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Simple Summary: Alanyl-glutamine dipeptide carries utmost importance for the poultry industry due to its potential for enhancing various aspects of health and performance in laying birds. Glutamine is an important energy source for highly prolific immune cells and intestinal epithelial cells, and it plays a role in protein degradation, cell defense, cell repair, and is a precursor of glutathione. By improving growth, nutrient digestibility, digestive enzyme activity, immunity and antioxidant status, it can lead to the development of more productive and stress tolerant laying birds which can ultimately benefit poultry producers and consumers by reducing feed costs, mortality rates and improving egg production. Alanyl-glutamine (Aln-Gln), a highly soluble and stable Glutamine-dipeptide, is known to improve the performance of poultry birds. This study aimed to investigate the effect of Aln-Gln during the rearing period on growth performance, nutrient digestibility, digestive enzyme activity, immunity, antioxidant status and relative gene expression of Hy-Line brown hens. A total of 480 healthy day-old Hy-line brown chicks with similar body weights were randomly divided into four dietary groups (8 replicates/group and 15 birds/replicate). Groups A, B, C and D were fed diets containing 0%, 0.1%, 0.2% and 0.3% Aln-Gln, respectively, for 6 weeks. The body weight (BW) and average daily gain (ADG) were higher in hens fed test diets compared with the control (p < 0.05). The feed conversion ratio (FCR) was better in test groups as compared to the control group (p < 0.05). The ADFI showed no significant difference between the groups. Dietary treatments had no effect on dry matter (DM), organic matter (OM) and crude fiber (CF) digestibility. The Aln-Gln also improved gross energy (GE) and crude protein (CP) digestibility (p < 0.05). It has also increased IgG levels in groups C and D. IgM levels were similar to the control in B, C and D. The Aln-Gln increased IL-1 in B and C, IL-2 in C and D, and IL-6 in all test groups (p < 0.05). The supplementation of Aln-Gln had no effect on serum antioxidant indices like CAT, MDA, GSH-PX, GSH, and SOD in 42-day-old growing hens. Aln-Gln supplementation had no significant effect (p > 0.05) on the activity of amylase and lipase, however, a significant improvement (p < 0.05) in the activities of trypsin and chymotrypsin was observed in the test groups. Supplemented Aln-Gln levels in the birds' diets led to an increase in the expression of genes related to growth factors (IGF-1, IGFBP-5), immune markers (IL-1, IL-2, IL-6) and antioxidant status (GSH-Px1), as compared to control group. Aln-Gln supplementation in Hy-Line brown hens during their growing period improved growth, nutrient digestibility, immunity and digestive enzymes activity. These findings suggest that Aln-Gln is a promising dietary additive for enhancing poultry performance. [ABSTRACT FROM AUTHOR]

Introduction: Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real‐world impact at the population level remains unclear. Methods: Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long‐term trends in the incidence, incidence‐based mortality (IBM), and survival of lung cancer patients in the United States. Results: The incidence and IBM of both non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1‐year survival (1‐YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1‐YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%–0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%–1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%–2.47%) from 2014 to 2019. The same two turning points in 1‐YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1‐YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period. Conclusion: This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real‐world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer. [ABSTRACT FROM AUTHOR]

EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is an uncommon disease with limited therapeutic options and dismal prognosis. Here we report the activity, tolerability, potential mechanisms of response and resistance for dual targeting EGFR 20ins with JMT101 (anti-EGFR monoclonal antibody) plus osimertinib from preclinical models and an open label, multi-center phase 1b trial (NCT04448379). Primary endpoint of the trial is tolerability. Secondary endpoints include objective response rate, duration of response, disease control rate, progression free survival, overall survival, the pharmacokinetic profile of JMT101, occurrence of anti-drug antibodies and correlation between biomarkers and clinical outcomes. A total of 121 patients are enrolled to receive JMT101 plus osimertinib 160 mg. The most common adverse events are rash (76.9%) and diarrhea (63.6%). The confirmed objective response rate is 36.4%. Median progression-free survival is 8.2 months. Median duration of response is unreached. Subgroup analyses were performed by clinicopathological features and prior treatments. In patients with platinum-refractory diseases (n = 53), confirmed objective response rate is 34.0%, median progression-free survival is 9.2 months and median duration of response is 13.3 months. Responses are observed in distinct 20ins variants and intracranial lesions. Intracranial disease control rate is 87.5%. Confirmed intracranial objective response rate is 25%. Patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions are resistant to early generation EGFR tyrosine kinase inhibitors (TKI). Here, the authors report the safety and preliminary efficacy of a phase I clinical trial JMT101, an anti-EGFR antibody, combined with EGFR-TKI, afatinib or osimertinib, in patients with NSCLC. [ABSTRACT FROM AUTHOR]

This study aimed to tentatively evaluate the effects of dietary vitamin E (VE) on goose reproductive physiology through the investigation of reproductive performance, egg characteristics, antioxidant capacity, and immune status in breeding geese. A total of 480 female and 96 male Jiangnan White breeding geese were randomly assigned to four treatments with four replicates, and each replicate had 30 females and six males. Four levels of VE were successively added to four treatment diets from 48 to 54 weeks of age, representing the effects of VE deficiency (0 IU/kg), basic-dose VE (40 IU/kg), middle-dose VE (200 IU/kg), and high-dose VE (2000 IU/kg). Neither the egg-laying rate nor the healthy-gosling rate were affected by any of the VE supplementations (p > 0.05). The qualified egg rate, hatchability of fertilized eggs, and spleen index were increased by each VE supplementation (p < 0.05). Egg fertility, the concentration of plasma reproductive hormones (i.e., the follicle-stimulating hormone, estradiol, and progesterone), follicular development, and antioxidant enzyme activities—i.e., the concentration of malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)—in the liver and ovary were improved by 200 IU/kg of dietary VE (p < 0.05). Plasma VE concentration, immunoglobulin A, and immunoglobulin G content were increased, whereas plasma vitamin D3 concentration was reduced by increasing dietary VE levels to 2000 IU/kg (p < 0.05). The VE deposition of yolk, the yolk color depth, and the albumen rate were increased by each VE supplementation (p < 0.05). Antioxidant enzyme activities (i.e., MDA concentration, T-AOC, SOD, and GSH) in yolk were improved by 200 IU/kg and 2000 IU/kg of dietary VE (p < 0.05), compared with 0 IU/kg. The VE deposition was significantly correlated with GSH activity and the MDA concentration in egg yolk (p < 0.05). However, the high intake of dietary VE (2000 IU/kg vs. 200 IU/kg) decreased egg fertility (p < 0.05) and reduced the antioxidant capacity in the liver and ovary (p < 0.05). The qualified egg rate was positively correlated to immunoglobulin production (p < 0.05). Egg fertility and hatchability were correlatively improved by increased antioxidant enzyme activity; decreased MDA in the liver and ovary; hatchability; and enhanced immune status (p < 0.05). To sum up, both VE deficiency and high-dose VE (2000 IU/kg) reduced reproductive performance, whereas a dose of 200 IU/kg VE achieved optimal fertility, possibly through enhancing antioxidant capacity and immune status. [ABSTRACT FROM AUTHOR]

