With the emergence of new materials for high-efficiency organic solar cells(OSCs),understanding and finetuning the interface energetics become increasingly important.Precise determination of the so-called pinning ener...With the emergence of new materials for high-efficiency organic solar cells(OSCs),understanding and finetuning the interface energetics become increasingly important.Precise determination of the so-called pinning energies,one of the critical characteristics of the material to predict the energy level alignment(ELA)at either electrode/organic or organic/organic interfaces,are urgently needed for the new materials.Here,pinning energies of a wide variety of newly developed donors and nonfullerene acceptors(NFAs)are measured through ultraviolet photoelectron spectroscopy.The positive pinning energies of the studied donors and the negative pinning energies of NFAs are in the same energy range of 4.3−4.6 eV,which follows the design rules developed for fullerene-based OSCs.The ELA for metal/organic and inorganic/organic interfaces follows the predicted behavior for all of the materials studied.For organic-organic heterojunctions where both the donor and the NFA feature strong intramolecular charge transfer,the pinning energies often underestimate the experimentally obtained interface vacuum level shift,which has consequences for OSC device performance.展开更多
One of the most enigmatic problems in biomedical research surrounds the phenomenon that neurodegenerative diseases target specific cell types and brain regions.This is difficult to explain because the proteins that ca...One of the most enigmatic problems in biomedical research surrounds the phenomenon that neurodegenerative diseases target specific cell types and brain regions.This is difficult to explain because the proteins that cause them are widely expressed,often highest in resistant regions.This mystery is further complicated by the fact that some disease-causing proteins are associated with multiple diseases.展开更多
This study uses the dynamic conditional correlation to investigate how technology subsector stocks interact with financial assets in the face of economic and financial uncertainty.Our results suggest that structural b...This study uses the dynamic conditional correlation to investigate how technology subsector stocks interact with financial assets in the face of economic and financial uncertainty.Our results suggest that structural breaks have diverse effects on financial asset connectedness and that the level of bond linkage increases when the trend breaks.We see a growing co-movement between the technology sector and major financial assets when uncertainty is considered.Overall,our findings indicate that the connectedness response varies depending on the type of uncertainty shock.展开更多
The grey wolf optimizer(GWO)is a swarm-based intelligence optimization algorithm by simulating the steps of searching,encircling,and attacking prey in the process of wolf hunting.Along with its advantages of simple pr...The grey wolf optimizer(GWO)is a swarm-based intelligence optimization algorithm by simulating the steps of searching,encircling,and attacking prey in the process of wolf hunting.Along with its advantages of simple principle and few parameters setting,GWO bears drawbacks such as low solution accuracy and slow convergence speed.A few recent advanced GWOs are proposed to try to overcome these disadvantages.However,they are either difficult to apply to large-scale problems due to high time complexity or easily lead to early convergence.To solve the abovementioned issues,a high-accuracy variable grey wolf optimizer(VGWO)with low time complexity is proposed in this study.VGWO first uses the symmetrical wolf strategy to generate an initial population of individuals to lay the foundation for the global seek of the algorithm,and then inspired by the simulated annealing algorithm and the differential evolution algorithm,a mutation operation for generating a new mutant individual is performed on three wolves which are randomly selected in the current wolf individuals while after each iteration.A vectorized Manhattan distance calculation method is specifically designed to evaluate the probability of selecting the mutant individual based on its status in the current wolf population for the purpose of dynamically balancing global search and fast convergence capability of VGWO.A series of experiments are conducted on 19 benchmark functions from CEC2014 and CEC2020 and three real-world engineering cases.For 19 benchmark functions,VGWO’s optimization results place first in 80%of comparisons to the state-of-art GWOs and the CEC2020 competition winner.A further evaluation based on the Friedman test,VGWO also outperforms all other algorithms statistically in terms of robustness with a better average ranking value.展开更多
In the hyperbolic research community,there exists the strong belief that a continuous Galerkin scheme is notoriously unstable and additional stabilization terms have to be added to guarantee stability.In the first par...In the hyperbolic research community,there exists the strong belief that a continuous Galerkin scheme is notoriously unstable and additional stabilization terms have to be added to guarantee stability.In the first part of the series[6],the application of simultaneous approximation terms for linear problems is investigated where the boundary conditions are imposed weakly.By applying this technique,the authors demonstrate that a pure continu-ous Galerkin scheme is indeed linearly stable if the boundary conditions are imposed in the correct way.In this work,we extend this investigation to the nonlinear case and focus on entropy conservation.By switching to entropy variables,we provide an estimation of the boundary operators also for nonlinear problems,that guarantee conservation.In numerical simulations,we verify our theoretical analysis.展开更多
