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ABSTRACT Many Gram-negative bacteria deploy a type VI secretion system (T6SS) to inject toxins into target cells to promote their survival and replication in complex environments. Here, we report that Acinetobacter baumannii uses its T6SS to kill fungi and that the effector TafE (ACX60_15365) is responsible for such killing. Although ectopically expressed TafE is toxic to both Escherichia coli and Saccharomyces cerevisiae, deletion of tafE only affects the antifungal activity of A. baumannii. We demonstrate that TafE is a DNase capable of targeting the nuclei of yeast cells and that an Ntox15 domain is essential for its ability to degrade DNA. Furthermore, our findings show that A. baumannii is protected from the toxicity of TafE by elaborating the immunity protein TaeI (ACX60_15360), which antagonizes the activity of the effector by direct binding. The discovery of A. baumannii T6SS effectors capable of killing multiple taxonomically distinct microbes has shed light on a mechanism of the high-level fitness of this pathogen in environments characterized by scarce nutrients and the potential presence of diverse microorganisms. IMPORTANCE Acinetobacter baumannii is an increasing important nosocomial pathogen that is difficult to combat due to its ability to survive in harsh environments and the emergence of isolates that are resistant to multiple antibiotics. A better understanding of the mechanism underlying the toughness of A. baumannii may identify its Achilles’ heel, which will facilitate the development of novel preventive and treatment measures. In this study, our findings show that A. baumannii kills fungi with the DNase effector TafE injected into competitor cells by its type VI secretion system. A. baumannii is protected from the activity of TafE by the immunity protein TaeI, which inactivates the effector by direct binding. Our results suggest that inactivation of its T6SS or effectors may reduce the fitness of A. baumannii and increase the effectiveness of treatment by means such as antibiotics. Furthermore, our finding suggests that targeted degradation of TaeI may be an effective strategy to kill A. baumannii.

Abstract Background The clinical features, survival outcomes and patterns of treatment failure of advanced non-small cell lung cancer (NSCLC) patients harboring distinct subtypes of EGFR mutations and receiving first-line EGFR tyrosine kinases inhibitor (TKIs) are not fully understood. Methods Consecutive metastatic EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs from October 2010 to March 2020 were enrolled and classified into two main groups based on the EGFR mutation subtypes: common mutation (L858R or exon 19 deletion), uncommon mutation (other EGFR mutations). Results Of the 1081 patients included, 74 (6.8%) harbored uncommon mutations. The baseline characteristics were generally balanced between the two groups, except that bone metastasis developed less frequently in patients with uncommon mutations (p = 0.02). No significant difference of survival outcomes was found between the two groups, except that among patients with baseline brain metastasis, the intracranial time to progression was significantly shorter in patients with uncommon mutations. Nine of the 17 patients with de novo T790M mutation received Osimertinib, whose overall survival tended to be longer than the remaining 8 patients without Osimertinib treatment (p = 0.08). The patterns of treatment failure were generally consistent between the two groups, except which patients with uncommon mutations had a higher risk developing progressive disease in the brain. Conclusion First-line EGFR-TKIs seemed to be less effective in controlling and preventing brain metastasis in patients with uncommon EGFR mutations and Osimertinib was associated with promising efficacy in patients with de novo T790M mutation, which warranted further validation.

Purpose: Lung adenocarcinoma (LUAD) is a highly lethal subtype of primary lung cancer with a poor prognosis. N6-methyladenosine (m6A), the most predominant form of RNA modification, regulates biological processes and has critical prognostic implications for LUAD. Our study aimed to mine potential target genes of m6A regulators to explore their biological significance in subtyping LUAD and predicting survival. Methods: Using gene expression data from TCGA database, candidate target genes of m6A were predicted from differentially expressed genes (DEGs) in tumor based on M6A2 Target database. The survival-related target DEGs identified by Cox-regression analysis was used for consensus clustering analysis to subtype LUAD. Uni-and multi-variable Cox regression analysis and LASSO Cox-PH regression analysis were used to select the optimal prognostic genes for constructing prognostic score (PS) model. Nomogram encompassing PS score and independent prognostic factors was built to predict 3-year and 5-year survival probability. Results: We obtained 2429 DEGs in tumor tissue, within which, 1267 were predicted to m6A target genes. A prognostic m6A-DEGs network of 224 survival-related target DEGs was established. We classified LUAD into 2 subtypes, which were significantly different in OS time, clinicopathological characteristics, and fractions of 12 immune cell types. A PS model of five genes (C1QTNF6, THSD1, GRIK2, E2F7 and SLCO1B3) successfully split the training set or an independent GEO dataset into two subgroups with significantly different OS time (p < 0.001, AUC = 0.723; p = 0.017, AUC = 0.705).A nomogram model combining PS status, pathologic stage, and recurrence was built, showing good performance in predicting 3-year and 5-year survival probability (C-index = 0.708, 0.723, p-value = 0). Conclusion: Using candidate m6A target genes, we obtained two molecular subtypes and designed a reliable five-gene PS score model for survival prediction in LUAD.