Background: The newly proposed Global Leadership Initiative on Malnutrition (GLIM) framework is promising to gain global acceptance for diagnosing malnutrition. However, the role of machine learning in facilitating its application in clinical practice remains largely unknown. Methods: We performed a multicenter, observational cohort study including 3998 patients with cancer. Baseline malnutrition was defined using the GLIM criteria, and the study population was randomly divided into a derivation group (n = 2998) and a validation group (n = 1000). A classification and regression trees (CART) algorithm was used to develop a decision tree for classifying the severity of malnutrition in the derivation group. Model performance was evaluated in the validation group. Results: GLIM criteria diagnosed 588 patients (14.7%) with moderate malnutrition and 532 patients (13.3%) with severe malnutrition among the study population. The CART cross‐validation identified 5 key predictors for the decision tree construction, including age, weight loss within 6 months, body mass index, calf circumference, and the Nutritional Risk Screening 2002 score. The decision tree showed high performance, with an area under the curve of 0.964 (κ = 0.898, P <.001, accuracy = 0.955) in the validation group. Subgroup analysis showed that the model had apparently good performance in different cancers. Among the 5 predictors constituting the tree, age contributed the least to the classification power. Conclusion: Using the machine learning, we visualized and validated a decision tool based on the GLIM criteria that can be conveniently used to accelerate the pretreatment identification of malnutrition in patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients. Patients and methods: A total of 8749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients' nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and decision curve analysis. Kaplan–Meier survival curves were used to compare the survival rate. Results: Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score < 18.5 and ≥ 18.5) for each TNM category (all Ps < 0.001). Conclusion: Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, and validated and shown a better predictive validity for the overall survival of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is prevalent that can impair multiple clinical outcomes in oncology populations. This study aimed to develop and utilize a tool to optimize the early identification of malnutrition in patients with cancer.Methods: We performed an observational cohort study including 3998 patients with cancer at two teaching hospitals in China. Hierarchical clustering was performed to classify the patients into well-nourished or malnourished clusters based on 17 features reflecting the phenotypic and etiologic dimensions of malnutrition. Associations between the identified clusters and patient characteristics were analyzed. A nomogram for predicting the malnutrition probability was constructed and independent validation was performed to explore its clinical significance.Results: The cluster analysis identified a well-nourished cluster (n = 2736, 68.4%) and a malnourished cluster (n = 1262, 31.6%) in the study population, which showed significant agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria (both P < 0.001). The malnourished cluster was negatively associated with the nutritional status, physical status, quality of life, short-term outcomes and was an independent risk factor for survival (HR = 1.38, 95%CI = 1.22-1.55, P < 0.001). Sex, gastrointestinal symptoms, weight loss percentages (within and beyond 6 months), calf circumference, and body mass index were incorporated to develop the nomogram, which showed high performance to predict malnutrition (AUC = 0.972, 95%CI = 0.960-0.983). The decision curve analysis and independent external validation further demonstrated the effectiveness and clinical usefulness of the tool.Conclusions: Nutritional features-based clustering analysis is a feasible approach to define malnutrition. The derived nomogram shows effectiveness for the early identification of malnutrition in patients with cancer. [ABSTRACT FROM AUTHOR]

Background: The stage‐specific roles of radiotherapy (RT) alone, chemotherapy alone, and combined RT and chemotherapy (CRT) for patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated. Methods: We analyzed patients with all stages of NLPHL enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching (PSM) was performed to ensure the well‐balanced characteristics of the comparison groups. Kaplan–Meier and Cox proportional‐hazards models were used to evaluate the overall survival (OS), cancer‐specific survival (CSS), hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses. Results: For early‐stage patients, CRT was associated with the best survival, the mean OS was significantly improved by approximately 20 months (20 m), and the risk of death was reduced by more than 80%, both before and after PSM (p < 0.05). For advanced‐stage patients, none of RT alone, chemotherapy alone, or CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long‐term survival (RMST120 m: neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104 m vs. 111 m vs. 108 m). Subgroup analysis of patients with early‐stage NLPHL showed that CRT was associated with better survival of elderly patients (improved OS = 43.8 m, HR = 0.14, p < 0.05). However, the survival benefits of treatments for young patients were not statistically significant. The efficacy of RT was significantly different between the age groups (pfor interaction = 0.020). Conclusions: These results from SEER data suggest that CRT may be considered for early‐stage NLPHL, especially for elderly patients. Further studies are needed to identify effective treatments in patients with advanced‐stage NLPHL. [ABSTRACT FROM AUTHOR]

