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INTRODUCTION AND OBJECTIVES: We initiated this multicenter study to integrate important risk factors to create a nomogram for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) for clinician decision-making. PATIENTS AND METHODS: Between April 2011 and March 2022, 2281 HCC patients with an HBV-related diagnosis were included. All patients were randomly divided into two groups in a ratio of 7:3 (training cohort, n = 1597; validation cohort, n = 684). The nomogram was built in the training cohort via Cox regression model and validated in the validation cohort. RESULTS: Multivariate Cox analyses revealed that the portal vein tumor thrombus, Child-Pugh class, tumor diameter, alanine aminotransferase level, tumor number, extrahepatic metastases, and therapy were independent predictive variables impacting overall survival. We constructed a new nomogram to predict 1-, 2-, and 3-year survival rates based on these factors. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.809, 0.806, and 0.764 in predicting 1-, 2-, and 3-year survival rates, respectively. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions. The decision curve analyses (DCA) curves demonstrated excellent therapeutic application potential. In addition, stratified by risk scores, low-risk groups had longer median OS than medium-high-risk groups (p < 0.001). CONCLUSIONS: The nomogram we constructed showed good performance in predicting the 1-year survival rate for HBV- related HCC.

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Breast cancer is an epithelial malignant tumor that occurs in the terminal ducts of the breast. Neoadjuvant chemotherapy (NACT) is an important part of breast cancer treatment. Its purpose is to use systemic treatment for some locally advanced breast cancer patients, to decrease the tumor size and clinical stage so that non-operable breast cancer patients can have a chance to access surgical treatment, or patients who are not suitable for breast-conserving surgery can get the opportunity of breast-conserving. However, some patients who do not respond to NACT will lead deterioration in their condition. Therefore, prediction of NACT efficacy in breast cancer is vital for precision therapy. The tumor microenvironment (TME) has a crucial role in the carcinogenesis and therapeutic response of breast cancer. In this review, we summarized the immune cells, immune checkpoints, and other biomarkers in the TME that can evaluate the efficacy of NACT in treating breast cancer. We believe that the detection and evaluation of the TME components in breast cancer are helpful to predict the efficacy of NACT, and the prediction methods are in the prospect. In addition, we also summarized other predictive factors of NACT, such as imaging examination, biochemical markers, and multigene/multiprotein profiling.

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Although some atomically thin 2D semiconductors have been found to possess good thermoelectric performance due to the quantum confinement effect, most of their behaviors occur at a higher temperature. Searching for promising thermoelectric materials at room temperature is meaningful and challenging. Inspired by the finding of moderate band gap and high carrier mobility in monolayer GeP3, we investigated the thermoelectric properties by using semi-classical Boltzmann transport theory and first-principles calculations. The results show that the room-temperature lattice thermal conductivity of monolayer GeP3 is only 0.43 Wm-1K-1 because of the low group velocity and the strong anharmonic phonon scattering resulting from the disordered phonon vibrations with out-of-plane and in-plane directions. Simultaneously, the Mexican-hat-shaped dispersion and the orbital degeneracy of the valence bands result in a large p-type power factor. Combining this superior power factor with the ultralow lattice thermal conductivity, a high p-type thermoelectric figure of merit of 3.33 is achieved with a moderate carrier concentration at 300 K. The present work highlights the potential applications of 2D GeP3 as an excellent room-temperature thermoelectric material.

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The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles experienced a reversal of fortune in the human lineage. We explored nonadaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Many nonadaptive hypotheses were tested, but failed to explain the data, which suggests that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This suggestion is supported by the fact that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and hundreds of CAP alleles are protective in genotype-phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of nonneutral candidate variants in the human proteome. We expect this collection to be enriched in beneficial variation. The EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.

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The development and evolution of organisms is heavily influenced by their environment. Thus, understanding the historical biogeography of taxa can provide insights into their evolutionary history, adaptations and trade-offs realized throughout time. In the present study we have taken a phylogenomic approach to infer New World monkey phylogeny, upon which we have reconstructed the biogeographic history of extant platyrrhines. In order to generate sufficient phylogenetic signal within the New World monkey clade, we carried out a large-scale phylogenetic analysis of approximately 40 kb of non-genic genomic DNA sequence in a 36 species subset of extant New World monkeys. Maximum parsimony, maximum likelihood and Bayesian inference analysis all converged on a single optimal tree topology. Divergence dating and biogeographic analysis reconstruct the timing and geographic location of divergence events. The ancestral area reconstruction describes the geographic locations of the last common ancestor of extant platyrrhines and provides insight into key biogeographic events occurring during platyrrhine diversification. Through these analyses we conclude that the diversification of the platyrrhines took place concurrently with the establishment and diversification of the Amazon rainforest. This suggests that an expanding rainforest environment rather than geographic isolation drove platyrrhine diversification.

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The molecular genetics of indole-3-acetic (IAA) synthesis and regulation in Azospirillum brasilense was investigated in this study. Tn5 mutagenesis was performed and five mutants with decreased IAA production were isolated. Five Tn5-inserted genes from these mutants were cloned and sequenced. Four genes were reported for the first time to be involved in IAA production, namely, atrA, ftsA, omaA and aldA that code for GntR-family transcriptional regulator, iron-binding protein component of ABC-type Fe(3+) transport system, outer membrane protein, and aldehyde dehydrogenase, respectively. In addition, two genes atrB and atrC, with predicted proteins that showed high homology to aminotransferases, were cloned from the downstream of atrA in this bacterium. Studies also showed that complementation of atrA, ftsA and omaA were able to restore the IAA production of the corresponding IAA(-) mutants. Comparison of Fe(3+) concentrations in culture supernatants of the wild-type strain, the ftsA mutant and the complemented strain revealed that the iron-uptake ability of the ftsA mutant was highly reduced. This result also points to the necessity of iron as a metal ion in IAA synthesis. Statistical analysis showed no significant difference in the IAA accumulated in cells between the omaA mutant and the wild-type strain, suggesting the omaA might not affect IAA secretion but be involved in IAA production in other unknown ways.

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OBJECTIVES: We investigated whether there were Mexican-American versus non-Hispanic white disparities in parents' reports of problems with 4 dimensions of children's medical care access after controlling for a range of demographic, social, economic, and health status factors. METHODS: Data were collected through a telephone survey of 5941 parents residing in Texas. The survey questionnaire included measures of the parent's demographic and socioeconomic status and the child's health-related quality of life. The behavioral model was used to guide the inclusion of factors in multivariate logistic regression analyses of parents' reports of their children's ability to obtain an appointment for routine/regular care, obtain care for illness/injury, obtain help/advice over the phone when calling the doctor's office, and having to wait more than 15 minutes in the doctor's office. RESULTS: Mexican-American parents had worse reports of all 4 dimensions of their children's access even after controlling for predisposing, enabling, and need factors. Among Mexican-Americans, there were no differences between those who primarily spoke English versus Spanish. Other factors that were significantly associated with at least 2 reports of access were household income, the child's insurance status, and the child's health-related quality of life. CONCLUSIONS: Mexican-American children face problems accessing medical care in a timely manner that are not fully explained by parents' demographic, social, and economic status or children's health-related quality of life. Health policy makers, managers, and clinicians should further consider how they could reduce the inequity of access to medical services among Mexican-American children.

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