A body map of somatic mutagenesis in morphologically normal human tissues.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

Application of individualized differential expression analysis in human cancer proteome.

Liquid chromatography-mass spectrometry-based quantitative proteomics can measure the expression of thousands of proteins from biological samples and has been increasingly applied in cancer research. Identifying differentially expressed proteins (DEPs) between tumors and normal controls is commonly used to investigate carcinogenesis mechanisms. While differential expression analysis (DEA) at an individual level is desired to identify patient-specific molecular defects for better patient stratification, most statistical DEP analysis methods only identify deregulated proteins at the population level. To date, robust individualized DEA algorithms have been proposed for ribonucleic acid data, but their performance on proteomics data is underexplored. Herein, we performed a systematic evaluation on five individualized DEA algorithms for proteins on cancer proteomic datasets from seven cancer types. Results show that the within-sample relative expression orderings (REOs) of protein pairs in normal tissues were highly stable, providing the basis for individualized DEA for proteins using REOs. Moreover, individualized DEA algorithms achieve higher precision in detecting sample-specific deregulated proteins than population-level methods. To facilitate the utilization of individualized DEA algorithms in proteomics for prognostic biomarker discovery and personalized medicine, we provide Individualized DEP Analysis IDEPAXMBD (XMBD: Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.) (https://github.com/xmuyulab/IDEPA-XMBD), which is a user-friendly and open-source Python toolkit that integrates individualized DEA algorithms for DEP-associated deregulation pattern recognition.

Using a Sensor-Embedded Baseball to Identify Finger Characteristics Related to Spin Rate and Pitching Velocity in Pitchers.

BACKGROUND: Previous investigations have shown a positive relationship between baseball pitching velocity and the kinetic chain involved in pitching motion. However, no study has examined the influence of finger characteristics on pitching velocity and rate of spin via a sensor-embedded baseball. METHODS: Twenty-one pitchers volunteered and were recruited for this study. An experimental baseball embedded with a force sensor and an inertial measurement unit was designed for pitching performance measurement. Finger length and strength were measured as dependent variables. Spin rate and velocity were independent variables. Pearson product-moment correlations (r) and intraclass correlation coefficients (ICCs) determined the relationship between finger characteristics and pitching performance. RESULTS: Finger length discrepancy, two-point pinch strength, index finger RFD (rate of force development), middle finger impulse, and force discrepancy had significant correlations with spin rate (r = 0.500~0.576, p ≤ 0.05). Finger length discrepancy, two-point pinch, three-point pinch strength, index and middle finger RFD, middle finger impulse, and force combination had significant correlations with fastball pitching velocity (r = 0.491~0.584, p ≤ 0.05). CONCLUSIONS: Finger length discrepancy, finger pinch strength, and pitching finger force including maximal force and RFD may be factors that impact fastball spin rate and fastball pitching velocity.

NLRP3 inflammasome is involved in the mechanism of the mitigative effect of lycopene on sulfamethoxazole-induced inflammatory damage in grass carp kidneys.

Freshwater environmental antibiotic pollution is becoming more severe because of the irregular use of sulfonamide antibiotics. Sulfamethoxazole (SMZ) is a kind of antibiotic that can cause harm to the urinary systems of organisms. However, the toxic impacts of environment-related concentrations of antibiotics in fish have not been thoroughly studied. Lycopene (LYC) has the property of alleviating antibiotic toxicity by diminishing oxidative stress and inflammation. This investigation is intended to examine the instrument of the mitigative part of LYC on SMZ-caused renal inflammatory injury in grass carp. Grass carp were born with SMZ (0. 3 µg L-1) and LYC (10 mg/kg body weight) for 30 days. Serum was used to measure creatinine (CREA) and urea nitrogen (BUN) contents; what is more, kidneys were used to measure histological structure, oxidative stress indicators, relative expressions of cytokines, and inflammatory factors. We found that SMZ exposure significantly increased oxidative stress, characterized by decreased catalase activity (CAT) and superoxide dismutase (SOD). In addition, inflammation-related factors: interleukin (IL-18, IL-6, and IL-1ß), an apoptotic speck-containing protein with a card (ASC), NOD-like receptor protein3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), tumor necrosis factor-α (TNF-α), and nuclear factor-activated B cells (NF-κB) expression increased significantly contrasted with those control group. Inflammatory reactions and ultrastructural changes accompany. LYC administration alleviated the changes mentioned above. In conclusion, In conclusion, these results suggest a protective effect of LYC dietary supplements against kidney damage caused by SMZ. LYC is expected to prevent and treat oxidative stress and chronic inflammation caused by antibiotics as a critical component in the fish breeding diet.

