Flexible triboelectric nanogenerators (TENGs)-based pressure sensors are very essential for the wide-range applications, comprising wearable healthcare systems, intuitive human-device interfaces, electronic-skin (e-sk...Flexible triboelectric nanogenerators (TENGs)-based pressure sensors are very essential for the wide-range applications, comprising wearable healthcare systems, intuitive human-device interfaces, electronic-skin (e-skin), and artificial intelligence. Most of conventional fabrication methods used to produce high-performance TENGs involve plasma treatment, photolithography, printing, and electro-deposition. However, these fabrication techniques are expensive, multi-step, time-consuming and not suitable for mass production, which are the main barriers for efficient and cost-effective commercialization of TENGs. Here, we established a highly reliable scheme for the fabrication of a novel eco-friendly, low cost, and TENG-based pressure sensor (TEPS) designed for usage in self-powered-human gesture detection (SP-HGD) likewise wearable healthcare applications. The sensors with microstructured electrodes performed well with high sensitivity (7.697 kPa^-1), a lower limit of detection (~ 1 Pa), faster response time (< 9.9 ms), and highly stable over > 4,000 compression-releasing cycles. The proposed method is suitable for the adaptable fabrication of TEPS at an extremely low cost with possible applications in self-powered systems, especially e-skin and healthcare applications.展开更多
Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-...Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β （Aβ） induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme （IDE）, which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 （200 μM, 5 μL） into the hippocampus and subsequently administered Kai Xin San （0.54 or 1.08 g/kg/d） intragastrically for 21 consecutive days. Hematoxylin eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation(LT) has become a curative treatment for patients with HCC. Howe...Hepatocellular carcinoma(HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation(LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment(chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy(radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.展开更多
Identifying pathogenetic variants and inferring their impact on protein-protein interactions sheds light on their functional consequences on diseases.Limited by the availability of experimental data on the consequence...Identifying pathogenetic variants and inferring their impact on protein-protein interactions sheds light on their functional consequences on diseases.Limited by the availability of experimental data on the consequences of protein interaction,most existing methods focus on building models to predict changes in protein binding affinity.Here,we introduced MIPPI,an end-to-end,interpretable transformer-based deep learning model that learns features directly from sequences by leveraging the interaction data from IMEx.MIPPI was specifically trained to determine the types of variant impact(increasing,decreasing,disrupting,and no effect)on protein-protein interactions.We demonstrate the accuracy of MIPPI and provide interpretation through the analysis of learned attention weights,which exhibit correlations with the amino acids interacting with the variant.Moreover,we showed the practicality of MIPPI in prioritizing de novo mutations associated with complex neurodevelopmental disorders and the potential to determine the pathogenic and driving mutations.Finally,we experimentally validated the functional impact of several variants identified in patients with such disorders.Overall,MIPPI emerges as a versatile,robust,and interpretable model,capable of effectively predicting mutation impacts on protein-protein interactions and facilitating the discovery of clinically actionable variants.展开更多
This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic studies.Using a photolit...This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic studies.Using a photolithographic biofabrication method with a photomask featuring hexagonal units,liver cells,including a human hepatic cell line(HepG2-C3A)and a human hepatic stellate cell line(LX-2)were embedded in gelatin methacryloyl hydrogel.Hepatic steatosis was induced by supraphysiological concentration of free fatty acids;hepatic fibrosis was induced by transforming growth factor-β1.Induction of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic acid.Induction of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin treatment.This model was further preliminarily validated using primary human hepatocytes in a similar setup.These constructs provide a viable,biologically relevant,and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.展开更多
Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to...Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to March 2021 at Paropakar Maternity and Women Hospital, a tertiary care hospital in Kathmandu, Nepal. Neonatal and maternal complications were analyzed. Results: Of 233 women, 102 (43.7%) and 131 (56.2%) had vacuum and forceps deliveries, respectively. The use of instruments was more frequent in infants with higher birth weight and gestational age. There were no significant differences in Apgar scores between the two groups. Two main indications of instrumental deliveries were fetal distress and prolonged second stage labor. Forceps, compared with vacuum, more often caused 3<sup>rd</sup>/4<sup>th</sup> perineal tears, tear extending to fornices, and postpartum hemorrhage. Neonatal outcomes were similar in both types of instrumental deliveries. Conclusion: Instrumental vaginal delivery caused maternal morbidity and procedure/judgment training for it is essential.展开更多
