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Background: Pericentric human satellite II (HSATII) and III (HSATIII) have been shown to be associated with stress response. Expression status of these satellite repeats has not yet been investigated under radiation-induced genotoxic stress. We evaluated the HSATII and HSATIII expression changes under genotoxic stress in cancer cells. Materials and Methods: Cell line MCF-7 and cell line HCT-15 were irradiated with 2 and 5 Gy of ionizing radiation, and cell death rates, as a consequence of genotoxic stress, were determined by flow cytometry. The expression of HSATII and HSATIII expressions was assessed by RT-qPCR. Results: Radiation exposure induced a considerable level of cell death in a dose-dependent manner in both cell types. Compared to untreated cells, HSATII expression declined in MCF-7 cells which were exposed to 2 and 5 Gy radiation, respectively. In HCT-15 cells, the effect of radiation on the HSATII expression was not unified; only higher radiation dose led to a decrease of HSATII expression while 2 Gy increased HSATII expression. The effect of radiation on the HSATIII repeat expression was more pronounced in HCT-15 cells: in MCF-7 cells, HSATIII expression was decreased by 2- and 5-Gy, respectively (p=0.01). In the HCT-15 cells, the rates of HSATIII down-regulation were 3-fold and 2.8 fold by 2- and 5 Gy (p=0.0002 and p=0.02, respectively). Conclusion: Our findings reveal that genotoxic stress induced by ionizing radiation is associated with a decrease in the expression of pericentric satellites and the expression status of HSATII in these conditions may be dose- and/or cellular context-specific. [ABSTRACT FROM AUTHOR]

There are significant technical challenges/shortcomings in recovering gold from thiosulphate leach solutions. This study presents a new approach for the recovery of gold from ammoniacal thiosulphate leach solutions using an environmentally friendly organo-sulphide reagent, trimercapto- s -triazine (TMT; C 3 N 3 S 3 3−). Precipitation of gold by TMT was investigated using synthetic gold and multi-metal solutions (Au-Ag, Au-Cu, Au-Ag-Cu) to investigate the effect of the co-presence of metals commonly present in thiosulphate leach solution. The effect of TMT concentration (by up to 115 mM), temperature (25–60 °C) and ammonia (0.25–1 M NH 3) on the precipitation of gold was also investigated. The results showed that gold precipitation with TMT was relatively low (i.e., limited to only 37.7% over 15 min) from the solution containing only gold. However, the presence of silver and/or copper significantly improved the precipitation of gold. Silver concentrations at ≥20 mg/L led to a complete recovery of gold in 15 min, producing stable gold precipitates. The results have also indicated that silver readily precipitates when compared to gold. The effectiveness of the TMT precipitation process was also tested on a real leach solution from which complete recovery of gold and silver was readily achieved. The findings demonstrated that gold could be readily but unselectively recovered by precipitation with TMT from ammoniacal thiosulphate leach solutions containing silver, in particular, at the expense of co-precipitation of other metals such as copper and zinc. • Au recovery from thiosulphate solutions by precipitation with TMT is remarkably low • Au recovery is substantially enhanced in the presence of Ag and/or Cu • Ag is readily recovered by precipitation with TMT • Temperature adversely affects Au recovery • Au and Ag can be completely recovered from pregnant leach solutions by TMT [ABSTRACT FROM AUTHOR]

The prognosis of patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (SCC) is poor (median overall survival [OS] 10–13 mo), and effective treatments are needed. The cell-adhesion molecule Nectin-4 is expressed in a majority of HNCs. EV is a Nectin-4–directed antibody–drug conjugate approved as monotherapy in previously treated locally advanced or metastatic (la/m) urothelial carcinoma (UC) and, in the US, with pembrolizumab for previously untreated la/mUC ineligible for cisplatin. EV was evaluated in previously treated HNC in EV-202 (NCT04225117). In this open-label phase 2 study, pts with la/m solid tumors enrolled in tumor-specific cohorts. In this cohort, pts had HNC not amenable to curative-intent treatment, radiographic progression on/after the last regimen, progression/relapse/discontinuation for toxicity after 1 platinum-based therapy for la/m disease, and ≤2 lines of cytotoxic therapy in the la/m setting. Pts had received prior programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor unless contraindicated. Pts received intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-d cycle (C) until disease progression or discontinuation criteria were met. Primary endpoint was confirmed objective response rate (ORR) per investigator assessment. Secondary endpoints were duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) per investigator assessment; OS; and safety/tolerability. Exploratory endpoints included immunogenicity, pharmacokinetic parameters, and pt-reported outcomes. As of April 11, 2022, 46 pts were enrolled; median follow-up was 9.3 mo. Median age was 65 y, 87.0% of pts were men, and 52.2% had ≥3 prior lines of systemic therapy in the metastatic setting. Forty-five pts had SCC; 1 had adenocarcinoma. Confirmed ORR was 23.9%; DCR was 56.5%. Median time to response was 1.7 mo. Median DOR was not estimable. Median PFS and OS were 3.9 and 6.0 mo, respectively. Common treatment-related adverse events (TRAEs) were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Grade ≥3 TRAEs occurring in >1 pt were anemia and decreased neutrophil count (both n=2). TRAEs of special interest were skin reactions (45.7%), peripheral neuropathy (32.6%), dry eye (6.5%), and hyperglycemia (4.3%). No antitherapeutic antibodies against EV were detected. Serum EV decreased substantially from end-of-infusion concentrations before subsequent doses in C1, while plasma concentration of free monomethyl auristatin E (drug component of EV) remained high between days 1 and 15 of C1. Median global pain assessment score was 4/10 at baseline, with numeric reduction in scores (indicating pain improvement) in C3 and beyond. EV demonstrated antitumor activity with manageable AEs in pts with heavily pretreated HNC post-platinum and PD-1/L1 inhibitor. [ABSTRACT FROM AUTHOR]

An amine-based microextraction method was established for preconcentration of mercury by forming a 1-(2-pyridylazo)-2-naphthol (PAN) chelate complex. The Hg (II)-PAN hydrophobic complex was extracted into the N,N-dimethyl-n-octylamine phase at pH 9.5, after the pre-concentration of Hg (II), the absorption spectrum was taken with UV–Vis spectrophotometer at 555.0 nm. The effects of important analytical parameters such as pH, PAN amount, N,N-dimethyl-n-octylamine volume, sample volume and matrix effects for quantitative recovery were investigated and optimized. 0.05% (w/v) PAN volume, N,N-dimethyl-n-octylamine volume, vortex time and centrifugation time were optimized as 0.4 mL, 0.1 mL, 1 min and 15 min, respectively. The validity of the developed liquid phase micro-extraction method was checked by standard addition-recovery experiments. The presented microextraction method was successfully applied for mercury determination in natural water samples. The mercury concentration in natural water samples ranged from 0.20 to 1.42 µg mL-1. The limit of detection (LOD), limit of quantification (LOQ) and preconcentration factor (PF) were found as 0.035 μg L−1, 0.12 μg L−1 and 26.67, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Instability of the posterior pelvic ring may be stabilized by lumbopelvic fixation. The optimal osseous corridor for iliac screw placement from the posterior superior iliac spine to the anterior inferior iliac spine requires multiple ap- and lateral-views with additional obturator-outlet and -inlet views. The purpose of this study was to determine if navigated iliac screw placement for lumbopelvic fixation influences surgical time, fluoroscopy time, radiation exposure, and complication rates. Methods: Bilateral lumbopelvic fixation was performed in 63 patients. Implants were inserted as previously described by Schildhauer. A passive optoelectronic navigation system with surface matching on L4 was utilized for navigated iliac screw placement. To compare groups, demographics were assessed. Operative time, fluoroscopic time, and radiation were delineated. Results: Conventional fluoroscopic imaging for lumbopelvic fixation was performed in 32 patients and 31 patients underwent the procedure with navigated iliac screw placement. No differences were found between the groups regarding demographics, comorbidities, or additional surgical procedures. Utilization of navigation led to fluoroscopy time reduction of more than 50% (3.2 vs. 8.6 min.; p < 0.001) resulting in reduced radiation (2004.5 vs. 5130.8 Gy*cm2; p < 0.001). Operative time was reduced in the navigation group (176.7 vs. 227.4 min; p = 0.002) despite the necessity of additional surface referencing. Conclusion: For iliac screws, identifying the correct entry point and angle of implantation requires detailed anatomic knowledge and multiple radiographic views. In our study, additional navigation reduced operative time and fluoroscopy time resulting in a significant reduction of radiation exposure for patients and OR personnel. [ABSTRACT FROM AUTHOR]

