LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA.

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

Kilohertz volumetric imaging of in-vivo dynamics using squeezed light field microscopy.

Volumetric functional imaging of transient cellular signaling and motion dynamics poses a significant challenge to current microscopy techniques, primarily due to limitations in hardware bandwidth and the restricted photon budget within short exposure times. In response to this challenge, we present squeezed light field microscopy (SLIM), a computational imaging method that enables rapid detection of high-resolution three-dimensional (3D) light signals using only a single, low-format camera sensor area. SLIM pushes the boundaries of 3D optical microscopy, achieving over one thousand volumes per second across a large field of view of 550 µm in diameter and 300 µm in depth. Using SLIM, we demonstrated blood cell velocimetry across the embryonic zebrafish brain and in a free-moving tail exhibiting high-frequency swinging motion. The millisecond temporal resolution also enables accurate voltage imaging of neural membrane potentials in the leech ganglion. These results collectively establish SLIM as a versatile and robust imaging tool for high-speed microscopy applications.

Transcriptomic Analysis of Postnatal Rat Carotid Body Development.

The carotid body (CB), located bilaterally at the carotid artery bifurcations, is the primary sensory organ for monitoring arterial blood O2 levels. Carotid bodies are immature at birth, exhibiting low sensitivity to hypoxia, and become more sensitive with maturation during the first few weeks of neonatal life. To understand the molecular basis for the postnatal developmental hypoxic responses of CB, we isolated CBs from 5-day and 21-day-old Sprague-Dawley rats and performed RNA sequencing, which allows comprehensive analysis of gene expression. Differentially expressed genes (DEGs) were generated using Edge R, while functional enrichment analysis was performed using gene-set enrichment analysis (GSEA). Analysis of RNA-Seq data showed 2604 DEGs of the total 12,696 genes shared between neonates and adults. Of the 2604 DEGs, 924 genes were upregulated, and 1680 genes were downregulated. Further analysis showed that genes related to oxidative phosphorylation (Ox/phos) and hypoxia-signaling pathways were significantly upregulated in neonatal CBs compared to adult CBs, suggesting a possible link to differential developmental hypoxic responses seen in CB. Genes related to cytokine signaling (INFγ and TNFα) and transcription factors (CREB and NFΚB) mediated pathways were enriched in adult CBs, suggesting that expression of these pathways may be linked to developmental regulation. The RNA-Seq results were verified by analyzing mRNA changes in selected genes by qRT-PCR. Our results of enrichment analysis of biological pathways offer valuable insight into CB hypoxic sensing responses related to the development process.

Prognostic value of plasma microRNAs for non-small cell lung cancer based on data mining models.

BACKGROUND: As biomarkers, microRNAs (miRNAs) are closely associated with the occurrence, progression, and prognosis of non-small cell lung cancer (NSCLC). However, the prognostic predictive value of miRNAs in NSCLC has rarely been explored. In this study, the value in prognosis prediction of NSCLC was mined based on data mining models using clinical data and plasma miRNAs biomarkers. METHODS: A total of 69 patients were included in this prospective cohort study. After informed consent, they filled out questionnaires and had their peripheral blood collected. The expressions of plasma miRNAs were examined by quantitative polymerase chain reaction (qPCR). The Whitney U test was used to analyze non-normally distributed data. Kaplan-Meier was used to plot the survival curve, the log-rank test was used to compare with the overall survival curve, and the Cox proportional hazards model was used to screen the factors related to the prognosis of lung cancer. Data mining techniques were utilized to predict the prognostic status of patients. RESULTS: We identified that smoking (HR = 2.406, 95% CI = 1.256-4.611), clinical stage III + IV (HR = 5.389, 95% CI = 2.290-12.684), the high expression group of miR-20a (HR = 4.420, 95% CI = 1.760-11.100), the high expression group of miR-197 (HR = 3.828, 95% CI = 1.778-8.245), the low expression group of miR-145 ( HR = 0.286, 95% CI = 0.116-0.709), and the low expression group of miR-30a (HR = 0.307, 95% CI = 0.133-0.706) was associated with worse prognosis. Among the five data mining models, the decision trees (DT) C5.0 model performs the best, with accuracy and Area Under Curve (AUC) of 93.75% and 0.929 (0.685, 0.997), respectively. CONCLUSION: The results showed that the high expression level of miR-20a and miR-197, the low expression level of miR-145 and miR-30a were strongly associated with poorer prognosis in NSCLC patients, and the DT C5.0 model may serve as a novel, accurate, method for predicting prognosis of NSCLC.

