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Chih-Weim Hsiang,1 Wen-Yen Huang,2,3 Jen-Fu Yang,2 Po-Chien Shen,2 Yang-Hong Dai,2 Ying-Fu Wang,2 Chun-Shu Lin,2 Wei-Chou Chang,1 Cheng-Hsiang Lo2 1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 3Institute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanCorrespondence: Cheng-Hsiang LoDepartment of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec 2, Cheng-Gong Road, Neihu, Taipei, 114, TaiwanTel +886-2-87927122Fax +886-2-66002357Email lsir183@yahoo.com.twPurpose: Immune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).Methods: Data on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined.Results: The study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p< 0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p< 0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child–Turcotte–Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥ 1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002).Conclusion: Baseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.Keywords: hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, stereotactic body radiotherapy, liver toxicity

Wei-Chou Chang,1 Hsian-He Hsu,1 Sung-Hua Chiu,1 Wen-Yen Huang,2 Cheng-Hsiang Lo,2 Hsuan-Hwai Lin,3 Pei-Ching Huang,4 Yu-Lueng Shih,3 Yung-Liang Wan4 1Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 4Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanCorrespondence: Yung-Liang WanDepartment of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanEmail ylw0518@cgmh.org.twAbstract: Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (< 100 μm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).Keywords: chemoembolization, HCC, TACE, DEB-TACE, liver, review

This study investigated the effects of food culture on the economic and ecological development of rural rivers and adolescents’ intentions toward tourism in high-risk leisure environments. The study applied a mixed-methods design. A questionnaire was designed and distributed to recruited participants, and 900 responses were collected and analyzed, with SPSS 26.0 used to perform basic statistical validation and Pearson’s correlation analysis. Structured interviews were conducted to collect the opinions of experts, tourists, and residents of the investigated areas. A multivariate analysis was used to analyze the results, which revealed that superior economic, societal, and ecological development is associated with greater leisure, tourism, and consumption intentions. However, varying levels of environmental literacy among tourists can present challenges. Problems such as tourism waste; overdevelopment; loss of historic architectural features; and pollution of water, forests, and air may deter young tourists from revisiting an area and diminish their willingness to engage in and share leisure experiences.

Study aim: This study aimed to investigate the effect of the FIFA 11+ injury prevention programme on strength and on muscle strength and landing biomechanical markers of anterior cruciate ligament (ACL) injury during fatigue among youth recreational soccer players.

Targeted therapies against human epidermal growth factor receptor 2 (HER2) are associated with increased interstitial lung disease (ILD). Trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine have markedly extended HER2 breast cancer survival but current knowledge on how these HER2-targeted agents induce interstitial lung disease is still poorly defined due to limited cases in the literature. Physicians mostly managed this complication by dose interruption, dose de-escalation, or discontinuation with success. In 2019, the FDA had granted accelerated approval on trastuzumab deruxtecan (T-Dxd) in HER2 breast cancer in the late line setting. Severe ILD incidence rate was over ten percent and led to fatal outcomes in 2.2% of patients in the T-Dxd trial. Searching for biomarkers to detect ILD incidence before it becomes clinically fulminant or for treatment response monitoring is of high clinical value.A Case of life-threatening trastuzumab-induced ILD was encountered in our facility. The ILD was confirmed to be antineutrophil cytoplasmic antibody (ANCA) pulmonary capillaritis. The biomarker of neutrophil extracellular traps (NETs), serum MPO-DNA complex, showed a good correlation with the clinical severity. Soon after B cell depleting agent rituximab usage, the serum MPO-DNA outperformed ANCA autoantibody and maintained its correlation with clinical severity. In addition to the trastuzumab-induced ILD case, a prospective cohort in our facility also confirmed the usefulness of MPO-DNA in monitoring vasculitis activity. We postulated that upfront testing with biomarkers of vasculitis during HER2 targeted treatment with high ILD incidence may be beneficial in the future.

Astragalus is a traditional herb which has been used in China for a long time. It regulates blood circulation (vital energy), invigorates body fluid circulation, protects the flow of blood to fight against the attack of pathogens, and strengthens “blood deficiencies” according to Bencao Congxin. Astragalus was approved by the Food and Drug Administration in 2009 as a dietary supplement for upper respiratory infections, allergic rhinitis (hay fever), asthma, chronic fatigue syndrome, and chronic kidney disease. Thirty journals published in the past ten years were reviewed by using library search engines such as SCI/SCIE, PubMed, and Scopus. In this mini-review, we focus on the anti-inflammatory of Astragalus features, discuss the background of Astragalus and its function in various diseases from water-extracted Astragalus membranaceus, Astragalus saponins, and Astragalus polysaccharides. Based on the traditional Chinese medicine theory, Astragalus is a potential candidate to treat and prevent COVID-19.

