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CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli . We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphology of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. [ABSTRACT FROM AUTHOR]

Quasi-equivalent viruses that infect animals and bacteria require a maturation process in which particles transition from initially assembled procapsids to infectious virions. Nudaurelia capensis ω virus (NωV) is a T = 4, eukaryotic, single-stranded ribonucleic acid virus that has proved to be an excellent model system for studying the mechanisms of viral maturation. Structures of NωV procapsids (diameter = 480 Å), a maturation intermediate (410 Å), and the mature virion (410 Å) were determined by electron cryo-microscopy and three-dimensional image reconstruction (cryoEM). The cryoEM density for each particle type was analyzed with a recently developed maximum likelihood variance (MLV) method for characterizing microstates occupied in the ensemble of particles used for the reconstructions. The procapsid and the mature capsid had overall low variance ( i. e., uniform particle populations) while the maturation intermediate (that had not undergone post-assembly autocatalytic cleavage) had roughly two to four times the variance of the first two particles. Without maturation cleavage, the particles assume a variety of microstates, as the frustrated subunits cannot reach a minimum energy configuration. Geometric analyses of subunit coordinates provided a quantitative description of the particle reorganization during maturation. Superposition of the four quasi-equivalent subunits in the procapsid had an average root mean square deviation (RMSD) of 3 Å while the mature particle had an RMSD of 11 Å, showing that the subunits differentiate from near equivalent environments in the procapsid to strikingly non-equivalent environments during maturation. Autocatalytic cleavage is clearly required for the reorganized mature particle to reach the minimum energy state required for stability and infectivity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: A three-dimensional reconstruction of Sindbis virus at 7.0 Å resolution presented here provides a detailed view of the virion structure and includes structural evidence for key interactions that occur between the capsid protein (CP) and transmembrane (TM) glycoproteins E1 and E2. Based on crystal structures of component proteins and homology modeling, we constructed a nearly complete, pseudo-atomic model of the virus. Notably, this includes identification of the 33-residue cytoplasmic domain of E2 (cdE2), which follows a path from the E2 TM helix to the CP where it enters and exits the CP hydrophobic pocket and then folds back to contact the viral membrane. Modeling analysis identified three major contact regions between cdE2 and CP, and the roles of specific residues were probed by molecular genetics. This identified R393 and E395 of cdE2 and Y162 and K252 of CP as critical for virus assembly. The N-termini of the CPs form a contiguous network that interconnects 12 pentameric and 30 hexameric CP capsomers. A single glycoprotein spike cross-links three neighboring CP capsomers as might occur during initiation of virus budding. [Copyright &y& Elsevier]

A bionic surface based on the wing structure of the dragon louse is developed and applied in the thermal management system of electronic components. Fe 3 O 4 -water nanofluids are introduced and their thermal-hydrodynamic behaviors under magnetic field are studied. The influence of nanofluids concentration (ξ = 0.1–0.5%), Reynolds numbers (Re = 712–1400), tilt angles of magnetic field (θ = 0°, 30°, 60°) and intensity of magnetic field (β = 0.0 T, 0.005 T, 0.010 T, 0.015 T) on the heat transfer are considered in the system. Exergy efficiency and entropy production of CPU cooling system are analyzed. Results presented that the bionic surface based on the wing structure of the dragon louse shows an excellent drag reduction effect compared with the smooth surface, which can reach 35.4%. The maximal reduced ratio of CPU surface temperature under magnetic field is 34.42% in comparison with that under no magnetic field, and the maximal reduced ratio of CPU surface temperature with θ = 60° is 14.96% in comparison with θ = 0°. It shows an augmentation of heat transfer for most cases with the identical rate of flow from the point of exergy efficiency. When nanofluids concentration is ξ = 0.3%, Reynolds number is Re = 1402, tilt angle is θ = 60°, and magnetic field strength is β = 0.015 T, the minimum entropy production is obtained. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved method of recycling cytoplasm components in eukaryotes. It plays an important role in plant growth and development, as well as in response to biotic and abiotic stresses. Although autophagy‐related genes (ATGs) have been identified in several crop species, their particular role in potato (Solanum tuberosum L.) remains unclear. Several transcription factors and signaling genes in the transgenic lines of the model plant Arabidopsis thaliana, such as AtTSPO, AtBES1, AtPIP2;7, AtCOST1 as well as AtATI1/2, ATG8f, GFP‐ATG8F‐HA, AtDSK2, AtNBR1, AtHKT1 play crucial functions under drought and salt stresses, respectively. In this study, a total of 29 putative StATGs from 15 different ATG subfamilies in the potato genome were identified. Their physicochemical properties, evolutionary connections, chromosomal distribution, gene duplication, protein–protein interaction network, conserved motifs, gene structure, interspecific collinearity relationship, and cis‐regulatory elements were analyzed. The results of qRT‐PCR detection of StATG expression showed that 29 StATGs were differentially expressed in potato's leaves, flowers, petiole, stem, stolon, tuber, and root. StATGs were dynamically modulated by salt and drought stresses and up‐regulated under salt and drought conditions. Our results showed that the StATG8a localized in the cytoplasm and the nucleus. Potato cultivar "Atlantic" overexpressing or downregulating StATG8a were constructed. Based on physiological, biochemical, and photosynthesis parameters, potato lines overexpressing StATG8a exhibited 9 times higher drought and salt tolerance compared to non‐transgenic plants. In contrast, the potato plants with knockdown expression showed a downtrend in drought and salt tolerance compared to non‐transgenic potato lines. These results could provide new insights into the function of StATG8a in salt and drought response and its possible mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic offloading devices, including insoles, shoes, and other orthoses, are some of the most commonly used interventions to treat or prevent diabetic foot ulceration. Custom-made offloading devices are increasingly used to offset the development of foot ulcers. However, whether these devices are more effective than prefabricated standard offloading devices is uncertain. Therefore, this systematic review collates and examines evidence on the efficacy of custom-made offloading devices in preventing foot ulcer incidence and recurrence in people diagnosed with diabetes. Methods: Five scientific databases were searched, covering 2011–2023. Initial searches and screening were carried out independently by two researchers. Studies meeting the inclusion criteria were further examined through additional screenings, and critical appraisal. Data relevant to the review aims were extracted and analysed within a narrative synthesis. Results: Of the 1,715 articles found in the initial searches, nine papers were found to meet inclusion criteria and were included in the review. The evidence shows that custom-made offloading devices are likely to be more effective for reducing or preventing diabetic foot ulcers than standard offloading devices. However, due to a lack of data it remains uncertain whether custom-made offloading devices are more cost-effective for preventing ulceration compared to standard insoles. Likewise, due to measurement heterogeneity between studies and lack of data, it is unclear whether adherence is higher in users of custom-made offloading devices, and whether such devices deliver significantly greater reductions in peak pressure as compared to standard offloading devices. Conclusion: Custom-made offloading devices are more effective than standard devices for preventing diabetic foot ulceration, and we recommended their use when feasible; however, there remains uncertainty regarding their cost-effectiveness compared to standard insoles and offloading devices. [ABSTRACT FROM AUTHOR]