Various composite materials used as biomaterials were tested by 20-, 50-, and 80-N chewing forces in distilled water and a poppy seed medium by using a computer-controlled chewing simulation procedure. In each chewing test, steatite balls 6 mm in diameter were used as an antagonist material. The mean volume loss of worn surfaces and the surface roughness of the composite materials was measured with a contactless 3D profilometer. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects that including different levels of oregano essential oil (Origanum syriacum L.) (200, 400, and 600 mg/kg) in the diets of laying hens had on performance, egg quality, and intestinal morphology, as well as egg malondialdehyde (MDA) levels, blood lipid peroxidation, and oxidative stress parameters. The study used a total of 120 Lohmann white laying hens aged 20 to 22 weeks. The experiment comprised the following three treatment groups, based on the dosages of oregano essential oil: 200 mg/kg (A), 400 mg/kg (B), 600 mg/kg (C); and a control group (K) that did not use oregano essential oil. Each group included 30 hens and each was divided into six subgroups with five hens each. In this study, feed intake and egg weight were significantly higher in the treatment groups than in the control group (P=0.046; P< 0.001). There was no difference among the groups in terms of eggshell strength, egg shape index, eggshell thickness, albumin index, or yolk index. However, there was a significant difference in eggshell weight, yolk color and Haugh unit in the experimental groups (P=0.015; P=0.031; P=0.042). The MDA levels in the yolk were lowest in group A (P< 0.05). In all groups with the exception of group A, yolk and serum MDA levels increased while superoxide dismutase, glutathione peroxidase, and catalase decreased as the doses of oregano essential oil increased (P< 0.001; P< 0.001; P< 0.01; P< 0.001). There was no significant serum glutathione level. In the histological analysis of the intestine, the villus height was higher in group C than in the control group (P=0.010). Based on these results, we concluded that 200 mg/kg was the most effective dose of oregano essential oil for improving performance, egg quality, and intestinal morphology while reducing oxidative stress in laying hens. [ABSTRACT FROM AUTHOR]

Background: Spondylodiscitis is a rare but complex disease with an increasing incidence. Diagnostic algorithms and treatment options for spondylodiscitis are controversially discussed. National guidelines for Germany do not currently exist but are planned for May 2020. Objective: A diagnostic algorithm and treatment recommendations are presented with a focus on antibiotic treatment. Methods: A comprehensive literature search was performed using the PubMed database to identify, analyze and discuss clinical studies, national guidelines, systematic and narrative reviews as well as expert opinions. Results: The diagnostics of spondylodiscitis are often delayed due to the nonspecific clinical manifestation. The correct diagnosis can mostly be made using a combination of clinical, laboratory and radiographic findings. An immediate empirical antimicrobial treatment is recommended until the pathogen has been identified. Conservative treatment can be considered in patients without neurological deficits, larger abscesses, bony destruction, instability or sepsis. A continuous re-evaluation and clinical control are essential in the posthospital follow-up treatment. The timely operative treatment can lead to a rapid improvement of neurological symptoms, diagnosis confirmation through intraoperative samples, stabilization and prevention of deformities. Conclusion: The diagnostics and treatment of spondylodiscitis are a challenge and it is still associated with a high morbidity and mortality. Rapid and correct diagnosis as well as an adequate antimicrobial therapy are key factors for a successful treatment of spondylodiscitis. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this study is to investigate the Gadolinium Oxide (Gd 2 O 3) as a gate dielectric/sensitive region in MOS based radiation sensors and to provide a detailed description of the frequency-dependent gamma irradiation response of a Gd 2 O 3 MOS capacitor. The 254 nm thick-Gd 2 O 3 films were deposited on p-type Si wafers by using RF magnetron sputtering. The radiation response of the Gd 2 O 3 MOS capacitors was investigated by 60Co irradiation in the range of 0.5–70 Gy. The capacitance-voltage (C-V) curves shifted to a more positive potential with increasing radiation dose due to there being more trapped electrons than holes. The variation in the oxide trap charge density was found to be in the range of − 3.21 × 1011 ± 1.57 × 1010 cm−2 – − 1.70 × 1012 ± 8.33 × 1010 cm−2 at 100 kHz and − 2.26 × 1011 ± 1.02 × 1010 cm−2 – − 1.30 × 1012 ± 6.02 × 1010 cm−2 (70 Gy) at 1 MHz. The maximum variation in the interface trap charge density was in order of 1011 cm−2 at 1 MHz. The results indicate that the contribution of the oxide trap charge to radiation response of the Gd 2 O 3 MOS capacitor is higher than that of the interface trap charges. The radiation sensitivities of the Gd 2 O 3 MOS capacitor for 100 kHz and 1 MHz were determined as 59.2 ± 2.9 mV/Gy and 62.7 ± 2.9 mV/Gy, respectively. The percentage fading values (dose storage capability) measured in the time range of 25–145 min for 100 kHz varied from 2.2% to 11.4%. Highlights • Frequency dependent radiation response of Gd 2 O 3 MOS capacitor was investigated. • RF/DC magnetron sputtering was used for the MOS fabrication. • The C-V curves shifted to positive voltages with respect to non-irradiated one. • Sensitivities were found to be the same within the error limits for both frequencies. • Electron trapping in the structure was dominant compared to positive charge trapping. [ABSTRACT FROM AUTHOR]

Pre-irradiation device characteristics, gamma radiation response, and possible use in radiation dosimetry have been investigated for MOSFETs with a 100 nm thick Er 2 O 3 gate dielectric. The performance of these novel devices has been compared with that of commercial pMOS dosimeters (RadFETs) with a standard SiO 2 gate oxide of the same thickness. The radiation sensitivity of the Er 2 O 3 is significantly higher than that of SiO 2 , and this is particularly pronounced at lower dose levels. Significantly larger numbers of positive charges are trapped in the Er 2 O 3 dielectric than in SiO 2 during irradiation exposure, resulting in increased threshold voltage shift. After two weeks of room temperature annealing, 11.9% and 24.0% fading have been observed in SiO 2 and Er 2 O 3 samples, respectively. Higher fading for Er 2 O 3 may be related to higher number of shallow traps close to the dielectric/silicon interface. These initial results are promising for the possible use of Er 2 O 3 as a new gate dielectric in pMOS dosimeters. The observed enhancement of device sensitivity can be a milestone for the introduction of the pMOS dosimeters in personal dosimetry applications. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate two and three-body wear resistance and hardness of eighth kinds of modern bulk-fill and resin-based composite materials — Grandio, Estelite Flow, Filtek bulk-fill, Charisma, Clearfil, Ultimate, Quadrant, and G-aenial. All samples were kept in distilled water for one week, and their Vickers hardness was determined before two- and three-body wear tests. The mean volume loss of all specimens after the wear tests was determined by the 3D profilometry. In addition, a random specimen was selected from each test group and scanning electron microscope images were taken for an analysis of wear tracks. The surface morphology of the Clearfil and Ultimate composite materials was damaged severely, whereas Grandio and Charisma had a very smooth surface after two-body wear tests. The lowest mean volume loss was measured in micro-fill Grandio two-body and three-body wear tests. The Filtek bulk-fill and resinbased composites showed similar two- and three-body wear behavior. For the composite materials considered, correlations between the filler volume loss, Vickers hardness, and two- and three-body wear resistances were found to be insignificant. [ABSTRACT FROM AUTHOR]