The present paper aims at using an artificial intelligence algorithm to minimize the fan power consumption in air-cooled servers. The proposed algorithm can handle the complex thermal environments within the servers to tailor the influences and interactions amid numerous heat sources, airflow, bypass phenomenon, fan operation, and the transient operations. Modified correlations are first proposed to effectively predict the thermal-hydraulic performance of heat sinks and the corresponding predictive ability against Nusselt number and pressure drop is within 5.0% and 10%, respectively. Without the algorithm control, the maximum deviation between the prediction and the experimental data is within 2.0 °C. By introducing the deep reinforcement learning (DRL) algorithm subject to the interactions of complex thermal environments, the fan power consumption can be saved by 55.7%, 40.3% and 26.3%, respectively, in comparison with the strategy with 100% fan duty. Yet the DRL agent still offers 16.7% energy saving when compared to a fixed 40% fan duty.

Background and aimsMethamphetamine (MA) is a psychostimulant associated with a high relapse rate among patients with MA use disorder (MUD). Long-term use of MA is associated with mental disorders, executive dysfunction, aggressive behaviors, and impulsivity among patients with MUD. However, identifying which factors may be more closely associated with relapse has not been investigated. Thus, we aimed to investigate the psychological factors and the history of MA use that may influence MA relapse.MethodsThis cross-sectional study included 168 male MUD patients (MUD group) and 65 healthy male residents (control group). Each patient was evaluated with self-report measures of executive dysfunction, psychopathological symptoms, impulsiveness, aggressiveness, and history of MA use. Data were analyzed with t-tests, analyses of variance, and correlation and regression analyses.ResultsThe MUD group reported greater executive dysfunction, psychopathological symptoms, impulsivity, and aggression than the control group. Lower age of first MA use was associated both with having relapsed one or more times and with having relapsed two or more times; greater executive dysfunction was associated only with having relapsed two or more times.ConclusionPatients with MUD reported worse executive function and mental health. Current results also suggest that lower age of first MA use may influence relapse rate in general, while executive dysfunction may influence repeated relapse in particular. The present results add to the literature concerning factors that may increase the risk of relapse in individuals with MUD.

Amid rising market competitiveness, Industry Revolution (IR) 4.0 oriented technological integration is considered an imperative driver of sustainable organizational performances and green supply chain management. This study explores the role of IR 4.0 powered process technology innovation in enhancing Leanness, Green Supply Chain Management, and Organizational Performance (including operational, economic, and environmental) during COVID-19. For this purpose, a novel conceptual framework was developed, and Partial Least Square-Structural Equation Modelling (PLSM) was employed on primary data of 314 respondents collected from Chinese manufacturing industries. Moreover, Multi-Group Analysis was also implemented to compare firms’ willingness to implement IR 4.0 technologies powered process innovation. The results exhibit that Green IR 4.0 powered process technology innovation improves firm’s leanness and stimulates environmental, optional, and economic performances. Similar findings are endorsed through the green supply chain management channel. Manifestly, COVID-19 instigated firms to adopt IR 4.0-based technological processes for efficient supply chain management. Based on these results, organizations are recommended to integrate IR 4.0 induced technology innovation to spur manufacturing firms’ eco-economic and operational performance.