Immunotherapy is reportedly effective in a subset of colorectal cancers (CRCs) with high microsatellite instability (MSI-H). Exploring the expression patterns and clinical values of immunologic molecules is critical in defining the specific responsive candidates. Here, we performed comprehensive molecular profiling of the B7 and TNFR family genes across 6 CRC datasets with over 1,000 patients’ details using cBioPortal TCGA data. About 20% of patients had B7 and TNFR family gene alterations. The frequency of B7 gene mutations (2.2%-5%) were similar to copy number alterations (0.53%-5.46%). TNFR amplifications were relatively more common (5.45-11.32%) than that of B7 (0.09-2.73%). B7 and TNFR gene mRNAs were upregulated in 26% of cases (102/379) and 16% of cases (61/379), respectively. The mRNA levels of B7 and TNFR genes were inversely correlated with promoter methylation status. Clinically, both B7-H3 and TNFSF7 mRNA overexpression were associated with unfavorable clinical outcomes, and the B7-H3 expression was increased gradually in cases with gene amplifications. Moreover, patients with MSI-H had significantly higher PD-L1 or PD-1 expression. Most importantly, in MSI-H group, patients with PD-L1 or PD-1 upregulation had poorer survivals than those with PD-L1/PD-1 downregulation. This is the first study drawing the immune landscapes of the co-stimulator B7 and TNFR families in CRC and showing that MSI-H patients with PD-1/PD-L1 upregulation are associated with poor clinical outcomes, providing potential markers to stratify patients responsive to immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

In this paper, TiO2–H2O nanofluids are used instead of traditional mediums such as water and oil as the heat transfer medium. For the purpose of research on the natural convection heat transfer characteristics of TiO2–H2O nanofluids in a cavity filled with metal foam, a natural convection experiment system filled with different pore density (PPI) copper foam was established. The experimental results showed that the filling of the metal foam greatly improves the heat transfer effect in the cavity. When the PPI of the metal foam copper is 5 and 25, the Nusselt numbers are similar and larger than that of PPI = 15. The heat transfer effect of water in a cavity with the PPI = 5, PPI = 15 and PPI = 25 metal foam can be enhanced by 58.8%, 31.4% and 63.3% compared with that without metal foam, respectively. The heat transfer effect increases with the concentration of nanofluids. TiO2–H2O nanofluids with 0.1%, 0.3% and 0.5% mass fraction can enhance heat exchange by 6.3%, 22.9% and 32.1% compared with water, respectively. In addition, as the heating power increases, the heat transfer is improved while the heat transfer enhancement efficiency deteriorates. [ABSTRACT FROM AUTHOR]

• Effect of tube structure on heat transfer and flow performance is studied. • Thermo-hydraulic performance is analyzed by thermal efficiency R 3. • Thermo-hydraulic performance is analyzed by exergy efficiency. An experiment is carried out to research the thermo-hydraulic performance of TiO 2 -H 2 O nanofluids in triangle tubes while taking the effect of twisted tapes into consideration. The theories of thermal and exergy efficiency are applied to estimate this system. The influence of mass fractions of nanoparticles (0.1 wt%, 0.3 wt% and 0.5 wt%), Reynolds numbers (Re = 800–9000), different structures of triangle tubes (isosceles right triangle tube (tube 1), isosceles 45° triangle tube (tube 2)) and twisted tape on the Nusselt number, Nusselt number ratio, resistance coefficient, resistance coefficient ratio and pressure drop are experimentally studied respectively. Results show that there are three positive factors for heat transfer performance including large nanoparticles concentration, large Reynolds number and existence of the twisted tape. Compared with the smooth tube, tubes (tubes 1 and 2) with twisted tape can enhance heat transfer, but that without twisted tape can deteriorate heat transfer, for heat transfer performance, tube 2 is better than tube 1. Tube 2 with twisted tape has the biggest value of comprehensive performance index R 3. A better exergy efficiency performance can be obtained when Reynolds number is greater than 5000 and the exergy efficiency reaches the best when Re = 8000. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is commonly seen after acute ischemic stroke (AIS). Sedentary behaviors increase the risk of dementia among community dwelling population. Objective: This study aims to investigate the association of sedentary behaviors with poststroke cognitive impairment among older adults with minor AIS. Methods: This cohort study recruited 594 older subjects with minor AIS from three hospitals in China during February 1, 2016, and December 31, 2018. Participants were followed up for two years and the sedentary time per day was self-reported at the end of follow-up. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). Participants were categorized into the high and low sedentary time group according to the median sedentary time of the participants. Results: At two years of follow-up, the long sedentary time group had significantly lower MMSE scores than the short sedentary time group [median, (IQR): 21 (18 to 25) versus 22 (18 to 25), p = 0.368]. The long sedentary time group had a higher speed of cognitive decline than the short sedentary time group. Excessive sedentary time was associated with a higher risk of longitudinal cognitive decline (OR: 2.267, 95% CI: 1.594 to 3.225), adjusting for age, sex, education, body mass index, APOE genotype, comorbidities, symptoms of depression, anxiety, and insomnia, baseline MMSE scores and National Institute of Health Stroke Scale scores, cognitive therapy, and TOAST ischemic stroke subtypes. Conclusions: This study identified a possible link between sedentary behaviors and longitudinal cognitive decline among older patients with minor AIS, suggesting that reducing sedentary time might be helpful for preventing poststroke dementia. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions. Methods: Bioinformatics and machine learning methods were used to evaluate CRC‐related genes within the TCGA database. By identifying the overlapped genes, potential biomarkers were selected for further validation. Methylation‐specific PCR (MSP) was utilized to identify the associated genes as biomarkers. Subsequently, a real‐time PCR assay for detecting the presence of neoplasia or cancer of the colon or rectum was established. This screening approach involved the recruitment of 978 participants from five cohorts. Results: The genes with the highest specificity and sensitivity were Septin9, AXL4, and SDC2. A total of 940 participants were involved in the establishment of the final PCR system and the subsequent performance evaluation test. A multiplex TaqMan real‐time PCR system has been illustrated to greatly enhance the ability to detect precancerous lesions and achieved an accuracy of 87.8% (95% CI 82.9–91.5), a sensitivity of 82.7% (95% CI 71.8–90.1), and a specificity of 90.1% (95% CI 84.3–93.9). Moreover, the detection rate of precancerous lesions of this assay reached 55.0% (95% CI 38.7–70.4). Conclusion: The combined detection of the methylation status of SEPT9, SDC2, and ALX4 in plasma holds the potential to further enhance the sensitivity of CRC detection. [ABSTRACT FROM AUTHOR]