Cyanide leaching is the most common method used for production of silver from gold/silver ores. Silver (and gold) can be recovered from pregnant leach solutions (PLSs) using Merrill-Crowe process (zinc cementation) and activated carbon adsorption. Due to their inherent limitations and paucity of selectivity, development of alternative processes for selective recovery of silver from PLSs is of great interest. In the current study, selective recovery of silver by precipitation from cyanide solutions using an environmentally friendly organic reagent i.e. Trimercapto- s -triazine (C 3 N 3 S 3 ; TMT) was investigated. The results have shown that precipitation of silver by TMT is a rapid process in that 87.9% of silver could be precipitated at the initial period of 5 min. Response surface methodology (i.e. central composite design) was adopted to examine the main and interaction effects of [TMT]/[Ag] ratio (0.09–36.52), [CN]/[Ag] ratio (3 − 10) and initial concentration of silver (1–40 mg/L Ag) on the precipitation of silver in five levels. The statistical analysis of the experimental data revealed that ratio of [TMT]/[Ag] (i.e. concentration of TMT) was the key parameter exerting a profound effect on the precipitation of silver. However, effects of [CN]/[Ag] ratio and Ag concentration appeared to be statistically insignificant. Complete precipitation of silver was found to be readily achieved under suitable conditions. The precipitation process was proved to be highly selective for silver over gold and copper as also confirmed by the tests on real pregnant leach solutions. It was found that the presence of TMT had no discernible effect on adsorption of gold by activated carbon, which was observed to even improve from copper containing solutions. Silver-TMT precipitates were characterised using SEM/EDS, FT-IR and other techniques. The current findings demonstrate that this precipitation process can be exploited as a potent alternative for selective recovery of silver from cyanide leach solutions of silver and gold/silver ores or purified/concentrated solutions ahead of gold electro-winning. [ABSTRACT FROM AUTHOR]

The usage of the Gadolinium oxide (Gd 2 O 3 ) as sensitive region in the MOS (Metal-Oxide-Semiconductor)-based dosimeters was investigated in the presented study. The Gd 2 O 3 films grown on p-type Si (100) by RF magnetron sputtering were annealed at 800 °C under N 2 ambient. The back and front metal contacts were establishes to produce MOS capacitors. The fabricated Gd 2 O 3 MOS capacitors were irradiated in the dose range 0.5–50 Gy by 60 Co gamma source. The performed Capacitance-Voltage (C-V) curves of the Gd 2 O 3 MOS capacitors shifted to right side relative to pre-irradiation one. While continuous increments in the oxide trapped charges with increasing in gamma dose were observed, interface trapped charges fluctuated in the studied dose range. However, the variation of the interface trapped charge densities was found in the order of 10 11 cm −2 and no significant variation was observed with applied dose. These results confirm that a significant deterioration does not occur in the capacitance during the irradiation. The higher oxide trapped charges compared to interface trapped charges showed that these traps were more responsible for the shift of the C-V curves. The sensitivity and percentage fading after 105 min of the Gd 2 O 3 MOS capacitor were found as 39.7±1.4 mV/Gy and ~14.5%, respectively. The devices sensitivity was found to be higher than that of capacitors composed of Er 2 O 3 , Sm 2 O 3 , La 2 O 3 , Al 2 O 3 , and SiO 2 , but, the high fading values is seen as a major problem for these capacitors. Finally, the barrier height was investigated with gamma exposure and the results showed that its value increased with increasing in radiation dose due to possible presence of the acceptor-like interface states. [ABSTRACT FROM AUTHOR]

The irradiation response of Radiation Sensing Field Effect Transistor (RadFET), also known as MOSFET/pMOS dosimeter, to high energy X-rays and electron beams was investigated. The threshold voltages before and after irradiation were measured and the trap densities in the gate oxide and oxide/silicon interface of the RadFETs are evaluated. The RadFETs were irradiated with 6 MV X-rays, and 10 and 18 MeV electron beams emitted from a Linear accelerator (LINAC). Linear and non-linear fits to experimental results showed that after an initial linear response up to several Gy, deviation from the linearity occurred due to electric field screening by the radiation induced oxide trapped charges. The radiation-induced fixed traps (FTs) and switching traps (STs) were analysed and the FT density was found to be higher than the ST density for all beam types and doses. The radiation response, fading characteristics, and variation of the trapped charges of the RadFETs showed similar behaviour in tests. [ABSTRACT FROM AUTHOR]

Background and objectives In this article, we propose a decision support system for effective classification of dental periapical cyst and keratocystic odontogenic tumor (KCOT) lesions obtained via cone beam computed tomography (CBCT). CBCT has been effectively used in recent years for diagnosing dental pathologies and determining their boundaries and content. Unlike other imaging techniques, CBCT provides detailed and distinctive information about the pathologies by enabling a three-dimensional (3D) image of the region to be displayed. Methods We employed 50 CBCT 3D image dataset files as the full dataset of our study. These datasets were identified by experts as periapical cyst and KCOT lesions according to the clinical, radiographic and histopathologic features. Segmentation operations were performed on the CBCT images using viewer software that we developed. Using the tools of this software, we marked the lesional volume of interest and calculated and applied the order statistics and 3D gray-level co-occurrence matrix for each CBCT dataset. A feature vector of the lesional region, including 636 different feature items, was created from those statistics. Six classifiers were used for the classification experiments. Results The Support Vector Machine (SVM) classifier achieved the best classification performance with 100% accuracy, and 100% F-score (F1) scores as a result of the experiments in which a ten-fold cross validation method was used with a forward feature selection algorithm. SVM achieved the best classification performance with 96.00% accuracy, and 96.00% F1 scores in the experiments in which a split sample validation method was used with a forward feature selection algorithm. SVM additionally achieved the best performance of 94.00% accuracy, and 93.88% F1 in which a leave-one-out (LOOCV) method was used with a forward feature selection algorithm. Conclusions Based on the results, we determined that periapical cyst and KCOT lesions can be classified with a high accuracy with the models that we built using the new dataset selected for this study. The studies mentioned in this article, along with the selected 3D dataset, 3D statistics calculated from the dataset, and performance results of the different classifiers, comprise an important contribution to the field of computer-aided diagnosis of dental apical lesions. [ABSTRACT FROM AUTHOR]

The aim of this study was to valorize orange (Citrus sinensis) seeds, which are generated as waste. This study presents data about raw orange seed, the meal gained after cold pressing, and characterization data of the cold pressed seed oils. Furthermore, the effects of microwave roasting of the seds compared to regular roasting (control) were determined. The oil yield of orange seed cold pressing was around 52.93-62.99%. After cold pressing, 13.57-17.97% oil remained in the meal together with 20.68-25.61% protein. Hence, pressed meals could be valorized for different purposes. Except for turbidity, the color b* value, free acidity, the p-anisidine value and antioxidant capacity, there was no significant difference between the two oil samples for the measured physicochemical properties. Six different fatty acids were quantified and the major fatty acids were linoleic, palmitic and oleic acids. The fatty acid composition of the orange seed oil can be accepted as nutritionally balanced. Among the fifteen sterols quantified, β-sitosterol was dominant (around 77-78%). Likewise, the α-tocopherol content of the samples was not significantly different. The thermal onset and peak temperatures, and enthalpies for crystallization and melting were also reported. This study showed that good quality orange seed oils can be produced by cold pressing, and the oils could be used in food and non-food applications. [ABSTRACT FROM AUTHOR]

The radiation sensing field effect transistor (RadFET) with SiO2gate oxide has been commonly used as a device component or dosimetry system in the radiation applications such as space research, radiotherapy, and high-energy physics experiments. However, alternative gate oxides and more suitable packaging materials are still demanded for these dosimeters. HfO2is one of the most attractive gate oxide materials that are currently under investigation by many researchers. In this study, Monte Carlo simulations of the average deposited energy in RadFET dosimetry systems with different package lid materials for point electron and photon sources were performed with the aim of evaluating the effects of package lids on the sensitivity of the RadFET by using HfO2as a gate dielectric material. The RadFET geometry was defined in a PENGEOM package and electron–photon transport was simulated by a PENELOPE code. The relatively higher average deposited energies in the sensitive region (HfO2layer) for electron energies of 250 keV–20 MeV were obtained from the RadFET with the Al2O3package lid despite of some deviations from the general tendency. For the photon energies of 20–100 keV, the average amount of energy deposited in RadFET with Al2O3package was higher compared with the other capped devices. The average deposited energy in the sensitive region was quite close to each other at 200 keV for both capped and uncapped devices. The difference in the average deposited energy of the RadFET with different package lid materials was not high for photon energies of 200–1200 keV. The increase in the average deposited energy in the HfO2layer of the RadFET with Ta package lid was higher compared with the other device configurations above 3 MeV. [ABSTRACT FROM PUBLISHER]

