Search

Abstract Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events.

Cross-sectional study is one of the classic research design methods, which is widely used in clinical research. Cross-sectional study designs are used to answer a large number of scientific questions in general practice research. This includes not only the investigation of population health characteristics, disease characteristics or health service status, but also a variety of research scenarios such as the construction of disease screening and diagnosis methods for community people. Therefore, this paper will sort out and summarize the key points of cross-sectional research in the field of general medicine, and provide reference for future research work. In the field of general practice, cross-sectional studies can be used for status description, comparative analysis, correlation factor analysis and exploration of community screening diagnostic methods. The clinical development of cross-sectional studies should include two stages, study design and study implementation. The design stage includes accurate extraction of study objectives, defining clinical factors such as study population, study factors and outcome indicators, and determining the method of sample acquisition, determining the basis for sample size and rational statistical analysis strategies. In the implementation stage, complete research plan and case report form should be used to present research design ideas, and data collection should be carried out under the premise of ethical approval. Meanwhile, quality of data management and statistical analysis methods in the plan should be strictly implem.

The optimization of a tourism economic network is critical in the promotion of the high-quality development of a regional tourism economy. In order to explore the spatial network structure of the tourism economy of the Yangtze River Delta urban agglomeration and its influencing factors, this study used a modified gravity model and social network analysis methods for evaluation and analysis. The results show the following: (1) the spatial network of the tourism economy in the Yangtze River Delta urban agglomeration in 2016–2021 was characterized by significant non-equilibrium; however, that trend has weakened, and the tourism connections are now stronger in economically developed regions. (2) The density of the network structure was slightly strengthened. The structure of the tourism economy network shows an obvious core–periphery distribution pattern. The external radiation of the center city was enhanced, and the core area of the network expanded. (3) The concept of the “small world” is characterized by a significant evolution from five major associations to four major associations during the study period. (4) The quadratic assignment method (QAP) of regression analysis showed that tourism service reception capacity, tourism information flow, tourism resource endowments and transportation convenience make a significant contribution to the formation of the spatial network of inter-city tourism economic connections. The results of this study can provide a theoretical basis for the optimization of the tourism economic network of urban agglomerations and the scientific decision-making underpinning tourism economic cooperation.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

ABSTRACTIn subtropical forest ecosystems with few phosphorus (P) inputs, P availability and forest productivity depend on soil organic P (Po) mineralization. However, the mechanisms by which the microbial community determines the status and fate of soil Po mineralization remain unclear. In the present study, soils were collected from three typical forest types: secondary natural forest (SNF), mixed planting, and monoculture forest of Chinese fir. The P fractions, Po-mineralization ability, and microbial community in the soils of different forest types were characterized. In addition, we defined Po-mineralizing taxa with the potential to interact with the soil microbial community to regulate Po mineralization. We found that a higher labile P content persisted in SNF and was positively associated with the Po-mineralization capacity of the soil microbial community. In vitro cultures of soil suspensions revealed that soil Po mineralization of three forest types was distinguished by differences in the composition of fungal communities. We further identified broad phylogenetic lineages of Po-mineralizing fungi with a high intensity of positive interactions with the soil microbial community, implying that the facilitation of Po-mineralizing taxa is crucial for soil P availability. Our dilution experiments to weaken microbial interactions revealed that in SNF soil, which had the highest interaction intensity of Po-mineralizing taxa with the community, Po-mineralization capacity was irreversibly lost after dilution, highlighting the importance of microbial diversity protection in forest soils. In summary, this study demonstrates that the interactions of Po-mineralizing microorganisms with the soil microbial community are critical for P availability in subtropical forests.IMPORTANCEIn subtropical forest ecosystems with few phosphorus inputs, phosphorus availability and forest productivity depend on soil organic phosphorus mineralization. However, the mechanisms by which the microbial community interactions determine the mineralization of soil organic phosphorus remain unclear. In the present study, soils were collected from three typical forest types: secondary natural forest, mixed planting, and monoculture forest of Chinese fir. We found that a higher soil labile phosphorus content was positively associated with the organic phosphorus mineralization capacity of the soil microbial community. Soil organic phosphorus mineralization of three forest types was distinguished by the differences in the composition of fungal communities. The positive interactions between organic phosphorus-mineralizing fungi and the rest of the soil microbial community facilitated organic phosphorus mineralization. This study highlights the importance of microbial diversity protection in forest soils and reveals the microbial mechanism of phosphorus availability maintenance in subtropical forest ecosystems.