Nav1.5, encoded by SCN5A, has been associated with metastasis in colorectal cancer (CRC). Here, we investigated the mechanism by which Nav1.5 regulates tumor progression and whether Nav1.5 influences chemosensitivity to 5-fluorouracil (5-FU) in CRCs. CRC cases were evaluated for Nav1.5 expression. Elevated Nav1.5 expression was associated with poor prognosis in CRCs, whereas stage II/III patients with upregulated SCN5A expression could have better survival after receiving 5-FU-based adjuvant chemotherapy. In CRC cells, SCN5A knockdown reduced the proliferation, migration and invasion. According to RNA sequencing, SCN5A knockdown inhibited both the cell cycle and epithelial-mesenchymal transition. In addition, Nav1.5 stabilized the KRas-calmodulin complex to modulate Ras signaling, promoting Ca2+ influx through the Na+-Ca2+ exchanger and Ca2+ release-activated calcium channel. Meanwhile, SCN5A knockdown increased the 50% inhibitory concentration to 5-FU by upregulating 5-FU-stimulated apoptosis in CRCs. In conclusion, Nav1.5 could progress to proliferation and metastasis through Ca2+/calmodulin-dependent Ras signaling in CRC, and it could also enhance 5-FU-stimulated apoptosis. Clinically, patients with stage II/III CRCs with elevated SCN5A expression demonstrated poor prognosis, yet those patients could benefit more from 5-FU-based chemotherapy than patients with lower SCN5A expression. [ABSTRACT FROM AUTHOR]

Background: It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear.Methods: CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted.Results: Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042).Conclusion: Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Schematic diagram of experimental system. Highlights • Effects of groove depth and arrangement mode on cooling performance are studied. • CPU temperature is reduced by about 3.3 °C(8.2%) compared with deionized water. • For aligned and staggered arrangement, Nusselt number increases by 31.3%, 30.9%. • Aligned arrangement shows more excellent entropy generation performance. Abstract An experiment set for researching the flow and heat transfer characteristics of nanofluids flowing through CPU is established and validated. The influences of groove depths (1 mm, 2 mm, 3 mm) and arrangement modes (aligned and staggered arrangements) on thermo-hydraulic performances of CPU cooled by TiO 2 -water nanofluids are explored. In addition, the influences of nanoparticle mass fractions (0.0, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%) and Reynolds numbers (472–1198) are studied. It is found that there is a most appropriate nanoparticle mass fraction (0.3%) and groove depth (2 mm) for the lowest CPU temperature. Heat transfer augmentation of CPU heat sink is more sensitive to staggered arrangement grooves and high Reynolds number. Nanofluids (0.3%) in CPU heat sink with staggered arrangement grooves (2 mm) show the best heat transfer performances. Lastly, thermal efficiency, exergy efficiency and entropy generation are applied to analyze the cooling performance of enhanced structure. Results show that the thermal efficiency decreases with mass fraction when Reynolds number is less than 791, but increases with the depth of groove. Exergy efficiency of the groove structure can be obviously strengthened under the same pumping power and mass flow rate. From entropy generation analysis, it is found that the aligned arrangement shows lower entropy generation performance than aligned arrangement. [ABSTRACT FROM AUTHOR]

Abstract: Single particle analysis is a valuable tool in cryo-electron microscopy for determining the structure of biological complexes. However, the conformational state and the preparation of the sample are factors that play a critical role in the ultimate attainable resolution. In some cases extensive analysis at the microscope of a sample under different conditions is required to derive the optimal acquisition conditions. Currently this analysis is limited to raw micrographs, thus conveying only limited information on the structure of the complex. We are developing a computing system that generates a three-dimensional reconstruction from a single micrograph acquired under cryogenic and low dose conditions, and containing particles with icosahedral symmetry. The system provides the microscopist with immediate structural information from a sample while it is in the microscope and during the preliminary acquisition stage. The system is designed to run without user intervention on a multi-processor computing resource and integrates all the processing steps required for the analysis. Tests performed on experimental data sets show that the probability of obtaining a reliable reconstruction from one micrograph is primarily determined by the quality of the sample, with success rates close to 100% when sample conditions are optimal, and decreasing to about 60% when conditions are sub-optimal. The time required to generate a reconstruction depends significantly on the diameter of the particles, and in most instances takes about 1min. The proposed approach can provide valuable three-dimensional information, albeit at low resolution, on conformational states, epitope binding, and stoichiometry of icosahedral multi-protein complexes. [Copyright &y& Elsevier]

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes ( Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene's persistent tolerance to heat stress in potato plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Li, Zhang, Duan, Jin, Chen, Chen, Zhou, Wang, Tang, Majeed, Zhang and Si.)

Backgrounds: As a conserved signaling pathway, mitogen-activated protein kinase (MAPK) cascade regulates cellular signaling in response to abiotic stress. High temperature may contribute to a significant decrease in economic yield. However, research into the expression patterns of StMAPKK family genes under high temperature is limited and lacks experimental validation regarding their role in supporting potato plant growth., Methods: To trigger heat stress responses, potato plants were grown at 35°C. qRT-PCR was conducted to analyze the expression pattern of StMAPKK family genes in potato plants. Plant with StMAPKK5 loss-of-function and gain-of-function were developed. Potato growth and morphological features were assessed through measures of plant height, dry weight, and fresh weight. The antioxidant ability of StMAPKK5 was indicated by antioxidant enzyme activity and H 2 O 2 content. Cell membrane integrity and permeability were suggested by relative electrical conductivity (REC), and contents of MDA and proline. Photosynthetic capacity was next determined. Further, mRNA expression of heat stress-responsive genes and antioxidant enzyme genes was examined., Results: In reaction to heat stress, the expression profiles of StMAPKK family genes were changed. The StMAPKK5 protein is located to the nucleus, cytoplasm and cytomembrane, playing a role in controlling the height and weight of potato plants under heat stress conditions. StMAPKK5 over-expression promoted photosynthesis and maintained cell membrane integrity, while inhibited transpiration and stomatal conductance under heat stress. Overexpression of StMAPKK5 triggered biochemical defenses in potato plant against heat stress, modulating the levels of H 2 O 2 , MDA and proline, as well as the antioxidant activities of CAT, SOD and POD. Overexpression of StMAPKK5 elicited genetic responses in potato plants to heat stress, affecting heat stress-responsive genes and genes encoding antioxidant enzymes., Conclusion: StMAPKK5 can improve the resilience of potato plants to heat stress-induced damage, offering a promising approach for engineering potatoes with enhanced adaptability to challenging heat stress conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Li, Zhang, Jin, Duan, Chen, Chen, Wang, Tang, Zhou, Zhang and Si.)

