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Objectives: The centrifugal ultrafiltration–high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P

Here we present a computational and experimental fluid dynamics study for the characterization of the flow field within the gas chamber of a Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) sensor, at different flow rates at the inlet of the chamber. The transition from laminar to turbulent regime is ruled both by the inlet flow conditions and dimension of the gas chamber. The study shows how the distribution of the flow field in the chamber can influence the QEPAS sensor sensitivity, at different operating pressures. When turbulences and eddies are generated within the gas chamber, the efficiency of photoacoustic generation is significantly altered.

Dual-comb photoacoustic spectroscopy (DC-PAS) advances spectral measurements by offering high-sensitivity and compact size in a wavelength-independent manner. Here, we present a novel cantilever-enhanced DC-PAS scheme, employing a high-sensitivity fiber-optic acoustic sensor based on an optical cantilever and a non-resonant photoacoustic cell (PAC) featuring a flat-response characteristic. The dual comb is down-converted to the audio frequency range, and the resulting multiheterodyne sound waves from the photoacoustic effect, are mapped into the response frequency region of the optical cantilever microphone. This cantilever-enhanced DC-PAS method provides advantages such as high sensitivity, compact design, and immunity to electromagnetic interference. Through 10 seconds averaging time, the proposed approach experimentally achieved a minimum detection limit of 860 ppb for acetylene. This technology presents outstanding opportunities for highly sensitive detection of trace gases in a wavelength-independent manner, all within a compact volume.

Summary: Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host’s energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.

Background: Hemihypertrophy (HH) is a rare congenital malformation usually recognized at birth. It is often diagnosed due to impaired aesthetics and mobility caused by asymmetry of the face, body, or limbs. Some patients are diagnosed due to the presence of tumors and mental abnormalities. Case presentation: A 14-year-old boy with hoarseness since infancy and progressively increasing with age. Laryngoscopy and CT of the larynx suggested bilateral asymmetry of the laryngeal structures, and voice analysis suggested severe voice disorders. The boy had no history of trauma or other medical conditions, but had physical asymmetry since birth, which coincided with the laryngeal asymmetry. After a detailed examination and evaluation, we considered that his voice disorders were unexpectedly caused by crossed idiopathic HH. Since the boy in his growth spurts is not a candidate for surgery, we implemented individualized voice correction therapy. After practicing, the boy's voice disorders were significantly relieved. Conclusion: Congenital HH can cause asymmetrical development of the larynx, which leads to voice disorders. Voice correction therapy is an effective treatment for patients unsuitable for surgery.

The historical sedimentary and evolutionary characteristics of persistent organic pollutants and endocrine disruptors in typical regions of the Three Gorges Reservoir are scarcely studied. Herein, the 96-year data on contaminated sediment history were reconstructed using Caesium 137 isotope dating. Polychlorinated biphenyl concentrations in the involved sediment cores ranged from non-detected (ND) to 11.39 ng/g. The concentrations of polycyclic aromatic hydrocarbons ranged from ND to 2075.20 ng/g and peaked in the 1970s owing to natural, agricultural and human activities. Further, phthalate esters (PAEs) and heavy metals (HMs) were detected at concentrations ranging from ND to 589.2 ng/g and 12.10–93.67 μg/g, respectively, with highest values recorded in the 1980s owing to rapid industrialisation and insufficient management during China's early reform and development stages. PAE and HM concentrations have increased in recent years, suggesting the need to focus on industrial and agricultural activities that have caused this impact. Although current pollutant concentrations in sediments do not pose a risk to the aquatic ecosystem, they should be continuously monitored.

The mortality rate of patients with sepsis-induced acute kidney injury (S-AKI) is notably elevated. The initial categorization of prognostic indicators has a beneficial impact on elucidating and enhancing disease outcomes. This study aimed to predict the mortality risk of S-AKI patients by employing machine learning techniques. The sample size determined by a four-step procedure yielded 1508 samples. The research design necessitated the inclusion of individuals with S-AKI from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The patients were initially admitted to the Intensive Care Unit (ICU) for their hospital stay. Additionally, these patients (aged from 18 to 89 years old) had encountered S-AKI on the day of their admittance. Forty-two predictive factors were analyzed, with hospitalization death as the outcome variable. The training set (4001 cases) consisted of 70 % of the participants, and the remaining (1714 cases) participants were allocated to the validation set. Furthermore, an additional validation set (MIMIC-III) consisted of 1757 patients from the MIMIC-III database. Moreover, an external validation set from the Intensive Care Department of Beijing Friendship Hospital (BFH) comprised 72 patients. Six machine learning models were employed in the prediction, namely the logistic, lasso, rpart, random forest, xgboost, and artificial neural network models. The comparative efficacy of the newly developed model in relation to the APACHE II model for predicting mortality risk was also assessed. The XGBoost model exhibited a superior performance with the training set. With the internal validation set and the two external validation sets (MIMIC-III and BFH), the xgboost algorithm demonstrated the highest performance. Meanwhile, APACHE II performed poorly at predicting the mortality risk with the BFH validation set. The mortality risk was influenced by three primary clinical parameters: urine volume, lactate, and Glasgow Coma Scale (GCS) score. Thus, we developed a prediction model for the risk of death among S-AKI patients that has an improved performance compared to previous models and is a potentially valuable tool for S-AKI prediction and treatment in the clinic.

ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the “ADSCs-scaffold composite” into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.

We report on a photoacoustic sensor system based on a differential photoacoustic cell to detect the concentration of CO impurities in hydrogen. A DFB-QCL laser with a central wavelength of 4.61 µm was employed as an exciting source with an optical power of 21 mW. Different concentrations of CO gas mixed with pure hydrogen were injected into the photoacoustic cell to test the linear response of the photoacoustic signal to the CO concentration. The stability of the long-term operation was verified by Allan-Werle deviation analysis. The minimum detection limit (MDL, SNR=1) results 8 ppb at 1 s and reaches a sub-ppb level at 100 s of integration time. Dynamic response of the system is linear and has been tested up to the concentration of 6 ppm. Saturation conditions are expected to be reached for CO concentration larger than 100 ppm.

