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We re-analyzed the data from a recent large-scale study that reported strong correlations between DNA signatures of microbial organisms and 33 different cancer types and that created machine-learning predictors with near-perfect accuracy at distinguishing among cancers. We found at least two fundamental flaws in the reported data and in the methods: (i) errors in the genome database and the associated computational methods led to millions of false-positive findings of bacterial reads across all samples, largely because most of the sequences identified as bacteria were instead human; and (ii) errors in the transformation of the raw data created an artificial signature, even for microbes with no reads detected, tagging each tumor type with a distinct signal that the machine-learning programs then used to create an apparently accurate classifier. Each of these problems invalidates the results, leading to the conclusion that the microbiome-based classifiers for identifying cancer presented in the study are entirely wrong. These flaws have subsequently affected more than a dozen additional published studies that used the same data and whose results are likely invalid as well. Recent reports showing that human cancers have a distinctive microbiome have led to a flurry of papers describing microbial signatures of different cancer types. Many of these reports are based on flawed data that, upon re-analysis, completely overturns the original findings. The re-analysis conducted here shows that most of the microbes originally reported as associated with cancer were not present at all in the samples. The original report of a cancer microbiome and more than a dozen follow-up studies are, therefore, likely to be invalid.

Excessive exposure to ultraviolet radiation B (UVB) has been shown to contribute to the aging of human skin cells. Previous research has demonstrated that atorvastatin calcium (Ato) can mitigate the aging effects caused by chemotherapy drugs. However, it remains unclear whether Ato can alleviate skin aging induced by ultraviolet radiation. In this study, through in vitro experiments with Hacat cells, we found that Ato can significantly reduce the UVB-induced increased expression of age-related protein p16 and age-related gene p21, and also reduce the up-regulation of inflammatory factors such as IL-1 and IL-6. Besides, it can reduce the expression of metallomatrix protein (MMP1 and MMP9), and inhibit cell senescence and inflammatory damage. Similarly, we found that Ato can enhance skin collagen fiber reduction and collagen volume decrease, repair skin photoaging and damage induced by UVB rays, and speed up the rate at which the wounded location heals in vivo using Balb/c mice. In the mechanism, Ato markedly decreased the expression of p-p38, p-p65, p-mTOR in vivo and in vitro, suggesting that it may act on Mitogen-activated protein kinase (MAPK), Nuclear factor κB (NF- κB) and Mammalian target of rapamycin (mTOR) signaling pathways to produce above marked effects. In conclusion, Ato obviously relieved UVB-induced photoaging and damage, thus providing evidence for its potential in mitigating skin aging caused by ultraviolet radiation.

Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or multiple myeloma. However, its effect on UVB-induced skin photoaging remains unclear. In this study, we used UVB to induce senescence in human immortalized keratinocyte cell line (HaCaT cells) and skin photoaging in Balb/c mice to investigate the potential of SAHA in mitigating photoaging. First, we established a UVB-induced photoaging model in HaCaT cells. We observed that UVB exposure significantly upregulated the activity of senescence-associated β-galactosidase, p16, p21, IL-1β, IL-6, and matrix metalloproteinases [collagenase (MMP-1), matrix metalloproteinase-3 (MMP-3), and gelatinase (MMP-9)]. Supplementation with SAHA effectively alleviated cellular senescence in HaCaT cells. Next, we used UVB to induce photoaging in Balb/c mouse skin. The study demonstrated that UVB markedly caused skin senescence in Balb/c mice, while SAHA effectively mitigated the changes induced by UVB irradiation. Mechanistically, we found that UVB activated the mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) signaling pathways, whereas SAHA inhibited the upregulation of both mTOR and NF-κB. In summary, these findings suggest that SAHA may protect against UVB-induced cellular senescence and skin photoaging by inhibiting the mTOR and NF-κB signaling pathways. Therefore, SAHA could be a potential anti-senescence agent for mitigating skin photoaging.

