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Abstract Background Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. Methods We utilized the linear‐quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal‐tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early‐stage lung cancer. Mean lung BED, Lyman–Kutcher–Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed‐rank test. Results The transition point occurs when the tumor‐to‐normal tissue ratio (TNR) of the physical dose equals the TNR of α/β in the BED dose‐volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p

Abstract Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (− 5.18 ± 9.52%; p

Abstract The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

It is inevitable to cut reinforced concrete (RC) appeared in cross passage of city metro by cutting tools when constructing in densely populated area. The previous cutters employed to cut RC are insufficient and easily damaged, so a new polycrystalline diamond compact (PDC) cutter is used to solve this question. Based on the theoretical analysis of cutting mechanism, both circular and tapered PDC cutters with cutting edge angle of 90° and negative front rack angle of 10° are used to cut RC. The peeling and breaking patterns of cutting concrete are proposed, the nodular and grainy chips are the preferred modes in cutting steel bars. The LS-DYNA is employed to investigate the cutting performance in advance. The simulation results show that the average and peak cutting forces increase with the growth of penetration depth, cutting speed, and roundness, and subsequently the recommended penetration depth less than 1.2 mm is obtained to cut RC due to the existence of steel bars. Moreover, the linear cutting platform is adopted to investigate the force ability and damage state of PDC cutters. It is concluded that the cutting force increases abruptly and fluctuates heavily when cutting the coarse aggregates. The patterns occurred in both numerical and experimental results are generally similar. Notably, the steel bar is pulled out and the PDC cutter is damaged at the penetration depth of 0.8 mm, while a good cut occurs at the penetration depth of 0.3 mm. The tapered PDC cutter with a relatively low cutting force is prone to be broken compared with circular PDC cutter. It is suggested that the circular PDC cutter at the penetration depth of 0.3 mm should be used to cut RC in practical engineering.

The quest for efficient and non-intrusive human activity recognition (HAR) in indoor environments has led to the burgeoning field of WiFi-based HAR. This method promises applications from healthcare monitoring to elderly care due to its cost-effectiveness and ease of deployment compared to traditional sensor-based systems. However, WiFi-based HAR faces significant challenges in maintaining performance across diverse environments and subjects, largely due to WiFi signal variability. Addressing this issue necessitates training models on extensive datasets. Recent studies have utilized conventional models, including Convolutional Neural Networks (CNNs), and sequence-to-sequence (Seq2Seq) models such as LSTM, GRU, or Transformer. Despite their precision, these models are computationally intensive and require more training data. To tackle these limitations, we propose a novel approach that leverages a Temporal Convolutional Network with Augmentations and Attention, referred to as TCN-AA. This model enhances computational efficiency and accuracy in the face of dataset variability by combining temporal convolutional layers with data augmentation strategies and an attention mechanism to focus on critical features. Our method is computationally efficient and significantly improves accuracy, even with a threefold increase in data size through augmentation techniques. Experiments on a public dataset indicate our approach outperforms state-of-the-art methods, achieving 99.42% accuracy. This work represents a significant step forward in the practical application of WiFi-based HAR, paving the way for broader adoption in critical areas like healthcare and security.

ABSTRACTThe Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rhodobacter nitrogen-fixation (Rnf) complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (ΔrnfC) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation is not due to reduced cell surface of RadD, but rather an increased level of extracellular lysine, which binds RadD and inhibits coaggregation. Indeed, removal of extracellular lysine via washing ΔrnfC cells restores coaggregation, while addition of lysine inhibits this process. These phenotypes mirror that of a mutant (ΔkamA) that fails to metabolize extracellular lysine. Strikingly, the ΔrnfC mutant is defective in ATP production, cell growth, cell morphology, and expression of the enzyme MegL that produces hydrogen sulfide (H2S) from cysteine. Targeted metabolic profiling demonstrated that catabolism of many amino acids, including histidine and lysine, is altered in ΔrnfC cells, thereby reducing production of ATP and metabolites including H2S and butyrate. Most importantly, we show that the ΔrnfC mutant is severely attenuated in a mouse model of preterm birth. The indispensable function of Rnf complex in fusobacterial pathogenesis via modulation of bacterial metabolism makes it an attractive target for developing therapeutic intervention.IMPORTANCEThis paper illuminates the significant question of how the oral commensal Fusobacterium nucleatum adapts to the metabolically changing environments of several extra-oral sites such as placenta and colon to promote various diseases as an opportunistic pathogen. We demonstrate here that the highly conserved Rhodobacter nitrogen-fixation complex, commonly known as Rnf complex, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of this Rnf complex causes global defects in polymicrobial interaction, biofilm formation, cell growth and morphology, hydrogen sulfide production, and ATP synthesis. Targeted metabolomic profiling demonstrates that the loss of this respiratory enzyme significantly diminishes catabolism of numerous amino acids, which negatively impacts fusobacterial virulence as tested in a preterm birth model in mice.

