Blood Lead Testing and Follow-up Testing Among Children Hospitalized for Lead Poisoning.

BACKGROUND AND OBJECTIVES: US children experience lead poisoning, which has detrimental health effects and significant individual and societal costs. This study aimed to describe the sociodemographic and hospitalization characteristics of children hospitalized for lead poisoning and assess the proportion of inpatients who received blood lead testing and appropriate follow-up testing before hospitalization. METHODS: 2015-2021 hospital discharge data were linked to lead surveillance data for Pennsylvania children aged 0 to 5 years. Demographics, hospitalization characteristics, and lead testing data from children with a primary diagnosis code of lead poisoning were used. The number of hospitalizations, associated hospital length of stay and charges, and the proportion of inpatients who received lead testing and follow-up testing after identification of high blood lead levels before hospitalization were analyzed by selected characteristics. RESULTS: During the study period, there were 93 children hospitalized for lead poisoning, incurring 443 inpatient days and approximately 6 million dollars in inpatient charges. Of these inpatients, 69.9% were males, 36.6% were non-Hispanic Black, 67.7% were aged 0 to 2 years, 14% had repeated admissions, and 88.2% of admissions were paid by Medicaid. In addition, 20.4% did not have lead testing, and 34.4% had appropriate follow-up testing before hospitalization. Non-Hispanic whites and children with developmental, behavioral, and emotional disorders had relatively low proportions of having appropriate follow-up testing. CONCLUSIONS: Severe childhood lead poisoning is a significant health and economic burden, especially among children with Medicaid. Further improvements in blood lead testing and follow-up testing can help prevent childhood lead poisoning.

Outcomes of laparoscopic, robotic and open nephroureterectomy with bladder cuff excision in patients with T3T4 upper urinary tract urothelial carcinoma: a multi-center retrospective study.

BACKGROUND: Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. METHODS: We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. RESULTS: The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p < 0.001). The robotic group had similar outcomes to the laparoscopic group. (p = 0.061, 0.825, 0.341 for OS, CSS, DFS respectively.) More lymph node dissections were performed and more lymph nodes were harvested in the robotic group (p = 0.009). CONCLUSIONS: Our results demonstrated that minimally invasive surgery, including laparoscopic and robotic surgery, for locally advanced UTUC resulted in oncological outcomes that are non-inferior to those of open surgery.

Correction: Behavioral Weight Loss Programs for Cancer Survivors Throughout Maryland: Protocol for a Pragmatic Trial and Participant Characteristics.

[This corrects the article DOI: 10.2196/54126.].

Effect of SARS-CoV-2 Infection on Incident Diabetes by Viral Variant: Findings From the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI). Cohorts were weighted on demographics, data site, and Charlson comorbidity index score. The primary outcome was the cumulative incidence ratio (CIR) of incident diabetes for each viral variant era. RESULTS: Risk of incident diabetes 1 year after COVID-19 was increased for patients with any viral variant compared with COVID-negative control patients (ancestral CIR 1.16 [95% CI 1.12-1.21]; Alpha CIR 1.14 [95% CI 1.11-1.17]; Delta CIR 1.17 [95% CI 1.13-1.21]; Omicron CIR 1.13 [95% CI 1.10-1.17]) and control patients with ARI (ancestral CIR 1.17 [95% CI 1.11-1.22]; Alpha CIR 1.14 [95% CI 1.09-1.19]; Delta CIR 1.18 [95% CI 1.11-1.26]; Omicron CIR 1.20 [95% CI 1.13-1.27]). There was latency in the timing of incident diabetes risk with the Omicron variant; in contrast with other variants, the risk presented after 180 days. CONCLUSIONS: Incident diabetes risk after COVID-19 was similar across different SARS-CoV-2 variants. However, there was greater latency in diabetes onset in the Omicron variant era.

Fluorogenic Aptamer Optimizations on a Massively Parallel Sequencing Platform.