Defect passivation is one of the most important strategies to boost both the efficiency and stability of perovskite solar cells(PSCs).Here,nontoxic and sustainable forest-based biomaterial,betulin,is first introduced ...Defect passivation is one of the most important strategies to boost both the efficiency and stability of perovskite solar cells(PSCs).Here,nontoxic and sustainable forest-based biomaterial,betulin,is first introduced into perovskites.The experiments and calculations reveal that betulin can effectively passivate the uncoordinated lead ions in perovskites via sharing the lone pair electrons of hydroxyl group,promoting charge transport.As a result,the power conversion efficiencies of the p-i-n planar PSCs remarkably increase from 19.14%to 21.15%,with the improvement of other parameters.The hydrogen bonds of betulin lock methylamine and halogen ions along the grain boundaries and on the film surface and thus suppress ion migration,further stabilizing perovskite crystal structures.These positive effects enable the PSCs to maintain 90%of the initial efficiency after 30 days in ambient air with 60%±5%relative humidity,75%after 300 h aging at 85℃,and 55%after 250 h light soaking,respectively.This work opens a new pathway for using nontoxic and low-cost biomaterials from forest to make highly efficient and stable PSCs.展开更多
Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been establishe...Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.展开更多
BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of ...BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer(CRC)and evaluate their prognostic significance.METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue(n=98),compared with paired normal tissue,and in plasma from patients with CRC(n=103),compared with healthy controls(n=97).Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery,Ryhov County Hospital,Jönköping,Sweden.Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue(n=101).Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue(90%,P<0.001 and 45%,P<0.05,respectively).CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease.Low CCL4 protein expression levels in CRC tissue were associated with a 30%lower cancer-specific survival rate in patients(P<0.01).The level of plasma CCL4 was 11%higher in CRC patients than in healthy controls(P<0.05)and was positively correlated(r=0.56,P<0.01)with the CCL4 protein level in CRC tissue.The analysis of CCL4 gene polymorphism rs10491121 showed a difference(P<0.05)between localized disease and disseminated disease in the right colon,with a dominance of allele A in localized disease.Moreover,the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer.CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121,particularly in the right colon,are associated with clinical outcome in CRC patients.展开更多
The Nepal Himalayas is the source of many glacial and spring-fed river systems crisscrossing the mountainous terrain.There is an increasing recognition of small mountain rivers(SMRs)to have a significant combined expo...The Nepal Himalayas is the source of many glacial and spring-fed river systems crisscrossing the mountainous terrain.There is an increasing recognition of small mountain rivers(SMRs)to have a significant combined export of dissolved and particulate organic carbon to the global carbon flux.We analyzed fluvial sediments from two SMRs and compared the results with two large mountain rivers(LMRs)in Nepal.We investigated the organic matter(OM),its compositional variability,and seasonal export using a suite of lipid biomarkers,namely n-alkanes,n-alkanoic acids,n-alkanols,and sterols.The SMRs indicated a similarity in lipid distribution and were affected by a strong seasonal variability.The LMRs showed a distinct contrast in the distribution of lipids in suspended sediments.Bedload sediments in SMRs were derived from diverse sources with weak terrigenous dominance all-year-round compared to the suspended load.Functional lipids(n-alkanoic acids and n-alkanols)were the major constituents in SMR sediments,indicating better preservation.In contrast,n-alkane concentration dominated over other fractions in suspended sediments retrieved from LMRs.The biomarker trends differentiate SMRs from LMRs with lower transformed/degraded OM in SMRs.A common observation was the strong presence of even carbon compounds in short-chain n-alkanes in SMR bedload sediments and their predominance in suspended sediments in LMRs.Such an unusual trend is attributed to specific biomarker sources from the catchment and ongoing processes in fluvial systems.Topsoil colonized by fungal species under moist acidic conditions and autochthonous bacteria contributes to the organic matter pool in shallow SMRs.In LMRs,the contribution from thermally mature sedimentary hydrocarbons and the diagenetic reduction of nalkanoic acids to n-alkanes are additional contributors to the allochthonous carbon pool.The differences in lipid concentrations,their distribution,seasonality,and the size of rivers suggest differential preservation/degradation of the organic matter pool and their importance in contributing to the carbon budget.展开更多
Background:Identification of relevant in vivo biomarkers for fertility remains a challenge for the livestock industry.Concentrations of the small peptide hormone oxytocin(OXT),involved in male reproductive function an...Background:Identification of relevant in vivo biomarkers for fertility remains a challenge for the livestock industry.Concentrations of the small peptide hormone oxytocin(OXT),involved in male reproductive function and present in the seminal plasma(SP)of several species could be a robust one.This study characterized concentrations of SPOXT in ejaculates from boars used in artificial insemination(AI)programs aiming to evaluate its relationship with sperm quality variables and in vivo fertility of their liquid-stored AI-semen.Seminal OXT concentrations(ng/mL)were measured in 169 ejaculates from 61 boars of the Duroc,Pietrain,Landrace and Large White breeds using a direct competitive immunoassay test based on AlphaLISA®technology.Ejaculate(ejaculate volume,sperm concentration,total sperm count)and sperm parameters(motility,viability,intracellular generation of reactive oxygen species,plasma membrane fluidity)were assessed at 0 h and 72 h in AI-semen samples stored at 17℃.In vivo fertility included only 18 Large White and Landrace boars whose AI-semen was used to inseminated>100 sows and evaluated both farrowing rate and litter size of 3,167 sows.Results:The results showed that SP-OXT differed between boars and between ejaculates within boar(P<0.05)but not between breeds(Duroc,Pietrain,Landrace and Large White).Ejaculates with higher SP-OXT concentration/mL(hierarchically grouped;P<0.001)had larger volume and came from younger boars(P<0.05).Ejaculates of boars showing positive farrowing rate deviation exhibited higher(P<0.05)SP-OXT concentration/mL than those with negative farrowing rate deviation.Conclusion:The SP concentrations of OXT are boar,ejaculate and age dependent,and positively related with ejaculate volume and farrowing rates of liquid-stored semen AI-doses.展开更多