Abstract Background Atypical teratoid rhabdoid tumor (AT/RT) occurs at a younger age and is associated with a worse prognosis than medulloblastoma; however, these two tumor entities are mostly indistinguishable on neuroimaging. The aim of our study was to differentiate AT/RT and medulloblastoma based on their clinical and MRI features to enhance treatment planning and outcome prediction. Methods From 2005–2021, we retrospectively enrolled 16 patients with histopathologically diagnosed AT/RT and 57 patients with medulloblastoma at our institute. We evaluated their clinical data and MRI findings, including lesion signals, intratumoral morphologies, and peritumoral/distal involvement. Results The age of children with AT/RT was younger than that of children with medulloblastoma (2.8 ± 4.9 [0–17] vs. 6.5 ± 4.0 [0–18], p

Abstract Background To investigate whether whole‐brain radiotherapy (WBRT) decreases lymphocyte counts and evaluate the impact of treatment‐related lymphopenia on survival in patients with brain metastasis. Methods Medical records from 60 small‐cell lung cancer patients treated with WBRT from January 2010 to December 2018 were included in the study. Total lymphocyte count (TLC) was obtained pre and post treatment (within 1 month). We performed linear and logistic regression analyses to identify predictors of lymphopenia. The association between lymphopenia and survival was analyzed using Cox regression analysis. Results Thirty‐nine patients (65%) developed treatment‐related lymphopenia. The median TLC decrease was −374 cells/μL (interquartile range −50 to −722, p

Abstract Background Stereotactic ablative radiotherapy (SABR) is now the standard of care for patients with inoperable early‐stage lung cancer. Many of these patients are elderly. EGFR (epidermal growth factor receptor) mutation is also common in the Asian population. Methods To evaluate the effects of old age and EGFR mutation on treatment outcomes and toxicity, we reviewed the medical records of 71 consecutive patients with inoperable early‐stage non‐small cell lung cancer (NSCLC) who received SABR at Taipei Veterans General Hospital between 2015 and 2021. Results The study revealed that median age, follow‐up, Charlson comorbidity index, and ECOG score were 80 years, 2.48 years, 3, and 1, respectively. Of these patients, 37 (52.1%) were 80 years or older, and 50 (70.4%) and 21 (29.6%) had T1 and T2 diseases, respectively. EGFR mutation status was available for 33 (46.5%) patients, of whom 16 (51.5%) had a mutation. The overall survival rates at 1, 3, and 5 years were 97.2, 74.9, and 58.3%, respectively. The local control rate at 1, 3, and 5 years was 97.1, 92.5, and 92.5%, respectively. Using Cox proportional hazards regression we found that male sex was a risk factor for overall survival (p = 0.036, 95% CI: 1.118–26.188). Two patients had grade 2 pneumonitis, but no other grade 2 or higher toxicity was observed. We did not find any significant differences in treatment outcomes or toxicity between patients aged 80 or older and those with EGFR mutations in this cohort. Conclusion These findings indicate that age and EGFR mutation status do not significantly affect the effectiveness or toxicity of SABR for patients with inoperable early‐stage NSCLC.

Objective: To study the inhibitory effects on colorectal cancer (CRC) and the underlying mechanism of the petroleum ether extract of Aegiceras corniculatum leaves (PACL). Materials and Methods: The effect of PACL on the proliferation of CRC cell lines DLD-1, HT-29, and SW480 was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and colony-forming assay. And then, a wound-healing assay was used to measure the migration ability of three CRC cells. The cell cycle and apoptosis of three CRC cells were measured by PI/RNase staining and annexin V-FITC/double staining, respectively, and the intrinsic apoptosis pathway was studied by the Western blot. The anti-CRC effect of PACL in vivo was evaluated by HT-29 xenograft zebrafish embryos. Results: PACL inhibited cell viability and proliferation in DLD-1, HT-29, and SW480 cells in a dose- and time-dependent manner. PACL can inhibit cell migration in DLD-1 and SW480 cells but not in the less mobile phenotype cell HT-29. PACL treatment resulted in cell cycle arrest of DLD-1 and HT-29 cells in the G2/M phase. Moreover, PACL can induce apoptosis in all three CRC cells, which may be achieved by regulating the intrinsic apoptosis pathway mediated by mitochondria and the endoplasmic reticulum. Interestingly, the tumor sizes were decreased after treatment with PACL and PACL combined with fluorouracil in HT-29 xenograft zebrafish embryos. Conclusions: These findings suggested that PACL may exert its anti-CRC effect by inducing apoptosis through the intrinsic apoptosis pathway and show a significant anti-CRC effect in vitro and in vivo, so it might be potentially developed as an anti-CRC agent.

