Search

While stereotactic body radiation therapy (SBRT) or hypofractionated radiation therapy (HFRT) is routinely used to treat early-stage non-small lung cancer (esNSCLC) patients with peripheral tumors, SBRT or HFRT for central (cenT) and ultracentral tumors (UCT) remains controversial. To treat patients with tumors located within 0.5 cm to 2 cm of critical mediastinal structures, we often utilize an institution-specific hypofractionated regimen (isHFR) using 17 fractions to a dose of 6987 cGy. Our study seeks to evaluate the safety and efficacy of this fractionation scheme, while comparing patients' adverse-event free survival (AEFS), overall survival (OS), and progression free survival (PFS) outcomes to historical data. We conducted a single-institution retrospective review of patients with eNSCLC treated with isHFR between 2011 and 2019, evaluating rates of Grade 2 or higher hemoptysis (HP), bronchial stricture or necrosis (BSN), radiation pneumonitis and cardiotoxicity (CardT) based on CTCAE criteria. Kaplan Meier survival models were created to assess OS, AEFS and PFS in cenTs and UCTs. Differences were assessed using log-rank tests. Relative frequencies for categorical variables of interest were also dichotomized by tumor centrality and then compared using Fisher's Exact tests while continuous variables of interest were compared using Wilcoxon Rank Sum Tests. Of the 32 patients evaluated, 62.5% of patients enrolled had UCTs while 37.5% of enrolled patients had cenTs. The rate of locoregional control was noted to be 87.5% while rate of distant control was 78.1%. The probability of survival at 1 year was noted to be 75.0% while median OS was 19.3 months, 95% CI [13.94, 29.42]. Median OS for cenTs was 21.2 months and 18.2 months for UCTs, 95% CI [5.13, 31.76] and [11.77, 31.43] (p = 0.7706). AEFS at 12 months was 68.8%. 2 patients (6.3% of the cohort) experienced Grade 5 toxicity with 1 UCT patient experiencing Grade 5 BSN and the other cenT patient experiencing Grade 5 HP. Our patient who experienced BSN did so about 9 months following treatment and had noted PET avid recurrent disease in the mediastinum. The second patient experienced G5 hemoptysis approximately 1 year following treatment. The patient's most recent CT scan demonstrated post-radiation changes, although recurrent disease could not be excluded. She was scheduled for a PET CT but expired shortly before this study was performed. Only 1 patient (3.1% of the cohort) experienced CardT, a myocardial infarction, approximately 3 years following treatment. While this patient did not have a known coronary artery disease, he did have significant risk factors including hypertension and hyperlipidemia, as well as a strong family history. Our isHFR for patients with esNSCLC proves a safe and effective treatment for medically inoperable esNSCLC patients with cenTs and UCTs with comparable rates of toxicity when compared to historical norms, as well as notably low rates of cardiotoxicity. [ABSTRACT FROM AUTHOR]

Older patients with hormone receptor-positive, HER2-negative, early-stage breast cancer (HPEsBC) are routinely treated with breast-conserving surgery (BCS) followed by adjuvant radiation therapy (RT), oral endocrine therapy (ET), or both. However, for patients who are unable to complete a full 5-year course of ET, RT may improve oncologic outcomes. Our study of HPEsBC was undertaken to identify predictors of low ET compliance and to assess the role of RT in altering survival for older ET low-compliant patients. Using the nationwide Flatiron Health electronic health record-derived de-identified database, patients ≥ 65 years old with clinical or pathologic T1-2N0 HPEsBC treated with BCS from 2011-2018 were reviewed. Four adjuvant groups were identified: ET, RT, ET + RT, and no therapy. A 60-day landmark Kaplan-Meier (KM) curve and Cox proportional hazards model were used to compare OS. Low ET compliance was defined as ET taken for <4 years (compliance < 80%). Multinomial logistic regression then isolated predictors of ET compliance. Using the Cox model with ET compliance as a time-varying covariate, hazard ratios for compliance and radiation were determined while adjusting for age, race, ethnicity, socioeconomic status quintile, insurance, clinic visits, practice type, ECOG, tumor grade, and histology. The study group included 1,488 HPEsBC patients (354 ET, 118 RT, 894 ET + RT, and 122 no therapy). Low compliance was recorded for 287 of 1248 ET-treated patients (23%). In an unadjusted analysis, median OS (mOS) was greater for patients treated with ET + RT than for patients receiving ET alone, RT alone, or no therapy (mOS not reached, mOS 125.1 mos, mOS 120.3 mos, mOS 97.4 mos, respectively; P <0.001). When the effect of treatment was adjusted for all covariates, mortality was greater for RT alone and no therapy than for ET + RT (HR = 1.77, P = 0.011; HR = 2.53, P <0.001, respectively). Increasing age and treatment at an academic practice (vs community) were associated with low ET compliance (OR = 1.06, P <0.010; OR = 2.58, P <0.001, respectively). The Cox model with a time-varying covariate demonstrated an increased risk of mortality when ET compliance declined 10% (HR = 1.17, P <0.001). An interaction between compliance and RT showed no differential effect of radiation based on levels of compliance. Low compliance was observed in almost 1 in 4 HPEsBC patients ≥ 65 years old and was associated with advancing age and treatment at an academic center. Declines in ET compliance as small as 10% were associated with significantly increased mortality. Further study to identify a possible survival benefit from RT for elderly HPEsBC patients with ET compliance levels much lower than 80% is warranted. [ABSTRACT FROM AUTHOR]

