Effect of drought acclimation on sugar metabolism in millet.

Drought stress triggers sugar accumulation in plants, providing energy and aiding in protection against oxidative damage. Plant hardening under mild stress conditions has been shown to enhance plant resistance to severe stress conditions. While sugar accumulation and metabolism under drought stress have been well-documented in crop plants, the effect of drought acclimation treatment on sugar accumulation and metabolism has not yet been explored. In this study, we investigated the impact of drought stress acclimation on sugar accumulation and metabolism in the leaves and root tissues of two commonly cultivated foxtail millet (Setaria italica L.) genotypes, 'PI 689680' and 'PI 662292'. Quantification of total sugars (soluble sugar, fructose, glucose, and sucrose), their related enzymes (SPS, SuSy, NI, and AI), and the regulation of their related transcripts (SiSPS1, SiSuSy1, SiSWEET6, SiA-INV, and SiC-INV) revealed that drought-acclimated (DA) plants exhibited levels of these indicators comparable to those of control plants. However, under subsequent drought stress conditions, both the leaves and roots of non-acclimated plants accumulated higher levels of total sugars, displayed increased activity of sugar metabolism enzymes, and showed elevated expression of sugar metabolism-related transcripts compared to drought-acclimated plants. Thus, acclimation-induced restriction of sugar accumulation, transport, and metabolism could be one of the metabolic processes contributing to enhanced drought tolerance in millet. This study advocates for the use of acclimation as an effective strategy to mitigate the negative impacts of drought-induced metabolic disturbances in millet, thereby enhancing global food security and promoting sustainable agricultural systems.

2020 CMS prior authorization for hospital outpatient departments: Associated surgical volume impact.

BACKGROUND: Prior authorization is common for privately administered Medicare Advantage plans but is rarely used for surgical care when considering publicly administered plans. A 2020 Centers for Medicare and Medicaid services (CMS) policy, CMS-1717-FC, requires prior authorization for Medicare Fee-for-Service beneficiaries undergoing select procedures (blepharoplasty, abdominoplasty, botulinum toxin injection, rhinoplasty, and vein ablation) in hospital outpatient departments. The impact of this policy on surgical volume at hospital outpatient departments and shifts in care to ambulatory surgery centers is unknown. METHODS: This study used a segmented interrupted time series and pre-post logistic regression model. This study was a retrospective cohort study using data from the Healthcare Cost and Utilization Project state ambulatory surgery database and state inpatient database. RESULTS: From 2016 through 2021, a total of 272,879 patients underwent the affected procedures. Pre-CMS-1717-FC, a trend of decreasing hospital outpatient department utilization was found for Medicare Fee-for-Service beneficiaries (-10.82, 95% confidence interval: -18.32 to -3.33, P = .01). In the post-implementation period, no change in the rate of decreasing hospital outpatient department utilization was found for Medicare Fee-for-Service beneficiaries (-3.45, 95% confidence interval: -36.15 to 29.25, P = .83). In the pre-policy period, Medicare Fee-for-Service beneficiaries were 46% less likely to use freestanding ambulatory surgery centers but 27% less likely to use hospital-owned ambulatory surgery centers. CONCLUSION: CMS-1717-FC was not associated with significant changes in hospital outpatient department volume beyond baseline trends. Policy aiming to right-size prior authorization for these procedures and considering site-of-service will balance the need to ensure medical necessity while constraining costs.

Employer-Sponsored Medicare Advantage Plans and the 2018 Therapy Cap Repeal: Reduced Overall Spending Does Not Constrain Out-of-Pocket Costs.

