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Abstract Background Therapeutic targets supported by genetic evidence from genome-wide association studies (GWAS) show higher probability of success in clinical trials. GWAS is a powerful approach to identify links between genetic variants and phenotypic variation; however, identifying the genes driving associations identified in GWAS remains challenging. Integration of molecular quantitative trait loci (molQTL) such as expression QTL (eQTL) using mendelian randomization (MR) and colocalization analyses can help with the identification of causal genes. Careful interpretation remains warranted because eQTL can affect the expression of multiple genes within the same locus. Methods We used a combination of genomic features that include variant annotation, activity-by-contact maps, MR, and colocalization with molQTL to prioritize causal genes across 4,611 disease GWAS and meta-analyses from biobank studies, namely FinnGen, Estonian Biobank and UK Biobank. Results Genes identified using this approach are enriched for gold standard causal genes and capture known biological links between disease genetics and biology. In addition, we find that eQTL colocalizing with GWAS are statistically enriched for corresponding disease-relevant tissues. We show that predicted directionality from MR is generally consistent with matched drug mechanism of actions (> 85% for approved drugs). Compared to the nearest gene mapping method, genes supported by multi-omics evidences displayed higher enrichment in approved therapeutic targets (risk ratio 1.75 vs. 2.58 for genes with the highest level of support). Finally, using this approach, we detected anassociation between the IL6 receptor signal transduction gene IL6ST and polymyalgia rheumatica, an indication for which sarilumab, a monoclonal antibody against IL-6, has been recently approved. Conclusions Combining variant annotation, activity-by-contact maps, and molQTL increases performance to identify causal genes, while informing on directionality which can be translated to successful target identification and drug development.

Abstract Background Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer. Methods The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac. The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI. Conclusion The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808 .

Abstract Background Accelerated partial breast irradiation (APBI) is an accepted treatment option for early breast cancer. Treatment delivered on the Magnetic Resonance integrated Linear Accelerator (MRL) provides the added assurance of improved soft tissue visibility, important in the delivery of APBI. This technique can be delivered in both the supine and prone positions, however current literature suggests that prone treatment on the MRL is infeasible due to physical limitations with bore size. This study aims to investigate the feasibility of positioning patients on a custom designed prone breast board compared with supine positioning on a personalised vacuum bag. Geometric distortion, the relative position of Organs at Risk (OAR) to the tumour bed and breathing motion (intrafraction motion) will be compared between the supine and prone positions. The study will also investigate the positional impact on dosimetry, patient experience, and position preference. Methods Up to 30 patients will be recruited over a 12-month period for participation in this Human Research Ethics Committee approved exploratory cohort study. Patients will be scanned on the magnetic resonance imaging (MRI) Simulator in both the supine and prone positions as per current standard of care for APBI simulation. Supine and prone positioning comparisons will all be assessed on de-identified MRI image pairs, acquired using appropriate software. Patient experience will be explored through completion of a short, anonymous electronic survey. Descriptive statistics will be used for reporting of results with categorical, parametric/non-parametric tests applied (data format dependent). Survey results will be interpreted by comparison of percentage frequencies across the Likert scales. Thematic content analysis will be used to interpret qualitative data from the open-ended survey questions. Discussion The results of this study will be used to assess the feasibility of treating patients with APBI in the prone position on a custom designed board on the MRL. It may also be used to assist with identification of patients who would benefit from this position over supine without the need to perform both scans. Patient experience and technical considerations will be utilised to develop a tool to assist in this process. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1262400067583. Registered 28th of May 2024. https://www.anzctr.org.au/ACTRN12624000679583.aspx

Objectives: Our objective was to assess the rate of complications and gastrointestinal adverse effects of rectal spacer insertion for salvage post prostatectomy radiation therapy. Methods: A retrospective observational study was performed. Between September 2018 and March 2022, 64 post-radical prostatectomy patients who were planned for salvage radiation therapy received a rectal spacer. The selected patients were those who had nerve-sparing prostatectomy with intrafascial or interfascial dissections (where Denonvillier’s fascia is retained). Radiation dose to the rectal wall and gastrointestinal symptoms were assessed. Symptoms were graded using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. A total of 39 patients had pre-spacer planning computer tomography (CT) scans, and the rectal dose before and after the spacer insertion was calculated. Comparisons were made using the Student’s t-test, with a p-value < 0.05 representing statistical significance. Finally, clinicians were surveyed to rate the ease of the procedure using a 5-point Likert scale of 1 to 5 (1: very difficult, 2: difficult, 3: moderate, 4: easy, 5: very easy). Results: A total of 64 patients successfully underwent rectal spacer insertion. The mean age was 64.4 years (standard deviation: 5.7 years). After a median of 14 months’ (range 6 to 35) follow up, acute grade 1 and above gastrointestinal (GI) toxicities were seen in 28% of patients (grade 2 in 1.5%), and late grade 1 and above GI toxicities were seen in 12% of patients (grade 2 in 1.5%). Amongst the 39 patients with pre-spacer planning CT images, the volume of the rectum receiving 60%, 70%, 80%, 90%, and 100% of the prescribed radiation dose was reduced by 25.9%, 34.2%, 35.4%, 43.7%, and 61.7%, respectively. All dose reductions were statistically significant. The procedure was rated as “easy” or “very easy” to perform in 56% of cases. Conclusions: The insertion of a rectal spacer in selected patients undergoing PPRT is feasible and safe and significantly improves rectal wall radiation dosimetry in salvage post prostatectomy radiation therapy. It was accomplished in >95% of patients, increasing vesico-rectal separation from ‘immediate vicinity’ to 11 mm without any post-operative complications in experienced hands. In addition, it achieved significant reduction in rectal radiation doses, leading to low rates of acute and late grade 2 toxicity.

