of-principle experiment, these porous platinum electrodes could be used to measure the Berger effect in a dry state using just one ear of a test person. Their signal-to-noise ration and frequency transfer function is comparable to gel-based silver/silver chloride electrodes.

Opportunistic Routing is a promising paradigm that has been proposed for efficient and reliable transfer of data packets in mobile ad hoc networks. This routing strategy takes advantage of the broadcasting nature of the wireless medium to increase the number of probable forwarding devices and improves the reliability of data transfer in the network. Opportunistic Routing utilizes the reception of the same broadcasted packet at multiple devices in the network and selects one best forwarder dynamically from the set of multiple receivers. A number of opportunistic routing protocols have been proposed over these years for effective data delivery in ad hoc networks. But as the speed and mobility of devices increases in the network, performances of the existing opportunistic routing protocols degrade considerably, leading to reduced Quality of Service and poor transmission efficiency. The exceptional potential of opportunistic routing is thus underutilized. In this research we introduce Optimized Opportunistic Routing (OOR) strategy that guarantee excellent Quality of Service and high transmission efficiency to the latest applications using opportunistic routing for communication in highly dynamic ad hoc networks. Simulation results show that our method achieve significant performance improvements compared to all other existing opportunistic routing protocols in highly dynamic mobile ad hoc networks.

Over the years, scarcity of fresh potable water has increased the demand for clean water. Meanwhile, with the advent of nanotechnology, the use of nanomaterials for photocatalytic degradation of pollutants in wastewaters has increased. Herein, a new type of nanohybrids of La and Mn co-doped bismuth ferrite (BiFeO₃) nanoparticles embedded into transition metal carbide sheets (MXene) were prepared by a low-cost double solvent sol-gel method, and investigated for their photocatalytic activity. The photoluminescence results showed that pure BFO has highest electron hole recombination rate as compared to all the co-doped BFO/MXene nanohybrids. The larger surface area and higher electron-hole pair generation rate provides suitable environment for fast photo-degradation of organic molecules. The band gap of the prepared nanohybrids was tuned to 1.96 eV having largest BiFeO₃ surface area (147 m²g⁻¹) reported till date. Moreover, the BLFO/MXene and BLFMO-5/Mxene degraded the 92% organic pollutant from water in dark and remaining in light spectrum as compare to undoped BFO/Mxene due to enhancement of the surface area and electron-hole recombination rate upon doping. Therefore, these synthesized nanohybrids could be a promising candidate for photocatalytic applications in future.

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85-90Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemotherapy (total dose 60-65Gy at point A), followed by surgery which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated patients compared to 62% for non-operated patients receiving suboptimal concurrent chemotherapy alone. In conclusion, In Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.

Radiotherapy, also known as radiation therapy, is a treatment modality based on the use of high energy rays or radioactive substances, to damage tumoral cells and halt their growth and division. It is an effective tool for treating cancer of different kinds for more than 100 years with remarkable outcomes for cancer patients. This technique is characterised by notable technological innovations and methodologies, enhanced precision and effectiveness. Initially, precision and efficacy of radiotherapy are improved by technological advancements, such as the development of linear accelerators and brachytherapy. As a result, Radiotherapy has transformed the prognosis for cancer patients enhancing survival rates and improving quality of life. Also, it offers targeted and personalized treatment with advancements in imaging techniques such as Intensity-Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT) and innovations like Image-Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART) and Artificial Intelligence (AI). Additionally, techniques like proton therapy result in reduced side effects and collateral damage. Although, among the challenges and future perspectives we note the issue of affordability and accessibility. Ongoing research into immunotherapy and nanotechnology and their synergy with radiation therapy shows potential for further improving treatment outcomes. In conclusion, the evolution of radiotherapy has been a transformative journey, reshaping the prognosis and outcomes for cancer patients.

Predicting nurse turnover is a growing challenge within the healthcare sector, profoundly impacting healthcare quality and the nursing profession. This study employs the Synthetic Minority Over-sampling Technique (SMOTE) to address class imbalance issues in the 2018 National Sample Survey of Registered Nurses (NSSRN) dataset and predict nurse turnover using machine learning (ML) algorithms. Four ML algorithms, namely logistic regression (LR), random forests (RF), decision tree (DT), and extreme gradient boosting (XGBoost), are applied to the SMOTE-enhanced dataset. The data is randomly split into an 80% training set and a 20% validation set. Eighteen carefully selected variables from the NSSRN database serve as predictive features, and the machine learning model identifies feature importance concerning nurse turnover. The study includes a performance comparison based on metrics such as Accuracy, Precision, Recall (Sensitivity), F1-score, and AUC. In summary, the results demonstrate that SMOTE-enhanced random forests (SMOTE_RT) exhibit the most robust predictive power, both in the classical approach (with all 18 predictive variables) and an optimized approach (utilizing eight key predictive variables). XGBoost, decision tree, and logistic regression follow in performance. Notably, age emerges as the most influential factor in nurse turnover, with working hours, EHR/EMR usability, individual income, and region also playing significant roles. This research offers valuable insights for healthcare researchers and stakeholders, aiding in selecting suitable ML algorithms for nurse turnover prediction.

Global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries with high dengue endemicity (>1.5 million cases/year) are observably less hit by COVID-19 in terms of infection, transmission and mortality. Based on non-overlap of dengue and COVID-19 severity maps and evidence of SARS-CoV-2 serological cross-reactions with dengue, we wonder whether immediate immunization of susceptible populations in Europe, North America and Asia (China, Iran) with available live-attenuated dengue vaccines, will cue the anti-viral immune response to thwart COVID-19 (viral interference). Risk of developing post-vaccination “Antibody-dependent Enhancement” is low as dengue is not endemic in the aforesaid regions.

Compounds with tyrosinase inhibitory efficacy could be effective as depigmenting agents. Although a large number of natural and synthetic tyrosinase inhibitors have been reported, few of them are used as skin-whitening agents due to poor activity and safety concerns. 3-(2,4-Dihydroxyphenyl)propionic acid (DPPA), a naturally occurring compound isolated from Ficus carica, was previously discovered as a moderate tyrosinase inhibitor. In this study, the structure-activity relationship study of DPPA was conducted. Compound 3g, with the 2,4-resorcinol subunit and terminal hydrophobic di-butylamino group, was identified with low nanomolar enzymatic IC₅₀ value. Additionally, compound 3g could effectively reduce melanin levels in B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH) without affecting cell viability and proliferation. All these results indicated that compound 3g could be considered as a promising candidate for the treatment of diseases associated with hyperpigmentation.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.