Dominant Population Research Articles

Efficacy and Safety of Chinese Medicine in the Treatment of Patients with Pulmonary Nodules-A Multicenter Open Label Randomized Controlled Study: A Study Protocol for a Randomized Controlled Trial

As the popularity of early screening of tumors, more and more people have detected pulmonary nodules, of which about 3.48% was lung cancer. However, false positive rates accounted for 1.4-23.3% according to trials reported. Therefore, pulmonary nodules may be over treated. In the clinical practice, we found that traditional Chinese medicine treatment makes some patients’ lung nodules shrink or even disappear but this effect needs to be approved. Therefore, we design this global network randomized controlled study (RCT) study to explore the efficacy and safety of traditional Chinese medicine in the treatment of pulmonary nodules. This study is a multicenter, open, prospective, randomized, controlled study. In this study, participants will be randomly assigned to traditional Chinese medicine or routine treatment observation group. About 166 patients with pulmonary nodules will be registered within 12 months and followed up for at least 2 years. The important feature of this clinical trial is to provide services to patients with pulmonary nodules worldwide by combining online and offline diagnosis and treatment, excluding interference factors such as region, climate, environment, eating habits etc. At the same time, it also will save costs and improves patient compliance. This trial design will also conduct subgroup analysis on the population of traditional Chinese medicine in the treatment of pulmonary nodules and establish a mathematical model to analyze the dominant population of traditional Chinese medicine in pulmonary nodules and the predictive factors of curative effect.

Single-cell sequencing reveals the evolution of immune molecules across multiple vertebrate species

IntroductionBoth innate and adaptive immune system undergo evolution from low to high vertebrates. Due to the limitation of conventional approaches in identifying broader spectrum of immune cells and molecules from various vertebrates, it remains unclear how immune molecules evolve among vertebrates. ObjectivesHere, we utilized carry out comparative transcriptome analysis in various immune cells across seven vertebrate species. MethodsSingle-cell RNA sequencing (scRNA-seq). ResultsWe uncovered both conserved and species-specific profiling of gene expression in innate and adaptive immunity. Macrophages exhibited highly-diversified genes and developed sophisticated molecular signaling networks along with evolution, indicating effective and versatile functions in higher species. In contrast, B cells conservatively evolved with less differentially-expressed genes in analyzed species. Interestingly, T cells represented a dominant immune cell populations in all species and unique T cell populations were identified in zebrafish and pig. We also revealed compensatory TCR cascade components utilized by different species. Inter-species comparison of core gene programs demonstrated mouse species has the highest similarity in immune transcriptomes to human. ConclusionsTherefore, our comparative study reveals gene transcription characteristics across multiple vertebrate species during the evolution of immune system, providing insights for species-specific immunity as well as the translation of animal studies to human physiology and disease.

An active microbiome in Old Faithful geyser.

Natural thermal geysers are hot springs that periodically erupt liquid water, steam, and gas. They are found in only a few locations worldwide, with nearly half located in Yellowstone National Park (YNP). Old Faithful geyser (OFG) is the most iconic in YNP and attracts millions of visitors annually. Despite extensive geophysical and hydrological study of geysers, including OFG, far less is known of the microbiology of geysed waters. Here, we report geochemical and microbiological data from geysed vent water and vent water that collects in a splash pool adjacent to OFG during eruptions. Both waters contained microbial cells, and radiotracer studies showed that they fixed carbon dioxide (CO2) when incubated at 70°C and 90°C. Shorter lag times in CO2 fixation activity were observed in vent and splash pool waters incubated at 90°C than 70°C, suggesting cells are better adapted or acclimated to temperatures like those in the OFG vent (∼92-93°C). 16S rDNA and metagenomic sequence data indicated that both communities are dominated by the autotroph Thermocrinis, which likely fuels productivity through the aerobic oxidation of sulfide/thiosulfate in erupted waters or steam. Dominant OFG populations, including Thermocrinis and subdominant Thermus and Pyrobaculum strains, exhibited high-strain level genomic diversity (putative ecotypes) relative to populations from nongeysing YNP hot springs that is attributed to the temporal chemical and temperature dynamics caused by eruptions. These findings show that OFG is habitable and that its eruption dynamics promote genomic diversity, while highlighting the need to further research the extent of life in geyser systems such as OFG.

