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Assessment of morbidity and mortality after liver transplantation for primary sclerosing cholangitis

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 154-156页

作者： Burcin Ekser Plamen Mihaylov richard S.Mangus Division of Transplant Surgery Department of SurgeryIndiana University School of MedicineIndianapolisINUSA

Primary sclerosing cholangitis(PSC)is a progressive liver disease that causes biliary inflammation,recurrent cholangitis,and liver fibrosis(1).Although there are therapeutic options that temporarily reduce the itching and jaundice caused by PSC,there is currently no effective definitive *** rate of disease progression varies among individuals,but it ultimately leads to end-stage liver disease and necessitates liver transplantation(2).

关键词： Complications liver transplantation outcomes primary sclerosing cholangitis(PSC)

Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

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Pedosphere 2024年第5期34卷 865-878页

作者： Megan L.SCHILL richard BAIRD Shawn P.BROWN Allison M.VEACH Department of Integrative Biology University of Texas at San Antonio Biochemistry Molecular Biology Entomology and Plant Pathology Department Mississippi State University Department of Biological Sciences The University of Memphis

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally. This effect has, and will continue,to increase fire occurrence across many regions of North America. In the southern Appalachian Mountains, wildfires with high burn severity occurred in 2016due to increased drought and human activity. To investigate the effects of burn severity on soil physicochemical properties, microbial extracellular enzyme production, and microbial abundances in a temperate region, surface soils (0–15 cm) were collected from two sites (the Great Smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina, USA) spanning lightly, moderately, and severely burned areas, accompanied by adjacent unburned locations that act as controls. The soil samples were collected at three time points between 2017 and 2019 (i.e., 0.5, 1, and 2.5 years post-fire)among burn severity plots. Total hydrolytic enzyme production varied over time, with severe burn plots having significantly lower enzyme production at 2.5years post-fire. Individual enzymes varied among burn severities and across time post-fire. Light burn plots showed greater carbon-specific (β-glucosidase and β-xylosidase) and phosphorus-specific (acid phosphatase) enzyme activities at 0.5 years post-fire, but this effect was transient. At 2.5 years post-fire, theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls. In contrast, the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire, but was the lowest in light burn plots at 2.5 years post-fire. The fungi:bacteria ratio declined with burn severity, indicating that fungi are sensitive or less resilient to high burn severity during recovery. These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe, which potentially

关键词： 16S carbon ITS nitrogen phosphorous

Conservation genomic investigation of an endangered conifer,Thuja sutchuenensis,reveals low genetic diversity but also low genetic load

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Plant Diversity 2024年第1期46卷 78-90页

作者： Tongzhou Tao richard IMilne Jialiang Li Heng Yang Shiyang Wang Sihan Chen Kangshan Mao Key Laboratory for Bio-Resource and Eco-Environment of Ministry of Education&Sichuan Zoige Alpine Wetland Ecosystem National Observation and Research Station College of Life ScienceSichuan UniversityChengduChina Institute of Molecular Plant Science School of Biological ScienceUniversity of EdinburghEdinburgh EH93BFUK College of Science Tibet UniversityLhasa 850000Xizang Autonomous RegionPR China

Endangered species generally have small populations with low genetic diversity and a high genetic *** sutchuenensis is an endangered conifer endemic to southwestern *** was once considered extinct in the wild,but in 1999 was ***,little is known about its genetic *** collected 67 individuals from five wild,isolated *** populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in *** to delineate the conservation units of ***,based on whole transcriptome sequencing data,as well as target capture sequencing *** found that populations of *** could be divided into three *** groups had low levels genetic diversity and were moderately genetically *** findings also indicate that *** suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial *** Thuja species,*** presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying ***,distribution of fitness effects analysis indicated a high extinction risk for *** lines of evidence identified three management units for *** *** possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare *** might also hold true for many endangered plant species in the mountains all over the world.