Because the average number of missing people in our country is more than 20,000 per year, determining how to efficiently locate missing people is important. The traditional method of finding missing people involves deploying fixed cameras in some hotspots to capture images and using humans to identify targets from these images. However, in this approach, high costs are incurred in deploying sufficient cameras in order to avoid blind spots, and a great deal of time and human effort is wasted in identifying possible targets. Further, most AI-based search systems focus on how to improve the human body recognition model, without considering how to speed up the search in order to shorten the search time and improve search efficiency, which is the aim of this study. Hence, by exploiting the high-mobility characteristics of unmanned aerial vehicles (UAVs), this study proposes an integrated YOLOv5 and hierarchical human-weight-first (HWF) path planning framework to serve as an efficient UAV searching system, which works by dividing the whole searching process into two levels. At level one, a searching UAV is dispatched to a higher altitude to capture images, covering the whole search area. Then, the well-known artificial intelligence model YOLOv5 is used to identify all persons in the captured images and compute corresponding weighted scores for each block in the search area, according to the values of the identified human bodies, clothing types, and clothing colors. At level two, the UAV lowers its altitude to sequentially capture images for each block, in descending order according to its weighted score at level one, and it uses the YOLOv5 recognition model repeatedly until the search target is found. Two improved search algorithms, HWFR-S and HWFR-D, which incorporate the concept of the convenient visit threshold and weight difference, respectively, are further proposed to resolve the issue of the lengthy and redundant flight paths of HWF. The simulation results suggest that the HWF, HWFR-S, and HWFR-D search algorithms proposed in this study not only effectively reduce the length of a UAV’s search path and the number of search blocks but also decrease the search time required for a UAV to locate the search target, with a much higher search accuracy than the two traditional search algorithms. Moreover, this integrated YOLOv5 and HWF framework is implemented and tested in a real scenario to demonstrate its capability in enhancing the efficiency of a search and rescue operation.

Abstract This paper proposes a generalized piecewise linear time‐variable droop frequency controller with a ramp‐up period for a de‐loaded wind turbine generator. The authors present an analytical model using a simplified system frequency response (SFR) to explain the need for a ramp‐up period under the conditions of variable wind speed. In order to achieve the highest frequency nadir under different operating conditions, the durations and peak value of the time‐variable droop function must be adapted in real time. This adaptation is achieved using an artificial neural network (ANN) based on current system variables such as wind speed, penetration, pitch angle, wind speed change, and outage capacity. Dynamic frequency responses for a power system subject to generator outages and wind speed changes are simulated using MATLAB/Simulink to demonstrate the effectiveness of the proposed droop controller. These results show that the frequency nadir can be improved by the proposed algorithm through adaption of the durations and peak value.

Abstract Spinal metastasis from malignant primary brain tumors (MPBTs) in pediatric patients is rare and often appears as enhancing lesions on MRI. However, some indolent enhancing spinal lesions (IESLs) resulting from previous treatment mimic metastasis on MRI, leading to unnecessary investigation and treatment. In 2005–2020, we retrospectively enrolled 12 pediatric/young patients with clinical impression of spinal metastasis and pathological diagnosis of their spinal lesions. Three patients had MPBT with IESL, and 9 patients had malignant tumors with metastases. The histopathologic diagnosis of IESL was unremarkable marrow change. We evaluated their MRI, CT, and bone scan findings. The following imaging findings of IESL vs. spinal metastasis were noted: (1) IESLs appeared round/ovoid (3/3, 100%), whereas spinal metastasis appeared irregular (9/9, 100%) (P = 0.005); (2) target-shaped enhancement was noted in (3/3, 100%) vs. (0/9, 0%) of cases, respectively (P = 0.005); (3) pathologic fracture of the vertebral body was noted in (1/3, 33.3%) vs. (9/9, 100%) of cases, respectively (P = 0.045); (4) expansile vertebral shape was noted in (0/3, 0%) vs. (9/9, 100%) of cases, respectively (P = 0.005); (5) obliteration of the basivertebral vein was noted in (0/3, 0%) vs. (9/9, 100%) of cases, respectively (P = 0.005); and (6) osteoblastic change on CT was noted in (3/3, 100%) vs. (2/9, 22.2%) of cases, respectively (P = 0.034). IESL in pediatric patients with MPBT can be differentiated from metastasis based on their imaging characteristics. We suggest close follow-up rather than aggressive investigation and treatment for IESL.

The engagement of target-interceptor is an extremely complicated and nonlinear problem. Most literatures of developed guidance algorithms are hard to work in real-time missile guidance systems because of the complicated design of controllers, restriction in specific condition or excess computing loading. In this paper, the proposed guidance algorithm computes the predicted interception point of target-interceptor and applies particle swarm optimization to optimize the lateral acceleration control commands of missile where the definition of fitness function can guide the missile toward the predicted interception point when the computed fitness value is the minimum. According to the results of simulation experiments, the proposed method has the satisfied target-kill performance to the superior aircraft with high agility. The missile can greatly revise the flight route toward the computed collision course at the initial pursuit stage and the course curve of missile is flatter than the other two guidance laws. Besides, the proposed method can reduce the occurrence of big lateral acceleration control commands acting on the missile to avoid unlocking the evasive target at the terminal stage. As a result, the proposed guidance algorithm based on particle swarm optimization is very effective without using the complicated nonlinear control methods and excess storage burden of computer. It is a simple and feasible missile guidance algorithm due to the advantages of simplicity and effectiveness just like the proportional navigation guidance law but the performance of proposed guidance algorithm is better than proportional navigation guidance law and the other guidance algorithm designed by particle swarm optimization.