MAX phases are gaining attention as precursors of two-dimensional MXenes that are intensively pursued in applications for electrochemical energy storage.Here,we report the preparation of V_(2)SnC MAX phase by the molt...MAX phases are gaining attention as precursors of two-dimensional MXenes that are intensively pursued in applications for electrochemical energy storage.Here,we report the preparation of V_(2)SnC MAX phase by the molten salt method.V_(2)SnC is investigated as a lithium storage anode,showing a high gravimetric capacity of 490 mAh g−1 and volumetric capacity of 570 mAh cm^(−3) as well as superior rate performance of 95 mAh g^(−1)(110 mAh cm^(−3))at 50 C,surpassing the ever-reported performance of MAX phase anodes.Sup-ported by operando X-ray diffraction and density functional theory,a charge storage mechanism with dual redox reaction is proposed with a Sn-Li(de)alloying reaction that occurs at the edge sites of V_(2)SnC particles where Sn atoms are exposed to the electrolyte followed by a redox reaction that occurs at V_(2)C layers with Li.This study offers promise of using MAX phases with M-site and A-site elements that are redox active as high-rate lithium storage materials.展开更多
The tremendous amount of wasted heat from solar radiation and industry dissipation has motivated the development of thermoelectric concepts that directly convert heat into electricity.The main challenge in practical a...The tremendous amount of wasted heat from solar radiation and industry dissipation has motivated the development of thermoelectric concepts that directly convert heat into electricity.The main challenge in practical applications for thermoelectrics is the high cost from both materials and manufacturing.Recently,breakthrough progresses in ionic thermoelectrics open up new possibilities to charge energy storage devices when submitted to a temperature gradient.The charging voltage is internally from the ionic Seebeck effect of the electrolyte between two electrodes.Hence electrolytes with high thermoelectric figure of merit are classified as ionic thermoelectric materials.Most ionic thermoelectric materials are composed of abundant elements,and they can generate hundreds of times larger thermal voltage than that of electronic materials.This emerging thermoelectric category brings new hope to fabricate low cost and large area heat-to-energy conversion devices,and triggers a renewed interest for ionic thermodiffusion.In this review,we summarize the state of the art in the new field of ionic thermoelectrics,from the driving force of the ionic thermodiffusion to material and application developments.We present a general map of ionic thermoelectric materials,discuss the unique characters of each type of the reported electrolytes,and propose potential optimization and future topics of ionic thermoelectrics.展开更多
BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-rep...BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-reported LBP.No study has previously investigated whether exposure to prolonged flexed sitting posture provokes discomfort/pain and decreased interspinous pressure pain thresholds for healthy young men and women without back pain,despite this being a suggested risk factor for LBP.AIM To investigate whether sitting in a prolonged flexed lumbar posture provokes discomfort and lowers interspinous pressure pain thresholds in the lumbar spine for healthy young men and women without previous LBP.METHODS This is a an observational before and after study of 26 participants(13 men,13 women)between 20-35 years old.Algometry was used to examine the pain threshold for pressure applied between spinous processes of the lumbar spine L1-L5.Pressure algometer measures were performed in prone before and after participants were instructed to sit in a fully flexed posture for a maximum of 15 min or until discomfort was experienced in the low back(Borg CR10=7/10).Wilcoxon signed-rank test was used for analyze values from the before and after test conditions.Mann-Whitney U test was used to investigate potential gender difference.RESULTS Fully flexed lumbar spine sitting posture up to 15 min provoked temporary discomfort but the proportion of participants experiencing discomfort 7/10 in the low back was 62%.For all pain pressure threshold locations tested,there was a significant difference for the study population with moderate-large decreased(r=-0.56)pressure pain threshold after exposure to prolonged flexed sitting posture(P<0.01).Comparisons between gender did not show any significant difference.CONCLUSION The result showed that exposure to fully flexed lumbar sitting posture for up to 15 min produced temporary discomfort in the low back in young healthy adults with no previous history of LBP and significantly reduced lumbar interspinous pressure pain thresholds.No gender-based differences were observed.展开更多
Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and e...Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.展开更多
Magnetotactic bacteria(MTB),ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals.MTB endogenously produce magnetic nanocrystals enabling them to orient a...Magnetotactic bacteria(MTB),ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals.MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields.Similar magnetite deposits have been found throughout the tissues of the human brain,including brain regions associated with orientation such as the cerebellum and hippocampus,the origins of which remain unknown.Speculation over the role and source of MTB in humans,as well as any association with the brain,remain unanswered.We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions.We identified seven MTB in the human gut microbiome:Magnetococcus marinus,Magnetospira sp.QH-2,Magnetospirillum magneticum,Magnetospirillum sp.ME-1,Magnetospirillum sp.XM-1,Magnetospirillum gryphiswaldense,and Desulfovibrio magneticus.Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus(adjusted for total intracranial volume,uncorrected P<0.05).These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation.These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans.Further studies will be necessary to validate and elucidate the relationship between these bacteria,magnetite concentrations,and brain function.展开更多
AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = ...AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.展开更多
Poor road conditions in underground mine tunnels can lead to decreased production efficiency and increased wear on production vehicles. A prototype system for road condition monitoring is presented in this paper to co...Poor road conditions in underground mine tunnels can lead to decreased production efficiency and increased wear on production vehicles. A prototype system for road condition monitoring is presented in this paper to counteract this. The system consists of three components i.e. localization, road monitoring, and scheduling. The localization of vehicles is performed using a Rao-Blackwellized extended particle filter, combining vehicle mounted sensors with signal strengths of Wi Fi access points. Two methods for road monitoring are described: a Kalman filter used together with a model of the vehicle suspension system, and a relative condition measure based on the power spectral density. Lastly, a method for taking automatic action on an ill-conditioned road segment is proposed in the form of a rescheduling algorithm.The scheduling algorithm is based on the large neighborhood search and is used to integrate road service activities in the short-term production schedule while minimizing introduced production disturbances.The system is demonstrated on experimental data collected in a Swedish underground mine.展开更多
BACKGROUND The majority of patients with newly diagnosed metastatic prostate cancer(PC)initially respond to androgen deprivation therapy(ADT)and are classified as metastatic castration-sensitive PC(mCSPC).Following mo...BACKGROUND The majority of patients with newly diagnosed metastatic prostate cancer(PC)initially respond to androgen deprivation therapy(ADT)and are classified as metastatic castration-sensitive PC(mCSPC).Following months to years of ADT,the disease tends to become resistant to ADT.Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC.Following its implementation in routine care,this combined treatment strategy requires more detailed evaluation in a real-world setting.AIM To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC.METHODS A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed.This region includes approximately 1.1 million citizens and the oncology departments of Linköping,Jönköping,and Kalmar.All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included.The primary endpoint was progression-free survival(PFS)at 12 mo,and the secondary endpoints were PFS at 24 mo,overall survival(OS),treatment intensity,adverse events,and unplanned hospitalizations.Exploratory analyses on potential prognostic parameters were performed.RESULTS Ninety-four patients were eligible and formed the study cohort.PFS at 12 and 24 mo was 75%(95%CI:66–84)and 58%(46–70),respectively.OS at 12 and 24 mo was 93%(87–99)and 86%(76–96).A total of 91%of patients(n=86)were given docetaxel according to the standard protocol of 75 mg/m2 every 3 wk(6 cycles),while 9%(n=8)received a modified protocol of 50 mg/m2 every 2 wk(9 cycles).The average overall dose intensity for those commencing standard treatment was 91%.Univariate Cox regression analyses show that baseline PSA>180 vs<180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors(HR 2.86,95%CI:1.39–5.87,P=0.0041 and 3.36,95%CI:1.03–10.96,P=0.045).Following multivariate analysis,statistical significance remained for PSA(2.51,95%CI:1.21–5.19,P=0.013)but not for metastatic status(2.60,95%CI:0.78–8.65,P=0.12).Febrile neutropenia was recorded in 21%(n=20)of patients,and 26%(n=24)had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course.CONCLUSION Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.展开更多
The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM ...The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM and the survival of patients with CRC is controversial.Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM.In our cohort,we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin.On the other hand,we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients.The dominance of the T bearing genotypes in patients with DM was statistically significant(P=0.038),with an odds ratio of 1.66(95%confidence interval:1.03-2.69).展开更多
基金the financial support from the Swedish Research Council(project grants no.2016-05498,2016-05990,and 2020-04538)the Swedish Energy Agency(grant.no.45411-1)+1 种基金by the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University(Faculty Grant SFO Mat LiU no.200900971)support from the Wallenberg Wood Science Center(WWSC).
文摘With the emergence of new materials for high-efficiency organic solar cells(OSCs),understanding and finetuning the interface energetics become increasingly important.Precise determination of the so-called pinning energies,one of the critical characteristics of the material to predict the energy level alignment(ELA)at either electrode/organic or organic/organic interfaces,are urgently needed for the new materials.Here,pinning energies of a wide variety of newly developed donors and nonfullerene acceptors(NFAs)are measured through ultraviolet photoelectron spectroscopy.The positive pinning energies of the studied donors and the negative pinning energies of NFAs are in the same energy range of 4.3−4.6 eV,which follows the design rules developed for fullerene-based OSCs.The ELA for metal/organic and inorganic/organic interfaces follows the predicted behavior for all of the materials studied.For organic-organic heterojunctions where both the donor and the NFA feature strong intramolecular charge transfer,the pinning energies often underestimate the experimentally obtained interface vacuum level shift,which has consequences for OSC device performance.
基金Wallenberg Center for Molecular Medicine,the Knut and Alice Wallenberg foundationthe King Gustaf and Queen Victoria foundation (to WSJ)。
文摘One of the most enigmatic problems in biomedical research surrounds the phenomenon that neurodegenerative diseases target specific cell types and brain regions.This is difficult to explain because the proteins that cause them are widely expressed,often highest in resistant regions.This mystery is further complicated by the fact that some disease-causing proteins are associated with multiple diseases.