ABSTRACT Globally dominant marine bacterioplankton lineages are often limited in metabolic versatility, owing to their extensive genome reductions, and thus cannot take advantage of transient nutrient patches. It is therefore perplexing how the nutrient-poor bulk seawater sustains the pelagic streamlined lineages, each containing numerous populations. Here, we sequenced the genomes of 33 isolates of the recently discovered CHUG lineage (~2.6 Mbp), which have some of the smallest genomes in the globally abundant Roseobacter group (commonly over 4 Mbp). These genome-reduced bacteria were isolated from a transient habitat: seawater surrounding the brown alga, Sargassum hemiphyllum. Population genomic analyses showed that: (i) these isolates, despite sharing identical 16S rRNA genes, were differentiated into several genetically isolated populations through successive speciation events; (ii) only the first speciation event led to the genetic separation of both core and accessory genomes; and (iii) populations resulting from this event are differentiated at many loci involved in carbon utilization and oxygen respiration, corroborated by BiOLOG phenotype microarray assays and oxygen uptake kinetics experiments, respectively. These differentiated traits match well with the dynamic nature of the macroalgal seawater, in which the quantity and quality of carbon sources and the concentration of oxygen likely vary spatially and temporally, though other habitats, like fresh organic aggregates, cannot be ruled out. Our study implies that transient habitats in the overall nutrient-poor ocean can shape the microdiversity and population structure of genome-reduced bacterioplankton lineages. IMPORTANCE Prokaryotic species, defined with operational thresholds, such as 95% of the whole-genome average nucleotide identity (ANI) or 98.7% similarity of the 16S rRNA gene sequences, commonly contain extensive fine-grained diversity in both the core genome and the accessory genome. However, the ways in which this genomic microdiversity and its associated phenotypic microdiversity are organized and structured is poorly understood, which disconnects microbial diversity and ecosystem functioning. Population genomic approaches that allow this question to be addressed are commonly applied to cultured species because linkages between different loci are necessary but are missing from metagenome-assembled genomes. In the past, these approaches were only applied to easily cultivable bacteria and archaea, which, nevertheless, are often not representative of natural communities. Here, we focus on the recently discovered cluster, CHUG, which are representative in marine bacterioplankton communities and possess some of the smallest genomes in the globally dominant marine Roseobacter group. Despite being over 95% ANI and identical in the 16S rRNA gene, the 33 CHUG genomes we analyzed have undergone multiple speciation events, with the first split event predominantly structuring the genomic diversity. The observed pattern of genomic microdiversity correlates with CHUG members’ differential utilization of carbon sources and differential ability to explore low-oxygen niches. The available data are consistent with the idea that brown algae may be home to CHUG, though other habitats, such as fresh organic aggregates, are also possible.

Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present study, a homogeneous exopolysaccharide from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ1-1, was obtained. The results of chemical and spectroscopic analyses showed that PJ1-1 was a novel galactomannan with a molecular weight of about 10.24 kDa. The backbone of PJ1-1 was composed of →2)-α-d-Manp-(1→, →4)-α-d-Manp-(1→, →3)-β-d-Galf-(1→ and →2)-β-d-Galf-(1→ units with partial glycosylation at C-3 of →2)-β-d-Galf-(1→ unit. PJ1-1 had a strong hypoglycemic activity in vitro, evaluated using the assay of α-glucosidase inhibition. The anti-diabetic effect of PJ1-1 in vivo was further investigated using mice with type 2 diabetes mellitus induced by a high-fat diet and streptozotocin. The results indicated that PJ1-1 markedly reduced blood glucose level and improved glucose tolerance. Notably, PJ1-1 increased insulin sensitivity and ameliorated insulin resistance. Moreover, PJ1-1 significantly decreased the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, enhanced the level of serum high-density lipoprotein cholesterol and alleviated dyslipidemia. These results revealed that PJ1-1 could be a potential source of anti-diabetic agent.

