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Rationale and Objectives: Few data were available regarding the underlying burden of specific plaque types with increasing ages. The aim of this study was to assess the relationship of coronary artery calcium (CAC) score with total coronary plaque burden and the difference of underlying coronary plaque composition across differing aging groups using 64-slice multidetector computed tomography. Materials and Methods: Multidetector computed tomographic images of 781 consecutive patients were evaluated using a 15-coronary segment model. Segment involvement score (the total number of segments with any plaque), segment stenosis score (the sum of maximal stenosis score per segment), total plaque score (the sum of the plaque amount per segment), and plaque composition were measured to compare with total CAC scores stratified by age tertile (lowest [n = 274], <55 years; middle [n = 242], 55-65 years; highest [n = 265], >65 years). Results: The mean age of the study population was 59 ± 13 years (481 men [62%]). With increasing age, higher segment involvement scores, segment stenosis scores, and total plaque scores were noted. Plaque burden was correlated significantly with total CAC scores in all tertiles. The percentage of partially calcified (P < .001) and calcified (P < .001) plaque increased with age, and in the highest age tertile, 87% of plaque contained calcium (calcified or mixed), compared to only 63% in the younger patients (P < .001). Those aged >65 years were highly unlikely to have isolated noncalcified plaque (in the setting of a calcium score of 0). Younger patients were 10 times more likely to have isolated noncalcified plaque (P < .001). Conclusions: The absence of CAC strongly excludes obstructive disease, and CAC predicts the presence of coronary atherosclerotic plaque. However, the absence of any CAC does not exclude the presence of coronary atherosclerotic plaque, especially in patients aged <55 years. Plaque composition shifted from noncalcified to calcified plaque with increasing age, which may affect the vulnerability of these lesions over time. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Left ventricular hypertrophy (LVH) is associated with an increased risk of cardiac death. The present study evaluates whether using computed tomographic (CT)-derived criteria for normal myocardial mass can improve detection of LVH on CT angiography (CTA). Materials and Methods: A total of 2238 subjects (63 +/- 9 years, 27% female) who underwent CTA were studied. To identify normal limits for CT-derived myocardial mass, we studied normal subjects (those without diabetes, hypertension, congestive heart failure, or coronary artery disease). Left ventricular mass (LVM) was measured manually using two different workstations. The CT criteria of LVH was defined as LVM above the 97th percentile per gender and compared to echocardiographic criteria (110 g/m(2) in women; 124 g/m(2) in men), and specificity and sensitivity of both models to detect LVH were calculated. Results: The LVM was higher in men than women in normal cohorts (75.5 +/- 14.0 vs. 63.1 +/- 12.8 g/m(2), P = .001 with electron beam CTA and 78.5 +/- 11.9 vs. 65.0 +/- 9.2 g/m(2), P = .001 with 64 multidetector [MD] CT, respectively). The coefficient of variation between electron beam CTA and 64 MDCT for measuring LVM was 3.1%. Comparing the new CTA/64 MDCT criteria of LVH (103.0 g/m(2) in men; 89.0 g/m(2) in women) to the previous echocardiographic criteria of LVH, the specificity in women and men decreased from 100% in both genders by echocardiography to 91.8% and 92.6%, respectively, but the sensitivity increased from 42.0% to 100% and from 41.1% to 100%. Conclusion: This study suggests that CT-measured LVM has low variability and normal values based on CT criteria will potentially increase the early detection of LVH. [ABSTRACT FROM AUTHOR]

Current 64-multidetector Computed Tomographic scanners (MDCT) utilize retrospective overlapping helical acquisition (RS-OHA) which imparts a higher than desired radiation dose. Although the radiation burden of computed tomographic angiography (CTA) can be efficiently reduced by dose modulation and limiting field of view, a further decrease in radiation without compromising diagnostic image quality would be indeed very desirable. An alternative imaging mode is the axial prospective ECG-triggering acquisition (prospective gating). This study was done to compare the effective radiation dose and the image quality with two techniques to reduce radiation doses with CTA studies utilizing 64-MDCT scanners. The study included 149 consecutive patients (48 females and 101 males) 64-MDCT (mean age = 67 +/- 11 years, 72.2% male). Patients underwent CT coronary angiography using one of three algorithms: retrospective triggering with dose modulation; prospective triggering with padding (step and shoot acquisition with additional adjacent phases); and prospective triggering without padding (single phase acquisition only). Based on body habitus, two different voltages were utilized: 100 kVp (<85 kg) or 120 kVp (>85 kg). Radiation doses and image quality (signal to noise ratio) was measured for each patient, and compared between different acquisition protocols. The signal to-noise ratio of the ascending aorta (SNR-AA) was calculated from the mean pixel values of the contrast-filled left ventricular chamber divided by the standard deviation of these pixel values. Use of 100 kVp reduced radiation dose 41.5% using prospective triggering and 39.6% using retrospective imaging as compared to 120 kVp (P < 0.001). Use of prospective imaging reduced radiation exposure by 82.6% as compared to retrospective imaging (P < 0.001). Using both prospective imaging and 100 kVp without padding (single phase data, no other phases obtained), radiation dose was reduced by 90% (P < 0.001). In terms of image quality, the coefficient of variation of ascending aortic contrast enhancement between kVp of 120 and kVp of 100 was 6% (1.05, 95 CI 0.93-1.17), and 7.8% (0.9, 95% CI 0.7-1.2) at the pulmonary artery. The prospective ECG-Triggered acquisition and 100 kVp images were of diagnostic quality, allowing adequate assessment in all patients. CTA using PA and 100 kVp reduced the radiation dose by up to 90% without compromising the image quality. [ABSTRACT FROM AUTHOR]

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m 2 , respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (- 20.25%, p = 0.006, η p 2  = 0.408), fat mass (FM, - 3.13%, p = 0.033, η p 2  = 0.269), and maximal oxygen consumption (VO 2 max, 11.51%, p = 0.000, η p 2  = 0.601), whereas the HIIT showed significant improvements in body weight (BW, - 1.78%, p = 0.006, η p 2  = 0.433), FM (- 3.94%, p = 0.033, η p 2  = 0.285), and BMI (- 1.80%, p = 0.006, η p 2  = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO 2 max levels than CG (HIIT 12.82%, p = 0.006, η p 2  = 0.088; YG: 11.90%, p = 0.009, η p 2  = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, η p 2  = 0.03) and CG (11.91%, p = 0.022, η p 2  = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness., (© 2024. The Author(s).)

