Loureirin B ameliorates cholestatic liver fibrosis via AKT/mTOR/ATG7-mediated autophagy of hepatic stellate cells.

AIM OF THE STUDY: Chronic cholestasis leads to liver fibrosis, which lacks effective treatment. In this study, we investigated the role and mechanisms of action of loureirin B (LB) in cholestatic liver fibrosis. MATERIALS AND METHODS: Bile duct ligation (BDL)-induced hepatic fibrosis mice were used as in vivo models. Transforming growth factor-ß1 (TGF-ß1)-pretreated HSC-T6 cells were used to explore the mechanism by which LB attenuates liver fibrosis in vitro. RNA sequencing, quantitative PCR (qPCR), western blotting, immunohistochemistry and immunofluorescence were performed to detect the fibrosis markers and measure autophagy levels. Flow cytometry, cell counting kit-8 (CCK-8) assay, and 5'-ethynyl-2'-deoxyuridine (EdU) assay were conducted to detect cell proliferation and viability. GFP-RFP-LC3 adenovirus, autophagy-related protein 7 (ATG7) siRNA, and bafilomycin A1 (BafA1) were used to verify autophagic flux. RESULTS: Our results showed that LB ameliorates liver injury, inhibits collagen deposition, and decreases the expressions of fibrosis-related markers in BDL-induced mouse livers. In vitro, we found that LB inhibited proliferation and migration, promoted apoptosis, and inhibited the activation of HSC-T6 cells pretreated with TGF-ß1. RNA sequencing analysis of HSC-T6 cells showed that LB treatment predominantly targeted autophagy-related pathways. Further protein analysis indicated that LB downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR), and upregulated LC3-II, p62, and ATG7 both in vivo and in vitro. Intriguingly, ATG7 inactivation reversed the antifibrotic effects of LB on HSC-T6 cells. CONCLUSIONS: LB can improve BDL-induced liver fibrosis by inhibiting the activation and proliferation of HSCs and is expected to be a promising antifibrotic drug.

Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies.

Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues. Methods: We analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes. Results: Elevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Conclusions: Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.

Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.

Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.

Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell type-specific profiling in monocytes further improved outcome predictions. Additional analyses of tumor-adjacent transcriptomic data from The Cancer Genome Atlas validated the association of the inflammatory signature with worse outcomes across cancers. Collectively, our study suggests that molecular profiling of tumor-adjacent tissue can identify patients at high risk for disease progression.

Digital measures of respiratory and upper limb function in spinal muscular atrophy: design, feasibility, reliability, and preliminary validity of a smartphone sensor-based assessment suite.

Spinal muscular atrophy (SMA) is characterized by progressive muscle weakness and paralysis. Motor function is monitored in the clinical setting using assessments including the 32-item Motor Function Measure (MFM-32), but changes in disease severity between clinical visits may be missed. Digital health technologies may assist evaluation of disease severity by bridging gaps between clinical visits. We developed a smartphone sensor-based assessment suite, comprising nine tasks, to assess motor and muscle function in people with SMA. We used data from the risdiplam phase 2 JEWELFISH trial to assess the test-retest reliability and convergent validity of each task. In the first 6 weeks, 116 eligible participants completed assessments on a median of 6.3 days per week. Eight of the nine tasks demonstrated good or excellent test-retest reliability (intraclass correlation coefficients >0.75 and >0.9, respectively). Seven tasks showed a significant association (P < 0.05) with related clinical measures of motor function (individual items from the MFM-32 or Revised Upper Limb Module scales) and seven showed significant association (P < 0.05) with disease severity measured using the MFM-32 total score. This cross-sectional study supports the feasibility, reliability, and validity of using smartphone-based digital assessments to measure function in people living with SMA.

Automatic speaker diarization for natural conversation analysis in autism clinical trials.