Interfacial oxygen atom modification of a PdSn alloy to boost oxygen reduction in zinc-air batteries.

Modifying the surface of a catalyst with heteroatoms can regulate the interfacial atomic valence state and adjust the charge distribution, which is promising for obtaining desirable platinum carbon catalyst (Pt/C)-matched oxygen reduction reaction (ORR) catalytic performance. Here, we developed an efficient method to access O-rich crystalline interfacial-exposed palladium-tin alloy (111) crystal surfaces [Pd3Sn (111)] for highly efficient ORR via direct reduction of Pd/Sn metal salt species that are well dispersed in a nitrogen, phosphorus-doped carbonaceous (NPC) substrate. In addition to the other materials, preembedded Pd/Sn metal salt species in NPC control the release of metal sources upon reduction in the liquid phase, resulting in the grafting of an as-prepared PdSn alloy with many merits, such as efficient electron conduction, short-range crystallinity and increased crystal interface exposure. The presence of a considerable quantity of oxygen atoms at the interface of small-sized PdSn alloys on NPC substrates has been methodically verified by powder X-ray diffraction, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy characterizations. The PdSn-O sample exhibited excellent ORR activity, achieving an onset potential of âˆ¼0.99 V and a half-wave potential of âˆ¼0.88 V at 1600 rpm in O2-saturated 1.0 M KOH. Density functional theory simulations of pure Pd, Pd-O, the PdSn alloy and PdSn-O suggest that interfacial oxygen atom modification is responsible for the significantly improved ORR activity. The assembled zinc-air battery provides a high specific power of 218.9 mW cm-2 and a specific capacity of 810.6 mAh gZn-1. Our approach has the potential to stimulate the preparation of O-rich crystalline interfacial-exposed alloy compounds for other energy conversion applications.

The sub-molecular characterization identification for cervical cancer.

Background: The efficacy of therapy in cervical cancer (CESC) is blocked by high molecular heterogeneity. Thus, the sub-molecular characterization remains primarily explored for personalizing the treatment of CESC patients. Methods: Datasets with 741 CESC patients were obtained from TCGA and GEO databases. The NMF algorithm, random forest algorithm, and multivariate Cox analysis were utilized to construct a classifier for defining the sub-molecular characterization. Then, the biological characteristics, genomic variations, prognosis, and immune landscape in molecular subtypes were explored. The significance of classifier genes was validated by quantitative Real-Time PCR, cell transfection, cell colony formation assay, wound healing assay, cell proliferation assay, and Western blot. Results: The CESC patients were classified into two subtypes, and the high classifier-score patients with significant differences in ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway showed a poorer prognosis in OS (p < 0.001), DFI (p = 0.016), PFI (p < 0.001) and DSS (p < 0.001), and with high the M0 Macrophage and resting Mast cells infiltration and low HLA family gene expression. Moreover, the constructed classifier owns a high identified accuracy in the tumor/normal groups (AUC: 0.993), the tumor/CIN1-CIN3 groups (AUC: 0.963), and normal/CIN1-CIN3 groups (AUC: 0.962), and the total prediction performance is better than currently published signatures in CESC (C-index: 0,763). The combined prediction performance further indicated that Nomogram (AUC = 0.837) is superior to the classifier (AUC = 0.835) and Stage (AUC = 0.568), and the C-index of calibration curves is 0.784. The potential biological function of classifier genes indicated that silencing GALNT2 inhibited the cancer cell's proliferation, migration, and colony formation; Conversely, the cancer cell's proliferation, migration, and colony formation were increased after the upregulation of GALNT2. The Epithelial-Mesenchymal Transition Experiment showed that GALNT2 knockdown might reduce the levels of Snail and Vimentin proteins and increase E-cadherin; Conversely, the levels of Snail and Vimentin proteins were increased, E-cadherin was reduced by GALNT2 upregulation. Conclusion: The classifier we constructed may help improve our understanding of subtype characteristics and provide a new strategy for developing CESC therapeutics. Remarkably, GALNT2 may be an option to directly target drivers in CESC cancer therapy.