Soil CO<sub>2</sub> efflux is an ongoing process of respiration from soil;plant parts/ microbes below the ground to the atmosphere which is known for faster cycling of carbon sources. A large portion of ca...Soil CO<sub>2</sub> efflux is an ongoing process of respiration from soil;plant parts/ microbes below the ground to the atmosphere which is known for faster cycling of carbon sources. A large portion of carbon sequestered and fixed by forests is returned to the atmosphere through soil CO<sub>2</sub> efflux and multiple controlling parameters mainly temperature, precipitation, and growth factors interact with the soil CO<sub>2</sub> efflux variation. This study assessed the soil CO<sub>2</sub> efflux every month for consecutive 2-years (August 2015 to July 2017) by using the closed chamber method to determine the role of ecological parameters that govern the soil CO<sub>2</sub> efflux and its temporal modification in a sub-tropical mixed forest of central region in Nepal. The results of this study manifested that soil CO<sub>2</sub> efflux accounted 63.2% (y = 31.96e<sup>0.128x</sup>), 71.3% (y = 44.77e<sup>0.123x</sup>) and 64.5% (y = 44.11e<sup>0.117x</sup>) variations in soil temperature with significantly (p < 0.05) exponential positive relation in the year 2015/2016, 2016/2017 and the two years when merged. And the temperature sensitivity value (Q<sub>10</sub>) of the soil CO<sub>2</sub> efflux was 3.6, 3.4, and 3.2, respectively. Soil water content also expressed significantly (p < 0.05) positive exponential effect on soil CO<sub>2</sub> efflux and accounted 62.0% (y = 138.3e<sup>0.057x</sup>), 46.1% (y = 88.42e<sup>0.052x</sup>) and 40.5% (y = 133.1e<sup>0.0447x</sup>) in its variability in different years and the merged years. Evident variations of soil CO<sub>2</sub> efflux, soil temperature, soil water content, and litter were observed in the forest seasonally and inter-annually. Two years mean total annual soil CO<sub>2</sub> efflux of the forest was estimated at 904.76 g C·m<sup>-2</sup>·y<sup>-1</sup>. The study revealed that sub-tropical forests could be more influenced by precipitation regimes in progressing warm climates i.e. vulnerable to climate change, illustrating the comprehensive dy展开更多
AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT). · METHODS: It was a prospective, non-controlled, case series study enro...AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT). · METHODS: It was a prospective, non-controlled, case series study enrolling 81 eyes of 64 patients with CSME between August 2008 and January 2010. All patients received modified grid photocoagulation with frequency doubled Nd: YAG laser. Each patient was evaluated in terms of best-corrected visual acuity (BCVA) and regression or progression of maculopathy after laser therapy at 1, 3 and 6 months. Spearman’s correlation test was used to show the correlation between BCVA and total macular volume (TMV). Analysis of variance (ANOVA) was used to compare among groups and independent t-test was used to compare in each group. · RESULTS: There is high correlation between BCVA and TMV (P ≤0.001). BCVA improved in 50.6%, remained static in 39.5 % and deteriorated in 9.9% patients after 6 month of treatment. The Baseline TMV (mean and SD) were 9.26±1.83, 10.4±2.38, 11.5±3.05, 8.89±0.75 and 9.47±1.98 mm3 for different OCT patterns, ST (sponge like thickening), CMO (cystoid macular edema), SFD (subfoveal detachment), VMIA (Vitreo macular interface abnormality) and average TMV respectively (P =0.04). After 6 months of laser treatment, the mean TMV decreased from 9.47±1.98mm3 to 8.77±1.31mm3(P =0.01). In ST there was significant decrease in TMV, P =0.01, Further within these groups at 6 months, they were significantly different, P =0.01. · CONCLUSION: OCT showed the different morphological variant of CSME while the response of treatment is different. TMV decreased the most and hence showed the improvement in vision after 6 months of laser treatment. In the era of Anti vascular endothelial growth factors (VEGFs), efficacy of laser seems to be in shadow but it is still first line of treatment in developing nation like Nepal where antiVEGFs may not be easily available and affordable.展开更多
Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its asso...Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.展开更多