Background/Purpose: The iASSIST system is a novel navigation system for total knee replacement. It is based on accelerometers built within electronic pods attached to the instruments within the operative field. The objective of this study was to compare the accuracy of iASSIST navigation with that of the conventional alignment technique. Methods: A total of 91 patients (92 knees) retrospectively matched for age, gender, preoperative range of motion, and lower limb deformity underwent total knee replacement using iASSIST navigation (45 patients, 46 knees) or conventional instrumentation (46 patients, 46 knees). Operative time and radiological alignments were compared. Results: The use of iASSIST navigation resulted in fewer outliners (as defined by >3° deviation from the neutral mechanical axis) in lower limb alignment. Operative time with iASSIST navigation was not longer than that using conventional instruments.Conclusion: iASSIST navigation reduces the incidence of lower limb malalignment without adding extra time to the procedure. 中文摘要: 簡介: iASSIST是一個全新的全膝關節置換術電腦導航系統。本研究的目的是比較iASSIST 導航系統及傳統全膝關節置換術的準確性。 方法: 回顧性分析91位病人(92膝) 的全膝關節置換術，病人、年齡、性別、術前活動範圍和下肢畸形的狀態匹配。45位病人(46膝) 接受了iASSIST電腦導航全膝關節置換術。46位病人接受了傳統全膝關節置換術。我們對两組病人的手術時間及術前術後的影像對線進行了比較。 結果: 使用iASSIST電腦導航全膝關節置換術之整體下肢對線較傳統全膝關節置換術較少 對線異常值 (>3°偏離中立機械軸)。而使用iASSIST電腦導航全膝關節置換術之手術時間並不比傳統全膝關節置換術長。 結論: iASSIST電腦導航降低整體下肢對線出現偏差的機會，同時無需增加額外手術時間。 Keywords: arthroplasty, case–control studies, computer assisted, knee, operative time, replacement, surgery

Lymphoma associated with total knee arthroplasty is a rare condition. We report a case of non-Hodgkin lymphoma mimicking an infected total knee arthroplasty. A 73-year-old woman who received left total knee replacement presented with fever and a discharging sinus over her left knee 12 weeks after surgery. The diagnosis of prosthetic joint infection was made and a two-stage revision arthroplasty planned. After implant removal and insertion of an antibiotic spacer in the first-stage operation, culture results of all intraoperative specimens were negative but the pathology report showed diffuse large B-cell lymphoma. She then received chemotherapy and a second-stage reconstruction operation. The wound healed uneventfully and she regained independent mobility.

The contamination of the aquatic ecosystem with heavy metals arising from the discharge of electronic waste (e-waste) or seepage of leachate from open waste dumpsites is on the increase. The impact of e-waste leachate on the micronucleus (MN) of Tilapia guineensis and the levels of heavy metals ( Pb, Cd, Cr, As, Hg, Al and Ba) in the sediments, water, leachate and aquatic fauna (Tilapia guineensis, Callinectes amnicola and Cardiosoma armatum) found in and around e-waste dumpsites in Lagos and Osun States was studied. The levels of heavy metals were determined using PyeUnicam model 969 Atomic Absorption Spectrophotometry and Inductive Coupling Plasma Atomic Absorption Spectrophotometry (ICP-AAS).The heavy metal concentrations decreased in the order: Pb ˃ Cd ˃ Cr ˃ Hg ˃ Al ˃Ba ˃As in the samples. The level of Cd in fish muscle from Lagos (1.4mg/kg) exceeded the Environment Canada threshold effect level (EC TEL, 2006) recommended for sea food (1.0mg/kg). The calculated bioconcentration factor (BCF) for fish gills (1.4 and1.0) and fish muscles. (3.6 and 1.2) from Lagos and Osun States respectively as well as the bioaccumulation factor (BAF) for crabs (1.78 and 1.36) are strong indications of the ability of the organisms to bioaccumulate the heavy metals. The MN assay showed an initial increase in the frequency of mionccronuclei on the 7th day which gradually decreased on the 14th and 21st day. The result of this study reveals the toxic impacts of e-waste contamination on ecological and human health in a developing economy.

In this study, a tour recommendation system based on social media photos is proposed. The proposed recommendation system can generate trip tours considering both the user’s current location and interests. First, we exploited the geotagged photo dataset from social media websites, which includes photo related information such as user ID numbers, timestamps, hashtags, and GPS coordinates. With this information, the second step is to group photos and identify those places that could be considered relevant for travellers using clustering algorithms. The third step characterizes the resulting clusters by grouping them into different categories using latent dirichlet allocation (LDA) topic modelling approach. The last step is the generation of tours using a long-short term memory neural network (LSTM). The experiments show that the proposed system can be efficient to advise future travellers about the places they would be more likely to visit and arrange trips for them.