关键词： Sichuan Arborvitae Genetic load Deleterious mutations Demographic history Conservation genomics

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A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang richard Jones Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical Co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

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Determining minimum sample size for the conditioned Latin hypercube sampling algorithm

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Pedosphere 2024年第3期34卷 530-539页

作者： Daniel D.SAURETTE Asim BISWAS richard J.HECK Adam W.GILLESPIE Aaron A.BERG School of Environmental Sciences University of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada) Ontario Ministry of Agriculture Food and Rural Affairs1 Stone Rd WestGuelph ON N1G 2Y4(Canada) Geography Environment&GeomaticsUniversity of Guelph50 Stone Rd EastGuelph ON N1G 2W1(Canada)

In digital soil mapping(DSM),a fundamental assumption is that the spatial variability of the target variable can be explained by the predictors or environmental *** to adequately sample the predictors have been well documented,with the conditioned Latin hypercube sampling(cLHS)algorithm receiving the most attention in the DSM *** advances in sampling design,a critical gap remains in determining the number of samples required for DSM *** propose a simple workflow and function coded in R language to determine the minimum sample size for the cLHS algorithm based on histograms of the predictor variables using the Freedman-Diaconis rule for determining optimal bin *** preprocessing was included to correct for multimodal and non-normally distributed data,as these can affect sample size determination from the *** on a user-selected quantile range(QR)for the sample plan,the densities of the histogram bins at the upper and lower bounds of the QR were used as a scaling factor to determine minimum sample *** technique was applied to a field-scale set of environmental covariates for a well-sampled agricultural study site near Guelph,Ontario,Canada,and tested across a range of *** results showed increasing minimum sample size with an increase in the QR *** sample size increased from 44 to 83 when the QR increased from 50% to 95% and then increased exponentially to 194 for the 99%*** technique provides an estimate of minimum sample size that can be used as an input to the cLHS algorithm.

关键词： bin width digital soil mapping normal distribution quantile range sampling design

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Survival outcomes in early-onset oesophageal adenocarcinoma patients:A systematic review and meta-analyses

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World Journal of Gastroenterology 2024年第38期30卷 4221-4231页

作者： Ashleigh Russell Shauna Mitchell richard C Turkington Helen G Coleman Centre for Public Health Queen's University BelfastBelfast BT126BAUnited Kingdom Patrick G Johnston Centre for Cancer Research Queen's University BelfastBelfast BT71NNUnited Kingdom

BACKGROUND The incidence of oesophageal adenocarcinoma(OAC)has been reported to be increasing in many *** this trend,an increase in incidence of early-onset OAC,defined as OAC in adults aged under 50 years,has been *** is unclear whether survival outcomes for early-onset OAC patients differ from older age *** To investigate survival outcomes in early-onset OAC *** Ovid Medline and Embase were searched from inception to January 2022 for relevant studies relating to early-onset OAC and survival *** regarding the overall five-year survival and risk of death of younger and older patients with OAC were extracted and pooled using meta-analyses to produce pooled estimates and 95%CIs where *** Eleven studies which compared survival of early-onset OAC,defined as age at diagnosis of<50 years,with older patients were included.A narrative review of median and mean survival demonstrated conflicting results,with studies showing early-onset OAC patients having both better and worse outcomes compared to older age groups.A meta-analysis of five-year survival demonstrated similar outcomes across age groups,with 22%-25%of patients in the young,middle and older age groups alive after five years.A meta-analysis of four studies demon-strated that early-onset OAC patients did not have a significantly increased risk of death compared to middle-aged patients(hazard ratio 1.12,95%CI:0.85-1.47).INTRODUCTION There is concern that the incidence of oesophageal adenocarcinoma(OAC)in patients under 50,described as early-onset OAC,is ***,data regarding survival of younger patients with OAC is ***,while increasing age remains a major non-modifiable risk factor for cancer,the incidence of early-onset cancers,largely accepted to be in adults aged under 50 years,is increasing[1].This includes an observed increase in the incidence of gastrointestinal malignancies such as colorectal,oesophageal,gastric and he