Classification-based myoelectric control has attracted significant interest in recent years, leading to prosthetic hands with advanced functionality, such as multi-grip hands. Thus far, high classification accuracies have been achieved by increasing the number of surface electromyography (sEMG) electrodes or adding other sensing mechanisms. While many prescribed myoelectric hands still adopt two-electrode sEMG systems, detailed studies on signal processing and classification performance are still lacking. In this study, nine able-bodied participants were recruited to perform six typical hand actions, from which sEMG signals from two electrodes were acquired using a Delsys Trigno Research+ acquisition system. Signal processing and machine learning algorithms, specifically, linear discriminant analysis (LDA), k-nearest neighbors (KNN), and support vector machines (SVM), were used to study classification accuracies. Overall classification accuracy of 93 ± 2%, action-specific accuracy of 97 ± 2%, and F1-score of 87 ± 7% were achieved, which are comparable with those reported from multi-electrode systems. The highest accuracies were achieved using SVM algorithm compared to LDA and KNN algorithms. A logarithmic relationship between classification accuracy and number of features was revealed, which plateaued at five features. These comprehensive findings may potentially contribute to signal processing and machine learning strategies for commonly prescribed myoelectric hand systems with two sEMG electrodes to further improve functionality.

This study focuses on novel design and evaluation of Elastic 50A (EL50) mechanical metamaterials with open-cell patterns for its potential application to lower limb residuum/socket interfaces, specifically that of a transtibial (TT) amputee. Mechanical characteristics, that is, effective Young's modulus ( E ), was tuned by altering metamaterial porosity, which was experimentally verified. Specifically, pore radius of the unit cell was varied to achieve a range of E -values (0.05-1.71 MPa) for these 3D printed metamaterials. Finite Element Analysis (FEA) was conducted to evaluate pressure distribution across key load-bearing anatomical sites of a TT residuum. Using designed metamaterials for homogeneous liners, pressure profiles were studied and compared with a silicone liner case. Additionally, a custom metamaterial liner was designed by assigning appropriate metamaterials to four load-sensitive and tolerant anatomical sites of the TT residuum. The results suggest that lowest pressure variation (PV), as a measure of pressure distribution levels and potential comfort for amputees, was achieved by the custom metamaterial liner compared to any of the homogeneous liners included in this study. It is envisaged that this work may aid future design and development of custom liners using now commonly available 3D printing technologies and available elastomer materials to maximise comfort, tissue safety and overall rehabilitation outcomes for lower limb amputees., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers., Methods: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses., Results: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs., Conclusions: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors., (© 2024. The Author(s).)

Radiotherapy (RT) is one of the important treatment modalities for non-small cell lung cancer (NSCLC). However, the maximum radiation dose that NSCLC patient can receive varies little. Therefore, the exploitation of novel RT sensitization approaches is a critical need for the clinical treatment. RT resistance in NSCLC is linked to tumor microenvironment (TME) hypoxia, cell cycle arrest and associated genetic alterations. Here, we designed a novel method for targeted delivery of quercetin (QT) and CeO 2 to enhance RT sensitivity. We loaded QT into CeO 2 @ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO 2 targeted to NSCLC tumors. Under the protection and targeted delivery of Zeolitic Imidazolate Framework-8 (ZIF-8), the nanocomplexes exhibited excellent catalytic mimetic activity in decomposing H 2 O 2 into O 2 , thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO 2 @ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO 2 @ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC., (© 2024. The Author(s).)