The increasing scourge of drug abuse among adolescents is a major challenge facing mankind. As the importance of health education in disease prevention is enormous, drug misuse prevention programme requires introducing innovations, flexibility and reinforcement which will be effective in shortest possible time among the greatest number of people. This study was undertaken to investigate the influence of health education on prevention of drug abuse. 192 adolescents comprising of male and females, randomly selected from two secondary schools and a university were used as sample with ages ranging from 12-22years with a mean of 17years. The questionnaire, “DA Behaviour Inventory” was administered on the sample. Data was collected and analyzed using the t-test statistics at 0.05 level of significant difference. The findings showed that there is no significant difference in the pattern of drug abuse between adolescents with knowledge of drug education and those without knowledge of drug education. There is no significant difference in the pattern of drug abuse between male and female adolescents, there is no significant difference between the pattern of drug abuse of adolescents from upper and lower socio-economic background. Also there is no significant difference in the pattern of drug abuse of early and late adolescents. These findings were discussed and the implications as well. Recommendations and suggestions for further research were given. Keywords: Adolescents, Alcohol, Drug abuse, Education, Pattern

Abstract Background Nucleic acid hybridization is an extensively adopted principle in biomedical research, in which the performance of any hybridization-based method depends on the specificity of probes to their targets. To determine the optimal probe(s) for detecting target(s) from a sample cocktail, we developed a novel algorithm, which has been implemented into a web platform for probe designing. This probe design workflow is now upgraded to satisfy experiments that require a probe designing tool to take the increasing volume of sequence datasets. Results Algorithms and probe parameters applied in UPS 2.0 include GC content, the secondary structure, melting temperature (Tm), the stability of the probe-target duplex estimated by the thermodynamic model, sequence complexity, similarity of probes to non-target sequences, and other empirical parameters used in the laboratory. Several probe background options,Unique probe within a group,Unique probe in a specific Unigene set,Unique probe based onthe pangenomic level, and Unique Probe in the user-defined genome/transcriptome, are available to meet the scenarios that the experiments will be conducted. Parameters, such as salt concentration and the lower-bound Tm of probes, are available for users to optimize their probe design query. Output files are available for download on the result page. Probes designed by the UPS algorithm are suitable for generating microarrays, and the performance of UPS-designed probes has been validated by experiments. Conclusions The UPS 2.0 evaluates probe-to-target hybridization under a user-defined condition to ensure high-performance hybridization with minimal chance of non-specific binding at the pangenomic and genomic levels. The UPS algorithm mimics the target/non-target mixture in an experiment and is very useful in developing diagnostic kits and microarrays. The UPS 2.0 website has had more than 1,300 visits and 360,000 sequences performed the probe designing task in the last 30 months. It is freely accessible at http://array.iis.sinica.edu.tw/ups/. Screen cast: http://array.iis.sinica.edu.tw/ups/demo/demo.htm

Abstract Background Proteins control and mediate many biological activities of cells by interacting with other protein partners. This work presents a statistical model to predict protein interaction networks of Drosophila melanogaster based on insight into domain interactions. Results Three high-throughput yeast two-hybrid experiments and the collection in FlyBase were used as our starting datasets. The co-occurrences of domains in these interactive events are converted into a probability score of domain-domain interaction. These scores are used to infer putative interaction among all available open reading frames (ORFs) of fruit fly. Additionally, the likelihood function is used to estimate all potential protein-protein interactions. All parameters are successfully iterated and MLE is obtained for each pair of domains. Additionally, the maximized likelihood reaches its converged criteria and maintains the probability stable. The hybrid model achieves a high specificity with a loss of sensitivity, suggesting that the model may possess major features of protein-protein interactions. Several putative interactions predicted by the proposed hybrid model are supported by literatures, while experimental data with a low probability score indicate an uncertain reliability and require further proof of interaction. Fly-DPI is the online database used to present this work. It is an integrated proteomics tool with comprehensive protein annotation information from major databases as well as an effective means of predicting protein-protein interactions. As a novel search strategy, the ping-pong search is a naïve path map between two chosen proteins based on pre-computed shortest paths. Adopting effective filtering strategies will facilitate researchers in depicting the bird's eye view of the network of interest. Fly-DPI can be accessed at http://flydpi.nhri.org.tw. Conclusion This work provides two reference systems, statistical and biological, to evaluate the reliability of protein interaction. First, the hybrid model statistically estimates both experimental and predicted protein interaction relationships. Second, the biological information for filtering and annotation itself is a strong indicator for the reliability of protein-protein interaction. The space-temporal or stage-specific expression patterns of genes are also critical for identifying proteins involved in a particular situation.

