Efficacy and safety of weekly versus triweekly cisplatin treatment concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma: A systematic review and pooled analysis

Background: Most nasopharyngeal carcinoma cases are diagnosed at an advanced stage due to their hidden anatomical structure and atypical clinical symptoms and often require chemoradiotherapy. Here, we present a systematic review and pooled analysis to synthesize existing research on the efficacy and adverse effects of weekly versus triweekly cisplatin chemotherapy concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma (LANPC).Methods: We searched the PubMed, Embase, and Cochrane Library databases from inception to 1 September 2021, for relevant original research articles published in English. The literature search and data extraction were done independently by two investigators. We used random-effects models to provide point estimates [95% confidence interval (CI)] of overall response rate (ORR), overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and the incidence rate of adverse effects (AEs) and with subgroup analysis according to each study type. The primary endpoints were ORR, OS, and PFS; LRFS, DMFS, and grade ≥3 acute AEs were secondary endpoints.Results: In total, 2,305 patients of eight studies were included in this review. We found that patients who were administered cisplatin weekly or triweekly had no differences in ORR, OS, PFS, DMFS, LRFS, severe mucositis, dermatitis, nausea/vomiting or nephrotoxicity. Patients who were administered weekly cisplatin were at a higher risk of hematological toxicity compared with patients who received the chemotherapy triweekly.Conclusion: Our findings suggest that both regimens could be recommended as the standard of care for the chemoradiotherapy treatment of LANPC, the perceived benefit of lower toxicity with weekly cisplatin could not be established

The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11). Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells

Stability of important antibodies for kidney disease: pre-analytic methodological considerations

Background The importance of circulating antibodies as biomarkers of kidney disease has recently been recognized. However, no study has systematically described the methodology of sample preparation and storage regarding antibodies as biomarkers of kidney disease. It remains unknown whether repetitive freeze-thaw cycles, physical disturbances, storage at different temperatures or for different periods of time, or haemolytic or turbid serum samples affect antibody measurements. The aim of this study was to investigate the stabilities of antibodies associated with kidney disease in serum samples under various relevant clinical and research conditions. Methods We stored serum samples in the following different conditions: repetitive freeze-thaw cycles (1, 6 or 12 times), long-term storage (7 or 12 months at −80 °C), physical disturbance (1 or 8 h), and storage at 4 °C (1, 3 or 6 weeks) and room temperature (1 or 7 days). The stabilities of the anti-phospholipase A2 receptor (anti-PLA2R), anti-glomerular basement membrane, anti-myeloperoxidase and anti-proteinase 3 antibodies were evaluated with enzyme-linked immunosorbent assays (ELISA). Results We found that repetitive freeze-thaw cycles did not have a significant effect on the stabilities of the abovementioned antibodies in clear serum samples. The ELISA readings of haemolytic and turbid serum samples tended to increase and decrease, respectively. Neither long-term storage at −80 °C nor physical disturbance had a significant effect on anti-PLA2R antibody stability in sealed serum samples. The concentrations of most of these antibodies increased in unsealed serum samples that were stored at 4 °C for more than 6 weeks or at room temperature for more than 7 days. Discussion Our findings revealed that the abovementioned circulating antibodies that are used as biomarkers for kidney disease had stable physicochemical properties, structures and immunoreactivities such that they were not influenced by repetitive freeze-thaw cycles, physical disturbances or long-term storage at −80 °C. However, the ELISA readings tended to change for haemolytic, turbid and unsealed serum samples

Maltose and Totally Impermeable Film Enhanced Suppression of Anaerobic Soil Disinfestation on Soilborne Pathogens and Increased Strawberry Yield

peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

THE IMPACT OF RURAL ENTERPRISES ON HOUSEHOLD SAVINGS IN CHINA

In view of development policy, capital formation is crucial for economic growth in a country. Since the reform in 1978, China has enjoyed high saving rates. However, in the late 1990s the saving rates rose to such a high level, therefore the economic policy to promote consumption in order to reduce savings was suggested,. This paper attempts explains this paradox of "excessively high saving rates" in relation to the capital accumulation mechanism in rural enterprise (TVEs: Township and Village Enterprises). The determinants of household savings in developing countries is one important topic of the development research. However most studies have ignored investment as one main determinant. In the famous Lewis' model, the savings of farm households for non-farm investment are not considered, because in most cases it is difficult to sort out capitalists from the rural households. The case of the capital formation of TVEs in China offers us an opportunity to test the non farm investment as a saving incentive, because there are no large or small capitalists and landlords available after the agriculture reform in China in 1978. With facts and statistical analyses, this paper has proved that the development of TVEs is an important factor of the high saving rates of rural households since the reform. The way of development of private TVEs and the process of the privatization of the collective showed that owing to the extreme financial discrimination, TVEs underwent an evolution into a financial institution. The demand of TVEs for private credits forced rural households to save and hence function as an informal financial market. The managers have the motivation to save because they want to run a collective TVE or to set up a private TVE. The workers have the motivation to save because they want to get a job or keep their job in TVEs. Using first hand data and statistical analyses, it was plausibly proved that households with manager in TVEs have higher saving rates than non-manager households. It is especially obvious in households with manager in shareholding and shareholding co-operative TVEs. Households with peasant worker in collective TVEs have higher saving rates than others. This implies that collective TVEs used many methods to force their workers to save