Lycopene attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/NF-κB balance in sulfamethoxazole-induced neurotoxicity in grass carp (Ctenopharyngodon Idella).

All drugs that can penetrate the blood-brain barrier (BBB) may lead to mental state changes, including the widely used anti-infective drug sulfamethoxazole (SMZ). Herein, we investigated whether lycopene (LYC) could ameliorate SMZ-induced brain injury and the postulated mechanisms involved. A total of 120 grass carps were exposed under SMZ (0.3 µg/L, waterborne) or LYC (10 mg/kg fish weight, diet) or their combination for 30 days. Firstly, brain injury induced by SMZ exposure was suggested by the damage of BBB (decreases of Claudins, Occludin and Zonula Occludens), and the decrease of neurotransmitter activity (AChE). Through inducing oxidative stress (elevations of malondialdehyde and 8-hydroxy-2 deoxyguanosine, inhibition of glutathione), SMZ increased the intra-nuclear level of NF-κB and its target genes (TNF-α and interleukins), creating an inflammatory microenvironment. As a positive feed-back mechanism, apoptosis begins with activation of pro-death proteins (Bax/Bcl-2) and activation of caspases (caspase-9 and caspase-3). Meanwhile, a compensatory upregulation of constitutive Nrf2 and its downstream antioxidative gene expression (NAD(P)H Quinone Dehydrogenase 1 and Heme oxygenase 1) and accelerated autophagy (increases of autophagy-related genes and p62 inhibition) were activated as a defense mechanism. Intriguingly, under SMZ stress, LYC co-administration decreased NF-κB/apoptosis cascades and restored Nrf2/autophagy levels. The neuroprotective roles of LYC make this natural compound a valuable agent for prevention SMZ stress in environment. This study suggests that LYC might be developed as a potential candidate for alleviating environmental SMZ stress in aquaculture.

ROS-Induced Hepatotoxicity under Cypermethrin: Involvement of the Crosstalk between Nrf2/Keap1 and NF-κB/iκB-α Pathways Regulated by Proteasome.

Cypermethrin (CMN) is a man-made insecticide, and its abuse has led to potential adverse effects, particularly in sensitive populations such as aquatic organisms. The present study was focused on the toxic phenotype and detoxification mechanism in grass carp (Ctenopharyngodon idella) after treatment with waterborne CMN (0.651 µg/L) for 6 weeks in vivo or 6.392 µM for 24 h in vitro. In vivo, we describe the toxic phenotype of the liver of grass carp in terms of pathological changes, serum transaminase levels, oxidative stress indexes, and apoptosis rates. RNA-Seq analysis (2 × 3 cDNA libraries) suggested a compromise of proteasome and oxidative phosphorylation signaling pathways under CMN exposure. Thus, these two pathways were chosen for the in vitro study, which suggested that the CMN intoxication-induced proteasome pathway caused hepatotoxicity in the liver cell line of grass carp (L8824 cells). Moreover, pretreatment with MG132, a proteasome inhibitor, displayed protection against the toxic effects of CMN by enhancing antioxidative and anti-inflammatory capability by directly inhibiting the proteasomal degradation of nuclear factor erythroid-2 related factor (Nrf2) and IκB-α, thus turning on the transcription of downstream genes of Nrf2 and NF-κB, respectively. Taken together, these results suggest proteasome activity as a reason for CMN-induced hepatotoxicity.