BACKGROUND: Policy impacting traditional Medicare beneficiaries may have unintended effects for privately insured patients. After the repeal of a longstanding $1500 outpatient therapy cap in 2018, we aimed to evaluate if this policy change was associated with differences in use of cost of postoperative therapy after common hand surgeries, including carpal tunnel release, trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture open reduction/internal fixation or percutaneous pinning. METHODS: The Medicare Supplement and Coordination of Benefits files from Marketscan were used. Frequency of therapy appointments, overall costs, and out-of-pocket costs were obtained. A segmented interrupted time series with Poisson and log-transformed linear regression was performed. RESULTS: No significant monthly change in odds of therapy use was found in the postpolicy period for patients who underwent trigger finger release, carpal tunnel release, Ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, or distal radius fracture, pinning, or open reduction/internal fixation. Overall cost decreased in the postpolicy period by 2% for comprehensive plans (95% confidence interval [CI]: -0.03 to -0.01, P < 0.001), by 7% for those with exclusive provider organizations (95% CI: -0.10 to -0.04, P < 0.001), by 1% for HMOs (95% CI: -0.01 to 0.002, P = 0.01), and by 3% for preferred provider organizations (95% CI: -0.03 to -0.02, P < 0.001). In the postpolicy period, no monthly change in out-of-pocket cost was observed for patients with comprehensive, exclusive provider organization, health maintenance organization, preferred provider organization, or point of service with capitation insurance plans. CONCLUSIONS: Patients with employer-sponsored Medicare Advantage plans experienced increased out-of-pocket costs for therapy despite lower net costs. These data highlight an urgent need for policy ensuring that patients benefit when overall costs of care decrease.

Paving the way for affordable and equitable liposomal amphotericin B access worldwide.

Amphotericin B has long been crucial for treating many serious infectious diseases, such as invasive fungal infections and visceral leishmaniasis, particularly for patients who are immunocompromised, including those with advanced HIV infection. The conventional amphotericin B deoxycholate formulation has largely been replaced in high-income countries with liposomal amphotericin B (LAmB), which has many advantages, including lower rates of adverse events, such as nephrotoxicity and anaemia. Despite an evident need for LAmB in low-income and middle-income countries, where mortality from invasive fungal infections is still substantial, many low-income and middle-income countries still often use the amphotericin B deoxycholate formulation because of a small number of generic formulations and the high price of the originator LAmB. The pricing of LAmB is also highly variable between countries. Overcoming supply barriers through the availability of additional quality-assured, generic formulations of LAmB at accessible prices would substantially facilitate equitable access and have a substantial effect on mortality attributable to deadly fungal infections.

The impact of Zika emergence in remote communities in northwestern Ecuador.

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV sero-epidemiology in six rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54% measured by NS1 blockade of binding ELISA. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-16 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-16 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives.

Evolutionary Strategies Enable Systematic and Reliable Uncertainty Quantification: A Proof-of-Concept Pilot Study on Resting-State Functional MRI Language Lateralization.

Reliable and trustworthy artificial intelligence (AI), particularly in high-stake medical diagnoses, necessitates effective uncertainty quantification (UQ). Existing UQ methods using model ensembles often introduce invalid variability or computational complexity, rendering them impractical and ineffective in clinical workflow. We propose a UQ approach based on deep neuroevolution (DNE), a data-efficient optimization strategy. Our goal is to replicate trends observed in expert-based UQ. We focused on language lateralization maps from resting-state functional MRI (rs-fMRI). Fifty rs-fMRI maps were divided into training/testing (30:20) sets, representing two labels: "left-dominant" and "co-dominant." DNE facilitated acquiring an ensemble of 100 models with high training and testing set accuracy. Model uncertainty was derived from distribution entropies over the 100 model predictions. Expert reviewers provided user-based uncertainties for comparison. Model (epistemic) and user-based (aleatoric) uncertainties were consistent in the independently and identically distributed (IID) testing set, mainly indicating low uncertainty. In a mostly out-of-distribution (OOD) holdout set, both model and user-based entropies correlated but displayed a bimodal distribution, with one peak representing low and another high uncertainty. We also found a statistically significant positive correlation between epistemic and aleatoric uncertainties. DNE-based UQ effectively mirrored user-based uncertainties, particularly highlighting increased uncertainty in OOD images. We conclude that DNE-based UQ correlates with expert assessments, making it reliable for our use case and potentially for other radiology applications.

Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project.

OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.