At current era of globalization, media is the double edged sword that is important both for health education as well as the stimulation of unhealthy behaviour. In Nepal, though there is ban on most forms of advertisin...At current era of globalization, media is the double edged sword that is important both for health education as well as the stimulation of unhealthy behaviour. In Nepal, though there is ban on most forms of advertising, it is not clear about placement of tobacco advertisement in TV, films and other forms of media. Studies about cigarette smoking and its association with media are inadequate in Nepal. The objective of this study was to explore the role of media in cigarette smoking habit of adolescents in Nepal. A cross-sectional study was conducted among 394 adolescent students by using questionnaire method in 3 randomly selected colleges of Kathmandu district, Nepal. Data were analysed by using bivariate and multinomial logistic regression analysis. Statistically significant relationship at 95% CI was found between cigarette smoking status and media related variables like: seeing cigarette advertisement, reading fashion magazine, attending musical program sponsored by cigarette companies, watching movies in cinema hall, liking heavy metal/hard rock music, television watching time and desire to smoke if favourite artist smokes. Multinomial logistic regression showed that those with high receptivity to cigarette advertisement were likely to be current smokers (OR = 71.416, CI: 8.796 - 579.823) and ever smokers (OR = 9.582, CI: 2.201 - 41.714) compared to never smokers. About 79% of respondents agreed that media teaches different ways of smoking to its audiences. Different forms of media including cinema, music, magazines, television, games and music sponsorship are found to be important predictors for smoking status of college students in urban Nepal. Thus smoking prevention activities should consider role of media in smoking provocation among adolescents.展开更多
Forests account for 80%of the total carbon exchange between the atmosphere and terrestrial ecosystems.Thus,to better manage our responses to global warming,it is important to monitor and assess forest aboveground carb...Forests account for 80%of the total carbon exchange between the atmosphere and terrestrial ecosystems.Thus,to better manage our responses to global warming,it is important to monitor and assess forest aboveground carbon and forest aboveground biomass(FAGB).Different levels of detail are needed to estimate FAGB at local,regional and national scales.Multi-scale remote sensing analysis from high,medium and coarse spatial resolution data,along with field sampling,is one approach often used.However,the methods developed are still time consuming,expensive,and inconvenient for systematic monitoring,especially for developing countries,as they require vast numbers of field samples for upscaling.Here,we recommend a convenient two-scale approach to estimate FAGB that was tested in our study sites.The study was conducted in the Chitwan district of Nepal using GeoEye-1(0.5 m),Landsat(30 m)and Google Earth very high resolution(GEVHR)Quickbird(0.65 m)images.For the local scale(Kayerkhola watershed),tree crowns of the area were delineated by the object-based image analysis technique on GeoEye images.An overall accuracy of 83%was obtained in the delineation of tree canopy cover(TCC)per plot.A TCC vs.FAGB model was developed based on the TCC estimations from GeoEye and FAGB measurements from field sample plots.A coefficient of determination(R2)of 0.76 was obtained in the modelling,and a value of 0.83 was obtained in the validation of the model.To upscale FAGB to the entire district,open source GEVHR images were used as virtual field plots.We delineated their TCC values and then calculated FAGB based on a TCC versus FAGB model.Using the multivariate adaptive regression splines machine learning algorithm,we developed a model from the relationship between the FAGB of GEVHR virtual plots with predictor parameters from Landsat 8 bands and vegetation indices.The model was then used to extrapolate FAGB to the entire district.This approach considerably reduced the need for field data and commercial very high resolution imagery while achie展开更多
Soil carbon dioxide emission: soil respiration is representing a major contributor of accumulating carbon dioxide in the atmosphere that aids to accelerate global warming and altering the climate. Soil temperature, so...Soil carbon dioxide emission: soil respiration is representing a major contributor of accumulating carbon dioxide in the atmosphere that aids to accelerate global warming and altering the climate. Soil temperature, soil water content, sun light and vegetation are considered most common regulators of soil respiration variations in ecosystem. The soil respiration was measured in grassland intended to examine how the soil respiration changed with varying climatic factors, for two years (2015 and 2016) in temperate grassland of Annapurna Conservation Area (ACA), Nepal. In the study, soil temperature accounted exponential function of soil respiration variation at 42.9%, 19.1% and 23.3%, and temperature sensitivity of the soil respiration (Q10) obtained at 6.2, 1.4 and 1.8 in October 2015 and April 2016 and both the measurements were combined, respectively. Significant negative (R2 = 0.50, p < 0.05, October 2015) and positive (R2 = 0.084, p < 0.05, April 2016) exponential function of soil respiration and soil water content were determined, where high soil respiration values were always measured between 30% and 35% of the soil water content. However, linear significant relationship was determined (R2 = 0.376, p < 0.05) between soil respiration and photosynthetic photon flux density (PPFD). Soil respiration value averaged in October 2015 was 357 mg CO2 m-2 h-1 and in April 2016 it was 444.6 mg CO2 m-2 h-1. Above- and below-ground plant biomasses were obtained at 231.1 g d w m-2 and 1538.8 g d w m-2 in October, and at 449.9 g d w m-2 and 349.0 g d w m-2 in April, respectively. This study showed variation of soil respiration in relation to the factors such as soil temperature, soil water content and photosynthetic photon flux density signifying their importance in governing ecosystem function and carbon balance of the temperate grassland ecosystem.展开更多
