Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.

Unveiling the micronutrient-immunity puzzle in inactivated COVID-19 vaccination: A comprehensive analysis of circulating micronutrient levels and humoral responses in healthy adults.

While micronutrients are crucial for immune function, their impact on humoral responses to inactivated COVID-19 vaccination remains unclear. We investigated the associations between seven key micronutrients and antibody responses in 44 healthy adults with two doses of an inactivated COVID-19 vaccine. Blood samples were collected pre-vaccination and 28 days post-booster. We measured circulating minerals (iron, zinc, copper, and selenium) and vitamins (A, D, and E) concentrations alongside antibody responses and assessed their associations using linear regression analyses. Our analysis revealed inverse associations between blood iron and zinc concentrations and anti-SARS-CoV-2 IgM antibody binding affinity (AUC for iron: ß = -258.21, p < 0.0001; zinc: ß = -17.25, p = 0.0004). Notably, antibody quality presented complex relationships. Blood selenium was positively associated (ß = 18.61, p = 0.0030), while copper/selenium ratio was inversely associated (ß = -1.36, p = 0.0055) with the neutralizing ability against SARS-CoV-2 virus at a 1:10 plasma dilution. There was no significant association between circulating micronutrient concentrations and anti-SARS-CoV-2 IgG binding affinity. These findings suggest that circulating iron, zinc, and selenium concentrations and copper/selenium ratio, may serve as potential biomarkers for both quantity (binding affinity) and quality (neutralization) of humoral responses after inactivated COVID-19 vaccination. Furthermore, they hint at the potential of pre-vaccination dietary interventions, such as selenium supplementation, to improve vaccine efficacy. However, larger, diverse studies are needed to validate these findings. This research advances the understanding of the impact of micronutrients on vaccine response, offering the potential for personalized vaccination strategies.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Assessing quality assurance of multi-leaf collimator using the structural similarity index.

PURPOSE: This study aims to evaluate the viability of utilizing the Structural Similarity Index (SSI*) as an innovative imaging metric for quality assurance (QA) of the multi-leaf collimator (MLC). Additionally, we compared the results obtained through SSI* with those derived from a conventional Gamma index test for three types of Varian machines (Trilogy, Truebeam, and Edge) over a 12-week period of MLC QA in our clinic. METHOD: To assess sensitivity to MLC positioning errors, we designed a 1 cm slit on the reference MLC, subsequently shifted by 0.5-5 mm on the target MLC. For evaluating sensitivity to output error, we irradiated five 25 cm × 25 cm open fields on the portal image with varying Monitor Units (MUs) of 96-100. We compared SSI* and Gamma index tests using three linear accelerator (LINAC) machines: Varian Trilogy, Truebeam, and Edge, with MLC leaf widths of 1, 0.5, and 0.25 mm. Weekly QA included VMAT and static field modes, with Picket fence test images acquired. Mechanical uncertainties related to the LINAC head, electronic portal imaging device (EPID), and MLC during gantry rotation and leaf motion were monitored. RESULTS: The Gamma index test started detecting the MLC shift at a threshold of 4 mm, whereas the SSI* metric showed sensitivity to shifts as small as 2 mm. Moreover, the Gamma index test identified dose changes at 95MUs, indicating a 5% dose difference based on the distance to agreement (DTA)/dose difference (DD) criteria of 1 mm/3%. In contrast, the SSI* metric alerted to dose differences starting from 97MUs, corresponding to a 3% dose difference. The Gamma index test passed all measurements conducted on each machine. However, the SSI* metric rejected all measurements from the Edge and Trilogy machines and two from the Truebeam. CONCLUSIONS: Our findings demonstrate that the SSI* exhibits greater sensitivity than the Gamma index test in detecting MLC positioning errors and dose changes between static and VMAT modes. The SSI* metric outperformed the Gamma index test regarding sensitivity across these parameters.

Evaluation of intrafraction couch shifts for proton treatment delivery in head-and-neck cancer patients: Toward optimal imaging frequency.