Kalman filter has been applied extensively to the target tracking. The estimation performance of Kalman filter is closely resulted by the quality of prior information about the process noise covariance (Q) and the measurement noise covariance (R). Therefore, the development of adaptive Kalman filter is mainly to reduce the estimation errors produced by the uncertainty of Q and R. In this paper, the proposed self-adaptive Kalman filter algorithm has solved the problems of covariance-matching method about the determination of the width of the window and the addition of storage burden and that can update Q and R simultaneously. Simulation results confirm that the proposed method outperforms the traditional Kalman filter and has the better estimation performance than the other two adaptive Kalman filters in the target tracking. The developed filtering algorithm has the following characteristics: high robustness, low computing load, easy operation and tuning Q, R simultaneously.

ABSTRACT The Gram-negative anaerobe Fusobacterium nucleatum is a major producer of hydrogen sulfide (H2S), a volatile sulfur compound that causes halitosis. Here, we dissected the genetic determinants of H2S production and its role in bacterial fitness and virulence in this important member of the oral microbiome. F. nucleatum possesses four enzymes, CysK1, CysK2, Hly, and MegL, that presumably metabolize l-cysteine to H2S, and CysK1 was previously shown to account for most H2S production in vitro, based on correlations of enzymatic activities with gene expression at mid-log phase. Our molecular studies showed that cysK1 and megL were highly expressed at the late exponential growth phase, concomitant with high-level H2S production, while the expression levels of the other genes remained substantially lower during all growth phases. Although the genetic deletion of cysK1 without supplementation with a CysK1-catalyzed product, lanthionine, caused cell death, the conditional ΔcysK1 mutant and a mutant lacking hly were highly proficient in H2S production. In contrast, a mutant devoid of megL showed drastically reduced H2S production, and a cysK2 mutant showed only minor deficiencies. Intriguingly, the exposure of these mutants to various antibiotics revealed that only the megL mutant displayed altered susceptibility compared to the parental strain: partial sensitivity to nalidixic acid and resistance to kanamycin. Most significantly, the megL mutant was attenuated in virulence in a mouse model of preterm birth, with considerable defects in the spread to amniotic fluid and the colonization of the placenta and fetus. Evidently, the l-methionine γ-lyase MegL is a major H2S-producing enzyme in fusobacterial cells that significantly contributes to fusobacterial virulence and antibiotic susceptibility. IMPORTANCE Fusobacterium nucleatum is a key commensal anaerobe of the human oral cavity that plays a significant role in oral biofilm development and contributes to additional pathologies at extraoral sites, such as promoting preterm birth and colorectal cancer. Although F. nucleatum is known as a major producer of hydrogen sulfide (H2S), its genetic determinants and physiological functions are not well understood. By a combination of bacterial genetics, biochemical methods, and in vivo models of infection, here, we demonstrate that the l-methionine γ-lyase MegL not only is a major H2S-producing enzyme of F. nucleatum but also significantly contributes to the antibiotic susceptibility and virulence of this organism.

Background/purpose: The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. Materials and methods: We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. Results: The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. Conclusion: Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT.

Abstract Background Definitive chemoradiotherapy (dCRT) is the first choice treatment for patients with locally advanced non-small cell lung cancer (NSCLC), but up to 35% of dCRT-treated tumors may have persistent or recurrent disease. Since the last decades, multimodality therapy showing potential for cure has become the mainstream for treatment of locally advanced NSCLCs, even some that were initially inoperable. Although salvage lung resection after dCRT has been reported with acceptable survivals, experiences in this respect are still limited. Other concerns remain debatable and inconclusive, such as dosage of radiation exposure, long interval between dCRT and surgery, and surgical comorbidity. Case presentation A 73-year-old male former smoker with diagnosis of right lower lobe of lung squamous cell carcinoma (SqCC) with multiple mediastinal lymphadenopathy, cT4N2M0, stage IIIB, received salvage right lower lobe + right middle lobe bilobectomy through video-assisted thoracoscopic surgery (VATS) after dCRT and adjuvant CRT to a total of 9000 cGy dosage of radiation. The interval from the 1st and 2nd ends of radiation to the salvage surgery was 980 and 164 days, respectively. The pre-operative forced expiratory volume in the first second was 2.33 L (101% predicted) and the diffusing capacity of the lungs for carbon monoxide was 56% predicted. The operating time was 6.5 h, and the total estimated blood loss was 50 ml. The patient was discharged on the 7th postoperative day without major complications or bronchopleural fistulas. The patient was still alive 42 months after the initial diagnosis of advanced N2 lung SqCC, and kept progression-free for 7 months after salvage lung resection. Conclusions Salvage lung resection performed long after high-dose radiation therapy of dCRT is technically feasible through VATS approach in a patient with initially inoperable cT4N2M0 stage IIIB NSCLC, and can be an alternative consolidative treatment for locally advanced NSCLC.