Chronic obstructive pulmonary disease (COPD) is associated with a substantial economic burden in the UK. Although previous analyses have compared the cost-effectiveness of single-inhaler triple therapy (SITT) versus dual therapy or multiple-inhaler triple therapy, there are no studies investigating the cost-effectiveness of individual SITTs versus other SITTs. This study assessed the cost-effectiveness of SITT with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus other SITTs for the treatment of COPD from a UK National Health Service perspective. The validated GALAXY-COPD model was populated with patient baseline characteristics from the IMPACT study and treatment effect data from a network meta-analysis, which compared FF/UMEC/VI with budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FOR; both 320 µg and 160 µg dosing; BUD320 and BUD160, respectively) and beclometasone dipropionate/formoterol fumarate/glycopyrrolate (BDP/FOR/GLY). UK healthcare resource unit and drug costs (Great British Pound, 2022) were applied, with costs and outcomes (except life years [LYs]) discounted at 3.5% annually. The base case was probabilistic (5000 iterations) with a lifetime horizon. FF/UMEC/VI provided an additional 0.620 (95% range: 0.255, 1.025) LYs and 0.283 (0.080, 0.501) quality-adjusted LYs (QALYs) with a cost saving of £1620 (£158, £3243) versus BUD320/GLY/FOR, an additional 0.627 (0.261, 1.053) LYs and 0.309 (0.097, 0.533) QALYs at a cost saving of £1721 (£261, £3345) versus BUD160/GLY/FOR, and an additional 0.328 (0.063, 0.654) LYs and 0.230 (0.035, 0.437) QALYs at a cost saving of £1221 (-£541, £2796) versus BDP/FOR/GLY. FF/UMEC/VI was less costly and showed higher QALYs in 98.2%, 98.9%, and 93.6% of simulations versus BUD360/GLY/FOR, BUD160/GLY/FOR, and BDP/FOR/GLY, respectively. At a willingness-to-pay threshold of £20,000 per QALY, the probability of FF/UMEC/VI being cost-effective was 99.9%, 100%, and 99.3% versus BUD320/GLY/FOR, BUD160/GLY/FOR, and BDP/FOR/GLY, respectively. Based on this analysis, FF/UMEC/VI is a dominant (improved outcomes with cost savings) treatment option compared with other SITTs for the treatment of patients with COPD in the UK.

In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high‐dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high‐dose irradiation‐induced damage to the surrounding normal tissues and the difficulty in distant metastasis control. To break these restraints, a gelatinase‐responsive amphiphilic methoxypolyethyleneglycol–PVGLIG–polycaprolactone (mPEG–PVGLIG–PCL) nanoparticles’ loading verteporfin (N@VP), a special photosensitizer that can also be excited by X‐rays to produce cytotoxic singlet oxygen and greatly enhance radiotherapy efficacy, is prepared in this study. Herein, it is shown that the formed N@VP combined with conventional‐dose radiation therapy (RT, 2 Gy (gray, a radiation dose unit)) can realize an antitumor effect no less than high‐dose RT (8 Gy) and minimize radiation dose necessary to achieve local tumor control. Moreover, this radiosensitive nanosystem can exert excellent systemic antitumor immunity and abscopal effect, providing a preferable “in situ vaccine” strategy based on conventional‐dose RT to achieve efficient systemic management of distant tumor metastasis. When combined with immunotherapy, this novel strategy for radiosensitization results in better immunotherapy sensitivity by stimulating significant immunogenic tumor cell death and synergistic antitumor immune responses. Here gelatinase‐responsive methoxypolyethyleneglycol–PVGLIG–polycaprolactone (mPEG–PVGLIG–PCL) nanoparticles’ loading verteporfin (N@VP) is developed, enhancing radiotherapy via X‐ray‐triggered singlet oxygen generation. Combined with 2 Gy (gray, a radiation dose unit) irradiation, N@VP achieves antitumor efficacy comparable to 8 Gy, and also promotes systemic antitumor immunity, abscopal effects, and synergizes with immunotherapy by inducing tumor cell pyroptosis, offering a more advantageous radiosensitization strategy for metastatic control based on conventional‐dose radiotherapy.