基金supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF-2022S1A5A2A01038422).
文摘This study uses the dynamic conditional correlation to investigate how technology subsector stocks interact with financial assets in the face of economic and financial uncertainty.Our results suggest that structural breaks have diverse effects on financial asset connectedness and that the level of bond linkage increases when the trend breaks.We see a growing co-movement between the technology sector and major financial assets when uncertainty is considered.Overall,our findings indicate that the connectedness response varies depending on the type of uncertainty shock.
文摘The grey wolf optimizer(GWO)is a swarm-based intelligence optimization algorithm by simulating the steps of searching,encircling,and attacking prey in the process of wolf hunting.Along with its advantages of simple principle and few parameters setting,GWO bears drawbacks such as low solution accuracy and slow convergence speed.A few recent advanced GWOs are proposed to try to overcome these disadvantages.However,they are either difficult to apply to large-scale problems due to high time complexity or easily lead to early convergence.To solve the abovementioned issues,a high-accuracy variable grey wolf optimizer(VGWO)with low time complexity is proposed in this study.VGWO first uses the symmetrical wolf strategy to generate an initial population of individuals to lay the foundation for the global seek of the algorithm,and then inspired by the simulated annealing algorithm and the differential evolution algorithm,a mutation operation for generating a new mutant individual is performed on three wolves which are randomly selected in the current wolf individuals while after each iteration.A vectorized Manhattan distance calculation method is specifically designed to evaluate the probability of selecting the mutant individual based on its status in the current wolf population for the purpose of dynamically balancing global search and fast convergence capability of VGWO.A series of experiments are conducted on 19 benchmark functions from CEC2014 and CEC2020 and three real-world engineering cases.For 19 benchmark functions,VGWO’s optimization results place first in 80%of comparisons to the state-of-art GWOs and the CEC2020 competition winner.A further evaluation based on the Friedman test,VGWO also outperforms all other algorithms statistically in terms of robustness with a better average ranking value.
基金funded by the SNF Grant(Number 200021175784)the UZH Postdoc grant+1 种基金funded by an SNF Grant 200021_153604The Los Alamos unlimited release number is LA-UR-19-32411.
文摘In the hyperbolic research community,there exists the strong belief that a continuous Galerkin scheme is notoriously unstable and additional stabilization terms have to be added to guarantee stability.In the first part of the series[6],the application of simultaneous approximation terms for linear problems is investigated where the boundary conditions are imposed weakly.By applying this technique,the authors demonstrate that a pure continu-ous Galerkin scheme is indeed linearly stable if the boundary conditions are imposed in the correct way.In this work,we extend this investigation to the nonlinear case and focus on entropy conservation.By switching to entropy variables,we provide an estimation of the boundary operators also for nonlinear problems,that guarantee conservation.In numerical simulations,we verify our theoretical analysis.
基金supported by the National Natural Science Foundation of China(21875067,51811530011,11604099)the Fundamental Research Funds for the Central Universities,Shanghai Rising-Star(19QA1403100)+2 种基金ECNU Multifunctional Platform for Innovation(006)the National Key Research and Development Program of China(2017YFA0206600)the National Natural Science Foundation of China(51773045,21772030,51922032,21961160720)for financial support。
文摘Defect passivation is one of the most important strategies to boost both the efficiency and stability of perovskite solar cells(PSCs).Here,nontoxic and sustainable forest-based biomaterial,betulin,is first introduced into perovskites.The experiments and calculations reveal that betulin can effectively passivate the uncoordinated lead ions in perovskites via sharing the lone pair electrons of hydroxyl group,promoting charge transport.As a result,the power conversion efficiencies of the p-i-n planar PSCs remarkably increase from 19.14%to 21.15%,with the improvement of other parameters.The hydrogen bonds of betulin lock methylamine and halogen ions along the grain boundaries and on the film surface and thus suppress ion migration,further stabilizing perovskite crystal structures.These positive effects enable the PSCs to maintain 90%of the initial efficiency after 30 days in ambient air with 60%±5%relative humidity,75%after 300 h aging at 85℃,and 55%after 250 h light soaking,respectively.This work opens a new pathway for using nontoxic and low-cost biomaterials from forest to make highly efficient and stable PSCs.
基金This study was supported by grants from the National Key Research and Development Program of China(2018YFC2000500)the National Natural Science Foundation of China(81790631 and 81330011).
文摘Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.
基金Medical Research Council of Southeast Sweden(FORSS)and Division of Medical Diagnostics(Futurum),Region Jönköping County,Sweden.