The paper presents a comparison of the nitrided layer structure and morphology formed with a conventional controlled gas method, widely use in industrial applications and a layer formed with cathode plasma nitriding (CPN) and active screen plasma nitriding (ASPN). Nitriding processes were realized at 793K for different times and altering parameters, depending on the nitriding process technique. Research have been realized on the Fe Armco material using light microscopy (LM), scanning electron microscopy (SEM, SEM/EBSD), X-ray diffraction (XRD-GID) and atomic force microscopy (AFM). Analysis of the results has confirmed that the structure of the nitrided layer depends mainly on process methodology. In addition Authors has also analyzed kinetics of the process which varies and depends mainly from the surface layer saturation mechanism and nitriding parameters. Acquired knowledge on the structural components of the nitrided layer made it possible to optimize the nitriding parameters in order to reduce or even eliminate the usually unfavorable, brittle compounds and porous zones and of the nitrided layer in the aspect of exploitation properties improvement of the metallic materials. [ABSTRACT FROM AUTHOR]

Biliary tract cancers (BTC) are rare and aggressive malignancies originating from intrahepatic and extrahepatic bile ducts and the gallbladder. Surgery is the only curative option, but due to late-stage diagnosis, is frequently not feasible, leaving chemotherapy as the primary treatment. Radiotherapy (RT) can be an effective alternative for patients with unresectable, non-metastatic BTC despite the generally poor prognosis and significant variability. We aimed to identify prognostic markers that could aid in predicting overall survival (OS) and guide patient management. A retrospective cohort study of 78 patients with unresectable BTC treated with definitive intent RT was conducted at a single institution. Comprehensive demographic, clinical, and treatment-related data were extracted from the electronic medical records. Univariate and multivariate Cox regressions were employed to identify OS predictors. A biomarker model was developed for refined survival prediction. The cohort primarily comprised patients with good performance status without significant hepatic dysfunction at presentation. The predominant treatment approach involved hypofractionated RT or concurrent 5-fluorouracil-based chemoRT. Median OS was 12.3 months, and 20 patients (15.6%) experienced local progression with a median time of 30.1 months. Univariate and multivariate analyses identified CA19-9 (above median) and higher albumin-bilirubin (ALBI) grades at presentation as significant predictors of poor OS. Median OS was 24 months for patients with no risk factors and 6.3 months for those with both. Our study demonstrates generally poor but significantly heterogeneous OS in patients with unresectable BTC treated with RT. We have developed a biomarker model based on CA19-9 and ALBI grade at presentation that can distinguish sub-populations with markedly diverse prognoses. This model can aid the clinical management of this challenging disease. [ABSTRACT FROM AUTHOR]