Background: Accurate prediction of response to neoadjuvant chemoradiotherapy is critical for subsequent treatment decisions for patients with locally advanced rectal cancer., Objective: To develop and validate a deep learning model based on the comparison of paired MRI before and after neoadjuvant chemoradiotherapy to predict pathological complete response., Design: By capturing the changes from MRI before and after neoadjuvant chemoradiotherapy in 638 patients, we trained a multitask deep learning model for response prediction (DeepRP-RC) that also allowed simultaneous segmentation. Its performance was independently tested in an internal and 3 external validation sets, and its prognostic value was also evaluated., Settings: Multicenter study., Patients: We retrospectively enrolled 1201 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy before total mesorectal excision. Patients had been treated at 1 of 4 hospitals in China between January 2013 and December 2020., Main Outcome Measures: The main outcome was the accuracy of predicting pathological complete response, measured as the area under receiver operating curve for the training and validation data sets., Results: DeepRP-RC achieved high performance in predicting pathological complete response after neoadjuvant chemoradiotherapy, with area under the curve values of 0.969 (0.942-0.996), 0.946 (0.915-0.977), 0.943 (0.888-0.998), and 0.919 (0.840-0.997) for the internal and 3 external validation sets, respectively. DeepRP-RC performed similarly well in the subgroups defined by receipt of radiotherapy, tumor location, T/N stages before and after neoadjuvant chemoradiotherapy, and age. Compared with experienced radiologists, the model showed substantially higher performance in pathological complete response prediction. The model was also highly accurate in identifying the patients with poor response. Furthermore, the model was significantly associated with disease-free survival independent of clinicopathological variables., Limitations: This study was limited by its retrospective design and absence of multiethnic data., Conclusions: DeepRP-RC could be an accurate preoperative tool for pathological complete response prediction in rectal cancer after neoadjuvant chemoradiotherapy., Un Sistema De Ia Basado En Resonancia Magntica Longitudinal Para Predecir La Respuesta Patolgica Completa Despus De La Terapia Neoadyuvante En El Cncer De Recto Un Estudio De Validacin Multicntrico: ANTECEDENTES:La predicción precisa de la respuesta a la quimiorradioterapia neoadyuvante es fundamental para las decisiones de tratamiento posteriores para los pacientes con cáncer de recto localmente avanzado.OBJETIVO:Desarrollar y validar un modelo de aprendizaje profundo basado en la comparación de resonancias magnéticas pareadas antes y después de la quimiorradioterapia neoadyuvante para predecir la respuesta patológica completa.DISEÑO:Al capturar los cambios de las imágenes de resonancia magnética antes y después de la quimiorradioterapia neoadyuvante en 638 pacientes, entrenamos un modelo de aprendizaje profundo multitarea para la predicción de respuesta (DeepRP-RC) que también permitió la segmentación simultánea. Su rendimiento se probó de forma independiente en un conjunto de validación interna y tres externas, y también se evaluó su valor pronóstico.ESCENARIO:Estudio multicéntrico.PACIENTES:Volvimos a incluir retrospectivamente a 1201 pacientes diagnosticados con cáncer de recto localmente avanzado y sometidos a quimiorradioterapia neoadyuvante antes de la escisión total del mesorrecto. Eran de cuatro hospitales en China en el período entre enero de 2013 y diciembre de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Los principales resultados fueron la precisión de la predicción de la respuesta patológica completa, medida como el área bajo la curva operativa del receptor para los conjuntos de datos de entrenamiento y validación.RESULTADOS:DeepRP-RC logró un alto rendimiento en la predicción de la respuesta patológica completa después de la quimiorradioterapia neoadyuvante, con valores de área bajo la curva de 0,969 (0,942-0,996), 0,946 (0,915-0,977), 0,943 (0,888-0,998), y 0,919 (0,840-0,997) para los conjuntos de validación interna y las tres externas, respectivamente. DeepRP-RC se desempeñó de manera similar en los subgrupos definidos por la recepción de radioterapia, la ubicación del tumor, los estadios T/N antes y después de la quimiorradioterapia neoadyuvante y la edad. En comparación con los radiólogos experimentados, el modelo mostró un rendimiento sustancialmente mayor en la predicción de la respuesta patológica completa. El modelo también fue muy preciso en la identificación de los pacientes con mala respuesta. Además, el modelo se asoció significativamente con la supervivencia libre de enfermedad independientemente de las variables clinicopatológicas.LIMITACIONES:Este estudio estuvo limitado por el diseño retrospectivo y la ausencia de datos multiétnicos.CONCLUSIONES:DeepRP-RC podría servir como una herramienta preoperatoria precisa para la predicción de la respuesta patológica completa en el cáncer de recto después de la quimiorradioterapia neoadyuvante. (Traducción-Dr. Felipe Bellolio )., (Copyright © The ASCRS 2023.)

Employing a large sample of Chinese firms, this study examined the influence of corporate green innovation on firms' access to trade credit. The results indicated a positive association between green innovation and firms' capability to access trade credit, suggesting that suppliers value firms' green innovation capabilities. This relationship was strengthened after the implementation of the new Environmental Protection Law (EPL) in 2015, which enhanced the value of green innovation. The findings remained robust to several robustness tests. The results suggest that green innovation helps firms access trade credit through better environmental, social, and governance (ESG) scores and more state subsidy channels and plays a more pronounced role for financially constrained firms, non-state-owned enterprises, firms with lower bargaining power, and firms located in regions with better intellectual property rights protections. Green innovation is valuable for future corporate growth and shareholder value. Overall, this study reveals the value of green innovation through informal corporate financing., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate reliability and changes of in-shoe plantar pressure and shear during walking at three cadences with two insole designs. This was a precursor to the investigation of plantar loading in people with diabetes for potential foot ulcer prevention., Method: A sensorised insole system, capable of measuring plantar pressure and shear at the heel, fifth metatarsal head (5MH), first metatarsal head (1MH) and hallux, was tested with ten healthy participants during level walking. Reliability was evaluated, using intra-class correlation coefficient (ICC), while varying the cadences and insole types. Percentage changes in pressure and shear relative to values obtained at self-selected cadence with a flat insole design were investigated., Results: Mean±standard deviation of maximum pressure, medial-lateral and anterior-posterior shear of up to 380±24kPa, 46±2kPa and -71±4kPa, respectively, were measured. The ICC in ranges of 0.762-0.973, 0.758-0.987 and 0.800-0.980 were obtained for pressure, anterior-posterior and medial-lateral shear, respectively. Opposite anterior-posterior shear directions between 5MH and 1MH (stretching), and between 1MH and hallux (pinching) were observed for some participants. Increasing cadence increased pressure and anterior-posterior shear (by up to +77%) but reduced medial-lateral shear at the heel and hallux (by up to -34%). Slower cadence increased anterior-posterior shear (+114%) but decreased medial-lateral shear (-46%) at the hallux. The use of a flexible contoured insole resulted in pressure reduction at the heel and 5MH but an increase in anterior-posterior shear at the heel (+69%) and hallux (+75%)., Conclusion: The insole system demonstrated good reliability and is comparable to reported pressure-only systems. Pressure measurements were sensitive to changes in cadence and insole designs in ways that were consistent with the literature. However, our plantar shear showed localised shear changes with cadences and insoles for the first time, as well as stretching and pinching effects on plantar tissue. This opens new possibilities to investigate plantar tissue viability, loading characteristics and orthotic designs aimed towards foot ulcer prevention., Competing Interests: Declaration of interest: This study was funded by the NIHR Invention for Innovation (i4i) Programme (NIHR201315). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The authors have no conflicts of interest to declare.

Fluctuations in residuum volume during daily activities are known to occur in lower-limb amputees. This can cause frequent changes to fit, which cannot be accommodated by commonly-used prosthetic sockets. The real-time effects, if any, of these minor socket fit changes on interface biomechanics have not been studied extensively. Amputees commonly use different layers of socks to accommodate frequent volume fluctuations, enabling adjustment of socket fit. We, thus, altered socket fit levels via addition/removal of sock layers to a transtibial amputee who habitually-donned two-sock layers to mimic relatively looser and tighter socket fits. Interface pressure and shear sensors were placed at known prominent load-bearing sites of the transtibial residuum/socket interface, i.e., patellar tendon (PT), popliteal fossa (PF), and anterior-distal (AD) end, to measure real-time biomechanical interactions during standing and level walking. Although socket fit level was only slightly modified, changes in interface pressure and shear across anatomical sites were still observed. Tighter fit corresponds to notable pressure reduction at AD during early stance and pressure increase at PT during terminal stance due to the residuum being pushed up. Shear-to-pressure ratios were used to assess comfort, while pressure- and shear-time integrals were used to assess tissue health. We observed more notable changes at tissue sites (e.g., AD and PF). Combined evaluation of pressure and shear, including shear-to-pressure ratio and time integrals, may offer insight for residuum care., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Kirstie M. Devin et al.)