Soil microbial community diversity and distribution characteristics under three vegetation types in the Qilian Mountains, China

Qilian Mountains in Northwest China is a significant ecological security barrier due to its distinctive geographic setting, which has significant biological resource and gene pool. In order to assess the soil quality and ecosystem health in this area, we identified the structural characteristics and functional groups of soil microbial communities. This study focused on Amidongsuo, a typical watershed of the Qilian Mountains, and researched the vertical distribution and dominant populations of soil microorganisms in different habitats, and the relationship between soil microorganisms and environmental factors. Soil microorganisms from three grassland plots, five shrubland plots, and five forest plots in Amidongsuo were studied using high-throughput sequencing. The Venn diagram showed that the types of bacteria were fewer than those of fungi in Amidongsuo. Soil bacteria Acidobacteriota, Proteobacteria, and Methylomirabilota as well as fungi Basidiomycota, Ascomycota, and Mortierellomycota played dominant roles in Amidongsuo, according to the LEfSe (linear discriminant analysis (LDA) effect size) and community structure analyses. According to the ANOSIM (analysis of similarities) result, for both bacteria and fungi, R values of grassland and shrubland were small (R2=0.045 and R2=0.256, respectively), indicating little difference between these two ecosystems. RDA (redundancy analysis) showed a closer relationship between soil nutrients and fungi, and a gradually decreasing correlation between soil nutrients and microorganisms with increasing soil depth. Bacteria were mainly affected by pH, nitrogen (N), and potassium (K), while fungi were mainly affected by K. Overall, fungi had more effect on soil quality than bacteria. Therefore, adjustment of soil K content might improve the soil environment of Amidongsuo in the Qilian Mountains.

Metagenomic and single-cell RNA-Seq survey of the Helicobacter pylori-infected stomach in asymptomatic individuals.

Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H. pylori-infected (HPI) stomachs, we collected human gastric tissues and performed metagenomic sequencing, single-cell RNA-Seq (scRNA-Seq), flow cytometry, and fluorescent microscopy. HPI asymptomatic individuals had dramatic changes in the composition of gastric microbiome and immune cells compared with noninfected individuals. Metagenomic analysis uncovered pathway alterations related to metabolism and immune response. scRNA-Seq and flow cytometry data revealed that, in contrast to murine stomachs, ILC2s are virtually absent in the human gastric mucosa, whereas ILC3s are the dominant population. Specifically, proportion of NKp44+ ILC3s out of total ILCs were highly increased in the gastric mucosa of asymptomatic HPI individuals, and correlated with the abundance of selected microbial taxa. In addition, CD11c+ myeloid cells and activated CD4+ T cells and B cells were expanded in HPI individuals. B cells of HPI individuals acquired an activated phenotype and progressed into a highly proliferating germinal-center stage and plasmablast maturation, which correlated with the presence of tertiary lymphoid structures within the gastric lamina propria. Our study provides a comprehensive atlas of the gastric mucosa-associated microbiome and immune cell landscape when comparing asymptomatic HPI and uninfected individuals.

The Effect of Schizochytrium sp. on Growth, Fatty Acid Profile and Gut Microbiota of Silver Pomfret (Pampus argenteus)

Schizochytrium sp. is a kind of heterotrophic protist, rich in docosahexaenoic acid (DHA). To study the application value of Schizochytrium sp. in fish diet, a 20-day feeding experiment was initiated to evaluate its effect on growth, fatty acid contents, and the gut microbiota of the important economic fish, silver pomfret. In this study, the diets of the treatment group were added with 2% Schizochytrium sp. The fish in the treatment group gained more weight and had a higher growth rate than the control group. The levels of DHA, eicosapentaenoic acid, and polyunsaturated fatty acids in the edible tissue of fish were highly increased in the treatment group after 20 days. After feeding Schizochytrium sp., high-throughput 16S rRNA sequencing showed that the Proteobacteria, Firmicutes and Bacteroidetes were the phyla with the highest abundance, and at the genus and species level, we observed an increased abundance of probiotics. The results indicated that ingestion of Schizochytrium sp. could change the dominant microbiota population, which might lead to accelerated growth and improved unsaturated fatty acid content and fish health. This study provides a reference for Schizochytrium sp. supplementation in fish diets and could aid in the industrialization of silver pomfret.