ABSTRACT Fusobacterium nucleatum, an anaerobic Gram-negative bacterium frequently found in the human oral cavity and some extra-oral sites, is implicated in several important diseases: periodontitis, adverse pregnancy outcomes, and colorectal cancer. To date, how this obligate anaerobe copes with oxidative stress and host immunity within multiple human tissues remains unknown. Here, we uncovered a critical role in this process of a multigene locus encoding a single, fused methionine sulfoxide reductase (MsrAB), a two-component signal transduction system (ModRS), and thioredoxin (Trx)- and cytochrome c (CcdA)-like proteins, which are induced when fusobacterial cells are exposed to hydrogen peroxide. Comparative transcriptome analysis revealed that the response regulator ModR regulates a large regulon that includes trx, ccdA, and many metabolic genes. Significantly, specific mutants of the msrAB locus, including msrAB, are sensitive to reactive oxygen species and defective in adherence/invasion of colorectal epithelial cells. Strikingly, the msrAB mutant is also defective in survival in macrophages, and it is severely attenuated in virulence in a mouse model of preterm birth, consistent with its failure to spread to the amniotic fluid and colonize the placenta. Clearly, the MsrAB system regulated by the two-component system ModRS represents a major oxidative stress defense pathway that protects fusobacteria against oxidative damage in immune cells and confers virulence by enabling attachment and invasion of multiple target tissues. IMPORTANCE F. nucleatum colonizes various human tissues, including oral cavity, placenta, and colon. How this obligate anaerobe withstands oxidative stress in host immune cells has not been described. We report here that F. nucleatum possesses a five-gene locus encoding a fused methionine sulfoxide reductase (MsrAB), a two-component signal transduction system (ModRS), and thioredoxin- and cytochrome c-like proteins. Regulated by ModRS, MsrAB is essential for resistance to reactive oxygen species, adherence/invasion of colorectal epithelial cells, and survival in macrophage. Unable to colonize placenta and spread to amniotic fluid, the msrAB mutant failed to induce preterm birth in a murine model.

Here, the authors follow a new approach using analytic solutions for Poiseuille-Couette channel flow to compute asthenospheric viscosities under the Caribbean. Active asthenospheric flow observed under the Caribbean contradicts the traditional view that the asthenosphere is only a passive lubricating layer for Earth’s tectonic plates.

Meningiomas are the most frequently diagnosed primary intracranial tumors in adults. Surgical resection is preferred if the meningioma is accessible; for those that are not suitable for surgical resection, radiotherapy should be considered to improve local tumor control. However, recurrent meningiomas are challenging to treat, as the recurrent tumor might be located in the previously irradiated area. Boron Neutron Capture Therapy (BNCT) is a highly selective radiotherapy modality in which the cytotoxic effect focuses mainly on cells with increased uptake of boron-containing drugs. In this article, we describe four patients with recurrent meningiomas treated with BNCT in Taiwan. The mean boron-containing drug tumor-to-normal tissue uptake ratio was 4.125, and the tumor mean dose was 29.414 GyE, received via BNCT. The treatment response showed two stable diseases, one partial response, and one complete response. We also introduce and support the effectiveness and safety of BNCT as an alternative salvage treatment for recurrent meningiomas.

The surface properties of a biomaterial play an important role in cell behavior, e.g., recolonization, proliferation, and migration. Collagen is known to favor wound healing. In this study, collagen (COL)-based layer-by-layer (LbL) films were built using different macromolecules as a partner, i.e., tannic acid (TA), a natural polyphenol known to establish hydrogen bonds with protein, heparin (HEP), an anionic polysaccharide, and poly(sodium 4-styrene sulfonate) (PSS), an anionic synthetic polyelectrolyte. To cover the whole surface of the substrate with a minimal number of deposition steps, several parameters of the film buildup were optimized, such as the pH value of the solutions, the dipping time, and the salt (sodium chloride) concentration. The morphology of the films was characterized by atomic force microscopy. Built at an acidic pH, the stability of COL-based LbL films was studied when in contact with a physiological medium as well as the TA release from COL/TA films. In contrast to COL/PSS and COL/HEP LbL films, COL/TA films showed a good proliferation of human fibroblasts. These results validate the choice of TA and COL as components of LbL films for biomedical coatings.