Folded-optics-based quartz-enhanced photoacoustic and photothermal hybrid spectroscopy (FO-QEPA-PTS) is reported for the first time. In FO-QEPA-PTS, the detection of the photoacoustic and photothermal hybrid signal is achieved through the use of a custom quartz tuning fork (QTF), thereby mitigating the issue of resonant frequency mismatch typically encountered in quartz-enhanced photoacoustic-photothermal spectroscopy employing multiple QTFs. A multi-laser beam, created by a multi-pass cell (MPC) with a designed single-line spot pattern, partially strikes the inner edge of the QTF and partially passes through the prong of the QTF, thereby generating photoacoustic and photothermal hybrid signals. To assess the performance of FO-QEPA-PTS, 1 % acetylene is selected as the analyte gas and the 2f signals produced by the photoacoustic, the photothermal, and their hybrid effects are measured. Comparative analysis against QEPAS and QEPTS reveals signal gain factors of ∼ 79 and ∼ 14, respectively, when these laser beams created by MPC excite the QTF operating at fundamental resonance mode in phase. In the FO-QEPA-PTS signal, the proportions of the photoacoustic and the photothermal effects induced by the multiple beams are ∼7 % and 93 %, respectively.

In this paper, UV/NH2Cl process was used to research the degradation of sulfathiazole (STZ) and the formation of disinfection by-products (DBPs) after disinfection were detected. UV and NH2Cl process showed a synergistic effect on the removal of STZ. Natural organic matter and CO32− inhibited the STZ degradation, NO3− promoted the degradation of STZ, whereas NH2Cl concentration, HCO3− and Cl− had dual effects on the removal of STZ. The removal of STZ by UV/NH2Cl was slightly influenced by pH. The contribution of reactive chlorine species and reactive nitrogen species to STZ degradation was significantly higher than that of HO·. Possible STZ degradation pathways were presented by analyzing intermediate products. In addition, the pretreatment of UV/NH2Cl significantly reduced the formation of DBPs during NH2Cl or NaClO disinfection. In conclusion, UV/NH2Cl process is an effective water treatment technology and can be well applied for practical purposes.

We present a quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensor designed for precise monitoring of ammonia (NH3) at ppb-level concentrations. The sensor is based on a novel custom quartz tuning fork (QTF) with a mid-infrared quantum cascade laser emitting at 9.55 µm. The custom QTF with a hammer-shaped prong geometry which is also modified by surface grooves is designed as the acoustic transducer, providing a low resonance frequency of 9.5 kHz and a high-quality factor of 10263 at atmospheric pressure. In addition, a temperature of 50 °C and a large gas flow rate of 260 standard cubic centimeters per minute (sccm) are applied to mitigate the adsorption and desorption effect arising from the polarized molecular of NH3. With 80-mW optical power and 300-ms lock-in integration time, the detection limit is achieved to be 2.2 ppb which is the best value reported in the literature so far for NH3 QEPAS sensors, corresponding to a normalized noise equivalent absorption coefficient of 1.4 × 10−8 W cm−1 Hz−1/2. A five-day continuous monitoring for atmospheric NH3 is performed, verifying the stability and robustness of the presented QEPAS-based NH3 sensor.

This paper focus on the cooling-down performance of the LHRS for a high-low temperature test chamber, and proposed a new method to optimize the cooling-down process of the LHRS based on a quasi-steady-state simulation model to investigated the optimal MR concentration and the shifting strategy of suction pressure during the cooling-down process. Targeted on the maximum cooling capacity, the optimal suction pressure-evaporating temperature curve at a specified mixed refrigerant concentration can be obtained, which can be matched by the sectional suction pressure adjustment in the practical cooling-down process to reduce the overall cooling-down time. As an example, the fastest overall cooling-down time is achieved using the R50/R1150/R290/R600a mixed refrigerant (0.3/0.4/0.05/0.25 b y mole) and corresponding shifting parameters (including two shifting temperatures and three shifting pressures) for the sectional suction pressure adjustment, when the air temperature in the test chamber is dropped from 20 °C to −80 °C. The investigation results can provide good references for the industrial design of a high-low temperature test chamber. The optimization method used in this paper can also provide references for researches on cooling-down processes of other refrigeration systems using multi-component mixed refrigerants.

We present an optical sensor based on light-induced thermoelastic spectroscopy for the detection of hydrogen sulfide (H2S) in sulfur hexafluoride (SF6). The sensor incorporates a compact multi-pass cell measuring 6 cm × 4 cm × 4 cm and utilizes a quartz tuning fork (QTF) photodetector. A 1.58 µm near-infrared distributed feedback (DFB) laser with an optical power of 30 mW serves as the excitation source. The sensor achieved a minimum detection limit (MDL) of ∼300 ppb at an integration time of 300 ms, corresponding to a normalized noise equivalent absorption coefficient (NNEA) of 3.96 × 10−9 W·cm−1·Hz−1/2. By extending the integration time to 100 s, the MDL can be reduced to ∼25 ppb. The sensor exhibits a response time of ∼1 min for a gas flow rate of 70 sccm.

A complex and vast biological network regulates all biological functions in the human body in a sophisticated manner, and abnormalities in this network can lead to disease and even cancer. The construction of a high-quality human molecular interaction network is possible with the development of experimental techniques that facilitate the interpretation of the mechanisms of drug treatment for cancer. We collected 11 molecular interaction databases based on experimental sources and constructed a human protein-protein interaction (PPI) network and a human transcriptional regulatory network (HTRN). A random walk-based graph embedding method was used to calculate the diffusion profiles of drugs and cancers, and a pipeline was constructed by using five similarity comparison metrics combined with a rank aggregation algorithm, which can be implemented for drug screening and biomarker gene prediction. Taking NSCLC as an example, curcumin was identified as a potentially promising anticancer drug from 5450 natural small molecules, and combined with differentially expressed genes, survival analysis, and topological ranking, we obtained BIRC5 (survivin), which is both a biomarker for NSCLC and a key target for curcumin. Finally, the binding mode of curcumin and survivin was explored using molecular docking. This work has a guiding significance for antitumor drug screening and the identification of tumor markers.

Here we report on a study of the non-radiative relaxation dynamic of 12CH4 and 13CH4 in wet nitrogen-based matrixes by using the quartz-enhanced photoacoustic spectroscopy (QEPAS) technique. The dependence of the QEPAS signal on pressure at fixed matrix composition and on H2O concentration at fixed pressure was investigated. We demonstrated that QEPAS measurements can be used to retrieve both the effective relaxation rate in the matrix, and the V-T relaxation rate associated to collisions with nitrogen and water vapor. No significant differences in measured relaxation rates were observed between the two isotopologues.

