Comparison of setup accuracy of optical surface image versus orthogonal x-ray images for VMAT of the left breast using deep-inspiration breath-hold.

To compare the setup accuracy of optical surface image (OSI) versus orthogonal x-ray images (2DkV) using cone beam computed tomography (CBCT) as ground truth for radiotherapy of left breast cancer in deep-inspiration breath-hold (DIBH). Ten left breast DIBH patients treated with volumetric modulated arc therapy (VMAT) were studied retrospectively. OSI, 2DkV, and CBCT were acquired weekly at treatment setup. OSI, 2DkV, and CBCT were registered to planning CT or planning DRR based on a breast surface region of interest (ROI), bony anatomy (chestwall and sternum), and both bony anatomy and breast surface, respectively. These registrations provided couch shifts for each imaging system. The setup errors, or the difference in couch shifts between OSI and CBCT were compared to those between 2DkV and CBCT. A second OSI was acquired during last beam delivery to evaluate intrafraction motion. The median absolute setup errors were (0.21, 0.27, 0.23 cm, 0.6°, 1.3°, 1.0°) for OSI, and (0.26, 0.24, 0.18 cm, 0.9°, 1.0°, 0.6°) for 2DkV in vertical, longitudinal and lateral translations, and in rotation, roll and pitch, respectively. None of the setup errors was significantly different between OSI and 2DkV. For both systems, the systematic and random setup errors were ≤0.6 cm and ≤1.5° in all directions. Nevertheless, larger setup errors were observed in some sessions in both systems. There was no correlation between OSI and CBCT whereas there was modest correlation between 2DkV and CBCT. The intrafraction motion in DIBH detected by OSI was small with median absolute translations <0.2 cm, and rotations ≤0.4°. Though OSI showed comparable and small setup errors as 2DkV, it showed no correlation with CBCT. We concluded that to achieve accurate setup for both bony anatomy and breast surface, daily 2DkV can't be omitted following OSI for left breast patients treated with DIBH VMAT.

The New Insight into the Effects of Different Fixing Technology on Flavor and Bioactivities of Orange Dark Tea.

Peach leaf orange dark tea (ODT) is a fruity tea made by removing the pulp from peach leaf orange and placing dry Qingzhuan tea into the husk, followed by fixing them together and drying. Since the quality of traditional outdoor sunlight fixing (SL) is affected by weather instability, this study explored the feasibility of two new fixing methods, including hot air fixing (HA) and steam fixing (ST). Results showed that fixing method had a great impact on ODT shape, aroma, and taste. Compared with SL and ST, HA endowed ODT with higher fruit aroma, mellow taste, better coordination, and higher sensory evaluation score. Physical-chemical composition analysis showed that SL-fixed orange peel was higher than HA- or ST-fixed peel in the content of polyphenols, flavonoids, soluble protein, hesperidin and limonin, while HA has a higher content of volatile substances and contains more alcohols, aldehydes and ketones, and acid and esters than ST and SL. Activity analysis showed that HA was superior to ST or SL in comprehensive antioxidant activity and inhibitory activity against α-glucosidase. Comprehensive results demonstrated that HA has better performance in improving ODT quality and can replace the traditional SL method in production.

Comparative Analysis of Brucepastera parasyntrophica gen. nov., sp. nov. and Teretinema zuelzerae gen. nov., comb. nov. (Treponemataceae) Reveals the Importance of Interspecies Hydrogen Transfer in the Energy Metabolism of Spirochetes.