The frequency dependent irradiation influences on Sm 2 O 3 MOS capacitors have been investigated and possible use of Sm 2 O 3 in MOS-based radiation sensor was discussed in this study. To examine their gamma irradiation response over a range of doses, the fabricated MOS capacitors were irradiated up to 30 grays. Capacitance–Voltage ( C – V ) measurements were recorded for various doses and the influences of irradiation were determined from the mid-gap and flat-band voltage shifts. In addition, the degradations of irradiation have been studied by impedance based leakage current–voltage ( J – V ) characteristics. The results demonstrate that J – V characteristics have not been significantly change by irradiation and implying that the excited traps have a minor effect on current for given dose ranges. However, the frequency of applied voltage during the C – V measurements affects the irradiation response of devices, significantly. The variations on the electrical characteristics may be attributed to the different time dependency of acceptor and donor-like interface states. In spite of the variations on the device characteristics, low frequency measurements indicate that Sm 2 O 3 is a potential candidate to be used as a dielectric layer in MOS based irradiation sensors. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to test the prediction that the unique manifestation of chemotherapeutic-induced peripheral neuropathy (CIPN) would be reflected in a specific pattern of changes in the regulation of the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in subpopulations of cutaneous neurons. To test this prediction, we characterized the pattern of changes in mechanical nociceptive threshold associated with paclitaxel administration (2 mg/kg, iv, every other day for four days), as well as the impact of target of innervation and paclitaxel treatment on the regulation of [Ca 2+ ] i in subpopulations of putative nociceptive and non-nociceptive neurons. Neurons innervating the glabrous and hairy skin of the hindpaw as well as the thigh were identified with retrograde tracers, and fura-2 was used to assess changes in [Ca 2+ ] i . Paclitaxel was associated with a persistent decrease in mechanical nociceptive threshold in response to stimuli applied to the glabrous skin of the hindpaw, but not the hairy skin of the hindpaw or the thigh. However, in both putative nociceptive and non-nociceptive neurons, resting [Ca 2+ ] i was significantly lower in neurons innervating the thigh after treatment. The magnitude of the depolarization-evoked Ca 2+ transient was also lower in putative non-nociceptive thigh neurons. More interestingly, while paclitaxel had no detectable influence on either resting or depolarization-evoked Ca 2+ transients in putative non-nociceptive neurons, in putative nociceptive neurons there was a subpopulation-specific decrease in the duration of the evoked Ca 2+ transient that was largely restricted to neurons innervating the glabrous skin. These results suggest that peripheral nerve length alone, does not account for the selective distribution of CIPN symptoms. Rather, they suggest the symptoms of CIPN reflect an interaction between the toxic actions of the therapeutic and unique properties of the neurons deleteriously impacted. [ABSTRACT FROM AUTHOR]

Context. Sleeve gastrectomy is an effective method for management of obesity. The Bariatric Analysis and Reporting Outcome System (BAROS) is a comprehensive and standard system for the assessment of outcomes of weight loss surgery. It is consisted of weight loss, changes in obesityrelated comorbidities and quality of life measurements. We investigated results of the sleeve gastrectomy based on the BAROS. Material and Methods. Outcomes of laparoscopic sleeve gastrectomy surgery was studied in 45 patients with obesity (11 male, 34 female), after 45 months in Turkey. Results. Total weight loss was 26.4±0.1% of body weight at 45 months. Weight regain was seen in 97.8% of the patients with an average 14.5 kg and 13.7% body mass index points. The surgery caused 76% decrease in incidence of obstructive sleep apnea, 73% decrease in type 2 diabetes, 63% decrease in hyperlipidemia and 62% decrease in hypertension. Significant improvement is observed in all quality-of-life parameters. The final score of the BAROS was 4.23±1.02. Conclusion. Based on BAROS, sleeve gastrectomy provides significant improvements in weight loss, incidence of medical comorbidities and quality of life after surgery. Future studies should address prevention of weight regain after the surgery. [ABSTRACT FROM AUTHOR]

New Ti based alloys with non-cytotoxic and biocompatible elements, such as Nb, Zr, Ta, Sn and Mo, have recently attracted much attention for orthopedic applications. The aim of this study was to investigate the effects of Sn content (2 and 4 wt%) on microstructure and mechanical properties of Ti16NbXSn sintered alloys. The results indicated that Ti16Nb(0-4)Sn alloys were composed of α+β phases. Hardness and Young's modulus E of the alloys measured using nanoindentation technique. These results show that there is a relationship between the mechanical properties and Nb-Sn content. It is concluded that addition of Nb to the cp-Ti resulted to a decrease in Young's modulus. [ABSTRACT FROM AUTHOR]

The Na+-Ca2+ exchanger (NCX) appears to play an important role in the regulation of the high K+-evoked Ca2+ transient in putative nociceptive dorsal root ganglion (DRG) neurons. The purpose of the present study was to (1) characterize the properties of NCX activity in subpopulations of DRG neurons, (2) identify the isoform(s) underlying NCX activity, and (3) begin to assess the function of the isoform(s) in vivo. In retrogradely labelled neurons from the glabrous skin of adult male Sprague-Dawley rats, NCX activity, as assessed with fura-2-based microfluorimetry, was only detected in putative nociceptive IB4+neurons. There were two modes of NCX activity: one was evoked in response to relatively large and long lasting (~325 nM for >12 s) increases in the concentration of intracellular Ca2+ ([Ca2+]i), and a second was active at resting [Ca2+]i > ~150 nM. There also were two modes of evoked activity: one that decayed relatively rapidly (<5 min) and a second that persisted (>10 min). Whereas mRNA encoding all three NCX isoforms (NCX1-3) was detected in putative nociceptive cutaneous neurons with single cell PCR, pharmacological analysis and small interfering RNA (siRNA) knockdown of each isoform in vivo suggested that NCX2 and 3 were responsible for NCX activity. We stern blot analyses suggested that NCX isoforms were differentially distributed within sensory neurons. Functional assays of excitability, action potential propagation, and nociceptive behaviour suggest NCX activity has little influence on excitability per se, but instead influences axonal conduction velocity, resting membrane potential, and nociceptive threshold. Together these results indicate that the function of NCX in the regulation of [Ca2+]i in putative nociceptive neurons may be unique relative to other cells in which these exchanger isoforms have been characterized and it has the potential to influence sensory neuron properties at multiple levels. [ABSTRACT FROM AUTHOR]

Let N be a submodule of a module M and a minimal primary decomposition of N is known. A formula to compute Baer's lower nilradical of N is given. The relations between classical prime submodules and their nilradicals are investigated. Some situations in which semiprime submodules can be written as finite intersection of classical prime submodule are stated. [ABSTRACT FROM AUTHOR]