Abstract Background Our interests lie in determining the genes and genetic pathways that are important for establishing and maintaining maternal-fetal interactions during pregnancy. Mutation analysis targeted to a 34 Mb domain flanked by Trp53 and Wnt3 demonstrates that this region of mouse chromosome 11 contains a large number of essential genes. Two mutant alleles (l11Jus1 and l11Jus4), which fall into the same complementation group, survive through implantation but fail prior to gastrulation. Results Through a positional cloning strategy, we discovered that these homozygous mutant alleles contain non-conservative missense mutations in the Notchless homolog 1 (Drosophila) (Nle1) gene. NLE1 is a member of the large WD40-repeat protein family, and is thought to signal via the canonical NOTCH pathway in vertebrates. However, the phenotype of the Nle1 mutant mice is much more severe than single Notch receptor mutations or even in animals in which NOTCH signaling is blocked. To test the hypothesis that NLE1 functions in multiple signaling pathways during pre-implantation development, we examined expression of multiple Notch downstream target genes, as well as select members of the Wnt pathway in wild-type and mutant embryos. We did not detect altered expression of any primary members of the Notch pathway or in Notch downstream target genes. However, our data reveal that Cdkn1a, a NOTCH target, was upregulated in Nle1 mutants, while several members of the Wnt pathway are downregulated. In addition, we found that Nle1 mutant embryos undergo caspase-mediated apoptosis as hatched blastocysts, but not as morulae or blastocysts. Conclusions Taken together, these results uncover potential novel functions for NLE1 in the WNT and CDKN1A pathways during embryonic development in mammals.

Abstract Introduction With evolutions in surgical techniques, minimally invasive surgical (MIS) repair with Achillon applicator has been introduced. However, there is still a lack of literature to investigate into the clinical merits of MIS over open surgery. This study aims to investigate the correlation between clinical outcome, gait analysis and biomechanical properties comparing both surgical methods. Materials and methods A single centre retrospective review on all the consecutive operated patients between January 2004 and December 2008 was performed. Twenty-six patients (19 male and 7 female; age 40.4 ± 9.2 years) had experienced a complete Achilles tendon rupture with operative repair. Nineteen of the patients, 10 MIS versus 9 open repairs (13 men with a mean age of 40.54 ± 10.43 (range 23-62 yrs) and 6 women with a mean age of 45.33 ± 7.71 (range 35-57 yrs) were further invited to attend a thorough clinical assessment using Holz's scale and biomechanical evaluation at a mean of 25.3 months after operation. This study utilized the Cybex II isokinetic dynamometer to assess the isokinetic peak force of plantar-flexion and dorsiflexion of both ankles. The patients were also invited to return to our Gait Laboratory for analysis. The eight-infrared camera motion capture system (VICON, UK) was utilized for the acquisition of kinematic variables. Their anthropometric data was measured according to the Davis and coworkers' standard. Results The mean operative time and length of hospital stay were shorter in the MIS group. The operative time was 54.55 ± 15.15 minutes versus 68.80 ± 18.23 minutes of the MIS group and Open group respectively (p = 0.045), whereas length of stay was 3.36 ± 1.21 days versus 6.40 ± 3.70 days respectively (p = 0.039). There is statistically significant decrease (p = 0.005) in incision length in MIS group than the open surgery group, 3.23 ± 1.10 cm versus 9.64 ± 2.55 cm respectively. Both groups attained similar Holz's scores, 11.70 ± 0.95 versus 12.0 ± 1.50 respectively (p = 0.262). The mean percentage stance time of the injured leg for MIS patient was 58.44% while the mean percentage stance time of the injured leg for patients with open repair was 56.57%. T-test has shown there were no significance differences between the results of the two groups of patients. The loss of peak torque and total work done with respect to the injured side were similar between the MIS and open group. Discussion and conclusion MIS using Achillon method can achieve smaller incisions, shorter operative time and hospital stay. There is no statistical significance difference in clinical outcome, the stance time to strike time ratio and biomechanical properties on the leg receiving Achilles tendon repair using MIS method and open surgery.