In this work, a comparison between Quartz Enhanced Photoacoustic Spectroscopy (QEPAS) and Beat Frequency-QEPAS (BF-QEPAS) techniques for environmental monitoring of pollutants is reported. A spectrophone composed of a T-shaped Quartz Tuning Fork (QTF) coupled with resonator tubes was employed as a detection module. An interband cascade laser has been used as an exciting source, allowing the targeting of two NO absorption features, located at 1900.07 cm−1 and 1900.52 cm−1, and a water vapor absorption feature, located at 1901.76 cm−1. Minimum detection limits of 90 ppb and 180 ppb were achieved with QEPAS and BF-QEPAS techniques, respectively, for NO detection. The capability to detect multiple components in the same gas mixture using BF-QEPAS was also demonstrated.

Background: Helicobacter pylori infection is related to the occurrence of various diseases, and its influencing factors have been studied worldwide. Research on the current status of H. pylori infection in underdeveloped rural areas in China is limited. Aim: This research aimed to understand the status of H. pylori infection and its risk factors in rural Yan'an city, Northwest China. Methods: This cross-sectional study was implemented in two villages in Yan'an city in 2018, and 226 individuals underwent the Carbon-14 urea breath test to detect H. pylori infection. Participants' demographic characteristics, socioeconomic status, dietary habits, and lifestyle were collected through structured questionnaires. Results: In this research, the overall infection rate of H. pylori was 32.7% (74/226). Multivariate logistic regression analysis showed that people with a body mass index (BMI)≥24 kg/m2 (OR = 3.03; 95% CI = 1.65–5.57) and people who frequently dined out (OR = 8.87; 95% CI = 1.43–54.97) were more likely to be infected H. pylori. Conversely, the H. pylori infection risk was reduced among people over 60 years of age (OR = 0.32; 95% CI = 0.17–0.62) as well as among those who ate sweet potatoes more than 7 times a week (OR = 0.23; 95% CI = 0.07–0.75). Conclusion: A BMI≥24 kg/m2 and frequent eating out were risk factors for H. pylori infection among the village inhabitants of Yan'an city. The consumption of sweet potatoes was related to a low risk of H. pylori infection.

Background: Since the outbreak of coronavirus disease (COVID-19), the high infection rate and mutation frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent, have contributed to the ongoing global pandemic. Vaccination has become the most effective means of controlling COVID-19. Traditional neutralizing tests of sera are complex and labor-intensive, therefore, a rapid test for detecting neutralizing antibodies and antibody status post-immunization is needed. Methods: Based on the fact that antibodies exhibit neutralizing activity by blocking the binding of the S protein receptor-binding domain (S-RBD) to ACE2, we developed a rapid neutralizing antibody test, ACE2-Block-ELISA. To evaluate the sensitivity and specificity, we used 54 positive and 84 negative serum samples. We also tested the neutralizing activities of monoclonal antibodies (mAbs) and 214 sera samples from healthy individuals immunized with the inactivated SARS-CoV-2 vaccine. Results: The sensitivity and specificity of the ACE2-Block ELISA were 96.3% and 100%, respectively. For neutralizing mAb screening, ch-2C5 was selected for its ability to block the ACE2–S-RBD interaction. A plaque assay confirmed that ch-2C5 neutralized SARS-CoV-2, with NT50 values of 4.19, 10.63, and 1.074 µg/mL against the SARS-CoV-2 original strain, and the Beta and Delta variants, respectively. For the immunized sera samples, the neutralizing positive rate dropped from 82.14% to 32.16% within 4 months post-vaccination. Conclusions: This study developed and validated an ACE2-Block-ELISA to test the neutralizing activities of antibodies. As a rapid, inexpensive and easy-to-perform method, this ACE2-Block-ELISA has potential applications in rapid neutralizing mAb screening and SARS-CoV-2 vaccine evaluation.

Rearranged renal cell carcinomas (RCC) are rare types of kidney cancer. The clinicopathological features of rearranged RCC require further validation. The pathological diagnosis usually depends on immunohistochemistry and molecular analysis. This study aimed to explore the expression features of anti-TFE3, TFEB, and ALK in different renal entities. In addition, we collected thirty-six TFE3-rearranged RCC, two TFEB-altered RCC, and one ALK-rearranged RCC to explore their clinicopathological features. We observed that TFE3 can sometimes be weakly expressed in non-TFE3-rearranged RCC. TFE3-rearranged RCC usually exhibited strong TFE3 expression. However, clear cell RCC and FH-deficient RCC also displayed strong TFE3 expression. TFEB also can be weakly expressed in clear cell RCC. However, ALK IHC showed a relatively high specificity and was negative for all non-ALK-rearranged RCC. The ALK-rearranged RCC was analyzed using next generation sequencing to explore gene alterations, and we identified a novel gene partner, SLIT1. ALK-rearranged RCC appears to have eosinophilic cytoplasm. Tumor cells with clear cytoplasm may exclude this diagnosis. Psammomatous bodies (22/38) and pattern multiplicity (35/38) were observed in more than half of the patients. In conclusion, weak TFE3 expression did not indicate TFE3 rearrangement. Strong TFE3 expression had a higher value for indicating TFE3-rearranged RCC, although other entities can also exhibit a strong pattern. Young age combined with morphological features (psammomatous calcification and pattern multiplicity) may indicate the diagnosis of rearranged RCC.

Facing a stressful environment of peer rejection and discrimination, Chinese migrant adolescents are at high risk of developing behavior problems while receiving insufficient family support. In this context, the current study aimed to explore the pathway from peer rejection to adolescent behavior problems via the mediating role of delinquent peer affiliation and with the moderating roles of parental company and parental monitoring taken into consideration. A sample of 2041 migrant adolescents (46.2% female, mean age = 13.595) was drawn from the first and second waves of the China Education Panel Survey (CEPS) for running a moderated mediation model. The results demonstrated that peer rejection positively predicted behavior problems through the mediator of delinquent peer affiliation (indirect effect = 0.007, 95% CI = [0.003, 0.014]). This mediating mechanism was moderated by parental company and by parental monitoring. Our study deepened the theoretical understanding and application of the general strain theory by showing how the interaction of peer stressors and parenting elements affected the behavior of migrant adolescents in a Chinese context. Further studies could pay more attention to the dynamic interplay between the family and peer systems, especially for rejected and marginalized adolescent groups. Limitations and implications for future school-based and family-based practices are also discussed.

Photoacoustic cells play an important role in photoacoustic trace gas analysis, as they can amplify the photoacoustic signal and improve detection limit. Therefore, the structure and dimensional design of a photoacoustic cell are very important for the performance of a photoacoustic sensing system. In this review, the theory and the method of acousto-electric analogy for the photoacoustic cell design are discussed in detail. Starting from the basics of the acousto-electric analogy, the counterparts of acoustic elements in electric circuits are first deduced from the analogies between acoustic and electric networks. Subsequently, an acoustic transmission line model is reviewed, and the model is demonstrated to optimize the geometry of the photoacoustic cell and investigate the properties of the cell. Finally, using the acousto-electric analogy method, the equivalent electric circuits of several types of photoacoustic cells, such as the Helmholtz resonant photoacoustic cell, the H-type resonant photoacoustic cell, the differential photoacoustic cell, etc., are presented.