Importance: Olaparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that provides benefit in combination with hormonal therapies in patients with metastatic prostate cancer who harbor homologous recombination repair (HRR) alterations. Its efficacy in the absence of androgen deprivation therapy has not been tested., Objective: To determine the activity of olaparib monotherapy among patients with high-risk biochemically recurrent (BCR) prostate cancer after radical prostatectomy., Design, Setting, and Participants: This phase 2, single-arm nonrandomized controlled trial enrolled genetically unselected patients across 4 sites in the US from May 2017 to November 2022. Eligible patients had BCR disease following radical prostatectomy, a prostate-specific antigen (PSA) doubling time of 6 months or shorter, an absolute PSA value of 1.0 ng/mL or higher, and a testosterone level of 150 ng/dL or higher., Intervention: Treatment was with olaparib, 300 mg, by mouth twice daily until doubling of the baseline PSA, clinical or radiographic progression, or unacceptable toxic effects., Main Outcome and Measure: The primary end point was a confirmed 50% or higher decline in PSA from baseline (PSA50). Key secondary end points were outcomes by HRR alteration status, as well as safety and tolerability., Results: Of the 51 male patients enrolled (mean [SD] age, 63.8 [6.8] years), 13 participants (26%) had a PSA50 response, all within the HRR-positive group (13 of 27 participants [48%]). All 11 participants with BRCA2 alterations experienced a PSA50 response. Common adverse events were fatigue in 32 participants (63%), nausea in 28 (55%), and leukopenia in 22 (43%), and were consistent with known adverse effects of olaparib., Conclusions and Relevance: In this nonrandomized controlled trial, olaparib monotherapy led to high and durable PSA50 response rates in patients with BRCA2 alterations. Olaparib warrants further study as a treatment strategy for some patients with BCR prostate cancer but does not have sufficient activity in those without HRR alterations and should not be considered for those patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03047135.

We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures., Purpose/introduction: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures., Method: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans., Results: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm 3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm 3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm 3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients., Conclusion: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: Nonalcoholic fatty liver disease not only shares multiple risk factors with cardiovascular disease but also independently predicts its increased risk and related outcomes. Here, we evaluate reproducibility of 3-dimensional (3D) liver volume segmentation method to identify fatty liver on noncontrast cardiac computed tomography (CT) and compare measures with previously validated 2-dimensional (2D) segmentation CT criteria for the measurement of liver fat., Methods: The study included 68 participants enrolled in the EVAPORATE trial and underwent serial noncontrast cardiac CT. Liver attenuation < 40 Hounsfield units (HU) was used for diagnosing fatty liver, as done in the MESA study. Two-dimensional and 3D segmentation of the liver were performed by Philips software. Bland-Altman plot analysis was used to assess reproducibility., Results: Interreader reproducibility of 3D liver mean HU measurements was 96% in a sample of 111 scans. Reproducibility of 2D and 3D liver mean HU measurements was 93% in a sample of 111 scans. Reproducibility of change in 2D and 3D liver mean HU was 94% in 68 scans. Kappa, a measure of agreement in which the 2D and 3D measures both identified fatty liver, was excellent at 96.4% in 111 scans., Conclusions: Fatty liver can be reliably diagnosed and measured serially in a stable and reproducible way by 3D liver segmentation of noncontrast cardiac CT scans. Future studies need to explore the sensitivity and stability of measures for low liver fat content by 3D segmentation, over the current 2D methodology. This measure can serve as an imaging biomarker to understand mechanistic correlations between atherosclerosis, fatty liver, and cardiovascular disease risk., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Atrial fibrillation (AF) is a common arrhythmia associated with poor outcomes. N-3 fatty acids have been shown to provide significant cardiovascular risk reduction, but they may exacerbate the risk of AF. The pathway by which N-3 fatty acids may be arrhythmogenic is unknown. One possible mechanism involves cardiac chamber morphology alteration. The purpose of this study was to investigate the effect of icosapent ethyl (IPE) on left atrial (LA) size and left ventricular (LV) mass. This study used coronary computed tomographic angiography images gathered from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis (EVAPORATE) trial. EVAPORATE was a randomised, double-blind, placebo-controlled study finding a significant reduction in coronary atherosclerosis progression in patients with residually elevated triglycerides despite statin therapy on 4 g IPE daily versus 4 g placebo daily. Computed tomography images were used to measure LA size and LV mass at 0 and 18 months. Of 80 enrolled patients, 68 were included in the final analysis. Baseline demographics and risk factors were similar between IPE and placebo cohorts. LA anterior- posterior diameter measured on axial (p=0.51) and sagittal (p=0.52) orientations were not different over time. Also, there was no difference between groups in the change in LA volume (p=0.84). Change in LV mass was similar between groups (p=0.13). In conclusion, this study did not detect differences in LA size or LV mass over 18 months between patients on 4 g daily IPE versus placebo., Competing Interests: Conflicts of interest MGR: Consultant for HeartFlow. DLB: Advisory boards for Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors for Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, and TobeSoft; Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, Svelte; Trustee: American College of Cardiology; Unfunded research: FlowCo, Merck, Takeda. MJB: Amarin grant support and speakers bureau, General electric grant support. SSK, SL, AK, SSM: None declared., (Copyright © 2023 Medinews (Cardiology) Limited.)