Summary: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare, immune-mediated disorder in which an aberrant immune response causes demyelination and axonal damage of the peripheral nerves. Genetic contribution to CIDP is unclear and no genome-wide association study (GWAS) has been reported so far. In this study, we aimed to identify CIDP-related risk loci, genes, and pathways. We first focused on CIDP, and 516 CIDP cases and 403,545 controls were included in the GWAS analysis. We also investigated genetic risk for inflammatory polyneuropathy (IP), in which we performed a GWAS study using FinnGen data and combined the results with GWAS from the UK Biobank using a fixed-effect meta-analysis. A total of 1,261 IP cases and 823,730 controls were included in the analysis. Stratified analyses by gender were performed. Mendelian randomization (MR), colocalization, and transcriptome-wide association study (TWAS) analyses were performed to identify associated genes. Gene-set analyses were conducted to identify associated pathways. We identified one genome-wide significant locus at 20q13.33 for CIDP risk among women, the top variant located at the intron region of gene CDH4. Sex-combined MR, colocalization, and TWAS analyses identified three candidate pathogenic genes for CIDP and five genes for IP. MAGMA gene-set analyses identified a total of 18 pathways related to IP or CIDP. Sex-stratified analyses identified three genes for IP among males and two genes for IP among females. Our study identified suggestive risk genes and pathways for CIDP and IP. Functional analyses should be conducted to further confirm these associations.

While there are various studies investigating the effect of freezing on palatability characteristics, thawing has not received the same level of interest. Therefore, the objective of this study was to investigate the effects of various thawing methods on beef palatability. Paired beef strip loins (n = 15 pairs) were obtained from a commercial processing facility for palatability evaluation, and 6 additional strip loins were collected for thawing characteristic data. The paired loins were sectioned into 6 sections of 4 steaks each, and each section assigned a thawing method. Thaw methods included thawing in the refrigerator, cold water, microwave, hot water, on the counter, and cooking from frozen. Steaks were aged a total of 21 d prior to freezing. Consumer sensory panelists (N = 120) found no differences (P > 0.05) among all thawing methods for each palatability characteristic. Within trained sensory panels (n = 8 panelists/session), thawing in the refrigerator and cold water were rated higher (P < 0.05) for overall tenderness than thawing in the microwave and cooking from frozen. Cooking steaks from frozen was rated higher (P < 0.05) for beef flavor intensity than all other thawing methods by trained sensory panelists. Steaks thawed in the microwave had the highest (P < 0.05) percentage of cook loss, followed by cooking from frozen, with all other methods being similar (P > 0.05). Similarly, steaks thawed in the microwave and in hot water had a higher (P < 0.05) thawing loss percentage than steaks thawed on the counter, in cold water, or in the refrigerator. These results indicate thawing method had minimal differences on overall beef palatability and objective quality measures. Therefore, consumers and foodservice establishments should use their preferred thaw method based on convenience, taking food safety and time into consideration.

While the factors impacting raw meat color have been extensively explored, the factors affecting cooked meat color have been largely ignored, leaving a gap in research. Establishing a baseline for the changes that accompany different degrees of doneness (DOD) could serve as the foundation for future studies to further understand what factors are impacting differences in cooked color of whole muscles. Beef strip loins (n=12) and top butts (n=12) were used to evaluate the Longissimus dorsi (LD), Biceps femoris (BF), and Gluteus medius (GM) between 3 DOD: medium rare (62.8°C), medium (71.1°C), and well-done (76.7°C). Immediately after cooking, steaks were sliced, evaluated for L*, a*, b*, frozen in liquid nitrogen, and blended into a powder for lab assays including myoglobin denaturation, metmyoglobin-reducing activity (MRA), surface hydrophobicity, proximate analysis, and lipid oxidation. An additional steak was cooked for shear force and cook loss. As expected, the a* values decreased (P0.05) either. Surface hydrophobicity, which is a measure of exposed hydrophobic groups caused by denaturation, increased (P

The objective of this study was to evaluate the impact of applying electrostatic field (EF)–assisted thawing on the quality attributes of previously frozen beef striploin. Beef striploins from both sides of 12 USDA Choice carcasses were halved, frozen at −40°C, and thawed under 4 EF voltage treatments: 0 kV (control), 2.5 kV, 5 kV, and 10 kV. After reaching the internal temperature of −1°C, striploins were weighed for yield calculation, swabbed for microbial analysis, fabricated into steaks, and assigned to either 0- or 14-d aging period and retail displayed for 0 or 7 d. Subjective and objective color measurements were taken during the retail display. Upon completion of retail display, Warner-Bratzler shear force (WBSF), cook loss, sarcomere length, troponin-T degradation, muscle fiber spacing, lipid oxidation, antioxidant capacity, pH, and proximate analysis were performed. All EF treatments increased purge loss compared to the control (P0.05). Overall, our study determined that there was no economic benefit to apply EF during thawing regarding yield and purge loss. However, the application of EF may improve tenderness and extend shelf life of beef during retail display.