The immune microenvironment plays an essential role in the progression of head and neck squamous cell carcinoma (HNSCC). The association of the tumor microbiota and immune microenvironment is not well defined. The Cancer Genome Atlas Project (TCGA) analysis provided the diversity of microbiota in different cancer types. We analyzed the TCGA microbiome database to better understand the role of the tumor microbiome in HNSCC. Human papillomavirus (HPV) positive and HPV negative HNSCC samples in the TCGA database were analyzed. Data were accessed using cBioPortal. Spearman's test was used to correlate Lachnoclostridium microbiome signature with immune-related gene expressions. Microbiome signatures were compared in PDL1 low and PDL1 high HNSCC. Lachnoclostridium was among the top genus enriched in the PDL1 high expression group in both HPV+ and HPV- HNSCC. Lachnoclostridium was correlated with immune inflamed gene expression profile. To evaluate the differential gene expressions in Lachnoclostridium enriched HNSCC, the gene expression profile of Lachnoclostridium high and low HNSCC samples were compared. MHC class I genes; HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, TAP1, and TAP2 were among the top differentially expressed genes. Then we evaluated the correlation of MHC-I genes with Lachnoclostridium enrichment. Lachnoclostridium signature was significantly correlated with expression of these MHC I genes, with Spearman's correlation coefficient ranging between 0.51-0.59. Lachnoclostridium is a recently defined genus found in the human gut microbiome. Here we, for the first time, identify the enrichment of this genus in high PDL1 expressing HNSCC. The association of Lachnoclostridium signature with the immune inflamed gene expression profile and MHC-I gene signature suggests its potential role in modulating the immune microenvironment in HNSCC. [ABSTRACT FROM AUTHOR]

Production of gold from copper-rich gold ores has received particular attention due to some technical and economic challenges associated with the ready dissolution of most copper minerals during cyanide leaching. This leads to excessive consumption of cyanide by forming copper cyanide complexes, which adversely affect downstream recovery and cyanide detoxification processes. In this study, a novel method is proposed to precipitate copper from cyanide solutions using sodium dimethyldithiocarbamate (C 3 H 6 NNaS 2 ; SDDC). The influence of various parameters (i.e., reaction period (0–360 min.), concentration of SDDC (165–992 mM), [CN−]/[Cu] ratio (3–8), pH (10–12.5) and temperature (20–60 °C) on the precipitation of copper were investigated using synthetic copper-cyanide solutions. Increasing reaction time, concentration of SDDC and temperature were found to significantly improve the precipitation of copper. Increasing the ratio of [CN−]/[Cu] adversely affected the precipitation of copper with no precipitation being occurred at ratios of ≥6. Strong alkaline conditions appeared to have a slightly negative impact on the process. In the light of these findings, the response surface methodology (i.e., central composite design; CCD) was adopted to reveal the influence and interactions of [SDDC]/[Cu] ratio (21.0–126), initial concentration of copper (50–950 mg/L) and reaction period (15–360 min.) on the precipitation of copper. The analysis of the data confirmed that statistically significant parameters affecting the process were reaction time and [SDDC]/[Cu] ratio. It was also found that initial copper concentration did not significantly influence the process. Tests on real cyanide leach solutions derived from gold ores/concentrates demonstrated that the SDDC could selectively precipitate copper (as well as zinc and silver) from gold-bearing solutions. The activation energy (i.e., ≈67 kJ/mol) calculated by Arrhenius equation has indicated that the precipitation of copper is a chemically controlled reaction. Detailed characterisation of Cu-DDC precipitates was performed using SEM-EDS, FT-IR and particle size analysis. The precipitates (d 80 = 16 μm) are thin, rod-like particles in brownish colour. The recovery of copper from Cu-DDC precipitates using acid solutions (HCl, H 2 SO 4 and HNO 3) was also investigated. Complete recovery of copper was achieved using HCl and HNO 3 solutions at high concentrations. The findings have suggested that SDDC is an effective reagent for selective precipitation of copper from cyanide leach solutions. • Sodium dimethyldithiocarbamate (SDDC) precipitates copper from cyanide solutions. • Time and [SDDC]/[Cu] ratio are the most influential parameters on Cu precipitation. • Copper is selectively precipitated over gold. • Mineral acids can be used to recover copper from Cu-DDC precipitate. [ABSTRACT FROM AUTHOR]

Substantial boron compounds such as colemanite, ulexite and tincalconite are found in Turkey with a worldwide share of 72% in terms of B2O3 content. They are utilized in agriculture, textile, cleaning products as well as glass, ceramic, cement and nuclear industry. Boron compounds have synergistic effects on the mechanical, wear, corrosion and thermal properties of the polymeric materials which are commonly used in transport, automotive, aerospace, construction and many engineering applications [1, 2]. In this study, epoxy composite materials including calcined colemanite as filler at different ratios (0, 5, 10, 15, 20 wt%) were prepared after calcination process of colemanite at 430 °C for 75 min. Amorphous structure of the epoxy composite materials was determined from XRD analysis. The dispersion of filler in the epoxy resin was investigated with SEM analysis. The mechanical, water sorption and corrosion resistance properties of the epoxy composite materials were examined according to ASTM Standards. And also, thermal properties of the composites were investigated with TGA and DSC analyses in details. As a result, it was revealed that the usage of environmentally friendly calcined colemanite enhanced the properties of polymeric materials. [ABSTRACT FROM AUTHOR]

A new amine based microextraction procedure has been established for the separation and preconcentration of lead (II). N , N -dimethyl-n-octylamine was used as extraction solvent and chelating agent for lead (II). Microsampling flame atomic absorption spectrometry was used for the determination of lead. The analytical parameters including pH, amounts of N , N -dimethyl-n-octylamine, sample volume etc. were optimized. The influences of the matrix components were also investigated. The validation of the procedure was done by the analysis of TMDA 64.2 certified reference material. The Limit of detection (LOD) of developed method was 2.6 μg L−1. The developed microextraction procedure was successfully applied to natural water samples. • A new amine based microextraction procedure has been established for the separation and preconcentration of lead. • N , N -dimethyl-n-octylamine was used as extraction solvent and chelating agent for lead. • The effects of analytical parameters were systematically investigated and optimized. • The method has been applied to the analysis of lead in water samples. [ABSTRACT FROM AUTHOR]

A fast and efficient preconcentration method was developed based on supramolecular microextraction for separation and preconcentration of nickel(II). The composition of supramolecular solvent includes 1-decanol and tetrahydrofuran. N,N′-Dihydroxy-1,2-cyclohexanediimine was applied as chelating agent for Ni(II) as well as to facilitate the transference of the complex from aqueous sample solution to the supramolecular organic layer. The developed preconcentration method was followed by flame atomic absorption spectroscopy measurement for nickel detection. The optimum conditions for the quantitative results were at the pH between 5.5 and 6.5, and volume of 0.1% N,N′-Dihydroxy-1,2-cyclohexanediimine between 100 μL and 200 μL. The developed procedure was applicable in case of applying different matrix. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 1.3 μg L − 1 and 3.9 μg L − 1 respectively. TMDA 64.2 and TMDA 53.3 certified reference materials were used to validate the proposed procedure and the results showed good agreement. The developed method was applied for determination of Ni(II) in water, tobacco and fertilizer samples. [ABSTRACT FROM AUTHOR]

In recent years, the use of unmanned aerial vehicles has increased rapidly. These vehicles have instant detection, tracking and destruction capabilities in military operations. In addition, when compared other conventional aerial vehicles, in the case of the vehicles down, any loss of driver life can be accounted for the most important factor in the view of widespread use of this vehicle. It is very important to make aerodynamic analyzes of unmanned aerial vehicles swarming behavior and to identify reliable zones for vehicles. It should be determined at what speeds and closeness of the flying vehicles along the specified routes the vehicles should be located within the frame. In this study, the models of an unmanned aerial vehicle and propellers of an UAV were designed with computational fluid dynamics. Especially turbulence, pressure, and speed changes have been investigated. Moreover, the range of interaction distance that they can create on each other is determined and reliable regions are determined. [ABSTRACT FROM AUTHOR]