Background: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results: The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients. [ABSTRACT FROM AUTHOR]

The survival advantage of radiotherapy for patients with stage IV classic Hodgkin lymphoma (HL) has not been adequately evaluated. We analyzed patients with stage IV HL enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2012. Propensity score (PS) analysis with 1:2 matching was performed to ensure well-balanced characteristics of the comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazards ratio (HR) and corresponding 95% confidence intervals (95% CI). Overall, for all patients with stage IV HL, receiving radiotherapy was associated with both significantly improved OS and CSS. Radiotherapy to any lesions could independently improve the OS and CSS by 30% to 36% in the multivariate analyses before and after PS matching (PSM), with the best improvement of 33% to 40% observed for patients with nodular sclerosis (P < 0.05) among all HL pathological types. In particular, radiotherapy, most likely to the residual site, was more pronouncedly associated with the improvement in survival for patients with stage IV HL who were young (age<45, P <.05) or without B symptoms (PInteraction for OS = 0.099, PInteraction for CSS = 0.255). For those patients without B symptoms, after PSM, the OS was improved by 65% (P =.021). The large SEER results support that radiotherapy is associated with better survival of patients with stage IV HL. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the chest computed tomography (CT) findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to clinical severity. We compared the CT features of common cases and severe cases, symptomatic patients and asymptomatic patients, and febrile and afebrile patients. Methods: This was a retrospective analysis of the clinical and thoracic CT features of 120 consecutive patients with confirmed SARS-CoV-2 pneumonia admitted to a tertiary university hospital between January 10 and February 10, 2020, in Wuhan city, China. Results: On admission, the patients generally complained of fever, cough, shortness of breath, and myalgia or fatigue, with diarrhea often present in severe cases. Severe patients were 20 years older on average and had comorbidities and an elevated lactate dehydrogenase (LDH) level. There were no differences in the CT findings between asymptomatic and symptomatic common type patients or between afebrile and febrile patients, defined according to Chinese National Health Commission guidelines. Conclusions: The clinical and CT features at admission may enable clinicians to promptly evaluate the prognosis of patients with SARS-CoV-2 pneumonia. Clinicians should be aware that clinically silent cases may present with CT features similar to those of symptomatic common patients. Key Points: • The clinical features and predominant patterns of abnormalities on CT for asymptomatic, typic common, and severe cases were summarized. These findings may help clinicians to identify severe patients quickly at admission. • Clinicians should be cautious that CT findings of afebrile/asymptomatic patients are not better than the findings of other types of patients. These patients should also be quarantined. • The use of chest CT as the main screening method in epidemic areas is recommended. [ABSTRACT FROM AUTHOR]

Background: To assess the role of nodal involvement in stage III renal cell carcinoma (RCC) according to the American Joint Committee on Cancer (AJCC) 8th staging system. We compared the survival outcomes of RCC patients with pT1−3N1M0 disease and those with pT3N0M0 or stage IV (stratified as pT4NanyM0 and pTanyNanyM1) disease in a large population-based cohort. Methods: A cohort of 3,112 eligible patients with RCC was identified from the Surveillance, Epidemiology, and End Results (SEER) database, registered between January 2004 and December 2015. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), and cancer-specific survival (CSS). The prognostic value of the modified stage for pT1−3N1M0 disease was assessed by nomogram-based analyses. Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results: Patients with pT1−3N1M0 disease showed similar survival outcomes (median OS 41.0 vs. 38.0 months, P = 0.77; CSS 45.0 vs. 39.0 months, P = 0.59) to pT4NanyM0 patients, whereas the significantly better survival outcome was found for pT3N0M0 patients. After PSM, comparable survival rates were observed between pT1−3N1M0 group and pT4NanyM0 group, which were still significantly worse than the survival of pT3N0M0 patients. The modified stage IIIA (pT3N0M0), IIIB (pT1−3N1M0, pT4NanyM0), and IV (pTanyNanyM1) showed higher predictive accuracy than AJCC stage system in the nomogram-based analyses (concordance index: 0.70 vs. 0.68, P < 0.001 for OS; 0.71 vs. 0.69, P < 0.001 for CSS). Conclusions: The pT1−3N1M0 RCC might be reclassified as stage IIIB together with pT4NanyM0 disease for better prediction of prognosis, further examination and validation are warranted. [ABSTRACT FROM AUTHOR]