Objectives To evaluate whether curettage with adjuvant microwave therapy was successful in the treatment of giant cell tumor of the bone (GCTB) in extremities, especially for GCTB with pathological fractures and GCTB of the distal radius. Methods This was a retrospective study of 54 cases of GCTB of the extremities treated by curettage with adjuvant microwave therapy between 2007 and 2019. Five patients were lost to follow up and excluded from the study. A total of 33 male and 21 female patients were included in this study. Patients were aged 15–57 years (mean 29.72 ± 10.48 years). Among these patients, there were 10 cases of GCTB with pathological fractures and eight cases of GCTB of the distal radius; one of these cases was combined with a pathological fracture. Comprehensive imaging examinations (X‐rays [including lesion site and chest], CT, MRI, emission computed tomography, and pathology examination) of all patients were reviewed. The clinical staging of these patients were evaluated radiologically using the Campanacci classification system based on the extent of spread of the tumor. All patients underwent curettage with adjuvant microwave therapy. Clinical and imaging evaluations were performed in all cases to check for recurrence or metastasis. Lower limb and upper limber function were assessed using the Musculoskeletal Tumor Society score (MSTS), and wrist function was assessed according to the disabilities of the arm, shoulder and hand (DASH) score. Data on surgical‐related complications were recorded. Results All cases were followed up for 24–126 months (mean 60.69 ± 29.61 months). There were 24 patients with a Campanacci grade of 3 and 30 with a Campanacci grade of 2. The 52 patients were continuously disease‐free. The local recurrence rate was 3.70% (2 patients). One patient had recurrence in the proximal femur, and the other developed in soft tissue of the calf muscle. No recurrence occurred for GCTB of the distal radius. One recurrence occurred in a GCTB with pathological fractures. The intervals were 9 and 28 months, respectively. The cases of recurrence all had a Campanacci grade of 3 (8.33%). The median MSTS among the 54 patients was 27.67 ± 3.81. The mean wrist function DASH score was 8.30 ± 2.53. The mean MSTS was 28.67 ± 1.63 and 26.71 ± 5.49 for patients with GCTB of the distal radius and for those with pathological fractures, respectively. In comparing patients with and without pathological fractures, there was no significant difference in the MSTS functional score. Five patients had complications after the surgery. Conclusion Curettage with adjuvant microwave ablation therapy provided favorable local control and satisfactory functional outcomes in the treatment of GCTB, especially for cases with pathological fractures and those with GCTB of the distal radius.

Background Recurrence is a risk factor for the prognosis of lung squamous carcinoma (LUSC). DNA methylation levels of RNAs are also associated with LUSC prognosis. This study aimed to construct a prognostic model with high performance in predicting LUSC prognosis using the methylation levels of lncRNAs and genes. Methods The differentially expressed RNAs (DERs) and differentially methylated RNAs (DMRs) between the recurrent and non-recurrent LUSC tissues in The Cancer Genome Atlas (TCGA; training dataset) were identified. Weighted correlation network analysis was performed to identify co-methylation networks. Differentially methylated genes and lncRNAs with opposite expression-methylation levels were used for the screening of prognosis-associated RNAs. The prognostic model was constructed and its performance was validated in the GSE39279 dataset. Results A total of 664 DERs and 981 DMRs (including 972 genes) in recurrent LUSC tissues were identified. Three co-methylation modules, including 226 differentially methylated genes, were significantly associated with LUSC. Among prognosis-associated RNAs, 18 DERs/DMRs with opposite methylation-expression levels were included in the methylation prognostic risk model. LUSC patients with high risk scores had a poor prognosis compared with patients who had low risk scores (TCGA: HR = 3.856, 95% CI [2.297–6.471]; GSE39279: HR = 3.040, 95% CI [1.435–6.437]). This model had a high accuracy in predicting the prognosis (AUC = 0.903 and 0.800, respectively), equivalent to the nomogram model inclusive of clinical variables. Conclusions Referring to the methylation levels of the 16-RNAs might help to predict the survival outcomes in LUSC.

IntroductionWe evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT in the detection of hilar lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) to determine their value in guiding hilar lymph node staging and delineating radiation target volume.MethodsConsecutive patients with ESCC who underwent both PET/CT and contrast-enhanced CT before radical lymphadenectomy and esophagectomy at our institution from September 2009 to November 2018 were enrolled. The sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of FDG-PET/CT and contrast-enhanced CT for diagnosing hilar LNM were calculated.ResultsOf the 174 patients included, contrast-enhanced CT predicted nine positive cases, while PET/CT predicted one, and eight (4.6%) were identified as pathologically positive for their resected hilar lymph nodes. The SE, SP, PPV, and NPV of PET/CT and contrast-enhanced CT were 0.000, 0.994, 0.000, and 0.954; and 0.125, 0.952, 0.111, and 0.958, respectively. The specificity showed a significant difference (P=0.037). PET/CT is slightly more specific than contrast-enhanced CT.ConclusionsPET/CT and contrast-enhanced CT may be useful tools for predicting the negativity of hilar LN status, but they are not recommended for guiding the hilar lymph node staging and the delineating of hilar LNM in radiotherapy planning of ESCC patients based on their low PPV.