Chitwan-Annapuma Landscape(CHAL)in central Nepal is known for its rich biodiversity and the landscape is expected to provide corridors for species range shift in response to climate change.Environmental assessments ha...Chitwan-Annapuma Landscape(CHAL)in central Nepal is known for its rich biodiversity and the landscape is expected to provide corridors for species range shift in response to climate change.Environmental assessments have identified biological invasions and other anthropogenic activities as major threats to the biodiversity in the CHAL.One of the rapidly spreading Invasive Alien Plant species(IAPs)in the CHAL is Parthenium hysterophorus L.,a neotropical invasive weed of global significance.This study aimed to investigate the current and future projected suitable habitat of P.hysterophorus in the CHAL using MaxEnt modelling in three'Representative Concentration Pathways'(RCPs 2.6,4.5 and 8.5)corresponding to different greenhouse gases emissiontrajectories for the year 2050 and 2070.A total of 288species occurrence points,six bioclimatic variablesmean diurnal range,isothermality,annual precipitation,precipitation of driest month,precipitation seasonality,precipitation of driest quarter and two topographic variables(aspect and slope)were selected for MaxEnt modelling.Potential range shift in terms of increase or decline in the suitable habitat areas under the projected scenarios were calculated.Slope and annual precipitation were the most important variables that explained the current distribution of P.hysterophorus.Twenty percent of the total area of CHAL was predicted to be suitable habitat for the growth of P.hysterophorus in the current climatic condition.Highest gain in the suitable habitat of this noxious weed was found under RCP 4.5 scenario in 2050 and 2070.whereas there will be a loss in thesuitable habitat under RCP 8.5 scenario in 2050 and2070.Out of four physiographic regions present in CHAL,three regions-Siwalik,Middle Mountain and High Mountain have suitable habitat for P.hysterophorus under current climatic condition.The mountainous region is likely to be affected more than the Siwalik region by further spread of P.fhysteropfhorus in the future under low(RCP 2.6)to medium(RCP 4.5)emission scenarios.The 展开更多
Two classification and identification methods based on pattern discrimination models and the majority-vote technique were investigated for implementing a World Wide Web-based system for the identification of rice dise...Two classification and identification methods based on pattern discrimination models and the majority-vote technique were investigated for implementing a World Wide Web-based system for the identification of rice diseases. The experiment was carried out using color and shape patterns in 425 images of three rice diseases, which were classified into four classes： two classes of leaf blast, and one class each of sheath blight and brown spot. A method consisting of two discrimination steps involving application of multiple discrimination models of a support vector machine gave the best result because of its capacity to evaluate the similarity of disease types. This accuracy of the method was 88% for leaf blast （A-type）, 94% for sheath blight, and 80% for leaf blast （B-type） and brown spot; on average, the accuracy of this method was 5% greater than that of the other method when three classes were used in the model. Although the accuracy of both methods was inadequate, the results of this study show that it is possible to estimate the least number of possible or similar diseases from a large number of diseases. Therefore, we conclude that there is merit in grouping classes into subgroups rather than attempting to discriminate between all classes simultaneously and that these methods are effective in identifying diseases for web-based diagnosis.展开更多
文摘Flexible triboelectric nanogenerators (TENGs)-based pressure sensors are very essential for the wide-range applications, comprising wearable healthcare systems, intuitive human-device interfaces, electronic-skin (e-skin), and artificial intelligence. Most of conventional fabrication methods used to produce high-performance TENGs involve plasma treatment, photolithography, printing, and electro-deposition. However, these fabrication techniques are expensive, multi-step, time-consuming and not suitable for mass production, which are the main barriers for efficient and cost-effective commercialization of TENGs. Here, we established a highly reliable scheme for the fabrication of a novel eco-friendly, low cost, and TENG-based pressure sensor (TEPS) designed for usage in self-powered-human gesture detection (SP-HGD) likewise wearable healthcare applications. The sensors with microstructured electrodes performed well with high sensitivity (7.697 kPa^-1), a lower limit of detection (~ 1 Pa), faster response time (< 9.9 ms), and highly stable over > 4,000 compression-releasing cycles. The proposed method is suitable for the adaptable fabrication of TEPS at an extremely low cost with possible applications in self-powered systems, especially e-skin and healthcare applications.