Prefabricated Expanded Flap Combined With Expanded Scalp Flap for Total Face Resurfacing.

ABSTRACT: Reconstruction of total facial deformities and defects has been a major challenge of reconstructive surgery. Allotransplantation is limited by the number of donors and the need for life-long immunosuppression. Autotransplantation, where multiple autogenous tissue grafts from various donor sites are used to repair facial defects, inevitably leaves conspicuous patchwork scars. A prefabricated monoblock flap, although the preferred treatment modality, is limited by insufficient blood supply and the large size of the flap. In the Journal of Craniofacial Surgery (2014;25:21-25), Li et al applied the technique of flap prefabrication and stem cell-assisted tissue expansion to reconstruct total facial injuries, but the operations were complicated and the final expanded flap area was also uncertain. This article introduces an approach to reconstruct total facial injuries with a prefabricated expanded thoracic flap combined with an expanded scalp flap (called combined flaps), which not only solves the limitations of blood supply and expanded volume but also reduces patchwork scars. The approach is a simple, feasible, and effective surgical method for total face resurfacing.

Zinc exerts its renal protection effect on arsenic-exposed common carp: A signaling network comprising Nrf2, NF-κB and MAPK pathways.

Epidemiological and laboratory investigations have extensively indicated that arsenic exposure accounts for several kidney diseases. Zinc has been suggested as a possible natural preventive and therapeutic agent. This study is designed to explore the beneficial effect of zinc supplementation against arsenic-induced renal toxicity in common carp, and the results point to signaling pathway possibly compromised. In the present study, renal injury was induced in common carp by waterborne exposure to arsenic (2.83 mg/L) for 30 days, and zinc (1 mg/L) was simultaneously supplemented. First, the arsenic-exposed fish showed histological and functional renal alterations (indicated by hematoxylin-eosin staining, biochemical indexes and a TUNEL assay). Moreover, as a reactive oxygen species (ROS) stimulant, arsenic was found to induce oxidative toxicity as determined by increased renal ROS, malondialdehyde, protein carbonyl and 8-hydroxydeoxyguanosine levels. When antioxidant-mediation attempts (through superoxide dismutase and glutathione)-mediated to restore homeostasis failed and ROS increased to extreme levels, inflammation (indicated by elevated inducible nitric oxide synthetase, tumor necrosis factor-alpha and interleukins levels) and apoptosis (through both mitochondrial- and death receptor-dependent pathways) were triggered. However, abnormalities in the upstream mediators Nrf2, NF-κB and MAPK were significantly ameliorated and blocked by treatment with zinc. In conclusion, zinc exerts a substantial protective effect against arsenic-triggered subchronic renal injury in common carp via the amelioration of oxidative stress, suppression of apoptosis and reduced inflammation through Nrf2, NF-κB and MAPK signaling.

As3+ or/and Cu2+ exposure triggers oxidative stress imbalance, induces inflammatory response and apoptosis in chicken brain.

Arsenic (As) and copper (Cu) are common environmental pollutants in nature. When they are excessively present in living organisms, they can cause heavy metal poisoning. There were relatively few studies of the toxicological concentrations of As and Cu in the brain using chicken as a model. Therefore, in this study, arsenic trioxide or/and copper sulfate were added to chicken diets for a 12-week toxicity test. The test results showed that excessive intake of As or/and Cu led to a significant reduction in the total antioxidant capacity (T-AOC), catalase (CAT) and hydroxyl radicals. And significant increase in nitric oxide synthase (NOS) indicates an imbalanced oxidation reaction. In addition, the increase in heat shock protein (HSPs), the increase of NF-κB pathway-related pro-inflammatory mediators, the change of apoptosis factors on the death receptor and mitochondrial apoptosis pathway show that, As or/and Cu exposure induced chicken brain has heat shock response (HSP), tissue inflammation and apoptosis. This damage is inseparable from the oxidative imbalance. It is worth noting that these injury changes are time-dependent, and the combined effect of these two metals is more severe than that of a single group of injuries. Our findings can inform the regulation of animal feed additives and avoid agricultural economic losses or biological health damage.