This study determines the possibilities of synthesis of porous glass-ceramic materials based on Bioglass 45S5 using different methods obtained porous materials. In this work used foaming with sintering method for the set: bioglass 45S5 + glass cullet (CRT) + glass water (WG) and method sintering with forming-pore agents for the: bioglass + glass water (WG) + dried banana peels. The sets were melting and the next step sintering process. The resulting foams were examined and analysed for structural, microstructural, and physical properties. The research allowed for a quantitative and qualitative assessment of the foaming process generated by the presence of WG with the addition of CRT cullet and WG together with dried banana peel. It was found that WG with the addition of CRT cullet was a solution that offered the possibility of obtaining a large number of evenly distributed pores and higher total porosity compared the second set (WG + banana peel). Moreover, the use of CRT cullet and banana peel allowed the introduction of biogenic elements such as strontium, barium and potassium into the obtained materials, which have a positive effect on the stimulation of osteogenesis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In this study, the vitrification of asbestos-cement waste (ACW) and glass cullet from cathode-ray tubes (CRTs) was performed. The resulting product of vitrification from the abovementioned waste was used as the reinforcing phase in a composite with the AA7075 alloy matrix. The composite was made by means of the FSP (friction stir processing) method. The main aim of this work was to determine whether the product of the vitrification can be utilized as the reinforcing phase in the composite. The tests show that introducing the vitrification product into the composite matrix increases both the hardness of the material and its wear resistance. The composite was characterized by a 39% higher hardness and 30.4% higher wear resistance compared to the initial AA7075 alloy. The changes in the properties were caused by strong refinement of the grains, but primarily by the presence of the hard particles of the reinforcing phase in the composite matrix. This research demonstrates that vitrified material, thanks to its properties, can constitute a full-value reinforcing material that can ultimately replace more expensive engineering materials in composites.

Synapses are organized into nanocolumns that control synaptic transmission efficacy through precise alignment of postsynaptic neurotransmitter receptors and presynaptic release sites. Recent evidence show that Leucine-Rich Repeat Transmembrane protein LRRTM2, highly enriched and confined at synapses, interacts with Neurexins through its C-terminal cap, but the role of this binding interface has not been explored in synapse formation and function. Here, we develop a conditional knock-out mouse model (cKO) to address the molecular mechanisms of LRRTM2 regulation, and its role in synapse organization and function. We show that LRRTM2 cKO specifically impairs excitatory synapse formation and function in mice. Surface expression, synaptic clustering, and membrane dynamics of LRRTM2 are tightly controlled by selective motifs in the C-terminal domain. Conversely, the N-terminal domain controls presynapse nano-organization and postsynapse AMPAR sub-positioning and stabilization through the recently identified Neurexin-binding interface. Thus, we identify LRRTM2 as a central organizer of pre- and post- excitatory synapse nanostructure through interaction with presynaptic Neurexins., (© 2024. The Author(s).)

Objective: Childhood cancer survivors are at risk for hypogonadism. The impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown; however, the relationship among the childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors., Design: Cross-sectional study using retrospective cohort., Methods: In total, 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, and global cognition) and self-reported emotional distress were included in our study. Participants were stratified by sex and gonadal status. Outcomes were compared between hypogonadal and eugonadal groups by multivariable analysis, adjusting for established predictors, and mediation analyses to determine the direct/indirect effects of hypogonadism on outcomes., Results: The hypogonadal group exhibited a higher prevalence of neurocognitive impairment across domains, but no difference in emotional distress. Hypogonadal females exhibited higher relative risk (1.7, 95% CI, 1.2-2.5) for impaired visual processing speed, compared to eugonadal females after adjusting for cancer-related variables. In mediation models, hypogonadism had a significant direct (P < .01) and indirect (from P < .01) impact on impairment in visual processing speed among females. Males demonstrated direct (P = .03) and indirect (P = .04) impact of hypogonadism on motor processing speed., Conclusion: Processing speed may be the most vulnerable neurocognitive domain associated with hypogonadism in survivors, while other domains were mainly impacted by cancer-related variables. Our findings support the need for further evaluation of the impact of sex hormone replacement therapy on neurocognitive function., Competing Interests: Conflict of interest: None of the authors have any conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The paper presents research on multicomponent glasses obtained from natural and secondary raw materials, i.e., basalt, amphibolite, and cullet. The raw materials were used as potential sets to produce mineral fibres or glass-ceramic materials. FTIR spectroscopy and XRD studies were carried out to identify the composition of the phase type in the glass sets. The results were supported by SEM-EDS microstructural studies of the obtained materials. The ability of the melts to crystallize and their basic properties required in producing mineral fibres, i.e., the hardness and the acidity modulus, were also determined. In the glass samples after the crystallization process, the spectroscopic studies revealed an increase in the half-width of the band at 1200-800 cm -1 and splitting at the values of about 870 cm -1 and 970 cm -1 . These changes probably indicate the formation of pyroxene-type crystalline phases. Moreover, based on the XRD results, it was confirmed that the obtained materials were fully amorphous. After annealing at 800 °C for 2 h, the materials show a small proportion of crystalline phases. For the materials annealed at higher temperatures, clear peaks from the crystalline phases were represented mainly by pyroxenes. The proportion of crystalline phases in the samples was also found to rise with increasing temperature, and the hardness values for the basalt glasses and glasses after crystallization rose from 753 to 946 HV0.05. Such an effect positively affects the properties of the obtained glass-ceramic materials based on the proposed sets. However, in the case of mineral fibres, crystallization at early 2 h at 800 °C can be a disadvantageous feature from the point of view of their application because crystalline phases can lead to fibre damage after a short period of operation; this will be confirmed in this study.