Cancer-associated fibroblasts (CAFs) can exert their immunosuppressive effects by secreting various effectors that are involved in the regulation of tumor-infiltrating immune cells as well as other immune components in the tumor immune microenvironment (TIME), thereby promoting tumorigenesis, progression, metastasis, and drug resistance. Although a large number of studies suggest that CAFs play a key regulatory role in the development of head and neck squamous cell carcinoma (HNSCC), there are limited studies on the relevance of CAFs to the prognosis of HNSCC. In this study, we identified a prognostic signature containing eight CAF-related genes for HNSCC by univariate Cox analysis, lasso regression, stepwise regression, and multivariate Cox analysis. Our validation in primary cultures of CAFs from human HNSCC and four human HNSCC cell lines confirmed that these eight genes are indeed characteristic markers of CAFs. Immune cell infiltration differences analysis between high-risk and low-risk groups according to the eight CAF-related genes signature hinted at CAFs regulatory roles in the TIME, further revealing its potential role on prognosis. The signature of the eight CAF-related genes was validated in different independent validation cohorts and all showed that it was a valid marker for prognosis. The significantly higher overall survival (OS) in the low-risk group compared to the high-risk group was confirmed by Kaplan-Meier (K-M) analysis, suggesting that the signature of CAF-related genes can be used as a non-invasive predictive tool for HNSCC prognosis. The low-risk group had significantly higher levels of tumor-killing immune cell infiltration, as confirmed by CIBERSORT analysis, such as CD8+ T cells, follicular helper T cells, and Dendritic cells (DCs) in the low-risk group. In contrast, the level of infiltration of pro-tumor cells such as M0 macrophages and activated Mast cells (MCs) was lower. It is crucial to delve into the complex mechanisms between CAFs and immune cells to find potential regulatory targets and may provide new evidence for subsequently targeted immunotherapy. These results suggest that the signature of the eight CAF-related genes is a powerful indicator for the assessment of the TIME of HNSCC. It may provide a new and reliable potential indicator for clinicians to predict the prognosis of HNSCC, which may be used to guide treatment and clinical decision-making in HNSCC patients. Meanwhile, CAF-related genes are expected to become tumor biomarkers and effective targets for HNSCC.

Sepsis often causes acute kidney injury (AKI). Autophagy of renal tubular epithelial cells is considered a cytoprotective mechanism in septic AKI; however, the role of autophagy of renal endothelial cells is uninvestigated. The current study examined whether autophagy was induced by sepsis in renal endothelial cells and whether induction of autophagy in these cells attenuated the degree of AKI. Cecal ligation and puncture (CLP) was used as a model of sepsis in rats. Four experimental groups included: sham, CLP alone, CLP + rapamycin (RAPA), and CLP + dimethyl sulfoxide (DMSO), where RAPA was used as an activator of autophagy. CLP increased renal LC3-II protein levels with an additional transient increase by RAPA at 18 h. In addition, CLP induced autophagosome formation in renal endothelial cells had an additional increase induced by RAPA. Interestingly, the levels of bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), an endothelial cell-specific protein in the kidney, were also increased by CLP, albeit it was transiently downregulated by RAPA at 18 h. Serum thrombomodulin increased and renal vascular endothelial (VE)-cadherin decreased following CLP, and these changes were attenuated by RAPA. The renal cortex exhibited and inflammatory tissue damage after CLP, and RAPA alleviated these histopathological injuries. The current findings indicate that autophagy was induced by sepsis in renal endothelial cells, and upregulation of autophagy in these cells alleviated endothelial injury and AKI. In addition, BAMBI was induced by sepsis in the kidney, which may play a role in regulating endothelial stability in septic AKI.

Advances in molecular biology techniques have led to the recognition of more molecularly defined renal entities. However, some molecular-defined renal cell carcinomas (RCC) exhibit heterogeneous morphologies. In recent years, TSC/mTOR and NF2 alterations in renal cancers have attracted considerable attention from pathologists, including several renal tumors that have been validated as different entities. The monoallelic MUTYH germline mutation has also recently been demonstrated to be a driver of tumorigenesis, which is relatively enriched in renal cancers and may predict the risk of metastasis. In the current study, we presented seven cases with TSC/mTOR alterations (two with fibromyomatous stroma, one concomitant with ELOC mutation, three eosinophilic solid and cystic RCC, and two RCC, NOS), four cases with NF2 mutations (one concomitant with FH mutation, one biphasic hyalinizing psammomatous RCC, and two RCC, NOS), and two cases with monoallelic MUTYH germline mutations (one collecting duct carcinoma and one papillary RCC). We observed that renal cancers harboring these mutations had a wide morphological spectrum. Renal neoplasms with TSC/mTOR mutations may have an indolent outcome. NF2-mutated RCC appeared to display calcification and sclerotic stroma. The identification of these renal cancers can help reduce the number of tumors diagnosed as RCC, NOS. However, whether they can be grouped into TSC/mTOR, NF2, or MUTYH -associated RCC requires further validation.

A gas sensor based on light-induced thermo-elastic spectroscopy (LITES) capable to detect methane (C1) and ethane (C2) in a wide concentration range, from percent down to part-per-billion (ppb), is here reported. A novel approach has been implemented, exploiting a compact sensor design that accommodates both a custom 9.8 kHz quartz tuning fork (QTF) used as photodetector and the gas sample in the same housing. The resulting optical pathlength was only 2.5 cm. An interband cascade laser (ICL) with emission wavelength of 3.345 µm was used to target absorption features of C1 and C2. The effects of high concentration analytes on sensor response were firstly investigated. C1 concentration varied from 1% to 10%, while C2 concentration varied from 0.1% to 1%. These ranges were selected to retrace the typical natural gas composition in a 1:10 nitrogen dilution. The LITES sensor was calibrated for both the gas species independently and returned nonlinear but monotonic responses for the two analytes. These univariate calibrations were used to retrieve the composition of C1-C2 binary mixtures with accuracy higher than 98%, without the need for further data analysis. Minimum detection limits of ∼650 ppb and ∼90 ppb were achieved at 10 s of integration time for C1 and C2, respectively, demonstrating the capability of the developed LITES sensor to operate with concentration ranges spanning over 6 orders of magnitude.

