Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the...Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.展开更多
Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a co...Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology.The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis,early metastasis of tumor,and resistance to almost all tested cytotoxic drugs.In this respect,the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer.Some studies have shown that the mitochondrial uncoupling protein 2(UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues.In addition,recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming,including aerobic glycolysis stimulation,promotion of cancer progression.These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer.In this editorial,recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.展开更多
The generally adopted worldwide target is to keep the increase in the global mean temperature lower than 2C by 2100, which is comparable with that of the preindustrial era. It is feasible for China to realize an emiss...The generally adopted worldwide target is to keep the increase in the global mean temperature lower than 2C by 2100, which is comparable with that of the preindustrial era. It is feasible for China to realize an emission pathway that is consistent with this target; however, we need to understand the roadmap to do so. In this paper, the results of a modeling study by the Integrated Policy Assessment Model for China(IPAC)concerning the investment required to realize the 2℃ scenario by examining the penetration of low-carbon technologies including energy supply and energy efficiency improvement in end-use sectors is presented. It is found that the investment required in the energy supply sector to realize the 2C scenario could reach CN$1.2 trillion by 2020, CN$1.0 trillion by 2030, and CN$1.4 trillion by 2050. The investment needed for energy saving could reach CN$1.6 trillion by 2020, CN$1.8 trillion by 2030, and CN$1.5 trillion by 2050, which represents the additional investment as compared with the use of old technologies. If the investment required both in the energy supply sector and in energy saving in enduse sectors is considered, the total investment is estimated to be CN$2.8 trillion by 2020, CN$2.8 trillion by 2030, and CN$2.9 trillion by 2050.These investments account for 2.5% of China's total GDP in 2020, 1.3% in 2030, and 0.6% by 2050, which represents quite a small investment percentage to realize the goal of low-carbon development.展开更多
Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted th...Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.展开更多
China has committed to achieving carbon neutrality by 2060.It is essential to develop representative CO_(2)emissions pathways at the provincial level that align with the national target to facilitate effective policy ...China has committed to achieving carbon neutrality by 2060.It is essential to develop representative CO_(2)emissions pathways at the provincial level that align with the national target to facilitate effective policy implementation and scientific research.To address inconsistencies between provincial aggregate emissions and national estimates,this study compares the 2021 CO_(2)emissions estimates of China's provinces from the bottom‒up emissions factor method and the top‒down atmospheric CO_(2)concentration inversion method.We find that these methods yield comparable results for the emissions from energy combustion and industrial processes at the provincial level.Based on a review of existing research on CO_(2)pathways for China's provinces,we propose a set of representative pathways for China's provinces.These pathways align with past practices of allocating national emissions intensity reduction targets to provinces and are consistent with the national Tsinghua‒CMA pathway.The proposed pathways require provinces to sequentially peak their emissions by 2030,followed by rapid emissions reduction.Compared to a reference scenario without the carbon neutrality target,these pathways would incur an estimated cumulative GDP loss of about 1%between 2020 and 2060.However,there are notable regional variations,with some regions in the northwest potentially experiencing higher economic growth due to the availability of high-quality low-carbon resources.We recommend that China enhance provincial-level CO_(2)emissions accounting by cross-validating bottom‒up and top‒down methods.Additionally,careful consideration should be given to aligning provincial targets with national and global commitments when updating pathways toward carbon neutrality.展开更多
To mitigate the deleterious effects of clutter and jammer, modern radars have adopted adaptive processing techniques such as constant false alarm rate(CFAR) detectors which are widely used to prevent clutter and noise...To mitigate the deleterious effects of clutter and jammer, modern radars have adopted adaptive processing techniques such as constant false alarm rate(CFAR) detectors which are widely used to prevent clutter and noise interference from saturating the radar’s display and preventing targets from being obscured.This paper concerns with the detection analysis of the novel version of CFAR schemes(cell-averaging generalized trimmed-mean,CATM) in the presence of additional outlying targets other than the target under research. The spurious targets as well as the tested one are assumed to be fluctuating in accordance with the χ~2-model with two-degrees of freedom. In this situation, the processor performance is enclosed by the swerling models(SWI and SWII). Between these bounds, there is an important class of target fluctuation which is known as moderately fluctuating targets. The detection of this class has many practical applications. Structure of the CATM detector is described briefly. Detection performances for optimal, CAM, CA, trimmed-mean(TM) and ordered-statistic(OS) CFAR strategies have been analyzed and compared for desired probability of false alarm and determined size of the reference window. False alarm rate performance of these processors has been evaluated for different strengths of interfering signal and the effect of correlation among the target returns on the detection and false alarm performances has also been studied. Our numerical results show that, with a proper choice of trimming parameters,the novel model CAM presents an ideal detection performance outweighing that of the Neyman-Pearson detector on condition that the tested target obeys the SWII model in its fluctuation. Although the new models CAS and CAM can be treated as special cases of the CATM algorithm, their multi-target performance is modest even it has an enhancement relative to that of the classical CAcheme. Additionally, they fail to maintain the false alarm rate constant when the operating environment is of type target multiplicity. Moreover, the non-coherent integration of M pulses ameliorates the processor performance either it operates in homogeneous or multi-target environment.展开更多
文摘Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.