Challenges in social communication is one of the core symptom domains in autism spectrum disorder (ASD). Novel therapies are under development to help individuals with these challenges, however the ability to show a benefit is dependent on a sensitive and reliable measure of treatment effect. Currently, measuring these deficits requires the use of time-consuming and subjective techniques. Objective measures extracted from natural conversations could be more ecologically relevant, and administered more frequently-perhaps giving them added sensitivity to change. While several studies have used automated analysis methods to study autistic speech, they require manual transcriptions. In order to bypass this time-consuming process, an automated speaker diarization algorithm must first be applied. In this paper, we are testing whether a speaker diarization algorithm can be applied to natural conversations between autistic individuals and their conversational partner in a natural setting at home over the course of a clinical trial. We calculated the average duration that a participant would speak for within their turn. We found a significant correlation between this feature and the Vineland Adaptive Behaviour Scales (VABS) expressive communication score (r = 0.51, p = 7 × 10-5). Our results show that natural conversations can be used to obtain measures of talkativeness, and that this measure can be derived automatically, thus showing the promise of objectively evaluating communication challenges in ASD.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch. It was studied in 316 early-stage PD participants who performed daily active tests at home then carried a smartphone and wore a smartwatch throughout the day for passive monitoring (study NCT03100149). Here, we report baseline data. Adherence was excellent (96.29%). All pre-specified sensor features exhibited good-to-excellent test-retest reliability (median intraclass correlation coefficient = 0.9), and correlated with corresponding Movement Disorder Society-Unified Parkinson's Disease Rating Scale items (rho: 0.12-0.71). These findings demonstrate the preliminary reliability and validity of remote at-home quantification of motor sign severity with the Roche PD Mobile Application v2 in individuals with early PD.

Consumption of Dehulled Adlay Improved Lipid Metabolism and Inflammation in Overweight and Obese Individuals after a 6-Week Single-Arm Pilot Study.

Obesity is a major public health concern worldwide with a rising prevalence. Diets containing whole grains have been demonstrated to benefit body composition and inflammatory conditions in individuals at a high risk of metabolic disorders. This study investigated the effects of dehulled adlay on blood lipids and inflammation in overweight and obese adults. We recruited 21 individuals with abdominal obesity to participate in a 6-week experiment, providing them 60 g of dehulled adlay powder per day as a substitute for their daily staple. Before and after the 6-week intervention, we performed anthropometric analyses and measured blood lipid profiles, adipokines, and markers of inflammation. At the end of the study, the percentage of body fat mass, blood total cholesterol, and triglyceride levels were significantly decreased compared with the baseline. Plasma tumor necrosis factor alpha, interleukin-6, leptin, and malondialdehyde levels were also reduced. In addition, participants with higher basal blood lipid levels exhibited enhanced lipid lowering effects after the dehulled adlay intervention. These results suggest that a dietary pattern containing 60 g of dehulled adlay per day may have a beneficial effect on lipid profiles and inflammatory markers in individuals that are overweight and obese.

Evaluation of radiological and temporal characteristics of acute appendicitis on the non-enhanced computed tomography images.

PURPOSES: To investigate the relationships and interactions between temporal and radiological features of gangrene and perforation of inflamed appendices. METHODS: A total of 402 patients were included who underwent laparoscopic appendectomies between January 1, 2016 and March 30, 2020 and had pathologically proved acute appendicitis and preoperative non-enhanced CT examinations. The radiological features (appendix diameter, appendicolith, appendiceal intraluminal gas, periappendiceal gas, periappendiceal fat stranding/fluid, and short axial diameter of the mesenteric lymph nodes) were obtained from the preoperative CT images of 382 patients with visible appendices. Clinical parameters and temporal variables (pre-CT delay, preoperative delay, estimated complication delay, symptom delay, and system delay) were recorded. RESULTS: Among simple/suppurative, gangrenous, and perforated appendicitis, the radiological characteristics except for short axial diameters of lymph nodes, and the temporal variables other than system delay were significantly different. The Cox regression analysis identified the appendicolith as the independent risk factor for both gangrene and perforation of inflamed appendices by using the preoperative delay or estimated complication delay. By the preoperative delay, the median time for gangrene and perforation was 76.23 (95%CI 73.89-78.58) h and 77.55 (95%CI 74.12-80.98) h, respectively, if appendicolith was present. If estimated complication delay was used as the elapsed time and the appendicolith was perceptible, the median time for gangrene and perforation and was 72.33 (95%CI 62.93-81.74) h and 75.07 (95%CI 69.48-80.65) h, respectively. CONCLUSION: There were interactions between the time evolution and radiological features of acute appendicitis. The evaluation of gangrene and perforation rate of acute appendicitis could be benefitted from combining the preoperative delay/estimated complication delay with CT characteristics in the preoperative urgent radiological analysis.

Diet containing dehulled adlay ameliorates hepatic steatosis, inflammation and insulin resistance in rats with non-alcoholic fatty liver disease.

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1ß and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.

Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults.