基金supported by the National Natural Science Foundation of China,No.81303248,81603321the Natural Science Foundation of Heilongjiang Province of China,No.H2015028+1 种基金a grant from the Nursing Program for Young Scholars of Heilongjiang Province of China,No.UNPYSCT-2016116the Scientific Research Fund for Doctors of Qiqihar Medical University in China,No.QY2016B-09
文摘Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β （Aβ） induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme （IDE）, which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 （200 μM, 5 μL） into the hippocampus and subsequently administered Kai Xin San （0.54 or 1.08 g/kg/d） intragastrically for 21 consecutive days. Hematoxylin eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.
基金Supported by National Natural Science Foundation of China,No.81371652(to Huang JH)
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation(LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment(chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy(radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.
基金supported by grants from STI 2030-Major Projects(no.2022ZD0209100)the National Natural Science Foundation of China(nos.81971292 and 82150610506)+3 种基金the Natural Science Foundation of Shanghai(no.21ZR1428600)the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(nos.YG2022ZD026 and YG2023ZD27)SJTU Trans-med Awards Research(no.20220103)the Paul K.and Diane Shumaker Endowment Fund at University of Missouri.
文摘Identifying pathogenetic variants and inferring their impact on protein-protein interactions sheds light on their functional consequences on diseases.Limited by the availability of experimental data on the consequences of protein interaction,most existing methods focus on building models to predict changes in protein binding affinity.Here,we introduced MIPPI,an end-to-end,interpretable transformer-based deep learning model that learns features directly from sequences by leveraging the interaction data from IMEx.MIPPI was specifically trained to determine the types of variant impact(increasing,decreasing,disrupting,and no effect)on protein-protein interactions.We demonstrate the accuracy of MIPPI and provide interpretation through the analysis of learned attention weights,which exhibit correlations with the amino acids interacting with the variant.Moreover,we showed the practicality of MIPPI in prioritizing de novo mutations associated with complex neurodevelopmental disorders and the potential to determine the pathogenic and driving mutations.Finally,we experimentally validated the functional impact of several variants identified in patients with such disorders.Overall,MIPPI emerges as a versatile,robust,and interpretable model,capable of effectively predicting mutation impacts on protein-protein interactions and facilitating the discovery of clinically actionable variants.
基金YSZ received funding from National Institutes of Health(K99CA201603,R00CA201603,R21EB025270,R21EB026175,R01EB028143,R03EB027984)National Science Foundation(1935105)+1 种基金Brigham Research Institute New England Anti-Vivisection Foundation,and American Fund for Alternatives to Animal Research(AFAAR).AZ received funding from National Institutes of Health(K08DK113244,R01MD012579)SD received funding from National Institutes of Health(R01MD012579-UT20664DS).
文摘This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic studies.Using a photolithographic biofabrication method with a photomask featuring hexagonal units,liver cells,including a human hepatic cell line(HepG2-C3A)and a human hepatic stellate cell line(LX-2)were embedded in gelatin methacryloyl hydrogel.Hepatic steatosis was induced by supraphysiological concentration of free fatty acids;hepatic fibrosis was induced by transforming growth factor-β1.Induction of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic acid.Induction of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin treatment.This model was further preliminarily validated using primary human hepatocytes in a similar setup.These constructs provide a viable,biologically relevant,and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.