Most members of the family Treponemataceae (Spirochaetales) are associated with vertebrate hosts. However, a diverse clade of uncultured, putatively free-living treponemes comprising several genus-level lineages is present in other anoxic environments. The only cultivated representative to date is Treponema zuelzerae, isolated from freshwater mud. Here, we describe the isolation of strain RmG11 from the intestinal tract of cockroaches. The strain represents a novel genus-level lineage of Treponemataceae and is metabolically distinct from T. zuelzerae. While T. zuelzerae grows well on various sugars, forming acetate and H2 as major fermentation products, strain RmG11 grew poorly on glucose, maltose, and starch, forming mainly ethanol and only small amounts of acetate and H2. In contrast to the growth of T. zuelzerae, that of strain RmG11 was strongly inhibited at high H2 partial pressures but improved considerably when H2 was removed from the headspace. Cocultures of strain RmG11 with the H2-consuming Methanospirillum hungatei produced acetate and methane but no ethanol. Comparative genomic analysis revealed that strain RmG11 possesses only a single, electron-confurcating hydrogenase that forms H2 from NADH and reduced ferredoxin, whereas T. zuelzerae also possesses a second, ferredoxin-dependent hydrogenase that allows the thermodynamically more favorable formation of H2 from ferredoxin via the Rnf complex. In addition, we found that T. zuelzerae utilizes xylan and possesses the genomic potential to degrade other plant polysaccharides. Based on phenotypic and phylogenomic evidence, we describe strain RmG11 as Brucepastera parasyntrophica gen. nov., sp. nov. and Treponema zuelzerae as Teretinema zuelzerae gen. nov., comb. nov. IMPORTANCE Spirochetes are widely distributed in various anoxic environments and commonly form molecular hydrogen as a major fermentation product. Here, we show that two closely related members of the family Treponemataceae differ strongly in their sensitivity to high hydrogen partial pressure, and we explain the metabolic mechanisms that cause these differences by comparative genome analysis. We demonstrate a strong boost in the growth of the hydrogen-sensitive strain and a shift in its fermentation products to acetate during cocultivation with a H2-utilizing methanogen. Our results add a hitherto unrecognized facet to the fermentative metabolism of spirochetes and also underscore the importance of interspecies hydrogen transfer in not-obligately-syntrophic interactions among fermentative and hydrogenotrophic guilds in anoxic environments.

A new family for 'termite gut treponemes': description of Breznakiellaceae fam. nov., Gracilinema caldarium gen. nov., comb. nov., Leadbettera azotonutricia gen. nov., comb. nov., Helmutkoenigia isoptericolens gen. nov., comb. nov., and Zuelzera stenostrepta gen. nov., comb. nov., and proposal of Rectinemataceae fam. nov.

The intestinal tracts of termites are abundantly colonized by a diverse assemblage of spirochetes. Most of them belong to 'termite cluster I', a monophyletic group within the radiation of the genus Treponema that occurs exclusively in termite guts. Phylogenomic analysis revealed that members of the genus Treponema are extremely diverse and represent two separate, family-level lineages: the Treponemataceae sensu stricto, which comprise the majority of the validly described Treponema species, and a second lineage that comprises the remaining members of the genus Treponema, including all members of 'termite cluster I' from termites and the recently isolated Breznakiella homolactica from cockroaches. Here, we present the formal description of Breznakiellaceae fam. nov. and of the new genera required to accommodate the misplaced Treponema species in the new family as new combinations (Leadbettera azotonutricia, Gracilinema caldarium, Helmutkoenigia isoptericolens and Zuelzera stenostrepta). To avoid paraphyly of Treponemataceae, we propose Rectinemataceae fam. nov. to include the genus Rectinema.

Optimal Surgical Treatment Method for Anterior Cruciate Ligament Rupture: Results from a Network Meta-Analysis.