A comparison of postoperative outcomes based on recipient vessels in scalp free flap reconstruction: A systematic review and meta-analysis.

PURPOSE: The superficial temporal artery (STA) and facial artery (FA) are two commonly used recipient vessels when performing free tissue transfer to the head and neck. This meta-analysis compares the impact of recipient vessel location on free flap outcomes in scalp reconstruction. METHODS: A systematic review was conducted following PRISMA-P guidelines using six databases. Studies reporting free tissue transfer using the STA or FA as a recipient vessel for reconstructing scalp defects were included. Outcomes of interest included flap loss, partial flap necrosis, wound dehiscence, venous thrombosis, and infection rates. Quality evaluation was performed using ASPS criteria and the ROBINS-I tool. RESULTS: Of 3270 identified articles, 12 were included for final analysis. In total, 125 free flaps were identified (75 STA, 50 FA). Pooled analysis demonstrated an overall flap survival rate of 98.4% (STA 98.7% vs. FA 98.0%; p = .782). The mean defect size was significantly greater for flaps using the STA compared with the FA (223.7 ± 119.4 cm2 vs. 157.1 ± 96.5 cm2, p = .001). The FA group had a higher incidence of wound dehiscence than the STA group (14.0% vs. 1.3%, p = .005). However, meta-analysis demonstrated no significant difference in rates of wound dehiscence, flap loss, partial flap necrosis, venous congestion, or postoperative infection between groups. CONCLUSION: This is the first systematic review and meta-analysis to assess recipient vessel selection in scalp reconstruction. Our results do not support a single vessel as the superior choice in scalp reconstruction. Rather, these findings suggest that the decision between using the STA or FA is multifaceted, requiring a flexible approach that considers the individual characteristics of each case. Further research is needed to explore additional factors influencing recipient vessel selection, including defect location, radiation therapy, and prior head and neck surgery.

Impact of Regional Surgeon Competition on Use, Cost, and Outcomes of Breast Reconstruction in the United States.

BACKGROUND: Breast reconstruction following mastectomy is underused in the United States. Evidence suggests that more competitive hospital markets offer increased access to procedural care across specialties. This study aims to determine the impact of regional plastic surgeon competition on use, outcomes, and cost of breast reconstruction following mastectomy for breast cancer. METHODS: We conducted a retrospective cross-sectional analysis using Marketscan claims data from 2009 to 2020. The Herfindahl-Hirschman Index (HHI), a measure of market concentration, was calculated using the sum-of-squares of the proportion of breast reconstruction cases performed by each surgeon in a metropolitan statistical area (MSA). Multivariable logistic regression was used to identify differences in rates, outcomes, and costs of reconstruction by HHI. RESULTS: Odds of receiving breast reconstruction within two years of mastectomy were higher for those in moderately competitive (OR: 1.51 [95% CI: 1.37 to 1.66]; p<0.001) or competitive (OR: 1.71 [95% CI: 1.58 to 1.86]; p<0.001) = regions compared to noncompetitive regions. Patient out-of-pocket costs decreased when comparing moderately competitive regions to noncompetitive regions (-$67.38, [95% CI: -$88.65 to -$46.11]; p=0.007), and further decreased when comparing competitive to non-competitive regions (-$113.06, [95% CI: -$137.00 to -$89.12]; p=0.02). No linear association between total, surgeon, or facility cost and market competition strata was identified. CONCLUSION: Greater competition among surgeons is associated with improved access to reconstructive surgery, but no difference in cost. Application of this evidence may include system-level strategies to bolster care coordination, while targeting drivers of cost, such as hospitals and hospital systems, through policy.

Mammography Screening Preferences Among Screening-Eligible Women in Their 40s : A National U.S. Survey.