Abstract The involvement of endothelial barrier function in abdominal aortic aneurysm (AAA) and its upstream regulators remains unknown. Single‐cell RNA sequencing shows that disrupted endothelial focal junction is an early (3 days) and persistent (28 days) event during Angiotensin II (Ang II)‐induced AAA progression. Consistently, mRNA sequencing on human aortic dissection tissues confirmed downregulated expression of endothelial barrier‐related genes. Aldehyde dehydrogenase 2 (ALDH2), a negative regulator of AAA, is found to be upregulated in the intimal media of AAA samples, leading to testing its role in early‐stage AAA. ALDH2 knockdown/knockout specifically in endothelial cells (ECs) significantly increases expression of EC barrier markers related to focal adhesion and tight junction, restores endothelial barrier integrity, and suppresses early aortic dilation of AAA (7 and 14 days post‐Ang II). Mechanically, ELK3 acts as an ALDH2 downstream regulator for endothelial barrier function preservation. At the molecular level, ALDH2 directly binds to LIN28B, a regulator of ELK3 mRNA stability, hindering LIN28B binding to ELK3 mRNA, thereby depressing ELK3 expression and impairing endothelial barrier function. Therefore, preserving vascular endothelial barrier integrity via ALDH2‐specific knockdown in ECs holds therapeutic potential in the early management of AAAs.

Based on his academic background in multicultural music education and ethnomusicology, Huib Schippers developed the Seven-Continuum Transmission Model (SCTM) in 2004 to describe the teaching situations of world music. The current study adopted the SCTM as a framework to investigate Chinese music teachers’ perceptions of context issues (tradition, authenticity, and context) and transmission modes (analytic/holistic, notation based/aural, and tangible/intangible) in world music teaching. Semi-structured in-depth interviews were conducted using a qualitative methodology with nine primary and secondary school music teachers from different provinces in China. This study found that Chinese music teachers’ perceptions of context issues and transmission modes in world music teaching were more inclined to the formal, institutional settings rather than the informal, often community-based process. In addition, the music teachers were also influenced more by the “Eurocentrism” values; however, their perceptions were less affected by ethnomusicology that interprets human music from a cultural perspective and by multicultural music education.

Background/purpose: Carbapenem-nonsusceptible Enterobacterales (CNSE) are a growing global threat. Carbapenemases are often produced by plasmids, which allow rapid transmission. This study aimed to investigate (1) the bacterial type (2) resistant genes (3) antimicrobial susceptibility and (4) risk factors for acquisition of carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (CP-CNSE) and non-carbapenemase-producing carbapenem-nonsusceptible Enterobacterales (non-CP-CNSE) bacteremia. Methods: There were a total of 113 isolates of Enterobacterales from 2013 to 2018. After excluding nonblood isolates and including only one sample from each patient, 99 isolates were analyzed and the medical charts of these patients were reviewed. Carbapenemase genes, β-lactamase genes and antimicrobial susceptibility of the isolates were determined. Multilocus sequence typing (MLST) was performed on CP-CNSE isolates. Results: CP-CNSE carried more blaSHV (P = 0.004) and were more resistant to imipenem than non-CP-CNSE (P

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

Spin-orbit torques driven by the conventional spin Hall effect are widely used to switch magnetization, but this approach is nondeterministic and inefficient for magnets with perpendicular magnetic anisotropy. Here, the authors demonstrate deterministic, field-free switching in a Ni/Co multilayer by exploiting the magnetic spin Hall effect in adjacent Mn3Sn.