Carotid artery stenosis (CAS) is a known potential late effect of neck radiation. There are varying estimates of its incidence and mixed consensus on whether screening for this late effect standard practice should be. As treatment techniques have evolved and the presence of HPV has increased, the impact on the future trajectory of this problem is unclear. A sample of head and neck cancer (HNC) patients treated from 1997 through 2022 who underwent carotid ultrasound (US) at any time after receiving radiation therapy to the neck were identified from an IRB-approved, single institution database. Patient treatment characteristics including radiation laterality, co-morbidities at consult, and smoking history were coded in addition to carotid US dates and results. CAS was defined as >40% stenosis of either side of the vessel, which prompted a vascular surgery consult. A total of 308 patients were included in this study with an average follow up of 70 months (range: 3.3-255.9 months). All included patients received bilateral neck radiation and had no evidence of disease at their last follow up. Most patients received definitive, concurrent chemoradiation (96.4%), were male (85.1%) and had a primary oropharyngeal tumor (64%). The most common co-morbidity at time of consult was hypertension (HTN, 45.8%). Median time to CAS was 10.7 years. The five- and ten-year rates of CAS were 15.4% and 39.6%, respectively. On Cox regression univariate analysis age at consult (HR=1.054, 95% CI= 0.649-1.941, p<0.001), having known HTN (HR=2.551, 95% CI=1.610-4.032, p<0.0001), hyperlipidemia (HR=1.658, 95% CI= 1.066-2.584, p=0.0248), diabetes (HR=2.398, 95% CI=1.397-4.115, p=0.0015), or cardiac disease (HR=2.283, 95% CI=1.333-3.922, p=0.0026) at time of consult, and being an ever smoker (HR=2.336, 95% CI=1.403-3.891, p=0.0011) were statistically predictive of CAS. On multivariate analysis, patients who were older (HR=1.037, 95% CI=1.008-1.068, p=0.0122), were an ever smoker (HR=2.375, 95% CI=1.425-3.968, p=0.0009), and having known hypertension (HR=2.037, 95% CI=1.235-3.356, 0.0053) at consult were at highest risk for CAS. CAS was frequently detected five and ten years after head and neck radiation. Carotid artery US screening should be strongly considered in these patients, especially older patients with a history of smoking and/or HTN. Future prospective studies are warranted to verify this finding. [ABSTRACT FROM AUTHOR]

The purpose of the study was to define whether circulating tumor DNA (ctDNA) can be used as a measure to detect minimal residual disease (MRD) following surgical intervention in high-risk positive patients for head and neck squamous cell carcinoma (HNSCC). IRB approval was obtained through our institution. Patients with HNSCC with surgical resection of their tumor were enrolled. Of these, 28 patients had ctDNA levels determined post-operatively (n = 28) using the Signatera test. Data were extracted from electronic medical records by trained abstractors. The patient cohort (20 male and 8 female) had an average age of 67.0 ± 9.82 years at the time of surgery. Patients were assessed using The Eastern Cooperative Oncology Group (ECOG) functional scores, with 17.9% scoring 0, 75.0% scoring ECOG 1, and 7.14% of patients with ECOG 2 or 3. All patients had primary laryngeal or oral cavity cancer, including gingival, tongue, and mandibular. The study had two patients with pathologic Stage I cancer, three with Stage II, five with Stage III, eleven with Stage IVA, and seven with Stage IVB. One patient received neoadjuvant chemotherapy prior to surgery. There were 19 high-risk positive cancers, defined as positive extranodal extension or positive margins during surgery. 15 of these 19 patients patients received adjuvant chemotherapy and radiation, with or without a platinum agent, depending on their chemotherapy eligibility. In these high-risk patients, 18 had data in the post-operative period, prior to adjuvant therapy, for which 61.1% had positive ctDNA. Conversely, there were 9 patients without high-risk features, of whom only two had positive MRD post-operatively, and two with disease recurrence. There was a significantly lower tumor recurrence in the patients without high-risk features compared to those with high-risk features (22.9% vs. 54.5%, respectively) which correlated with ctDNA. At the time of data collection, 7 patients had disease recurrence for which 5 were post-operative ctDNA positive. Two patients were ongoing adjuvant treatment and follow-up without recurrence data. ctDNA was detected frequently in the HNSCC patients with high-risk features post-operatively. Although we have a small number of the patients, the patients with recurrence following adjuvant treatment had high rates of positive ctDNA after the surgery. Therefore post-operative ctDNA for high-risk patients may be prognostic and considered in clinical trials designed for treatment intensification. [ABSTRACT FROM AUTHOR]

A dispersive liquid-liquid microextraction ( DLLME) procedure for determination of Pb(II) in water and tobacco samples has been developed using rac-(E,E)-N,N′-bis(2-chlorobenzylidene)cyclohexane-1,2-diamine as a chelating agent. Factors influencing the efficiency of DLLME have been optimised, including metal solution pH, type and amount of dispersing solvent, type and amount of extraction solvent, amount of chelating agent and sample volume. The optimized conditions for maximum recovery were as follows: sample pH 6; dispersing solvent, 500 μL of ethanol; extraction solvent, 150 μL of chloroform; chelating agent, 150 μL of 0.01% rac-(E,E)-N,N′-bis(2-chlorobenzylidene)cyclohexane-1,2-diamine; and sample volume, 15 mL. The method was validated using the certified reference material SPS-WW2 waste water. The method offered a limit of detection (LOD) of 2.6 μg/L, a limit of quantification (LOQ) of 8.5 μg/L, and a relative standard deviation (RSD) of 5.2%. [ABSTRACT FROM AUTHOR]

• TMT effectively precipitates Ag from ammoniacal thiosulphate solutions. • Precipitation of Ag with TMT occurs fast. • TMT dosage is the most influential parameter on the recovery of silver. • Efficiency of the method is also demonstrated using real leach solutions. • A comprehensive characterisation of Ag-TMT precipitate is provided. In recent years, the demand for silver has increased due to its use in green technologies such as photovoltaic cells and electric vehicles (EVs). Due to environmental concerns associated with the use of cyanide leaching for gold/silver production, alternative lixiviants have received particular attention with thiosulphate having been often quoted as the most prominent one owing to its environmentally friendly characteristics and some technical advantages. However, thiosulphate leaching suffers from technical difficulties encountered particularly in the metal recovery from pregnant leach solutions. This study presents a novel approach for the recovery of silver from ammoniacal thiosulphate solutions through its precipitation using trimercapto- s -triazine (TMT), which is a non-toxic organo-sulphide reagent. Effects of concentration of TMT (0.07–0.33 mM), thiosulphate (0.20–1.00 M), and ammonia (0.40–1.00 M NH 3) on silver precipitation from synthetic Cu(II)–S 2 O 3 2−–NH 3 solutions were investigated by adopting the response surface methodology i.e., central composite design (CCD). The statistical analysis of the experimental data showed that the concentration of TMT had the highest impact on the extent of silver precipitation. Separate tests were also carried out to obtain the kinetic profiles of silver precipitation under varying concentrations of TMT (0.69–6.84 mM), copper (2.00–20.0 mM), and ammonia (0.10–1.00 NH 3) over 60 min. These results have also confirmed that silver can be readily and rapidly precipitated to the extent of 96.5% within a minute at a TMT concentration of 0.69 mM. The performance of the proposed method was also tested using real leach solutions derived from ammoniacal thiosulphate leaching of silver ore. It was found that extensive precipitation of silver (i.e., 99.0% Ag at 6.84 mM TMT) could be achieved with co-precipitation of copper (94.7%) and zinc (34.6%). SEM-EDS and FT-IR analyses were performed to characterise the precipitates obtained. This study has demonstrated that TMT can be used as a potent, non-toxic reagent for the recovery of silver from ammoniacal thiosulphate solutions. [ABSTRACT FROM AUTHOR]