文摘BACKGROUND Leukocytes,such as T cells and macrophages,play an important role in tumorigenesis.CC chemokine ligand(CCL)4,which is produced by lymphocytes and macrophages,has been found to be expressed in the mucosa of the gastrointestinal tract and is a potent chemoattractant for various leukocytes.AIM To examine CCL4 expression and its genetic polymorphism rs10491121 in patients with colorectal cancer(CRC)and evaluate their prognostic significance.METHODS Luminex technology was used to determine CCL4 Levels in CRC tissue(n=98),compared with paired normal tissue,and in plasma from patients with CRC(n=103),compared with healthy controls(n=97).Included patients had undergone surgical resection for primary colorectal adenocarcinomas between 1996 and 2019 at the Department of Surgery,Ryhov County Hospital,Jönköping,Sweden.Reverse transcription quantitative PCR was used to investigate the CCL4 gene expression in CRC tissue(n=101).Paired normal tissue and TaqMan single nucleotide polymorphism assays were used for the CCL4 rs10491121 polymorphism in 610 CRC patients and 409 healthy controls.RESULTS The CCL4 protein and messenger RNA expression levels were higher in CRC tissue than in normal paired tissue(90%,P<0.001 and 45%,P<0.05,respectively).CRC tissue from patients with localized disease had 2.8-fold higher protein expression levels than that from patients with disseminated disease.Low CCL4 protein expression levels in CRC tissue were associated with a 30%lower cancer-specific survival rate in patients(P<0.01).The level of plasma CCL4 was 11%higher in CRC patients than in healthy controls(P<0.05)and was positively correlated(r=0.56,P<0.01)with the CCL4 protein level in CRC tissue.The analysis of CCL4 gene polymorphism rs10491121 showed a difference(P<0.05)between localized disease and disseminated disease in the right colon,with a dominance of allele A in localized disease.Moreover,the rate of the A allele was higher among CRC patients with mucinous cancer than among those with nonmucinous cancer.CONCLUSION The present study indicates that the CRC tissue levels of CCL4 and CCL4 gene polymorphism rs10491121,particularly in the right colon,are associated with clinical outcome in CRC patients.
基金This work was supported by the funding provided by Ventenskapsådet(Grant No.2016-05642)to JR.
文摘The Nepal Himalayas is the source of many glacial and spring-fed river systems crisscrossing the mountainous terrain.There is an increasing recognition of small mountain rivers(SMRs)to have a significant combined export of dissolved and particulate organic carbon to the global carbon flux.We analyzed fluvial sediments from two SMRs and compared the results with two large mountain rivers(LMRs)in Nepal.We investigated the organic matter(OM),its compositional variability,and seasonal export using a suite of lipid biomarkers,namely n-alkanes,n-alkanoic acids,n-alkanols,and sterols.The SMRs indicated a similarity in lipid distribution and were affected by a strong seasonal variability.The LMRs showed a distinct contrast in the distribution of lipids in suspended sediments.Bedload sediments in SMRs were derived from diverse sources with weak terrigenous dominance all-year-round compared to the suspended load.Functional lipids(n-alkanoic acids and n-alkanols)were the major constituents in SMR sediments,indicating better preservation.In contrast,n-alkane concentration dominated over other fractions in suspended sediments retrieved from LMRs.The biomarker trends differentiate SMRs from LMRs with lower transformed/degraded OM in SMRs.A common observation was the strong presence of even carbon compounds in short-chain n-alkanes in SMR bedload sediments and their predominance in suspended sediments in LMRs.Such an unusual trend is attributed to specific biomarker sources from the catchment and ongoing processes in fluvial systems.Topsoil colonized by fungal species under moist acidic conditions and autochthonous bacteria contributes to the organic matter pool in shallow SMRs.In LMRs,the contribution from thermally mature sedimentary hydrocarbons and the diagenetic reduction of nalkanoic acids to n-alkanes are additional contributors to the allochthonous carbon pool.The differences in lipid concentrations,their distribution,seasonality,and the size of rivers suggest differential preservation/degradation of the organic matter pool and their importance in contributing to the carbon budget.
基金supported by MICINN and FEDER [AGL2016-79096-R and PID2020-113493RB-I00] Madrid (Spain)Seneca Foundation [19892/GERM/15]Murcia (Spain)+2 种基金European Union’s Horizon 2020 research and innovation program (H2020-MSCA-IF-2019-891382)financially supported by MINECO (BES-2016-076404)MECD (FPU16/02170),Spain,respectively。
文摘Background:Identification of relevant in vivo biomarkers for fertility remains a challenge for the livestock industry.Concentrations of the small peptide hormone oxytocin(OXT),involved in male reproductive function and present in the seminal plasma(SP)of several species could be a robust one.This study characterized concentrations of SPOXT in ejaculates from boars used in artificial insemination(AI)programs aiming to evaluate its relationship with sperm quality variables and in vivo fertility of their liquid-stored AI-semen.Seminal OXT concentrations(ng/mL)were measured in 169 ejaculates from 61 boars of the Duroc,Pietrain,Landrace and Large White breeds using a direct competitive immunoassay test based on AlphaLISA®technology.Ejaculate(ejaculate volume,sperm concentration,total sperm count)and sperm parameters(motility,viability,intracellular generation of reactive oxygen species,plasma membrane fluidity)were assessed at 0 h and 72 h in AI-semen samples stored at 17℃.In vivo fertility included only 18 Large White and Landrace boars whose AI-semen was used to inseminated>100 sows and evaluated both farrowing rate and litter size of 3,167 sows.Results:The results showed that SP-OXT differed between boars and between ejaculates within boar(P<0.05)but not between breeds(Duroc,Pietrain,Landrace and Large White).Ejaculates with higher SP-OXT concentration/mL(hierarchically grouped;P<0.001)had larger volume and came from younger boars(P<0.05).Ejaculates of boars showing positive farrowing rate deviation exhibited higher(P<0.05)SP-OXT concentration/mL than those with negative farrowing rate deviation.Conclusion:The SP concentrations of OXT are boar,ejaculate and age dependent,and positively related with ejaculate volume and farrowing rates of liquid-stored semen AI-doses.