Rapid diversification underlying the global dominance of a cosmopolitan phytoplankton

Marine phytoplankton play important roles in the global ecosystem, with a limited number of cosmopolitan keystone species driving their biomass. Recent studies have revealed that many of these phytoplankton are complexes composed of sibling species, but little is known about the evolutionary processes underlying their formation. Gephyrocapsa huxleyi, a widely distributed and abundant unicellular marine planktonic algae, produces calcified scales (coccoliths), thereby significantly affects global biogeochemical cycles via sequestration of inorganic carbon. This species is composed of morphotypes defined by differing degrees of coccolith calcification, the evolutionary ecology of which remains unclear. Here, we report an integrated morphological, ecological and genomic survey across globally distributed G. huxleyi strains to reconstruct evolutionary relationships between morphotypes in relation to their habitats. While G. huxleyi has been considered a single cosmopolitan species, our analyses demonstrate that it has evolved to comprise at least three distinct species, which led us to formally revise the taxonomy of the G. huxleyi complex. Moreover, the first speciation event occurred before the onset of the last interglacial period (~140 ka), while the second followed during this interglacial. Then, further rapid diversifications occurred during the most recent ice-sheet expansion of the last glacial period and established morphotypes as dominant populations across environmental clines. These results suggest that glacial-cycle dynamics contributed to the isolation of ocean basins and the segregations of oceans fronts as extrinsic drivers of micro-evolutionary radiations in extant marine phytoplankton.

A Nearby Isolated Dwarf: Star Formation and Structure of ESO 006–001

Observations with the Hubble Space Telescope unexpectedly revealed that the dwarf galaxy ESO 006–001 is a near neighbor to the Local Group at a distance of 2.70 ± 0.11 Mpc. The stellar population in the galaxy is well resolved into individual stars to a limit of M I ∼ − 0.5 mag. The dominant population is older than 12 Gyr yet displays a significant range in metallicity of −2 < [Fe/H] < − 1, as evidenced by a red giant branch with substantial width. Superimposed on the dominant population are stars on the main sequence with ages less than 100 Myr and helium burning blue loop stars with ages of several hundred Myr. ESO 006–001 is an example of a transition dwarf; a galaxy dominated by old stars but one that has experienced limited recent star formation in a swath near the center. No H i gas is detected at the location of the optical galaxy in spite of the evidence for young stars. Intriguingly, an H i cloud with a similar redshift is detected 9 kpc away in projection. Otherwise, ESO 006–001 is a galaxy in isolation with its nearest known neighbor IC 3104, itself a dwarf, at a distance of ∼500 kpc.

M dwarf stars in the b294 field from the VISTA Variables in the Vía Láctea (VVV)

ABSTRACT M dwarf stars are the dominant stellar population in the Milky Way, and they are important for a wide variety of astrophysical topics. The Gaia mission has delivered a superb collection of data, nevertheless, ground-based photometric surveys are still needed to study faint objects. Therefore, the present work aims to identify and characterize M dwarf stars in the direction of the Galactic bulge using photometric data and with the help of Virtual Observatory tools. Using parallax measurements and proper motions from Gaia Data Release 3, in addition to different colour-cuts based on VISTA filters, we identify and characterize 7 925 M dwarf stars in the b294 field from the Vista Variables in the Vía Láctea (VVV) survey. We performed a spectral energy distribution fitting to obtain the effective temperature for all objects using photometric information available at Virtual Observatory archives. The objects in our sample have temperatures varying from 2800–3900 K. We also search for periodic signals in VVV light curves with up to 300 epochs, approximately. As a secondary outcome, we obtain periods for 82 M dwarfs by applying two methods: the Lomb–Scargle and Phase Dispersion Minimization methods, independently. These objects, with periods ranging from 0.14–34 d, are good candidates for future ground-based follow up. Our sample has increased significantly the number of known M dwarfs in the direction of the Galactic bulge and within 500 pc, showing the importance of ground-based photometric surveys in the near-infrared.