The paper presents the results of studies on the viscosity of the glass mass in various temperature ranges, determining the basic technological parameter, very important from the point of view of melting and forming. For this purpose, six sets based on natural raw materials such as basalt, dolomite, and amphibolite, modified with different amounts of float glass cullet, were melted. The melting process was carried out in an electric furnace at the temperature of 1450 °C for 2 h. Using the dilatometric method, high-temperature microscopy and theoretical calculation methods, the viscosity of the produced glasses was determined in various temperature ranges. Comparative analyses of the employed methods were carried out. The significance of the applied calculation methods for aluminosilicate glasses depending on the basic chemical composition of the glasses was presented. The relationship between the manner of incorporating amphoteric ions Al 3+ , Fe 3+ and Mg 2+ into the glass structure and the change in viscosity in the temperature range corresponding to the working point range at 10 4 [dPa·s] viscosity and the relaxation range- T g temperature at 10 13 [dPa·s] viscosity was justified. It was justified that in order to plot the viscosity curve with the correct slope in the forming range for aluminosilicate glasses, it is appropriate to use the two-point method based on the fixed viscosity points of 10 4 [dPa·s] and 10 13 [dPa·s].

Introduction: New low-cost technologies are needed to salvage lost blood in low-resource settings and large animal laboratories. The Hemafuse device is a simple mechanical device that can recover lost blood during surgery. The aim of this study is to assess the feasibility of this device for resuscitating large animals with controlled and unintended hemorrhage and to provide device considerations for use in this context., Methods: This study had two experimental components: (1) the Hemafuse device was kept on-shelf and used as needed to assess real-world use for unintended hemorrhage during experiments, and (2) animals underwent a controlled hemorrhage protocol, where four anesthetized swine underwent aortic and external jugular vein catheterization for pressure monitoring. Animals were hemorrhaged into the pelvis, and the Hemafuse device was used to suction the blood through a filter and pushed into a heparinized bag for subsequent retransfusion. Blood samples were collected at baseline, hemorrhage, within the device, and post-retransfusion and laboratory tests were performed., Results: Animals that underwent controlled hemorrhage had a baseline mean arterial pressure of 83.6 ± 7.8 mmHg, and central venous pressure of 12.8 ± 1.9 mmHg, with expected changes throughout hemorrhage and resuscitation. Following resuscitation, pH was similar to baseline (7.39 ± 0.05 vs. 7.31 ± 0.03, p = 0.24). Lactate increased throughout the experiment with no significant differences after autotransfusion compared to baseline (2.7 ± 0.7 vs. 4.1 ± 1.4 mmol/L, p = 0.37). There were no significant changes in metabolic physiology. Compared to baseline, the hemoglobin (7.8 ± 2.4 vs. 7.3 ± 1.8 g/dL, p = 0.74), hematocrit (23% ± 6.9 vs. 21.3% ± 5.6, p = 0.71), and activated clotting time (268.5 ± 44.5 vs. 193 ± 24.6 s, p = 0.35) were similar after retransfusion. When used for unintended hemorrhage, the animals were resuscitated using the device with a mean time to retransfusion time of 128.7 ± 13.3 s and 100% survival throughout the experiment., Conclusion: The Hemafuse device is feasible and efficacious for supporting large animal resuscitation. This is preliminary evidence that the device is a low-risk and low-cost off-the-shelf option for resuscitation using autologous blood with no significant effect on physiology post-retransfusion. We recommend that research laboratories consider the Hemafuse device for emergency use, particularly for highly invasive surgical laboratories where banked blood is not readily available., Competing Interests: DS receives payments from Catalio Capital Management LP for investment analysis. Sisu Global Health is a Catalio portfolio company. ML is an employee of Sisu Global Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Treffalls, Lubas, Morrison and Stonko.)