基金Supported by grants from Associazione Italiana Ricerca Cancro,Milan,ItalyFondazione Cari Pa Ro,Padova,ItalyMinistero dell’Istruzione,dell’Universitàe della Ricerca,Rome,Italy
文摘Overall 5-years survival of pancreatic cancer patients is nearly 5%,making this cancer type one of the most lethal neoplasia.Furthermore,the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology.The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis,early metastasis of tumor,and resistance to almost all tested cytotoxic drugs.In this respect,the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer.Some studies have shown that the mitochondrial uncoupling protein 2(UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues.In addition,recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming,including aerobic glycolysis stimulation,promotion of cancer progression.These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer.In this editorial,recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.
基金supported by National Science and Technology Program (2012CB955801)Basic Research and National Objectives& National Basic Research Program of China (2014CB441300)National Social Science Foundation (15ZDA055)
文摘The generally adopted worldwide target is to keep the increase in the global mean temperature lower than 2C by 2100, which is comparable with that of the preindustrial era. It is feasible for China to realize an emission pathway that is consistent with this target; however, we need to understand the roadmap to do so. In this paper, the results of a modeling study by the Integrated Policy Assessment Model for China(IPAC)concerning the investment required to realize the 2℃ scenario by examining the penetration of low-carbon technologies including energy supply and energy efficiency improvement in end-use sectors is presented. It is found that the investment required in the energy supply sector to realize the 2C scenario could reach CN$1.2 trillion by 2020, CN$1.0 trillion by 2030, and CN$1.4 trillion by 2050. The investment needed for energy saving could reach CN$1.6 trillion by 2020, CN$1.8 trillion by 2030, and CN$1.5 trillion by 2050, which represents the additional investment as compared with the use of old technologies. If the investment required both in the energy supply sector and in energy saving in enduse sectors is considered, the total investment is estimated to be CN$2.8 trillion by 2020, CN$2.8 trillion by 2030, and CN$2.9 trillion by 2050.These investments account for 2.5% of China's total GDP in 2020, 1.3% in 2030, and 0.6% by 2050, which represents quite a small investment percentage to realize the goal of low-carbon development.
基金KAKENHI(Grant-in-Aid for Scientific Research),No.23390329the National Cancer Center Research and Development Fund(23-A-9)
文摘Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2(HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancerresistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.
基金supported by the National Natural Science Foundation(42341202,72140005,and 42090030)the China Three Gorges Corporation research project(202303160)the Hainan Institute of National Park grant(KY-23ZK01).
文摘China has committed to achieving carbon neutrality by 2060.It is essential to develop representative CO_(2)emissions pathways at the provincial level that align with the national target to facilitate effective policy implementation and scientific research.To address inconsistencies between provincial aggregate emissions and national estimates,this study compares the 2021 CO_(2)emissions estimates of China's provinces from the bottom‒up emissions factor method and the top‒down atmospheric CO_(2)concentration inversion method.We find that these methods yield comparable results for the emissions from energy combustion and industrial processes at the provincial level.Based on a review of existing research on CO_(2)pathways for China's provinces,we propose a set of representative pathways for China's provinces.These pathways align with past practices of allocating national emissions intensity reduction targets to provinces and are consistent with the national Tsinghua‒CMA pathway.The proposed pathways require provinces to sequentially peak their emissions by 2030,followed by rapid emissions reduction.Compared to a reference scenario without the carbon neutrality target,these pathways would incur an estimated cumulative GDP loss of about 1%between 2020 and 2060.However,there are notable regional variations,with some regions in the northwest potentially experiencing higher economic growth due to the availability of high-quality low-carbon resources.We recommend that China enhance provincial-level CO_(2)emissions accounting by cross-validating bottom‒up and top‒down methods.Additionally,careful consideration should be given to aligning provincial targets with national and global commitments when updating pathways toward carbon neutrality.
文摘To mitigate the deleterious effects of clutter and jammer, modern radars have adopted adaptive processing techniques such as constant false alarm rate(CFAR) detectors which are widely used to prevent clutter and noise interference from saturating the radar’s display and preventing targets from being obscured.This paper concerns with the detection analysis of the novel version of CFAR schemes(cell-averaging generalized trimmed-mean,CATM) in the presence of additional outlying targets other than the target under research. The spurious targets as well as the tested one are assumed to be fluctuating in accordance with the χ~2-model with two-degrees of freedom. In this situation, the processor performance is enclosed by the swerling models(SWI and SWII). Between these bounds, there is an important class of target fluctuation which is known as moderately fluctuating targets. The detection of this class has many practical applications. Structure of the CATM detector is described briefly. Detection performances for optimal, CAM, CA, trimmed-mean(TM) and ordered-statistic(OS) CFAR strategies have been analyzed and compared for desired probability of false alarm and determined size of the reference window. False alarm rate performance of these processors has been evaluated for different strengths of interfering signal and the effect of correlation among the target returns on the detection and false alarm performances has also been studied. Our numerical results show that, with a proper choice of trimming parameters,the novel model CAM presents an ideal detection performance outweighing that of the Neyman-Pearson detector on condition that the tested target obeys the SWII model in its fluctuation. Although the new models CAS and CAM can be treated as special cases of the CATM algorithm, their multi-target performance is modest even it has an enhancement relative to that of the classical CAcheme. Additionally, they fail to maintain the false alarm rate constant when the operating environment is of type target multiplicity. Moreover, the non-coherent integration of M pulses ameliorates the processor performance either it operates in homogeneous or multi-target environment.