A high-efficiency gene silencing in plants using two-hit asymmetrical artificial MicroRNAs.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme-guided process called dicing and have an asymmetrical structure with two nucleotide overhangs at the 3' ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem-loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called "two-hit" amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional "one-hit" amiRNAs. The authors also demonstrated the effectiveness of "two-hit" amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, "two-hit" amiRNAs were also able to over-express endogenous miRNAs for their functions. The authors compare "two-hit" amiRNA technology with CRISPR/Cas9 and provide a web-based amiRNA designer for easy design and wide application in plants and even animals.

On-axis deflectometric system for freeform surface measurement.

We propose an on-axis deflectometric system for the accurate measurement of freeform surfaces with large slope ranges. A miniature plane mirror is attached on the illumination screen to fold the optical path and achieve the on-axis deflectometric testing. Due to the existence of the miniature folding mirror, the deep-learning method is applied to recover the missing surface data in a single measurement. Low sensitivity to the calibration error of system geometry and high testing accuracy can be achieved with the proposed system. The feasibility and accuracy of the proposed system have been validated. The system is low in cost and simple in configuration, and it provides a feasible way for the flexible and general testing of freeform surfaces, with a significant potential of the application in on-machine testing.

The global burden of colorectal cancer attributable to high plasma glucose in 204 countries and territories, 1990-2019: an analysis of the Global Burden of Disease Study.

OBJECTIVES: This study aimed to estimate the burden of colorectal cancer (CRC) attributable to high plasma glucose from 1990 to 2019. STUDY DESIGN AND METHODS: Data on the disease burden were retrieved from the Global Burden of Disease online database. Estimated average percentage change (EAPC) was used to quantify the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate (ASDR) of high plasma glucose-related CRC trends by sex and location between 1990 and 2019. RESULTS: Globally, the death number and DALYs of CRC attributable to high plasma glucose remained a steady increase at global level from 1990 to 2019, and similar trends have been reported in age-standardized rate. The country with the largest number of death cases and DALYs of high plasma glucose-related CRC in 2019 was China, followed by the United States of America and India. Nearly three-quarters of total countries experienced an increase in the ASMR and ASDR, and the greatest increase of ASMR and ASDR was found in Uzbekistan (EAPC = 5.32) and Equatorial Guinea (EAPC = 4.65), respectively. A negative correlation was found between sociodemographic indices and the EAPC of ASMR and ASDR (rASMR = -0.259, p < 0.001; rASDR = -0.282, p < 0.001). CONCLUSIONS: A significant increase in mortality and DALYs of CRC attributable to high plasma glucose was observed in global and most countries, especially in the developing countries. Public health policies and targeted programs are needed to reduce the burden of disease.

Targeting Class I Histone Deacetylases in Human Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is the most frequent subtype of uterine sarcoma that presents a poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is unknown. Class I histone deacetylases (including HDAC1, 2, 3, and 8) are one of the major classes of the HDAC family and catalyze the removal of acetyl groups from lysine residues in histones and cellular proteins. Class I HDACs exhibit distinct cellular and subcellular expression patterns and are involved in many biological processes and diseases through diverse signaling pathways. However, the link between class I HDACs and uLMS is still being determined. In this study, we assessed the expression panel of Class I HDACs in uLMS and characterized the role and mechanism of class I HDACs in the pathogenesis of uLMS. Immunohistochemistry analysis revealed that HDAC1, 2, and 3 are aberrantly upregulated in uLMS tissues compared to adjacent myometrium. Immunoblot analysis demonstrated that the expression levels of HDAC 1, 2, and 3 exhibited a graded increase from normal and benign to malignant uterine tumor cells. Furthermore, inhibition of HDACs with Class I HDACs inhibitor (Tucidinostat) decreased the uLMS proliferation in a dose-dependent manner. Notably, gene set enrichment analysis of differentially expressed genes (DEGs) revealed that inhibition of HDACs with Tucidinostat altered several critical pathways. Moreover, multiple epigenetic analyses suggested that Tucidinostat may alter the transcriptome via reprogramming the oncogenic epigenome and inducing the changes in microRNA-target interaction in uLMS cells. In the parallel study, we also determined the effect of DL-sulforaphane on the uLMS. Our study demonstrated the relevance of class I HDACs proteins in the pathogenesis of malignant uLMS. Further understanding the role and mechanism of HDACs in uLMS may provide a promising and novel strategy for treating patients with this aggressive uterine cancer.