关键词： Early-onset cancer Early-onset oesophageal adenocarcinoma Survival Cancer epidemiology Systematic review Meta-analysis

A Many Worlds Interpretation of the Dark Universe

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第2期10卷 828-835页

作者： richard Douglas Bateson Cavendish Laboratory Cambridge UK

In this paper, we discuss a Many Worlds Interpretation (MWI) of Dark Energy and Dark Matter. The universe is viewed cosmologically as a fermionic fluid with a hydrostatic pressure from “Zitterbewegung”, the quantum “zig-zagging” of Dirac particles. At each point in space-time, the pressure from all possible velocity states existing in the Many Worlds sums to provide a dark energy. This provides a ratio of matter energy to pressure energy close to that observed experimentally. Visible matter is the matter observed or measured in a particular velocity state and dark matter is then considered as the unobserved fermion contributions from different orthogonal spatial directions.

关键词： Dark Energy Dark Matter Many Worlds

Improved Units of Measure in Rotational Mechanics

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World Journal of Mechanics 2024年第1期14卷 1-7页

作者： richard James Petti Independent Researcher Arlington USA

The SI system of units in rotational mechanics yields correct numerical results, but it produces physically incorrect units of measure in many cases. SI units also violate the principle of general covariance—the general rule for defining continuous coordinates and units in mathematics and mathematical physics. After 30+ years of wrestling with these problems, the ultimate authority on units of measure has declared that Newton–meter and Joule are not equivalent in rotational mechanics, as they are in the rest of physics. This article proposes a simple modification to SI units called “Nonstandard International units” (“NI units”) until a better name is agreed upon. NI units yield correct numerical results and physically correct units of measure, and they satisfy the principle of general covariance. The main obstacle to the adoption of NI units is the consensus among users that the radius of rotation should have the unit meter because the radius can be measured with a ruler. NI units assigned to radius should have units meter/radian because the radius is a conversion factor between angular size and circumferential length, as in arclength = rθ. To manage the social consensus behind SI units, the author recommends retaining SI units as they are, and informing users who want correct units that NI units solve the technical problems of SI units.

关键词： Rotational Mechanics Angular Unit Torque Moment of Inertia Angular Momentum General Covariance

Fire and retention island remnants have similar deadwood carbon stock a decade after disturbances in boreal forests of Alberta

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Forest Ecosystems 2024年第5期11卷 677-684页

作者： richard Osei Lance P.Moore Rosanise A.Odell Marcel Schneider Tanvir Ahmed Shovon Charles A.Nock Department of Renewable Resources University of AlbertaEdmontonCanada Institut des Sciences de La For^et Temperee Universite Du Quebec en Outaouais58 Rue PrincipaleRiponJ0V 1V0QCCanada

In an attempt to reconcile wood extraction and forest biodiversity in managed boreal forests,ecosystem-based forest management(EBM)has become the de facto management *** forestry represents one prominent way that EBM is implemented in many parts of the *** patches commonly left after harvesting serve as analogues of fire island remnants,which are patches of unburned forests in the burned forest *** the persistence of retention patches has been questioned,few studies have attempted to quantitatively compare forest attributes in both burned and harvested *** part of a larger program examining multiple aspects of ecosystem function in fire and harvest island remnants,we investigated the impact of disturbance type(fire/harvest)and forest edges on C stock in snags and coarse woody debris(CWD)found in island remnants in mixedwood boreal forests of Alberta,*** C stock(in snags and CWD)was similar between the two disturbance types and edge plots had similar total deadwood C stocks to *** edges of island remnants had about two-fold more snag C stock than their interiors in both disturbance types,but C stock in CWD was unaffected by edge effects and disturbance *** results suggest that deadwood C dynamics in island remnants in fire and harvest disturbed boreal forests were similar,thus lending support for the continued implementation of retention forestry in Alberta.

关键词： Retention forestry Deadwood Ecosystem-based management Wildfires Boreal forest