The increase in fatal accidents and chronic illnesses caused by hydrogen sulfide (H2S) exposure occurring in various workplaces is pushing the development of sensing systems for continuous and in-field monitoring of this hazardous gas. We report here on the design and realization of a Near-IR quartz-enhanced photoacoustic sensor (QEPAS) for H2S leaks detection. H2S QEPAS signal was measured in matrixes containing up to 1 % of methane (CH4) and nitrogen (N2) which were chosen as the laboratory model environment for leakages from oil and gas wells or various industrial processes where H2S and CH4 can leak simultaneously. An investigation of the influence of CH4 on H2S relaxation and photoacoustic generation was proposed in this work and the sensor performances were carefully assessed with respect to CH4 content in the mixture. We demonstrated the high selectivity, with no cross talk between H2S, H2O and CH4 absorption lines, high sensitivity, and fast response time of the developed sensor, achieving a minimum detection limit (MDL) of 2.5 ppm for H2S with 2 s lock-in integration time. The employed 2.6 µm laser allowed us to employ the sensor also for CH4 detection, achieving an MDL of 85 ppm. The realized QEPAS sensor lends itself to the development of a portable and compact device for industrial monitoring.

ABSTRACT: Objectives: Here we describe the first draft genome analysis of a CRISPR-carrying, multidrug-resistant, candidate novel Pseudomonas sp. NCCP-436T isolated from faeces of a neonatal diarrhoeic calf.Methods: The genome of strain NCCP-436T was sequenced using an Illumina NovaSeq PE150 platform and analysed using various bioinformatic tools. The virulence factors and resistome were identified using PATRIC and CARD servers, while CGView Server was used to construct a circular genome map. Antimicrobial susceptibility was determined by the disk diffusion technique.Results: The draft genome of strain NCCP-436T contains 43 contigs with a total genome size of 3,683,517 bp (61.4% GC content). There are 3,452 predicted genes, including 60 tRNAs, 7 rRNAs and 12 sRNAs. CRISPR analysis revealed two CRISPR arrays with lengths of 1103 bp and 867 bp. Strain NCCP-436T was highly resistant to fluoroquinolone, β-lactam, cephalosporin, aminoglycoside, penicillin, rifamycin, macrolide, glycopeptide, trimethoprim/sulfonamide and tetracycline antibiotic classes. Additionally, 22 antibiotic resistance genes, 313 virulence genes and 253 pathogen–host interactor genes were predicted. Comparison of the average nucleotide identity and digital DNA–DNA hybridisation values with the closely-related strain Pseudomonas khazarica (TBZ2) was found to be 82.08% and 34.90%, respectively, illustrating strain NCCP-436T as a potentially new species of Pseudomonas.Conclusion: Substantial number of antibiotic resistance and virulence genes and homology with human pathogens were predicted, exposing the pathogenic and zoonotic potential of strain NCCP-436T to public health. These findings may be used to better understand the genomic epidemiological features and drug resistance mechanisms of pathogenic Pseudomonas spp. in Pakistan.

Soil wind erosion has consistently been a serious ecological problem in northern China. In recent decades, the grasslands of Inner Mongolia have suffered severe degradation due to overgrazing. After vegetation degradation, the surface roughness and ability to intercept wind and sand decrease, resulting in severe soil wind erosion. Soil particles of different sizes have different sensitivities to wind erosion; those with smaller particle sizes are usually more susceptible to wind erosion. Therefore, the composition of surface soil particles can be an indicator of the local soil wind erosion status and risk. In this study, we used the typical grasslands of Inner Mongolia as the object and set different grazing intensities (i.e., low grazing, moderate grazing, high grazing and no grazing). We assessed the risk of grazing-induced grassland degradation and soil erosion by analyzing changes in vegetation and surface soil particle composition. We found that wind erosion mainly occurred in soils with particle sizes of 0.075–0.5 mm. Low grazing had little influence on aboveground biomass but increased topsoil compaction when compared with no grazing. High grazing reduced aboveground biomass, while trampling caused surface fragmentation and increased the risk of soil erosion, resulting in a coarser soil texture. We suggest that in practical management, the occurrence of soil wind erosion can be reduced by appropriately reducing grazing pressure, and the cessation of grazing is not the best method for grassland utilization and restoration.

A role for ferroptosis in articular cartilage destruction associated with rheumatoid arthritis (RA) has not been identified. We previously reported transient receptor potential melastatin 7 (TRPM7) expression was correlated with RA cartilage destruction. Herein, we further characterized a role for TRPM7 in chondrocyte ferroptosis. The expression of TRPM7 was found to be elevated in articular chondrocytes derived from adjuvant arthritis (AA) rats, human RA patients, and cultured chondrocytes treated with the ferroptosis inducer, erastin. TRPM7 knockdown or pharmacological inhibition protected primary rat articular chondrocytes and human chondrocytes (C28/I2 cells) from ferroptosis. Moreover, TRPM7 channel activity was demonstrated to contribute to chondrocyte ferroptosis by elevation of intracellular Ca2+. Mechanistically, the PKCα-NOX4 axis was found to respond to stimulation with erastin, which resulted in TRPM7-mediated chondrocyte ferroptosis. Meanwhile, PKCα was shown to directly bind to NOX4, which could be reduced by TRPM7 channel inhibition. Adeno-associated virus 9-mediated TRPM7 silencing or TRPM7 blockade with 2-APB alleviated articular cartilage destruction in AA rats and inhibited chondrocyte ferroptosis. Collectively, both genetic and pharmacological inhibitions of TRPM7 attenuated articular cartilage damage and chondrocyte ferroptosis via the PKCα-NOX4 axis, suggesting that TRPM7-mediated chondrocyte ferroptosis is a promising target for the prevention and treatment of RA.

All-optical light-induced thermoacoustic spectroscopy (AO-LITS) is reported for the first time for highly sensitive and selective gas sensing, in which a commercial standard quartz tuning fork (QTF) is employed as a photothermal detector. The vibration of the QTF was measured by the highly sensitive fiber-optic Fabry-Pérot (FP) interferometry (FPI) technique, instead of the piezoelectric detection in the conventional LITS. To improve the stability of the sensor system, a compact QTF-based fiber-optic FPI module is fabricated by 3D printing technique and a dual-wavelength demodulation method with the ellipse-fitting differential-cross-multiplication algorithm (DW-EF-DCM) is exploited for the FPI measurement. The all-optical detection scheme has the advantages of remote detection and immunity to electromagnetic interference. A minimum detection limit (MDL) of 422 ppb was achieved for hydrogen sulfide (H2S), which was ~ 3 times lower than a conventional electrical LITS sensor system. The AO-LITS can provide a promising approach for remote and non-contact gas sensing in the whole infrared spectral region.