Abstract Background Liver cancer (LC) is one of the most fatal cancers throughout the world. More efficient and sensitive gene signatures that could accurately predict survival in LC patients are vitally needed to promote a better individualized and effective treatment. Material/methods 422 LC and adjacent normal tissues with both RNA-Seq and clinical data in TCGA were embedded in our study. Gene set enrichment analysis (GSEA) was applied to identify genes and hallmark gene sets that are more valuable for liver cancer therapy. Cox regression analysis was used to identify genes related to overall survival (OS) and build the prediction model. cBioPortal database was used to examine the alterations of the panel mRNA signature. ROC curves and Kaplan–Meier curves were used to validate the prediction model. Besides, the expression of the genes in the model were validated using quantitative real-time PCR in clinical tissue specimens. Results The panel of DNA repair-related mRNA signature consisted of seven mRNAs: RFC4 (replication factor C subunit 4), ZWINT (ZW10 interacting kinetochore protein), UPF3B (UPF3B regulator of nonsense mediated mRNA decay), NCBP2 (nuclear cap binding protein subunit 2), ADA (adenosine deaminase), SF3A3 (splicing factor 3a subunit 3) and GTF2H1 (general transcription factor IIH subunit 1). On-line analysis of cBioPortal database found that the expression of the panel mRNA has a wide variation ranging from 7 to 10%. All the mRNAs were significantly upregulated in LC tissues compared to normal tissues (P

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80–0.89) and 0.80 (95% confidence interval: 0.71–0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044–1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM.

CP symmetry violation is one of the fundamental requirements for having more matter than antimatter in our universe. However, the observed CP violation is not enough to explain the matter dominance. Searching for the new CP violation in the hyperon sector is therefore attracting people’s interests. In this article, we review the theoretical description of the spin one-half hyperon nonleptonic decay. In order to test the CP conservation, the asymmetry decay parameters might be compared between hyperon and antihyperon. The fixed-target experiments achieved the relevant measurements of the hyperon parameters but in the absence of the antihyperon results. The BESIII experiment with e+e− collision provided an entanglement environment to measure Σ+ and Σ¯− simultaneously. The important role of experimental inputs in CP violation evaluation is discussed in this paper, underlying the great potential of the future collider, which may allow us to reach the precision of the Standard Model predictions.

Purpose: To explore the clinical characteristics, management, and survival outcomes of advanced NSCLC patients treated with PD-1/PD-L1 inhibitors who presented with an atypical response (AR). Methods: A total of 926 PD-1/PD-L1-inhibitor-treated patients with metastatic NSCLC from three academic centers were retrospectively reviewed. All measurable lesions were evaluated by RECIST version 1.1. Results: Fifty-six (6.1%) patients developed AR. The median time to the occurrence of AR was 2.0 months. Patients with no fewer than 3 metastatic organs at baseline were more prone to develop AR in advanced NSCLC (p = 0.038). The common sites of progressive lesions were lymph nodes (33.8%) and lungs (29.7%). The majority (78.2%) of patients with AR had only 1–2 progressive tumor lesions, and most (89.1%) of the progressive lesions developed from originally existing tumor sites. There was no significance in terms of survival between patients with AR and those with typical response (TR). Local therapy was an independent predictor for PFS of patients with AR (p = 0.025). Conclusions: AR was not an uncommon event in patients with metastatic NSCLC treated with PD-1/PD-L1 inhibitors, and it had a comparable prognosis to those with TR. Proper local therapy targeting progressive lesions without discontinuing original PD-1/PD-L1 inhibitors may improve patient survival.