PURPOSE: Treatment planning for head-and-neck (H&N) cancer, in particular oropharynx, nasopharynx, and paranasal sinus cases, at our center requires noncoplanar proton beams due to the complexity of the anatomy and target location. Targeting accuracy for all beams is carefully evaluated by using image guidance before delivering proton beam therapy (PBT). In this study, we analyzed couch shifts to evaluate whether imaging is required before delivering each field with different couch angles. METHODS: After the Institutional Review Board approval, a retrospective analysis was performed on data from 28 H&N patients treated with PBT. Each plan was made with two-to-three noncoplanar and two-to-three coplanar fields. Cone-beam computed tomography and orthogonal kilovoltage (kV) images were acquired for setup and before delivering each field, respectively. The Cartesian (longitudinal, vertical, and lateral) and angular (pitch and roll) shifts for each field were recorded from the treatment summary on the first two fractions and every subsequent fifth fraction. A net magnitude of the three-dimensional (3D) shift in Cartesian coordinates was calculated, and a 3D vector was created from the 6 degrees of freedom coordinates for transforming couch shifts in the system coordinate to the beam's-eye view. RESULTS: A total of 3219 Cartesian and 2146 angular shift values were recorded for 28 patients. Of the Cartesian shifts, 2069 were zero (64.3%), and 1150 (35.7%) were nonzero (range, -7 to 11 mm). Of the angular shifts, 1034 (48.2%) were zero, and 1112 (51.8%) were nonzero (range, -3.0° to 3.2°). For 17 patients, the couch shifts increased toward the end of the treatment course. We also found that patients with higher body mass index (BMI) presented increased net couch shifts (p < 0.001). With BMI < 27, all overall net shift averages were <2 mm, and overall maximum net shifts were <6 mm. CONCLUSIONS: These results confirm the need for orthogonal kV imaging before delivering each field of H&N PBT at our center, where a couch rotation is involved.

A study of skin marker alignment using different diamond-shaped light fields for prone breast external-beam radiation therapy.

For breast cancer patients treated in the prone position with tangential fields, a diamond-shaped light field (DSLF) can be used to align with corresponding skin markers for image-guided radiation therapy (IGRT). This study evaluates and compares the benefits of different DSLF setups. Seventy-one patients who underwent daily tangential kilovoltage (kV) IGRT were categorized retrospectively into four groups: (1) DSLF field size (FS) = 10 × 10 cm2 , gantry angle = 90° (right breast)/270° (left breast), with the same isocenter as treatment tangential beams; (2) same as group 1, except DSLF FS = 4 × 4 cm2 ; (3) DSLF FS = 4 × 4-6 × 8 cm2 , gantry angle = tangential treatment beam, off-isocenter so that the DSLF was at the approximate breast center; and (4) No-DSLF. We compared their total setup time (including any DSLF/marker-based alignment and IGRT) and relative kV-based couch shift corrections. For groups 1-3, DSLF-only dose distributions (excluding kV-based correction) were simulated by reversely shifting the couch positions from the computed tomography plans, which were assumed equivalent to the delivered dose when both DSLF and IGRT were used. For patient groups 1-4, the average daily setup time was 2.6, 2.5, 5.0, and 8.3 min, respectively. Their mean and standard deviations of daily kV-based couch shifts were 0.64 ± 0.4, 0.68 ± 0.3, 0.8 ± 0.6, and 1.0 ± 0.6 cm. The average target dose changes after excluding kV-IGRT for groups 1-3 were-0.2%, -0.1%, and +0.4%, respectively, whereas DSLF-1 was most efficient in sparing heart and chest wall, DSLF-2 had lowest lung Dmax ; and DSLF-3 maintained the highest target coverage at the cost of highest OAR dose. In general, the use of DSLF greatly reduces patient setup time and may result in smaller IGRT corrections. If IGRT is limited, different DSLF setups yield different target coverage and OAR dose sparing. Our findings will help DSLF setup optimization in the prone breast treatment setting.

Is a weekly qualitative picket fence test sufficient? A proposed alternate EPID-based weekly MLC QA program.