F luorogenic ap tamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ( vs. 0.82 µM), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime (τ: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the π-π stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

Ketomimetic Nutrients Trigger a Dual Metabolic Defense in Breast Cancer Cells.

While the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decode the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body rich, low glucose) medium affects Doxorubicin (DOX) susceptibility and invasive disposition of BC cells. We quantified glycocalyx sialylation and found an inverse correlation with DOX-induced cytotoxicity and DOX internalization. These measurements were coupled with single-cell metabolic imaging, bulk migration studies, along with transcriptomic and metabolomic analyses. Our findings revealed that a ketomimetic medium enhances chemoresistance and invasive disposition of BC cells via two main oncogenic pathways: hypersialylation and lipid synthesis. We propose that the crosstalk between these pathways, juxtaposed at the synthesis of the glycan precursor UDP-GlcNAc, furthers advancement of a metastatic phenotype in BC cells under ketomimetic conditions.

Bariatric surgery and COVID-19 outcomes: results from the PaTH to Health: Diabetes study.

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for severe COVID-19 infection. Bariatric surgery (BSG) is an effective treatment of obesity through weight loss and may reduce COVID-19 severity. OBJECTIVES: We examined the effect of BSG on COVID-19 outcomes in patients with or at risk of T2DM. SETTING: Electronic health record data from the PaTH Clinical Data Research Network, a partnership of 5 health systems reviewed from March 1, 2020, to December 31, 2020. METHODS: Ambulatory and in-hospital patient encounters with COVID-19 diagnosis and obesity were identified. We constructed 2 patient groups: BSG and non-BSG (NBSG). The BSG group included patients with at least 1 encounter for the BSG procedure code and/or 1 BSG diagnosis code; the NBSG group included patients with no procedure or diagnosis code for BSG with body mass index (BMI) ≥40 or BMI ≥35 and at least 2 obesity-related co-morbidities. We matched 1 patient in the BSG group to 2 patients in the NBSG group based on age, gender (sex defined at birth), race and ethnicity, group (T2DM and at risk of T2DM), and site. The primary outcome was 30-day outcomes of COVID-19 severity. RESULTS: After matching, we found that patients with BSG had lower odds of respiratory failure (41%) and ventilation/intensive care unit (ICU) admission/death (52%). Patients in the BSG group had lower odds of hospitalization, pneumonia, respiratory failure, and the most severe COVID-19 outcomes combined (ventilation/ICU admission/death). T2DM was identified as a risk factor for COVID-19 severity in the BSG group. CONCLUSIONS: This retrospective, matched-cohort analysis found BSG to have a protective effect against severe COVID-19 outcomes.

Equitable Care for Hypertension: Blood Pressure and Patient-Reported Outcomes of the RICH LIFE Cluster Randomized Trial.