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group's systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

U-turn speed is a valid and reliable smartphone-based measure of multiple sclerosis-related gait and balance impairment.

BACKGROUND: People living with multiple sclerosis (MS) experience impairments in gait and mobility, that are not fully captured with manually timed walking tests or rating scales administered during periodic clinical visits. We have developed a smartphone-based assessment of ambulation performance, the 5 U-Turn Test (5UTT), a quantitative self-administered test of U-turn ability while walking, for people with MS (PwMS). RESEARCH QUESTION: What is the test-retest reliability and concurrent validity of U-turn speed, an unsupervised self-assessment of gait and balance impairment, measured using a body-worn smartphone during the 5UTT? METHODS: 76 PwMS and 25 healthy controls (HCs) participated in a cross-sectional non-randomised interventional feasibility study. The 5UTT was self-administered daily and the median U-turn speed, measured during a 14-day session, was compared against existing validated in-clinic measures of MS-related disability. RESULTS: U-turn speed, measured during a 14-day session from the 5UTT, demonstrated good-to-excellent test-retest reliability in PwMS alone and combined with HCs (intraclass correlation coefficient [ICC] = 0.87 [95 % CI: 0.80-0.92]) and moderate-to-excellent reliability in HCs alone (ICC = 0.88 [95 % CI: 0.69-0.96]). U-turn speed was significantly correlated with in-clinic measures of walking speed, physical fatigue, ambulation impairment, overall MS-related disability and patients' self-perception of quality of life, at baseline, Week 12 and Week 24. The minimal detectable change of the U-turn speed from the 5UTT was low (19.42 %) in PwMS and indicates a good precision of this measurement tool when compared with conventional in-clinic measures of walking performance. SIGNIFICANCE: The frequent self-assessment of turn speed, as an outcome measure from a smartphone-based U-turn test, may represent an ecologically valid digital solution to remotely and reliably monitor gait and balance impairment in a home environment during MS clinical trials and practice.

Deep Learning-Based Human Activity Recognition for Continuous Activity and Gesture Monitoring for Schizophrenia Patients With Negative Symptoms.

BACKGROUND: We aimed to develop a Human Activity Recognition (HAR) model using a wrist-worn device to assess patient activity in relation to negative symptoms of schizophrenia. METHODS: Data were analyzed in a randomized, three-way cross-over, proof-of-mechanism study (ClinicalTrials.gov: NCT02824055) comparing two doses of RG7203 with placebo, given as adjunct to stable antipsychotic treatment in patients with chronic schizophrenia and moderate levels of negative symptoms. Baseline negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS). Patients were given a GeneActiv™ wrist-worn actigraphy device to wear over a 15-week period. For this analysis, actigraphy data and behavioral and clinical assessments obtained during placebo treatment were used. Motivated behavior was evaluated with a computerized effort-choice task. A trained HAR model was used to classify activity and an activity-time ratio was derived. Gesture events and features were inferred from the HAR-detected activities and the acceleration signal. RESULTS: Thirty-three patients were enrolled: mean (±SD) age 36.6 ± 7 years; mean (±SD) baseline PANSS negative symptom factor score 23.0 ± 3.5; and mean (±SD) baseline BNSS total score 36.0 ± 11.5. Activity data were collected for 31 patients with a median monitoring time of 1,859 h per patient, equating to ~11 weeks or 74% monitoring ratio. The trained HAR model demonstrated >95% accuracy in separating ambulatory and stationary activities. A positive correlation was seen between the activity-time ratio and the percent of high-effort choices (Spearman r = 0.58; P = 0.002) in the effort-choice task. Median daily gesture counts correlated negatively with the BNSS total score (Spearman r = -0.44; P = 0.03), specifically with the diminished expression sub-score (Spearman r = -0.42; P = 0.03). Gesture features also correlated negatively with the BNSS total score and diminished expression sub-scores. Activity measures showed similar correlations with PANSS negative symptom factor but did not reach significance. CONCLUSION: Our findings support the use of wrist-worn devices to derive activity and gesture-based digital outcome measures for patients with schizophrenia with negative symptoms in a clinical trial setting.

Beneficial Effects of Golden Kiwifruit Consumption in Overweight and Obese Young Adults.

