ACR benchmark testing of a novel high-speed ring-gantry linac kV-CBCT system.

A new generation cone-beam computed tomography (CBCT) system with new hardware design and advanced image reconstruction algorithms is available for radiation treatment simulation or adaptive radiotherapy (HyperSight CBCT imaging solution, Varian Medical Systems-a Siemens Healthineers company). This study assesses the CBCT image quality metrics using the criteria routinely used for diagnostic CT scanner accreditation as a first step towards the future use of HyperSight CBCT images for treatment planning and target/organ delineations. Image performance was evaluated using American College of Radiology (ACR) Program accreditation phantom tests for diagnostic computed tomography systems (CTs) and compared HyperSight images with a standard treatment planning diagnostic CT scanner (Siemens SOMATOM Edge) and with existing CBCT systems (Varian TrueBeam version 2.7 and Varian Halcyon version 2.0).  Image quality performance for all Varian HyperSight CBCT vendor-provided imaging protocols were assessed using ACR head and body ring CT phantoms, then compared to existing imaging modalities. Image quality analysis metrics included contrast-to-noise (CNR), spatial resolution, Hounsfield number (HU) accuracy, image scaling, and uniformity. All image quality assessments were made following the recommendations and passing criteria provided by the ACR. The Varian HyperSight CBCT imaging system demonstrated excellent image quality, with the majority of vendor-provided imaging protocols capable of passing all ACR CT accreditation standards. Nearly all (8/11) vendor-provided protocols passed ACR criteria using the ACR head phantom, with the Abdomen Large, Pelvis Large, and H&N vendor-provided protocols produced HU uniformity values slightly exceeding passing criteria but remained within the allowable minor deviation levels (5-7 HU maximum differences). Compared to other existing CT and CBCT imaging modalities, both HyperSight Head and Pelvis imaging protocols matched the performance of the SOMATOM CT scanner, and both the HyperSight and SOMATOM CT substantially surpassed the performance of the Halcyon 2.0 and TrueBeam version 2.7 systems. Varian HyperSight CBCT imaging system could pass almost all tests for all vendor-provided protocols using ACR accreditation criteria, with image quality similar to those produced by diagnostic CT scanners and significantly better than existing linac-based CBCT imaging systems.

Acute and long-term toxicity of whole pelvis proton radiation therapy for definitive or adjuvant management of gynecologic cancers.

OBJECTIVE: To characterize long-term toxicity and disease outcomes with whole pelvis (WP) pencil beam scanning proton radiation therapy (PBS PRT) for gynecologic malignancies. METHODS: We reviewed 23 patients treated from 2013 to 2019 with WP PBS PRT for endometrial, cervical, and vaginal cancer. We report acute and late Grade (G)2+ toxicities, graded by Common Terminology Criteria for Adverse Events, Version 5. Disease outcomes were assessed by Kaplan-Meier method. RESULTS: Median age was 59 years. Median follow up was 4.8 years. 12 (52.2%) had uterine cancer, 10 (43.5%) cervical, 1 (4.3%) vaginal. 20 (86.9%) were treated post-hysterectomy. 22 (95.7%) received chemotherapy, 12 concurrently (52.2%). The median PBS PRT dose was 50.4GyRBE (range, 45-62.5). 8 (34.8% had para-aortic/extended fields. 10 (43.5%) received brachytherapy boost. Median follow up was 4.8 years. 5-year actuarial local control was 95.2%, regional control 90.9%, distant control 74.7%, both disease control and progression-free survival 71.2%. Overall survival was 91.3%. In the acute period, 2 patients (8.7%) had G2 genitourinary (GU) toxicity, 6 (26.1%) had gastrointestinal (GI) G2-3 toxicity, 17 (73.9%) had G2-4 hematologic (H) toxicity. In the late period, 3 (13.0%) had G2 GU toxicity, 1 (4.3%) had G2 GI toxicity, 2 (8.7%) had G2-3H toxicity. The mean small bowel V15Gy was 213.4 cc. Mean large bowel V15 Gy was 131.9 cc. CONCLUSIONS: WP PBS PRT for gynecologic malignancies delivers favorable locoregional control. Rates of GU and GI toxicity are low. Acute hematologic toxicity was most common, which may be related to the large proportion of patients receiving chemotherapy.