BACKGROUND Previous studies have shown that primary repair (PR) and anterior cruciate ligament reconstruction (ACLR) can effectively treat ACL injuries. Our study aimed to compare different treatments of ACL tears, including autograft, allograft, hybrid graft ACLR, and PR, by assessing clinical outcomes and adverse events. MATERIAL AND METHODS PubMed, Cochrane Library, Embase, and CNKI databases were searched and a frequentist-framework network meta-analysis was used. RESULTS Overall, PR with augmentation was superior to ACLR only for activity recovery (WMD 0.28 95%CI [0.07 to 0.49]), and there was no significant difference shown between PR without augmentation and ACLR. ACLR with irradiated allograft was a poor option for the treatment of ACL rupture, showing the weakest subjective evaluations and functional outcomes and worst safety profile. PR with or without augmentation provided fairly good postoperative efficacy results and produced less postoperative knee laxity than irradiated allograft ACLR (PR: standardized mean difference [SMD] -1.27 [-1.80 to -0.74]; ACLR: SMD -1.36 [-1.88 to -0.83]). However, PR without augmentation showed a high failure rate compared with autograft ACLR (autograft vs PR without augmentation: risk ratio 0.29 [0.10 to 0.85]). CONCLUSIONS For surgical treatment of ACL rupture, irradiated allograft ACLR had the worst efficacy and safety and is not recommended. PR may be an ideal treatment method in terms of efficacy but it is related to a significantly higher revision risk if without augmentation. Autograft ACLR may be the preferred method currently available for most patients requiring surgical treatment of ACL rupture.

Altered Effective Connectivity of the Primary Motor Cortex in Transient Ischemic Attack.

Objective: This study is aimed at exploring alteration in motor-related effective connectivity in individuals with transient ischemic attack (TIA). Methods: A total of 48 individuals with TIA and 41 age-matched and sex-matched healthy controls (HCs) were recruited for this study. The participants were scanned using MRI, and their clinical characteristics were collected. To investigate motor-related effective connectivity differences between individuals with TIA and HCs, the bilateral primary motor cortex (M1) was used as the regions of interest (ROIs) to perform a whole-brain Granger causality analysis (GCA). Furthermore, partial correlation was used to evaluate the relationship between GCA values and the clinical characteristics of individuals with TIA. Results: Compared with HCs, individuals with TIA demonstrated alterations in the effective connectivity between M1 and widely distributed brain regions involved in motor, visual, auditory, and sensory integration. In addition, GCA values were significantly correlated with high- and low-density lipoprotein cholesterols in individuals with TIA. Conclusion: This study provides important evidence for the alteration of motor-related effective connectivity in TIA, which reflects the abnormal information flow between different brain regions. This could help further elucidate the pathological mechanisms of motor impairment in individuals with TIA and provide a new perspective for future early diagnosis and intervention for TIA.

Evidence-based region of interest (ROI) definition for surface-guided radiotherapy (SGRT) of abdominal cancers using deep-inspiration breath-hold (DIBH).

To define and evaluate the appropriate abdominal region of interest (ROI) as a surrogate of diaphragm positioning in deep-inspiration breath-hold (DIBH) for surface-guided radiotherapy (SGRT) of abdominal cancers using 3D optical surface imaging (OSI). Six potential abdominal ROIs were evaluated to calculate their correlations with the diaphragm position using 4DCT images of 20 abdominal patients. Twelve points of interest (POIs) were defined (six on the central soft tissue and six on the bilateral ribs) at three superior-inferior levels, and different sub-groups represented different ROIs. ROI-1 was the largest, containing all 12 POIs from the xiphoid to the umbilicus and between the lateral body midlines while ROI-2 had only eight inferior POIs, ROI-3 had six lateral POIs, and ROI-4 had four superior-lateral POIs over the ribs, ROI-5 contained six central and two most inferior-lateral POIs and ROI-6 contained six central and four inferior-lateral POIs. Internally, the right diaphragm dome was used to represent its positions in 4DCT (0% and 50% within the cycle). The Pearson correlation coefficients were calculated between the diaphragm dome and all 12 external POIs individually or grouped as six ROIs. The quality of the abdominal ROIs was evaluated as potential internal surrogates and, therefore, potential ROIs for SGRT DIBH setup. The four most inferior POIs show the highest mean correlation (r = 0.75) with diaphragmatic motion, and the correlation decreases as POIs move superiorly. The mean correlations are the highest for ROIs with little or no rib support: r = 0.67 for ROI-2, r = 0.64 for ROI-5, and r = 0.63 for ROI-6, while lower for ROIs with rib support: ROI-1 has r = 0.60, ROI-3 has r = 0.50, and ROI-4 has only r = 0.28. This study demonstrates that the rectangular/triangular soft-tissue ROI (with little rib support) is an optimal surrogate for body positioning and diaphragmatic motion, even when treating tumors under the rib cage. This evidence-based ROI definition should be utilized when treating abdominal cancers with free-breathing (FB) and/or DIBH setup.