Overweight and obesity are associated with many chronic diseases. This study aimed to clarify the possible effects of consuming golden kiwifruit as daily fruit intake on body composition, lipid metabolism and inflammatory responses. METHODS: We recruited twenty-two overweight and obese subjects and they were asked to consume two golden kiwifruit every day during the 6-wk experimental period. At the baseline and end of the study, fasting blood samples were collected and anthropometric and blood pressure measurement were conducted. RESULTS: During the experimental period, no adverse effect and dropout were reported. At the end of the study, a significant decrease in body fat and circulatory tumor necrosis factor (TNF)-α concentration were found. In addition, there was a reduction of angiotensin II (AgII) concentration and systolic blood pressure in subjects with baseline systolic blood pressure (SBP) ≥125 mmHg. CONCLUSION: Our results suggested that daily golden kiwifruit intake can reduce body fat mass, improve blood pressure and regulating inflammatory responses in overweight and obese young adults.

Crude extract of Camellia oleifera pomace ameliorates the progression of non-alcoholic fatty liver disease via decreasing fat accumulation, insulin resistance and inflammation.

Consumption of a high-fat diet increases fat accumulation and may further lead to inflammation and hepatic injuries. The aim of the study was to investigate the effects of Camellia oleifera seed extract (CSE) on non-alcoholic fatty liver disease (NAFLD). After a 16-week NAFLD-inducing period, rats were assigned to experimental groups fed an NAFLD diet with or without CSE. At the end of the study, we found that consuming CSE decreased the abdominal fat weight and hepatic fat accumulation and modulated circulating adipokine levels. We also found that CSE groups had lower hepatic cytochrome P450 2E1 and transforming growth factor (TGF)-ß protein expressions. In addition, we found that CSE consumption may have affected the gut microbiota and reduced toll-like receptor (TLR)-4, myeloid differentiation primary response gene 88, toll/IL-1 receptor domain-containing adaptor-inducing interferon-ß (TRIF) expression and proinflammatory cytokine concentrations in the liver. Our results suggest that CSE may alleviate the progression of NAFLD in rats with diet-induced steatosis through reducing fat accumulation and improving lipid metabolism and hepatic inflammation.

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition.

Small cell lung cancer (SCLC) is a recalcitrant, aggressive neuroendocrine-type cancer for which little change to first-line standard-of-care treatment has occurred within the last few decades. Unlike nonsmall cell lung cancer (NSCLC), SCLC harbors few actionable mutations for therapeutic intervention. Lysine-specific histone demethylase 1A (LSD1 also known as KDM1A) inhibitors were previously shown to have selective activity in SCLC models, but the underlying mechanism was elusive. Here, we found that exposure to the selective LSD1 inhibitor ORY-1001 activated the NOTCH pathway, resulting in the suppression of the transcription factor ASCL1 and the repression of SCLC tumorigenesis. Our analyses revealed that LSD1 bound to the NOTCH1 locus, thereby suppressing NOTCH1 expression and downstream signaling. Reactivation of NOTCH signaling with the LSD1 inhibitor reduced the expression of ASCL1 and neuroendocrine cell lineage genes. Knockdown studies confirmed the pharmacological inhibitor-based results. In vivo, sensitivity to LSD1 inhibition in SCLC patient-derived xenograft (PDX) models correlated with the extent of consequential NOTCH pathway activation and repression of a neuroendocrine phenotype. Complete and durable tumor regression occurred with ORY-1001-induced NOTCH activation in a chemoresistant PDX model. Our findings reveal how LSD1 inhibitors function in this tumor and support their potential as a new and targeted therapy for SCLC.

[A case control study of lumbar fusion surgery with the Wiltse approach and the traditional approach].