Rationale and Objectives: We previously reported a novel manual method for measuring bone mineral density (BMD) in coronary artery calcium (CAC) scans and validated our method against Dual X-Ray Absorptiometry (DEXA). Furthermore, we have developed and validated an artificial intelligence (AI) based automated BMD (AutoBMD) measurement as an opportunistic add-on to CAC scans that recently received FDA approval. In this report, we present evidence of equivalency between AutoBMD measurements in cardiac vs lung CT scans., Materials and Methods: AI models were trained using 132 cases with 7649 (3 mm) slices for CAC, and 37 cases with 21918 (0.5 mm) slices for lung scans. To validate AutoBMD against manual measurements, we used 6776 cases of BMD measured manually on CAC scans in the Multi-Ethnic Study of Atherosclerosis (MESA). We then used 165 additional cases from Harbor UCLA Lundquist Institute to compare AutoBMD in patients who underwent both cardiac and lung scans on the same day., Results: Mean±SD for age was 69 ± 9.4 years with 52.4% male. AutoBMD in lung and cardiac scans, and manual BMD in cardiac scans were 153.7 ± 43.9, 155.1 ± 44.4, and 163.6 ± 45.3 g/cm 3 , respectively (p = 0.09). Bland-Altman agreement analysis between AutoBMD lung and cardiac scans resulted in 1.37 g/cm 3 mean differences. Pearson correlation coefficient between lung and cardiac AutoBMD was R 2 = 0.95 (p < 0.0001)., Conclusion: Opportunistic BMD measurement using AutoBMD in CAC and lung cancer screening scans is promising and yields similar results. No extra radiation plus the high prevalence of asymptomatic osteoporosis makes AutoBMD an ideal screening tool for osteopenia and osteoporosis in CT scans done for other reasons., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Morteza Naghavi reports financial support was provided by American Technologies LLC and HeartLung.AI. Morteza Naghavi reports a relationship with American Technologies LLC and HeartLung.AI that includes: board membership, consulting or advisory, employment, and equity or stocks. Song Shou Mao reports a relationship with The Lundquist Institute that includes: consulting or advisory. Venkat Manubolu reports a relationship with HeartLung.AI that includes: consulting or advisory. Dong Li reports a relationship with HeartLung.AI that includes: consulting or advisory. Thomas Atlas reports a relationship with HeartLung.AI that includes: consulting or advisory. Anthony Reeves reports a relationship with HeartLung.AI that includes: consulting or advisory. Claudia Henschke reports no financial relationship with HeartLung.AI or American Heart Technologies LLC. David Yankelevitz reports a relationship with HeartLung.AI that includes: consulting or advisory. Matthew Budoff reports a relationship with HeartLung.AI that includes: consulting or advisory. Amirhossein Jaberzadeh reports a relationship with HeartLung.AI that includes: employment. Chenyu Zhang reports a relationship with HeartLung.AI that includes: employment. Marlon Montes reports a relationship with HeartLung.AI that includes: employment. Mathew Budoff has patent #US 9119,590 B2 issued to Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA. Mathew Budoff has patent #US 10,695,022,B2 issued to Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA., (© 2023 Published by Elsevier Ltd.)

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Background: Urachal carcinoma (UrC) is a rare, aggressive cancer with a poor prognosis that is frequently diagnosed in advanced stages. Due to its rarity, the current staging systems, namely Sheldon, Mayo, and Ontario were established based on relatively small patient cohorts, necessitating further validation. We used a large patient population from the National Cancer Database to model a novel staging system based on the Tumor (T), Node(N), and Metastasis (M) (TNM) staging system and compared it to established staging systems., Methods: We identified patients diagnosed with UrC between the years of 2004-2016. To determine median overall survival (OS), a Kaplan-Meier (KM) curve was generated using the Sheldon, Mayo, Ontario, and TNM staging system. A cox proportional-hazards regression model was developed to highlight predictors of overall survival., Results: A total of 626 patients were included in the analysis. The OS for the entire cohort was 58.2 months (50.1-67.8) with survival rates at 12, 24, and 60 months of 83%, 70%, and 49%, respectively (p < 0.0001). As compared to the Sheldon, Mayo, and Ontario staging system, our TNM staging system had a more balanced sample and survival distribution per stage and no overlap among stages on KM survival curves. The Mayo, Ontario, and TNM staging systems were more accurate in terms of stage-survival correlation than the Sheldon staging system (p < 0.05 for all stages)., Conclusions: The proposed novel TNM staging system for UrC has a more balanced sample distribution and a more accurate stage-survival correlation than the traditional Mayo, Sheldon, and Ontario staging systems. It is clinically applicable and enables better risk stratification, prognosis, and therapeutic decision-making., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t -test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 ( P =0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t =-4.13, P <0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t =-0.24, 1.36, 1.21; all P >0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z =-3.01, P =0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z =2.44, 3.11, P =0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.

Objective: To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy. Methods: The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children's Hospital, Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected. The general data (gender, age, genotype, and clinical classification, etc.), motor function, nutritional status, scoliosis and respiratory function were analyzed. Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment. Results: The age of 15 cases (7 males, 8 females) was 6.8 (2.8, 8.3) years, with 2 cases of type 1, 6 cases of type 2, and 7 cases of type 3 respectively, and the course of disease was 55.0 (21.0, 69.0) months. After 9.0 (9.0, 24.0) months of treatment, the motor function scale evaluations of the Hammersmith neurological examination section 2 (13.0 (7.0, 23.0) vs. 18.0 (10.0, 25.0) scores, Z =-2.67, P =0.018) of 15 children, the Hammersmith functional motor scale expanded (38.0 (18.5, 45.5) vs. 42.0 (23.0, 51.0) scores, Z =-2.38, P =0.018), and the revised upper limb module (27.0 (19.5, 32.0) vs. 33.0 (22.5, 35.5) scores, Z =-2.52, P =0.012) of children with type 2 and 3 had significantly improved. Thirteen patients achieved clinically significant motor function improvement, and 2 of them had kept stable scale scores. Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment, and no serious adverse reactions were reported. Supplemented by the multi-disciplinary team management, the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved (all P <0.05). Conclusions: Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy, which is also proved safe to be used in children. The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atrophy.