Abstract Background The black tiger shrimp (Penaeus monodon) is one of the most important aquaculture species in the world, representing the crustacean lineage which possesses the greatest species diversity among marine invertebrates. Yet, we barely know anything about their genomic structure. To understand the organization and evolution of the P. monodon genome, a fosmid library consisting of 288,000 colonies and was constructed, equivalent to 5.3-fold coverage of the 2.17 Gb genome. Approximately 11.1 Mb of fosmid end sequences (FESs) from 20,926 non-redundant reads representing 0.45% of the P. monodon genome were obtained for repetitive and protein-coding sequence analyses. Results We found that microsatellite sequences were highly abundant in the P. monodon genome, comprising 8.3% of the total length. The density and the average length of microsatellites were evidently higher in comparison to those of other taxa. AT-rich microsatellite motifs, especially poly (AT) and poly (AAT), were the most abundant. High abundance of microsatellite sequences were also found in the transcribed regions. Furthermore, via self-BlastN analysis we identified 103 novel repetitive element families which were categorized into four groups, i.e., 33 WSSV-like repeats, 14 retrotransposons, 5 gene-like repeats, and 51 unannotated repeats. Overall, various types of repeats comprise 51.18% of the P. monodon genome in length. Approximately 7.4% of the FESs contained protein-coding sequences, and the Inhibitor of Apoptosis Protein (IAP) gene and the Innexin 3 gene homologues appear to be present in high abundance in the P. monodon genome. Conclusions The redundancy of various repeat types in the P. monodon genome illustrates its highly repetitive nature. In particular, long and dense microsatellite sequences as well as abundant WSSV-like sequences highlight the uniqueness of genome organization of penaeid shrimp from those of other taxa. These results provide substantial improvement to our current knowledge not only for shrimp but also for marine crustaceans of large genome size.

Abstract Nanocrystalline Co40Fe40B20 films, with film thickness t f = 100 nm, were deposited on glass substrates by the magnetron sputtering method at room temperature. During the film deposition period, a dc magnetic field, h = 40 Oe, was applied to introduce an easy axis for each film sample: one with h||L and the other with h||w, where L and w are the length and width of the film. Ferromagnetic resonance (FMR), ultrahigh frequency impedance (IM), dc electrical resistivity (ρ), and magnetic hysteresis loops (MHL) of these films were studied. From the MHL and r measurements, we obtain saturation magnetization 4πMs = 15.5 kG, anisotropy field H k = 0.031 kG, and r = 168 mW.cm. From FMR, we can determine the Kittel mode ferromagnetic resonance (FMR-K) frequency f FMRK = 1,963 MHz. In the h||L case, IM spectra show the quasi-Kittel-mode ferromagnetic resonance (QFMR-K) at f 0 and the Walker-mode ferromagnetic resonance (FMR-W) at fn , where n = 1, 2, 3, and 4. In the h||w case, IM spectra show QFMR-K at F 0 and FMR-W at Fn . We find that f 0 and F 0 are shifted from f FMRK, respectively, and fn = Fn . The in-plane spin-wave resonances are responsible for those relative shifts. PACS No. 76.50.+q; 84.37.+q; 75.70.-i

Abstract Background Pandemic influenza H1N1 (pdmH1N1) virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. Methods We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Results Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN) response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNβ and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO) and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. Conclusions Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses lay in the ability of seasonal H1N1 virus to down regulate zinc finger proteins and small nucleolar RNAs, which are possible viral transcriptional suppressors and eukaryotic translation initiation factors respectively. These differences may be biologically relevant and may represent better adaptation of seasonal H1N1 influenza virus to the host.

Abstract Background Safety activities have been initiated at many hospitals in Taiwan, but little is known about the safety culture at these hospitals. The aims of this study were to verify a safety culture survey instrument in Chinese and to assess hospital safety culture in Taiwan. Methods The Taiwan Patient Safety Culture Survey was conducted in 2008, using the adapted Safety Attitude Questionnaire in Chinese (SAQ-C). Hospitals and their healthcare workers participated in the survey on a voluntary basis. The psychometric properties of the five SAQ-C dimensions were examined, including teamwork climate, safety climate, job satisfaction, perception of management, and working conditions. Additional safety measures were asked to assess healthcare workers' attitudes toward their collaboration with nurses, physicians, and pharmacists, respectively, and perceptions of hospitals' encouragement of safety reporting, safety training, and delivery delays due to communication breakdowns in clinical areas. The associations between the respondents' attitudes to each SAQ-C dimension and safety measures were analyzed by generalized estimating equations, adjusting for the clustering effects at hospital levels. Results A total of 45,242 valid questionnaires were returned from 200 hospitals with a mean response rate of 69.4%. The Cronbach's alpha was 0.792 for teamwork climate, 0.816 for safety climate, 0.912 for job satisfaction, 0.874 for perception of management, and 0.785 for working conditions. Confirmatory factor analyses demonstrated a good model fit for each dimension and the entire construct. The percentage of hospital healthcare workers holding positive attitude was 48.9% for teamwork climate, 45.2% for perception of management, 42.1% for job satisfaction, 37.2% for safety climate, and 31.8% for working conditions. There were wide variations in the range of SAQ-C scores in each dimension among hospitals. Compared to those without positive attitudes, healthcare workers with positive attitudes to each SAQ dimension were more likely to perceive good collaboration with coworkers, and their hospitals were more likely to encourage safety reporting and to prioritize safety training programs (Wald chi-square test, p < 0.001 for all). Conclusions Analytical results verified the psychometric properties of the SAQ-C at Taiwanese hospitals. The safety culture at most hospitals has not fully developed and there is considerable room for improvement.