Abstract Background Clinical medical education is essential in physician training. This study developed recommendations for medical residency course design on the basis of the perspectives of learners in China and how they interact with their environment. The central research topic was the professional development and learning process of residents, including the obstacles that hinder and factors that promote their learning, their views on existing teaching methods, interaction between teachers and medical teams, and suggestions for designing future residency training programs. Methods This study had a qualitative research design. Interviews were conducted between July and October 2019 with 17 specialist residents and 12 assistant general practitioner residents from the department of education of the hospital. The participants were recruited from Qingyuan People’s Hospital in Guangdong Province, China. The interview outlines focused on the following four themes: clinical learning experiences and reflections on learning, experience of interaction with patients, experience of working with other medical personnel, and future learning directions. Results To overcome challenges in clinical learning, the residents mainly learned from their teachers and focused specifically on their own experiences. Regarding teaching methods and designs in clinical medicine, the residents preferred large-group, small-group, and bedside teaching and reported that bedside teaching enables the resolution of clinical problems, initiates self-learning, and improves diagnostic thinking. They disliked teachers with low teaching motivation or who were reluctant to interact with them and favored teachers who had strong teaching skills and respect for their students. Conclusions The residents suggested that clinical and active learning must be the main learning method for developing general medical competencies. Residency training must be conducted in an environment that facilitates residents’ learning and meaningful learning activities. The interdependent symbiotic relationships in the education ecosystem can serve as a reference for designing residency courses.

Background: Carbapenem-resistant Acinetobacter species have emerged as notorious pathogens causing nosocomial infections. Several phenotypic methods have been developed for detecting carbapenemase production in Enterobacteriaceae. The accuracy of these methods in the prediction of carbapenemase production in Acinetobacter species has not been studied well. Methods: This retrospective study enrolled adult patients with Acinetobacter bacteremia from four medical centers in Taiwan between 2012 and 2016. Their demographics and clinical outcomes were recorded. The carbapenem susceptibility of the Acinetobacter species was determined using the agar diffusion method. The carbapenemase genes were detected by PCR. Four phenotypic methods, including the modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), Carba NP test, and CarbAcineto NP test were carried out to determine the production of carbapenemase. Results: We analyzed 257 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia. Shock within three days of bacteremia and acquisition of carbapenem non-susceptible isolates were independently associated with a higher 14-day and 30-day mortality in patients with Acinetobacter bacteremia. Among the four phenotypic tests for carbapenemase detection, MHT using the imipenem disc displayed the greatest sensitivity (94%; 95% confidence interval [CI], 89–97%) and specificity (81%; 95% CI, 73–88%) for predicting imipenem non-susceptibility. Conclusion: Carbapenem non-susceptibility and shock were independent risk factors for mortality in patients with Acinetobacter bacteremia. The MHT could predict the carbapenem susceptibility of Acinetobacter isolates. It is a cheap and quick assay, which could be applied in clinical practice.

Background/purpose: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Abstract Aldehyde dehydrogenases (ALDHs) play an essential role in regulating malignant tumor progression; however, their role in cholangiocarcinoma (CCA) has not been elucidated. We analyzed the expression of ALDHs in 8 paired tumor and peritumor perihilar cholangiocarcinoma (pCCA) tissues and found that ALDH3B1 and ALDH3B2 were upregulated in tumor tissues. Further survival analysis in intrahepatic cholangiocarcinoma (iCCA, n = 27), pCCA (n = 87) and distal cholangiocarcinoma (dCCA, n = 80) cohorts have revealed that ALDH3B2 was a prognostic factor of CCA and was an independent prognostic factor of iCCA and pCCA. ALDH3B2 expression was associated with serum CEA in iCCA and dCCA, associated with tumor T stage, M stage, neural invasion and serum CA19-9 in pCCA. In two cholangiocarcinoma cell lines, overexpression of ALDH3B2 promoted cell proliferation and clone formation by promoting the G1/S phase transition. Knockdown of ALDH3B2 inhibited cell migration, invasion, and EMT in vitro, and restrained tumor metastasis in vivo. Patients with high expression of ALDH3B2 also have high expression of ITGB1 in iCCA, pCCA, and dCCA at both mRNA and protein levels. Knockdown of ALDH3B2 downregulated the expression of ITGB1 and inhibited the phosphorylation level of c-Jun, p38, and ERK. Meanwhile, knockdown of ITGB1 inhibited the promoting effect of ALDH3B2 overexpression on cell proliferation, migration, and invasion. ITGB1 is also a prognostic factor of iCCA, pCCA, and dCCA and double-positive expression of ITGB1 and ALDH3B2 exhibits better performance in predicting patient prognosis. In conclusion, ALDH3B2 promotes tumor proliferation and metastasis in CCA by regulating the expression of ITGB1 and upregulating its downstream signaling pathway. The double-positive expression of ITGB1 and ALDH3B2 serves as a better prognostic biomarker of CCA.