PURPOSE: Well-designed routine multileaf collimator (MLC) quality assurance (QA) is important to assure external-beam radiation treatment delivery accuracy. This study evaluates the clinical necessity of a comprehensive weekly (C-Weekly) MLC QA program compared to the American Association of Physics in Medicinerecommended weekly picket fence test (PF-Weekly), based on our seven-year experience with weekly MLC QA. METHODS: The C-Weekly MLC QA program used in this study includes 5 tests to analyze: (1) absolute MLC leaf position; (2) interdigitation MLC leaf position; (3) picket fence MLC leaf positions at static gantry angle; (4) minimum leaf-gap setting; and (5) volumetric-modulated arc therapy delivery. A total of 20,226 QA images from 16,855 tests (3,371 tests × 5) for 11 linacs at 5 photon clinical sites from May 2014 to June 2021 were analyzed. Failure mode and effects analysis was performed with 5 failure modes related to the 5 tests. For each failure mode, a risk probability number (RPN) was calculated for a C-Weekly and a PF-Weekly MLC QA program. The probability of occurrence was evaluated from statistical analyses of the C-Weekly MLC QA. RESULTS: The total number of failures for these 16,855 tests was 143 (0.9%): 39 (27.3%) for absolute MLC leaf position, 13 (9.1%) for interdigitation position, 9 (6.3%) for static gantry picket fence, 2 (1.4%) for minimum leaf-gap setting, and 80 (55.9%) for VMAT delivery. RPN scores for PF-Weekly MLC QA ranged from 60 to 192 and from 48 to 96 for C-Weekly MLC QA. CONCLUSION: RPNs for the 5 failure modes of MLC QA tests were quantitatively determined and analyzed. A comprehensive weekly MLC QA is imperative to lower the RPNs of the 5 failure modes to the desired level (<125); those from the PF-Weekly MLC QA program were found to be higher (>125). This supports the clinical necessity for comprehensive weekly MLC QA.

Development of an Electronic Stethoscope and a Classification Algorithm for Cardiopulmonary Sounds.

With conventional stethoscopes, the auscultation results may vary from one doctor to another due to a decline in his/her hearing ability with age or his/her different professional training, and the problematic cardiopulmonary sound cannot be recorded for analysis. In this paper, to resolve the above-mentioned issues, an electronic stethoscope was developed consisting of a traditional stethoscope with a condenser microphone embedded in the head to collect cardiopulmonary sounds and an AI-based classifier for cardiopulmonary sounds was proposed. Different deployments of the microphone in the stethoscope head with amplification and filter circuits were explored and analyzed using fast Fourier transform (FFT) to evaluate the effects of noise reduction. After testing, the microphone placed in the stethoscope head surrounded by cork is found to have better noise reduction. For classifying normal (healthy) and abnormal (pathological) cardiopulmonary sounds, each sample of cardiopulmonary sound is first segmented into several small frames and then a principal component analysis is performed on each small frame. The difference signal is obtained by subtracting PCA from the original signal. MFCC (Mel-frequency cepstral coefficients) and statistics are used for feature extraction based on the difference signal, and ensemble learning is used as the classifier. The final results are determined by voting based on the classification results of each small frame. After the testing, two distinct classifiers, one for heart sounds and one for lung sounds, are proposed. The best voting for heart sounds falls at 5-45% and the best voting for lung sounds falls at 5-65%. The best accuracy of 86.9%, sensitivity of 81.9%, specificity of 91.8%, and F1 score of 86.1% are obtained for heart sounds using 2 s frame segmentation with a 20% overlap, whereas the best accuracy of 73.3%, sensitivity of 66.7%, specificity of 80%, and F1 score of 71.5% are yielded for lung sounds using 5 s frame segmentation with a 50% overlap.

Gastrointestinal bleeding with Klippel-Trenaunay syndrome: a case report.

BACKGROUND: Gastrointestinal bleeding caused by gastrointestinal tract involvement in patients with Klippel-Trenaunay syndrome (KTS) is extremely rare and often overlooked. Case presentation A 9-year-old girl who presented with chronic gastrointestinal bleeding was admitted to our hospital. Laboratory examinations revealed microcytic hypochromic anemia and a positive fecal occult blood test. Computed tomography (CT) of the lower limbs combined with physical examination confirmed KTS. The pelvic CT showed concentric thickening of the sigmoid colon and rectum, with progressive enhancement after the administration of a contrast agent. Colonoscopy demonstrated vascular malformations of the sigmoid colon and rectum. The patient was finally diagnosed with KTS with gastrointestinal tract involvement. The patient improved after receiving conservative treatment. CONCLUSIONS: A suspicion of gastrointestinal tract involvement as an etiology for gastrointestinal bleeding should not be overlooked in patients with KTS. Endoscopy and imaging modalities can synergistically help diagnose this condition.