Characterization and phylogenomic analysis of Breznakiella homolactica gen. nov. sp. nov. indicate that termite gut treponemes evolved from non-acetogenic spirochetes in cockroaches.

Spirochetes of the genus Treponema are surprisingly abundant in termite guts, where they play an important role in reductive acetogenesis. Although they occur in all termites investigated, their evolutionary origin is obscure. Here, we isolated the first representative of 'termite gut treponemes' from cockroaches, the closest relatives of termites. Phylogenomic analysis revealed that Breznakiella homolactica gen. nov. sp. nov. represents the most basal lineage of the highly diverse 'termite cluster I', a deep-branching sister group of Treponemataceae (fam. 'Termitinemataceae') that was present already in the cockroach ancestor of termites and subsequently coevolved with its host. Breznakiella homolactica is obligately anaerobic and catalyses the homolactic fermentation of both hexoses and pentoses. Resting cells produced acetate in the presence of oxygen. Genome analysis revealed the presence of pyruvate oxidase and catalase, and a cryptic potential for the formation of acetate, ethanol, formate, CO2 and H2 - the fermentation products of termite gut isolates. Genes encoding key enzymes of reductive acetogenesis, however, are absent, confirming the hypothesis that the ancestral metabolism of the cluster was fermentative, and that the capacity for acetogenesis from H2 plus CO2 - the most intriguing property among termite gut treponemes - was acquired by lateral gene transfer.

Multiparametric and multilevel characterization of morphological alterations in patients with transient ischemic attack.

Transient ischemic attack (TIA), an important risk factor for stroke, is associated with widespread disruptions of functional brain architecture. However, TIA-related structural alterations are not well established. By analyzing structural MRI data from 50 TIA patients versus 40 healthy controls (HCs), here we systematically investigated TIA-related morphological alterations in multiple cortical surface-based indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]) at multiple levels (local topography, interregional connectivity and whole-brain network topology). For the observed alterations, their associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers were further examined. We found that compared with the HCs, the TIA patients showed widespread morphological alterations and the alterations depended on choices of morphological index and analytical level. Specifically, the patients exhibited: (a) regional CT decreases in the transverse temporal gyrus and lateral sulcus; (b) impaired FD- and GI-based connectivity mainly involving visual, somatomotor and ventral attention networks and interhemispheric connections; and (c) altered GI-based whole-brain network efficiency and decreased FD-based nodal centrality in the middle frontal gyrus. Moreover, the impaired morphological connectivity showed high sensitivities and specificities for distinguishing the patients from HCs. Altogether, these findings demonstrate the emergence of morphological index-dependent and analytical level-specific alterations in TIA, which provide novel insights into neurobiological mechanisms underlying TIA and may serve as potential biomarkers to help diagnosis of the disease. Meanwhile, our findings highlight the necessity of using multiparametric and multilevel approaches for a complete mapping of cerebral morphology in health and disease.

Commissioning of optical surface imaging systems for cranial frameless stereotactic radiosurgery.