Using radiomics-based modelling to predict individual progression from mild cognitive impairment to Alzheimer's disease.

BACKGROUND: Predicting the risk of disease progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) has important clinical significance. This study aimed to provide a personalized MCI-to-AD conversion prediction via radiomics-based predictive modelling (RPM) with multicenter 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data. METHOD: FDG PET and neuropsychological data of 884 subjects were collected from Huashan Hospital, Xuanwu Hospital, and from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. First, 34,400 radiomic features were extracted from the 80 regions of interest (ROIs) for all PET images. These features were then concatenated for feature selection, and an RPM model was constructed and validated on the ADNI dataset. In addition, we used clinical data and the routine semiquantification index (standard uptake value ratio, SUVR) to establish clinical and SUVR Cox models for further comparison. FDG images from local hospitals were used to explore RPM performance in a separate cohort of individuals with healthy controls and different cognitive levels (a complete AD continuum). Finally, correlation analysis was conducted between the radiomic biomarkers and neuropsychological assessments. RESULTS: The experimental results showed that the predictive performance of the RPM Cox model was better than that of other Cox models. In the validation dataset, Harrell's consistency coefficient of the RPM model was 0.703 ± 0.002, while those of the clinical and SUVR models were 0.632 ± 0.006 and 0.683 ± 0.009, respectively. Moreover, most crucial imaging biomarkers were significantly different at different cognitive stages and significantly correlated with cognitive disease severity. CONCLUSION: The preliminary results demonstrated that the developed RPM approach has the potential to monitor progression in high-risk populations with AD.

High-Capacity, Dendrite-Free, and Ultrahigh-Rate Lithium-Metal Anodes Based on Monodisperse N-Doped Hollow Carbon Nanospheres.

To unlock the great potential of lithium metal anodes for high-performance batteries, a number of critical challenges must be addressed. The uncontrolled dendrite growth and volume changes during cycling (especially, at high rates) will lead to short lifespan, low Coulombic efficiency (CE), and security risks of the batteries. Here it is reported that Li metal anodes, employing the monodisperse, lithiophilic, robust, and large-cavity N-doped hollow carbon nanospheres (NHCNSs) as the host, show remarkable performances-high areal capacity (10 mAh cm-2), high CE (up to 99.25% over 500 cycles), complete suppression of dendrite growth, dense packing of Li anode, and an extremely smooth electrode surface during repeated Li plating/stripping. In symmetric cells, a highly stable voltage hysteresis over a long cycling life >1200 h is achieved, and a low and stable voltage hysteresis can be realized even at an ultrahigh current density of 64 mA cm-2. Furthermore, the NHCNSs-based anodes, when paired with a LiFePO4 (LFP) cathode in full cells, give rise to highly improved rate capability (104 mAh g-1 at 10 C) and cycling stability (91.4% capacity retention for 200 cycles), enabling a promising candidate for the next-generation high energy/power density batteries.

Intravenous methylprednisolone or immunoglobulin for anti-glutamic acid decarboxylase 65 antibody autoimmune encephalitis: which is better?

BACKGROUND: Patients positive for anti-glutamic acid decarboxylase 65 (GAD65) antibodies have attracted increasing attention. Their clinical manifestations are highly heterogeneous and can be comorbid with tumors. Currently, there is no consensus on the therapeutic regimen for anti-GAD65-associated neurological diseases due to the clinical complexity, rarity and sporadic distribution. We reported six anti-GAD65 autoimmune encephalitis (AE) patients who received intravenous methylprednisolone (IVMP) or immunoglobulin (IVIG) or both. Then, we evaluated the therapeutic effect of both by summarizing results in previous anti-GAD65 AE patients from 70 published references. RESULTS: Our six patients all achieved clinical improvements in the short term. Unfortunately, there was no significant difference between IVMP and IVIG in terms of therapeutic response according to the previous references, and the effectiveness of IVMP and IVIG was 45.56% and 36.71%, respectively. We further divided the patients into different subgroups according to their prominent clinical manifestations. The response rates of IVMP and IVIG were 42.65% and 32.69%, respectively, in epilepsy patients; 60.00% and 77.78%, respectively, in patients with stiff-person syndrome; and 28.57% and 55.56%, respectively, in cerebellar ataxia patients. Among 29 anti-GAD65 AE patients with tumors, the response rates of IVMP and IVIG were 29.41% and 42.11%, respectively. There was no significant difference in effectiveness between the two regimens among the different subgroups. CONCLUSION: Except for stiff-person syndrome, we found that this kind of AE generally has a poor response to IVMP or IVIG. Larger prospective studies enrolling large numbers of patients are required to identify the optimal therapeutic strategy in the future.