Comparison of the dosimetric accuracy of proton breast treatment plans delivered with SGRT and CBCT setups.

PURPOSE: To compare the dosimetric accuracy of surface-guided radiation therapy (SGRT) and cone-beam computed tomography (CBCT) setups in proton breast treatment plans. METHODS: Data from 30 patients were retrospectively analyzed in this IRB-approved study. Patients were prescribed 4256-5040 cGy in 16-28 fractions. CBCT and AlignRT (SGRT; Vision RT Ltd.) were used for treatment setup during the first three fractions, then daily AlignRT and weekly CBCT thereafter. Each patient underwent a quality assurance CT (QA-CT) scan midway through the treatment course to assess anatomical and dosimetric changes. To emulate the SGRT and CBCT setups during treatment, the planning CT and QA-CT images were registered in two ways: (1) by registering the volume within the CTs covered by the CBCT field of view; and (2) by contouring and registering the surface surveyed by the AlignRT system. The original plan was copied onto these two datasets and the dose was recalculated. The clinical treatment volume (CTV): V95% ; heart: V25Gy , V15Gy , and mean dose; and ipsilateral lung: V20Gy , V10Gy , and V5Gy , were recorded. Multi and univariate analyses of variance were performed to assess the differences in dose metric values between the planning CT and the SGRT and CBCT setups. RESULTS: The CTV V95% and lung V20Gy , V10Gy , and V5Gy dose metrics were all significantly (p < 0.01) lower on the QA-CT in both the CBCT and SGRT setup. The differences were not clinically significant and were, on average, 1.4-1.6% lower for CTV V95% and 1.8%-6.0% lower for the lung dose metrics. When comparing the lung and CTV V95% dose metrics between the CBCT and SGRT setups, no significant difference was observed. This indicates that the SGRT setup provides similar dosimetric accuracy as CBCT. CONCLUSION: This study supports the daily use of SGRT systems for the accurate dose delivery of proton breast treatment plans.

Toward automation of initial chart check for photon/electron EBRT: the clinical implementation of new AAPM task group reports and automation techniques.

PURPOSE: The recently published AAPM TG-275 and the public review version of TG-315 list new recommendations for comprehensive and minimum physics initial chart checks, respectively. This article addresses the potential development and benefit of initial chart check automation when these recommendations are implemented for clinical photon/electron EBRT. METHODS: Eight board-certified physicists with 2-20 years of clinical experience performed initial chart checks using checklists from TG-275 and TG-315. Manual check times were estimated for three types of plans (IMRT/VMAT, 3D, and 2D) and for prostate, whole pelvis, lung, breast, head and neck, and brain cancers. An expert development team of three physicists re-evaluated the automation feasibility of TG-275 checklist based on their experience of developing and implementing the in-house and the commercial automation tools in our institution. Three levels of initial chart check automation were simulated: (1) Auto_UMMS_tool (which consists of in-house program and commercially available software); (2) Auto_TG275 (with full and partial automation as indicated in TG-275); and (3) Auto_UMMS_exp (with full and partial automation as determined by our experts' re-evaluation). RESULTS: With no automation of initial chart checks, the ranges of manual check times were 29-56 min (full TG-315 list) and 102-163 min (full TG-275 list), which varied significantly with physicists but varied little at different tumor sites. The 69 of 71 checks which were considered as "not fully automated" in TG-275 were re-evaluated with more automation feasibility. Compared to no automation, the higher levels of automation yielded a great reduction in both manual check times (by 44%-98%) and potentially residual detectable errors (by 15-85%). CONCLUSION: The initial chart check automation greatly improves the practicality and efficiency of implementing the new TG recommendations. Revisiting the TG reports with new technology/practice updates may help develop and utilize more automation clinically.

Reproducibility of a novel, vacuum-assisted immobilization for breast stereotactic radiotherapy.