BACKGROUND: The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years. OBJECTIVE: To conduct a national probability-based U.S. survey to investigate breast cancer screening preferences among women aged 39 to 49 years. DESIGN: Pre-post survey with a breast cancer screening decision aid (DA) intervention. (ClinicalTrials.gov: NCT05376241). SETTING: Online national U.S. survey. PARTICIPANTS: 495 women aged 39 to 49 years without a history of breast cancer or a known BRCA1/2 gene mutation. INTERVENTION: A mammography screening DA providing information about screening benefits and harms and a personalized breast cancer risk estimate. MEASUREMENTS: Screening preferences (assessed before and after the DA), 10-year Gail model risk estimate, and whether the information was surprising and different from past messages. RESULTS: Before viewing the DA, 27.0% of participants preferred to delay screening (vs. having mammography at their current age), compared with 38.5% after the DA. There was no increase in the number never wanting mammography (5.4% before the DA vs. 4.3% after the DA). Participants who preferred to delay screening had lower breast cancer risk than those who preferred not to delay. The information about overdiagnosis was surprising for 37.4% of participants versus 27.2% and 22.9% for information about false-positive results and screening benefits, respectively. LIMITATION: Respondent preferences may have been influenced by the then-current USPSTF guideline. CONCLUSION: There are women in their 40s who would prefer to have mammography at an older age, especially after being informed of the benefits and harms of screening. Women who wanted to delay screening were at lower breast cancer risk than women who wanted screening at their current age. Many found information about the benefits and harms of mammography surprising. PRIMARY FUNDING SOURCE: National Cancer Institute.

The N-glycosylation defect in Lec5 and Lec9 CHO cells is caused by absence of the DHRSX gene.

Glycosylation-deficient Chinese hamster ovary (CHO) cell lines have been instrumental in the discovery of N-glycosylation machinery. Yet, the molecular causes of the glycosylation defects in the Lec5 and Lec9 mutants have been elusive, even though for both cell lines a defect in dolichol formation from polyprenol was previously established. We recently found that dolichol synthesis from polyprenol occurs in three steps consisting of the conversion of polyprenol to polyprenal by DHRSX, the reduction of polyprenal to dolichal by SRD5A3 and the reduction of dolichal to dolichol, again by DHRSX. This led us to investigate defective dolichol synthesis in Lec5 and Lec9 cells. Both cell lines showed increased levels of polyprenol and its derivatives, concomitant with decreased levels of dolichol and derivatives, but no change in polyprenal levels, suggesting DHRSX deficiency. Accordingly, N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3. Furthermore, the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected. Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent. Lastly, we established the sequence of Chinese hamster DHRSX and validated that this protein has similar kinetic properties to the human enzyme. Our work therefore identifies the basis of the dolichol synthesis defect in CHO Lec5 and Lec9 cells.

The Association Between the We Can Do This Campaign and Vaccination Beliefs in the United States, January 2021-March 2022.

Public health campaigns addressing COVID-19 vaccination beliefs may be effective in changing COVID-19 vaccination behaviors, particularly among people who remain vaccine hesitant. The "We Can Do This" COVID-19 public education campaign (the Campaign) was designed to increase COVID-19 vaccine confidence and uptake. This study aims to evaluate whether Campaign dose was associated with changes in vaccination beliefs related to COVID-19 vaccine concerns and perceived risks, the importance of COVID-19 vaccines, the perceived benefits of COVID-19 vaccination, normative beliefs about COVID-19 vaccination, and perceptions about general vaccine safety and effectiveness. The study linked data from four waves of a nationally representative longitudinal panel of U.S. adults (January 2021-March 2022) with Campaign paid digital media data (April 2021-May 2022). We used mixed-effects linear regressions to examine the association between Campaign paid digital impressions and changes in vaccination beliefs. The results provide evidence that Campaign digital impressions were significantly associated with changes in respondent beliefs regarding COVID-19 vaccine concerns and perceived risks, perceived benefits of COVID-19 vaccination, and perceptions about general vaccine safety and effectiveness. Findings suggest that public education campaigns may influence vaccine confidence and uptake by increasing positive vaccination beliefs and reducing vaccine concerns.

Postoperative hand therapy and the 2018 Medicare therapy cap repeal: Appraising cost and use changes.