Clinical Presentation and Outcomes of Opioid-Induced Adrenal Insufficiency.

OBJECTIVE: Opioid-induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due to suppression of the hypothalamic-pituitary-adrenal axis. Our objective was to describe the clinical manifestations, biochemical presentation, and clinical course of OIAI. METHODS: A retrospective study of adults diagnosed with OIAI between 2006 and 2018 at an academic center. Opioid daily dose was converted into morphine milligram equivalents (MMEs). RESULTS: Forty patients (women, n = 29 [73%]) taking chronic opioids at a daily median MME dose of 105 (60 to 200) mg and median duration of 60 (3 to 360) months were diagnosed with OIAI. Patients reported fatigue (n = 29, 73%), musculoskeletal pain (n = 21, 53%), and weight loss (n = 17, 53%) for a median of 12 (range, 1 to 132) months prior to diagnosis, and only 7.5% (n = 3) of patients were identified with OIAI through case detection. Biochemical diagnosis of OIAI was based on (1) low morning cortisol, baseline adrenocorticotropic hormone and/or dehydroepiandrosterone sulfate in 59% (n = 26) of patients or (2) abnormal cosyntropin stimulation test in 41% (n = 14) of patients. With glucocorticoid replacement, 16/23 (70%) patients with available follow-up experienced improvement in symptoms. Opioids were tapered or discontinued in 15 patients, of whom 10 were followed for adrenal function and of which 7 (70%) recovered from OIAI. CONCLUSION: Minimum daily MME in patients diagnosed with OIAI was 60 mg. OIAI causes significant morbidity, and recognition requires a high level of clinical suspicion. Appropriate glucocorticoid treatment led to improvement of symptoms in 70%. Resolution of OIAI occurred following opioid cessation or reduction.

Relationship between Urinary Alzheimer-Associated Neuronal Thread Protein and Apolipoprotein Epsilon 4 Allele in the Cognitively Normal Population.

We investigated the relationship between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) levels and apolipoprotein epsilon 4 (ApoE ɛ4) alleles, as well as other factors that cause cognitive decline, in the cognitively normal population. We recruited 329 cognitively normal right-handed Han Chinese subjects who completed ApoE gene testing and urinary AD7c-NTP testing. There was no significant difference in urinary AD7c-NTP levels between the normal control and subjective cognitive decline groups. Urinary AD7c-NTP levels were significantly higher in subjects with ApoE ɛ3/4 and 4/4 [0.6074 (0.6541) ng/mL] than in subjects without ApoE ɛ4 [0.4368 (0.3392) ng/mL and 0.5287 (0.3656) ng/mL], and urinary AD7c-NTP levels positively correlated with ApoE genotype grade (r = 0.165, p = 0.003). There were significant differences in urinary AD7c-NTP levels between subjects with and without a history of coronary heart disease or diabetes. Urinary AD7c-NTP levels were not related to years of education, nature of work, family history of dementia, a history of hypertension, stroke, anemia, or thyroid dysfunction. Urinary AD7c-NTP levels were positively correlated with ApoE grade in the cognitively normal population. The relationship between risk factors of cognitive decline and urinary AD7c-NTP levels provides a new way for us to understand AD and urinary AD7c-NTP.

Circular RNA: a new star in neurological diseases.

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. In this review, we summarize a number of the latest theories regarding the biogenesis, properties and functions of circRNAs. Specifically, we focus on the advancing characteristics and functions of circRNAs in the brain and neurological diseases. CircRNAs exhibit the characteristics of species conservation, abundance and tissue/developmental-stage-specific expression in the brain. We also describe the relationship between circRNAs and several neurological diseases and highlight their functions in neurological diseases.

Diode-based transmission detector for IMRT delivery monitoring: a validation study.