PURPOSE: This study aimed to evaluate and compare different system calibration methods from a large cohort of systems to establish a commissioning procedure for surface-guided frameless cranial stereotactic radiosurgery (SRS) with intrafractional motion monitoring and gating. Using optical surface imaging (OSI) to guide non-coplanar SRS treatments, the determination of OSI couch-angle dependency, baseline drift, and gated-delivered-dose equivalency are essential. METHODS: Eleven trained physicists evaluated 17 OSI systems at nine clinical centers within our institution. Three calibration methods were examined, including 1-level (2D), 2-level plate (3D) calibration for both surface image reconstruction and isocenter determination, and cube phantom calibration to assess OSI-megavoltage (MV) isocenter concordance. After each calibration, a couch-angle dependency error was measured as the maximum registration error within the couch rotation range. A head phantom was immobilized on the treatment couch and the isocenter was set in the middle of the brain, marked with the room lasers. An on-site reference image was acquired at couch zero, the facial region of interest (ROI) was defined, and static verification images were captured every 10° for 0°-90° and 360°-270°. The baseline drift was assessed with real-time monitoring of the motionless phantom over 20 min. The gated-delivered-dose equivalency was assessed using the electron portal imaging device and gamma test (1%/1mm) in reference to non-gated delivery. RESULTS: The maximum couch-angle dependency error occurs in longitudinal and lateral directions and is reduced significantly (P < 0.05) from 1-level (1.3 ± 0.4 mm) to 2-level (0.8 ± 0.3 mm) calibration. The MV cube calibration does not further reduce the couch-angle dependency error (0.8 ± 0.2 mm) on average. The baseline drift error plateaus at 0.3 ± 0.1 mm after 10 min. The gated-delivered-dose equivalency has a >98% gamma-test passing rate. CONCLUSION: A commissioning method is recommended using the 3D plate calibration, which is verified by radiation isocenter and validated with couch-angle dependency, baseline drift, and gated-delivered-dose equivalency tests. This method characterizes OSI uncertainties, ensuring motion-monitoring accuracy for SRS treatments.

Participation of a MADS-box transcription factor, Mb1, in regulation of the biocontrol potential in an insect fungal pathogen.

The cell wall is crucial for fungal growth, proliferation and interaction with the environment and host. Understanding the regulatory mechanism of cell wall integrity may help with improvement of fungal biocontrol agents. Here, a putative target of the cell wall integrity pathway-involved Slt2 MAP kinase, Mb1, an orthologue of MADS-box transcription factor Rlm1, was characterized in an economically important insect fungal pathogen, Beauveria bassiana. Mb1 disruption mutant (ΔMb1) displayed reduced growth and increased conidial production on minimal medium but not on rich-nutrient media, which is different from ΔSlt2 to a great extent. Loss of Mb1 resulted in a significant increase in sensitivity to cell wall-perturbing agents (Congo red and calcofluor white), with alteration in cell composition that was inconsistent with ΔSlt2 strain, including increased chitin content and reduced chitin-binding ß-1, 3/1,6-glucan levels in the absence of any stress. Transcription levels of 15 chitin synthesis and metabolism-associated and 17 Pkc1-Slt2 CWI (cell wall integrity) pathway, glucan synthesis, and cell wall remodeling enzyme synthesis-involved genes were significantly increased and repressed in ΔMb1 strain, respectively, some of which were verified to be the targets of Mb1. Insect bioassays revealed decreased virulence for the ΔMb1 strain in both topical and intrahemocoel injection assays. Our results demonstrated that Mb1 control fungal biocontrol potential-associated traits, including growth, conidiation and cell wall integrity, in B. bassiana. The difference of Mb1 and Slt2 in contribution to cell wall integrity is discussed.

A Sensor Fusion Based Nonholonomic Wheeled Mobile Robot for Tracking Control.