基金The Chinese Academy of Sciences President's International Fellowship Initiative (PIFI) for Visiting Scientist (Grant No.2023VMC0003)The National Science Foundation of China (Grant No.42230307)The Strategic Priority Research Program (A) of the Chinese Academy of Sciences (Grant No.XDA20070302)。
文摘Aim: To determine maternal and neonatal morbidities associated with instrumental vaginal delivery. Methods: This retrospective study consisted of 233 women undergoing instrumental vaginal deliveries from April 2020 to March 2021 at Paropakar Maternity and Women Hospital, a tertiary care hospital in Kathmandu, Nepal. Neonatal and maternal complications were analyzed. Results: Of 233 women, 102 (43.7%) and 131 (56.2%) had vacuum and forceps deliveries, respectively. The use of instruments was more frequent in infants with higher birth weight and gestational age. There were no significant differences in Apgar scores between the two groups. Two main indications of instrumental deliveries were fetal distress and prolonged second stage labor. Forceps, compared with vacuum, more often caused 3<sup>rd</sup>/4<sup>th</sup> perineal tears, tear extending to fornices, and postpartum hemorrhage. Neonatal outcomes were similar in both types of instrumental deliveries. Conclusion: Instrumental vaginal delivery caused maternal morbidity and procedure/judgment training for it is essential.
文摘Soil CO<sub>2</sub> efflux is an ongoing process of respiration from soil;plant parts/ microbes below the ground to the atmosphere which is known for faster cycling of carbon sources. A large portion of carbon sequestered and fixed by forests is returned to the atmosphere through soil CO<sub>2</sub> efflux and multiple controlling parameters mainly temperature, precipitation, and growth factors interact with the soil CO<sub>2</sub> efflux variation. This study assessed the soil CO<sub>2</sub> efflux every month for consecutive 2-years (August 2015 to July 2017) by using the closed chamber method to determine the role of ecological parameters that govern the soil CO<sub>2</sub> efflux and its temporal modification in a sub-tropical mixed forest of central region in Nepal. The results of this study manifested that soil CO<sub>2</sub> efflux accounted 63.2% (y = 31.96e<sup>0.128x</sup>), 71.3% (y = 44.77e<sup>0.123x</sup>) and 64.5% (y = 44.11e<sup>0.117x</sup>) variations in soil temperature with significantly (p < 0.05) exponential positive relation in the year 2015/2016, 2016/2017 and the two years when merged. And the temperature sensitivity value (Q<sub>10</sub>) of the soil CO<sub>2</sub> efflux was 3.6, 3.4, and 3.2, respectively. Soil water content also expressed significantly (p < 0.05) positive exponential effect on soil CO<sub>2</sub> efflux and accounted 62.0% (y = 138.3e<sup>0.057x</sup>), 46.1% (y = 88.42e<sup>0.052x</sup>) and 40.5% (y = 133.1e<sup>0.0447x</sup>) in its variability in different years and the merged years. Evident variations of soil CO<sub>2</sub> efflux, soil temperature, soil water content, and litter were observed in the forest seasonally and inter-annually. Two years mean total annual soil CO<sub>2</sub> efflux of the forest was estimated at 904.76 g C·m<sup>-2</sup>·y<sup>-1</sup>. The study revealed that sub-tropical forests could be more influenced by precipitation regimes in progressing warm climates i.e. vulnerable to climate change, illustrating the comprehensive dy
基金Supported by Natinoal Academy of Medical Sciences, Bir Hospital, Nepal
文摘AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT). · METHODS: It was a prospective, non-controlled, case series study enrolling 81 eyes of 64 patients with CSME between August 2008 and January 2010. All patients received modified grid photocoagulation with frequency doubled Nd: YAG laser. Each patient was evaluated in terms of best-corrected visual acuity (BCVA) and regression or progression of maculopathy after laser therapy at 1, 3 and 6 months. Spearman’s correlation test was used to show the correlation between BCVA and total macular volume (TMV). Analysis of variance (ANOVA) was used to compare among groups and independent t-test was used to compare in each group. · RESULTS: There is high correlation between BCVA and TMV (P ≤0.001). BCVA improved in 50.6%, remained static in 39.5 % and deteriorated in 9.9% patients after 6 month of treatment. The Baseline TMV (mean and SD) were 9.26±1.83, 10.4±2.38, 11.5±3.05, 8.89±0.75 and 9.47±1.98 mm3 for different OCT patterns, ST (sponge like thickening), CMO (cystoid macular edema), SFD (subfoveal detachment), VMIA (Vitreo macular interface abnormality) and average TMV respectively (P =0.04). After 6 months of laser treatment, the mean TMV decreased from 9.47±1.98mm3 to 8.77±1.31mm3(P =0.01). In ST there was significant decrease in TMV, P =0.01, Further within these groups at 6 months, they were significantly different, P =0.01. · CONCLUSION: OCT showed the different morphological variant of CSME while the response of treatment is different. TMV decreased the most and hence showed the improvement in vision after 6 months of laser treatment. In the era of Anti vascular endothelial growth factors (VEGFs), efficacy of laser seems to be in shadow but it is still first line of treatment in developing nation like Nepal where antiVEGFs may not be easily available and affordable.