The purpose of this work was to evaluate the potential of a new transmission detector for real-time quality assurance of dynamic-MLC-based radiotherapy. The accuracy of detecting dose variation and static/dynamic MLC position deviations was measured, as well as the impact of the device on the radiation field (surface dose, transmission). Measured dose variations agreed with the known variations within 0.3%. The measurement of static and dynamic MLC position deviations matched the known deviations with high accuracy (0.7-1.2 mm). The absorption of the device was minimal (~ 1%). The increased surface dose was small (1%-9%) but, when added to existing collimator scatter effects could become significant at large field sizes (≥ 30 × 30 cm2). Overall the accuracy and speed of the device show good potential for real-time quality assurance.

Quantitative comparison of automatic and manual IMRT optimization for prostate cancer: the benefits of DVH prediction.

A recent publication indicated that the patient anatomical feature (PAF) model was capable of predicting optimal objectives based on past experience. In this study, the benefits of IMRT optimization using PAF-predicted objectives as guidance for prostate were evaluated. Three different optimization methods were compared.1) Expert Plan: Ten prostate cases (16 plans) were planned by an expert planner using conventional trial-and-error approach started with institutional modified OAR and PTV constraints. Optimization was stopped at 150 iterations and that plan was saved as Expert Plan. 2) Clinical Plan: The planner would keep working on the Expert Plan till he was satisfied with the dosimetric quality and the final plan was referred to as Clinical Plan. 3) PAF Plan: A third sets of plans for the same ten patients were generated fully automatically using predicted DVHs as guidance. The optimization was based on PAF-based predicted objectives, and was continued to 150 iterations without human interaction. DMAX and D98% for PTV, DMAX for femoral heads, DMAX, D10cc, D25%/D17%, and D40% for bladder/rectum were compared. Clinical Plans are further optimized with more iterations and adjustments, but in general provided limited dosimetric benefits over Expert Plans. PTV D98% agreed within 2.31% among Expert, Clinical, and PAF plans. Between Clinical and PAF Plans, differences for DMAX of PTV, bladder, and rectum were within 2.65%, 2.46%, and 2.20%, respectively. Bladder D10cc was higher for PAF but < 1.54% in general. Bladder D25% and D40% were lower for PAF, by up to 7.71% and 6.81%, respectively. Rectum D10cc, D17%, and D40% were 2.11%, 2.72%, and 0.27% lower for PAF, respectively. DMAX for femoral heads were comparable (< 35 Gy on average). Compared to Clinical Plan (Primary + Boost), the average optimization time for PAF plan was reduced by 5.2 min on average, with a maximum reduction of 7.1min. Total numbers of MUs per plan for PAF Plans were lower than Clinical Plans, indicating better delivery efficiency. The PAF-guided planning process is capable of generating clinical-quality prostate IMRT plans with no human intervention. Compared to manual optimization, this automatic optimization increases planning and delivery efficiency, while maintainingplan quality.

Impact of dose calculation accuracy during optimization on lung IMRT plan quality.