OBJECTIVE: To compare the clinical results between the Wiltse approach and traditional approach in lumbar fusion. METHODS: The clinical data of 70 patients with lumbar disc herniation or lumbar spondylolisthesis within Meyerding II degree who underwent lumbar fusion surgery from May 2016 to May 2017 were retrospectively analyzed. According to the surgical approach, the patients were divided into Wiltse approach group and traditional approach group. A total of 35 patients in Wiltse approach group, included 18 males and 17 females, with an average age of (52±11) years old;other 35 patients in traditional approach group, included 19 males and 16 females, with an average age of (51±14) years old. Included 38 patients with lumbar disc herniation and 32 patients with spondylolisthesis of Meyerding II degree. The operation time, intraoperative blood loss and postoperative drainage, the VAS score of low back pain and leg pain, the level of creatine phosphokinase (CK) and the cross-sectional area of multifidus muscl on MRI were recorded. RESULTS: The operation time, intraoperative blood loss and postoperative drainage in Wiltse approach group were less than in traditional approach group(P<0.05). There were significant differences in VAS score of low back pain at 7 days and 3 months after operation between two groups(P<0.05). VAS of back pain at both 7 days and 3 months showed better results (P<0.05); VAS of leg pain showed better results in 3 months but had no significant difference in 7 days. There was no significant difference in VAS score of leg pain at 7 days after operation between two groups(P>0.05), but at 3 months had significant difference(P<0.05). The peripheral blood CK levels at 1 day and 3 days after operation respectively were(400±103)U/L and (176±58)U/L in Wiltse approach group, while in traditional approach group were (598±57) U/L and (222±50) U/L, with statistical significance between the two groups(P<0.05). Preoperative cross-sectional area of multifidus muscl on MRI was (424±66) mm² in Wiltse approach group and (428±82) mm² in traditional approach group, there was no significant difference between two groups(P=0.8); at 3 months after operation, in Wiltse approach group was (347±73) mm² and in traditional approach group was(239±78)mm², there was significant difference between two groups(P<0.05). CONCLUSIONS: For lumbar spinal fusion surgery, compared with the traditional approach, Wiltse approach has advantages of shorter operation time, smaller paravertebral muscles injury, and obviously releasing postoperative low back and leg pain. However, in determining the surgery program, the surgical operater also should fully recognize that the anatomical differences of Wiltse approach may influence on operation.

Evaluation of smartphone-based testing to generate exploratory outcome measures in a phase 1 Parkinson's disease clinical trial.

BACKGROUND: Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases such as PD, creating a new domain of digital biomarkers. OBJECTIVES: The present study assessed the feasibility, reliability, and validity of smartphone-based digital biomarkers of PD in a clinical trial setting. METHODS: During a 6-month, phase 1b clinical trial with 44 Parkinson participants, and an independent, 45-day study in 35 age-matched healthy controls, participants completed six daily motor active tests (sustained phonation, rest tremor, postural tremor, finger-tapping, balance, and gait), then carried the smartphone during the day (passive monitoring), enabling assessment of, for example, time spent walking and sit-to-stand transitions by gyroscopic and accelerometer data. RESULTS: Adherence was acceptable: Patients completed active testing on average 3.5 of 7 times/week. Sensor-based features showed moderate-to-excellent test-retest reliability (average intraclass correlation coefficient = 0.84). All active and passive features significantly differentiated PD from controls with P < 0.005. All active test features except sustained phonation were significantly related to corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS clinical severity ratings. On passive monitoring, time spent walking had a significant (P = 0.005) relationship with average postural instability and gait disturbance scores. Of note, for all smartphone active and passive features except postural tremor, the monitoring procedure detected abnormalities even in those Parkinson participants scored as having no signs in the corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS items at the site visit. CONCLUSIONS: These findings demonstrate the feasibility of smartphone-based digital biomarkers and indicate that smartphone-sensor technologies provide reliable, valid, clinically meaningful, and highly sensitive phenotypic data in Parkinson's disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.

Background: The tumor microenvironment is an important factor in cancer immunotherapy response. To further understand how a tumor affects the local immune system, we analyzed immune gene expression differences between matching normal and tumor tissue.Methods: We analyzed public and new gene expression data from solid cancers and isolated immune cell populations. We also determined the correlation between CD8, FoxP3 IHC, and our gene signatures.Results: We observed that regulatory T cells (Tregs) were one of the main drivers of immune gene expression differences between normal and tumor tissue. A tumor-specific CD8 signature was slightly lower in tumor tissue compared with normal of most (12 of 16) cancers, whereas a Treg signature was higher in tumor tissue of all cancers except liver. Clustering by Treg signature found two groups in colorectal cancer datasets. The high Treg cluster had more samples that were consensus molecular subtype 1/4, right-sided, and microsatellite-instable, compared with the low Treg cluster. Finally, we found that the correlation between signature and IHC was low in our small dataset, but samples in the high Treg cluster had significantly more CD8+ and FoxP3+ cells compared with the low Treg cluster.Conclusions: Treg gene expression is highly indicative of the overall tumor immune environment.Impact: In comparison with the consensus molecular subtype and microsatellite status, the Treg signature identifies more colorectal tumors with high immune activation that may benefit from cancer immunotherapy. Cancer Epidemiol Biomarkers Prev; 27(1); 103-12. ©2017 AACR.