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration. Therefore, investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system. In this study, we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury. We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments, respectively. Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration, while the differentially expressed genes in distal modules promoted neurodegeneration. Next, we constructed hub gene networks for selected modules and identified a key hub gene, Kif22, which was up-regulated in both nerve segments. In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway. Collectively, our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments, and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration. All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University, China (approval No. S20210322-008) on March 22, 2021., Competing Interests: None

Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC)., Objective: To compare the efficacy and safety of the two most commonly used cisplatin-based regimens; gemcitabine, and cisplatin (GC) vs. accelerated (dose-dense: dd) or conventional methotrexate, vinblastine, adriamycin, and cisplatin (MVAC)., Methods: We searched MEDLINE, Embase, Scopus and other sources. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model., Results: We identified 24 studies. Efficacy outcomes were comparable between MVAC and GC for MIBC. dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95%CI 1.15-1.82) and all-cause mortality at longest follow-up (OR 0.63; 95%CI 0.44-0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95%CI 0.13-0.80), anemia (OR 0.32; 95%CI 0.18-0.54), nausea and vomiting (OR 0.27; 95%CI 0.12-0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3-4 thrombocytopenia (OR 4.70; 95%CI 1.59-13.89) and a lower risk of nausea and vomiting (OR 0.05; 95%CI 0.01-0.31). Certainty in the estimates was very low for most outcomes., Conclusions: Efficacy and safety outcomes were comparable between MVAC and GC for MIBC. Including non-peer-reviewed studies showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice., Competing Interests: Raed Benkhadra, Tarek Nayfeh, Sai Krishna Patibandla, Chelsea Peterson, Larry Prokop, Omar Alhalabi, M. Hassan Murad and Shifeng S. Mao declare that they have no conflict of interest., (© 2022 – The authors. Published by IOS Press.)

Background and Aims: Obesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT)., Methods and Results: We retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20-90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm 3 ) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45-55, 55-65, >65 yrs in females; <40,40-60,>60 yrs in Males) and weight by BMI (kg/m 2 ) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40-60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts., Conclusions: We concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population., Competing Interests: Declaration of competing interest Matthew J. Budoff, M.D., FACC discloses work for the National Institutes of Health and General Electric Healthcare; All other authors have no conflicts of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To analyze the trends of HIV/syphilis/HSV-2 seropositive rate and explore the related factors with HSV-2 infection to provide the basis for adjusting STD intervention strategies and formulating prevention and control measures among MSM in Shenzhen., Methods: Time-location sampling was conducted among MSM in Shenzhen in 2012, 2014, 2016, and 2018. Data on demographics, sexual behaviors and the laboratory test results of HIV, syphilis, HSV-2 were collected. The χ2 trend test was used to analyze the trends of HIV/syphilis/HSV-2 seropositive rate. The binary logistic regression model was used to explore the factors associated with HSV-2 infection., Results: The seropositive rate of HIV fell significantly from 15.9% in 2012 to 8.7% in 2018 (Ptrend = 0.003), syphilis seropositive rate was significantly decreased from 20.4% in 2012 to 14.8% in 2018 (Ptrend = 0.025), HSV-2 seropositive rate had no significant change (16.7% in 2012 to 14.0% in 2018; Ptrend = 0.617). In principal component logistic regression analysis showed that FAC1&#95;1 (X1 = Ever had sex with female, X2 = Gender of first sexual partner, X3 = Marital status, X4 = Age group), FAC2&#95;1 (X5 = Education, X6 = Monthly income (RMB), X7 = Frequency of condom use in anal sex with men in the past 6 months), and FAC4&#95;1 (X9 = History of STDs) were significantly associated with HSV-2 infection., Conclusions: The seropositive rates of HIV and syphilis have dropped significantly but are still high. HSV-2 seropositive rate had no significant change and maintained a high level. It is necessary to continue strengthening HIV and syphilis interventions among MSM in Shenzhen. HSV-2 detection and intervention are urgently required for MSM, which might be another effective biological strategy further to control the HIV epidemic among MSM in Shenzhen., Competing Interests: The authors have declared that no competing interests exist.

We intended to assess the ability of current-generation 256-slice coronary CT angiography (CCTA) to measure left atrial volume (LAV), comparing patients with a high heart rate (HiHR) of at least 70 bpm and patients with heart rate variability such as atrial fibrillation (AFib). Methods: Using the prospective Converge Registry of patients undergoing 256-detector CCTA on a Revolution scanner, we enrolled 121 HiHR patients (74 men; mean age, 62.7 ± 12.5 y) and 102 AFib patients (72 men; mean age, 60.5 ± 11.0 y) after obtaining informed consent. Quantitative data analysis of LAV was performed using automated methods, and end-systolic phases were chosen for measurements from CCTA. A Student t test, Wilcoxon rank-sum test, or χ 2 test assessed baseline parameters. Univariate and multivariate linear regression analysis was used to assess LAV and LAV index (LAVI) while adjusting potentially confounding variables. Results: Mean LAV was significantly higher in AFib subjects (148.6 ± 57.2 mL) than in HiHR subjects (102.1 ± 36.5 mL) ( P < 0.0001). Similarly, mean LAVI was significantly higher in AFib subjects (72.4 ± 28.1 mL/m 2 ) than in HiHR subjects (51.5 ± 19.0 mL/m 2 ) ( P < 0.0001). After adjusting for age, body mass index, sex, diabetes, hypertension, hyperlipidemia, and smoking, subjects with AFib had, on average, LAV measures higher by 41.2 ± 6.7 mL and LAVI values higher by 23.1 ± 3.4 mL/m 2 ( P < 0.0001). Conclusion : Misalignment and motion artifacts in CCTA images affect diagnostic CT performance, especially in patients with elevated heart rates or profound arrhythmia. However, the new-generation Revolution CCTA provides detailed information on left-atrium-complex morphology and function, in addition to coronary anatomy, in HiHR and AFib patients without additional radiation, scanning, or contrast requirements., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti-SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens , and Mentha haplocalyx were effective in a challenge study using hamsters as disease model., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

A novel metal/semiconductor photocatalyst, Cu nanoparticles (NPs) modified TiO 2 hollow spheres (Cu/TiO 2 ), was designed for efficient photocatalytic overall water splitting (POWS) under both ultraviolet (UV) and visible (Vis) light. This Cu/TiO 2 photocatalyst possesses excellent POWS performance under Vis light at the highest level among the reported TiO 2 -based photocatalysts. Interestingly, the metal/semiconductor junction formed between Cu and TiO 2 enables controlled water-oxidation product selectivity (H 2 O 2 or O 2 ) via different reaction pathways regulated by irradiation wavelengths. Under UV light, the electrons excited in TiO 2 are captured by Cu NPs through the Cu/TiO 2 Schottky interface for H 2 production, with the photoholes in TiO 2 producing H 2 O 2 through a two-electron process; whilst under Vis light, Cu NPs act as plasmon to inject hot electrons to TiO 2 for H 2 production, while O 2 is produced by hot holes on Cu NPs via a four-electron process. This rational design of function-switchable metal/semiconductor junction may be helpful to understand the mechanisms for POWS with desired gas/liquid water-oxidation products., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020 Science China Press. Published by Elsevier B.V. All rights reserved.)