In this paper, a detail design procedure of the real-time trajectory tracking for the nonholonomic wheeled mobile robot (NWMR) is proposed. A 9-axis micro electro-mechanical systems (MEMS) inertial measurement unit (IMU) sensor is used to measure the posture of the NWMR, the position information of NWMR and the hand-held device are acquired by global positioning system (GPS) and then transmit via radio frequency (RF) module. In addition, in order to avoid the gimbal lock produced by the posture computation from Euler angles, the quaternion is utilized to compute the posture of the NWMR. Furthermore, the Kalman filter is used to filter out the readout noise of the GPS and calculate the position of NWMR and then track the object. The simulation results show the posture error between the NWMR and the hand-held device can converge to zero after 3.928 seconds for the dynamic tracking. Lastly, the experimental results show the validation and feasibility of the proposed results.

Toward neuroimaging-based network biomarkers for transient ischemic attack.

Stroke is associated with topological disruptions of large-scale functional brain networks. However, whether these disruptions occur in transient ischemic attack (TIA), an important risk factor for stroke, remains largely unknown. Combining multimodal MRI techniques, we systematically examined TIA-related topological alterations of functional brain networks, and tested their reproducibility, structural, and metabolic substrates, associations with clinical risk factors and abilities as diagnostic and prognostic biomarkers. We found that functional networks in patients with TIA exhibited decreased whole-brain network efficiency, reduced nodal centralities in the bilateral insula and basal ganglia, and impaired connectivity of inter-hemispheric communication. These alterations remained largely unchanged when using different brain parcellation schemes or correcting for micro head motion or for regional gray matter volume, cerebral blood flow or hemodynamic lag of BOLD signals in the patients. Moreover, some alterations correlated with the levels of high-density lipoprotein cholesterol (an index related to ischemic attacks via modulation of atherosclerosis) in the patients, distinguished the patients from healthy individuals, and predicted future ischemic attacks in the patients. Collectively, these findings highlight the emergence of characteristic network dysfunctions in TIA, which may aid in elucidating pathological mechanisms and establishing diagnostic and prognostic biomarkers for the disease.

Biofunctionalized self-assembly of peptide amphiphile induces the differentiation of bone marrow mesenchymal stem cells into neural cells.

Bone marrow mesenchymal stem cells (BMSCs) are multipotential differentiation cells which can differentiate into different cell types such as osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial cells, and neuronal cells. Such multipotential differentiation makes them attractive for stem cell-based therapy aimed at treating previously incurable disorders. In the present work, we encapsulated BMSCs into a hydrogel with a three-dimensional (3D) network of nanofibers, formed from self-assembling of peptide amphiphile. The self-assembling of peptide amphiphile into hydrogel was triggered by mixing cell suspensions with dilute aqueous solutions of amphipathic peptide. Moreover, this hydrogel was designed to present cells the neurite-promoting laminin epitope IKVAV at nearly van der Waals density, which induced the successful differentiation of BMSCs into neural cells.

Altered Functional Connectivity within Default Mode Network in Patients with Transient Ischemic Attack: A Resting-State Functional Magnetic Resonance Imaging Study.

Default mode network (DMN) is an important functional brain network that supports aspects of cognition. Stroke has been reported to be associated with functional connectivity (FC) impairments within DMN. However, whether FC within DMN changes in transient ischemic attack (TIA), an important risk factor for stroke, remains unclear. Forty-eight TIA patients and 41 age- and sex-matched healthy controls (HCs) were recruited in this study. Using resting-state functional magnetic resonance imaging seed-based FC methods, we examined FC alterations within DMN in TIA patients, tested its associations with clinical information, and further explored the ability of FC abnormalities to predict follow-up ischemic attacks. We found significantly decreased FC of left middle temporal gyrus/angular gyrus both with medial prefrontal cortex (mPFC) and posterior cingulate cortex/precuneus (PCC/Pcu) and significantly decreased FC among each pair of mPFC, left PCC, and right Pcu in patients with TIA as compared with HCs. Moreover, the connectivity between mPFC and left PCC could predict future ischemic attacks of the patients. Collectively, these findings may provide insights into further understanding of the underlying pathological mechanism in TIA, and aberrant FC between the hubs within DMN may provide a reference for the imaging diagnosis and early intervention of TIA.