ABSTRACT: Objectives: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017–2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. Methods: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. Results: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. Conclusion: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

In the past decades, due to the high prevalence of the antibiotic-resistant isolates of Acinetobacter baumannii, it has emerged as one of the most troublesome pathogens threatening the global healthcare system. Furthermore, this pathogen has the ability to form biofilms, which is another effective mechanism by which it survives in the presence of antibiotics. However, the clinical impact of biofilm-forming A. baumannii isolates on patients with bacteremia is largely unknown. This retrospective study was conducted at five medical centers in Taiwan over a 9-year period. A total of 252 and 459 patients with bacteremia caused by biofilm- and non-biofilm-forming isolates of A. baumannii, respectively, were enrolled. The clinical demographics, antimicrobial susceptibility, biofilm-forming ability, and patient clinical outcomes were analyzed. The biofilm-forming ability of the isolates was assessed using a microtiter plate assay. Multivariate analysis revealed the higher APACHE II score, shock status, lack of appropriate antimicrobial therapy, and carbapenem resistance of the infected strain were independent risk factors of 28-day mortality in the patients with A. baumannii bacteremia. However, there was no significant difference between the 28-day survival and non-survival groups, in terms of the biofilm forming ability. Compared to the patients infected with non-biofilm-forming isolates, those infected with biofilm-forming isolates had a lower in-hospital mortality rate. Patients with either congestive heart failure, underlying hematological malignancy, or chemotherapy recipients were more likely to become infected with the biofilm-forming isolates. Multivariate analysis showed congestive heart failure was an independent risk factor of infection with biofilm-forming isolates, while those with arterial lines tended to be infected with non-biofilm-forming isolates. There were no significant differences in the sources of infection between the biofilm-forming and non-biofilm-forming isolate groups. Carbapenem susceptibility was also similar between these groups. In conclusion, the patients infected with the biofilm-forming isolates of the A. baumannii exhibited different clinical features than those infected with non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii may also influence the antibiotic susceptibility of its isolates. However, it was not an independent risk factor for a 28-day mortality in the patients with bacteremia.

Background: In-hospital cardiac arrest (IHCA) is a common clinical event with poor outcomes. Former IHCA registries in China were local, inconsistent in data reporting, and lacked attention to the process of care. Therefore, we designed and implemented the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA), the first national IHCA registry in China. Methods: BASIC-IHCA is a prospective, multicenter, observational study with a nationwide surveillance network covering urban and rural hospitals from seven geographic regions of China. IHCA patients were enrolled continuously, and data were collected from medical records by investigators at participating hospitals. Key variables referring to the updated Utstein Template included patient information, event variables, process of care, and outcomes. Follow-up was conducted by telephone interview to obtain details on long-term survival and neurological status. Results: Thirty-two urban hospitals and eight rural hospitals from twenty-nine provinces in seven geographic regions of China participated in BASIC-IHCA. The starting time of enrollment ranged from July 1, 2019, to January 1, 2020. By December 31, 2020, 35,451 IHCAs were enrolled in all participating hospitals, of which 19,493 (55%) received CPR, with a predominance of males (65%) and a median age of 65 years. Conclusion: BASIC-IHCA is the first national registry for IHCA in China. It will describe the epidemiology and outcomes of IHCA from a nationwide perspective, with a particular focus on details of the process of care for quality improvement. Meanwhile, it will help to facilitate the standardization of IHCA-related data reporting in China.