In recent years, global automotive industries are going through a significant revolution from traditional internal combustion engine vehicles (ICEVs) to electric vehicles (EVs) for CO2 emission reduction. Very similarly, the aviation industry is developing towards more electric aircraft (MEA) in response to the reduction in global CO2 emission. To promote this technology revolution and performance advancement, plenty of electronic devices with high heat flux are implemented on board automobiles and aircraft. To cope with the thermal challenges of electronics, in addition to developing wide bandgap (WBG) semiconductors with satisfactory electric and thermal performance, providing proper thermal management solutions may be a much more cost-effective way at present. This paper provides an overview of the thermal management technologies for electronics used in automobiles and aircraft. Meanwhile, the active methods include forced air cooling, indirect contact cold plate cooling, direct contact baseplate cooling, jet impingement, spray cooling, and so on. The passive methods include the use of various heat pipes and PCMs. The features, thermal performance, and development tendency of these active and passive thermal management technologies are reviewed in detail. Moreover, the environmental influences introduced by vibrations, shock, acceleration, and so on, on the thermal performance and reliability of the TMS are specially emphasized and discussed in detail, which are usually neglected in normal operating conditions. Eventually, the possible future directions are discussed, aiming to serve as a reference guide for engineers and promote the advancement of the next-generation electronics TMS in automobile and aircraft applications.

Background: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. Objective: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. Methods: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non‐EDS group (score < 10). The Jaw Functional Limitation Scale 8‐item (JFLS‐8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7‐item (GAD‐7) and the Patient Health Questionnaire 9‐item (PHQ‐9). All included patients were diagnosed with pain‐related TMD (PT), intra‐articular TMD (IT) or combined TMD (CT). Results: Compared with non‐EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ‐9 scores (p <.05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD‐7 score (B = 0.73) were significantly associated with an increased score on the JFLS‐8 (p <.05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p =.007). Conclusion: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype. [ABSTRACT FROM AUTHOR]

Starting from the molecular picture for the D s 1 (2460) and D s 1 (2536) resonances, which are dynamically generated by the interaction of coupled channels, the most important of which are the D ∗ K for the D s 1 (2460) and D K ∗ for the D s 1 (2536) , we evaluate the ratio of decay widths for the B ¯ s 0 → D s 1 (2460) + K - and B ¯ s 0 → D s 1 (2536) + K - decays, the latter of which has been recently investigated by the LHCb collaboration, and we obtain a ratio of the order of unity. The present results should provide an incentive for the related decay into the D s 1 (2460) resonance to be performed, which would provide valuable information on the nature of these two resonances. [ABSTRACT FROM AUTHOR]

Abstract Background There was no study investigating real-world utilization and outcome of LCT in Osimertinib-treated NSCLC with oligo-residual disease. This study was to analyze the clinical value of local consolidative therapy (LCT) in Osimertinib-treated non-small cell lung cancer (NSCLC) patients with oligo-residual disease. Methods Patients receiving standard Osimertinib treatment and developing oligo-residual disease (five or fewer residual metastatic lesions) were retrospectively reviewed. Local therapies performed to the oligo-residual tumor lesions or primary lung site before Osimertinib treatment failure were considered as LCT. Results Of 108 patients recruited, first-line and second-line Osimertinib were administered in 25 and 83 patients, respectively, while LCT was performed in 14 patients. With a median follow-up of 43.6 months, 69 patients developed progressive disease. LCT significantly improved progression-free survival (PFS) (NR vs 12.8 months, p = 0.01) and was independently associated with prolonged PFS (HR = 0.29, 95%CI 0.12 to 0.68, p = 0.004). Patients receiving LCT had a numerically longer overall survival (OS) (85.8 vs 77.1 months, p = 0.58) and after adjusting for potentially confounding factors, LCT was associated with a non-significantly prolonged OS (HR = 0.37, 95%CI 0.12–1.16, p = 0.089). Pattern of failure analyses indicated that progressive disease developed at the originally existed oligo-residual lesions in 76.2% of the 63 patients who didn’t receive LCT and had Osimertinib treatment failure. Of note, 7 (70%) of the 10 patients who had oligo-residual cranial disease but didn’t receive LCT, developed more than five progressive lesions in the brain, which were no longer suitable for stereotactic radiosurgery. Conclusion Among Osimertinib-treated NSCLC patients having oligo-residual lesions, LCT could improve local control and significantly increase PFS, which need to be verified by further investigations.