A novel, breast-specific stereotactic radiotherapy device has been developed for delivery of highly conformal, accelerated partial breast irradiation. This device employs a unique, vacuum-assisted, breast cup immobilization system that applies a gentle, negative pressure to the target breast with the patient in the prone position. A device-specific patient loader is utilized for simulation scanning and device docking. Prior to clinical activation, a prospective protocol enrolled 25 patients who had been or were to be treated with breast conservation surgery and adjuvant radiotherapy for localized breast cancer. The patients underwent breast cup placement and two separate CT simulation scans. Surgical clips within the breast were mapped and positions measured against the device's integrated stereotactic fiducial/coordinate system to confirm reproducible and durable immobilization during the simulation, treatment planning, and delivery process for the device. Of the enrolled 25 patients, 16 were deemed eligible for analysis. Seventy-three clips (median, 4; mean, 4.6; range, 1-8 per patient) were mapped in these selected patients on both the first and second CT scans. X, Y, and Z coordinates were determined for the center point of each clip. Length of vector change in position was determined for each clip between the two scans. The mean displacement of implanted clips was 1.90 mm (median, 1.47 mm; range, 0.44-6.52 mm) (95% CI, 1.6-2.20 mm). Additional analyses stratified clips by position within the breast and depth into the immobilization cup. Overall, this effort validated the clinically utilized 3-mm planning target volume margin for accurate, reliable, and precise employment of the device.

A practical cyberattack contingency plan for radiation oncology.

PURPOSE: This article presents a solution for continuing radiation therapy without interruption in the event of a cyberattack to the radiation oncology information systems (ROIS). This process could be easily deployed to any radiation oncology practice, with little clinical overhead or burden. METHODS AND MATERIALS: The solution automatically retrieves all essential information from the clinical ROIS for each under-treatment patient and periodically (e.g., daily) saves these data to a dedicated secure server for recovery. In the event that the clinical ROIS is not functioning as a result of a cyberattack, this essential information is used to build a new secondary ROIS server to continue radiotherapy treatments until the main ROIS is recovered. Once the cyberattack threat is cleared, the clinical ROIS server is rebuilt from the institution's enterprise backup. The newly accumulated treatment information for each patient is then exported from the secondary ROIS to bring the clinical ROIS up to date. RESULTS: The Department of Radiation Oncology at the University of Maryland Medical System implemented this solution for clinical use with the Varian ARIA ROIS in the management of ~250 daily radiotherapy treatments, inclusive of a proton center. This solution was determined to be a feasible and affordable business continuity plan for the radiation oncology practice by minimizing radiation treatment downtime to a couple of hours in a simulated cyberattack drill. CONCLUSIONS: The proposed solution can achieve continuation of radiation therapy treatment without treatment breaks in the event of a cyberattack. It also provides cushion time for radiation oncology departments to rebuild their clinical ROIS systems from the enterprise data backup.

Development and validation of a comprehensive patient-specific quality assurance program for a novel stereotactic radiation delivery system for breast lesions.

PURPOSE: The GammaPod is a dedicated prone breast stereotactic radiosurgery (SRS) machine composed of 25 cobalt-60 sources which rotate around the breast to create highly conformal dose distributions for boosts, partial-breast irradiation, or neo-adjuvant SRS. We describe the development and validation of a patient-specific quality assurance (PSQA) system for the GammaPod. METHODS: We present two PSQA methods: measurement based and calculation based PSQA. The measurements are performed with a combination of absolute and relative dose measurements. Absolute dosimetry is performed in a single point using a 0.053-cc pinpoint ionization chamber in the center of a polymethylmethacrylate (PMMA) breast phantom and a water-filled breast cup. Relative dose distributions are verified with EBT3 film in the PMMA phantom. The calculation-based method verifies point doses with a novel semi-empirical independent-calculation software. RESULTS: The average (± standard deviation) breast and target sizes were 1263 ± 335.3 cc and 66.9 ± 29.9 cc, respectively. All ion chamber measurements performed in water and the PMMA phantom agreed with the treatment planning system (TPS) within 2.7%, with average (max) difference of -1.3% (-1.9%) and -1.3% (-2.7%), respectively. Relative dose distributions measured by film showed an average gamma pass rate of 97.0 ± 3.2 when using a 3%/1 mm criteria. The lowest gamma analysis pass rate was 90.0%. The independent calculation software had average agreements (max) with the patient and QA plan calculation of 0.2% (2.2%) and -0.1% (2.0%), respectively. CONCLUSION: We successfully implemented the first GammaPod PSQA program. These results show that the GammaPod can be used to calculate and deliver the predicted dose precisely and accurately. For routine PSQA performed prior to treatments, the independent calculation is recommended as it verifies the accuracy of the planned dose without increasing the risk of losing vacuum due to prolonged waiting times.