Highly aneuploid non-small cell lung cancer shows enhanced responsiveness to concurrent radiation and immune checkpoint blockade.

Over 500 clinical trials are investigating combination radiotherapy and immune checkpoint blockade (ICB) as cancer treatments; however, the majority of trials have found no positive interaction. Here we perform a comprehensive molecular analysis of a randomized phase I clinical trial of patients with non-small cell lung cancer (NSCLC) treated with concurrent or sequential ablative radiotherapy and ICB. We show that concurrent treatment is superior to sequential treatment in augmenting local and distant tumor responses and in improving overall survival in a subset of patients with immunologically cold, highly aneuploid tumors, but not in those with less aneuploid tumors. In addition, radiotherapy alone decreases intratumoral cytotoxic T cell and adaptive immune signatures, whereas radiotherapy and ICB upregulates key immune pathways. Our findings challenge the prevailing paradigm that local ablative radiotherapy beneficially stimulates the immune response. We propose the use of tumor aneuploidy as a biomarker and therapeutic target in personalizing treatment approaches for patients with NSCLC treated with radiotherapy and ICB.

Rare FGFR Oncogenic Alterations in Sequenced Pediatric Solid and Brain Tumors Suggest FGFR Is a Relevant Molecular Target in Childhood Cancer.

PURPOSE: Multiple FGFR inhibitors are currently in clinical trials enrolling adults with different solid tumors, while very few enroll pediatric patients. We determined the types and frequency of FGFR alterations (FGFR1-4) in pediatric cancers to inform future clinical trial design. METHODS: Tumors with FGFR alterations were identified from two large cohorts of pediatric solid tumors subjected to targeted DNA sequencing: The Dana-Farber/Boston Children's Profile Study (n = 888) and the multi-institution GAIN/iCAT2 (Genomic Assessment Improves Novel Therapy) Study (n = 571). Data from the combined patient population of 1,395 cases (64 patients were enrolled in both studies) were reviewed and cases in which an FGFR alteration was identified by OncoPanel sequencing were further assessed. RESULTS: We identified 41 patients with tumors harboring an oncogenic FGFR alteration. Median age at diagnosis was 8 years (range, 6 months-26 years). Diagnoses included 11 rhabdomyosarcomas, nine low-grade gliomas, and 17 other tumor types. Alterations included gain-of-function sequence variants (n = 19), amplifications (n = 10), oncogenic fusions (FGFR3::TACC3 [n = 3], FGFR1::TACC1 [n = 1], FGFR1::EBF2 [n = 1], FGFR1::CLIP2 [n = 1], and FGFR2::CTNNA3 [n = 1]), pathogenic-leaning variants of uncertain significance (n = 4), and amplification in combination with a pathogenic-leaning variant of uncertain significance (n = 1). Two novel FGFR1 fusions in two different patients were identified in this cohort, one of whom showed a response to an FGFR inhibitor. CONCLUSION: In summary, activating FGFR alterations were found in approximately 3% (41/1,395) of pediatric solid tumors, identifying a population of children with cancer who may be eligible and good candidates for trials evaluating FGFR-targeted therapy. Importantly, the genomic and clinical data from this study can help inform drug development in accordance with the Research to Accelerate Cures and Equity for Children Act.

Experimental Studies on Fabricating Lenslet Array with Slow Tool Servo.

On the demand of low-cost, lightweight, miniaturized, and integrated optical systems, precision lenslet arrays are widely used. Diamond turning is often used to fabricate lenslet arrays directly or molds that are used to mold lenslet arrays. In this paper, mainly by real-time monitoring position following error for slow tool servo, different fabrication parameters are quantitatively studied and optimized for actual fabrication, then by actual fabrication validation, uniform and high-fidelity surface topography across the actual whole lenslet array is achieved. The evaluated fabrication parameters include sampling strategy, inverse time feed, arc-length, etc. The study provides a quick, effective, and detailed reference for both convex and concave lenslet array cutting parameter selection. At the end, a smooth zonal machining strategy toolpath is demonstrated for fabricating concave lenslet arrays.

N6-adenomethylation of GsdmC is essential for Lgr5+ stem cell survival to maintain normal colonic epithelial morphogenesis.