THE IMPACT OF RURAL ENTERPRISES ON HOUSEHOLD SAVINGS IN CHINA

In view of development policy, capital formation is crucial for economic growth in a country. Since the reform in 1978, China has enjoyed high saving rates. However, in the late 1990s the saving rates rose to such a high level, therefore the economic policy to promote consumption in order to reduce savings was suggested,. This paper attempts explains this paradox of "excessively high saving rates" in relation to the capital accumulation mechanism in rural enterprise (TVEs: Township and Village Enterprises). The determinants of household savings in developing countries is one important topic of the development research. However most studies have ignored investment as one main determinant. In the famous Lewis' model, the savings of farm households for non-farm investment are not considered, because in most cases it is difficult to sort out capitalists from the rural households. The case of the capital formation of TVEs in China offers us an opportunity to test the non farm investment as a saving incentive, because there are no large or small capitalists and landlords available after the agriculture reform in China in 1978. With facts and statistical analyses, this paper has proved that the development of TVEs is an important factor of the high saving rates of rural households since the reform. The way of development of private TVEs and the process of the privatization of the collective showed that owing to the extreme financial discrimination, TVEs underwent an evolution into a financial institution. The demand of TVEs for private credits forced rural households to save and hence function as an informal financial market. The managers have the motivation to save because they want to run a collective TVE or to set up a private TVE. The workers have the motivation to save because they want to get a job or keep their job in TVEs. Using first hand data and statistical analyses, it was plausibly proved that households with manager in TVEs have higher saving rates than non-manager households. It is especially obvious in households with manager in shareholding and shareholding co-operative TVEs. Households with peasant worker in collective TVEs have higher saving rates than others. This implies that collective TVEs used many methods to force their workers to save.Community/Rural/Urban Development, Consumer/Household Economics,

ECONOMIC INSTITUTIONAL EVOLUTION AND FURTHER NEEDS FOR ADJUSTMENTS: TOWNSHIP VILLAGE ENTERPRISES IN CHINA

Township Village Enterprises (TVEs) have essentially contributed to China's economic development and institutional transformation over the last twenty years. One of the explanations for the mechanism of TVEs' growth is the co-operative culture theory which claims that Chinese - compared with other nationalities - could better resolve "free riding problems" and work more efficiently under collective TVEs. In this paper, based on official documents, statistical data and results from important surveys, we analyze the historic development of property rights in TVEs. We have proved that the evolution of TVEs' property rights depended on the interaction between peasants and policy makers. In this interaction process peasants showed strong pursuit of private ownership and policy makers reacted with delay towards owner interests. Owing to the delay of political adjustments, peasants had to adopt various ownership forms for their enterprises - joint households, collective and shareholding cooperative - in order to struggle against a discriminating environment for private ownership. This institutional evolution is not a proof for the co-operative culture theory, but instead for the conventional theory of property rights because the long struggle of the peasants finally led to one clearly defined form of ownership - private property rights. We have tested our hypothesis in view of the following process: In the collective economy under the commune system, policy-makers changed the size of owner units of TVEs from "big" (commune) to "small" (production brigade or production group) and back in accordance with the importance of TVEs to the national economy. In the individual economy after the reform of land use rights, the property rights of TVEs were forced to change step by step to private property rights under the pressure of farm households striving for private ownership. The peasants instrumentalized the various vaguely defined property rights in order to avoid political risks. Due to the "principal agent problem", the collective-owned TVEs went down despite political and financial support. The financial viability of private TVEs however grew in spite of their competition with collective-owned TVEs and severe political and financial discrimination. With the evolution of property rights in TVEs, at present private enterprises dominate the non farm sector in China's rural areas. These structural changes require adjustments of China's financial policy: Formerly, formal financial institutions directed their support mainly towards collective enterprises, whereas private TVEs depended on informal capital sources. In order to meet private TVEs' financial demands, the rural financial market which officially is still dominated by formal financial institutions should be replaced with a financial market consisting of legally recognized multiform-intermediaries

ECONOMIC INSTITUTIONAL EVOLUTION AND FURTHER NEEDS FOR ADJUSTMENTS: TOWNSHIP VILLAGE ENTERPRISES IN CHINA

Township Village Enterprises (TVEs) have essentially contributed to China's economic development and institutional transformation over the last twenty years. One of the explanations for the mechanism of TVEs' growth is the co-operative culture theory which claims that Chinese - compared with other nationalities - could better resolve "free riding problems" and work more efficiently under collective TVEs. In this paper, based on official documents, statistical data and results from important surveys, we analyze the historic development of property rights in TVEs. We have proved that the evolution of TVEs' property rights depended on the interaction between peasants and policy makers. In this interaction process peasants showed strong pursuit of private ownership and policy makers reacted with delay towards owner interests. Owing to the delay of political adjustments, peasants had to adopt various ownership forms for their enterprises - joint households, collective and shareholding cooperative - in order to struggle against a discriminating environment for private ownership. This institutional evolution is not a proof for the co-operative culture theory, but instead for the conventional theory of property rights because the long struggle of the peasants finally led to one clearly defined form of ownership private property rights. We have tested our hypothesis in view of the following process: In the collective economy under the commune system, policy-makers changed the size of owner units of TVEs from "big" (commune) to "small" (production brigade or production group) and back in accordance with the importance of TVEs to the national economy. In the individual economy after the reform of land use rights, the property rights of TVEs were forced to change step by step to private property rights under the pressure of farm households striving for private ownership. The peasants instrumentalized the various vaguely defined property rights in order to avoid political risks. Due to the "principal agent problem", the collective-owned TVEs went down despite political and financial support. The financial viability of private TVEs however grew in spite of their competition with collective-owned TVEs and severe political and financial discrimination. With the evolution of property rights in TVEs, at present private enterprises dominate the non farm sector in China's rural areas. These structural changes require adjustments of China's financial policy: Formerly, formal financial institutions directed their support mainly towards collective enterprises, whereas private TVEs depended on informal capital sources. In order to meet private TVEs' financial demands, the rural financial market which officially is still dominated by formal financial institutions should be replaced with a financial market consisting of legally recognized multiform-intermediaries.Institutional and Behavioral Economics,