A breath sensor for real-time measurement of human exhaled carbon monoxide is reported. This breath sensor is based on a novel photoacoustic heterodyne gas sensing technique, which combines the conventional photoacoustic spectroscopy with the beat-frequency detection algorithm, thus offering a fast response time and a convenient optical alignment, as well as eliminating the needs for frequency calibration and wavelength locking. The principle of photoacoustic heterodyne gas sensing was explained in detail. The performance of the photoacoustic heterodyne breath sensor was evaluated in terms of minimum detection limit, response time, and linearity. The exhaled carbon monoxide levels of eight volunteers were measured and the results demonstrate the reliability and feasibility of this breath sensor.

Purpose: To describe an implementation of dual-energy computed tomography (DECT) for calculation of proton stopping-power ratios (SPRs) in a commercial treatment-planning system. The process for validation and the workflow for safe deployment of DECT is described, using single-energy computed tomography (SECT) as a safety check for DECT dose calculation. Materials and Methods: The DECT images were acquired at 80 kVp and 140 kVp and were processed with computed tomography scanner software to derive the electron density and effective atomic number images. Reference SPRs of tissue-equivalent plugs from Gammex (Middleton, Wisconsin) and CIRS (Computerized Imaging Reference Systems, Norfolk, Virginia) electron density phantoms were used for validation and comparison of SECT versus DECT calculated through the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California) application programming interface scripting tool. An in-house software was also used to create DECT SPR computed tomography images for comparison with the script output. In the workflow, using the Eclipse system application programming interface script, clinical plans were optimized with the SECT image set and then forward-calculated with the DECT SPR for the final dose distribution. In a second workflow, the plans were optimized using DECT SPR with reduced range-uncertainty margins. Results: For the Gammex phantom, the root mean square error in SPR was 1.08% for DECT versus 2.29% for SECT for 10 tissue-surrogates, excluding the lung. For the CIRS Phantom, the corresponding results were 0.74% and 2.27%. When evaluating the head and neck plan, DECT optimization with 2% range-uncertainty margins achieved a small reduction in organ-at-risk doses compared with that of SECT plans with 3.5% range-uncertainty margins. For the liver case, DECT was used to identify and correct the lipiodol SPR in the SECT plan. Conclusion: It is feasible to use DECT for proton-dose calculation in a commercial treatment planning system in a safe manner. The range margins can be reduced to 2% in some sites, including the head and neck.

Glioma is one of the most common primary brain tumors. Gambogic acid (GA) is widely used in tumor chemotherapy. However, GA has poor water solubility, low bioavailability, and difficult permeability across the blood–brain barrier (BBB), leading to poor efficacy against brain tumors. In our study, we developed negatively charged GA-loaded PLGA nanobubbles [GA/poly(lactic-co-glycolic acid) (PLGA)] and conjugated them onto the surface of cationic lipid microbubbles (CMBs) through electrostatic interactions. The resulting GA/PLGA–CMB complex was characterized for its particle size, distribution, drug encapsulation efficiency, and ultrasound imaging property, revealing a high drug encapsulation efficiency and excellent contrast imaging capability. Importantly, significantly enhanced GA delivery into the brain could be observed after the intravenous administration of GA/PLGA–CMBs combined with low-intensity focused ultrasound (FUS) due to the cavitation from CMBs, which mediated blood–brain barrier (BBB) opening. Taking advantage of the opened BBB, GA/PLGA nanobubbles could be delivered into the tumor. Then, the second FUS irradiation at higher energy was used to induce the cavitation of GA/PLGA nanobubbles, producing the second cavitation on tumor cells, significantly enhancing the ability of GA to enter tumor cells and inhibit tumor growth inhibition efficacy.

A quartz enhanced photoacoustic spectroscopy (QEPAS) sensor capable to detect high concentrations of methane (C1) and ethane (C2) is here reported. The hydrocarbons fingerprint region around 3 µm was exploited using an interband cascade laser (ICL). A standard quartz tuning fork (QTF) coupled with two resonator tubes was used to detect the photoacoustic signal generated by the target molecules. Employing dedicated electronic boards to both control the laser source and collect the QTF signal, a shoe-box sized QEPAS sensor was realized. All the generated mixtures were downstream humidified to remove the influence of water vapor on the target gases. Several natural gas-like samples were generated and subsequently diluted 1:10 in N2. In the concentration ranges under investigation (1%−10% for C1 and 0.1%−1% for C2), both linear and nonlinear responses of the sensor were measured and signal variations due to matrix effects were observed. Partial least squares regression (PLSR) was employed as a multivariate statistical tool to accurately determine the concentrations of C1 and C2 in the mixtures, compensating the matrix relaxation effects. The achieved results extend the range of C1 and C2 concentrations detectable by QEPAS technique up to the percent scale.

A sensor system for exhaled ammonia (NH3) monitoring exploiting quartz-enhanced photoacoustic spectroscopy (QEPAS) was demonstrated. An erbium-doped fiber amplifier (EDFA) with an operating frequency band targeting an NH3 absorption line falling at 1531.68 nm and capable to emit up to 3 W of optical power was employed. A custom T-shaped grooved QTF with prong spacing of 1 mm was designed and realized to allow a proper focusing of the high-power optical beam exiting the EDFA between the prongs. The performance of the realized sensor system was optimized in terms of spectrophone parameters, laser power and modulation current, resulting in a NH3 minimum detectable concentration of 14 ppb at 1 s averaging time, corresponding to a normalized noise equivalent absorption coefficient (NNEA) of 8.15 × 10−9 cm−1 W/√Hz. Continuous measurements of the NH3 level exhaled by 3 healthy volunteers was carried out to demonstrate the potentiality of the developed sensor for breath analysis applications.

Compared with photon stereotactic body radiotherapy (SBRT) plans that may have to use many more penetrating x-ray beams for each isocenter, proton SBRT with ultrahypofractionated doses use fewer beam angles and offer significantly reduced low-dose radiation bath to normal liver tissue. We demonstrate techniques to deliver safe and effective proton SBRT, where planning and organ motion complexity further increased with multiple liver lesions. For treatment planning, we recommend robust and logical beam angles, avoiding devices and encouraging entry perpendicular to the dominant motion, as well as volumetric repainting to mitigate the interplay effect to clinically acceptable levels. This report highlights the significant technical challenges with ultrahypofractionated proton pencil beam scanning liver therapy, how they are managed, and the effectiveness of this treatment.