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

Feasibility study of individualized optimal positioning selection for left-sided whole breast radiotherapy: DIBH or prone.

The deep inspiration breath hold (DIBH) and prone (P) position are two common heart-sparing techniques for external-beam radiation treatment of left-sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left-sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patient's data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k-fold cross-validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity-based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities-based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity-based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities-based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.

Serum Soluble Corin is Decreased in Stroke.

BACKGROUND AND PURPOSE: Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. METHODS: Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. RESULTS: Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001). CONCLUSIONS: Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke.

A novel mitochondrial membrane protein, Ohmm, limits fungal oxidative stress resistance and virulence in the insect fungal pathogen Beauveria bassiana.

The Hog1 mitogen-activated protein (MAP) kinase regulates environmental stress responses and virulence in the entomopathogenic fungus Beauveria bassiana. To further characterize this pathway, we constructed a subtraction library enriched for genes regulated by Hog1. One targeted gene, encoding a novel membrane protein, Ohmm (oxidative homeostasis membrane-protein-mitochondria), was uniquely identified as being downregulated in the ΔHog1 background during growth under non-stress and osmotic stress conditions, but upregulated under oxidative stress. Ohmm was an experimentally validated flavin-binding protein and targeted to the mitochondria. Deletion of Ohmm resulted in increased oxidative stress resistance, whereas overexpression caused an opposite phenotype. The ΔOhmm showed accumulation of reactive oxygen species with alterations in cell wall composition and compatible solute accumulation evident as compared with the wild type parent. Conidiation was reduced > 80%; however, conidia produced by the ΔOhmm strain germinated significantly faster than wild type cells. Insect bioassays using the greater wax moth revealed increased virulence for the ΔOhmm strain in both topical and intrahemocoel injection assays, indicating a negative effect of the presence of Ohmm with respect to pathogenesis. As predicted from our characterization, deletion of Ohmm in a ΔHog1 background rescued its oxidative sensitivity phenotype, confirming that Ohmm acts downstream of the Hog1 MAP-kinase.

Interplay between calcineurin and the Slt2 MAP-kinase in mediating cell wall integrity, conidiation and virulence in the insect fungal pathogen Beauveria bassiana.

The entomopathogenic fungus, Beauveria bassiana, is of environmental and economic importance as an insect pathogen, currently used for the biological control of a number of pests. Cell wall integrity and conidiation are critical parameters for the ability of the fungus to infect insects and for production of the infectious propagules. The contribution of calcineurin and the Slt2 MAP kinase to cell wall integrity and development in B. bassiana was investigated. Gene knockouts of either the calcineurin CNA1 subunit or the Slt2 MAP kinase resulted in decreased tolerance to calcofluor white and high temperature. In contrast, the Δcna1 strain was more tolerant to Congo red but more sensitive to osmotic stress (NaCl, sorbitol) than the wild type, whereas the Δslt2 strain had the opposite phenotype. Changes in cell wall structure and composition were seen in the Δslt2 and Δcna1 strains during growth under cell wall stress as compared to the wild type. Both Δslt2 and Δcna1 strains showed significant alterations in growth, conidiation, and viability. Elevation of intracellular ROS levels, and decreased conidial hydrophobicity and adhesion to hydrophobic surfaces, were also seen for both mutants, as well as decreased virulence. Under cell wall stress conditions, inactivation of Slt2 significantly repressed CN-mediated phosphatase activity suggesting some level of cross talk between the two pathways. Comparative transcriptome profiling of the Δslt2 and Δcna1 strains revealed alterations in the expression of distinct gene sets, with overlap in transcripts involved in cell wall integrity, stress response, conidiation and virulence. These data illustrate convergent and divergent phenotypes and targets of the calcineurin and Slt2 pathways in B. bassiana.