Although studies evaluating freezing are prevalent, most have used varied postmortem aging times to facilitate study design. The lack of a comprehensive study evaluating equally aged fresh and frozen steaks prevents a true under-standing of the impact of freezing. Therefore, the objective of this study was to determine the eating quality and consumer perception differences between fresh and frozen beef steaks of 3 equal aging periods. Beef carcasses were selected from a processing plant on 2 kill dates 1 wk apart to allow for a 1-wk freezing period, fabricated, and aged for 21, 28, or 35 d. On the same day, all samples of equal aging periods were fed to consumer and trained sensory panelists, sheared for shear force, and powdered for lab assays. For consumer panels, the first 4 steaks were given with no additional information, whereas the last 4 steaks were served with the labels “previously frozen” or “fresh, never frozen.” The consumer panelists rated the frozen samples as more tender (P0.05). Even when given additional information, the perception of quality was not impacted (P>0.05). Similarly, the trained panelists rated the frozen samples higher (P

Introduction: Consistent delineation of the breast conserving surgery (BCS) tumour bed (TB) for breast cancer remains a challenge for radiation oncologists. Accurate delineation allows for better local control and reduces toxicity when planning partial breast or TB boost radiation therapy (RT). Methods: In the operating theatre (OT) breast surgeons inserted stabilised hyaluronic acid (sHA) gel as small drops approximately one cm into the walls surrounding the resection cavity. Surgical feasibility was determined by the rate of successful sHA gel insertion procedure, the ease of insertion as rated by surgeons, the time required for insertion procedure, the quantity used, and any adverse events (AE) relating to sHA gel insertion. Results: Thirty-five patients were enrolled. All patients underwent sHA gel insertion successfully. The procedure added a median of 2.8 min to the OT time and was rated as ‘easy’ in 89 % of patients. There were no immediate AE in OT. Five (14 %) patients experienced a grade 2 or higher AE. Three of the five patients were prescribed oral antibiotics for breast infection. Two of the five patients experienced a grade 3 AE – haematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS. All five patients recovered and underwent the planned adjuvant therapies for their BC. The AE data reflects common risks with standard BCS and are not clearly attributed to sHA gel insertion alone. Conclusion: We show that sHA gel is surgically feasible as a marker to help define the TB cavity for post-BCS adjuvant MRI-based RT planning.

Purpose: We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body compositi on or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods: We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results: Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was −1.54 cm2 (95% CI: −14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increa ses in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and expl oratory outcomes was observed between groups. Conclusions: While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-asso ciated effect and more on the general development of cardiovascular risk over time.

Abstract Background Alzheimer’s disease (AD) is a progressive and age-associated neurodegenerative disorder that affects women disproportionally. However, the underlying mechanisms are poorly characterized. Moreover, while the interplay between sex and ApoE genotype in AD has been investigated, multi-omics studies to understand this interaction are limited. Therefore, we applied systems biology approaches to investigate sex-specific molecular networks of AD. Methods We integrated large-scale human postmortem brain transcriptomic data of AD from two cohorts (MSBB and ROSMAP) via multiscale network analysis and identified key drivers with sexually dimorphic expression patterns and/or different responses to APOE genotypes between sexes. The expression patterns and functional relevance of the top sex-specific network driver of AD were further investigated using postmortem human brain samples and gene perturbation experiments in AD mouse models. Results Gene expression changes in AD versus control were identified for each sex. Gene co-expression networks were constructed for each sex to identify AD-associated co-expressed gene modules shared by males and females or specific to each sex. Key network regulators were further identified as potential drivers of sex differences in AD development. LRP10 was identified as a top driver of the sex differences in AD pathogenesis and manifestation. Changes of LRP10 expression at the mRNA and protein levels were further validated in human AD brain samples. Gene perturbation experiments in EFAD mouse models demonstrated that LRP10 differentially affected cognitive function and AD pathology in sex- and APOE genotype-specific manners. A comprehensive mapping of brain cells in LRP10 over-expressed (OE) female E4FAD mice suggested neurons and microglia as the most affected cell populations. The female-specific targets of LRP10 identified from the single cell RNA-sequencing (scRNA-seq) data of the LRP10 OE E4FAD mouse brains were significantly enriched in the LRP10-centered subnetworks in female AD subjects, validating LRP10 as a key network regulator of AD in females. Eight LRP10 binding partners were identified by the yeast two-hybrid system screening, and LRP10 over-expression reduced the association of LRP10 with one binding partner CD34. Conclusions These findings provide insights into key mechanisms mediating sex differences in AD pathogenesis and will facilitate the development of sex- and APOE genotype-specific therapies for AD.

The objective of this study was to evaluate the palatability of 3 plant-based ground beef alternatives (GBA) in comparison to ground beef under real-world hamburger and taco scenarios. The 3 plant-based GBA alternatives used represented a modern GBA sold at retail (RGBA), a modern GBA sold in foodservice (FGBA), and a traditional soy-based GBA (TGBA). Additionally, 80% lean ground beef was evaluated. Consumers (N=240; n=120 per panel type) evaluated samples for juiciness, tenderness, texture, beef flavor, overall flavor, overall liking, purchase intent,and purchase price and rated traits as either acceptable or unacceptable. For hamburger panels, consumers were served samples on buns and were given the option to add cheese, lettuce, pickles, ketchup, and/or mustard. For taco panels, samples were seasoned with a taco seasoning blend and served on flour tortillas, with consumers given the option to add cheese, lettuce, and/or tomatoes. In both scenarios, ground beef was rated higher (P0.05) for tenderness to FGBA and RGBA. Additionally, a higher (P0.05) to only RGBA for beef flavor and overall flavor liking within hamburger panels. These results indicate that GBA currently available to consumers do not have improved palatability characteristics when used as an ingredient in a taco or hamburger scenario.