Colorectal carcinoma is the leading cause of cancer-related death. Previously we have shown that tumor suppressor single immunoglobulin interleukin-1-related receptor (SIGIRR) is frequently inactivated in human colorectal cancer by the increased expression of a novel SIGIRR isoform (SIGIRR ΔE8 ). SIGIRR ΔE8 showed increased retention in the cytoplasm and loss of complex glycan modification compared to the full-length SIGIRR. Now we found that the arginine residues located in the C-terminus of SIGIRR ΔE8 serve as an endoplasmic reticulum retention signal and are required for resident protein ribophorin 1 (RPN1) interaction. In addition, we found that SIGIRR ΔE8 exerts a direct impact on cell metabolism through interaction with the adenosine triphosphate synthase in the colorectal cancer cells. SIGIRR ΔE8 expression promoted the metabolic shift through upregulation of mammalian target of rapamycin signaling pathway and dysregulation of mitochondrial function to promote survival and proliferation of colon cancer cells in xenograft model.

The structure and properties of the glass can be modified by introducing appropriate additives. Dolomite is one of the primary raw materials modifying the properties of glass, in which the essential component is calcium-magnesium double carbonate CaCO 3 ∙MgCO 3 . The paper presents the research results on glasses obtained by smelting pure amphibolite and amphibolite modified with 10 and 20% dolomite additives. The raw material used was mined in the Poland region of Lower Silesia. The glass melting process was carried out in an electric furnace at 1450 °C for 2 h. The structure and properties of the glasses and crystallization products were determined by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS). Viscosity and Vickers microhardness were also measured. It was found that the modification of amphibolite glass by adding dolomite affects the glasses' properties and structure. The research results determined the effect of dolomite addition on the properties of alumino-silicate glasses in terms of the mineral fibre products used in the construction industry.

Factors released from glioma-associated microglia/macrophages (GAMs) play a crucial role in glioblastoma multiforme (GBM) progression. Here, we study the importance of CCL18, a cytokine expressed in human but not in rodent GAMs, as a modulator of glioma growth. Since CCL18 signaling could not be studied in classical mouse glioma models, we developed an approach by transplanting induced pluripotent stem cell-derived human microglia and human glioma cells into mouse brain slices depleted of their intrinsic microglia. We observe that CCL18 promotes glioma cell growth and invasion. Chemokine (C-C motif) receptor 8 (CCR8) is identified as a functional receptor for CCL18 on glioma cells, and ACP5 (acid phosphatase 5) is revealed as an important part of the downstream signaling cascade for mediating glioma growth. We conclude, based on the results from an in vitro, ex vivo humanized glioma model and an in vivo GBM model that microglia/macrophage-derived CCL18 promotes glioma growth., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The metal-ceramic interface requires proper surface preparation of both metal and ceramic substrates. This process is complicated by the differences in chemical bonds and physicochemical properties that characterise the two materials. However, adequate bond strength at the interface and phase composition of the titanium-bioceramics system is essential for the durability of dental implants and improving the substrates' functional properties. In this paper, the authors present the results of a study determining the effect of mechanical and chemical surface treatment (sandblasting and etching) on the strength and quality of the titanium-low-fusing dental porcelain bond. To evaluate the strength of the metal-ceramic interface, the authors performed mechanical tests (three-point bending) according to EN ISO 9693 standard, microscopic observations (SEM-EDS), and Raman spectroscopy studies. The results showed that depending on the chemical etching medium used, different bond strength values and failure mechanisms of the metal-ceramic system were observed. The analyzed samples met the requirements of EN ISO 9693 for metal-ceramic systems and received strength values above 25 MPa. Higher joint strength was obtained for the samples after sandblasting and chemical etching compared to the samples subjected only to sandblasting.

During autophagy, the coordinated actions of autophagosomes and lysosomes result in the controlled removal of damaged intracellular organelles and superfluous substrates. The evolutionary conservation of this process and its requirement for maintaining cellular homeostasis emphasizes the need to better dissect the pathways governing its molecular regulation. In our previously performed high-content screen, we assessed the effect of 1530 RNA-binding proteins on autophagy. Among the top regulators, we identified the eukaryotic translation initiation factor 4A-3 (eIF4A3). Here we show that depletion of eIF4A3 leads to a potent increase in autophagosome and lysosome biogenesis and an enhanced autophagic flux. This is mediated by the key autophagy transcription factor, TFEB, which becomes dephosphorylated and translocates from the cytoplasm to the nucleus where it elicits an integrated transcriptional response. We further identified an exon-skipping event in the transcript encoding for the direct TFEB kinase, GSK3B, which leads to a reduction in GSK3B expression and activity. Through analysis of TCGA data, we found a significant upregulation of eIF4A3 expression across several cancer types and confirmed the potential relevance of this newly identified signaling axis in human tumors. Hence, our data suggest a previously unrecognized role for eIF4A3 as a gatekeeper of autophagy through the control of TFEB activation, revealing a new mechanism for autophagy regulation., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)