Backgrounds: Potato is sensitive to heat stress particularly during plant seedling growth. However, limited studies have characterized the expression pattern of the StGATA family genes under heat stress and lacked validation of its function in potato plants., Methods: Potato plants were cultivated at 30°C and 35°C to induce heat stress responses. qRT-PCR was carried out to characterize the expression pattern of StGATA family genes in potato plants subjected to heat stress. StGATA2 loss-of-function and gain-of-function plants were established. Morphological phenotypes and growth were indicated by plant height and mass. Photosynthesis and transpiration were suggested by stomatal aperture, net photosynthetic rate, transpiration rate, and stomatal conductance. Biochemical and genetic responses were indicated by enzyme activity and mRNA expression of genes encoding CAT, SOD, and POD, and contents of H 2 O 2 , MDA, and proline., Results: The expression patterns of StGATA family genes were altered in response to heat stress. StGATA2 protein located in the nucleus. StGATA2 is implicated in regulating plant height and weight of potato plants in response to heat stresses, especially acute heat stress. StGATA2 over-expression promoted photosynthesis while inhibited transpiration under heat stress. StGATA2 overexpression induced biochemical responses of potato plant against heat stress by regulating the contents of H 2 O 2 , MDA and proline and the activity of CAT, SOD and POD. StGATA2 overexpression caused genetic responses (CAT, SOD and POD) of potato plant against heat stress., Conclusion: Our data indicated that StGATA2 could enhance the ability of potato plants to resist heat stress-induced damages, which may provide an effective strategy to engineer potato plants for better adaptability to adverse heat stress conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Duan, Jin, Chen, Chen, Shao, Tang and Zhang.)

Background and Aims: Mitogen-activated protein kinases (MAPKs) have been reported to respond to various stimuli including heat stress. This research aimed to investigate whether StMAPK1 is implicated in the transduction of the heat stress signal to adapt heat stress as a thermos-tolerant gene., Materials and Methods: Potato plants were cultivated under mild (30°C) and acute (35°C) heat stress conditions to analyze mRNA expression of StMAPKs and physiological indicators. StMAPK1 was up-regulated and down-regulated by transfection. Subcellular localization of StMAPK1 protein was observed by fluorescence microscope. The transgenic potato plants were assayed for physiological indexes, photosynthesis, cellular membrane integrity, and heat stress response gene expression., Results: Heat stress altered the expression prolife of StMAPKs . StMAPK1 overexpression changed the physiological characteristics and phenotypes of potato plants under heat stresses. StMAPK1 mediates photosynthesis and maintains membrane integrity of potato plants in response to heat stress. Stress response genes ( StP5CS , StCAT , StSOD , and StPOD ) in potato plants were altered by StMAPK1 dysregulation. mRNA expression of heat stress genes ( StHSP90 , StHSP70 , StHSP20 , and StHSFA3 ) was affected by StMAPK1 ., Conclusions: StMAPK1 overexpression increases the heat-tolerant capacity of potato plants at the morphological, physiological, molecular, and genetic levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Duan, Zhang, Jin, Xu, Chen, Zhou, Chen, Tang and Zhang.)

Pressure coupled with shear stresses are the critical external factors for diabetic foot ulceration assessment and prevention. To date, a wearable system capable of measuring in-shoe multi-directional stresses for out-of-lab analysis has been elusive. The lack of an insole system capable of measuring plantar pressure and shear hinders the development of an effective foot ulcer prevention solution that could be potentially used in a daily living environment. This study reports the development of a first-of-its-kind sensorised insole system and its evaluation in laboratory settings and on human participants, indicating its potential as a wearable technology to be used in real-world applications. Laboratory evaluation revealed that the linearity error and accuracy error of the sensorised insole system were up to 3% and 5%, respectively. When evaluated on a healthy participant, change in footwear resulted in approximately 20%, 75% and 82% change in pressure, medial-lateral and anterior-posterior shear stress, respectively. When evaluated on diabetic participants, no notable difference in peak plantar pressure, as a result of wearing the sensorised insole, was measured. The preliminary results showed that the performance of the sensorised insole system is comparable to previously reported research devices. The system has adequate sensitivity to assist footwear assessment relevant to foot ulcer prevention and is safe to use for people with diabetes. The reported insole system presents the potential to help assess diabetic foot ulceration risk in a daily living environment underpinned by wearable pressure and shear sensing technologies.

Background: For clinically low-risk stage III colorectal cancer, the decision on cycles of adjuvant chemotherapy after surgery is disputed. The present study investigates the use of additional biomarkers of ploidy and stroma-ratio(PS) to stratify patients with low-risk stage III colorectal cancer, providing a basis for individualized treatment in the future., Methods: This study retrospectively enrolled 198 patients with clinical-low-risk stage III colorectal cancer (T1-3N1M0) and analyzed the DNA ploidy and stroma ratio of FFPE tumor tissues. The patients were divided into PS-low-risk group (Diploidy or Low-stroma) and PS-high-risk group (Non-diploid and High-stroma). For survival analyses, Kaplan-Meier and Cox regression models were used., Results: The results showed that the 5-year DFS of the PS-high-risk group was significantly lower than that in the PS-low-risk group (78.6 vs. 91.2%, HR = 2.606 [95% CI: 1.011-6.717], P = 0.039). Besides, in the PS-low-risk group, the 5 year OS (98.2 vs. 86.7%, P = 0.022; HR = 5.762 [95% CI: 1.281-25.920]) and DFS (95.6, vs 79.9%, P = 0.019; HR = 3.7 [95% CI: 1.24-11.04]) of patients received adjuvant chemotherapy for > 3 months were significantly higher than those received adjuvant chemotherapy for < 3 months. We also found that the PS could stratify the prognosis of patients with dMMR tumors. The 5-year OS (96.3 vs 71.4%, P = 0.037) and DFS (92.6 vs 57.1%, P = 0.015) were higher in the PS-low-risk dMMR patients than those in the PS-high-risk dMMR patients., Conclusion: In this study, we found that PS can predict the prognosis of patients with stage III low-risk CRC. Besides, it may guide the decision on postoperative adjuvant chemotherapy., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response., (© 2022. The Author(s).)