Fish scales serve as a dermal armor that provides protection from physical injury. Owing to a number of outstanding properties, fish scales are inspiring new concepts for layered engineered materials and next-generation flexible armors. Although past efforts have primarily focused on the structure and mechanical behavior of ontogenetic scales, the structure-property relationships of regenerated scales have received limited attention. In the present study, common carp ( Cyprinus carpio ) acquired from the wild were held live in an aquatic laboratory at 10°C and 20°C. Ontogenetic scales were extracted from the fish for analysis, as well as regenerated scales after approximately 1 year of development and growth. Their microstructure was characterized using microscopy and Raman spectroscopy, and the mechanical properties were evaluated in uniaxial tension to failure under hydrated conditions. The strength, strain to fracture and toughness of the regenerated scales were significantly lower than those of ontogenetic scales from the same fish, regardless of the water temperature. Scales that regenerated at 20°C exhibited significantly higher strength, strain to fracture and toughness than those regenerated at 10°C. The regenerated scales exhibited a highly mineralized outer layer, but no distinct limiting layer or external elasmodine; they also possessed a significantly lower number of plies in the basal layer than the ontogenetic scales. The results suggest that a mineralized layer develops preferentially during scale regeneration with the topology needed for protection, prior to the development of other qualities., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM., (Copyright: © Hutchins et al.)

Rett syndrome (RTT) is a neurodevelopmental disease in children that is mainly caused by mutations in the MeCP2 gene, which codes for a transcriptional regulator. The expression of insulin-like growth factor-1 (IGF-1) is reduced in RTT patients and animal models, and IGF-1 treatment is a promising therapeutic strategy for RTT. However, the mechanism underlying the effects of IGF-1 remains to be further explored. FXYD1 is an auxiliary subunit of Na, K-ATPase. Overexpression of FXYD1 is involved in the pathogenesis of RTT. However, whether IGF-1 exerts its effect through normalizing FXYD1 is completely unknown. To this end, we evaluated the effect of IGF-1 on FXYD1 expression and posttranslational modification in a mouse model of RTT (MeCP2 308 ) using both in vitro and in vivo experiments. The results show that FXYD1 mRNA and phosphorylated protein (p-FXYD1) were significantly elevated in the frontal cortex in RTT mice, compared to wild type. In RTT mice, IGF-1 treatment significantly reduced levels of FXYD1 mRNA and p-FXYD1, in parallel with improvements in behavior, motor coordination, and cognitive function. For mechanistic insight into the effect of IGF-1 on p-FXYD1, we found the decreased phosphorylated forms of PI3K-AKT-mTOR signaling pathway components in the frontal cortex of RTT mice and the normalizing effect of IGF-1 on the phosphorylated forms of these components. Interestingly, blocking the PI3K/AKT pathway by PI3K inhibitor could abolish the effect of IGF-1 on p-FXYD1 level, in addition to the effect of IGF-1 on the phosphorylation of other components in the PI3K/AKT pathway. Thus, our study has provided new insights into the mechanism of IGF-1 treatment for RTT, which appears to involve FXYD1., (Copyright © 2020 Yuan, Mao, Shen, Jiang, Xu, Xu and Gao.)

While the survival rate of preterm infants has continually increased with the development of perinatal and neonatal monitoring techniques, the incidence of brain injury in preterm infants has been increasing, resulting in varying degrees of cognitive impairment and movement disorders. Measuring the biomarkers of brain damage is an important means to diagnose brain injury. The biomarkers can be divided into neuroglial damage markers, neuronal damage markers and other markers according to the features of injured cells. The biomarkers widely used in clinical practice include S100B protein, myelin basic protein and neuron-specific enolase. Recent studies have newly discovered a collection of markers that can suggest potential brain injury in preterm infants, such as glial fibrillary acidic protein, neurofilament light chain protein, α-II spectrin breakdown products, chemokines, melatonin and urinary metabolomics. These biomarkers can contribute to the early diagnosis and treatment of preterm brain injury, essential for improving neural development and prognosis. This article reviews the latest research advances in the biomarkers of preterm brain injury, in order to provide evidence for the early diagnosis and treatment of this condition.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which has increased markedly during the last decades. Essential trace elements play an important role in neurological function and their imbalances are common in children with ASD. The objective of the present study was to investigate whole blood levels of trace elements including zinc (Zn), copper (Cu), iron (Fe), and magnesium (Mg) in Chinese children with ASD. In total, 113 children diagnosed with ASD and 141 age-matched and gender-matched neurotypical children, divided into two gender and age groups of preschool age (2-5 years old) and school (6-10 years old) age, were examined. The quantitative analyses of whole blood trace element contents were performed by using flame atomic absorption spectroscopy. In the present study, the children with ASD generally had lower whole blood levels of Zn than the neurotypical controls. No significant differences in the whole blood Cu, Zn/Cu ratio, Fe, or Mg was detected between the ASD group and the control group. It is notable that whole blood Fe level in boys with ASD was significantly higher than in girls with ASD, and was nearly significant when compared with the control level of boys. After stratification for age, a significant 6% decrease in whole blood Zn levels was detected in preschool-aged children with ASD as compared to the control values. However, this significant ASD-related change was not detected in school-aged children. The whole blood Zn level and Zn/Cu ratio were significantly increased in school-aged children than in preschool-aged children in both ASD and control group. In addition, school-aged children with ASD had a significantly higher level of whole blood Fe than preschool-aged children with ASD. The results of the present study suggest an association between whole blood levels of Zn in Chinese children with ASD.