Abstract Objective To compute penetrance and recurrence risk using a genome‐wide PRS (including and excluding the APOE region) in families with Alzheimer's disease. Methods Genotypes from the National Institute on Aging Late‐Onset Alzheimer's Disease Family‐Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE‐ε4 carriers and non‐carriers. Results PRS excluding the APOE region was strongly associated with clinical and neuropathological diagnosis of AD. PRS association with AD was similar in participants who did not carry an APOE‐ε4 allele (OR = 1.74 [1.53–1.91]) compared with APOE‐ε4 carriers (1.53 [1.4–1.68]). Compared to the lowest quintile, the highest PRS quintile had a 10% higher penetrance at age 70 (p = 0.0006) and a 20% higher penetrance at age 80 (p

Pork branding is a common tool used to differentiate products based on quality to assist consumers in making purchasing decisions. Most pork processers have premium pork programs with different parameters related to color, mar-bling, and other quality factors, though many differences in specific criteria exist among programs. The objective of this study was to assess differences in pork quality and the associated eating experience of different premium and commodity pork loin programs available in the retail market. Loins (n=30/brand) from 7 branded (PRE A, B, C, D, and E) and commodity (COM A and B) programs were acquired and fabricated at 14–15 d post-box date into 2.54-cm chops for visual color, marbling, pH, intramuscular fat, drip loss, purge loss, shear force, and trained sensory panels. Overall, few differences were found among products for most of the quality traits evaluated. One commodity brand, COM B, had higher (P0.05) in initial juiciness, sustained juiciness, or any tenderness measurement. The only quality measurement that was associated with changes in eating experience was shear force value, with the PRE C product having the highest (P0.05) among any treatment for initial juiciness, sustained juiciness, and pork flavor intensity. The results from this study indicate that the range of pork quality differences sold domestically among the evaluated premium and commodity programs is minimal and does not result in associated differences in eating experience.

The objective of this study was to identify the threshold for color and discoloration for consumers to purchase ground beef and to determine the best objective measurement to predict consumer purchase intent. This study was designed in 2 phases, with Phase 1 requiring consumers to evaluate ground beef samples of multiple days of display simultaneously, and Phase 2 having consumers evaluate samples of only a single day of display. Ground beef packages (80% lean) were evaluated for overall appearance liking and purchase intent (yes/no) by consumers (n=216 and 318). Additionally, packages were evaluated for L*, a*, b*, calculated percentage of metmyoglobin, oxymyoglobin, chroma, hue angle, and trained sensory panel redness and discoloration scores. Models showed that each of the objective measures evaluated were predictors (P

Lipid oxidation in beef may be enhanced by the hydrolysis of phospholipids by phospholipaseα2 (PLA2) during postmortem storage. Anti-phospholipaseα2 (aPLA2) is an antibody that can inhibit PLA2 activity. Past research has shown that aPLA2 can be mass-produced in the form of egg powder (EP) from hens immunized against PLA2. Therefore, the present study aimed to determine the effects of incorporating different levels of EP containing aPLA2 into ground striploin (GS) to assess its ability to extend beef shelf-life. Ten striploins were collected from 10 USDA Choice beef carcasses. Each striploin was ground and equally divided into 4 batches, and each batch was mixed with 0%, 0.4%, 0.8%, or 1.6% dried EP containing aPLA2. Each treatment batch was further divided into 3 smaller batches and subjected to retail display (0, 4, or 7d). Color descriptors, pH, proximate analysis, lipid oxidation, antioxidant capacity, and phospholipid and fatty acid (FA) profiles were measured. Percent visual discoloration and instrumental color measurements of GS were unaffected by aPLA2 EP treatments (P>0.05). The 1.6% treatment GS had a higher relative percentage of phosphatidylcholine compared with those from the 0% treatment (P

BackgroundThe clinical narrative in electronic health records (EHRs) carries valuable information for predictive analytics; however, its free-text form is difficult to mine and analyze for clinical decision support (CDS). Large-scale clinical natural language processing (NLP) pipelines have focused on data warehouse applications for retrospective research efforts. There remains a paucity of evidence for implementing NLP pipelines at the bedside for health care delivery. ObjectiveWe aimed to detail a hospital-wide, operational pipeline to implement a real-time NLP-driven CDS tool and describe a protocol for an implementation framework with a user-centered design of the CDS tool. MethodsThe pipeline integrated a previously trained open-source convolutional neural network model for screening opioid misuse that leveraged EHR notes mapped to standardized medical vocabularies in the Unified Medical Language System. A sample of 100 adult encounters were reviewed by a physician informaticist for silent testing of the deep learning algorithm before deployment. An end user interview survey was developed to examine the user acceptability of a best practice alert (BPA) to provide the screening results with recommendations. The planned implementation also included a human-centered design with user feedback on the BPA, an implementation framework with cost-effectiveness, and a noninferiority patient outcome analysis plan. ResultsThe pipeline was a reproducible workflow with a shared pseudocode for a cloud service to ingest, process, and store clinical notes as Health Level 7 messages from a major EHR vendor in an elastic cloud computing environment. Feature engineering of the notes used an open-source NLP engine, and the features were fed into the deep learning algorithm, with the results returned as a BPA in the EHR. On-site silent testing of the deep learning algorithm demonstrated a sensitivity of 93% (95% CI 66%-99%) and specificity of 92% (95% CI 84%-96%), similar to published validation studies. Before deployment, approvals were received across hospital committees for inpatient operations. Five interviews were conducted; they informed the development of an educational flyer and further modified the BPA to exclude certain patients and allow the refusal of recommendations. The longest delay in pipeline development was because of cybersecurity approvals, especially because of the exchange of protected health information between the Microsoft (Microsoft Corp) and Epic (Epic Systems Corp) cloud vendors. In silent testing, the resultant pipeline provided a BPA to the bedside within minutes of a provider entering a note in the EHR. ConclusionsThe components of the real-time NLP pipeline were detailed with open-source tools and pseudocode for other health systems to benchmark. The deployment of medical artificial intelligence systems in routine clinical care presents an important yet unfulfilled opportunity, and our protocol aimed to close the gap in the implementation of artificial intelligence–driven CDS. Trial RegistrationClinicalTrials.gov NCT05745480; https://www.clinicaltrials.gov/ct2/show/NCT05745480