The purpose of this study was to evaluate the effect of dose calculation accuracy and the use of an intermediate dose calculation step during the optimization of intensity-modulated radiation therapy (IMRT) planning on the final plan quality for lung cancer patients. This study included replanning for 11 randomly selected free-breathing lung IMRT plans. The original plans were optimized using a fast pencil beam convolution algorithm. After optimization, the final dose calculation was performed using the analytical anisotropic algorithm (AAA). The Varian Treatment Planning System (TPS) Eclipse v11, includes an option to perform intermediate dose calculation during optimization using the AAA. The new plans were created using this intermediate dose calculation during optimization with the same planning objectives and dose constraints as in the original plan. Differences in dosimetric parameters for the planning target volume (PTV) dose coverage, organs-at-risk (OARs) dose sparing, and the number of monitor units (MU) between the original and new plans were analyzed. Statistical significance was determined with a p-value of less than 0.05. All plans were normalized to cover 95% of the PTV with the prescription dose. Compared with the original plans, the PTV in the new plans had on average a lower maximum dose (69.45 vs. 71.96Gy, p = 0.005), a better homogeneity index (HI) (0.08 vs. 0.12, p = 0.002), and a better conformity index (CI) (0.69 vs. 0.59, p = 0.003). In the new plans, lung sparing was increased as the volumes receiving 5, 10, and 30 Gy were reduced when compared to the original plans (40.39% vs. 42.73%, p = 0.005; 28.93% vs. 30.40%, p = 0.001; 14.11%vs. 14.84%, p = 0.031). The volume receiving 20 Gy was not significantly lower (19.60% vs. 20.38%, p = 0.052). Further, the mean dose to the lung was reduced in the new plans (11.55 vs. 12.12 Gy, p = 0.024). For the esophagus, the mean dose, the maximum dose, and the volumes receiving 20 and 60 Gy were lower in the new plans than in the original plans (17.91 vs. 19.24 Gy, p = 0.004; 57.32vs. 59.81 Gy, p = 0.020; 39.34% vs. 41.59%, p = 0.097; 12.56%vs. 15.35%, p = 0.101). For the heart, the mean dose, the maximum dose, and the volume receiving 40 Gy were also lower in new plans (11.07 vs. 12.04 Gy, p = 0.007; 56.41 vs. 57.7 Gy, p = 0.027; 7.16% vs. 9.37%, p= 0.012). The maximum dose to the spinal cord in the new plans was significantly lower than in the original IMRT plans (29.1 vs. 31.39Gy, p = 0.014). Difference in MU between the IMRT plans was not significant (1216.90 vs. 1198.91, p = 0.328). In comparison to the original plans, the number of iterations needed to meet the optimization objectives in the new plans was reduced by a factor of 2 (2-3 vs. 5-6 iterations). Further, optimization was 30% faster corresponding to an average time savings of 10-15 min for the reoptimized plans. Accuracy of the dose calculation algorithm during optimization has an impact on planning efficiency, as well as on the final plan dosimetric quality. For lung IMRT treatment planning, utilizing the intermediate dose calculation during optimization is feasible for dose homogeneity improvement of the PTV and for improvement of optimization efficiency.

Liquid Glycan Array.

The M13 phage platform is a stable and monodisperse nanoscale carrier, which can be modified with different molecules by chemical conjugation strategies. Here, we describe M13 phage acylated on pVIII protein with a dibenzocyclooctyne reacting with azido glycan to yield 30-1500 copy numbers of glycan per phage and monitored by MALDI-TOF spectrometry to generate multivalent glycoconjugates that contain desired densities of glycans. We prepared the liquid glycan arrays (LiGA) such that both the structure and density of glycans were encoded in the DNA of the bacteriophage. The LiGA can be used to validate the binding properties of glycans to purified lectins and explore the effect of glycan density on such binding. From a mixture of multivalent glycan probes, LiGAs can also identify the glycoconjugates with optimal avidity necessary for binding to lectins on living cells in vitro and live animals in vivo.

Glucose metabolism in posterior cingulate cortex has supplementary value to predict the progression of cognitively unimpaired to dementia due to Alzheimer's disease: an exploratory study of 18F-FDG-PET.

Amyloid-ß (Aß) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aß positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in the PCC as a biomarker supplement to Aß and tau biomarkers. First, we calculated the standard uptake value ratio (SUVR) of PCC based on fluorodeoxyglucose positron emission computed tomography (FDG PET) imaging. Secondly, we performed Kaplan-Meier (KM) survival analyses to explore the predictive performance of PCC SUVR, and the hazard ratio (HR) was calculated. Finally, we performed Pearson correlation analyses to explore the physiological significance of PCC SUVR. As a result, the PCC SUVR showed a consistent downward trend along the AD continuum. KM analyses showed better predictive performance when we combined PCC SUVR with cerebro-spinal fluid (CSF) Aß42 (from HR = 2.56 to 3.00 within 5 years; from HR = 2.76 to 4.20 within 10 years) and ptau-181 (from 2.83 to 3.91 within 5 years; from HR = 2.32 to 4.17 within 10 years). There was a slight correlation between Aß42/Aß40 and PCC SUVR (r = 0.14, p = 0.02). In addition, several cognition scales were also correlated to PCC SUVR (from r = -0.407 to 0.383, p < 0.05). Our results showed that glucose metabolism in PCC may be a potential biomarker supplement to the Aß and tau biomarkers to predict the progression of CU to AD.

Five-Year Outcomes of a Phase 1/2 Trial of Accelerated Partial Breast Irradiation Using Proton Therapy for Women With Stage 0-IIA Breast Cancer.