Radiographic imaging is routinely used to evaluate treatment response in solid tumors. Current imaging response metrics do not reliably predict the underlying biological response. Here, we present a multi-task deep learning approach that allows simultaneous tumor segmentation and response prediction. We design two Siamese subnetworks that are joined at multiple layers, which enables integration of multi-scale feature representations and in-depth comparison of pre-treatment and post-treatment images. The network is trained using 2568 magnetic resonance imaging scans of 321 rectal cancer patients for predicting pathologic complete response after neoadjuvant chemoradiotherapy. In multi-institution validation, the imaging-based model achieves AUC of 0.95 (95% confidence interval: 0.91-0.98) and 0.92 (0.87-0.96) in two independent cohorts of 160 and 141 patients, respectively. When combined with blood-based tumor markers, the integrated model further improves prediction accuracy with AUC 0.97 (0.93-0.99). Our approach to capturing dynamic information in longitudinal images may be broadly used for screening, treatment response evaluation, disease monitoring, and surveillance.

Na v 1.5, encoded by SCN5A, has been associated with metastasis in colorectal cancer (CRC). Here, we investigated the mechanism by which Na v 1.5 regulates tumor progression and whether Na v 1.5 influences chemosensitivity to 5-fluorouracil (5-FU) in CRCs. CRC cases were evaluated for Na v 1.5 expression. Elevated Na v 1.5 expression was associated with poor prognosis in CRCs, whereas stage II/III patients with upregulated SCN5A expression could have better survival after receiving 5-FU-based adjuvant chemotherapy. In CRC cells, SCN5A knockdown reduced the proliferation, migration and invasion. According to RNA sequencing, SCN5A knockdown inhibited both the cell cycle and epithelial-mesenchymal transition. In addition, Na v 1.5 stabilized the KRas-calmodulin complex to modulate Ras signaling, promoting Ca 2+ influx through the Na + -Ca 2+ exchanger and Ca 2+ release-activated calcium channel. Meanwhile, SCN5A knockdown increased the 50% inhibitory concentration to 5-FU by upregulating 5-FU-stimulated apoptosis in CRCs. In conclusion, Na v 1.5 could progress to proliferation and metastasis through Ca 2+ /calmodulin-dependent Ras signaling in CRC, and it could also enhance 5-FU-stimulated apoptosis. Clinically, patients with stage II/III CRCs with elevated SCN5A expression demonstrated poor prognosis, yet those patients could benefit more from 5-FU-based chemotherapy than patients with lower SCN5A expression., (Copyright © 2020 Elsevier B.V. All rights reserved.)

BRAF and MLH1 promoter methylation testings have been proven effective prescreens for Lynch Syndrome. We aimed to compare different screening strategies for Lynch Syndrome in patients with MLH1(-) CRC. Patients with MLH1(-) CRC who had been tested for BRAF mutation and germline variants of DNA mismatch repair genes were included. We compared the sensitivities and specificities for identifying Lynch Syndrome and the cost-effectiveness of four screening approaches that used the following tests as prescreens: BRAF testing, MLH1 methylation testing, MLH1 methylation & BRAF testing, and MLH1 methylation testing & Revised Bethesda Criteria. Of 109 patients included, 23 (21.1%) were Lynch Syndrome patients. BRAF mutation and MLH1 methylation occurred in 6 (5.5%) and 40 (36.7%) patients, respectively. The sensitivity for identifying Lynch syndrome of BRAF testing was 100%, but the specificity was only 7%. MLH1 methylation testing had a lower sensitivity than BRAF testing (97.5% vs 100%), but had a markedly higher specificity (45.3% vs 7%). The combination of the two testings had a slightly higher specificity than MLH1 methylation testing alone (47.7% vs 45.3%). The MLH1 methylation testing approach had a 10% lower cost of identifying MLH1(-) Lynch syndrome carriers per case than universal genetic testing, but it missed 4.5% of patients. BRAF and MLH1 promoter methylation testings as prescreens for Lynch syndrome are less effective in Chinese patients with MLH1(-) CRC than in their Western counterparts. Universal genetic testing could be considered an up-front option for this population.

Background: A fixed 8-cycle oxaliplatin and capecitabine (XELOX) regimen has been the standard adjuvant therapy for patients with stage III colon cancer. However, completing the full-cycle of oxaliplatin is often associated with severe neurotoxicity. To spare patients from the toxic effects, without comprising the required efficacy, we evaluated the safety and efficacy of a modified XELOX (mXELOX) adjuvant chemotherapy regimen with 6 cycles of oxaliplatin and a full cycle of capecitabine., Methods: We retrospectively analyzed 330 eligible patients with stage III colon cancer who underwent curative tumor resection followed by mXELOX, standard XELOX or unfinished XELOX adjuvant chemotherapy between December 2007 and April 2015. Associated prognostic factors were investigated and their disease-free survival (DFS) and overall survival (OS) rates were also determined and compared among the different regimen groups., Results: Compared with the standard XELOX group, the mXELOX group had lower total incidence rates of neurotoxicity (39.3% vs. 76.2%, P < 0.001), leucopenia (53.6% vs. 69.8%, P = 0.017) and thrombocytopenia (38.1% vs. 56.3%, P = 0.011). The standard XELOX and mXELOX adjuvant chemotherapy regimens presented with comparable 3-year DFS rates (86.3% vs. 89.2%; P = 0.838) and 3-year OS rates (92.7% vs. 97.6%; P = 0.227). Compared to unfinished XELOX chemotherapy, the oncologic benefits of the mXELOX regimen were greater for patients with T4 tumors (3-year DFS: Hazard ratio [HR], 2.184; 95% confidence interval [CI], 1.051-4.540; P = 0.036; 3-year OS: HR, 4.529; 95% CI 1.245-16.479; P = 0.022) and for high-risk patients (3-year DFS: HR, 1.962; 95% CI 0.964-3.993; P = 0.044; 3-year OS: HR, 4.193; 95% CI 1.182-14.874; P = 0.026)., Conclusions: The mXELOX adjuvant chemotherapy presented a comparable survival benefit and lower incidence of toxicity than standard XELOX chemotherapy. It could be an alternative treatment for high-risk patients with operated stage III colon cancer.