Colony-stimulating factor 1 positive (CSF1+ ) secretory epithelial cells induce excessive trophoblast invasion in tubal pregnancy rupture.

Tubal ectopic pregnancy (TEP) occurs when an embryo aberrantly implants in the fallopian tube, leading to abortive or ruptured tubal ectopic pregnancy (AEP or REP). Poor outcomes of REP include maternal infertility or mortality. Current studies on the prevention and treatment of ruptured tubal ectopic pregnancy (REP) are unfortunately hampered by a lack of the cell spectrum and cell-cell communications in the maternal-foetal interface. Here, we investigate the mechanisms of tubal rupture through single-cell transcriptome profiling of the fallopian tube-trophoblast interface in REP, AEP and intrauterine pregnancy patients. In REP, extravillous trophoblast (EVTs) cells form a dominant cell population, displaying aggressive invasion and proliferation, with robust differentiation into three subsets. Cell communication analysis identified colony-stimulating factor 1 (CSF1), overexpressed by fallopian tube secretory epithelial cells in REP, with CSF1R on EVTs and macrophages, as a ligand/receptor pair that stimulates EVT invasion and macrophage accumulation. CSF1+ secretory epithelial cells stimulate EVTs migration and invasion, leading to a tubal rupture in REP. These results provide a mechanistic context and cellular milieu leading to tubal rupture, facilitating further study and development of therapeutics for REP in early pregnancy.

MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle

Fatty infiltration, the ectopic deposition of adipose tissue within skeletal muscle, is mediated via the adipogenic differentiation of fibro-adipogenic progenitors (FAPs). We used single-nuclei and single-cell RNA sequencing to characterize FAP heterogeneity in patients with fatty infiltration. We identified an MME+ FAP subpopulation which, based on ex vivo characterization as well as transplantation experiments, exhibits high adipogenic potential. MME+ FAPs are characterized by low activity of WNT, known to control adipogenic commitment, and are refractory to the inhibitory role of WNT activators. Using preclinical models for muscle damage versus fatty infiltration, we show that many MME+ FAPs undergo apoptosis during muscle regeneration and differentiate into adipocytes under pathological conditions, leading to a reduction in their abundance. Finally, we utilized the varying fat infiltration levels in human hip muscles and found less MME+ FAPs in fatty infiltrated human muscle. Altogether, we have identified the dominant adipogenic FAP subpopulation in skeletal muscle.

Thermal and reionization history within a large-volume semi-analytic galaxy formation simulation

ABSTRACTWe predict the 21-cm global signal and power spectra during the Epoch of Reionization using the meraxes semi-analytic galaxy formation and reionization model, updated to include X-ray heating and thermal evolution of the intergalactic medium. Studying the formation and evolution of galaxies together with the reionization of cosmic hydrogen using semi-analytic models (such as M eraxes) requires N-body simulations within large volumes and high-mass resolutions. For this, we use a simulation of side-length 210 h−1 Mpc with 43203 particles resolving dark matter haloes to masses of $5\times 10^8 \rm{ }h^{-1}\, \mathrm{M_\odot }$. To reach the mass resolution of atomically cooled galaxies, thought to be the dominant population contributing to reionization, at z = 20 of $\sim 2\times 10^7 \text{ }h^{-1}\, \mathrm{M_\odot }$, we augment this simulation using the darkforest Monte Carlo merger tree algorithm (achieving an effective particle count of ∼1012). Using this augmented simulation, we explore the impact of mass resolution on the predicted reionization history as well as the impact of X-ray heating on the 21-cm global signal and the 21-cm power spectra. We also explore the cosmic variance of 21-cm statistics within 703 h−3 Mpc3 sub-volumes. We find that the midpoint of reionization varies by Δz ∼ 0.8 and that the cosmic variance on the power spectrum is underestimated by a factor of 2–4 at k ∼ 0.1–0.4 Mpc−1 due to the non-Gaussian nature of the 21-cm signal. To our knowledge, this work represents the first model of both reionization and galaxy formation which resolves low-mass atomically cooled galaxies while simultaneously sampling sufficiently large scales necessary for exploring the effects of X-rays in the early Universe.