(1) Background: A well-established Boron Neutron Capture Therapy (BNCT) facility includes many essential systems, which are the epithermal neutron beam system, on-line monitoring system (OMS), QA/QC (quality assurance or quality control) system, boron concentration (BC) measurement system, and treatment planning system (TPS). Accurate data transmission, monitoring, and deposition among these systems are of vital importance before, during, and after clinical, animal, and cell BNCT irradiation. This work developed a novel integrated platform NeuTHOR Station (NeuTHORS) for BNCT at Tsing Hua Open-pool Reactor (THOR). Apart from the data of the OMS and QA/QC system, the data of BC and TPS can be loaded on NeuTHORS before BNCT clinical, animal, and cell irradiation. (2) Methods: A multi-paradigm computer programming language c# (c sharp) was used to develop the integrated platform NeuTHORS. The design of NeuTHORS is based on the standard procedures of BNCT treatment or experiment at THOR. Moreover, parallel testing with OMS-BNCT (the former OMS) and QA/QC of THOR was also performed for more than 70 times to verify the validation of NeuTHORS. (3) Results: According to the comparisons of the output, NeuTHORS and OMS-BNCT and QA/QC of THOR show very good consistency. NeuTHORS is now installed on an industrial PC (IPC) and successfully performs the monitoring of BNCT Treatment at THOR. Patients’ f BC and TPS data are also input into NeuTHORS and stored on IPC through an internal network from BC measurement room and TPS physicist. Therefore, the treatment data of each patient can be instantaneously established after each BNCT treatment for further study on BNCT. NeuTHORS can also be applied on data acquisition for a BNCT-related study, especially for animal or cell irradiation experiments. (4) Conclusions: A novel integrated platform NeuTHOR Station for monitoring BNCT clinical treatment and animal and cell irradiation study has been successfully established at THOR. With this platform, BNCT radiobiology investigations will be efficiently performed and a thorough data storage and analysis system of BNCT treatments or experiments can thus be systematically built up for the further investigation of BNCT at THOR.

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case–control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52–4.25) and OR = 1.54 (1.02–2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.

Aeromonas dhakensis is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against A. dhakensis infection is urgent. To understand its pathogenesis, we created an A. dhakensis AAK1 mini-Tn10 transposon library to study the mechanism of A. dhakensis infection. By using a Caenorhabditis elegans model, we established a screening platform for the purpose of identifying attenuated mutants. The uvrY mutant, which conferred the most attenuated toxicity toward C. elegans, was identified. The uvrY mutant was also less virulent in C2C12 fibroblast and mice models, in line with in vitro results. To further elucidate the mechanism of UvrY in controlling the toxicity in A. dhakensis, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin ahh1 and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of uvrY mutant in C. elegans; however, complementation of ahh1 endogenous promoter-driven ahh1 could not produce Ahh1 and rescue the virulence in the uvrY mutant. These findings suggest that UvrY is required for the expression of Ahh1 in A. dhakensis. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of A. dhakensis. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.

Objectives: The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT). Materials and Methods: Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7–81.0 months). Results: The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed. Conclusions: Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

Objectives Mental health resources are an important basis for coping with mental health services. The equity is an important index of a reasonable allocation of health resources. This study aims to evaluate the mental health resources and its equity allocation in Hunan Province, which is one of the typical central south areas of China, so as to provide reference for the development of mental health in China and other areas. Methods Data related to mental health resources was obtained from the Project of Mental Health Resources in Hunan Province, which was conducted by the Department of Hunan Mental Health Center in 2019. The Gini coefficient, the Theil index and other indicators were employed to quantitatively evaluate the equity of mental health resources’ allocation. Results By the end of 2018, there were a total of 141 mental health institutions in Hunan Province of China, the bed density was 5.31 beds per 10,000 people, the ratio of doctors to nurses was 2.20, the number of outpatients of mental health institutions was 1288,047 per year. The mental health resources’ allocation in terms of demographic dimension were in a preferred status with the Gini values all less than 0.3, and the Gini values for mental health resources`allocation in terms of geographical dimension ranged from 0.24 to 0.35. The Theil index for mental health allocation in terms of demographic dimension was lower than 0.05, and the Theil index for mental health allocation in terms of geographical dimension ranged from 0.04 to 0.11. Conclusions The shortage of mental health resources is still the priority issue to be increased and optimized by policy-makers in Hunan in the future, especially the human resources. Moreover, the utilization of mental health resources was low though its equity was fair. Policy-makers need to consider the high utilization and geographical accessibility of health resources among different regions to ensure people in different regions could get access to available health services.

Intracranial germinoma (IG) rarely occurs in adults. Its optimal treatment strategy is unclear. We evaluated the outcomes of radiotherapy in adults with intracranial germinoma. Data of 29 adult patients (age, 18–52 years; median age, 24.3 years) with IG treated with radiotherapy at Taipei Veterans General Hospital were retrospectively reviewed. They were followed up for a median time of 5.9 years (range, 1.0–12.8 years). We used the Kaplan–Meier method to estimate the progression-free survival (PFS) and overall survival (OS), and univariate and multivariate Cox proportional hazards regression models to identify the factors affecting PFS. PFS and OS were compared between adult and pediatric patients with IG. The 1-, 3-, and 5-year PFS rates were 96.6%, 85.8%, and 77.8%, respectively, in the adult patients, and the OS rate were all 100%. Seven patients (24.1%) experienced recurrence, and in six of them, salvage therapy successfully controlled the disease. Two patients (6.9%) died after 5 years of follow-up due to disease progression and central pontine myelinolysis. In the univariate and multivariate Cox analysis, bifocal lesions had a significantly lower PFS than those with single lesions (p = 0.008). Kaplan–Meier survival analysis showed that adult patients had a poorer PFS (p = 0.06) and OS (p = 0.025) than pediatric patients. Our study showed bifocal lesions were associated with lower PFS than a single lesion among adult IG patients, and adult IG patients tended to have poorer PFS and OS compared to pediatric IG patients. For adult patients with bifocal IG, we recommend treatment with craniospinal irradiation, whole ventricle irradiation (WVI) with chemotherapy, or frequent spine images follow-up for patients who received only WVI.