Abstract Background Prophylactic cranial irradiation (PCI) is indicated for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy (CRT). However, brain metastasis (BM) developed in LS-SCLC before PCI is not rare. In this study, we comprehensively investigated the features of pre-PCI BMs, aiming to explore the potential of PCI optimization for LS-SCLC. Methods One-hundred-ten LS-SCLC patients achieving clinical complete remission after definitive CRT with contrast-enhanced cranial magnetic resonance imaging (MRI) at baseline and immediately before PCI were included. The time trend and risk factors for pre-PCI BM were evaluated. Several radiological features, including numbers, sizes, and locations of pre-PCI BMs, were investigated to explore the technical feasibility of stereotactic radiotherapy and hippocampal-avoidance (HA) PCI. Results Twenty-four (21.8%) of the LS-SCLC patients harbored pre-PCI BM, all except one were asymptomatic. CRT duration (CRT-D) was the only independent risk factor for pre-PCI BM. The pre-PCI BM rate gradually increased in line with a growing time interval between treatment initiation and pre-PCI MRI. Pre-PCI BM and prolonged CRT-D were both correlated with worse overall survival. Of 129 pre-PCI intracranial lesions, 2 (1.5%) were in the HA region. Eight of the 24 (33.3%) pre-PCI BM patients were ineligible for stereotactic radiotherapy. Conclusion Our findings suggest that PCI is still of importance in LS-SCLC, and MRI evaluation before PCI is indispensable. Investigations are warranted to explore the possibility of moving PCI up to before CRT completion in LS-SCLC patients with prolonged CRT-D. HA-PCI could be considered to reduce neurotoxicity.

Abstract Background Follicular dendritic cell sarcoma (FDCS) is a rare malignancy. In addition to the classical histopathologic features, it has also some special morphological variants that can present a challenge in the diagnosis of this disease. Case presentation A 45-year-old male who presented with a left supraclavicular mass was given a final diagnosis of FDCS after lymph node biopsy. The specimen obtained during radical resection revealed five different morphologies, including the classical histological appearance and atypical areas resembling desmoplastic infiltrative carcinoma, anaplastic large cell lymphoma (ALCL), hemangiopericytoma and classical Hodgkin’s lymphoma (CHL). Immunohistochemistry was notable for positive CD21 and CD23 expression across all morphologies. Given the atypical appearance and location, the specimen was initially misdiagnosed as a metastatic carcinoma based on histology alone at an outside institution. The patient eventually underwent surgical resection followed by adjuvant chemotherapy and radiation. Despite treatment, the disease progressed, and the patient passed away 36 months after surgery. Conclusions This unusual case of FDCS contains four types of atypical histomorphologies within a single tumor specimen, including those resembling ALCL and hemangiopericytoma which are described here for the first time. Our report further expands the histopathologic spectrum of FDCS and may help assist in the diagnosis of other such challenging cases.

Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by water extraction, anion-exchange, and size-exclusion chromatography purification, and its structure was characterized by a combination of chemical and spectroscopic methods. UCP mainly consisted of →4)-α/β-l-Rhap-(1→, →4)-β-d-Xylp-(1→ and →4)-β-d-GlcAp-(1→ residues. Sulfate ester groups were substituted mainly at C-3 of →4)-l-Rhap-(1→ and C-2 of →4)-β-d-Xylp-(1→. Partial glycosylation was at C-2 of →4)-α-l-Rhap-(1→ residues. UCP possessed a potent immunomodulatory effect in vitro, evaluated by the assays of lymphocyte proliferation and macrophage phagocytosis. The immunomodulatory activity of UCP in vivo was further investigated using immunosuppressive mice induced by cyclophosphamide. The results showed that UCP markedly increased the spleen and thymus indexes and ameliorated the cyclophosphamide-induced damage to the spleen and thymus. UCP could increase the levels of white blood cells, lymphocytes, and platelets, and improve the hematopoietic inhibition caused by cyclophosphamide. Moreover, UCP significantly promoted the secretions of the immunoglobulin (Ig)G, IgE, and IgM. The data demonstrated that UCP is a novel sulfated polysaccharide and may be a promising immunomodulatory agent.