Abstract Background Intraluminal migration of a drain through an anastomotic site is a rare complication of gastric surgery. Case Presentation We herein report the intraluminal migration of a drain placed after a lower esophagectomy and total gastrectomy with Roux-en-Y anastomosis for gastric small cell carcinoma. Persistent drainage was noted 1 month after surgery, and radiographic studies were consistent with drain tube migration. Endoscopy revealed the drain had migrated into the esophagojejunostomy anastomotic site. The drain was removed from outside of abdominal wound while observing the anastomotic site endoscopically. The patient was treated with suction via a nasogastric tube drain for 5 days, and thereafter had an uneventful recovery. Conclusions Though drain tube migration is a rare occurrence, it should be considered in patients with persistent drainage who have undergone gastric surgery.

Abstract Background Outbreaks of the casuarina moth, Lymantria xylina Swinehoe (Lepidoptera: Lymantriidae), which is a very important forest pest in Taiwan, have occurred every five to 10 years. This moth has expanded its range of host plants to include more than 65 species of broadleaf trees. LyxyMNPV (L. xylina multiple nucleopolyhedrovirus) is highly virulent to the casuarina moth and has been investigated as a possible biopesticide for controlling this moth. LdMNPV-like virus has also been isolated from Lymantria xylina larvae but LyxyMNPV was more virulent than LdMNPV-like virus both in NTU-LY and IPLB-LD-652Y cell lines. To better understand LyxyMNPV, the nucleotide sequence of the LyxyMNPV DNA genome was determined and analysed. Results The genome of LyxyMNPV consists of 156,344 bases, has a G+C content of 53.4% and contains 157 putative open reading frames (ORFs). The gene content and gene order of LyxyMNPV were similar to those of LdMNPV, with 151 ORFs identified as homologous to those reported in the LdMNPV genome. Two genes (Lyxy49 and Lyxy123) were homologous to other baculoviruses, and four unique LyxyMNPV ORFs (Lyxy11, Lyxy19, Lyxy130 and Lyxy131) were identified in the LyxyMNPV genome, including a gag-like gene that was not reported in baculoviruses. LdMNPV contains 23 ORFs that are absent in LyxyMNPV. Readily identifiable homologues of the gene host range factor-1 (hrf-1), which appears to be involved in the susceptibility of L. dispar to NPV infection, were not present in LyxyMNPV. Additionally, two putative odv-e27 homologues were identified in LyxyMNPV. The LyxyMNPV genome encoded 14 bro genes compared with 16 in LdMNPV, which occupied more than 8% of the LyxyMNPV genome. Thirteen homologous regions (hrs) were identified containing 48 repeated sequences composed of 30-bp imperfect palindromes. However, they differed in the relative positions, number of repeats and orientation in the genome compared to LdMNPV. Conclusion The gene parity plot analysis, percent identity of the gene homologues and a phylogenetic analysis suggested that LyxyMNPV is a Group II NPV that is most closely related to LdMNPV but with a highly distinct genomic organisation.

Abstract Paediatric supracondylar fractures of the femur are not common. The treatment options depend on the age of child, the site of the fracture, the pattern of injury and the surgeon's preference. We report a case of an 11-year old boy who sustained a comminuted displaced supracondylar fracture of the femur and was treated with indirect reduction and internal fixation with the Less Invasive Stabilization System (LISS) tibial plate.