BACKGROUND: Therapy use is common following carpal tunnel release (CTR), trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture, open reduction internal fixation or percutaneous pinning (DRF). Policy that improves coverage influences the cost and use of health care services. PURPOSE: This study aims to evaluate changes to the cost and use of postoperative hand therapy by race and procedure following the repeal of a longstanding annual Medicare outpatient therapy cap. STUDY DESIGN: Retrospective cohort study. METHODS: This is a longitudinal retrospective cohort study using a quasi-experimental interrupted time series design, including patients who underwent common hand surgeries from January 1, 2016-December 31, 2019. RESULTS: This study included 203,672 patients with a mean age of 71.4 years. Neither White (1.00, 95% confidence interval [CI]: 0.999-1.007, p = 0.45) nor non-White (1.00, 95% CI: 1.00-1.01, p = 0.06) patients experienced monthly changes in therapy use before policy implementation. Therapy frequency increased following CTR (odds ratio [OR] 1.12, 95% CI: 1.11-1.14, p < 0.001), trigger finger release (OR 1.09, 95% CI: 1.07-1.10, p < 0.001), and DRF (OR 1.05, 95% CI: 1.03-1.06, p < 0.001) following implementation. CONCLUSIONS: This study found that improved coverage was associated with increased postoperative therapy use among some subsets, including CTR and DRF, suggesting the need to optimize coverage by means such as prior authorization or bundled payments, rather than only increasing coverage benefits.

Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial.

Background: Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24-45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. Protocol: The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants. Discussion: The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN registration: ISRCTN18437550 (05/11/2021).

Understanding the burden of poor mental health and wellbeing among persons affected by leprosy or Buruli ulcer in Nigeria: A community based cross-sectional study.

BACKGROUND: Skin neglected tropical diseases including leprosy and Buruli ulcer (BU)are a group of stigmatizing and disability-inducing conditions and these aspects of the diseases could lead to poor mental health. The study was designed to assess the burden of poor mental health and wellbeing among persons affected by leprosy or BU in Nigeria. METHODS: A community based cross-sectional study design was employed. The study involved persons affected by leprosy or BU. Ten local government areas with the highest number of notified leprosy or BU cases between 2014 and 2018 in southern Nigeria were purposively selected. Information were obtained using Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorders-7 (GAD-7), Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and OSLO Social Support Scale. Outcome measure was poor mental health/wellbeing and was determined by proportion of respondents who had depressive symptoms, anxiety disorder and poor mental wellbeing. RESULTS: A total of 635 persons affected by leprosy or BU participated in the study. The mean age of respondents was 43.8±17.0 years and highest proportion, 22.2% were in age group, 40-49 years. Majority of respondents, 50.7% were males. A higher proportion of respondents, 89.9% had depressive symptoms, 79.4% had anxiety disorders and 66.1% had poor mental wellbeing. Majority, 57.2% had poor mental health/wellbeing. Among the respondents, there was a strong positive correlation between depression and anxiety scores, (r = 0.772, p<0.001). There was a weak negative correlation between depression score and WEMWBS score, (r = -0.457, p<0.001); anxiety score and WEMWBS score, (r = -0.483, p<0.001). Predictors of poor mental health/wellbeing included having no formal education, (AOR = 1.9, 95%CI: 1.1-3.3), being unemployed, (AOR = 3.4, 95%CI: 2.2-5.3), being affected by leprosy, (AOR = 0.2, 95%CI: 0.1-0.4) and having poor social support, (AOR = 6.6, 95%CI: 3.7-11.8). CONCLUSIONS: The burden of poor mental health/wellbeing among persons affected by leprosy or BU is very high. There is need to include mental health interventions in the management of persons affected with leprosy or BU. Equally important is finding a feasible, cost-effective and sustainable approach to delivering mental health care for persons affected with leprosy or BU at the community level. Improving educational status and social support of persons affected by leprosy or BU are essential. Engaging them in productive activities will be of essence.

Evolutionary Strategies AI Addresses Multiple Technical Challenges in Deep Learning Deployment: Proof-of-Principle Demonstration for Neuroblastoma Brain Metastasis Detection.