Dosimetric effects of the kV based image-guided radiation therapy of prone breast external beam radiation: Towards the optimized imaging frequency.

PURPOSE: For prone breast treatment, daily image-guided radiation therapy (IGRT) allows couch shifting to correct breast position relative to the treatment field. This work investigates the dosimetric effect of reducing kV imaging frequencies and the feasibility of optimizing the frequency using patient anatomy or their first 3-day shifts. METHOD: Thirty-seven prone breast patients who had been treated with skin marker alignment followed by daily kV were retrospectively analyzed. Three IGRT schemes (daily-kV, weekly-kV, no-kV) were simulated, assuming that fractions with kV imaging deliver a dose distribution equivalent to that in computed tomography (CT) planning, whereas other fractions yield a dose distribution as recreated by shifting the CT plan isocenter back to its position before the couch shift was applied. Treatment dose to targets (breast and lumpectomy cavity [LPC]) and organs at risks (OAR)s (heart, ipsilateral lung) in different schemes were calculated. Patient anatomy information on CT plans and first 3-day couch shift data were analyzed to investigate whether these factors could guide imaging scheme optimization. RESULTS: When kV imaging frequency was reduced, the percentage dose changes (δD) for breast and LPC objectives (average <1%) were smaller than those for heart and lung (average 28%-31% for Dmean ). In general, the δD of no-kV imaging was approximately that of weekly kV imaging × a factor of 1.2-1.4. Although most dose objectives were not affected, the potential higher heart dose may be of concern. No strong correlation was found between δD for different kV frequencies and patient anatomy size/distance or the first 3-day couch shift data. CONCLUSIONS: Despite resulting in lower imaging dose, time, cost, and similar target coverage, a reduction in kV imaging frequency may introduce higher heart complication risk. Daily kVs are needed more in left-sided breast patients. A less frequent imaging schedule, if considered, cannot be individually optimized using CT anatomic features or early shift data.

Characterization and discrimination of raw and vinegar-baked Bupleuri radix based on UHPLC-Q-TOF-MS coupled with multivariate statistical analysis.

Bupleuri Radix is a commonly used herb in clinic, and raw and vinegar-baked Bupleuri Radix are both documented in the Pharmacopoeia of People's Republic of China. According to the theories of traditional Chinese medicine, Bupleuri Radix possesses different therapeutic effects before and after processing. However, the chemical mechanism of this processing is still unknown. In this study, ultra-high-performance liquid chromatography with quadruple time-of-flight mass spectrometry coupled with multivariate statistical analysis including principal component analysis and orthogonal partial least square-discriminant analysis was developed to holistically compare the difference between raw and vinegar-baked Bupleuri Radix for the first time. As a result, 50 peaks in raw and processed Bupleuri Radix were detected, respectively, and a total of 49 peak chemical compounds were identified. Saikosaponin a, saikosaponin d, saikosaponin b3 , saikosaponin e, saikosaponin c, saikosaponin b2 , saikosaponin b1 , 4''-O-acetyl-saikosaponin d, hyperoside and 3',4'-dimethoxy quercetin were explored as potential markers of raw and vinegar-baked Bupleuri Radix. This study has been successfully applied for global analysis of raw and vinegar-processed samples. Furthermore, the underlying hepatoprotective mechanism of Bupleuri Radix was predicted, which was related to the changes of chemical profiling.

Prostate bed target interfractional motion using RTOG consensus definitions and daily CT on rails : Does target motion differ between superior and inferior portions of the clinical target volume?