Abstract In recent years, we have seen the integration of magnetic resonance imaging (MRI) simulators into radiotherapy centres and the emergence MR linear accelerators (MR‐linac). Currently, there are limited studies to demonstrate the clinical effectiveness of MRI guided radiotherapy (MRIgRT) treatment for breast cancer patients. The objective of this scoping review was to identify and map the existing evidence surrounding the clinical implementation of MRIgRT for breast cancer patients. We also identified the challenges and knowledge gaps in the literature. The scoping review was reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) extension for Scoping Reviews reporting guidelines. Titles and abstracts were screened by two independent reviewers. Quantitative and qualitative data were extracted and summarised using thematically organised tables. Results identify that accelerated partial breast irradiation (APBI) is the most common form of treatment for MRIgRT. The presence of the magnet does not affect target coverage or violate organ at risk (OAR) constraints compared to standard radiotherapy methods. Consideration is advised for skin and chest wall (CW) due to the electron return effect (ERE) and areas such as armpit and chin due to the electron stream effect (ESE). Clinically, bolus has been used to protect and prevent unwanted dose in these areas. Overall treatment for APBI on the MR‐linac is feasible.

IntroductionImage guidance with gold fiducials improves outcomes of prostate radiotherapy. However, gold produces artefact on CT imaging, interfering with contouring and verification. The purpose of this study was to compare polymer to standard gold fiducials using radiotherapy imaging modalities to assess the visibility and artefact.MethodsTwenty eight patients with locally advanced prostate cancer were enrolled, half had three polymer fiducials implanted into the prostate and half underwent insertion of gold fiducials. Patients were imaged with CT, T2 weighted MRI, cone-beam CT (CBCT) and planar KV images. Fiducials were scored for visibility and assessed for CT artefact in surrounding prostate tissue. The artefact was quantified from Hounsfield number histograms and separated into percentile ranges and proportion of voxels in HU normal tissue range of a 2cm sphere surrounding the fiducial.ResultsGold and polymer fiducials were sufficiently visible for CT and CBCT verification. The gold fiducials could be visualized well on KV planar imaging; however, the polymer markers were obscured by pelvic bones. Neither polymer nor gold fiducials could be visualized on MRI. The polymer fiducial produced less artefact than gold on CT, having less voxel spread for the HU percentile ranges and a greater proportion of voxels in the normal tissue range.ConclusionsPolymer fiducials are a more suitable fiducial than gold for CT/CBCT in prostate cancer radiotherapy, demonstrating minimal artefact and good visibility on CT. However, they were not well seen on MRI or KV imaging and thus not suitable for co-registration or planar KV verification.

Palatability traits of ribeye, strip loin, and tenderloin steaks were evaluated in a bone-in versus boneless format.Sensory characteristics of these cuts were also evaluated in 2 quality grade categories; upper 2/3 USDA Choice and USDA Select to evaluate the interactions of marbling level and bone state. Subprimals were collected from both sides of 12 beef carcasses per quality grade and aged for 28 d. Product was fabricated into 2.5-cm-thick steaks and designated for either trained sensory analysis, consumer sensory analysis, Warner-Bratzler shear force (WBSF), or fat and moisture determination. Results from trained sensory analysis showed bone-in tenderloins and bone-in ribeyes as more flavorful (P0.05) on trained sensory initial juiciness, myofibrillar tenderness, and overall tenderness scores, or WBSF for any cut. Furthermore, tenderloin samples were rated higher (P0.05). Bone state had no impact (P>0.05) on consumer tenderness and flavor ratings for any of the 3 cuts.However, bone-in strip loin samples were rated juicier and higher (P0.05) between strip loin and ribeye steaks for flavor liking by consumers and no difference (P>0.05) in overall liking rating between ribeyes and boneless striploin steaks. Overall, bone status had a minimal impact on beef palatability traits, providing evidence that eating quality is not greatly impacted by bone status for any of the cuts evaluated.

The objective of this study was to evaluate consumers’ palatability ratings of ground beef from the same source when provided information about the labeling prior to evaluation. Chubs (n=15) from the same production lot and day of 80% lean/20% fat ground beef were procured and fabricated into 151.2 g patties. Pairs of patties from each chub were randomly assigned to one consumer panel session and to 1 of 8 different labeling terms: all natural, animal raised without added antibiotics (WA), animal raised without added hormones (WH), fresh never frozen (FNF), grass-fed, locally sourced, premium quality, USDA organic (ORG), and a blank sample (NONE). Consumers (N=105) evaluated each sample on 0-to-100-point line scales for tenderness, juiciness, flavor liking, texture liking, overall liking, and purchasing intent and also evaluated each palatability trait as either acceptable or unacceptable. Prior to sample evaluation, the consumers were provided additional labeling information about the ground beef. Consumers found no differences (P>0.05) among the samples with the different labeling terms for tenderness, juiciness, texture liking, overall liking, tenderness acceptability, flavor acceptability, and texture acceptability for all the treatments evaluated. For flavor liking, there was a larger increase (P