Two significant obstacles hinder the advancement of Radiology AI. The first is the challenge of overfitting, where small training data sets can result in unreliable outcomes. The second challenge is the need for more generalizability, the lack of which creates difficulties in implementing the technology across various institutions and practices. A recent innovation, deep neuroevolution (DNE), has been introduced to tackle the overfitting issue by training on small data sets and producing accurate predictions. However, the generalizability of DNE has yet to be proven. This paper strives to overcome this barrier by demonstrating that DNE can achieve satisfactory results in diverse external validation sets. The main innovation of the work is thus showing that DNE can generalize to varied outside data. Our example use case is predicting brain metastasis from neuroblastoma, emphasizing the importance of AI with limited data sets. Despite image collection and labeling advancements, rare diseases will always constrain data availability. We optimized a convolutional neural network (CNN) with DNE to demonstrate generalizability. We trained the CNN with 60 MRI images and tested it on a separate diverse collection of images from over 50 institutions. For comparison, we also trained with the more traditional stochastic gradient descent (SGD) method, with the two variants of (1) training from scratch and (2) transfer learning. Our results show that DNE demonstrates excellent generalizability with 97% accuracy on the heterogeneous testing set, while neither form of SGD could reach 60% accuracy. DNE's ability to generalize from small training sets to external and diverse testing sets suggests that it or similar approaches may play an integral role in improving the clinical performance of AI.

Identification of skin bacterial profiles of early deceased bodies and the relation to post-mortem interval.

Post-mortem microbiology (PMM) is an important tool in identifying possible causes of sudden unexpected death, as an infectious cause is highly suspected. However, contamination is a major problem in microbiology, and this has increased the difficulty determining the true pathogen that contributes to death in post-mortem cases. Skin commensals are common contaminants in blood cultures. This study was conducted to investigate the skin flora on early deceased bodies and observe the bacteria detected at different post-mortem intervals (PMIs). As blood is usually drawn from the neck and femoral sites for PMM examination, the two body sites were chosen as the sampling sites. Skin swab samples from the neck and femoral (n=80) of each early deceased body were collected by sterile cotton swabs. DNA was extracted from the swabs and then subjected to high-throughput 16S rRNA sequencing by using the Illumina MiSeq platform. Staphylococcus was found to be the most dominant genus in both neck and femoral sites. LEfSe results showed that Cutibacterium is significantly different at the neck site while Corynebacterium is more abundant at femoral site. There are significant differences at genus level between PMI<5H and PMI>5H at both neck and femoral sites. The findings of the present study may act as a reference for microbiologists and forensic pathologists when mixed growth or contamination occurs in post-mortem blood cultures.

Industry affiliation does not predict outcomes of randomized controlled trials for mesenchymal stem cells in knee osteoarthritis.

BACKGROUND: This research aims to determine the influence of industry on the outcomes of randomized controlled trials (RCTs) for Mesenchymal Stem Cell (MSC) treatments in knee osteoarthritis (OA). METHODS: PubMed, Scopus, and Web of Science were searched from 2010 onwards using the terms "knee osteoarthritis" and "mesenchymal stem cells". After identifying relevant RCTs, studies were categorized as industry-affiliated or non-industry-affiliated. They were also classified as favorable if they achieved statistically significant (p < 0.05) results with MSC injections compared to control. Chi-squared tests were employed to analyze the relationship between industry affiliation and study outcome. RESULTS: Post exclusion criteria, 38 studies were analyzed. Of these, there were 20 (52.6%) industry affiliated (IA) and 18 (47.4%) non-industry affiliated (NIA) studies. Among the 20 IA studies, 17 (85.0%) reported favorable outcomes for MSC treatment arm, with the remaining 3 (15.0%) showing analogous (no difference between treatment arms) results. For the 18 NIA studies, 15 (83.3%) were favorable, and 3 (16.6%) were analogous. No significant difference in outcomes was observed between IA and NIA studies (p = 0.888). Analysis of patient reported outcomes also revealed no significant difference. Of note, studies using allogeneic MSCs were more likely to be IA than studies using autologous MSCs (p = 0.005) CONCLUSION: This study demonstrated no strong association between industry affiliation and the outcomes of RCTs for MSC treatments in knee OA. Despite this, the potential influence of industry ties should always be considered when applying study findings to new treatment modalities for patient care.