Abstract Background Eosinophilic granulocytes are important for the human immune system. Many cationic proteins with cytotoxic activities, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), are released from activated eosinophils. ECP, with low RNase activity, is widely used as a biomarker for asthma. ECP inhibits cell viability and induces apoptosis to cells. However, the specific pathway underlying the mechanisms of ECP-induced cytotoxicity remains unclear. This study investigated ECP-induced apoptosis in bronchial epithelial BEAS-2B cells and elucidated the specific pathway during apoptosis. Results To address the mechanisms involved in ECP-induced apoptosis in human BEAS-2B cells, investigation was carried out using chromatin condensation, cleavage of poly (ADP-ribose) polymerase (PARP), sub-G1 distribution in cell cycle, annexin V labeling, and general or specific caspase inhibitors. Caspase-8-dependent apoptosis was demonstrated by cleavage of caspase-8 after recombinant ECP treatment, accompanied with elevated level of tumor necrosis factor alpha (TNF-α). Moreover, ECP-induced apoptosis was effectively inhibited in the presence of neutralizing anti-TNF-α antibody. Conclusion In conclusion, our results have demonstrated that ECP increased TNF-α production in BEAS-2B cells and triggered apoptosis by caspase-8 activation through mitochondria-independent pathway.

Abstract Background White spot syndrome (WSS) is a viral disease that affects most of the commercially important shrimps and causes serious economic losses to the shrimp farming industry worldwide. However, little information is available in terms of the molecular mechanisms of the host-virus interaction. In this study, we used an expressed sequence tag (EST) approach to observe global gene expression changes in white spot syndrome virus (WSSV)-infected postlarvae of Penaeus monodon. Results Sequencing of the complementary DNA clones of two libraries constructed from normal and WSSV-infected postlarvae produced a total of 15,981 high-quality ESTs. Of these ESTs, 46% were successfully matched against annotated genes in National Center of Biotechnology Information (NCBI) non-redundant (nr) database and 44% were functionally classified using the Gene Ontology (GO) scheme. Comparative EST analyses suggested that, in postlarval shrimp, WSSV infection strongly modulates the gene expression patterns in several organs or tissues, including the hepatopancreas, muscle, eyestalk and cuticle. Our data suggest that several basic cellular metabolic processes are likely to be affected, including oxidative phosphorylation, protein synthesis, the glycolytic pathway, and calcium ion balance. A group of immune-related chitin-binding protein genes is also likely to be strongly up regulated after WSSV infection. A database containing all the sequence data and analysis results is accessible at http://xbio.lifescience.ntu.edu.tw/pm/. Conclusion This study suggests that WSSV infection modulates expression of various kinds of genes. The predicted gene expression pattern changes not only reflect the possible responses of shrimp to the virus infection but also suggest how WSSV subverts cellular functions for virus multiplication. In addition, the ESTs reported in this study provide a rich source for identification of novel genes in shrimp.

Operational research as a tool for farming research in Thies-Diourbel (Senegal). The paper is concerned with the choice procedure of production plans at the farm level in Senegal. Two ways of intensification have been selected in order to improve the present farming system ; the first one is characterized by an averaged use of fertilizer coming along with horse power mechanization, the second one promotes high dosis of fertilizers and oxen drawn tools. Different models have been set up assuming a fair matching of the basic needs of rural population and an optimization of family welfare. Optimal solutions are displaying gross margin per labor unit much higher (73 %) when applying oxen traction rather than horse traction. Risk and uncertainty are fairly taken into account in the chosen plans.

Retinitis pigmentosa (RP) is a complex group of inherited retinal diseases characterized by progressive death of photoreceptor cells and eventual blindness. Pde6a, which encodes a cGMP-specific phosphodiesterase, is a crucial pathogenic gene for autosomal recessive RP (RP43); there is no effective therapy for this form of RP. The compact CRISPR/SaCas9 system, which can be packaged into a single adeno-associated virus, holds promise for simplifying effective gene therapy. Here, we demonstrated that all-in-one AAV-SaCas9-mediated Nrl gene inactivation can efficiently prevent retinal degeneration in a RP mouse model with Pde6anmf363/nmf363 mutation. We screened single guide RNAs (sgRNAs) capable of efficiently editing mouse Nrl gene in N2a cells and then achieved effective gene editing by using a single AAV to co-deliver SaCas9 and an optimal Nrl-sg2 into the mouse retina. Excitingly, in vivo inactivation of Nrl improved photoreceptor cell survival and rescued retinal function in treated Pde6a deficient mice. Thus, we showed that a practical, gene-independent method, AAV-SaCas9-mediated Nrl inactivation, holds promise for future therapeutic applications in patients with RP.