PURPOSE: Using high-quality CT-on-rails imaging, the daily motion of the prostate bed clinical target volume (PB-CTV) based on consensus Radiation Therapy Oncology Group (RTOG) definitions (instead of surgical clips/fiducials) was studied. It was assessed whether PB motion in the superior portion of PB-CTV (SUP-CTV) differed from the inferior PB-CTV (INF-CTV). PATIENTS AND METHODS: Eight pT2-3bN0-1M0 patients underwent postprostatectomy intensity-modulated radiotherapy, totaling 300 fractions. INF-CTV and SUP-CTV were defined as PB-CTV located inferior and superior to the superior border of the pubic symphysis, respectively. Daily pretreatment CT-on-rails images were compared to the planning CT in the left-right (LR), superoinferior (SI), and anteroposterior (AP) directions. Two parameters were defined: "total PB-CTV motion" represented total shifts from skin tattoos to RTOG-defined anatomic areas; "PB-CTV target motion" (performed for both SUP-CTV and INF-CTV) represented shifts from bone to RTOG-defined anatomic areas (i. e., subtracting shifts from skin tattoos to bone). RESULTS: Mean (± standard deviation, SD) total PB-CTV motion was -1.5 (±â€¯6.0), 1.3 (±â€¯4.5), and 3.7 (±â€¯5.7) mm in LR, SI, and AP directions, respectively. Mean (±â€¯SD) PB-CTV target motion was 0.2 (±1.4), 0.3 (±2.4), and 0 (±3.1) mm in the LR, SI, and AP directions, respectively. Mean (±â€¯SD) INF-CTV target motion was 0.1 (±â€¯2.8), 0.5 (±â€¯2.2), and 0.2 (±â€¯2.5) mm, and SUP-CTV target motion was 0.3 (±â€¯1.8), 0.5 (±â€¯2.3), and 0 (±â€¯5.0) mm in LR, SI, and AP directions, respectively. No statistically significant differences between INF-CTV and SUP-CTV motion were present in any direction. CONCLUSION: There are no statistically apparent motion differences between SUP-CTV and INF-CTV. Current uniform planning target volume (PTV) margins are adequate to cover both portions of the CTV.

Predictive Value of Circulating Tumor Cells for Evaluating Short- and Long-Term Efficacy of Chemotherapy for Breast Cancer.

BACKGROUND The present study investigated the role of circulating tumor cells (CTCs) counts in predicting the short- and long-term efficacy of chemotherapy for breast cancer (BC). MATERIAL AND METHODS Peripheral venous blood was extracted from 187 BC patients. CTCs were measured by flow cytometry. Spearman's correlation analysis was performed to examine the correlation between the efficacy of chemotherapy and CTC counts. A receiver operating characteristic (ROC) curve was plotted to estimate the predictive value of CTC counts. The Kaplan-Meier method was employed to calculate disease-free survival (DFS) and overall survival (OS). Cox regression analysis was used to determine risk factors for prognosis of BC. RESULTS Complete response (CR) + partial response (PR) was achieved by 65.8% of BC patients. After chemotherapy, CTC counts were decreased in both the CR + PR and SD + PD groups. Spearman's correlation analysis indicated that CTC counts before chemotherapy were positively correlated with clinical response to chemotherapy (r=0.45, P<0.05). For predicting clinical response to chemotherapy, CTC counts yielded an area under the curve (AUC) of 0.958, with sensitivity reaching 96.9% and specificity reaching 85.4%. The Kaplan-Meier method and Cox regression analysis indicated that tumor node metastasis (TNM) staging, lymph node metastasis (LNM), ki-67, endocrine therapy, and CTC counts were risk factors for prognosis of BC. CONCLUSIONS These findings indicate that BC patients with CTCs ³8 exhibited poor response to chemotherapy and poor OS. CTC counts can serve as an indicator in predicting short- and long-term efficacy of chemotherapy for BC.

Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning.

PURPOSE: (a) To investigate the accuracy of cone-beam computed tomography (CBCT)-derived dose distributions relative to fanbeam-based simulation CT-derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. METHODS AND MATERIALS: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity-modulated radiation therapy and volumetric-modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient-specific stepwise curve (Hounsfield units-to-density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation-CT-derived treatment plans and CBCT-based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT-derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source-to-skin-distance change-derived approach. RESULTS: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high-, medium-, and low-dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT-based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. CONCLUSIONS: CBCT-based dose calculations produced accuracy comparable to that of simulation CT. CBCT-based dosimetry can guide the decision to replan during the course of treatment.

ß-selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: the synthesis of SGLT2 inhibitors.

The stereoselective arylation of hydroxy protected 1,6-anhydro-ß-d-glucose with arylalanes to provide ß-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Brønsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.