Gut epithelial morphogenesis is maintained by intestinal stem cells. Here, we report that depletion of N6-adenosine methyltransferase subunit Mettl14 from gut epithelial cells in mice impaired colon mucosal morphogenesis, leading to increased mucosal permeability, severe inflammation, growth retardation, and premature death. Mettl14 ablation triggered apoptosis that depleted Lgr5+ stem cells and disrupted colonic organoid growth and differentiation, whereas the inhibition of apoptosis rescued Mettl14-deleted mice and organoids. Mettl14 depletion disrupted N6-adenomethylation on GsdmC transcripts and abolished GsdmC expression. Reconstitution of Mettl14-deleted organoids or mice with GSDMC rescued Lgr5 expression and prevented apoptosis and mouse premature death, whereas GSDMC silence eliminated LGR5 and triggered apoptosis in human colonic organoids and epithelial cells. Mechanistically, Mettl14 depletion eliminated mitochondrial GsdmC, disrupted mitochondrial membrane potential, and triggered cytochrome c release that activates the pro-apoptotic pathway. In conclusion, GsdmC N6-adenomethylation protects mitochondrial homeostasis and is essential for Lgr5+ cell survival to maintain normal colonic epithelial regeneration.

Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer.

To evaluate the clinical impact of molecular tumor profiling (MTP) with targeted sequencing panel tests, pediatric patients with extracranial solid tumors were enrolled in a prospective observational cohort study at 12 institutions. In the 345-patient analytical population, median age at diagnosis was 12 years (range 0-27.5); 298 patients (86%) had 1 or more alterations with potential for impact on care. Genomic alterations with diagnostic, prognostic or therapeutic significance were present in 61, 16 and 65% of patients, respectively. After return of the results, impact on care included 17 patients with a clarified diagnostic classification and 240 patients with an MTP result that could be used to select molecularly targeted therapy matched to identified alterations (MTT). Of the 29 patients who received MTT, 24% had an objective response or experienced durable clinical benefit; all but 1 of these patients received targeted therapy matched to a gene fusion. Of the diagnostic variants identified in 209 patients, 77% were gene fusions. MTP with targeted panel tests that includes fusion detection has a substantial clinical impact for young patients with solid tumors.

Determining the Case Fatality Rate of COVID-19 in Italy: Novel Epidemiological Study.

BACKGROUND: COVID-19, which emerged in December 2019, has spread rapidly around the world and has become a serious public health event endangering human life. With regard to COVID-19, there are still many unknowns, such as the exact case fatality rate (CFR). OBJECTIVE: The main objective of this study was to explore the value of the discharged CFR (DCFR) to make more accurate forecasts of epidemic trends of COVID-19 in Italy. METHODS: We retrieved the epidemiological data of COVID-19 in Italy published by the John Hopkins Coronavirus Resource Center. We then used the proportion of deaths to discharged cases（including deaths and recovered cases） to calculate the total DCFR (tDCFR), monthly DCFR (mDCFR), and stage DCFR (sDCFR). Furthermore, we analyzed the trend in the mDCFR between January and December 2020 using joinpoint regression analysis, used ArcGIS version 10.7 to visualize the spatial distribution of the epidemic CFR, and assigned different colors to each province based on the CFR or tDCFR. RESULTS: We calculated the numbers and obtained the new indices of the tDCFR and mDCFR for calculating the fatality rate. The results showed that the tDCFR and mDCFR fluctuated greatly from January to May. They first showed a rapid increase followed by a rapid decline after reaching the peak. The map showed that the provinces with a high tDCFR were Emilia-Romagna, Puglia, and Lombardia. The change trend of the mDCFR over time was divided into the following 2 stages: the first stage (from January to May) and the second stage (from June to December). With regard to worldwide COVID-19 statistics, among 6 selected countries, the United States had the highest tDCFR (4.26%), while the tDCFR of the remaining countries was between 0.98% and 2.72%. CONCLUSIONS: We provide a new perspective for assessing the fatality of COVID-19 in Italy, which can use ever-changing data to calculate a more accurate CFR and scientifically predict the development trend of the epidemic.

Germline Sequencing Improves Tumor-Only Sequencing Interpretation in a Precision Genomic Study of Patients With Pediatric Solid Tumor.