Training Program With Outdoor Fitness Equipment in Parks Offers No Substantial Benefits for Functional Fitness in Active Seniors: A Randomized Controlled Trial.

Outdoor fitness equipment (OFE) is installed in parks to promote health, particularly among seniors. However, no quantitative study has investigated its effectiveness. Therefore, this study aimed to examine the effectiveness of 12 weeks of OFE training on functional fitness in seniors. Forty-two active seniors were recruited and randomly assigned into OFE and control groups. The OFE group underwent 12 weeks of training using popular OFE for cardiorespiratory function, flexibility, and strength, whereas participants in the control group were asked to maintain their previous lifestyles. The senior fitness test was assessed before and after the 12-week period. Unexpectedly, the results showed no significant improvement within or between the groups after the 12-week training in all parameters (p > .05). In conclusion, the 12-week OFE training failed to enhance functional fitness among active seniors. Potential reasons for the limited training effects might be lack of resistance components and diversity of the OFE design and installation.

Personalized analysis of human cancer multi-omics for precision oncology.

Multi-omics technologies, encompassing genomics, proteomics, and transcriptomics, provide profound insights into cancer biology. A fundamental computational approach for analyzing multi-omics data is differential analysis, which identifies molecular distinctions between cancerous and normal tissues. Traditional methods, however, often fail to address the distinct heterogeneity of individual tumors, thereby neglecting crucial patient-specific molecular traits. This shortcoming underscores the necessity for tailored differential analysis algorithms, which focus on particular patient variations. Such approaches offer a more nuanced understanding of cancer biology and are instrumental in pinpointing personalized therapeutic strategies. In this review, we summarize the principles of current individualized techniques. We also review their efficacy in analyzing cancer multi-omics data and discuss their potential applications in clinical practice.

What determinants of COVID-19 vaccine hesitancy among Chinese nursing students? A cross-sectional study.

Background: The coronavirus disease 2019 (COVID-19) continues to threaten human health, and health professionals, including nursing students, usually work in healthcare frontiers with a high risk of infection. Vaccination is currently one of the most effective preventive measures. This study aimed to explore the determinants of COVID-19 vaccine hesitancy in nursing students. Methods: In November 2022, a sample of undergraduate nursing students was recruited from several medical schools in Anhui Province, China, and an online cross-sectional survey was conducted using the questionnaire star platform (Wenjuanxin). A Chi-square test was used to explore vaccine hesitancy among nursing students with different social demographic characteristics and vaccine attitudes. Binary logistic regression analysis was then used to determine the influence factors of vaccine hesitancy among nursing students. Results: A total of 1,090 valid samples were collected in this study. Of these, 27.06% (295) of nursing students reported COVID-19 vaccine hesitancy. The results showed "the need to go out of town recently" (OR = 0.670), "very confident that the outbreak could be controlled sustainably" (OR = 0.393), "feeling at risk of infection" (OR = 0.658), "not being worried/being generally worried about the vaccine's safety" (OR = 0.226 and OR = 0.686, respectively), and "not being worried about the vaccine's effectiveness" (OR = 0.411). These five factors are protective factors associated with COVID-19 vaccine hesitancy in nursing students. The factors "considering the country completely safe from an outbreak" (OR = 3.436), "considering themselves safe because others are vaccinated" (OR = 2.239), and "Agreeing that other protective measures can be relaxed after vaccination with the COVID-19 vaccine" (OR = 2.007) are risk factors associated with COVID-19 vaccine hesitancy among nursing students (P < 0.05). Conclusion: Overall, relatively few nursing students had COVID-19 vaccine hesitancy. Schools and relevant institutions still need to actively guide them to improve their confidence in the COVID-19 vaccine, strengthen the prevention and control measures of the epidemic, and improve their awareness of the crisis to improve the vaccination rate to reduce the COVID-19 vaccine hesitancy in nursing students.