Introduction: The intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation. Patients and Methods: Fourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed. Results: The target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was − 11 ± 52 cGy and − 45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had

Background & Aims: Epithelial cells form a monolayer at mucosal surface that functions as a highly selective barrier. Lysophosphatidic acid (LPA) is a bioactive lipid that elicits a broad range of biological effects via cognate G protein-coupled receptors. LPA receptor 5 (LPA5) is highly expressed in intestinal epithelial cells, but its role in the intestine is not well-known. Here we determined the role of LPA5 in regulation of intestinal epithelial barrier. Methods: Epithelial barrier integrity was determined in mice with intestinal epithelial cell (IEC)-specific LPA5 deletion, Lpar5ΔIEC. LPA was orally administered to mice, and intestinal permeability was measured. Dextran sulfate sodium (DSS) was used to induce colitis. Human colonic epithelial cell lines were used to determine the LPA5-mediated signaling pathways that regulate epithelial barrier. Results: We observed increased epithelial permeability in Lpar5ΔIEC mice with reduced claudin-4 expression. Oral administration of LPA decreased intestinal permeability in wild-type mice, but the effect was greatly mitigated in Lpar5ΔIEC mice. Serum lipopolysaccharide level and bacterial loads in the intestine and liver were elevated in Lpar5ΔIEC mice. Lpar5ΔIEC mice developed more severe colitis induced with DSS. LPA5 transcriptionally regulated claudin-4, and this regulation was dependent on transactivation of the epidermal growth factor receptor, which induced localization of Rac1 at the cell membrane. LPA induced the translocation of Stat3 to the cell membrane and promoted the interaction between Rac1 and Stat3. Inhibition of Stat3 ablated LPA-mediated regulation of claudin-4. Conclusions: This study identifies LPA5 as a regulator of the intestinal barrier. LPA5 promotes claudin-4 expression in IECs through activation of Rac1 and Stat3.

The capacitors and inductors in actual circuits often fail to exhibit the ideal integer-order characteristics, so as the circuits containing these types of electronic components. The errors can be compensated by introducing the concept of fractional calculus. The Caputo–Fabrizio​ fractional derivative, which fixes the defect of the singularity problem in Caputo derivative, has been proposed in recent years. This work uses Caputo–Fabrizio fractional derivative to model the fractional Buck converter working in continuous conduction mode and to deduce its analytical solutions by Laplace transformation and its inverse transformation. The analytical solution of the output voltage is obtained and the waveform of the output voltage is simulated. The correctness of the model is verified and the impact of the fractional order on the dynamic performance of the Buck converter is analyzed. The steady-state average output voltage of the open-loop fractional Buck converter is also calculated.

In SF6 insulated high-voltage gas power systems, H2O is the most problematic impurity which not only decreases insulation performance but also creates an acidic atmosphere that promotes corrosion. Corrosion damages electrical equipment and leads to leaks, which pose serious safety hazards to people and the environment. A QEPAS-based sensor system for the sub-ppm level H2O detection in SF6 buffer gas was developed by use of a near-infrared commercial DFB diode laser. Since the specific physical constants of SF6 are strongly different from that of N2 or air, the resonant frequency and Q-factor of the bare quartz tuning fork (QTF) had changed to 32,763 Hz and 4173, respectively. The optimal vertical detection position was 1.2 mm far from the QTF opening. After the experimental optimization of acoustic micro-resonator (AmR) parameters, gas pressures, and modulation depths, a detection limit of 0.49 ppm was achieved for an averaging time of 1 s, which provided a powerful prevention tool for the safety monitoring in power systems.

In this paper, an on-beam quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor based on a custom quartz tuning fork (QTF) acting as a photoacoustic transducer, was realized and tested. The QTF is characterized by a resonance frequency of 28 kHz, ~15% lower than that of a commercially available 32.7 kHz standard QTF. One-dimensional acoustic micro resonator (AmR) was designed and optimized by using stainless-steel capillaries. The 28 kHz QTF and AmRs are assembled in on-beam QEPAS configuration. The AmR geometrical parameters have been optimized in terms of length and internal diameter. The laser beam focus position and the AmR coupling distance were also adjusted to maximize the coupling efficiency. For comparison, QEPAS on-beam configurations based on a standard QTF and on the 28 kHz QTF were compared in terms of H2O and CO2 detection sensitivity. In order to better characterize the performance of the system, H2O, C2H2 and CO2 were detected for a long time and the long-term stability was analyzed by an Allan variance analysis. With the integration time of 1 s, the detection limits for H2O, C2H2 and CO2 are 1.2 ppm, 28.8 ppb and 2.4 ppm, respectively. The detection limits for H2O, C2H2 and CO2 can be further improved to 325 ppb, 10.3 ppb and 318 ppb by increasing the integration time to 521 s, 183 s and 116 s

A compact quartz-enhanced photoacoustic sensor for ppb-level ambient NO2 detection is demonstrated, in which a high-power blue laser diode module with a small divergence angle was employed to take advantages of the directly proportional relationship between sensitivity and power, hence improving the detection sensitivity. In order to extend the stability time, a custom grooved quartz tuning fork with 800-μm prong spacing is employed to avoid complex signal balance and/or optical spatial filter components. The sensor performance is optimized and assessed in terms of optical coupling, power, gas flow rate, pressure, signal linearity and stability. A minimum detectable concentration (1σ) of 7.3 ppb with an averaging time of 1 s is achieved, which can be further improved to be 0.31 ppb with an averaging time of 590 s. Continuous measurements covering a five-day period are performed to demonstrate the stability and robustness of the reported NO2 sensor system.

Background and purpose: Scatter correction of cone-beam computed tomography (CBCT) projections may enable accurate online dose-delivery estimations in photon and proton-based radiotherapy. This study aimed to evaluate the impact of scatter correction in CBCT-based proton range/dose calculations, in scans acquired in both proton and photon gantries. Material and methods: CBCT projections of a Catphan and an Alderson phantom were acquired on both a proton and a photon gantry. The scatter corrected CBCTs (corrCBCTs) and the clinical reconstructions (stdCBCTs) were compared against CTs rigidly registered to the CBCTs (rigidCTs). The CBCTs of the Catphan phantom were segmented by materials for CT number analysis. Water equivalent path length (WEPL) maps were calculated through the Alderson phantom while proton plans optimized on the rigidCT and recalculated on all CBCTs were compared in a gamma analysis. Results: In medium and high-density materials, the corrCBCT CT numbers were much closer to those of the rigidCT than the stdCBCTs. E.g. in the 50% bone segmentations the differences were reduced from above 300 HU (with stdCBCT) to around 60–70 HU (with corrCBCT). Differences in WEPL from the rigidCT were typically well below 5 mm for the corrCBCTs, compared to well above 10 mm for the stdCBCTs with the largest deviations in the head and thorax regions. Gamma pass rates (2%/2mm) when comparing CBCT-based dose re-calculations to rigidCT calculations were improved from around 80% (with stdCBCT) to mostly above 90% (with corrCBCT). Conclusion: Scatter correction leads to substantial artefact reductions, improving accuracy of CBCT-based proton range/dose calculations.