Effects of a humid environment on the degradation of semiconductors were studied to understand the role of the surface charge on material stability. Two distinctly different semiconductors with the Fermi level stabilization energy E FS located inside the conduction band (CdO) and valence band (SnTe) were selected, and effects of an exposure to 85 °C and 85% relative humidity conditions on their electrical properties were investigated. Undoped CdO films with bulk Fermi level E F below E FS and positively charged surface are very unstable. The stability greatly improves with doping when E F shifts above E FS , and the surface becomes negatively charged. This charge-controlled reactivity is further confirmed by the superior stability of undoped p-type SnTe with E F above E FS . These distinct reactivities are explained by the surface attracting either the reactive OH - or passivating H + ions. The present results have important implications for understanding the interaction of semiconductor surfaces with water or, in general, ionic solutions.

The trap-assisted charge injection in polyfluorene-poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) model systems with an Al or Al/LiF cathode is investigated. We find that inserting 1.3 nm LiF increases electron and hole injections simultaneously and the increase of holes is greater than electrons. The evolution of internal interfaces within polymer light-emitting diodes is observed by transmission electron microscopy, which reveals that the introduction of LiF improves the interface stability at both the cathode (cathode/polymer) and the anode (indium tin oxide (ITO)/PEDOT:PSS). Above-mentioned experimental results have been compared to the numerical simulations with a revised Davids model and potential physical mechanisms for the trap-assisted charge injection are discussed.

Background: Lung cancer screening (LCS) via chest computed tomography (CT) scans can save lives by identifying early-stage tumors. However, most smokers die of comorbid smoking-related diseases. LCS scans contain information about smoking-related conditions that is not currently systematically assessed. Identifying these common comorbid diseases on CT could increase the value of screening with minimal impact on LCS programs. We determined the prevalence of 3 comorbid diseases from LCS eligible scans and quantified related adverse outcomes., Methods: We studied COPD Genetic Epidemiology study (COPDGene ® ) participants (n=4078) who met criteria for LCS screening at enrollment (age > 55 years, and < 80 years, > 30 pack years smoking, current smoker or former smoker within 15 years of smoking cessation). CT scans were assessed for coronary artery calcification (CAC), emphysema, and vertebral bone density. We tracked the following clinically significant events: myocardial infarctions (MIs), strokes, pneumonia, respiratory exacerbations, and hip and vertebral fractures., Results: Overall, 77% of eligible CT scans had one or more of these diagnoses identified. CAC (> 100 mg) was identified in 51% of scans, emphysema in 44%, and osteoporosis in 54%. Adverse events related to the underlying smoking-related diseases were common, with 50% of participants reporting at least one. New diagnoses of cardiovascular disease, emphysema and osteoporosis were made in 25%, 7% and 46%, of participants respectively. New diagnosis of disease was associated with significantly more adverse events than in participants who did not have CT diagnoses for both osteoporosis and cardiovascular risk., Conclusions: Expanded analysis of LCS CT scans identified individuals with evidence of previously undiagnosed cardiovascular disease, emphysema or osteoporosis that corresponded with adverse events. LCS CT scans can potentially facilitate diagnoses of these smoking-related diseases and provide an opportunity for treatment or prevention., Competing Interests: Jeffrey L. Curtis reports grants from the National Heart Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases and the Departments of Defense and Veterans Affairs, outside the scope of this project. Russell P. Bowler reports serving on advisory boards for GlaxoSmithKline, Boehringer Ingelheim and Mylan Pharmaceuticals and has received research grants from GlaxoSmithKline and Boehringer Ingelheim. Meilan K. Han reports consulting work for GlaxoSmithKline, Boehringer Ingelheim, Astra Zeneca and Mylan Pharmaceuticals and research support from Novartis and Sunovion. Edwin K. Silverman reports grant and travel support from GlaxoSmithKline in the past 3 years. Ms. Lowe and Drs. Regan, Make, Lynch, Kinny, Budoff, Mao, Dyer, Beaty, Hokanson, Kern, Humphries, Curran-Everett, van Beek, Crapo and Finigan have nothing to declare., (JCOPDF © 2019.)

Expected for many promising applications in the field of electronics and optoelectronics, a reliable method for the characterization of graphene electrical transport properties is desired to predict its device performance or provide feedback for its synthesis. However, the commonly used methods of extracting carrier mobility from graphene field effect transistor or Hall-bar is time consuming, expensive, and significantly affected by the device fabrication process other than graphene itself. Here we reported a general and simple method to evaluate the electrical transport performance of graphene by the van der Pauw-Hall measurement. By annealing graphene in vacuum to remove the adsorbed dopants and then exposing it in ambient surroundings, carrier mobility as a function of density can be measured with the increase of carrier density due to the dopant re-adsorption from the surroundings. Further, the relationship between the carrier mobility and density can be simply fitted with a power equation to the first level approximation, with which any pair of measured carrier mobility and density can be normalized to an arbitrary carrier density for comparison. We experimentally demonstrated the reliability of the method, which is much simpler than making devices and may promote the standard making for graphene characterization., (Copyright © 2018 Science China Press. Published by Elsevier B.V. All rights reserved.)

An advanced in vitro cervical tumor model was established by 3D printing to study the epithelial-to-mesenchymal transition (EMT), which is a very important stage of dissemination of carcinoma leading to metastatic tumors. A HeLa/hydrogel grid construct composed of gelatin, alginate, Matrigel and HeLa cells was fabricated by forced extrusion in a layer-by-layer fashion. HeLa cells rapidly proliferated, formed spheroids and presented tumorigenic characteristic in the 3D-printed structure. With the supplement of TGF-β, aggregated HeLa cells started to disintegrate, and some of them changed into fibroblast-like spindle morphology, which indicated that EMT was induced. The down-regulation of epithelial marker E-cadherin, and up-regulation of mesenchymal markers such as snail, vimentin and N-cadherin were all observed in the 3D-printed model, and performed differently in 3D and 2D models. The TGF-β induced EMT was inhibited by the treatment of disulfiram and EMT pathway inhibitor C19 in a dose dependent manner, showing great potential for future studies of a therapeutic program towards cervical tumor metastasis.