基金supported by the National Natural Science Foundation of China(Grants No.51902215,91426304,21671195,21805295,51902320,51902319,21875271,and U2004212)the China Postdoctoral Science Foundation(Grant No.2020M680082)+7 种基金the International Partnership Program of Chinese Academy of Sciences(Grants 174433KYSB20190019)the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(Grant No.2019R01003)the Ningbo top-talent team program for financial supportsupport from the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Link?ping University(Faculty Grant SFO Mat LiU No.200900971)support of the electron microscopy laboratory in Link?ping(Grant KAW 2015.0043)an Academy Fellow Grant(P.E.,2020.0196)the Swedish Foundation for Strategic Research(SSF)through project funding(EM16-0004)a Research Infrastructure Fellow Grant(RIF 14-0074)。
文摘MAX phases are gaining attention as precursors of two-dimensional MXenes that are intensively pursued in applications for electrochemical energy storage.Here,we report the preparation of V_(2)SnC MAX phase by the molten salt method.V_(2)SnC is investigated as a lithium storage anode,showing a high gravimetric capacity of 490 mAh g−1 and volumetric capacity of 570 mAh cm^(−3) as well as superior rate performance of 95 mAh g^(−1)(110 mAh cm^(−3))at 50 C,surpassing the ever-reported performance of MAX phase anodes.Sup-ported by operando X-ray diffraction and density functional theory,a charge storage mechanism with dual redox reaction is proposed with a Sn-Li(de)alloying reaction that occurs at the edge sites of V_(2)SnC particles where Sn atoms are exposed to the electrolyte followed by a redox reaction that occurs at V_(2)C layers with Li.This study offers promise of using MAX phases with M-site and A-site elements that are redox active as high-rate lithium storage materials.
基金support by the French National Research Agency through grant ANR-19-CE300012by the European Research Council(ERC)through grant No.772725。
文摘The tremendous amount of wasted heat from solar radiation and industry dissipation has motivated the development of thermoelectric concepts that directly convert heat into electricity.The main challenge in practical applications for thermoelectrics is the high cost from both materials and manufacturing.Recently,breakthrough progresses in ionic thermoelectrics open up new possibilities to charge energy storage devices when submitted to a temperature gradient.The charging voltage is internally from the ionic Seebeck effect of the electrolyte between two electrodes.Hence electrolytes with high thermoelectric figure of merit are classified as ionic thermoelectric materials.Most ionic thermoelectric materials are composed of abundant elements,and they can generate hundreds of times larger thermal voltage than that of electronic materials.This emerging thermoelectric category brings new hope to fabricate low cost and large area heat-to-energy conversion devices,and triggers a renewed interest for ionic thermodiffusion.In this review,we summarize the state of the art in the new field of ionic thermoelectrics,from the driving force of the ionic thermodiffusion to material and application developments.We present a general map of ionic thermoelectric materials,discuss the unique characters of each type of the reported electrolytes,and propose potential optimization and future topics of ionic thermoelectrics.
基金National Natural Science Foundation of China(51873146)Ningbo Municipal Natural Science Foundation(2018A610005)+1 种基金Major Project of the Ministry of Science and Technology of China(2015ZX06004-001)Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University(Faculty Grant SFO-Mat-LiU No.200900971)。
文摘BACKGROUND Low back pain(LBP)is a common condition with large burden worldwide.Exposure to prolonged sitting with a flexed lumbar posture has been suggested in the literature to be a potential risk factor for self-reported LBP.No study has previously investigated whether exposure to prolonged flexed sitting posture provokes discomfort/pain and decreased interspinous pressure pain thresholds for healthy young men and women without back pain,despite this being a suggested risk factor for LBP.AIM To investigate whether sitting in a prolonged flexed lumbar posture provokes discomfort and lowers interspinous pressure pain thresholds in the lumbar spine for healthy young men and women without previous LBP.METHODS This is a an observational before and after study of 26 participants(13 men,13 women)between 20-35 years old.Algometry was used to examine the pain threshold for pressure applied between spinous processes of the lumbar spine L1-L5.Pressure algometer measures were performed in prone before and after participants were instructed to sit in a fully flexed posture for a maximum of 15 min or until discomfort was experienced in the low back(Borg CR10=7/10).Wilcoxon signed-rank test was used for analyze values from the before and after test conditions.Mann-Whitney U test was used to investigate potential gender difference.RESULTS Fully flexed lumbar spine sitting posture up to 15 min provoked temporary discomfort but the proportion of participants experiencing discomfort 7/10 in the low back was 62%.For all pain pressure threshold locations tested,there was a significant difference for the study population with moderate-large decreased(r=-0.56)pressure pain threshold after exposure to prolonged flexed sitting posture(P<0.01).Comparisons between gender did not show any significant difference.CONCLUSION The result showed that exposure to fully flexed lumbar sitting posture for up to 15 min produced temporary discomfort in the low back in young healthy adults with no previous history of LBP and significantly reduced lumbar interspinous pressure pain thresholds.No gender-based differences were observed.