Purpose: Radiation therapy (RT) is commonly used in the treatment of gynecologic cancers. Intensity-modulated RT (IMRT) has been shown to reduce gastrointestinal toxicity compared with 2-dimensional and 3-dimensional RT modalities. We report the initial clinical experience using IMRT for gynecologic cancers with a novel 6MV flattening filter free O-ring linear accelerator (6X-FFF ORL). Methods and Materials: We retrospectively identified consecutive women with uterine or cervical cancer who received pelvic RT on Halcyon (Varian Medical Systems, Palo Alto, CA), a novel 6X-FFF ORL. We report their clinicopathologic data, RT details, early disease-control outcomes, acute toxicities, dose-volume histogram data, couch corrections, and treatment times. Results: Seventeen women received RT on a 6X-FFF ORL for uterine cancer (76%) or cervical cancer (24%) between January 2017 and September 2019. RT was delivered postoperatively (82%) or to intact disease (18%), to a median dose of 50.4 Gy (range, 19.8-55.0 Gy) in 25 fractions (range, 11-28), with 12% receiving extended-field RT and 65% receiving chemotherapy. Target and organ-at-risk constraints were met in all plans. The 3-dimensional vector couch correction average was 0.90 ± 0.37 cm. The mean beam-on time was 2.9 ± 0.4 min and mean treatment time, from imaging start to beam-off, was 3.6 ± 0.4 min. Grade 2 fatigue, anorexia, diarrhea, bloating, and nausea occurred in 41%, 12%, 12%, 6%, and 6% of patients, respectively. There were no grade ≥3 toxicities. Conclusions: In the initial clinical report of pelvic RT for gynecologic cancers using a 6X-FFF ORL, the linac showed versatility in treatment; comparability to flattening-filtered IMRT for early disease-control, toxicity, and dosimetry; and treatment speed that compared favorably to IMRT on a C-arm gantry. Accordingly, a 6X-FFF ORL may increase throughput or reduce day length in departments with high gynecologic cancer volumes, without compromising clinical outcomes.

Purpose: The dosimetric parameters used clinically to reduce the likelihood of radiation pneumonitis (RP) for lung cancer radiation therapy have traditionally been V20Gy ≤ 30% to 35% and mean lung dose ≤ 20 to 23 Gy; however, these parameters are derived based on studies from photon therapy. The purpose of this study is to evaluate whether such dosimetric predictors for RP are applicable for locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with proton therapy. Methods and Materials: In the study, 160 (78 photon, 82 proton) patients with LA-NSCLC treated with chemoradiotherapy between 2011 and 2016 were retrospectively identified. Forty (20 photon, 20 proton) patients exhibited grade ≥2 RP after therapy. Dose volume histograms for the uninvolved lung were extracted for each patient. The percent lung volumes receiving above various dose levels were obtained in addition to V20Gy and Dmean. These dosimetric parameters and patient characteristics were evaluated with univariate and multivariate logistic regression tests. Receiver operating characteristic curves were generated to obtain the optimal dosimetric constraints through analyzing RP and non-RP sensitivity and specificity values. Results: The multivariate analysis showed V40Gy and Dmean to be statistically significant for proton and photon patients, respectively. V35Gy to V50Gy were strongly correlated to V40Gy for proton patients. Based on the receiver operating characteristic curves, V35Gy to V50Gy had the highest area under the curve compared with other dose levels for proton patients. A potential dosimetric constraint for RP predictor in proton patients is V40Gy ≤ 23%. Conclusions: In addition to V20Gy and Dmean, the lung volume receiving higher doses, such as V40Gy, may be used as an additional indicator for RP in LA-NSCLC patients treated with proton therapy.

Purpose: Superficial dose is an important parameter in breast cancer radiation therapy. When treated with conventional linacs, bolus is commonly applied to improve target coverage near the surface while also managing the risk of severe skin reactions and negative cosmesis. With the introduction of modern linacs with 6X flattening filter free (FFF) photon beams, the effect on superficial dose and the need for bolus must be evaluated. Methods and Materials: In vivo measurements of superficial dose were made with optically stimulated luminescence dosimeters on 11 breast cancer patients treated with the Halcyon 6X FFF linac (Varian Medical Systems, Palo Alto, CA). Additionally, measurements were made with the Halycon 6X FFF beam and a 6X beam with flattening filter (FF) delivered to an anthropomorphic phantom. A planning study was carried out in which 14 patients treated on the Halcyon were replanned with a conventional linac to determine the difference in superficial dose predicted by the treatment planning system. Measures were taken to increase the accuracy of the treatment planning system superficial dose. Results: The use of the Halcyon 6X FFF beam led to higher superficial dose compared with 6X FF beams. The in vivo measurements show an average superficial dose of 83.8% ± 0.6%, which is an increase of approximately 10% compared with published measurements for a 6X FF linac. Comparison of superficial dose for 6X FF and 6X FFF beams in the phantom measurements show an increase from 70% ± 1.3% to 84% ± 1.3%, which is consistent with the in vivo measurements. The planning comparison shows an increase in V70%Rx from 62% ± 4.4% to 81% ± 2.2% for the superficial breast tissue for the Halcyon 6X FFF beam compared with a standard C-arm linac with FF. Conclusions: The use of the Halcyon 6X FFF beam was associated with higher superficial dose which may obviate the use of bolus.

Currently, density determination method which is based on the density verification of the liquid is the most popular method for volume of weights measurement. A novel set of apparatus combined with automatic measuring devices and weighing instruments for weight the volume measurement is proposed in this paper. The mechanical structure of the device is optimized. For example, the rod structure of the suspension mechanism avoids the eccentric load error caused by the eccentricity of the lower hook and improves the measurement accuracy. The bubble removal device is added to reduce the error caused by the bubble adhering to the surface of the weight when the weight is immersed in the liquid. After weighing, turn on the drying function to quickly remove the residual liquid on the weight surface.