BCA101 is a first-in-class bifunctional EGFR/TGFβ inhibitor with a manageable safety profile and preliminary efficacy in advanced solid tumors (ESMO 2022 731MO). Pembrolizumab is approved for recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the CPS≥1 population. Here we report updated results from the fully enrolled expansion cohort combining BCA101 + pembrolizumab as first line therapy in R/M HNSCC. This ongoing single-arm, multicenter dose expansion cohort enrolled patients (pts) with R/M HNSCC as part of a phase 1/1b trial. Pts with tumor PD-L1 CPS≥1 with no prior systemic therapy for R/M disease, ECOG 0-1, and measurable disease (RECIST v1.1) were eligible. Pts received BCA101 (1500 mg IV on days 1, 8, 15) with pembrolizumab (200 mg IV on day 1) every 21-days. Primary endpoint: safety; secondary endpoints: overall response rate (ORR), duration of response, progression-free survival (PFS), overall survival. Exploratory: molecular and immunologic predictors of response. Forty-two pts received at least one dose of study drug and 39 pts were evaluable for efficacy. Pts were more often men (30, 71%); median age: 63 (range: 31-84). Twenty pts (48%) had baseline PD-L1 CPS scores of 1-19 and 22 (52%) were ≥20. Oropharynx (20, 48%) [12/20 (60%) HPV/p16-positive] and oral cavity (13, 31%) were the most common subsites. Thirty-three pts (79%) had distant metastases. The ORR was 46% (5 CR, 13 PRs) with 57% (16/28) of HPV/p16-negative pts achieving response. Similar response rates were observed for HPV-negative pts with CPS scores 1-19 (54%, 7/13) and CPS≥20 (60%, 9/15), as well as in pts with distant metastasis (55%, 12/22) and locoregional disease (67%, 4/6). Median PFS (mPFS) continues to mature and currently has not been reached among HPV-negative pts with 13/28 responses ongoing (>30% for more than 6 months), with updates expected to be available at the time of the meeting. Grade 3+ treatment-related adverse events (TRAEs) were observed in 17/42 pts (40%). There were no treatment-related deaths. Acneiform rash was the most common TRAE of any grade (31/42, 74%). Permanent discontinuation of study treatment due to TRAEs was required in 6/42 pts (14%). BCA101 + pembrolizumab exhibits encouraging safety and anti-tumor activity in first line R/M HNSCC, particularly among HPV-negative pts in both CPS 1-19 and ≥20. Further investigation in HPV-negative pts is planned in a larger randomized study. Study funded by Bicara Therapeutics Inc. and conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (NCT04429542). [ABSTRACT FROM AUTHOR]

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, with only ∼20% of patients responding to anti-PD-1 checkpoint immunotherapy. CD47 is another targetable immune checkpoint. By interacting with SIRPα, CD47 triggers a "don't eat me" signal to inhibit macrophage phagocytosis which is upregulated in the HNSCC tumor microenvironment. The aim of our study was to examine the effect of anti-CD47 as monotherapy and in combination with anti-PD-L1/PD-1 checkpoint blockade, on tumor growth response and survival in syngeneic orthotopic models of HNSCC. Syngeneic murine HNSCC cell lines were injected orthotopically (tongue) into C57/B6 mice: MOC1, ROC1, and ROC3 (n=5-10 per group). The MOC1 mice were then subjected to immunotherapy intraperitoneally with either control (IgG), anti-CD47, anti-PD-L1 or the combination. ROC1 and ROC3 mice were injected intratumorally with anti-CD-47 and anti-PD-1 was administered intraperitoneally to ROC3 mice in combination with anti-PD-1. Tumor rechallenge (via inoculation of cancer cells was performed in mice exhibiting complete responses to therapy). Tumor volumes were recorded, and survival curves were generated. RNA was isolated from treated tumors and mRNA expression data was collected. Statistical analysis was performed. In MOC1 implanted mice, anti-CD47 monotherapy resulted in no significant difference in tumor volume or survival compared to control (IgG). However, when used in combination with anti-PD-L1, anti-CD47 treatment resulted in a statistically significant decrease in tumor volume and significantly increased overall survival (p<0.05). There were 6/10 complete responders in the combination group (and no mice grew tumors after re-challenge at 100 days). ROC3 implanted mice treated with anti-CD47 treatment showed a significant decrease in tumor volume with monotherapy, compared to control, and maintained complete responses after tumor cell re-challenge (p<0.05). Conversely, the more aggressive ROC1 mouse model showed no significant difference in treatment arms which included anti-CD47, anti-PD-1 and the combination. RNA expression analysis of MOC1 tumors treated with anti-PD-L1 demonstrated significantly increased CD47 expression. We have demonstrated that anti-CD47 and anti-PD-L1 have a synergistic effect in MOC1 tumor models while monotherapy with anti-CD47 works effectively in the ROC3 model. Combination therapy showed no response in the ROC1 model. PD-L1 treatment of MOC1 tumors caused increased expression of CD47 in tumors, indicating that increased CD47 may be an immunosuppressive mechanism that may contribute to PD-L1 immune checkpoint inhibitor resistance. Combining anti-CD47 with anti-PD-L1 immunotherapy may be effective in HNSCC patients with higher baseline immune cell infiltration. [ABSTRACT FROM AUTHOR]

Treatment of oropharyngeal cancer with definitive radiation/chemoradiation (RT/CRT) is an effective treatment and rapid regression of tumor can occur. Following treatment some patients will develop a pharyngeal ulcer which may or may not be associated with disease persistence. Data for the management of ulcers could improve post radiation care. From an IRB approved database of head and neck cancer cases at a tertiary care center, we reviewed patients with non-metastatic squamous cell carcinoma of the oropharynx treated curatively in non-operative fashion with RT/CRT between 1/1/2011 and 1/1/2022. Patients were reviewed for clinical, radiographic and laryngoscopic evidence of pharyngeal ulcer development following completion of radiation. Pharyngeal ulcer patients were evaluated for management strategy of the ulcer and associated complications and association with recurrence. A total of 45 patients with a pharyngeal ulceration following RT/CRT with a median follow up of 30.8 months were identified. The median age of patients was 60 (range 35-82) years, 80% of patients were caucasian, 82% were male, and 42% of patients were active smokers at the time of RT/CRT. 75% of patients had p16/HPV+ disease with T stages of T1/2, T3 and T4 of 44, 20 and 36% respectively. 93% of patients were treated with concurrent chemotherapy (74% cisplatin) to a median dose of 70 Gy (range 60-74 Gy). The median time to development of ulcer was 3.1 months (range 0.2-31.4 months). 19 patients (42%) underwent biopsy of their ulcer of whom 9 (47%) where found to have disease persistence. Ultimately thirteen patients (29%) had associated tumor persistence. Among the 32 patients with ulcer not associated with recurrence, 28 (87.5%) were p16/HPV+ and 90.6% has received chemotherapy. 3 ulcers (9.4%) were associated with exposed bone. Treatment of ulcers revealed 15 (46%) received antibiotics, 23 (72%) needed narcotics and 5 (16%) required feeding tube placement for pharyngeal rest. Three patients (9.4%) required surgical reconstruction to facilitate resolution. Overall, at time of last follow up 28 (88%) of ulcers not associated cancer had resolved with a median time to resolution of 3.6 months (range 1.3-75.2) months. The overall survival of the non-malignant ulcer group was 83% at 3 years compared to 28% in the patients with ulcers associated with persistent cancer. Pharyngeal ulceration is a significant potential complication of RT/CRT in oropharyngeal cancer. Ulceration is frequently identified around 3 months post treatment and when not associated with disease persistence has a high rate of resolution with conservative measures including antibiotics and pain control. Severe case may necessitate feeding tube and rarely surgical reconstruction. [ABSTRACT FROM AUTHOR]

Tumor mutational burden (TMB) is an emerging biomarker utilized in some cancers as a predictive tool to determine benefit to immune checkpoint inhibitor therapy and high TMB alone is an indication for pembrolizumab monotherapy, tumor agnostic. For head and neck squamous cell carcinoma (HNSCC), there is limited data utilizing TMB as a biomarker to predict response to PD-L1 inhibitors. This study assesses TMB score and progression of disease in HNSCC patients treated with immunotherapy. From an IRB-approved database, we retrospectively analyzed 51 patients treated between 2016 and 2023 with HNSCC who had at least one dose of pembrolizumab and known next generation sequencing (NGS). Patients were stratified between high TMB (≥10 mutations/Mb) and low (<10 mutations/Mb). Of the 51 patients, 40 (78%) had progression of disease while on pembrolizumab. The median TMB of those who progressed was 6.9 mutations/Mb. The median time to disease progression was 5.8 months. There were 37 patients who were classified as low TMB with a median 5.0 mutations/Mb. Of these 37, 29 (78%) had progression while on pembrolizumab with a median time to progression of 3.5 months. For the 14 patients with high TMB scores, the median was 12.0 mutations/Mb. Of these 14, 11 (79%) had progression while on pembrolizumab with a median time to progression of 5.8 months. There was no statistical difference in time to progression between high and low TMB cohorts (p=0.3483). Of the 11 (22%) without progression, all patients started pembrolizumab in the setting of recurrent HNSCC (7 metastatic, 4 locoregionally recurrent). The majority in this cohort are classified as having low TMB (n=8/11) with a median TMB of 5.0 mutations/Mb. Of the 10 patients who actively remain on pembrolizumab, they have been on pembrolizumab for a median of 14.7 months. A multivariable analysis revealed that TMB as a continuous variable (i.e., increase in TMB mutations), the risk of progression decreased (p=0.0238, HR 0.940). Although there was no statistical difference in time to progression between our high TMB and low TMB cohorts, a higher TMB score correlated with decreased risk of progression in our cohort of HNSCC patients. Further research is needed to better understand the utility of TMB as a biomarker in HNSCC. [ABSTRACT FROM AUTHOR]