Eddington accreting black holes in the epoch of reionization

ABSTRACT The evolution of the luminosity function (LF) of active galactic nuclei (AGNs) at redshift $z {\,\, \gtrsim \,\,}5$ represents a key constraint to understand their contribution to the ionizing photon budget necessary to trigger the last phase transition in the Universe, i.e. the epoch of reionization. Recent searches for bright high-z AGNs suggest that the space densities of this population at z &amp;gt; 4 have to be revised upwards, and spark new questions about their evolutionary paths. Gas accretion is the key physical mechanism to understand both the distribution of luminous sources and the growth of central supermassive black holes (SMBHs). In this work, we model the high-z AGN-LF assuming that high-z luminous AGNs shine at their Eddington limit: We derive the expected evolution as a function of the ‘duty cycle’ (fdc), i.e. the fraction of lifetime that a given SMBH spends accreting at the Eddington rate. Our results show that intermediate values (fdc ≃ 0.1) predict the best agreement with the ionizing background and photoionization rate, but do not provide enough ionizing photons to account for the observed evolution of the hydrogen neutral fraction. Smaller values ($f_{\rm dc} {\,\, \lesssim \,\,}0.05$) are required for AGNs to be the dominant population responsible for hydrogen reionization in the early Universe. We then show that this low-fdc evolution can be reconciled with the current constraints on helium reionization, although it implies a relatively large number of inactive SMBHs at $z{\,\, \gtrsim \,\,}5$, in tension with SMBH growth models based on heavy seeding.

Ageing and quenching through the ageing diagram: predictions from simulations and observational constraints

ABSTRACT We study recent changes on the star-formation history (SFH) of galaxies by means of the ageing diagram (AD), tracing the fraction of stars formed during the last ∼20 Myr through the equivalent width of the $\rm H\alpha$ line and ∼1−3 Gyr through the dust-corrected optical colour (g − r)0or the Balmer break. We provide a physical characterization by using Pipe3Destimates of the SFH of Calar Alto Legacy Integral Field Area and Mapping Nearby Galaxies at Apache Point Observatory galaxies, in combination with the predictions from IllustrisTNG-100. Our results show that the AD may be divided into four domains that correlate with the stellar mass fractions formed in the last 20 Myr and 3 Gyr: ageing systems, whose star formation rate changes on scales of several Gyr, account for $70-80{{\ \rm per\ cent}}$ of the galaxy population. Objects whose SFH was abruptly truncated in the last ∼1 Gyr arrange along a detached quenched sequence that represents $\sim 5-10{{\ \rm per\ cent}}$ by (volume-corrected) number for 109 &amp;lt; M*/M⊙ &amp;lt; 1012. Undetermined systems represent an intermediate population between the ageing and quenched regimes. Finally, Retired galaxies, dominated by old stellar populations, are located at the region in the AD where the ageing and quenched sequences converge. Defining different star formation activity levels in terms of the birth rate parameter $b\equiv \frac{SFR}{\langle SFR \rangle }$, we find that galaxies transit from the ageing to quenched sequences on scales ∼500 Myr. We conclude that the AD provides a useful tool to discern recently quenched galaxies from the dominant ageing population.

Peripheral and tumor-infiltrating immune cells are correlated with patient outcomes in ovarian cancer.

At present, there is still a lack of reliable biomarkers for ovarian cancer (OC) to guide prognosis prediction and accurately evaluate the dominant population of immunotherapy. In recent years, the relationship between peripheral blood markers and tumor-infiltrating immune cells (TICs) with cancer has attracted much attention. However, the relationship between the survival of OC patients and intratumoral- or extratumoral-associated immune cells remains controversial. In this study, four machine-learning algorithms were used to predict overall survival in OC patients based on peripheral blood indicators. To further screen out immune-related gene and molecular targets, we systematically explored the correlation between TICs and OC patient survival based on The Cancer Genome Atlas database. Using the TICs score method, patients were divided into a low immune infiltrating cell group and a high immune infiltrating cell group. The results showed that there was a significant statistical significance between the peripheral blood indicators and the survival prognosis of OC patients. Survival analysis showed that TICs play a crucial role in the survival of OC patients. Four core genes, CXCL9, CD79A, MS4A1, and MZB1, were identified by cross-PPI and COX regression analysis. Further analysis found that these genes were significantly associated with both TICs and survival in OC patients. These results suggest that both peripheral blood markers and TICs can be used as prognostic predictors in patients with OC, and CXCL9, CD79A, MS4A1, and MZB1 may be potential therapeutic targets for OC immunotherapy.