The peripheral nervous system has the potential to regenerate after nerve injury owing to the intrinsic regrowth ability of neurons and the permissive microenvironment. The regenerative process involves numerous gene expression changes, in which transcription factors play a critical role. Previously, we profiled dysregulated genes in dorsal root ganglion neurons at different time points (0, 3 and 9 hours, and 1, 4 and 7 days) after sciatic nerve injury in rats by RNA sequencing. In the present study, we investigated differentially expressed transcription factors following nerve injury, and we identified enriched molecular and cellular functions of these transcription factors by Ingenuity Pathway Analysis. This analysis revealed the dynamic changes in the expression of transcription factors involved in cell death at different time points following sciatic nerve injury. In addition, we constructed regulatory networks of the differentially expressed transcription factors in cell death and identified some key transcription factors (such as STAT1, JUN, MYC and IRF7). We confirmed the changes in expression of some key transcription factors (STAT1 and IRF7) by quantitative reverse transcription-polymerase chain reaction. Collectively, our analyses provide a global overview of transcription factor changes in dorsal root ganglia after sciatic nerve injury and offer insight into the regulatory transcription factor networks involved in cell death., Competing Interests: The authors declare that there are no conflicts of interest associated with this manuscript

Osteoporosis and atherosclerosis are two prevalent major healthcare concerns that frequently coexist. The clinical outcome of 5590 consecutive subjects who underwent coronary artery calcium (CAC) scanning and thoracic bone mineral density (BMD) measurement was assessed. A significant link between low BMD levels and CAC with increased risk of mortality in both genders across ethnicities noted., Introduction: While a relation of CAC with lower levels of BMD reported previously; it is unclear whether low levels of BMD would be an independent risk factor for CAC and mortality. This study investigated the relation of BMD levels with CAC and mortality in both genders across ethnicities., Methods: This study consisted of 5590 consecutive at-risk subjects without known coronary artery disease (CAD), age 57 ± 12, and 69% male, who underwent non-enhanced cardiac computed tomography, and were followed for mean of 8 years. The subjects' CAC (Agatston score) and thoracic BMD levels (mg/cm 3 ) were measured. CAC stratified based on the severity to CAC 0, 1-100, 101-400, and 400+. Low-BMD levels defined as BMD levels below median (180 mg/cm 3 ). Physician verified that all-cause mortality was assessment hard-endpoint. Multivariate regression analysis, adjusted for age, gender, and other cardiovascular risk factors, was used to assess the relationship between BMD and CAC., Results: The BMD levels were proportionally lowering with the severity of CAC in both genders, especially in postmenopausal women (p < 0.05). The risk of each standard deviation reduce in BMD levels increased with the severity of CAC, as compared to CAC = 0 across ethnicities (p < 0.05). Low BMD levels were an independent predictor of mortality and event-free survival rate decreased from 99% in those within normal BMD levels to 93% in those with low BMD levels (p = 0.0001). Furthermore, a significant link between low BMD levels and CAC > 0 with increased risk of mortality was noted (p = 0.0001). The relative risk of death was 2.8, 5.9, and 14.3-folds higher in CAC 1-100, 101-400, and 400+ with low BMD levels, compared to CAC = 0 and within normal BMD levels, respectively (p < 0.05)., Conclusions: The lower BMD levels are independently associated with the severity of CAC that predicts mortality.

Oxidative stress is known to be associated with various age-related diseases. D-galactose (D-gal) has been considered a senescent model which induces oxidative stress response resulting in memory dysfunction. Pyrroloquinoline quinone (PQQ) is a redox cofactor which is found in various foods. In our previous study, we found that PQQ may be converted into a derivative by binding with amino acid, which is beneficial to several pathological processes. In this study, we found a beneficial glutamate mixture which may diminish neurotoxicity by oxidative stress in D-gal induced mouse. Our results showed that PQQ may influence the generation of proinflammatory mediators, including cytokines and prostaglandins during aging process. D-gal-induced mouse showed increased MDA and ROS levels, and decreased T-AOC activities in the hippocampus, these changes were reversed by PQQ supplementation. Furthermore, PQQ statistically enhanced Superoxide Dismutase SOD2 mRNA expression. PQQ could ameliorate the memory deficits and neurotoxicity induced by D-gal via binding with excess glutamate, which provide a link between glutamate-mediated neurotoxicity, inflammation and oxidative stress. In addition, PQQ reduced the up-regulated expression of p-Akt by D-gal and maintained the activity of GSK-3β, resulting in a down-regulation of p-Tau level in hippocampus. PQQ modulated memory ability partly via Akt/GSK-3β pathway.

Food restriction (FR) is the most commonly used intervention to prevent the overweight. However, the lost weight is usually followed by "compensatory growth" when FR ends, resulting in overweight. The present study was aimed to examining the behavior patterns and hormones mechanisms underpinning the over-weight. Energy budget and body fat content, and several endocrine markers related to leptin signals were examined in the striped hamsters under 20% FR refed by either low-fat diet (LF group) or high-fat diet (HF group). Body mass and fat content significantly regained when FR ended, and the hamsters in HF group showed 49.1% more body fat than in LF group (P < 0.01). Digestive energy intake was higher by 20.1% in HF than LF group, while metabolic thermogenesis and behavior patterns did not differed between the two groups. Gene expression of leptin receptor and anorexigenic peptides of pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript in hypothalamus were significantly up-regulated in LF group, but down-regulated in HF group. It suggests that effective leptin signals to the brain were involved in attenuation of hyperphagia in hamsters refed with LF. However, "leptin resistance" probably occurred in hamsters refed with HF, which impaired the control of hyperphagia, resulting in development of over-weight.