文摘Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.
文摘At current era of globalization, media is the double edged sword that is important both for health education as well as the stimulation of unhealthy behaviour. In Nepal, though there is ban on most forms of advertising, it is not clear about placement of tobacco advertisement in TV, films and other forms of media. Studies about cigarette smoking and its association with media are inadequate in Nepal. The objective of this study was to explore the role of media in cigarette smoking habit of adolescents in Nepal. A cross-sectional study was conducted among 394 adolescent students by using questionnaire method in 3 randomly selected colleges of Kathmandu district, Nepal. Data were analysed by using bivariate and multinomial logistic regression analysis. Statistically significant relationship at 95% CI was found between cigarette smoking status and media related variables like: seeing cigarette advertisement, reading fashion magazine, attending musical program sponsored by cigarette companies, watching movies in cinema hall, liking heavy metal/hard rock music, television watching time and desire to smoke if favourite artist smokes. Multinomial logistic regression showed that those with high receptivity to cigarette advertisement were likely to be current smokers (OR = 71.416, CI: 8.796 - 579.823) and ever smokers (OR = 9.582, CI: 2.201 - 41.714) compared to never smokers. About 79% of respondents agreed that media teaches different ways of smoking to its audiences. Different forms of media including cinema, music, magazines, television, games and music sponsorship are found to be important predictors for smoking status of college students in urban Nepal. Thus smoking prevention activities should consider role of media in smoking provocation among adolescents.
基金supported by the CAS Strategic Priority Research Program(No.XDA19030402)the National Key Research and Development Program of China(No.2016YFD0300101)+2 种基金the Natural Science Foundation of China(Nos.31571565,31671585)the Key Basic Research Project of the Shandong Natural Science Foundation of China(No.ZR2017ZB0422)Research Funding of Qingdao University(No.41117010153)
文摘Forests account for 80%of the total carbon exchange between the atmosphere and terrestrial ecosystems.Thus,to better manage our responses to global warming,it is important to monitor and assess forest aboveground carbon and forest aboveground biomass(FAGB).Different levels of detail are needed to estimate FAGB at local,regional and national scales.Multi-scale remote sensing analysis from high,medium and coarse spatial resolution data,along with field sampling,is one approach often used.However,the methods developed are still time consuming,expensive,and inconvenient for systematic monitoring,especially for developing countries,as they require vast numbers of field samples for upscaling.Here,we recommend a convenient two-scale approach to estimate FAGB that was tested in our study sites.The study was conducted in the Chitwan district of Nepal using GeoEye-1(0.5 m),Landsat(30 m)and Google Earth very high resolution(GEVHR)Quickbird(0.65 m)images.For the local scale(Kayerkhola watershed),tree crowns of the area were delineated by the object-based image analysis technique on GeoEye images.An overall accuracy of 83%was obtained in the delineation of tree canopy cover(TCC)per plot.A TCC vs.FAGB model was developed based on the TCC estimations from GeoEye and FAGB measurements from field sample plots.A coefficient of determination(R2)of 0.76 was obtained in the modelling,and a value of 0.83 was obtained in the validation of the model.To upscale FAGB to the entire district,open source GEVHR images were used as virtual field plots.We delineated their TCC values and then calculated FAGB based on a TCC versus FAGB model.Using the multivariate adaptive regression splines machine learning algorithm,we developed a model from the relationship between the FAGB of GEVHR virtual plots with predictor parameters from Landsat 8 bands and vegetation indices.The model was then used to extrapolate FAGB to the entire district.This approach considerably reduced the need for field data and commercial very high resolution imagery while achie
文摘Soil carbon dioxide emission: soil respiration is representing a major contributor of accumulating carbon dioxide in the atmosphere that aids to accelerate global warming and altering the climate. Soil temperature, soil water content, sun light and vegetation are considered most common regulators of soil respiration variations in ecosystem. The soil respiration was measured in grassland intended to examine how the soil respiration changed with varying climatic factors, for two years (2015 and 2016) in temperate grassland of Annapurna Conservation Area (ACA), Nepal. In the study, soil temperature accounted exponential function of soil respiration variation at 42.9%, 19.1% and 23.3%, and temperature sensitivity of the soil respiration (Q10) obtained at 6.2, 1.4 and 1.8 in October 2015 and April 2016 and both the measurements were combined, respectively. Significant negative (R2 = 0.50, p < 0.05, October 2015) and positive (R2 = 0.084, p < 0.05, April 2016) exponential function of soil respiration and soil water content were determined, where high soil respiration values were always measured between 30% and 35% of the soil water content. However, linear significant relationship was determined (R2 = 0.376, p < 0.05) between soil respiration and photosynthetic photon flux density (PPFD). Soil respiration value averaged in October 2015 was 357 mg CO2 m-2 h-1 and in April 2016 it was 444.6 mg CO2 m-2 h-1. Above- and below-ground plant biomasses were obtained at 231.1 g d w m-2 and 1538.8 g d w m-2 in October, and at 449.9 g d w m-2 and 349.0 g d w m-2 in April, respectively. This study showed variation of soil respiration in relation to the factors such as soil temperature, soil water content and photosynthetic photon flux density signifying their importance in governing ecosystem function and carbon balance of the temperate grassland ecosystem.