Abstract Introduction Guidelines recommend that the proximal seminal vesicles (PrSV) should be included in the clinical target volume for locally advanced prostate cancer patients undergoing radiotherapy. Verification and margins for the prostate may not necessarily account for PrSV displacement. The purpose was to determine the inter‐fraction displacement of the PrSV relative to the prostate during radiotherapy. Methods Fiducials were inserted into the prostate, and right and left PrSV (RSV and LSV) in 30 prostate cancer patients. Correctional shifts for the prostate, right and left PrSV and pelvic bones were determined from each patient's 39 daily orthogonal portal images relative to reference digitally reconstructed radiographs. Results There was a significant displacement of the RSV relative to the prostate in all directions: on average 0.38 mm (95% confidence interval (CI) 0.26 to 0.50) to the left, 0.80–0.81 mm (CI 0.68 to 0.93) superiorly and 1.51 mm (CI 1.36 to 1.65) posteriorly. The LSV was significantly displaced superiorly to the prostate 1.09–1.13 mm (CI 0.97 to 1.25) and posteriorly 1.81 mm (CI 1.67 to 1.96), but not laterally (mean 0.06, CI −0.06 to 0.18). The calculated PTV margins (left–right, superior–inferior, posterior–anterior) were 4.9, 5.3–5.6 and 4.8 mm for the prostate, 5.2, 7.1–8.0 and 9.7 mm for the RSV, and 7.2, 7.5–7.6 and 8.6 mm for the LSV. Conclusion There is a significant displacement of the PrSV relative to the prostate during radiotherapy. Greater margins are recommended for the PrSV compared to the prostate.

The objective of this study was to evaluate the effect of providing information about the fat content, primal source,and price on consumers’ palatability ratings of ground beef from the same source. Ground beef chubs that were 80% lean/20% fat (n=15/panel type) were obtained, and 151.2 g patties were manufactured from the chubs. Chubs were assigned randomly to panels for 1 of 3 different panel types. The fat content panels had samples labeled as 90% lean/10% fat (90/10), 80% lean/20% fat (80/20), 73% lean/27% fat (73/27), lean, and extra lean. Price point samples were assigned to 1 of 5 different points: ultra-high, high, medium, low, and ultra-low. Primal panel samples were labeled as ground chuck, ground round, ground sirloin, and store ground. Each panel had one sample with no information given (NONE). Samples were evaluated by consumers (N=305), who were informed of the treatment prior to evaluation for tenderness, juiciness, flavor, texture, overall liking, and purchasing intent and rated each trait as acceptable or unacceptable. Labeling ground beef as 90/10, 80/20, and 73/27 resulted in increased (P

This study’s objective was to understand the relationships between biochemical tenderness components andobjective/sensory measure of tenderness of 8 muscles from beef carcasses. Longissimus thoracis (LT), pectoralis profundus (PP), supraspinatus, triceps brachii (TB), gluteus medius (GM), rectus abdominus (RA), rectus femoris, and semitendinosus (ST) were collected from 10 USDA upper 2/3 Choice beef carcasses and assigned to a 2- or 21-d aging period (n=160). Troponin-T degradation, desmin degradation, sarcomere length, collagen content, mature collagen crosslink density, intramuscular lipid content, pH, Warner-Bratzler Shear Force (WBSF), and trained sensory panel analyses were measured. A Pearson correlation analysis was conducted to determine the relationship between each tenderness contributor measured in this study with WBSF or the overall tenderness evaluated by the trained panelist for each of the 8 muscles.In addition, multivariate regression models were constructed to confirm this relationship. The results showed that muscle anatomical locations and physiological functions driven by muscle fiber types may explain some of the biochemical/tenderness differences found in this study. The correlation analysis showed that each muscle had a specific tenderness factor(s)that contributed to the overall tenderness. For instance, tenderness for LT, TB, GM, RA, and ST may be influenced more by proteolytic degradation, while the collagen characteristics may primarily influence tenderness for PP. Also, lipid content has a significant influence on GM tenderness. Finally, the multivariate regression model showed that almost all of the biochemical measurements conducted in this study contributed to overall tenderness to some degree across muscles.Increasing the knowledge base on the various tenderness components’ level of contribution will allow end-users to develop specific tenderness management strategies to ensure consistent tenderness in beef products.

Abstract To assess visibility and artifact characteristics of polymer fiducials compared to standard gold fiducials for radiotherapy CT and MRI simulation. Three gold and three polymer fiducials were inserted into a CT and MRI tissue-equivalent phantom that approximated the prostate cancer radiotherapy configuration. The phantom and fiducials were imaged on CT and MRI. Images were assessed in terms of fiducial visibility and artifact. ImageJ was employed to quantify the pixel gray-scale of each fiducial and artifact. Fiducial gray-scale histograms and profiles were generated for analysis. Objective measurements of the contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and artifact index (AI) were calculated. The CT images showed that the gold fiducials are visually brighter, with greater contrast than the polymer. The higher peak values illustrate this in the line profiles. However, they produce bright radiating and dark shadowing artifacts. This is depicted by the greater width of line profiles and the disruption of phantom area profiles. Quantitatively this results in greater percentile ranges of the histograms. Furthermore, for CT, gold had a higher CNR than polymer, relative to the phantom. However, the gold CNR and SNR were degraded by the greater artifact and thus AI. Both fiducials were visible on MRI and had similar histograms and profiles that were also reflected in comparable CNR, SNR and AI. Polymer fiducials were well visualized in a phantom on CT and MR and produce less artifact than the gold fiducials. Polymer markers could enhance the quality and accuracy of radiotherapy co-registration and planning but require clinical confirmation.