Purpose: We report the results of a phase 1/2 trial of external beam partial breast radiation using proton therapy. Methods and Materials: Eligible patients included stage 0-IIA breast cancer pTis-T2, N0, and size ≤3 cm. Proton beam radiation was used to deliver 3.85 Gy twice daily to 38.5 Gy. The phase 1 portion determined feasibility based on criteria of successful plan creation, treatment delivery, and acute toxicity grade ≥3 in ≤20% of patients. The phase 2 portion had efficacy goals of acute toxicity grade ≥3 in ≤20% of patients and observing physician-rated cosmesis of excellent or good >85% of patients at 2 years. Results: From April 2013 to March 2015, there were 12 patients enrolled onto the phase 1 portion, and the preplanned analysis of feasibility was met in all 4 required criteria. From July 2015 through December 2019 there were 28 patients with 29 treated breasts (1 bilateral) enrolled onto the phase 2 portion of the trial out of 45 originally planned. The trial was closed to accrual because of the coronavirus pandemic and not reopened. Thirty-eight breasts were treated with double-scattering and 3 pencil-beam scanning protons. The median follow-up of the 40 patients is 5.4 years (range, 2.3-8.6 years). There was 1 local recurrence. There was no grade ≥3 acute or late toxicity. At baseline all patients had physician-rated cosmesis good or excellent but at 2 years was excellent in 56%, good in 19%, and fair in 25%. Conclusions: Proton-accelerated partial breast irradiation delivered with a twice-daily fractionation was feasible and associated with very low acute and long-term toxicity. However, the trial did not meet goals for cosmesis outcomes and was closed prematurely. Future study is needed to determine whether pencil-beam scanning protons or different fractionation could improve these outcomes.

Breast Reconstruction Complications After Postmastectomy Proton Radiation Therapy for Breast Cancer.

Purpose: Our purpose was to report complications requiring surgical intervention among patients treated with postmastectomy proton radiation therapy (PMPRT) for breast cancer in the setting of breast reconstruction (BR). Methods and Materials: Patients enrolled on a prospective proton registry who underwent BR with immediate autologous flap, tissue expander (TE), or implant in place during PMPRT (50/50.4 Gy +/- chest wall boost) were eligible. Major reconstruction complication (MRC) was defined as a complication requiring surgical intervention. Absolute reconstruction failure was an MRC requiring surgical removal of BR. A routine revision (RR) was a plastic surgery refining cosmesis of the BR. Kaplan-Meier method was used to assess disease outcomes and MRC. Cox regression was used to assess predictors of MRC. Results: Seventy-three courses of PMPRT were delivered to 68 women with BR between 2013 and 2021. Median follow-up was 42.1 months. Median age was 47 years. Fifty-six (76.7%) courses used pencil beam scanning PMPRT. Of 73 BR, 29 were flaps (39.7%), 30 implants (41.1%), and 14 TE (19.2%) at time of irradiation. There were 20 (27.4%) RR. There were 9 (12.3%) MRC among 5 implants, 2 flaps, and 2 TE, occurring a median of 29 months from PMPRT start. Three-year freedom from MRC was 86.9%. Three (4.1%) of the MRC were absolute reconstruction failure. Complications leading to MRC included capsular contracture in 5, fat necrosis in 2, and infection in 2. On univariable analysis, BR type, boost, proton technique, age, and smoking status were not associated with MRC, whereas higher body mass index trended toward significance (hazard ratio, 1.07; 95% CI, 0.99-1.16; P = .10). Conclusions: Patients undergoing PMPRT to BR had a 12.3% incidence of major complications leading to surgical intervention, and total loss of BR was rare. MRC rates were similar among reconstruction types. Minor surgery for RR is common in our practice.

Association of plasma BDNF levels with different stages of Alzheimer's disease: a cross-sectional study.

BACKGROUND: Growing evidence shows that the expression of brain-derived neurotrophic factor (BDNF) is altered in the peripheral blood of participants with Alzheimer's disease (AD). It is unclear, however, whether altered BDNF expression is also observed in the early stages of AD. METHODS: In the present study, 138 normal controls (NC), 57 participants with subjective cognitive decline (SCD), and 37 participants with amnestic mild cognitive impairment (aMCI) and AD were included. Plasma BDNF protein levels were assessed using a commercial multiplex Luminex-based kit. Patient samples were also probed for the presence of BDNF gene variant rs6265. RESULTS: Pairwise comparisons between the groups showed that there was not a significant difference in BDNF levels when comparing SCD with NC and when comparing SCD with aMCI/AD, but BDNF levels in aMCI/AD samples were increased when compared with NC samples. For models differentiating clinical groups, discriminant analysis was performed by including education, APOE genotype, and BDNF levels in the model. This approach distinguishes participants with SCD (AUC = 0.630) and aMCI/AD (AUC = 0.665) from NC. CONCLUSION: Our results suggest that expression of BDNF in plasma is altered at the clinical stage of AD.