Rationale and Objective: Sensitive detection of bone mineral density (BMD) change is a key issue to monitor and evaluate the individual bone health status, as well as bone metabolism and bone mineral status. The ability to use thoracic quantitative computed tomography (QCT) to detect the annual change of BMD remains unclear. We aimed to investigate the sensitivity in detecting age-related bone mineral loss using the thoracic QCT from the electrocardiographically gated heart scans in comparison to whole-body dual-energy X-ray absorptiometry (DXA) and standard lumbar QCT., Materials and Methods: A total of 121 asymptomatic patients' imaging data, including DXA whole body scan, cardiac CT scan, and abdomen scans were analyzed. The BMD of the thoracolumbar spine, upper, and lower extremities were measured using QCT and DXA, respectively. The age-related annual rate of bone density loss was computed and compared to the thoracic and lumbar QCT, as well DXA measures., Results: The age-related annual rate of bone loss with QCT was -0.70 mg/mL 3 (-0.75%/y) in women, -0.83 mg/mL 3 (-0.86%/y) in men in the thoracic and the lumbar trabecular QCT, respectively. Compared to the QCT, DXA demonstrates a lower annual rate of bone loss in the area of BMD measurement (P < .05 in all, excluding legs of women) in -0.45, -0.42, -0.67, and -0.46 in women, in -0.32, -0.02, -0.12, and -0.08 in men for thoracic, lumbar, leg, and arm, respectively., Conclusion: We conclude that the thoracic and the lumbar QCT provide a similar and more sensitive method for detecting bone mineral loss when compared to DXA., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The overexpression of heat shock protein 70 (HSP70), a major stress-inducible heat shock protein, has been identified to enhance the proliferation, survival, invasion and metastasis of diverse types of human cancer. However, its role in hepatocellular carcinoma (HCC) remains poorly understood. The present study demonstrated that HSP70 expression was higher in tested HCC cell lines, compared with the normal hepatocyte LO2, and the suppression of HSP70 significantly inhibited the proliferation of SMMC-7721 and Hep3B cells. The growth inhibitory effect was mediated by cell cycle arrest at the G 1 /S phase with reduced cyclin D1 and increased p27Kip1 expression. Furthermore, HSP70 knockdown significantly inhibited the migration and invasion abilities of HCC cells. In conclusion, HSP70 is a key regulator involved in the proliferation, migration and invasion of HCC, and it may be used as a potential therapeutic target for HCC.

Three-dimensional (3D) printing (3DP) is a rapid prototyping technology that has gained increasing recognition in many different fields. Inherent accuracy and low-cost property enable applicability of 3DP in many areas, such as manufacturing, aerospace, medical, and industrial design. Recently, 3DP has gained considerable attention in the medical field. The image data can be quickly turned into physical objects by using 3DP technology. These objects are being used across a variety of surgical specialties. The shortage of cadaver specimens is a major problem in medical education. However, this concern has been solved with the emergence of 3DP model. Custom-made items can be produced by using 3DP technology. This innovation allows 3DP use in preoperative planning and surgical training. Learning is difficult among medical students because of the complex anatomical structures of the liver. Thus, 3D visualization is a useful tool in anatomy teaching and hepatic surgical training. However, conventional models do not capture haptic qualities. 3DP can produce highly accurate and complex physical models. Many types of human or animal differentiated cells can be printed successfully with the development of 3D bio-printing technology. This progress represents a valuable breakthrough that exhibits many potential uses, such as research on drug metabolism or liver disease mechanism. This technology can also be used to solve shortage of organs for transplant in the future.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Src is involved in multiple processes of cancer metastasis; however, its significance in HCC is not well defined. In the present study, overexpression of Src phosphorylation (Y416) was observed in the highly metastatic MHCC97H cell line; additionally, through inhibition of Src kinase activation, HCC cell proliferation, migration, invasion and colony formation were significantly reduced in vitro. Tumour growth was not affected in the orthotopic xenograft HCC model, but the metastasic potential was inhibited as revealed by reduced lung metastasic foci after administration of saracatinib. Phosphorylation level of Src pathway signalling molecules, such as Src, FAK and Stat3, were also reduced in vitro and in vivo, as a result of the anti-metastasic effects caused by saracatinib treatment. In conclusion, we demonstrated the pro-metastasic role of Src in HCC, and further experiments suggest the use of the Src inhibitor in combination with cytotoxic agents and other anticancer treatments to improve HCC prognosis.

Background: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS., Case Presentation: Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS., Conclusion: Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.

Osteoporosis is a common metabolic bone disease, causing increased skeletal fragility characterized by a low bone mass and trabecular microarchitectural deterioration. Assessment of the bone mineral density (BMD) is the primary determinant of skeletal fragility. Computed tomography (CT)-based trabecular microarchitectural and mechanical assessments are important methods to evaluate the skeletal strength. In this review, we focus the feasibility of QCT BMD measurement using a calibration phantom or phantomless. The application of QCT could extend the bone mineral density assessment to all patients who underwent a heart, lung, whole-body, and as well as all routine clinical implications of CT scan., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Reversible bilateral striatal necrosis associated with Mycoplasma pneumoniae (M. pneumoniae) infection is a rare neurological disease. The exact pathogenic mechanism remains unknown., Patient: We report reversible bilateral striatal lesions with a favorable outcome secondary to M. pneumoniae infection in an 8-year-old Chinese girl. Cranial MRI showed abnormal signals in bilateral striatum, which disappeared 8 months later. To better understand the pathogenesis of this encephalopathy, we examined cytokines levels in serum and cerebrospinal fluid from this patient. The results revealed the concentrations of interleukin-6 and interleukin-8 increased significantly in serum (26 pg/mL and 66 pg/mL, respectively) and cerebrospinal fluid (122 pg/mL and 325 pg/mL, respectively), and were reduced markedly after the therapy. Intrathecal production of interleukin-6 and interleukin-8 is probably related to the pathogenesis of striatal lesions caused by M. pneumoniae. These cytokines may cause local vascular injury, and finally leading to local vascular occlusion., Conclusion: Our results suggest that interleukin-6 and interleukin-8 may play important roles in the pathogenesis of this disease. This is the first report to describe the role of cytokines in this condition and relevant literature is reviewed. Our findings may lead to better understanding of the pathogenesis of M. pneumoniae-associated striatal lesions., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to assess accuracy and precision of quantitative computed tomography (QCT) and phantomless in thoracic bone mineral density (BMD) assessment using coronary artery calcium scan (CACS)., Methods: A total of 513 subjects underwent CACS with a calibration phantom. The thoracic spine BMD and concentration of calcium hydroxyapatite in phantom rods, as well CT Hounsfield unit of both, were measured. The thoracic BMD and phantom-rods calcium concentration were obtained using phantomless. The accuracy and precision error of QCT and phantomless were compared., Results: The mean biases from true calcium concentration of phantom rods were 2.9% and 3.8% for the QCT and phantomless, respectively (P < 0.001). The biases of thoracic BMD from QCT by phantomless were 3.8% with a similar precision error in both methods., Conclusions: The thoracic BMD can be assessed accurately and precisely using QCT and phantomless with a routine CACS.