Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-ß expression.

Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-ß and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

Selenium - An environmentally friendly micronutrient in agroecosystem in the modern era: An overview of 50-year findings.

Agricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.

Betaine ameliorates doxorubicin-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF-ß expression.

Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to its life-threatening side effects, such as cardiotoxicity. It is evident that betaine has anti-oxidant, and anti-inflammatory activity and has several beneficial effects, such as decreasing the amyloid-ß generation, reducing obesity, improving steatosis and fibrosis, and activating AMP-activated protein kinase (AMPK). However, whether betaine could mitigate DOX-induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co-treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX-induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX-induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX-induced increased expression of phospho-p53, phospho-p38 MAPK, NF-kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT-PCR experiments show that betaine treatment alleviates the DOX-induced increase in inflammatory (TNF-α, NLRP3, and IL-6) and fibrosis (TGF-ß and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF-ß expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.

Out of field scatter from electron applicator in modern linear accelerators.

BACKGROUND: Electron out-of-field scatter is generally not given importance mainly in electron fields. However, this is important when applicator down and boost treatments are given usually at an angle from the central axis. The electron scatter dose is found to be far away from the central axis which could be easily ignored. PURPOSE: This study aims to investigate the out-of-field radiation doses from electron applicators and their effects on clinical treatment. By identifying the parameters that contribute to out-of-field doses and to explore potential strategies for reducing these doses in order to improve patient outcomes from modern machines. METHODS: Measurements were performed in water phantom using electron diode for modern Elekta and Varian machines. Dose profiles were acquired at surface and dmax with 0° and 90° collimation angle. Various gantry angles were also studied for some data with IC Profiler. The profiles were normalized with respect to the central axis dose. RESULTS: The scatter dose peaks were found at a distance between 11 and 28 cm from the central axis on all machines. However, the peak shifts to 15 cm at 90° collimator when beam is tilted. The position and intensity of the dose varies with depth, collimator, and gantry angles for both Elekta and Varian machines. Due to clearance issues more gantry angles were studied for Elekta applicator compared to Varian. In general, Varian TrueBeam has a lower scatter that Elekta Infinity. The 90° collimator angle has a higher scatter compared to zero degree for both machines. CONCLUSIONS: There are clinically significant peripheral doses around 3% of the central axis dose from the electron applicator. Elekta has a slightly higher scatter (3%) than Varian (2%) that peaks at 25 cm which is clinically important but often overlooked.

Characteristics of a plastic scintillation detector in photon beam dosimetry.

BACKGROUND: Plastic scintillating detectors (PSD) have gained popularity due to small size and are ideally suited in small-field dosimetry due to no correction needed and hence detector reading can be compared to dose. Likewise, these detectors are active and water equivalent. A new PSD from Blue Physics is characterized in photon beam. PURPOSE: Innovation in small-field dosimetry detector has led us to examine Blue Physics PSD (BP-PSD) for use in photon beams from linear accelerator. METHODS: BP-PSD was acquired and its characteristics were evaluated in photon beams from a Varian TrueBeam. Data were collected in a 3D water tank. Standard parameters; dose, dose rate, energy, angular dependence and temperature dependence were studied. Depth dose, profiles and output in a reference condition as well as small fields were measured. RESULTS: BP-PSD is versatile and provides data very similar to an ion chamber when Cerenkov radiation is properly accounted. This device measures data pulse by pulse which very few detectors can perform. The differences between ion chamber data and PSD are < 2% in most cases. The angular dependence is a bit pronounces to 1.5% which is due to PSD housing. Depth dose and profiles are comparable within < 1% to an ion chamber. For small fields this detector provides suitable field output factor compared to other detectors and Monte Carlo (MC) simulated data without any added correction factor. CONCLUSIONS: The characteristics of Blue Physics PSD is uniquely suitable in photon beam and more so in small fields. The data are reproducible compared to ion chamber for most parameters and ideally suitable for small-field dosimetry without any correction factor.

A multicenter study of modified electron beam output calibration.