Background: The survival advantage of radiotherapy for patients with extensive-disease small-cell lung cancer (ED-SCLC) has not been adequately evaluated.Methods: We analyzed stage IV SCLC patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 and December 2012. Propensity score analysis with 1:1 matching was performed to ensure well-balanced characteristics of all comparison groups. Kaplan–Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% CI.Results: Overall, for all metastatic ED-SCLC, receiving radiotherapy was associated with both improved OS and CSS. Radiotherapy for thoracic lesion and any metastatic sites could significantly improve the OS and CSS, except for brain metastasis. For M1a-SCLC patient, radiotherapy, most likely to the primary site, significantly improved the survival (P<0.001). Furthermore, for those ED-SCLC patients with ≥ 2 metastatic sites, that is, polymetastatic ED-SCLC patients, radiation also significantly improved the median OS from 6.0 to 8.0 months (P=0.015) and the median CSS from 7.0 to 8.0 months (P=0.020).Conclusion: The large SEER results support that radiotherapy in addition to chemotherapy might improve the survival of patients with metastatic ED-SCLC. [ABSTRACT FROM AUTHOR]

Objectives: The survival advantage of radiotherapy (RT) for patients with stage IV non‐small cell lung cancer (NSCLC) has not been adequately evaluated. Methods: We analyzed stage IV NSCLC patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 to December 2012. Propensity score (PS) analysis with 1:1 nearest neighbor matching method was used to ensure well‐balanced characteristics of all comparison groups by histological types and metastatic sites. Kaplan‐Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer‐specific survival (CSS), and corresponding 95% confidence interval (95%CI). Results: Generally speaking, there was a trend toward improved OS and CSS for using RT to stage IV NSCLC patients for any metastatic sites and for any histological types except adenocarcinoma (AD). Radiotherapy significantly improved the survival of NSCLC patients with metastasis to brain (P < 0.001), especially for AD (P < 0.001). For stage IV lung cancer patients with squamous cell carcinoma (SQC), RT for any metastatic sites could universally improve the OS (P < 0.001) and CSS (P < 0.001). In particular, RT was also associated with improving OS (P < 0.001) and CSS (P = 0.012) for stage IV patients with metastases of two or more sites, ie, polymetastatic disease. Furthermore, for those stage IV SQC patients without metastasis, RT, most likely to the primary site, also significantly improved the survival (P < 0.001). Conclusions: The results support that RT might improve the survival of patients with metastatic NSCLC in a PS‐matched patient cohort from the large SEER database. It is prudent to carefully select patients for RT in metastatic NSCLC. Radiotherapy (RT) improved the survival of stage IV adenocarcinoma (AD) patients with metastasis to brain; stage IV squamous cell carcinoma (SQC) with metastasis to bone, liver and lung. Even for polymetastatic disease (metastases of two or more sites) patients had a trend in getting survival benefits from RT. [ABSTRACT FROM AUTHOR]

Although this is an exciting time for translational medicine, systematic approaches and strategies to conduct translational research are sparse. We highlight in this editorial the opportunities to collaborate across disciplines and to forge new interdisciplinary collaborative ventures from the perspective of epidemiology. We specifically outline some feasible research areas, wherein Translational Epidemiology may readily speed up the translation of research for Precision Medicine. [ABSTRACT FROM AUTHOR]