Human brain development is a complex process that requires intricate coordination of multiple cellular and developmental events. Dysfunction of lipid metabolism can lead to neurodevelopmental disorders. Lowe syndrome (LS) is a recessive X-linked disorder associated with proximal tubular renal disease, congenital cataracts and glaucoma, and central nervous system developmental delays. Mutations in OCRL, which encodes an inositol polyphosphate 5-phosphatase, lead to the development of LS. The cellular mechanism responsible for neuronal dysfunction in LS is unknown. Here we show depletion of mitochondrial DNA and decrease in mitochondrial activities result in neuronal differentiation defects. Increased astrocytes, which are secondary responders to neurodegeneration, are observed in neuronal (iN) cells differentiated from Lowe patient-derived iPSCs and an LS mouse model. Inactivation of cilia-related sonic hedgehog signaling, which organizes the pattern of cellular neuronal differentiation, is observed in an OCRL knockout, iN cells differentiated from Lowe patient-derived iPSCs, and an LS mouse model. Taken together, our findings indicate that mitochondrial dysfunction and impairment of the ciliary sonic hedgehog signaling pathway represent a novel pathogenic mechanism underlying the disrupted neuronal differentiation observed in LS.

Retinitis pigmentosa (RP) is a complex spectrum of inherited retinal diseases marked by the gradual loss of photoreceptor cells, ultimately leading to blindness. Among these, mutations in PDE6A, responsible for encoding a cGMP-specific phosphodiesterase, stand out as pivotal in autosomal recessive RP (RP43). Unfortunately, no effective therapy currently exists for this specific form of RP. However, recent advancements in genome editing, such as base editing (BE) and prime editing (PE), offer a promising avenue for precise and efficient gene therapy. Here, it is illustrated that the engineered BE and PE systems, particularly PE, exhibit high efficiency in rescuing a target point mutation with minimal bystander effects in an RP mouse model carrying the Pde6a (c.2009A > G, p.D670G) mutation. The optimized BE and PE systems are first screened in N2a cells and subsequently assessed in electroporated mouse retinas. Notably, the optimal PE system, delivered via dual adeno-associated virus (AAV), precisely corrects the pathogenic mutation with average 9.4% efficiency, with no detectable bystander editing. This correction restores PDE6A protein expression, preserved photoreceptors, and rescued retinal function in Pde6a mice. Therefore, this study offers a proof-of-concept demonstration for the treatment of Pde6a-related retinal degeneration using BE and PE systems., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background & Aims: Ultra-processed foods (UPFs) may have a negative impact on bowel habits. We aimed to assess the association between UPF and unprocessed or minimally processed food (MPF) intake and bowel habits among adults in the United States (U.S.)., Methods: We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (2005-2010). We used two 24-hour dietary recalls and, based on the Nova classification, calculated intakes of UPFs and MPFs. Constipation and diarrhea were defined using the Bristol Stool Form Scale and stool frequency. We performed survey-weighted logistic regression and substitution analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Among 12,716 U.S. adults, there were 1290 cases of constipation and 1067 cases of diarrhea. Median UPF and MPF intakes were 26.5% and 66.2% of total grams per day, respectively. Greater UPF consumption (in % gram/d) was associated with higher odds of constipation (adjusted OR [aOR Q4 vs Q1 ], 2.20; 95% CI, 1.76-2.74) (P trend < .001) but not diarrhea (aOR Q4 vs Q1 , 0.82; 95% CI, 0.62-1.09) (P trend  = .12). Increased MPF consumption was associated with lower odds of constipation (aOR Q4 vs Q1 , 0.46; 95% CI, 0.370-0.57) (P trend < .001). Associations with constipation were attenuated after adjusting for diet quality (aOR Q4 vs Q1 , UPF, 1.53; MPF, 0.69). Substituting 10% of UPF intake with an equivalent proportion of MPFs was associated with lower odds of constipation (aOR, 0.90; 95% CI, 0.87-0.93)., Conclusions: UPF intake was associated with higher odds of constipation, whereas the odds were lower with greater MPF consumption. The effect of food processing on bowel habits was independent of diet quality., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Tumor necrosis factor receptors (TNFR1 and TNFR2) play key roles in mediating inflammatory response and cell death signaling, which are associated with autoimmune disorders, neurodegenerative diseases, and cancers. The structure-function relationships of TNF receptors and their ligands determine the activation or inhibition of downstream signaling pathways. Available crystal structures have provided critical insights into the therapeutic targeting strategies of TNF receptors and their signaling networks. In this review, we discuss the potential of targeting receptor-ligand and receptor-receptor interactions in a competitive manner as well as perturbing receptor conformational dynamics through an allosteric mechanism to modulate TNF receptor signaling. We propose that conformational states of TNF receptors can act as a molecular switch in determining their functions and are important therapeutic targets. The knowledge of the structure-function relationships of TNF receptors can be applied to translational high-throughput drug screening and design of novel receptor-specific modulators with enhanced pharmacological properties., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)