PURPOSE: This study aims to assess the accuracy of a modified electron beam calibration based on the IAEA TRS-398 and AAPM-TG-51 in multicenter radiotherapy. METHODS: This study was performed using the Elekta and Varian Linear Accelerator electron beams with energies of 4-22 MeV under reference conditions using cylindrical (PTW 30013, IBA FC65-G, and IBA FC65-P) and parallel-plate (PTW 34045, PTW 34001, and IBA PPC-40) chambers. The modified calibration used a cylindrical chamber and an updated k ' Q $k{^{\prime}}_Q$ based on Monte Carlo calculations, whereas TRS-398 and TG-51 used cylindrical and parallel-plate chambers for reference dosimetry. The dose ratio of the modified calibration procedure, TRS-398 and TG-51 were obtained by comparing the dose at the maximum depth of the modified calibration to TRS-398 and TG-51. RESULTS: The study found that all cylindrical chambers' beam quality conversion factors determined with the modified calibration ( k ' Q ) $( {{{k^{\prime}}}_Q} )$ to the TRS-398 and TG-51 vary from 0.994 to 1.003 and 1.000 to 1.010, respectively. The dose ratio of modified/TRS-398cyl and modified/TRS-398parallel-plate, the variation ranges were 0.980-1.014 and 0.981-1.019, while for the counterpart modified/TG-51cyl was found varying between 0.991 and 1.017 and the ratio of modified/TG-51parallel-plate varied in the range of 0.981-1.019. CONCLUSION: This multi-institutional study analyzed a modified calibration procedure utilizing new data for electron beam calibrations at multiple institutions and evaluated existing calibration protocols. Based on observed variations, the current calibration protocols should be updated with detailed metrics on the stability of linac components.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

The Neuroimmune Axis and Its Therapeutic Potential for Primary Liver Cancer.

The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).

Proteomic profiling of Arabidopsis G-protein ß subunit AGB1 mutant under salt stress.

Salt stress is a limiting environmental factor that inhibits plant growth in most ecological environments. The functioning of G-proteins and activated downstream signaling during salt stress is well established and different G-protein subunits and a few downstream effectors have been identified. Arabidopsis G-protein ß-subunit (AGB1) regulates the movement of Na+ from roots to shoots along with a significant role in controlling Na+ fluxes in roots, however, the molecular mechanism of AGB1 mediated salt stress regulation is not well understood. Here, we report the comparative proteome profiles of Arabidopsis AGB1 null mutant agb1-2 to investigate how the absence of AGB1 modulates the protein repertoire in response to salt stress. High-resolution two-dimensional gel electrophoresis (2-DE) showed 27 protein spots that were differentially modulated between the control and NaCl treated agb1-2 seedlings of which seven were identified by mass spectrometry. Functional annotation and interactome analysis indicated that the salt-responsive proteins were majorly associated with cellulose synthesis, structural maintenance of chromosomes, DNA replication/repair, organellar RNA editing and indole glucosinolate biosynthesis. Further exploration of the functioning of these proteins could serve as a potential stepping stone for dissection of molecular mechanism of AGB1 functions during salt stress and in long run could be extrapolated to crop plants for salinity stress management.

An independent Monte Carlo-based IMRT QA tool for a 0.35 T MRI-guided linear accelerator.

PURPOSE: To develop an independent log file-based intensity-modulated radiation therapy (IMRT) quality assurance (QA) tool for the 0.35 T magnetic resonance-linac (MR-linac) and investigate the ability of various IMRT plan complexity metrics to predict the QA results. Complexity metrics related to tissue heterogeneity were also introduced. METHODS: The tool for particle simulation (TOPAS) Monte Carlo code was utilized with a previously validated linac head model. A cohort of 29 treatment plans was selected for IMRT QA using the developed QA tool and the vendor-supplied adaptive QA (AQA) tool. For 27 independent patient cases, various IMRT plan complexity metrics were calculated to assess the deliverability of these plans. A correlation between the gamma pass rates (GPRs) from the AQA results and calculated IMRT complexity metrics was determined using the Pearson correlation coefficients. Tissue heterogeneity complexity metrics were calculated based on the gradient of the Hounsfield units. RESULTS: The median and interquartile range for the TOPAS GPRs (3%/3 mm criteria) were 97.24% and 3.75%, respectively, and were 99.54% and 0.36% for the AQA tool, respectively. The computational time for TOPAS ranged from 4 to 8 h to achieve a statistical uncertainty of <1.5%, whereas the AQA tool had an average calculation time of a few minutes. Of the 23 calculated IMRT plan complexity metrics, the AQA GPRs had correlations with 7 out of 23 of the calculated metrics. Strong correlations (|r| > 0.7) were found between the GPRs and the heterogeneity complexity metrics introduced in this work. CONCLUSIONS: An independent MC and log file-based IMRT QA tool was successfully developed and can be clinically deployed for offline QA. The complexity metrics will supplement QA reports and provide information regarding plan complexity.

Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Advances in Engineered Biomaterials Targeting Angiogenesis and Cell Proliferation for Cancer Therapy.

Antiangiogenic therapy in combination with chemotherapeutic agents is an effective strategy for cancer treatment. However, this combination therapy is associated with several challenges including non-specific biodistribution leading to systemic toxicity. Biomaterial-mediated codelivery of chemotherapeutic and anti-angiogenic agents can exploit their passive and active targeting abilities, leading to improved drug accumulation at the tumor site and therapeutic outcomes. In this review, we present the progress made in the field of engineered biomaterials for codelivery of chemotherapeutic and antiangiogenic agents. We present advances in engineering of liposome/hydrogel/micelle-based biomaterials for delivery of combination of anticancer and anti-angiogenesis drugs, or combination of anticancer and siRNA targeting angiogenesis, and targeted nanoparticles. We then present our perspective on developing strategies for targeting angiogenesis and cell proliferation for cancer therapy.

Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective.

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH.

Zebrafish as an emerging tool for drug discovery and development for thyroid diseases.

Zebrafish is a useful model for understanding human genetics and diseases and has evolved into a prominent scientific research model. The genetic structure of zebrafish is 70% identical to that of humans. Its small size, low cost, and transparent embryo make it a valuable tool in experimentation. Zebrafish and mammals possess the same molecular mechanism of thyroid organogenesis and development. Thus, thyroid hormone signaling, embryonic development, thyroid-related disorders, and novel genes involved in early thyroid development can all be studied using zebrafish as a model. Here in this review, we emphasize the evolving role of zebrafish as a possible tool for studying the thyroid gland in the context of physiology and pathology. The transcription factors nkx2.1a, pax2a, and hhex which contribute a pivotal role in the differentiation of thyroid primordium are discussed. Further, we have described the role of zebrafish as a model for thyroid cancer, evaluation of defects in thyroid hormone transport, thyroid hormone (TH) metabolism, and as a screening tool to study thyrotoxins. Hence, the present review highlights the role of zebrafish as a novel approach to understand thyroid development and organogenesis.

Abiological catalysis by myoglobin mutant with a genetically incorporated unnatural amino acid.

To inculcate biocatalytic activity in the oxygen-storage protein myoglobin (Mb), a genetically engineered myoglobin mutant H64DOPA (DOPA = L-3,4-dihydroxyphenylalanine) has been created. Incorporation of unnatural amino acids has already demonstrated their ability to accomplish many non-natural functions in proteins efficiently. Herein, the presence of redox-active DOPA residue in the active site of mutant Mb presumably stabilizes the compound I in the catalytic oxidation process by participating in an additional hydrogen bonding (H-bonding) as compared to the WT Mb. Specifically, a general acid-base catalytic pathway was achieved due to the availability of the hydroxyl moieties of DOPA. The reduction potential values of WT (E° = -260 mV) and mutant Mb (E° = -300 mV), w.r.t. Ag/AgCl reference electrode, in the presence of hydrogen peroxide, indicated an additional H-bonding in the mutant protein, which is responsible for the peroxidase activity of the mutant Mb. We observed that in the presence of 5 mM H2O2, H64DOPA Mb oxidizes thioanisole and benzaldehyde with a 10 and 54 folds higher rate, respectively, as opposed to WT Mb. Based on spectroscopic, kinetic, and electrochemical studies, we deduce that DOPA residue, when present within the distal pocket of mutant Mb, alone serves the role of His/Arg-pair of peroxidases.