Chain drive system is widely used in the conditions of high-speed, overload, variable speed and load. Many studies are focused on the meshing theory and wear characteristics of chain drive system, but system design, analysis, and noise characteristics of the chain drive system are weak. System design and noise characteristic are studied for a new type Gemini chain of dual-clutch automatic transmission. Based on the meshing theory of silent chain, the design parameters of the Gemini chain system are calculated and the mathematical models and dynamic analysis models of the Gemini chain system are established. Dynamic characteristics of the Gemini chain system is simulated and the contact force of plate and pin, plate and sprockets, the chain tension forces, the transmission error and the stress of plates and pins are analyzed. According to the simulation results of the Gemini chain system, the noise experiment about system is carried out. The noise values are tested at different speed and load and spectral characteristics are analyzed. The results of simulation and experimental show that the contact forces of plate and pin, plate and sprockets are smaller than the allowable stress values, the chain tension force is less than ultimate tension and transmission error is limited in 1.2%. The noise values can meet the requirements of industrial design, and it is proved that the design and analysis method of the Gemini chain system is scientific and feasible. The design and test system is built from analysis to test of Gemini chain system. This research presented will provide a corresponding theoretical guidance for the design and dynamic characteristics and noise characteristics of chain drive system. [ABSTRACT FROM AUTHOR]

: Wei Zheng and colleagues quantify the burden of tobacco-smoking-related deaths for adults in Asia. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

The causal role of cigarette smoking in the risk of colorectal neoplasm has been suggested but not established. In a case–control study including 2060 colorectal polyp patients and 3336 polyp-free controls, we evaluated 21 functional genetic variants to construct a tobacco-carcinogen-metabolizing genetic risk score. Data regarding cigarette smoking were obtained through telephone interviews. Cigarette smoking was associated with an elevated risk of both adenomas and hyperplastic polyps. The association with smoking was stronger in participants with a high carcinogen-metabolizing risk score than those with a low risk score. Smoking 30 or more cigarettes per day was associated with a 1.7-fold elevated risk of any polyps (95% confidence interval = 1.3–2.2) among those with a low genetic risk score and 2.9-fold elevated risk (95% confidence interval = 1.8–4.8) among those with a high genetic risk score (Pinteraction = 0.025). A similar pattern of interaction was observed in analyses conducted separately for those with adenomas only (Pinteraction = 0.039) and hyperplastic polyps only (Pinteraction = 0.024). Interaction between carcinogen-metabolizing genetic risk and cigarette smoking was found in relation to high-risk adenomas (Pinteraction = 0.010) but not low-risk adenomas (Pinteraction = 0.791). No apparent interaction was found for duration of smoking. This study shows that the association between cigarette smoking and colorectal polyp risk is modified by tobacco-carcinogen-metabolizing polymorphisms, providing support for a causal role of cigarette smoking in the etiology of colorectal tumors. [ABSTRACT FROM AUTHOR]

Understanding patterns of shared and type-specific etiologies for colorectal polyps may provide insights into colorectal carcinogenesis. The authors present the first systematic comparison of risk factors by colorectal polyp type in a large colonoscopy-based case-control study of 3,764 polyp-free controls and 2,543 polyp patients, including 1,444 cases with adenomas only, 662 cases with hyperplastic polyps (HPPs) only, and 437 cases with synchronous HPPs and adenomas. Surveys were completed to obtain information on usual dietary intake and other lifestyle factors. Six lifestyle factors, including cigarette smoking, obesity, no regular use of nonsteroidal anti-inflammatory drugs, high intake of red meat, low intake of fiber, and low intake of calcium, were found to be independently associated with the risk of polyps. The risk of polyps increased progressively with an increasing number of adverse lifestyle factors. Compared with participants with no or only 1 risk factor, odds ratios for those with 5 to 6 risk factors were 2.72 (95% confidence interval: 1.94, 3.79) for adenoma only, 4.12 (95% confidence interval: 2.78, 6.09) for HPPs only, and 9.03 (95% confidence interval: 5.69, 14.34) for synchronous HPPs and adenomas. This study provides strong evidence that lifestyle modification is important for the prevention of colorectal polyps, especially advanced and multiple adenomas, which are established precursors of colorectal cancer. [ABSTRACT FROM AUTHOR]