Background/purpose: There are few attempts at diagnosis among physicians who pay less attention to Clostridiodes difficile infection (CDI) and think that one-step enzyme immunoassay (EIA) toxin tests and anaerobic cultures are untrustworthy. Methods: This study investigated patients that had loose stool more than 3 times/day after admission from April 2016 to January 2017. We replaced the one-step toxin rapid test and culture with a two-step rapid test of glutamate dehydrogenase (GDH) and toxins, and we optimized the process of microbiology culture. PCR for toxin genes (tcdA and tcdB) and PCR ribotyping of the isolates were also performed. We compared the results obtained from enzyme linked immunosorbent assay (ELISA), EIA kits for GDH and toxins, and culture in terms of accuracy. Results: A total of 52 cases were enrolled and 22 isolates were identified, which comprised 20 ribotypes017 and 2 ribotypes078. ELISA and EIA (QuikChek) had the best results in GDH detection with sensitivities of 86.4% and 81.8%, respectively. CLO and CHROMagar methods showed 100% positive predictive value, but CLO agar had better negative predictive value (81.1%). According to the receiver operating characteristic (ROC) curve, VIDAS (ELISA), QuikChek (EIA), and CLO agar showed the best performance with areas under the curve of 0.932, 0.909, and 0.841, respectively. Veda (EIA) presented the highest false-positive rate of 26.7%. VIDAS showed the least positive toxin findings but zero falsepositive findings. Conclusions: Ribotype 017 prevailed in our hospital. ELISA and QuickChek (EIA) showed better sensitivity and specificity in GDH detection than most EIA rapid kits.

Abstract Background Certain sequences of genomic mutations can lead to cancer formation and affect treatment outcomes and drug resistance. We constructed a cancer evolutionary tree using bulk-targeted deep sequencing to explore the impact of sequential and co-occurring somatic mutations on patients with stage III colorectal cancer (CRC). Methods A total of 108 stage III CRC patients from National Cheng Kung University Hospital (NCKUH) were recruited for this study between Jan. 2014 and Jan. 2019. Clinical information and tumor-targeted deep sequencing data were collected. Phylogenetic trees were reconstructed for evolutionary trajectories. We used a machine learning model for survival analysis. Results Six sequential somatic mutations stratified patients into seven subgroups based on survival. Patients carrying sequential germline followed by DNA damage response-related ATM or BRCA2 somatic mutations or non-TP53, APC somatic mutations had a better outcome than those without such mutations. The 4-year recurrence-free survival (RFS) probability was 88% in the low-risk group (G1) and 46% in the high-risk group (G2) (log-rank p-value 2e-05). The predictive efficacy by the area under the curve (AUC) was 0.73, 0.7, 0.797, and 0.88 at 2, 4, 6, and 8 years, respectively. The mutation status of mismatch repair (MMR) genes was not associated with RFS. Different genomic features were found between the groups. The orders of APC, KRAS and APC, BRCA2 sequential somatic mutations were associated with clinical outcomes. The occurrence of somatic mutations in BRCA2, such as TP53 somatic mutations, affected recurrence-free survival. Conclusions According to the evolution model, DNA damage response (DDR)-related ATM or BRCA2 somatic mutations are promising biomarkers for assessing the response of stage III CRC patients to oxaliplatin-based chemotherapy. The sequential order and co-occurring DDR somatic mutations are associated with recurrence-free survival.

Abstract Background The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. Methods This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. Results A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34–0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005–0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score > 35 (OR 0.0098; 95% CI 0.0005–0.1885). Conclusion Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.