Benefit-Cost Analysis of the HHS COVID-19 Campaign: April 2021-March 2022.

INTRODUCTION: This study estimated the benefits and costs of the U.S. Department of Health and Human Services' We Can Do This COVID-19 public education campaign (the Campaign) and associated vaccination-related impacts. METHODS: Weekly media market and national Campaign expenditures were used to estimate weekly first-dose vaccinations that would not have occurred absent the Campaign, weekly Campaign-attributed complete vaccinations, and corresponding COVID-19 cases, hospitalizations, and deaths averted. Benefits were valued using estimated morbidity and mortality reductions and associated values of a statistical life and a statistical case. Costs were estimated using Campaign paid media expenditures and corresponding vaccination costs. The net Campaign and vaccination benefit and return on investment were calculated. Analyses were conducted from 2022 to 2024. RESULTS: Between April 2021 and March 2022, an estimated 55.9 million doses of COVID-19 vaccines would not have been administered absent the Campaign. Campaign-attributed vaccinations resulted in 2,576,133 fewer mild COVID-19 cases, 243,979 fewer nonfatal COVID-19 hospitalizations, and 51,675 lives saved from COVID-19. The total Campaign benefit was $740.2 billion, and Campaign and vaccination costs totaled $8.3 billion, with net benefits of approximately $732.0 billion. For every $1 spent, the Campaign and corresponding vaccination costs resulted in benefits of approximately $89.54. CONCLUSIONS: The We Can Do This COVID-19 public education campaign saved more than 50,000 lives and prevented hundreds of thousands of hospitalizations and millions of COVID-19 cases, representing hundreds of billions of dollars in benefits in less than one year. Findings suggest that public education campaigns are a cost-effective approach to reducing COVID-19 morbidity and mortality.

Most Major Hospitals Fail to Comply With Federal Price Transparency Regulations.

PURPOSE: To present hospital compliance with federal price transparency regulations for sports medicine procedures. METHODS: Online price estimator and machine-readable files were recovered for U.S. News and World Report's top 100 orthopaedic hospitals. From June to November 2023, compliance and monetary values were recorded for each of Centers for Medicare and Medicaid Services price transparency regulations. Price estimator data were assessed on the basis of hospital placement in the bottom and top 50 of the 100 institutions under review, as well as by region (Northeast, South, Midwest, West). Statistical analyses included 2-sample t tests and Kruskal-Wallis tests. RESULTS: In total, 95% of hospitals had a price estimator tool for both subacromial decompression (Current Procedural Terminology [CPT] code 29826) and meniscectomy (CPT code 29881). Only 38% were compliant with all regulations for subacromial decompression and 39% for meniscectomy; the remaining did not list minimum or maximum procedure charges. Higher-ranked hospitals were significantly more likely to charge a greater cash price for subacromial decompression and meniscectomy (P = .040 and P = .009, respectively). Compliance with machine-readable file reporting was poor, with less than 20% meeting requirements for each CPT code. Reported prices varied greatly by hospital. CONCLUSIONS: This study demonstrates that U.S. News and World Report's top 100 orthopaedic hospitals exhibit poor overall compliance with federal price transparency regulations for sports medicine procedures. Most often they lack full compliance by not reporting minimum or maximum charges as part of their price estimator tool or do not report procedure prices in their machine-readable files. Hospitals also exhibit wide variation in prices reported for specific procedures. CLINICAL RELEVANCE: Consumer price transparency continues to be an important goal in health care, as it allows patients to make informed decisions when selecting appropriate treatment options and providers. To realize the full benefits of price transparency, hospitals should address areas of improvement.