Performance enhancement among adolescent players after 10 weeks of pitching training with appropriate baseball weights.

Compared with regulation-weight baseballs, lightweight baseballs generate lower torque on the shoulder and elbow joints without altering the pitching movement and timing. This study investigates the throwing accuracy, throwing velocity, arm swing velocity, and maximum shoulder external rotation (MSER) of adolescent players after 10 weeks of pitching training with appropriate lightweight baseballs. We assigned 24 adolescent players to a lightweight baseball group (group L) and a regulation-weight baseball group (group R) based on their pretraining throwing velocity. Both groups received pitching training 3 times per week for 10 weeks with 4.4- and 5-oz baseballs. The players' throwing accuracy, throwing velocity, arm swing velocity, and MSER were measured from 10 maximum efforts throws using a regulation-weight baseball before and after undergoing the pitching training. The results showed that the players in group L significantly increased their throwing velocity and arm swing velocity (p < 0.05) after 10 weeks of pitching training with the 4.4-oz baseball, whereas group R did not (p > 0.05). Furthermore, the percentage change in the throwing velocity and arm swing velocity of group L was significantly superior to that of group R (p < 0.05). Thus, we concluded that the 10 weeks of pitching training with an appropriate lightweight baseball substantially enhanced the arm swing velocity and throwing velocity of the adolescent baseball players. These findings suggest that using a lightweight baseball, which can reduce the risk of injury without altering pitching patterns, has positive training effects on players in the rapid physical growth and technique development stage.

Zinc-Mediated Endoplasmic Reticulum Stress and Metallothionein Alleviate Arsenic-Induced Cardiotoxicity in Cyprinus Carpio.

Arsenic (As) is a natural component of the Earth's crust, and its inorganic form is highly toxic. The problem of As pollution in water is extremely urgent, and its impact on aquatic organisms should be widely considered. Here, 120 common carp were selected as the test subjects and were exposed to environmentally relevant concentrations of As (2.83 mg L- 1) for 30 days. Histomorphological observations showed the adverse effects of As on the heart: irregular arrangement of myocardial fibers, rupture of muscle fiber bundles, inflammatory infiltration, and hemorrhages. Mechanistically, abnormal expression of factors related to As-induced inflammation (TLR4/MYD88/NF-κB pathway), endoplasmic reticulum stress (CHOP, GRP78, ATF6, PERK, IRE1) and oxidative stress (SOD, CAT, Nrf2, HO-1) was observed. Then, we tried to find a protective agent against As-induced myocardial injury. As one of the important metal elements for maintaining cell growth and immunity, zinc (Zn, 1 mg L- 1) significantly alleviated the pathological abnormalities induced by As, and the changes in physiological and biochemical indices in response to As exposure were significantly alleviated by Zn administration, which was accompanied by the restoration of metallothionein (ZIP8, Znt1, Znt5, Znt7) and heat shock protein (HSP60, HSP70, HSP90) expression. These results suggest for the possibilty of developing Zn as a candidate therapeutic agent for As induced aquatic toxicology.

PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.

BACKGROUND: The ubiquitin-proteasome and autophagy-lysosomal systems collaborate in regulating the levels of intracellular proteins. Dysregulation of protein homeostasis is a central feature of malignancy. The gene encoding 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) of the ubiquitin-proteasome system is an oncogene in various types of cancer. However, the detailed role of PSMD2 in autophagy and its relationship to tumorigenesis in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we have investigated the tumor-promoting roles of PSMD2 in the context of autophagy in ESCC. METHODS: Molecular approaches including DAPgreen staining, 5-Ethynyl-2'-deoxyuridine (EdU), cell counting kit 8 (CCK8), colony formation, transwell assays, and cell transfection, xenograft model, immunoblotting and Immunohistochemical analysis were used to investigate the roles of PSMD2 in ESCC cells. Data-independent acquisition (DIA) quantification proteomics analysis and rescue experiments were used to study the roles of PSMD2 in ESCC cells. RESULTS: We demonstrate that the overexpression of PSMD2 promotes ESCC cell growth by inhibiting autophagy and is correlated with tumor progression and poor prognosis of ESCC patients. DIA quantification proteomics analysis shows a significant positive correlation between argininosuccinate synthase 1 (ASS1) and PSMD2 levels in ESCC tumors. Further studies indicate that PSMD2 activates the mTOR pathway by upregulating ASS1 to inhibit autophagy. CONCLUSIONS: PSMD2 plays an important role in repressing autophagy in ESCC, and represents a promising biomarker to predict prognosis and a therapeutic target of ESCC patients.