Recombinant virus-vectored vaccines are novel agents that can effectively activate specific and nonspecific immunity, are multivalent and multieffective, and have high safety ratings. Animal alphaherpesviruses have a large genome, contain multiple nonessential regions that do not affect viral replication and are capable of accepting the insertion of an exogenous gene and expressing the antigen protein. Furthermore, animal alphaherpesviruses have a wide host spectrum, can replicate in the host and continuously stimulate the animal to produce immunity to the corresponding pathogen, thus making them ideal carriers for recombinant virus-vectored vaccines. With the development of gene-editing technology, recombinant viruses capable of expressing foreign genes can be constructed by various methods. Currently, studies on recombinant virus-vectored vaccines constructed based on animal alphaherpesviruses have involved poultry, pigs, cattle, sheep, and companion animals. Studies have shown that the construction of recombinant animal alphaherpesviruses enables the acquisition of immunity to multiple diseases. This article mainly summarizes the current progress on animal alphaherpesvirus-vectored vaccines, aiming to provide reference for the development of new animal alphaherpesvirus-vectored vaccines.

Using only local gene pools to restore native vegetation is challenging. This practice enabled native forest in a post-fired pine and silvergrass woodland to be rehabilitated by reusing indigenous materials in a simple and effective manner. We designed vegetation restoration processes, including uprooting silvergrass and removing pine leaf from woodland ground, collecting tree saplings on sliding slopes and transplanting them, and collecting humus and seeds from roadsides and redistributing them at restoration sites. Volunteers, tourists, and employees of Shei-Pa National Park participated in the restoration practices. Through 5-year practices, the native vegetation and forest floor environment exhibited a remarkable recovery, inducing the reappearance of the Guanwu salamander. This restoration practice cost little money but required much time and labor. The approach may be suitable for small restoration sites. We believe that this practice could enhance knowledge, technology, and enthusiasm for local ecological restoration.

Background: Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated. Methods: Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression. Results: Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50–71] vs. 72 [50.25–71], p

Biliary tract cancers (BTCs), including cholangiocarcinoma (CCA) and gallbladder cancer (GC), are malignancies originating from the biliary tract with poor prognosis. In the early stage of BTCs, surgery is the only choice for cure. Unfortunately, most patients with BTC are diagnosed at an advanced stage and lose the opportunity for surgery. For many advanced solid tumors, antiangiogenic therapy has achieved encouraging results. While most clinical studies on antiangiogenic therapy in advanced BTCs have shown an excellent disease control rate (DCR), the improvement in overall survival (OS) is controversial. Understanding how the relevant signaling molecules influence the angiogenic response and the functional interaction is necessary for the formulation of new treatment regimens and the selection of enrolled patients. In this review, we aim to summarize and discuss the latest advances in antiangeogenesis for BTCs, mainly focusing on the molecular mechanism of angiogenesis in BTCs and the therapeutic effects from clinical trials. Furthermore, the horizon of antiangiogenesis for BTCs is highlighted.

Particulate matter (PM) is one of the reasons that exacerbate skin diseases. Impaired barrier function is a common symptom in skin diseases, including atopic dermatitis, eczema and psoriasis. Herbal extracts rich in antioxidants are thought to provide excellent pharmacological activities; however, the anti-pollution activity of Artocarpus altilis extract (AAM) has not been investigated yet. The present study demonstrated that 5 μg/mL of AAM was considered to be a safe dose for further experiments without cytotoxicity. Next, we evaluated the anti-pollution activity of AAM through the PM-induced keratinocytes damage cell model. The results showed that AAM could reduce PM-induced overproduction of intracellular ROS and the final product of lipid peroxidation, 4-hydroxynonenal (4HNE). In addition, AAM not only reduced the inflammatory protein expressions, including tumor necrosis factor α (TNFα), TNF receptor 1 (TNFR1) and cyclooxygenase-2 (COX-2), but also balanced the aging protein ratio of matrix metalloproteinase (MMPs) and tissue inhibitors of metalloproteases (TIMPs) through downregulating the phosphorylation of mitogen-activated protein kinase (MAPK) signaling. For skin barrier protection, AAM could repair PM-induced barrier function proteins damage, including filaggrin, loricrin and aquaporin 3 for providing anti-aging bioactivity. In conclusion, AAM has the potential to be developed as an anti-pollution active ingredient for topical skin products to prevent skin oxidation, inflammation and aging, and restore the skin barrier function.

China and Great Power Responsibility for Climate Change. By Sanna Kopra. New York: Routledge, 2018. 186 pp. $136.87 (cloth). China's rise to a great power and its increasing engagement with [...]