Background: Metagenomic sequencing has the potential to identify a wide range of pathogens in human tissue samples. Sarcoidosis is a complex disorder whose etiology remains unknown and for which a variety of infectious causes have been hypothesized. We sought to conduct metagenomic sequencing on cases of ocular and periocular sarcoidosis, none of them with previously identified infectious causes. Methods: Archival tissue specimens of 16 subjects with biopsies of ocular and periocular tissues that were positive for non-caseating granulomas were used as cases. Four archival tissue specimens that did not demonstrate non-caseating granulomas were also included as controls. Genomic DNA was extracted from tissue sections. DNA libraries were generated from the extracted genomic DNA and the libraries underwent next-generation sequencing. Results: We generated between 4.8 and 20.7 million reads for each of the 16 cases plus four control samples. For eight of the cases, we identified microbial pathogens that were present well above the background, with one potential pathogen identified for seven of the cases and two possible pathogens for one of the cases. Five of the eight cases were associated with bacteria ( Campylobacter concisus, Neisseria elongata, Streptococcus salivarius, Pseudopropionibacterium propionicum, and Paracoccus yeei), two cases with fungi ( Exophiala oligosperma, Lomentospora prolificans and Aspergillus versicolor) and one case with a virus (Mupapillomavirus 1). Interestingly, four of the five bacterial species are also part of the human oral microbiome. Conclusions: Using a metagenomic sequencing we identified possible infectious causes in half of the ocular and periocular sarcoidosis cases analyzed. Our findings support the proposition that sarcoidosis could be an etiologically heterogenous disease. Because these are previously banked samples, direct follow-up in the respective patients is impossible, but these results suggest that sequencing may be a valuable tool in better understanding the etiopathogenesis of sarcoidosis and in diagnosing and treating this disease.

We sequenced the genome of the North American groundhog, Marmota monax, also known as the woodchuck. Our sequencing strategy included a combination of short, high-quality Illumina reads plus long reads generated by both Pacific Biosciences and Oxford Nanopore instruments. Assembly of the combined data produced a genome of 2.74 Gbp in total length, with an N50 contig size of 1,094,236 bp. To annotate the genome, we mapped the genes from another M. monax genome and from the closely related Alpine marmot, Marmota marmota, onto our assembly, resulting in 20,559 annotated protein-coding genes and 28,135 transcripts. The genome assembly and annotation are available in GenBank under BioProject PRJNA587092.

As a fundamental and critical task in multi-source image fusion, the registration of optical image and synthetic aperture radar (SAR) image can identify corresponding identical or similar structures from two heterogeneous images. Although Pseudo Siamese network has achieved notable success in matching heterogeneous images, the network prone to mismatch when there are blurred, duplicate or similar scenes appeared in the search image. To improve the performance, in this paper, the OPT-to-SAR image pair is cut into sub-patch pairs through a pre-defined sliding window. Then a two-stage image filtering mechanism is proposed to maintain candidate sub-patches with ideal texture information. After sending all the qualified sub-patch pairs into the Pseudo Siamese network, the final matching result will be passed through a RANSAC module. In this way, the interference from invalid image areas can be reduced and the model robustness can be ensured by using the statistic information of the whole image pair. A series of experiments conducted under various data scenarios proved the effectiveness of the method.

Since the traditional CFAR algorithm is not suitable for high-resolution target detection of synthetic aperture radar (SAR) images, a new two-stage target detection method based on variance weighted information entropy is proposed in this paper. On the first stage, the regions of interest (ROIs) in SAR image is extracted based on the variance weighted information entropy (WIE), which has been proved to be a simple and effective quantitative description index for the complex degree of infrared image background. Considering that SAR images are nonuniform, an experiment is conducted ahead, in which the value of the variance WIE from a real SAR image in three areas with significant different uniform levels are tested and compared. The results preliminarily verified that the variance WIE is able to measure the complex degree of SAR images. After that, in order to make the segmentation efficient, the rough ROIs are further processed with a series of methods which adjust ROIs into regular pieces. On the second stage, for each of the ROIs, a variational segmentation algorithm based on the Split-Bregman algorithm is adopted to extract the target. In our experiment, the proposed method is tested on two kinds of SAR images, and its effectiveness is successfully demonstrated.

Since the traditional CFAR algorithm is not suitable for high-resolution target detection of synthetic aperture radar (SAR) images, a new two-stage target detection method based on variance weighted information entropy is proposed in this paper. On the first stage, the regions of interest (ROIs) in SAR image is extracted based on the variance weighted information entropy (WIE), which has been proved to be a simple and effective quantitative description index for the complex degree of infrared image background. Considering that SAR images are nonuniform, an experiment is conducted ahead, in which the value of the variance WIE from a real SAR image in three areas with significant different uniform levels are tested and compared. The results preliminarily verified that the variance WIE is able to measure the complex degree of SAR images. After that, in order to make the segmentation efficient, the rough ROIs are further processed with a series of methods which adjust ROIs into regular pieces. On the second stage, for each of the ROIs, a variational segmentation algorithm based on the Split-Bregman algorithm is adopted to extract the target. In our experiment, the proposed method is tested on two kinds of SAR images, and its effectiveness is successfully demonstrated.[PUBLICATION ABSTRACT]