PURPOSE: Molecular tumor profiling is becoming a routine part of clinical cancer care, typically involving tumor-only panel testing without matched germline. We hypothesized that integrated germline sequencing could improve clinical interpretation and enhance the identification of germline variants with significant hereditary risks. MATERIALS AND METHODS: Tumors from pediatric patients with high-risk, extracranial solid malignancies were sequenced with a targeted panel of cancer-associated genes. Later, germline DNA was analyzed for a subset of these genes. We performed a post hoc analysis to identify how an integrated analysis of tumor and germline data would improve clinical interpretation. RESULTS: One hundred sixty participants with both tumor-only and germline sequencing reports were eligible for this analysis. Germline sequencing identified 38 pathogenic or likely pathogenic variants among 35 (22%) patients. Twenty-five (66%) of these were included in the tumor sequencing report. The remaining germline pathogenic or likely pathogenic variants were single-nucleotide variants filtered out of tumor-only analysis because of population frequency or copy-number variation masked by additional copy-number changes in the tumor. In tumor-only sequencing, 308 of 434 (71%) single-nucleotide variants reported were present in the germline, including 31% with suggested clinical utility. Finally, we provide further evidence that the variant allele fraction from tumor-only sequencing is insufficient to differentiate somatic from germline events. CONCLUSION: A paired approach to analyzing tumor and germline sequencing data would be expected to improve the efficiency and accuracy of distinguishing somatic mutations and germline variants, thereby facilitating the process of variant curation and therapeutic interpretation for somatic reports, as well as the identification of variants associated with germline cancer predisposition.

Severity of Downgaze Palsy in the Context of Disease Duration Could Estimate Survival Duration in Patients With Progressive Supranuclear Palsy.

It is an unmet need to estimate survival duration for patients with progressive supranuclear palsy (PSP). The objective of this study was to identify factors associated with the survival duration in patients with PSP. We followed up 23 patients with probable PSP-RS (Richardson syndrome) or PSP-P (parkinsonism) in our PSP center until death from 2011 to 2019. We prospectively and quantitatively rated their downgaze palsy whenever first noticed in our clinic. This was utilized along with the disease duration, motor function, medication use for parkinsonism, sex, age at onset of PSP, comorbid pulmonary and cardiovascular diseases, and the total survival duration from the onset of PSP to death for prediction analysis. A well-fitted linear regression model and a multivariant Cox model were applied to identify predicting factors for total survival duration. All patients had the specific hummingbird sign on brain MRI for PSP when downgaze palsy was documented. We found that the severity of downgaze palsy and the disease duration at the assessment were consistently correlated with the total survival duration in both models. The total survival duration could be further estimated by a formed regression equation. We conclude that severity and time to develop downgaze palsy could help to estimate the total survival duration in patients with probable PSP-RS and PSP-P, the major forms of PSP, which has significant clinical applications in clinical counseling and trial enrollment.

Disparities in diagnosis, treatment and survival between Black and White Parkinson patients.

INTRODUCTION: Racial disparities in diagnosis, treatment and survival in Black patients with Parkinson's disease (PD) compared to White patients have not been well studied, largely due to limited number of studies and information on Black patients in healthcare systems. Studying racial disparities and identifying underlying factors in large populations are important to understand PD and improve care. METHODS: We retrospectively identified PD patients on both races from 1/1/2006 to 10/31/2017 and compared demographics, socioeconomic status (educations, incomes and insurances), comorbidities (all categories, including mood, cognition and psychosis), treatment (medications for parkinsonism and major non-motor symptoms, and frequency and locations of healthcare) and survival, and identified factors associated with medication usage and survival. RESULTS: We retrospectively studied 2033 PD patients, of whom 725 were Black. Black patients lacked male predominance, were 4 years older at first diagnosis here, more likely to smoke and live in a low education and income community, and possessed limited insurances compared to White patients. Black patients also had more comorbidities and were more likely to receive care through emergency or inpatient service, but less likely to be on medications for parkinsonism and mood disorders. Race, age, smoking status, insurance type, frequency and locations of healthcare and comorbidities were associated with medication usage. Black race, older age, inpatient admission and malignancy were associated with increased risk of death. CONCLUSION: We revealed racial disparities in diagnosis, treatment and survival, and factors associated with medication usage and survival in the largest reported Black PD cohort from a single center.