Evaluation of morphological, histological, and immune-related cellular changes in ligature-induced experimental periodontitis in mice

Background/purposeThe ligature-induced periodontitis model is an effective approach to induce inflammation and bone loss similar to that of human periodontitis. Previous clinical and in vitro studies have shown the involvement of lymphocytes in periodontitis, while, the local and systemic profile of immune cells associated with periodontitis in the ligature-induced periodontitis model in mice remains unclear. Materials and methodsExperimental periodontitis was constructed in mice by ligating around the maxillary second molars for 14 and 28 days, respectively. Alveolar bone loss was assessed by micro-computed tomography (micro-CT). Hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate the histological changes in the periodontal tissues. B and T cells in the cervical lymph nodes, spleen, and peripheral blood were analyzed by flow cytometry. ResultsThe 14-day ligation effectively induced significant periodontal inflammation and alveolar bone loss in C57BL/6J mice, which were progressive and maintained for a relatively long-term period until day 28. In addition, CD3+ T cells and CD19+ B cells were the dominant population in both health and disease, and the B cell population within the cervical lymph nodes (LN) increased significantly under periodontitis condition, while, no significant differences of the T and B cell population among the spleen and peripheral blood were observed. ConclusionThe ligature-induced periodontitis mice model was established to perform a longitudinal assessment of changes in periodontal tissues morphologically and histologically, meanwhile, explore the local and systemic changes of the predominant immune-associated cells.

Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy.

Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single-cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM-targeted therapeutics for GBM patients.

Минеральные Воды: столица Северо-Кавказского края – решение, оставшееся в проекте

The article is devoted to the discussion of the issue of the new administrative center of the North-Caucasus Region (NCR), formed in January 1934, after the separation of the Azov-Black Sea Region from it. The then leadership of the country decided to place the capital of the NCR in the city of Georgievsk, but as a result of further discussion, two months later – in Mineral Waters. At the same time, it was planned that before the construction of administrative buildings in the new center, the regional authorities were to be located in the resort city of Pyatigorsk. The author reveals the main reasons for making a decision in favor of Mineralnye Vody. This city as the center of the North-Caucasus Region had the following advantages: 1. Mineralnye Vody was the largest railway transport hub in the region. 2. The largest airport in the South of Russia was located there. 3. Industry was developing dynamically in the city, and the working class was the dominant population – this was important for the state of the «dictatorship of the proletariat». 4. Proximity to the resort town allowed the leadership of the region to live in Pyatigorsk, and work in Mineralnye Vody. The article provides some reasons why the central and regional authorities reconsidered the decision to build the administrative center of the North-Caucasus Region in Mineralnye Vody. Firstly, there was the need to invest significant financial resources in the construction of the center. Secondly, it was the reluctance of regional officials to leave the temporary center of the region, Pyatigorsk. Thirdly, the central authorities of the country continued to search for the optimal, from their point of view, administrative-territorial structure, which could once again change the decision on the regional center. A way out of this situation was found in the official consolidation of the status of the permanent center of the North-Caucasus Region for Pyatigorsk.

Fibrosis-4 index, a predictor for prognosis of hepatocellular carcinoma patients after curative hepatectomy even in hepatitis B virus dominant populations.