Background: Osteosarcoma (OS) is the most common primary malignancy of the bone and is notoriously resistant to radiation therapy. High-dose cytotoxic chemotherapy and surgical resection have improved the survival rate and prognosis of patients with OS. Nonetheless, treatment challenges remain when the tumor cannot be removed by surgery. Boron neutron capture therapy (BNCT) provides high linear energy transfer (LET) radiation, and its internal targeted characteristics make BNCT a novel therapy for removing OS and reducing radiation damage to adjacent healthy tissues. Methods: In this study, a UMR-106-grafted OS rat model was developed, and boric acid (BA) was used as the boron drug for BNCT. The pharmacokinetics of BA, following intravenous injection, were evaluated to determine the optimal time window for neutron irradiation. OS-bearing rats were irradiated by an epithermal neutron beam at Tsing Hua Open-Pool Reactor (THOR). The therapeutic efficacy of and tissue response after BNCT were evaluated by radiographic and histopathological observations. Results: OS-bearing rats were irradiated by neutrons in the first hour following the intravenous injection of BA. The prescription-absorbed doses in the tumor regions were 5.8 and 11.0 Gy. BNCT reduced the body weight of the tumor-bearing rats, but they recovered after a few days. The BA-mediated BNCT effectively controlled the orthotopic OS tumor, reduced osteolysis, and induced bone healing. Autoradiography and histological analysis confirmed that the BA retention region is consistent with the calcification region in OS tissue. Conclusion: BA is specifically retained in OS, and the BA-mediated BNCT can significantly reduce the tumor burden and osteolysis in OS-bearing rats.

Student populations are susceptible to the COVID-19 pandemic and may easy develop mental health problems related to their immaturity of psychological development and fluctuation of mood. However, little has been known about the effects of the pandemic on college students and the associated influencing factors. This study aimed to explore the role of psychological resilience as a mediator between general self-efficacy and mental health. A cross-sectional survey was conducted with 480 Chinese college students from 12 universities in Hunan province of China. The participants responded anonymously to the Generalized Self-Efficacy Scale (GSES), the Chinese version of the Resilience Scale for College Students (RSCS), and the 12-item General Health Questionnaire (GHQ-12). Hierarchical linear regression and structural equation modeling were used in this study. The average of GSES and RSCS scores of college students were 25.00 ± 4.68 and 137.97 ± 15.50, which were at a medium level. The average score for the GHQ-12 was 1.59 ± 1.59, and 22.03% of the college students scored ≥ 3 on the GHQ-12, indicating that they were at risk of developing mental disorders. According to the analyses of mediation effect, psychological resilience played a fully mediating role in the relationship between general self-efficacy and mental health. In conclusion, Chinese college students were at high risk of developing mental disorders during the COVID-19 period. General self-efficacy was positively associated with psychological resilience, and psychological resilience played a fully mediating role in the relationship between general self-efficacy and mental health. Future studies and interventions should aim to promote psychological resilience and general self-efficacy.

Disease and treatment-related symptoms and dysfunctions can interfere with the psychosocial adjustment of patients with oral cancer. Identifying factors influencing psychosocial maladjustment is important because at-risk individuals can be targeted for early intervention. This prospective longitudinal study investigated psychosocial adjustment changes and associated factors in postoperative oral cancer patients. Data on psychosocial adjustment, facial disfigurement, symptoms, and social support were collected before surgery (T1) at one month (T2), three months (T3), and five months after discharge (T4). Fifty subjects completed the study, and their data were included in the analysis. Psychosocial maladjustment was reported in 50%, 59.2%, 66%, and 62% of subjects at T1, T2, T3, and T4, respectively. The subjects’ psychosocial adjustment deteriorated after surgery. Results from generalized estimating equations indicated that financial status, cancer stage, pain, speech problems, social eating problems, and less sexuality were significant predictors of changes in psychosocial adjustment. Patients with insufficient income, stage III/IV cancer, severe pain, speech problems, social eating problems, and less sexuality were at higher risk for postoperative psychosocial maladjustment. Continued psychosocial assessment and appropriate supportive measures are needed to strengthen the psychosocial adjustment of these high-risk groups.