Abstract Background In recent years, we have seen the incorporation of magnetic resonance imaging (MRI) simulators into radiotherapy centres and the emergence of the new technology of MR linacs. However, the significant health care resources associated with this advanced technology impact immediate widespread use and availability. There are currently limited studies to demonstrate the clinical effectiveness and inform decision-making on the use of MRI in radiotherapy. The objective of this scoping review is to identify and map the existing evidence surrounding the clinical implementation of MRI-guided radiotherapy in patients with breast cancer. It also aims to identify challenges and knowledge gaps in the literature. Methods We will perform a comprehensive search in MEDLINE and EMBASE databases from January 2010 onwards. Grey literature sources will include the WHO International Clinical Trials Registry Platform. We will include systematic reviews, randomised and non-randomised controlled studies published in English. Literature should examine the use of magnetic resonance imaging-guided radiotherapy in adults with breast cancer, regardless of cancer stage or severity. Two reviewers will independently screen all titles, abstracts and full-text reports. Data will be extracted and summarised using qualitative (e.g. content and thematic analysis) methods and presented in tables. Discussion The results from this review will consolidate the evidence surrounding MRI-guided radiotherapy for breast cancer, contributing to the development and optimisation of patient selection, simulation, planning, treatment delivery, quality assurance and research, to help improve patient outcomes, cancer care and treatment for women with breast cancer. Systematic review registration The protocol is available on Open Science Framework at DOI https://doi.org/10.17605/OSF.IO/8TEV6

Background and purpose: Image-guidance with fiducials has been shown to improve pelvic radiotherapy outcome. However, bladder fiducials using ethiodized oil (EO) alone can disperse widely, and gold causes Computed Tomography scan (CT) metal artifacts. The study's purpose was to investigate the ability to deliver EO-tissue glue fiducials and compare them to gold for bladder radiotherapy image guidance. Materials and methods: A fluid-filled porcine bladder model was used to assess the ability to cystoscopically inject visible EO glue fiducials into the submucosa. We then transferred the bladders into a porcine pelvis for imaging and compared them to gold fiducials using CT, Cone Beam CT (CBCT), and kilovoltage (KV) planar views. A tissue-equivalent phantom was utilized to analyze the CT number Hounsfield Unit (HU) characteristics and artifacts of the glue and gold fiducials. Percentile ranges and normal tissue voxel percentages of the subsequent CT number voxel histogram from a 2 cm sphere surrounding the fiducial was used to characterize the artifact. Results: We successfully delivered all EO glue fiducials into the porcine bladders as discrete fiducials. They were well seen on CT, CBCT, and KV imaging. The glue fiducials had lower CT number values, but less CT number spread of the voxel percentile ranges consistent with the diminished contrast and less artifact than gold. The glue fiducial types had similar CT number characteristics. Conclusion: This study has shown that EO glue fiducials can be delivered with online visualization qualities comparable to gold fiducials without metal-related artifacts.

Peri-rectal spacers provide protection to the rectum for patients receiving radiation therapy treating prostate cancers. Commonly used hydrogel spacers hold the disadvantage that they cannot be readily reversed should inadvertent injection outside of the target area occurs, potentially leading to ischemia of the rectal mucosa leading to severe pain and ulceration, which can then lead to superinfection and pelvic abscess formation, and subsequently recto-prostatic fistulas. This could require major surgical intervention. New hyaluronic acid spacers are readily reversible with hyaluronidase and provide a valuable means to correct any misinjected spacer. We present a patient with prostate cancer who was planned for radiation therapy and required a rectal spacer. The hyaluronic acid rectal spacer was injected in part into the rectal wall. The patient was asymptomatic, and a sigmoidoscopy confirms healthy bowel mucosa only. The misinjected hyaluronic acid was successfully treated with targeted injection of hyaluronidase into only the rectal wall portion. Serial follow-up imaging demonstrated rapid dissolution of the misinjected hyaluronic acid with the well-positioned hyaluronic acid remaining. The patient did not experience any side effects of the hyaluronidase.

Abstract Background Radiation therapy to upper abdominal sites is technically challenging due to motion of tumors and surrounding organs resulting from normal respiration. Breath-hold, using an Active Breathing Coordinator is one strategy used to reduce motion in these tumor sites. Though widely used, no studies have prospectively compared the different breath-hold techniques (inspiration, deep-inspiration and expiration) using ABC in the same patient cohort. Methods Patients planned for radiation therapy to upper abdominal tumors are invited to participate in this prospective study. Participants attempt three breath hold techniques: inspiration, deep-inspiration and expiration breath-hold, in random order. kV fluoroscopy images of the dome of diaphragm are taken of five consecutive breath-holds in each technique. Reproducibility and stability of tumour position are measured, and used to select the technique with which to proceed to planning and treatment. Reproducibility at planning and each treatment fraction is measured, along with breath hold time, treatment efficiency and patient experience. Discussion The screening method was validated after the first three participants. This screening process may be able to select the best breath-hold technique for an individual, which may lead to improved reproducibility. The screening process is being piloted as a prospective clinical trial. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): 12618001691235. Registered 12th October 2018. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376109&isReview=true .