文摘Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.
基金supported by the US National Science Foundation(No.EAR-1423939)。
文摘Magnetotactic bacteria(MTB),ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals.MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields.Similar magnetite deposits have been found throughout the tissues of the human brain,including brain regions associated with orientation such as the cerebellum and hippocampus,the origins of which remain unknown.Speculation over the role and source of MTB in humans,as well as any association with the brain,remain unanswered.We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions.We identified seven MTB in the human gut microbiome:Magnetococcus marinus,Magnetospira sp.QH-2,Magnetospirillum magneticum,Magnetospirillum sp.ME-1,Magnetospirillum sp.XM-1,Magnetospirillum gryphiswaldense,and Desulfovibrio magneticus.Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus(adjusted for total intracranial volume,uncorrected P<0.05).These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation.These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans.Further studies will be necessary to validate and elucidate the relationship between these bacteria,magnetite concentrations,and brain function.
基金Supported by The Selander Foundation and the Foundation for Clinical Cancer Research in Jönköping
文摘AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.
基金partially supported by the Wallenberg AIAutonomous Systems and Software Program (WASP) funded by the Knut and Alice Wallenberg Foundation
文摘Poor road conditions in underground mine tunnels can lead to decreased production efficiency and increased wear on production vehicles. A prototype system for road condition monitoring is presented in this paper to counteract this. The system consists of three components i.e. localization, road monitoring, and scheduling. The localization of vehicles is performed using a Rao-Blackwellized extended particle filter, combining vehicle mounted sensors with signal strengths of Wi Fi access points. Two methods for road monitoring are described: a Kalman filter used together with a model of the vehicle suspension system, and a relative condition measure based on the power spectral density. Lastly, a method for taking automatic action on an ill-conditioned road segment is proposed in the form of a rescheduling algorithm.The scheduling algorithm is based on the large neighborhood search and is used to integrate road service activities in the short-term production schedule while minimizing introduced production disturbances.The system is demonstrated on experimental data collected in a Swedish underground mine.
基金the Declaration of Helsinki and was approved by the Regional Ethics Review board in Linköping,RegionÖstergötland,Sweden,No.2018/139–31.
文摘BACKGROUND The majority of patients with newly diagnosed metastatic prostate cancer(PC)initially respond to androgen deprivation therapy(ADT)and are classified as metastatic castration-sensitive PC(mCSPC).Following months to years of ADT,the disease tends to become resistant to ADT.Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC.Following its implementation in routine care,this combined treatment strategy requires more detailed evaluation in a real-world setting.AIM To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC.METHODS A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed.This region includes approximately 1.1 million citizens and the oncology departments of Linköping,Jönköping,and Kalmar.All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included.The primary endpoint was progression-free survival(PFS)at 12 mo,and the secondary endpoints were PFS at 24 mo,overall survival(OS),treatment intensity,adverse events,and unplanned hospitalizations.Exploratory analyses on potential prognostic parameters were performed.RESULTS Ninety-four patients were eligible and formed the study cohort.PFS at 12 and 24 mo was 75%(95%CI:66–84)and 58%(46–70),respectively.OS at 12 and 24 mo was 93%(87–99)and 86%(76–96).A total of 91%of patients(n=86)were given docetaxel according to the standard protocol of 75 mg/m2 every 3 wk(6 cycles),while 9%(n=8)received a modified protocol of 50 mg/m2 every 2 wk(9 cycles).The average overall dose intensity for those commencing standard treatment was 91%.Univariate Cox regression analyses show that baseline PSA>180 vs<180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors(HR 2.86,95%CI:1.39–5.87,P=0.0041 and 3.36,95%CI:1.03–10.96,P=0.045).Following multivariate analysis,statistical significance remained for PSA(2.51,95%CI:1.21–5.19,P=0.013)but not for metastatic status(2.60,95%CI:0.78–8.65,P=0.12).Febrile neutropenia was recorded in 21%(n=20)of patients,and 26%(n=24)had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course.CONCLUSION Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.
基金Supported by the Medical Research Council of Southeast Sweden,No.FORSS-931897the Division of Medical Diagnostics of Region Jönköping County,No.Futurum-970572.
文摘The association between type 2 diabetes mellitus(DM)and colorectal cancer(CRC)has been thoroughly investigated and reports have demonstrated that the risk of CRC is increased in DM patients.The association between DM and the survival of patients with CRC is controversial.Evidence suggests that metformin with its anti-inflammatory effects is a protective factor against the development of CRC among DM patients and that metformin therapy is associated with a better prognosis in patients with DM.In our cohort,we did not find any associations between the presence of DM or metformin and cancer specific survival or any relation to plasma levels of a panel of 40 inflammatory factors and irisin.On the other hand,we identified that the insulin-like growth factor binding protein 7 single nucleotide polymorphism rs2041437 was associated with DM in CRC patients.The dominance of the T bearing genotypes in patients with DM was statistically significant(P=0.038),with an odds ratio of 1.66(95%confidence interval:1.03-2.69).