Liver fibrosis plays an important role in the development of hepatocellular carcinoma (HCC) and determining its prognosis. Although many staging systems and liver reserve models have been developed without the intention of predicting prognosis of HCC, some studies have investigated their prognostic values in HCC after curative liver resection (LR). The aim of this study is to evaluate prognostic value of non-invasive biomarkers after curative LR. Between 2006 and 2013, HCC patients underwent LR were included and total 962 patients were enrolled. All non-invasive biomarkers (fibrosis 4 index (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and albumin-bilirubin (ALBI) score) were measured at the time of HCC diagnosis. To binarize each biomarker, an optimal cut-off value for fibrosis stage was selected using the value of minimum distance from the left-upper corner of the receiver operating characteristic curve with a specificity >60%. We performed Cox regression analysis on 2-year recurrence-free survival (RFS) and overall survival (OS). The area under curve values for FIB-4 and APRI were the largest for fibrosis stage compared to other biomarkers, 0.669 (95% confidential interval (CI), 0.610-0.719) and 0.748 (95% CI, 0.692-0.800), respectively. Between those two indices, FIB-4 is considered a statistically significant prognostic factor of RFS in HCC patients after LR. The HR for 2-year RFS and OS were 1.81 (95% CI, 1.18-2.77; P = 0.007) and 2.36 (95% CI, 0.99-5.65; P = 0.054), respectively. FIB-4 is identified as a statistically significant predictor of HCC prognosis after curative LR even in HBV dominant populations.

A Bounded Land: Reflections on Settler Colonialism in Canada

Divided into five sections, A Bounded Land is a career-spanning collection of essays, journal articles, and book chapters by historical geographer Cole Harris, all related in one way or another to settler colonialism. Most of this material was previously published, some as far back as the early 1970s, and, while portions are edited for length and clarity, the book holds together well, exploring a set of connected themes over four centuries and across a broad set of spaces in northern North America.Over his career, Harris made several critical contributions to the history of what is now Canada, including his editorial work on the Historical Atlas of Canada, his essential study of the formation of reserves in British Columbia (Making Native Space), and his excellent historical geographical synthesis of early Canada (The Reluctant Land). This collection demonstrates the depth of his thinking and the breadth of his interest. Ranging from Acadia, to the seigneuries of Lower Canada (Quebec) and the early townships of Upper Canada (Ontario), and finally to the contested Indigenous and settler spaces of British Columbia, A Bounded Land is breathtaking in its scale and ambition, all while being eminently approachable for a wide audience.Harris wrote much of the material in the book well before settler colonialism’s rise to scholarly prominence. He includes the concept here as a means of both signaling the themes he treats and, more importantly, demonstrating how a commitment to the specificity of place, space, society, population, and period are necessary for histories of colonial dispossession and settlement. Even in those pieces written before he had the term, Harris focuses squarely on “that form of colonialism associated with immigrants who became the dominant population in the territories they occupied, and, in so doing, displaced the Indigenous peoples who previously lived there” (3). This bare-bones definition coupled with a commitment to empirical historical research makes the book a valuable contribution to the literature on settler colonialism and its limitations. The book’s introduction and postscript succinctly and effectively tie its many pieces together while also inserting Harris’s writing into the larger literature, both explaining those works that influenced him (some of which are no longer widely read) and underlining scholarship that, while appearing after A Bounded Land’s individual chapters were first published, resonates with the book’s themes.As he moves through the book, Harris raises several powerful phenomena that he sees reproduced, though always in slightly different ways depending on place and time, across northern North America. Several of these will be of interest to readers of Ethnohistory. Harris returns frequently to conservative migrations, as rural residents threatened with displacement in industrializing and urbanizing Europe sought to maintain their status as independent producers elsewhere. He also focuses on the limits settler migration encountered where climate and soil—the “bounded land”—made the family farm impossible or its poverty a foregone conclusion. Harris ascribes Indigenous peoples’ differing historical experience in part to whether they lived within or beyond this “bounded land” (in Canada, he writes, “settler colonialism . . . has been a bounded project” [10]). Harris also focuses on the different human geography, population, and relative value of land and labor that made settler societies distinct from the European cultures and social structures from which they, in conversation and contestation with Indigenous societies and lands, emerged.While Harris concentrates on Indigenous experience in several chapters, A Bounded Land is primarily concerned with analyzing settlers, their claims to space, and their social and cultural adaptation to their new surroundings. This is critical since, as he rightly highlights in several distinct historical and geographical contexts, settler societies were not simple transplants from Europe but were shaped by the land to which they had moved and, in doing so, the peoples they worked to dispossess.