BACKGROUND: Disparities in hypertension control are well documented but underaddressed. METHODS: RICH LIFE (Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone) was a 2-arm, cluster randomized trial comparing the effect on blood pressure (BP) control (systolic BP ≤140 mm Hg, diastolic BP ≤90 mm Hg), patient activation, and disparities in BP control of 2 multilevel interventions, standard of care plus (SCP) and collaborative care/stepped care (CC/SC). SCP included BP measurement standardization, audit and feedback, and equity-leadership training. CC/SC added roles to address social or medical needs. Primary outcomes were BP control and patient activation at 12 months. Generalized estimating equations and mixed-effects regression models with fixed effects of time, intervention, and their interaction compared change in outcomes at 12 months from baseline. RESULTS: A total of 1820 adults with uncontrolled BP and ≥1 other risk factors enrolled in the study. Their mean age was 60.3 years, and baseline BP was 152.3/85.5 mm Hg; 59.4% were women; 57.4% were Black, 33.2% were White, and 9.4% were Hispanic; 74% had hyperlipidemia; and 45.1% had type 2 diabetes. CC/SC did not improve BP control rates more than SCP. Both groups achieved statistically and clinically significant BP control rates at 12 months (CC/SC: 57.3% [95% CI, 52.7%-62.0%]; SCP: 56.7% [95% CI, 51.9%-61.5%]). Pairwise comparisons between racial and ethnic groups showed overall no significant differences in BP control at 12 months. Patients with coronary heart disease showed greater achievement of BP control in CC/SC than in SCP (64.0% [95% CI, 54.1%-73.9%] versus 50.8% [95% CI, 42.6%-59.0%]; P=0.04), as did patients in rural areas (67.3% [95% CI, 49.8%-84.8%] versus 47.8% [95% CI, 32.4%-63.2%]; P=0.01). Individuals in both arms experienced statistically and clinically significant reductions in mean systolic BP (CC/SC: -13.8 mm Hg [95% CI, -15.2 to -12.5]; SCP: -14.6 mm Hg [95% CI, -15.9 to -13.2]) and diastolic BP (CC/SC: -6.9 mm Hg [95% CI, -7.8 to -6.1]; SCP: -5.5 mm Hg [95% CI, -6.4 to -4.6]) over time. The difference in diastolic BP reduction between CC/SC and SCP over time was statistically significant (-1.4 mm Hg [95% CI, -2.6 to -0.2). Patient activation did not differ between arms. CC/SC showed greater improvements in patient ratings of chronic illness care (Patient Assessment of Chronic Illness Care score) over 12 months (0.12 [95% CI, 0.02-0.22]). CONCLUSIONS: Adding a collaborative care team to enhanced standard of care did not improve BP control but did improve patient ratings of chronic illness care.

Harnessing Viral Promoters for Targeted RNAi: Engineering Phloem-Specific Resistance Against Tomato Yellow Leaf Curl Thailand Virus.

Phloem-specific promoter efficiently triggers graft-transmissible RNA interference (gtRNAi). We leveraged a phloem-specific promoter derived from the Rice tungro bacilliform virus, optimizing the RNAi mechanism's efficiency and specificity. Here, we detail the construction of phloem-specific promoter-based gtRNAi system and its application through grafting experiments, demonstrating its effectiveness in inducing tomato yellow leaf curl Thailand virus (TYLCHTV) resistance in non-transgenic scions. This strategy presents a practical application for protecting crops against viruses without genetically modifying the entire plant.

Two-photon autofluorescence lifetime assay of rabbit photoreceptors and retinal pigment epithelium during light-dark visual cycles in rabbit retina.

Two-photon excited fluorescence (TPEF) is a powerful technique that enables the examination of intrinsic retinal fluorophores involved in cellular metabolism and the visual cycle. Although previous intensity-based TPEF studies in non-human primates have successfully imaged several classes of retinal cells and elucidated aspects of both rod and cone photoreceptor function, fluorescence lifetime imaging (FLIM) of the retinal cells under light-dark visual cycle has yet to be fully exploited. Here we demonstrate a FLIM assay of photoreceptors and retinal pigment epithelium (RPE) that reveals key insights into retinal physiology and adaptation. We found that photoreceptor fluorescence lifetimes increase and decrease in sync with light and dark exposure, respectively. This is likely due to changes in all-trans-retinol and all-trans-retinal levels in the outer segments, mediated by phototransduction and visual cycle activity. During light exposure, RPE fluorescence lifetime was observed to increase steadily over time, as a result of all-trans-retinol accumulation during the visual cycle and decreasing metabolism caused by the lack of normal perfusion of the sample. Our system can measure the fluorescence lifetime of intrinsic retinal fluorophores on a cellular scale, revealing differences in lifetime between retinal cell classes under different conditions of light and dark exposure.

A Pandemic of Misinformation: Understanding Influences on Beliefs in Health and Conspiracy Myths.