This paper presents the performance of polystrene based plastic scintillator produced in Turkish Energy, Nuclear and Mineral Research Agency (TENMAK). The scintillator is manufactured using thermal polymerization of commercially available styrene monomer doped with first and second fluorescent dyes. The absorption spectrum of the scintillator exhibited two absorption bands at 225 nm and 340 nm, with an absorption edge observed at 410 nm. The wavelength of the emitted light was measured in the range of 400–800 nm, with a maximum intensity at 427 nm. Internal conversion electrons from the 137Cs source were used to evaluate the characteristics of the new scintillator, particularly its light yield. As the light readout the MAPD-3NM type silicon photomultiplier array (4 × 4) with an active area of 15 × 15 mm 2 , assembled using single MAPDs with an active area of 3.7 × 3.7 mm 2 , was used. The light yield of the scintillator was determined to be 6134 photons/MeV. In addition, the efficiency of the scintillator for gamma rays with an energy of 662 keV was found out to be approximately 1.8%. CmBe neutron source was employed to evaluate its fast neutron detection performance. However, neutron/gamma discrimination using pulse shape discrimination (charge integration) method was not observed. The results demonstrate the potential of produced plastic scintillator for various applications, particularly in radiation monitoring and detection systems. • The scintillator is manufactured using thermal polymerization of commercially available styrene monomer doped with first and second fluorescent dyes. • Plastic scintillator exhibits two absorption bands at 225 and 340 nm, with an absorption edge observed at 410 nm. • The efficiency of the scintillator for gamma rays with an energy of 662 keV was found out to be approximately 1.8%. • The plastic scintillator coupled to micropixel avalanche photodiode demonstrated effective detection of beta particles emitted by 137Cs and 90Sr sources, with an energy resolution of 25% for monoenergetic (626 keV) electrons. [ABSTRACT FROM AUTHOR]

While surgery (with or without radioactive iodine (RAI)) is the mainstay of locoregional control in differentiated thyroid cancer (DTC), patients with unresectable disease present a clinical challenge. Uncontrolled disease in the neck can lead to substantial morbidity and mortality in DTC and obtaining locoregional control is vital to preserving quality of life and longevity. High dose definitive radiotherapy (RT) for gross disease in DTC is understudied. This study examines the efficacy of definitive RT in this setting. From an IRB-approved registry of head and neck cancer cases treated at a tertiary care center over a period of 8 years (2014-2022), patients with incompletely resected or unresectable DTC including papillary, follicular, mixed, medullary, and poorly differentiated types were identified. All patients were treated to the neck and/or thyroid regions with visible gross disease to a definitive dose of radiation. The primary endpoint was local control within the radiated portal with a secondary endpoint of locoregional control within the neck. A total of 31 patients were identified, of whom 74.2% were Caucasian. Fourteen were female (45.2%), and 17 (54.8%) were male. The median age was 68 years (range 26-90) and the median follow-up was 31 months. Histologically, 19 (61.3%) cases were papillary, 4 (12.9%) were follicular, 2 (6.5%) were mixed, 3 (9.7%) were medullary, and 3 (9.7%) were poorly differentiated. Among patients with non-medullary DTC 18 (69.2%) received prior RAI. Twelve patients were treated with radiation at initial diagnosis, while 19 patients were treated at the time of recurrence; two patients received concurrent chemotherapy. Twenty-eight patients (90.3%) were treated with IMRT and 3 (9.7%) were treated with SBRT. The median dose to the gross disease was 66 Gy (range 30-70.4) in 32 fractions (range 5-35). Overall, 5 patients (16.1%) experienced a locoregional failure after RT and all experienced failure in the RT portal. The actuarial infield control/locoregional control of radiation therapy at 3 and 5 years was 84.8% and 74.2%, respectively. Overall survival at 3 and 5 years was 68.5% and 47.4%, respectively. Among patients who had a locoregional failure after RT, 2 patients were salvaged with systemic therapy, 2 patients with surgery, and 1 patient with SBRT re-irradiation (40 Gy/5 fractions). The patient salvaged with SBRT remains without disease 8 months post-RT. Definitive radiotherapy is a highly effective strategy to obtain durable control of unresected DTC. It should be standard for unresected disease and considered as a viable alternative for patients with borderline resectable disease for whom resection would be highly morbid. [ABSTRACT FROM AUTHOR]

Background: The purpose of this exploratory study was to examine positive psychology constructs (life orientation/optimism, life satisfaction, happiness, psychological well‐being and personal well‐being) that may predict the family quality of life (FQOL) of parents of children with intellectual and developmental disabilities (IDD) in Turkey. Methods: Data were obtained from a convenience sample of 660 parents of children with IDD who responded to six assessments, including a measure of FQOL. An analysis using stepwise multiple regression was conducted to identify predictors of FQOL as rated by parents. Results: The four constructs including personal well‐being, psychological well‐being, life orientation (optimism) and life satisfaction significantly explained 60% of the total variance of FQOL. The amount of explained variance, beta scores and correlations suggests that these positive psychology constructs are significant predictors of FQOL of parents of children with IDD in Turkey. Conclusion: The study findings suggested that positive psychological constructs at the individual level were positively related to FQOL at the group level. Personal well‐being was the strongest predictor of FOQL of parents who have children with IDD in Turkey. The results also indicated that other constructs including psychological well‐being, an optimistic life orientation and life satisfaction contribute significantly to the FQOL of parents of children with IDD. [ABSTRACT FROM AUTHOR]

Cyanide leach solutions produced from gold/silver ores can be contaminated with zinc due to the gold/silver cementation in Merrill-Crowe process and/or the dissolution of zinc minerals present in the ore. Zinc levels in cyanide solutions should be controlled to avoid potential problems in leaching and downstream processes associated with the accumulation of zinc. In this study, the application of a novel method was demonstrated for the precipitation of zinc from synthetic/real cyanide solutions using Trimercapto- s -triazine (TMT), a non-toxic organic reagent. Experimental studies have shown that precipitation of zinc with TMT is a fast process occurring in a short period of time i.e., ≤15 min. Increasing the concentration of TMT (33–90 mM) and pH (10–12.5) was found to improve the precipitation of zinc, which was unaffected by increasing the temperature (20–60 °C). Response surface methodology was adopted for detailed investigation of the effect of [TMT]/[Zn] ratio (2.70–16.25), [CN−]/[Zn] ratio (3.00–8.00) and initial concentration of Zn (50–950 mg/L) on the precipitation of zinc. High recoveries (≤95.4%) were obtained under suitable conditions. Precipitation tests were also performed using synthetic multi-metal and real leach solutions. The complete recovery/dissolution of zinc from the precipitates was also demonstrated using different acids (HCl and H 2 SO 4). The findings have shown that TMT can be effectively used as an environmentally friendly reagent for removal of zinc from cyanide leach solutions. • Trimercapto- s -triazine (TMT) efficiently precipitates zinc from cyanide solutions. • Precipitation of zinc by TMT occurs rapidly within ≤15 min. • [TMT]/[Zn] ratio is the most influential parameter on the precipitation process. • TMT selectively precipitates zinc from gold and copper. • TMT can be readily recovered from Zn-TMT precipitates by mineral acids. [ABSTRACT FROM AUTHOR]