Comparison of Efficacy of Dexmedetomidine and Clonidine Infusion to Produce Hypotensive Anesthesia in Patients Undergoing Orthognathic Surgery: A Randomized Controlled Trial.

PURPOSE: The purpose of the study was to compare the efficacy of dexmedetomidine (DEX) and clonidine (CLON) infusion to produce hypotensive anesthesia in patients undergoing orthognathic surgery. MATERIAL AND METHODS: The investigators designed a randomized controlled trial on patients undergoing orthognathic surgery. Patients were randomized into 2 groups (DEX and CLON group). The DEX group patients received loading dose of 1 ug/kg DEX over 10 minutes followed by 0.2 to 0.5 ug/kg/hour as maintenance dose. Similarly, CLON group patients received 3 ug/kg loading dose followed by maintenance dose of 0.3 to 2 ug/kg/hour. Primary objectives were to compare the quality of surgical field, duration of surgery, amount of blood loss and secondary objectives were to compare total and rescue analgesia used, need for blood transfusion and associated adverse effects. The P value of <.05 was taken significant at confidence interval of 95%. RESULTS: The study sample included 30 patients (15 in each group), (m:f = 1:1.1) requiring orthognathic surgery. Single jaw cases were 11 (DEX:CLON = 4:7) and bijaw cases were 19 (DEX:CLON = 11:8) in number. There was statistically insignificant difference in quality of surgical field between 2 groups (P = .15). Duration of surgery was 293.33 ± 58.75 and 247 ± 70.45 minutes in the DEX and the CLON group, respectively (P = .06). Blood loss was more in the DEX group (316.61 ± 147.19 mL) than the CLON group (263.33 ± 112.54 mL), (P = .71). Total drug used (P = .33) and rescue analgesia (P = .25) was less in the DEX group. Adverse effects were more in the CLON than the DEX group. CONCLUSION: The results of the present study showed no significant difference between the 2 groups for any parameter. It can be concluded that both dexmedetomidine and clonidine are effective and safe in achieving controlled hypotension and safe operative field visibility.

Transferability of patients for radiation treatment between unmatched machines.

PURPOSE: The feasibility of transferring patients between unmatched machines for a limited number of treatment fractions was investigated for three-dimensional conformal radiation therapy (3DCRT) and volumetric modulated arc therapy (VMAT) treatments. METHODS: Eighty patient-plans were evaluated on two unmatched linacs: Elekta Versa HD and Elekta Infinity. Plans were equally divided into pelvis 3DCRT, prostate VMAT, brain VMAT, and lung VMAT plans. While maintaining the number of monitor units (MUs), plans were recalculated on the machine not originally used for treatment. Relative differences in dose were calculated between machines for the target volume and organs at risk (OARs). Differences in mean dose were assessed with paired t-tests (p < 0.05). The number of interchangeable fractions allowable before surpassing a cumulative ±5% difference in dose was determined. Additionally, patient-specific quality assurance (PSQA) measurements using ArcCHECK for both machines were compared with distributions calculated on the machine originally used for treatment using gradient compensation (GC) with 2%/2-mm criteria. RESULTS: Interchanging the two machines for pelvic 3DCRT and VMAT (prostate, brain, and lung) plans resulted in an average change in target mean dose of 0.9%, -0.5%, 0.6%, 0.5%, respectively. Based on the differences in dose to the prescription point when changing machines, statistically, nearly one-fourth of the prescribed fractions could be transferred between linacs for 3DCRT plans. While all of the prescribed fractions could typically be transferred among prostate VMAT plans, a rather large number of treatment fractions, 31% and 38%, could be transferred among brain and lung VMAT plans, respectively, without exceeding a ±5% change in the prescribed dose for two Elekta machines. Additionally, the OAR dosage was not affected within the given criterion with change of machine. CONCLUSIONS: Despite small differences in calculated dose, transferring patients between two unmatched Elekta machines with similar multileaf collimator (MLC)-head for target coverage and minimum changes in OAR dose is possible for a limited number of fractions (≤3) to improve clinical flexibility and institutional throughput along with patient satisfaction. A similar study could be carried out for other machines for operational throughput.

Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

Proteomic analysis of radio-resistant breast cancer xenografts: Increased TGF-ß signaling and metabolism.

Our previous studies have shown that MCF-7 breast cancer cell line exposed to 6 Gy and allowed to recover for 7 days (D7-6G) developed radio-resistance. In this study, we have tested the ability of these cells to form tumors in severe combined immunodeficiency (SCID) mice and characterized these tumors by proteomic analyses. Untreated (MCF-C) and D7-6G cells (MCF-R) were injected s.c. in SCID mice and tumor growth monitored. On Day 18, the mice were killed and tumor tissues were fixed in formalin or RNA later. Expression of genes was assessed by reverse transcription-polymerase chain reaction and proteins by enzyme-linked immunosorbent assay/antibody labeling and flow cytometry. Label free proteomic analyses was carried out by liquid chromatography-mass spectrometry. Metabolic analysis was carried out using Seahorse analyzer. MCF-R cells had a shorter latency and formed larger tumors. These tumors were characterized by an increased expression of transforming growth factor ß (TGF-ß) isoforms; its downstream genes pSMAD3, Snail-1, Zeb-1, HMGA2; hybrid epithelial/mesenchymal phenotype; migration, enrichment of cancer stem cells and radioresistance following challenge dose of radiation. Proteomic analysis of MCF-7R tumors resulted in identification of a total of 649 differentially expressed proteins and pathway analyses using protein annotation through evolutionary relationship indicated enrichment of genes involved in metabolism. Data are available via ProteomeXchange with identifier PXD022506. Seahorse analyzer confirmed increased metabolism in these cells with increased oxidative phosphorylation as well as glycolysis. Increased uptake of 2-NBDG further confirmed increased glycolysis. In summary, we demonstrate that radioresistant breast cancer cells had an enrichment of TGF-ß signaling and increased metabolism.

Outcome of Stock Total Joint Replacement With Fat Grafting in Adult Temporomandibular Joint Ankylosis Patients.

PURPOSE: Adult temporomandibular joint ankylosis (TMJA) lacks a uniform management protocol. The purpose of the study was to evaluate the outcome of stock total joint replacement (TJR) along with fat grafting around the joint in adult TMJA patients. Specific aim was to find out whether TJR can be a definitive management for adult TMJA. METHODS: The investigators implemented a prospective study on adult TMJA patients treated with ostearthrectomy of ankylosis and stock temporomandibular joint (TMJ) TJR with fat grafting. Concomitant orthognathic correction of facial asymmetry was performed in some unilateral cases. Follow-up was carried out at regular intervals for assessing primary outcome variable of maximal incisal opening (MIO) and reankylosis. Secondary outcome variable included demographic data, etiology, duration of ankylosis (DOA), correlation between DOA and preoperative and postoperative MIO, occlusion and complications of hemorrhage, facial nerve paresis, periprosthetic joint infection, dislocation, and implant failure. RESULTS: The study sample was composed of 41 patients (54 joints) (bilateral, n = 13; unilateral, n = 28 [right side, n = 12; left side, n = 16]). The number of recurrent cases was 15. Trauma as etiology of ankylosis was seen in n = 30 (73.2%), infection in n = 7 (17.1%), unknown in n = 3 (7.3%), and ankylosing spondylitis in n = 1 (2.4%) cases. Mean DOA was 11.95 years. Paired t test revealed a statistically significant difference between preoperative and follow-up MIO (P < .001). None of the cases showed reankylosis in the follow-up period. Pearson correlation revealed statistically negative correlation between DOA and postoperative MIO. CONCLUSIONS: The result of this study suggests that stock TMJ TJR along with fat grafting around the joints provides adequate mouth opening without any sign and symptoms of reankylosis. Stock TMJ TJR with fat grafting can be considered as a definitive treatment modality in adult TMJA with minimum comorbidity.