BACKGROUND: Personal characteristics may be associated with believing misinformation and not believing in best practices to protect oneself from COVID-19. OBJECTIVE: To examine the associations of a person's age, race/ethnicity, education, residence, health literacy, medical mistrust level, and sources of health-related information with their COVID-19 health and conspiracy myth beliefs. DESIGN: We surveyed adults with hypertension in Maryland and Pennsylvania between August 2020 and March 2021. Incorrect responses were summed for eight health (mean = 0.68; range 0-5) and two conspiracy (mean = 0.92; range 0-2) COVID-19 questions. Higher scores indicated more incorrect responses. Statistical analyses included two-sample t-tests, Spearman's correlation, and log binomial regression. PARTICIPANTS: In total, 561 primary care patients (mean age = 62.3 years, 60.2% female, 46.0% Black, 10.2% Hispanic, 28.2% with a Bachelor's degree or higher, 42.8% with annual household income less than $60,000) with a diagnosis of hypertension and at least one of five commonly associated conditions. MAIN MEASURES: Sociodemographic characteristics, health literacy, medical mistrust level, source of health-related information, and COVID-19 conspiracy and health myth beliefs. KEY RESULTS: In multivariable analyses, participants who did not get information from medical professional sources (prevalence ratio (PR) = 1.28; 95% CI = 1.06-1.55), had less than a bachelor's degree (PR = 1.49; 95% CI = 1.12-1.99), were less confident filling out medical forms (PR = 1.24; 95% CI = 1.02-1.50), and had higher medical mistrust (PR = 1.34; 95% CI = 1.05-1.69) were more likely to believe any health myths. Participants who had less than a bachelor's degree (PR = 1.22; 95% CI = 1.02-1.45), were less confident filling out medical forms (PR = 1.21; 95% CI = 1.09-1.34), and had higher medical mistrust (PR = 1.72; 95% CI = 1.43-2.06) were more likely to believe any conspiracy myths. CONCLUSIONS: Lower educational attainment and health literacy, greater medical mistrust, and certain sources of health information are associated with misinformed COVID-19 beliefs. Programs addressing misinformation should focus on groups affected by these social determinants of health by encouraging reliance on scientific sources.

Assessing the impact of extracellular matrix fiber orientation on breast cancer cellular metabolism.

The extracellular matrix (ECM) is a dynamic and complex microenvironment that modulates cell behavior and cell fate. Changes in ECM composition and architecture have been correlated with development, differentiation, and disease progression in various pathologies, including breast cancer [1]. Studies have shown that aligned fibers drive a pro-metastatic microenvironment, promoting the transformation of mammary epithelial cells into invasive ductal carcinoma via the epithelial-to-mesenchymal transition (EMT) [2]. The impact of ECM orientation on breast cancer metabolism, however, is largely unknown. Here, we employ two non-invasive imaging techniques, fluorescence-lifetime imaging microscopy (FLIM) and intensity-based multiphoton microscopy, to assess the metabolic states of cancer cells cultured on ECM-mimicking nanofibers in a random and aligned orientation. By tracking the changes in the intrinsic fluorescence of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, as well as expression levels of metastatic markers, we reveal how ECM fiber orientation alters cancer metabolism and EMT progression. Our study indicates that aligned cellular microenvironments play a key role in promoting metastatic phenotypes of breast cancer as evidenced by a more glycolytic metabolic signature on nanofiber scaffolds of aligned orientation compared to scaffolds of random orientation. This finding is particularly relevant for subsets of breast cancer marked by high levels of collagen remodeling (e.g. pregnancy associated breast cancer), and may serve as a platform for predicting clinical outcomes within these subsets [3-6].

Behavioral Weight Loss Programs for Cancer Survivors Throughout Maryland: Protocol for a Pragmatic Trial and Participant Characteristics.