Previous studies of the association of meat intake and meat-derived mutagen exposure with breast cancer risk have produced inconsistent results. We evaluated this association in a population-based case-control study of incident breast cancer conducted in Nashville, Tennessee, United States, including 2,386 breast cancer cases and 1,703 healthy women controls. Telephone interviews were conducted to obtain information related to meat intake including amount, cooking methods, and doneness levels, as well as other known or hypothesized risk factors for breast cancer. Unconditional logistic regression was used to derive odds ratios (ORs) after adjusting for potential confounders. High intake of red meat was associated with a significantly elevated risk of breast cancer ( P- trend < 0.001). The association was particularly strong for high intake of well-done red meat ( P- trend < 0.001), with an adjusted OR of 1.5 (95% CI = 1.3-1.9) for the highest versus the lowest quartile. Associations between red meat and breast cancer risk were slightly stronger for postmenopausal women than for premenopausal women. Meat-derived mutagens such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, were significantly associated with increased breast cancer risk among postmenopausal women only ( P- trend = 0.002 and 0.003, respectively). The results from this study provide strong support for the hypotheses that high red meat intake and meat-derived mutagen exposure may be associated with an increase in breast cancer risk. [ABSTRACT FROM AUTHOR]

Chinese women in Hong Kong have among the highest incidence and mortality of lung cancer in the world, in spite of a low prevalence of smoking. We carried out this population-based case–control study to evaluate the associations of previous lung disease and family cancer history with the occurrence of lung cancer among them. We selected 212 cases that were newly diagnosed with primary lung cancer, and randomly sampled 292 controls from the community, frequency matched by age group. All the cases and controls were lifetime nonsmokers. We estimated the main effects of preexisting asthma, pulmonary tuberculosis, pneumonia, chronic bronchitis, and family lung/all cancer history, using unconditional logistic regression, accounting for various potential risk factors and confounders. All of the previous lung diseases, except chronic bronchitis, were related to an elevated risk for lung cancer, and the association with asthma was significant. Those who had more than one previous lung disease tended to be at higher risk than those with only one of them. Positive family history of any cancer was associated with over 2-fold risk than negative family history. The joint effect of positive history of previous pulmonary diseases and positive family cancer history appeared to be additive, indicating the two factors acted independently. The results support an etiological link of preexisting lung disease and family cancer history to the risk of lung cancer. [ABSTRACT FROM AUTHOR]

yki -induced gut tumors in Drosophila are associated with host wasting, including muscle dysfunction, lipid loss, and hyperglycemia, a condition reminiscent of human cancer cachexia. We previously used this model to identify tumor-derived ligands that contribute to host wasting. To identify additional molecular networks involved in host-tumor interactions, we develop PathON, a web-based tool analyzing the major signaling pathways in Drosophila , and uncover the Upd3/Jak/Stat axis as an important modulator. We find that yki -gut tumors secrete Upd3 to promote self-overproliferation and enhance Jak/Stat signaling in host organs to cause wasting, including muscle dysfunction, lipid loss, and hyperglycemia. We further reveal that Upd3/Jak/Stat signaling in the host organs directly triggers the expression of ImpL2 , an antagonistic binding protein for insulin-like peptides, to impair insulin signaling and energy balance. Altogether, our results demonstrate that yki -gut tumors produce a Jak/Stat pathway ligand, Upd3, that regulates both self-growth and host wasting. [Display omitted] • yki 3SA -gut tumors produce Upd3 to autonomously promote self-growth • yki 3SA -gut tumors produce Upd3 to cause host wasting • Upd3/Jak/Stat axis impairs muscle mitochondrial functions and carbolipid metabolism • Upd3/Jak/Stat axis induces host ImpL2 production to hamper insulin response Ding et al. show that yki 3SA -gut tumors produce Upd3 as a cachectic ligand to simultaneously promote self-growth and host organ wasting via systemic activation of Jak/Stat signaling in Drosophila. The Upd3/Jak/Stat axis induces host ImpL2 production and perturbs insulin response, leading to muscle mitochondrial dysfunction, lipid loss, and carbohydrate elevation. [ABSTRACT FROM AUTHOR]