The bespoke interface between a lower limb residuum and a prosthetic socket is critical for an amputee's comfort and overall rehabilitation outcomes. Analysis of interface kinematics and kinetics is important to gain full understanding of the interface biomechanics, which could aid clinical socket fit, rehabilitation and amputee care. This pilot study aims to investigate the dynamic correlation between kinematic movement and kinetic stresses at the interface during walking tests on different terrains. One male, knee disarticulation amputee participated in the study. He was asked to walk on both a level surface and a 5° ramped surface. The movement between the residuum and the socket was evaluated by the angular and axial couplings, based on the outputs from a 3D motion capture system. The corresponding kinetic stresses at anterior-proximal (AP), posterior-proximal (PP) and anterior-distal (AD) locations of the residuum were measured, using individual stress sensors. Approximately 8° of angular coupling and up to 32 mm of axial coupling were measured when walking on different terrains. The direction of the angular coupling shows strong correlation with the pressure difference between the PP and AP sensors. Higher pressure was obtained at the PP location than the AP location during stance phase, associated with the direction of the angular coupling. A strong correlation between axial coupling length, L, and longitudinal shear was also evident at the PP and AD locations i.e. the shortening of L corresponds to the increase of shear in the proximal direction. Although different terrains did not affect these correlations in principle, interface kinematic and kinetic values suggested that gait changes can induce modifications to the interface biomechanics. It is envisaged that the reported techniques could be potentially used to provide combined kinematics and kinetics for the understanding of biomechanics at the residuum/socket interface, which may play an important role in the clinical assessment of prosthetic component settings, including socket fit quality., (Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.)

A fluoride-anion-induced, regioselective ring expansion of benzocyclic ketones and α-aryl cycloketones has been developed via insertion of arynes into unactivated benzylic C-C bonds. This reaction provides a straightforward, transition-metal-free avenue to prepare medium ring-fused benzocarbocycles by creating "noble" seven-, eight-, and nine-membered rings. Applications of this method in the creation of medium-sized exocyclic and inner benzocyclic olefins, nine-membered lactones, and lactams are described., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sindbis virus (SINV) is an enveloped, mosquito-borne alphavirus. Here we generated and characterized a fluorescent protein-tagged (FP-tagged) SINV and found that the presence of the FP-tag (mCherry) affected glycoprotein transport to the plasma membrane whereas the specific infectivity of the virus was not affected. We examined the virions by transmission electron cryo-microscopy and determined the arrangement of the FP-tag on the surface of the virion. The fluorescent proteins are arranged icosahedrally on the virus surface in a stable manner that did not adversely affect receptor binding or fusion functions of E2 and E1, respectively. The delay in surface expression of the viral glycoproteins, as demonstrated by flow cytometry analysis, contributed to a 10-fold reduction in mCherry-E2 virus titer. There is a 1:1 ratio of mCherry to E2 incorporated into the virion, which leads to a strong fluorescence signal and thus facilitates single-particle tracking experiments. We used the FP-tagged virus for high-resolution live-cell imaging to study the spatial and temporal aspects of alphavirus assembly and budding from mammalian cells. These processes were further analyzed by thin section microscopy. The results demonstrate that SINV buds from the plasma membrane of infected cells and is dispersed into the surrounding media or spread to neighboring cells facilitated by its close association with filopodial extensions.

Unlabelled: Members of the family Partitiviridae have bisegmented double-stranded RNA (dsRNA) genomes and are not generally known to cause obvious symptoms in their natural hosts. An unusual partitivirus, Sclerotinia sclerotiorum partitivirus 1 (SsPV1/WF-1), conferred hypovirulence on its natural plant-pathogenic fungal host, Sclerotinia sclerotiorum strain WF-1. Cellular organelles, including mitochondria, were severely damaged. Hypovirulence and associated traits of strain WF-1 and SsPV1/WF-1 were readily cotransmitted horizontally via hyphal contact to different vegetative compatibility groups of S. sclerotiorum and interspecifically to Sclerotinia nivalis and Sclerotinia minor. S. sclerotiorum strain 1980 transfected with purified SsPV1/WF-1 virions also exhibited hypovirulence and associated traits similar to those of strain WF-1. Moreover, introduction of purified SsPV1/WF-1 virions into strain KY-1 of Botrytis cinerea also resulted in reductions in virulence and mycelial growth and, unexpectedly, enhanced conidial production. However, virus infection suppressed hyphal growth of most germinating conidia of B. cinerea and was eventually lethal to infected hyphae, since very few new colonies could develop following germ tube formation. Taken together, our results support the conclusion that SsPV1/WF-1 causes hypovirulence in Sclerotinia spp. and B. cinerea. Cryo-EM (cryo-electron microscopy) reconstruction of the SsPV1 particle shows that it has a distinct structure with similarity to the closely related partitiviruses Fusarium poae virus 1 and Penicillium stoloniferum virus F. These findings provide new insights into partitivirus biological activities and clues about molecular interactions between partitiviruses and their hosts., Importance: Members of the Partitiviridae are believed to occur commonly in their phytopathogenic fungal and plant hosts. However, most partitiviruses examined so far appear to be associated with latent infections. Here we report a partitivirus, SsPV1/WF-1, that was isolated from a hypovirulent strain of Sclerotinia sclerotiorum and describe its biological and molecular features. We have demonstrated that SsPV1 confers hypovirulence. Furthermore, SsPV1 can infect and cause hypovirulence in Botrytis cinerea. Our study also suggests that SsPV1 has a vigorous ability to proliferate and spread via hyphal contact. SsPV1 can overcome vegetative incompatibility barriers and can be transmitted horizontally among different vegetative compatibility groups of S. sclerotiorum, even interspecifically. Cryo-EM reconstruction of SsPV1 shows that it has a distinct structure with similarity to closely related partitiviruses. Our studies exploit a novel system, SsPV1 and its hosts, which can provide the means to explore the mechanisms by which partitiviruses interact with their hosts., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Partitiviruses constitute one of the nine currently recognized families of viruses with encapsidated, double-stranded (ds)RNA genomes. The partitivirus genome is bisegmented, and each genome segment is packaged inside a separate viral capsid. Different partitiviruses infect plants, fungi, or protozoa. Recent studies have shed light on the three-dimensional structures of the virions of three representative fungal partitiviruses. These structures include a number of distinctive features, allowing informative comparisons with the structures of dsRNA viruses from other families. The results and comparisons suggest several new conclusions about the functions, assembly, and evolution of these viruses., (Copyright © 2013 Elsevier Inc. All rights reserved.)