Polystyrene microplastics up-regulates liver glutamine and glutamate synthesis and promotes autophagy-dependent ferroptosis and apoptosis in the cerebellum through the liver-brain axis.

Microplastics (MPs), which are emerging environmental pollutants, remain uncertainties in their toxic mechanism. MPs have been linked to severe liver metabolic disorders and neurotoxicity, but it is still unknown whether the abnormal metabolites induced by MPs can affect brain tissue through the liver-brain axis. Exposed to MPs of chickens results in liver metabolic disorders and increased glutamine and glutamate synthesis. The relative expression of glutamine in the C group was -0.862, the L-PS group was 0.271, and the H-PS group was 0.592. The expression of tight junction proteins in the blood-brain barrier (BBB) was reduced by PS-MPs. Occludin protein expression decreased by 35.8%-41.2%. Claudin 3 decreased by 19.6%-42.3%, and ZO-1 decreased by 28.3%-44.6%. Excessive glutamine and glutamate cooperated with PS-MPs to inhibit the Nrf2-Keap1-HO-1/NQO1 signaling pathway and triggered autophagy-dependent ferroptosis and apoptosis. GPX protein expression decreased by 30.9%-38%. LC3II/LC3I increased by 54%, and Caspase 3 increased by 45%. Eventually, the number of Purkinje cells was reduced, causing neurological dysfunction. In conclusion, this study provides new insights for revealing the mechanism of nervous system damaged caused by PS-MPs exposed in chickens.

Oxidative stress is involved in the activation of NF-κB signal pathway and immune inflammatory response in grass carp gill induced by cypermethrin and/or sulfamethoxazole.

At present, the concentration of environmental pollutants, such as pesticides and antibiotics exposed in environment, especially in aquatic environment is increasing. Research on environmental pollutants has exploded in the last few years. However, studies on the combined effects of pesticides and antibiotics on fish are rare, especially the toxic damage to gill tissue is vague. In this paper, cypermethrin (CMN) and sulfamethoxazole (SMZ) were analyzed and found that there was a strong correlation between the pathways affected by the first 30 genes regulated by CMN and SMZ, respectively. Therefore, the toxic effects of CMN (0.651 µg L-1) and/or SMZ (0.3 µg L-1) on grass carp gill were studied in this paper. Histopathology, quantitative real-time PCR, and other methods were used to detect the tissue morphology, oxidative stress level, inflammation, and apoptosis-related indicators of the fish gills after exposure of 42 days. It was found that compared with the single exposure (CMN/SMZ) group, the combined exposure (MIX) group had a more pronounced oxidative stress index imbalance. At the same time, nuclear factor-κB (NF-κB) signal pathway was activated and immuno-inflammatory reaction appeared in MIX group. The expression of tumor necrosis factor (TNF-α) in the rising range is 2.94 times that of the C group, while the expression of interleukin 8 (IL-8) is as high as 32.67 times. This study reveals the harm of CMN and SMZ to fish, and provides a reference and basis for the rational use of pesticides and antibiotics.

Validity of the Favero Assioma Duo Power Pedal System in Maximal-Effort Cycling Tests.