The objective of this study was to compare the quality characteristics of current plant-based protein ground beef alternatives (GBA) to ground beef (GB) patties of varying fat percentages. Fifteen different production lots (n = 15/fat level) of 1.36 kg GB chubs of 3 different fat levels (10%, 20%, and 27%) were collected from retail markets in the Manhattan, KS area. Additionally, GBA products including a foodservice GBA (FGBA), a retail GBA (RGBA), and a traditional soy protein–based GBA (TGBA) currently available through commercial channels were collected. Consumers (n = 120) evaluated sample appearance, juiciness, tenderness, overall flavor liking, beef flavor liking, texture liking, and overall liking. Additionally, samples were evaluated for color, texture profile, shear force, pressed juiciness percentage (PJP), pH, and fat and moisture percentage. All 3 GB samples rated higher (P < 0.05) than the 3 GBA samples for appearance liking, overall flavor liking, beef flavor liking, and overall liking by consumers. Similar results were found with trained sensory panelists, which rated the GBA as less (P < 0.05) juicy, softer (P < 0.05), and lower (P < 0.05) for beef flavor and odor intensity and higher (P < 0.05) for off-flavor intensity than the GB. Moreover, the GBA had less (P < 0.05) change in shape through cooking and a lower (P < 0.05) percentage of cooking loss and cooking time than the GB. Also, the GBA all had lower (P < 0.05) shear force and PJP values than the GB. The color of the GBA differed (P < 0.05) from the GB, with the GB samples being more (P < 0.05) red in the raw state. These results indicate that the GBA provide different eating and quality experiences than GB and should thus be considered as different products by consumers and retailers.

Sirloin cap steaks from 4 different USDA quality grades were evaluated to determine the effect of marbling on eating experience. Top sirloin cap steaks (N = 60) of 4 different quality grades (Prime, Top Choice, Low Choice, and Select) were evaluated in the current study. Top sirloin butts were collected, and the biceps femoris was removed, trimmed, and sliced into twelve 2.54-cm-thick steaks. The steaks from each subprimal were aged for 28 d and designated for either trained sensory panels, consumer sensory panels, Warner-Bratzler shear force, or moisture and fat determination. The Prime steaks were rated the highest (P < 0.05) for overall liking and were higher (P < 0.05) for flavor liking than Low Choice and Select steaks within the consumer panels. However, all quality treatments were similar (P > 0.05) in juiciness and tenderness for the consumer panels. Additionally, a similar (P > 0.05) percentage of samples from each treatment were rated acceptable for tenderness, juiciness, flavor liking, and overall liking, with each trait having greater than 70% of samples rated acceptable. Also, Prime steaks were rated the highest (P < 0.05) for sustained juiciness and overall tenderness within the trained sensory panels. Similarly, Prime steaks were rated higher (P 0.05) to Top Choice. These results indicate that USDA quality grades impact the eating quality of sirloin cap steaks, especially within the Prime grade, and could provide an opportunity for refined marketing and added economic value for the cut.

The objective of this study was to evaluate biochemical factors affecting Warner-Bratzler shear force (WBSF) and East Asian consumers’ eating preferences of 6 different beef shank cuts cooked by moist heat. Six different beef shank muscles were collected from 12 USDA Choice beef carcasses (N = 72). Shank cuts from the left sides were cooked with moist heat and used for East Asian consumer sensory evaluation and WBSF, and shank cuts from the right sides were left uncooked and used for biochemical analysis and visual panels utilizing the same group of consumers. A correlation analysis was conducted to determine the driving factors that contributed to WBSF and East Asian consumers’ overall liking for beef shanks. Biceps brachii and flexor digitorum superficialis-pelvic received the greatest sensory overall liking, with deep digital flexor from the foreshank having the lowest scores (P < 0.01). Deep digital flexor from the foreshank had the greatest WBSF value, most cooked collagen content, and greatest insoluble collagen percentage as well as the greatest raw and cooked pyridinoline (PYD) densities among all the beef shank cuts (P < 0.05). For visual overall liking, shank cuts at approximately 700–750 g such as biceps brachii and extensor carpi radialis received the highest ratings (P < 0.01), and consumers indicated that there was no visual difference in surface color among the shank cuts (P > 0.10). Correlation analysis showed that cooked collagen content and insoluble collagen percentage as well as raw PYD densities had positive correlations with WBSF (P < 0.05) and negative correlations with consumer overall liking (P < 0.01). Surprisingly, collagen content from uncooked shank cuts did not have a direct relationship with consumers’ overall liking nor with WBSF. The results demonstrated that raw PYD density may be a great indicator for cooked beef tenderness in beef cuts with a high concentration of connective tissue prepared with moist heat cookery.

Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18−31 (beta coefficients ranged from 0.02−0.06, p-values ranged from 10−6−10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.

Providing care to a spouse can be especially challenging for older adults given their compounding stressors resulting from aging and caregiving. This cross-sectional study examines the relationships between caregiving stressors and caregiver mental health problems and the potential mediator (i.e., caregiving relationship quality) of these associations. A total of 431 Americans (≥65 years) were selected from the National Study of Caregiving. Path analysis shows that care assistance was positively associated with caregiver mental health problems, and this association was mediated by negative relationship quality (Indirect effect =.14, p =.016). Moreover, role overload was positively associated with caregiver mental health problems, which was mediated by negative relationship quality (indirect effect =.13, p =.002). Findings suggest that caregiving stressors can adversely affect mental health by exacerbating negative relationship quality. Interventions that limit negative exchanges and increase compassionate communications between older spousal caregivers and their care-receiving partners are needed. [ABSTRACT FROM AUTHOR]