Abstract Engineered cartilage derived from mesenchymal stromal cells (MSCs) always fails to maintain the cartilaginous phenotype in the subcutaneous environment due to the ossification tendency. Vascular invasion is a prerequisite for endochondral ossification during the development of long bone. As an oral antitumor medicine, Inlyta (axitinib) possesses pronounced antiangiogenic activity, owing to the inactivation of the vascular endothelial growth factor (VEGF) signaling pathway. In this study, axitinib‐loaded poly(ε‐caprolactone) (PCL)/collagen nanofibrous membranes are fabricated by electrospinning for the first time. Rabbit‐derived MSCs‐engineered cartilage is encapsulated in the axitinib‐loaded nanofibrous membrane and subcutaneously implanted into nude mice. The sustained and localized release of axitinib successfully inhibits vascular invasion, stabilizes cartilaginous phenotype, and helps cartilage maturation. RNA sequence further reveals that axitinib creates an avascular, hypoxic, and low immune response niche. Timp1 is remarkably upregulated in this niche, which probably plays a functional role in inhibiting the activity of matrix metalloproteinases and stabilizing the engineered cartilage. This study provides a novel strategy for stable subcutaneous chondrogenesis of mesenchymal stromal cells, which is also suitable for other medical applications, such as arthritis treatment, local treatment of tumors, and regeneration of other avascular tissues (cornea and tendon).

Trismus is a severe complication of oral cancer treatment. Oral exercise is a potentially helpful approach for preventing or improving trismus. The study aimed to test the efficacy of an oral exercise for enhancing the maximum inter-incisal opening (MIO) in patients undergoing surgery and radiotherapy for oral cancer. This is a quasi-experimental study. A sample of 69 oral cancer patients completed the study, with 35 in the control group and 34 in the intervention group. Intervention subjects were asked to perform three 20-min oral exercise sessions per day for six months. Data on oral exercise practicing time, MIO, and mandibular function impairment were collected at the last radiotherapy exposure (T1), three months (T2), and six months (T3) after the radiotherapy. At T3, the intervention group exercised 217.1 min (95%CI: 107.4~326.7) more than the control group. The generalized estimation equations showed a statistically significant group-by-time interaction in MIO. The change in MIO score from T1 to T3, as indicated by the regression slope, was 2.5 mm (95%CI: 0.4~4.6) greater in the intervention group than in the control group. The results support the efficacy of the study intervention for improving patient exercise adherence and MIO.

In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid Emax model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin.

Abstract Background Cryptosporidium viatorum is a minor Cryptosporidium pathogen in humans. Currently, there is limited information regarding the prevalence and genotypes of C. viatorum in animals in China. Methods In this study, 228 faecal samples were collected from two wild rat species (Leopoldamys edwardsi and Berylmys bowersi) in Chongqing Municipality and Guangdong Province, China. These specimens were analyzed for C. viatorum and then subtyped it using PCR and sequence analysis of the small subunit ribosomal RNA (SSU rRNA) and 60-kilodalton glycoprotein (gp60) genes, respectively. Results A total of 25 (11.0%) faecal samples were tested positive for C. viatorum by SSU rRNA assay. Of these samples, 4 (3.6%) came from L. edwardsi and 21 (18.0%) from B. bowersi. Of the 25 C. viatorum-positive samples, 17 were successfully amplified at the gp60 gene locus, which represented four subtypes belonging to two subtype families, including XVa (XVaA6, XVaA3g, XVaA3h) and XVc (XVcA2G1). Phylogenetic analysis based on the gp60 amino acid sequences indicated that all of the C. viatorum isolates grouped together, supporting the conclusion that C. viatorum from the wild rats represent two subtype families. Conclusions These results indicate an occurrence of C. viatorum XVa subtype family from rats which is genetically identical to those found in humans. Our findings suggest that wild rats may be a potential source of human cryptosporidiosis.

[This corrects the article DOI: 10.1371/journal.pone.0247597.].

This study aimed to investigate the possible incidence of visual light perceptions (VLPs) during radiation therapy (RT). We analyzed whether VLPs could be affected by differences in the radiation energy, prescription doses, age, sex, or RT locations, and whether all VLPs were caused by radiation. From November 2016 to August 2018, a total of 101 patients who underwent head-and-neck or brain RT were screened. After receiving RT, questionnaires were completed, and the subjects were interviewed. Random forests (RF), a tree-based machine learning algorithm, and logistic regression (LR) analyses were compared by the area under the curve (AUC), and the algorithm that achieved the highest AUC was selected. The dataset sample was based on treatment with non-human units, and a total of 293 treatment fields from 78 patients were analyzed. VLPs were detected only in 122 of the 293 exposure portals (40.16%). The dataset was randomly divided into 80% and 20% as the training set and test set, respectively. In the test set, RF achieved an AUC of 0.888, whereas LR achieved an AUC of 0.773. In this study, the retina fraction dose was the most important continuous variable and had a positive effect on VLP. Age was the most important categorical variable. In conclusion, the visual light perception phenomenon by the human body during RT is induced by radiation rather than being a self-suggested hallucination or induced by phosphenes.

In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake of HEK293 cells. The biological data retrieved from the DAHMI experiments indicated that while the structures of tested compounds may be highly similar, their bio-distribution profile could be vastly distinctive. The reported optimized one-pot synthetic strategy along the linker-free in vitro testing protocol could provide an efficient platform to accelerate the development of boron-containing drugs.

Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.