PURPOSE: The pedal-based power meter has its advantages, so it has become a popular monitoring tool in cycling. This study aimed to examine the validity of the Favero Assioma Duo power pedal system (FAD) in comparison with the SRM, which is considered the gold standard under maximal-effort cycling conditions, and a widely used cycling test, the 20-minute Functional Threshold Test. METHODS: Fourteen male adolescent cyclists completed a series of cycling intervals including 5, 15, 30, 60, 240, 600, and 1200 seconds (20-min Functional Threshold Test) with their maximal-effort performance on 2 separate days. Power output data were collected from the FAD and the SRM for analysis. RESULTS: Extremely strong correlations and excellent intraclass correlation coefficients (ICCs) were found between the power output values registered with the FAD and the SRM overall (r > .999, ICC = .996) and each power test (r > .98, ICC > .91). A low bias was found in power tests of longer durations (-3.2% at 240-s test, -3.3% at 600-s test, and -3.1% at 20-min Functional Threshold Test), while the bias augmented in shorter intervals (-2.7% at 5-s test, -3.6% at 15-s test, and -2.6% at 30-s test and -3.3% at 60-s test). A regression equation was proposed as y = -2.943 + 0.976x to diminish the bias (-0.2 W) with increased r value (>.98) and ICC (>.98). CONCLUSION: The FAD appears to be a valid tool for the measures of maximal-effort performance. The recorded power value reflects the true value with proposed regression equation.

Multi-omic characterization of genome-wide abnormal DNA methylation reveals diagnostic and prognostic markers for esophageal squamous-cell carcinoma.

This study investigates aberrant DNA methylations as potential diagnosis and prognosis markers for esophageal squamous-cell carcinoma (ESCC), which if diagnosed at advanced stages has <30% five-year survival rate. Comparing genome-wide methylation sites of 91 ESCC and matched adjacent normal tissues, we identified 35,577 differentially methylated CpG sites (DMCs) and characterized their distribution patterns. Integrating whole-genome DNA and RNA-sequencing data of the same samples, we found multiple dysregulated transcription factors and ESCC-specific genomic correlates of identified DMCs. Using featured DMCs, we developed a 12-marker diagnostic panel with high accuracy in our dataset and the TCGA ESCC dataset, and a 4-marker prognostic panel distinguishing high-risk patients. In-vitro experiments validated the functions of 4 marker host genes. Together these results provide additional evidence for the important roles of aberrant DNA methylations in ESCC development and progression. Our DMC-based diagnostic and prognostic panels have potential values for clinical care of ESCC, laying foundations for developing targeted methylation assays for future non-invasive cancer detection methods.

Effects of training with a dynamic moment of inertia bat on swing performance.

The purpose of this study was to investigate the effects of the 8-week dynamic moment of inertia (DMOI) bat training on swing velocity, batted-ball speed, hitting distance, muscle power, and grip force. The DMOI bat is characterized in that the bat could be swung more easily by reducing the moment of inertia at the initial stage of swing without decreasing the bat weight and has a faster swing velocity and lower muscle activity. Seventeen varsity baseball players were randomly assigned to the DMOI bat training group (n = 9) and the normal bat training group (n = 8). The training protocol was 7 swings each set, 5-8 sets each time, 3 times each week, and 8 weeks' training period. The results showed that the swing training with the DMOI bat for 8 weeks significantly increased swing velocity by about 6.20% (96.86 ± 8.48 vs. 102.82 ± 9.93 km·h(-1)), hitting distance by about 6.69% (80.06 ± 9.16 vs. 84.99 ± 7.26 m), muscle power of the right arm by about 12.04% (3.34 ± 0.41 vs. 3.74 ± 0.61 m), and muscle power of the left arm by about 8.23% (3.36 ± 0.46 vs. 3.61 ± 0.39 m) (p < 0.05). Furthermore, the DMOI bat training group had a significantly better change percentage in swing velocity, hitting distance, and grip force of the left hand than did the normal bat training group (p < 0.05). The findings suggested that the swing training with the DMOI bat has a positive benefit on swing performance and that the DMOI bat could be used as a new training tool in baseball.