Associations Between Levels of Peripheral NCAPH2 Promoter Methylation and Different Stages of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Several studies have examined NCAPH2 methylation in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), but little is known of NCAPH2 methylation in subjective cognitive decline (SCD). OBJECTIVE: To examine whether methylation of peripheral NCAPH2 are differentially changed at various phases of AD, and whether it could serve as a diagnostic biomarker for SCD. METHODS: A total of 40 AD patients, 52 aMCI patients, 148 SCD patients, and 193 cognitively normal controls (NCs) were recruited in the current case-control study. Besides, 54 cognitively normal individuals have received amyloid positron emission tomography (amyloid PET) scans. Using bisulfite pyrosequencing method, we measured blood DNA methylation in the NCAPH2 gene promoter. RESULTS: The main outcomes were: 1) For SCD, there was no significant difference between SCD and NC regarding NCAPH2 methylation; 2) For aMCI, NCAPH2 methylation at CpG2 were significantly lower in aMCI compared with NC and SCD in the entire population and male subgroup; 3) For AD, NCAPH2 methylation at CpG1 were significantly lower in AD compared with NC among females; 4) A relationship with apolipoprotein E (APOE) ɛ4 status was shown. Receiver operating characteristic (ROC) analysis by combining NCAPH2 methylation, age, education, and APOEɛ4 status could distinguish between patients with aMCI (area under the curve (AUC): 0.742) and AD (AUC: 0.873) from NCs. CONCLUSION: NCAPH2 methylation levels were altered at the aMCI and AD stage and may be convenient and cost-effective biomarkers of AD and aMCI.

Comparison of surface dose during whole breast radiation therapy on Halcyon and TrueBeam using Cherenkov imaging.

The emergence of the Halcyon linear accelerator has allowed for increased patient throughput and improved treatment times for common treatment sites in radiation oncology. However, it has been shown that this can lead to increased surface dose in sites like breast cancer compared with treatments on conventional machines with flattened radiation beams. Cherenkov imaging can be used to estimate surface dose by detection of Cherenkov photons emitted in proportion to energy deposition from high energy electrons in tissue. Phantom studies were performed with both square beams in reference conditions and with clinical treatments, and dosimeter readings and Cherenkov images report higher surface dose (25% for flat phantom entrance dose, 5.9% for breast phantom treatment) from Halcyon beam deliveries than for equivalent deliveries from a TrueBeam linac. Additionally, the first Cherenkov images of a patient treated with Halcyon were acquired, and superficial dose was estimated.

Effect of polysaccharides on conformational changes and functional properties of protein-polyphenol binary complexes: A comparative study.

This study aimed to investigate the effect of different polysaccharides on the binding behavior and functional properties of soybean protein isolate (SPI)-quercetin (Que) complex. The binding behavior was assessed using multi-spectral technique with the Stern-Volmer equation, which confirmed the presence of static fluorescence quenching in Que and SPI. The addition of sodium alginate (SA) resulted in a reduction of the binding affinity between SPI and Que, while dextran (DX) exhibited some promoting effect. A slight blue shift was observed in amide I and amide II bands, indicating the presence of hydrophobic and electrostatic interactions. Circular dichroism spectra revealed the ordered structures transformed into a more disordered state when polysaccharides were added, leading to an increase in random coils (SA: 18.5 %, DX: 15.4 %). Docking and dynamic simulations demonstrated that SA displayed greater stability within the hydrophobic compartments of SPI than DX, increased rigidity and stability of the SPI structure in SPI-Que-SA complexes. Electrostatic forces played a significant role between SPI and SA, while van der Waals forces were the main driving forces in SPI-DX complexes. Overall, the introduction of SA led to a looser and stable structure of SPI-Que complexes, resulting in an improvement of their emulsifying, foaming, and antioxidant properties.