Simple Summary: The poultry industry faces challenges such as a shortage of protein feed and increased feed cost. Compared to soybean meal, rapeseed meal (RSM) is a cheaper protein source that can be used in poultry diets. China is both the largest RSM and geese producer in the world. Therefore, the active use of RSM for geese diets can contribute to the development of poultry production. We found that geese had a good adaptation to the diet containing 16% dietary RSM through the investigation. The use of inexpensive nonconventional feed materials, such as rapeseed meal (RSM), could help alleviate the shortage of feed materials in the poultry industry. This study was to investigate the effects of dietary double-low RSM on growth performance, carcass traits, serum parameters, and intestinal development of geese. A total of 270 healthy 35-day-old male Jiangnan White geese were randomly divided into five treatments, with six replicate pens of nine geese each. The geese were fed five isonitrogenous and isocaloric diets containing 0%, 4%, 8%, 12%, and 16% RSM replacing dietary soybean meal for 35 days. At 35, 49, and 70 d, the BW and feed intake were recorded. All Samples were collected at 70 d of age. The results showed that dietary RSM up to 16% did not affect the BW, ADFI, ADG, and feed/gain ratio (F/G) during 35 to 49 d, 49 to 70 d, and 35 to 70 d periods (p > 0.05). At 70 d, no difference was observed in carcass yield or serum biochemical parameters among groups (p > 0.05). Dietary 12% and 16% RSM significantly increased the concentration of serum GH compared with 0%, 4%, 8% groups (p < 0.01), but serum TSH, T3 and T4 were unaffected (p > 0.05). The relative weights of heart, liver, spleen, proventriculus, gizzard, and small intestine were similar among groups (p > 0.05). However, the geese fed dietary 16% RSM had greater bursa of Fabricius than geese in the 8% group (p < 0.05). Intestinal morphology was unaffected by treatments (p > 0.05). According to the findings, dietary RSM up to 16% can be used in geese diets without impact on production performance. [ABSTRACT FROM AUTHOR]

The survival advantage of surgery to the primary tumor for patients with distant metastatic esophageal cancer has not been adequately evaluated. This study aims to investigate the role of surgery to the primary tumor in distant metastatic esophageal cancer and to evaluate possible different effects of surgery on survival of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). This study included a cohort of 4,367 metastatic esophageal cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, registered from January 2004 to December 2014. Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS) and corresponding 95% confidence interval (CI). Propensity score matching (PSM) was used to adjust for potential baseline confounding. Both EAC (median OS for surgery group vs. no-surgery group–14.0 vs. 9.0 months, P < 0.001) and ESCC (median OS for surgery vs. no-surgery group–11.0 vs. 7.0 months, P = 0.002) experienced survival benefits from surgery. We found that surgery to the primary tumor, when combined with chemotherapy, was associated with improved survival for patients with M1b disease, both EAC and ESCC, with a greater benefit observed in younger patients, and those with EAC. While the present data indicate a potential survival benefit from surgery for some patients with metastatic esophageal cancer, it is possible that performance status and metastatic disease burden impacted patient selection, influencing these results. Further studies are needed to determine the role of surgery for patients with metastatic esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.Methods and Findings: We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.Conclusions: Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary. [ABSTRACT FROM AUTHOR]