BACKGROUND: Clinical trials examining lifestyle interventions for weight loss in cancer survivors have been demonstrated to be safe, feasible, and effective. However, scalable weight loss programs are needed to support their widespread implementation. The ASPIRE trial was designed to evaluate real-world, lifestyle-based, weight loss programs for cancer survivors throughout Maryland. OBJECTIVE: The objectives of this protocol paper are to describe the design of a nonrandomized pragmatic trial, study recruitment, and baseline characteristics of participants. METHODS: Participants were aged ≥18 years, residing in Maryland, with a BMI ≥25 kg/m2, who reported a diagnosis of a malignant solid tumor, completed curative treatment, and had no ongoing or planned cancer treatment. Enrollment criteria were minimized to increase generalizability. The primary recruitment source was the Johns Hopkins Health System electronic health records (EHRs). Participants selected 1 of 3 remotely delivered weight loss programs: self-directed, app-supported, or coach-supported program. RESULTS: Participants were recruited across all 5 geographic regions of Maryland. Targeted invitations using EHRs accounted for 287 (84.4%) of the 340 participants enrolled. Of the 5644 patients invited through EHR, 5.1% (287/5644) enrolled. Participants had a mean age of 60.7 (SD 10.8) years, 74.7% (254/340) were female, 55.9% (190/340) identified as non-Hispanic Black, 58.5% (199/340) had a bachelor's degree, and the average BMI was 34.1 kg/m2 (SD 5.9 kg/m2). The most common types of cancers were breast (168/340, 49.4%), prostate (72/340, 21.2%), and thyroid (39/340, 8.5%). The self-directed weight loss program (n=91) included 25 participants who agreed to provide weights through a study scale; the app-supported program (n=142) included 108 individuals who agreed to provide their weight measurements; and the coach-supported weight loss program included 107 participants. We anticipate final analysis will take place in the fall of 2024. CONCLUSIONS: Using EHR-based recruitment efforts, this study took a pragmatic approach to reach and enroll cancer survivors into remotely delivered weight loss programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04534309; https://clinicaltrials.gov/study/NCT04534309. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54126.

Diagnostic Accuracy of Transthoracic Echocardiography for Acute Type A Aortic Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS. METHODS: We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio [1], and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria. RESULTS: Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38-76%) and 94% (95% CI, 89-97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85-94%) and 74% (95% CI, 61-84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)] in four studies. CONCLUSIONS: Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.

New infundibulopelvic angle measurement method can predict stone-free rates following retrograde intrarenal surgery.

To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma.

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Neurobiologically realistic neural network enables cross-scale modeling of neural dynamics.

Fundamental principles underlying computation in multi-scale brain networks illustrate how multiple brain areas and their coordinated activity give rise to complex cognitive functions. Whereas brain activity has been studied at the micro- to meso-scale to reveal the connections between the dynamical patterns and the behaviors, investigations of neural population dynamics are mainly limited to single-scale analysis. Our goal is to develop a cross-scale dynamical model for the collective activity of neuronal populations. Here we introduce a bio-inspired deep learning approach, termed NeuroBondGraph Network (NBGNet), to capture cross-scale dynamics that can infer and map the neural data from multiple scales. Our model not only exhibits more than an 11-fold improvement in reconstruction accuracy, but also predicts synchronous neural activity and preserves correlated low-dimensional latent dynamics. We also show that the NBGNet robustly predicts held-out data across a long time scale (2 weeks) without retraining. We further validate the effective connectivity defined from our model by demonstrating that neural connectivity during motor behaviour agrees with the established neuroanatomical hierarchy of motor control in the literature. The NBGNet approach opens the door to revealing a comprehensive understanding of brain computation, where network mechanisms of multi-scale activity are critical.

Diagnostic accuracy of procalcitonin in adult non-neutropenic cancer patients with suspected infection: a systematic review and meta-analysis.

BACKGROUND: Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. RESULTS: Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45-74%]) and 78% (95% CI [69-86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86-10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26-83%]) and 75% (95% CI [68-82%]), and those for CRP were 67% (95% CI [35-88%]) and 73% (95% CI [69-77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93). CONCLUSION: While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.