基金support provided by the Feed the Future Innovation Lab for Integrated Pest Management of the U.S. Agency for International Development, under the terms of Cooperative Agreement No. AID–OAA-L-15-00001supported by International Foundation for Science (Sweden), Nepal Academy of Science and Technology (Nepal), and National Trust for Nature Conservation (Nepal)
文摘Chitwan-Annapuma Landscape(CHAL)in central Nepal is known for its rich biodiversity and the landscape is expected to provide corridors for species range shift in response to climate change.Environmental assessments have identified biological invasions and other anthropogenic activities as major threats to the biodiversity in the CHAL.One of the rapidly spreading Invasive Alien Plant species(IAPs)in the CHAL is Parthenium hysterophorus L.,a neotropical invasive weed of global significance.This study aimed to investigate the current and future projected suitable habitat of P.hysterophorus in the CHAL using MaxEnt modelling in three'Representative Concentration Pathways'(RCPs 2.6,4.5 and 8.5)corresponding to different greenhouse gases emissiontrajectories for the year 2050 and 2070.A total of 288species occurrence points,six bioclimatic variablesmean diurnal range,isothermality,annual precipitation,precipitation of driest month,precipitation seasonality,precipitation of driest quarter and two topographic variables(aspect and slope)were selected for MaxEnt modelling.Potential range shift in terms of increase or decline in the suitable habitat areas under the projected scenarios were calculated.Slope and annual precipitation were the most important variables that explained the current distribution of P.hysterophorus.Twenty percent of the total area of CHAL was predicted to be suitable habitat for the growth of P.hysterophorus in the current climatic condition.Highest gain in the suitable habitat of this noxious weed was found under RCP 4.5 scenario in 2050 and 2070.whereas there will be a loss in thesuitable habitat under RCP 8.5 scenario in 2050 and2070.Out of four physiographic regions present in CHAL,three regions-Siwalik,Middle Mountain and High Mountain have suitable habitat for P.hysterophorus under current climatic condition.The mountainous region is likely to be affected more than the Siwalik region by further spread of P.fhysteropfhorus in the future under low(RCP 2.6)to medium(RCP 4.5)emission scenarios.The
文摘Two classification and identification methods based on pattern discrimination models and the majority-vote technique were investigated for implementing a World Wide Web-based system for the identification of rice diseases. The experiment was carried out using color and shape patterns in 425 images of three rice diseases, which were classified into four classes： two classes of leaf blast, and one class each of sheath blight and brown spot. A method consisting of two discrimination steps involving application of multiple discrimination models of a support vector machine gave the best result because of its capacity to evaluate the similarity of disease types. This accuracy of the method was 88% for leaf blast （A-type）, 94% for sheath blight, and 80% for leaf blast （B-type） and brown spot; on average, the accuracy of this method was 5% greater than that of the other method when three classes were used in the model. Although the accuracy of both methods was inadequate, the results of this study show that it is possible to estimate the least number of possible or similar diseases from a large number of diseases. Therefore, we conclude that there is merit in grouping classes into subgroups rather than attempting to discriminate between all classes simultaneously and that these methods are effective in identifying diseases for web-based diagnosis.
