Search

This research proposes a low-cost system consisting of a hardware setup and a deep learning-based model to estimate broiler chickens’ feed intake, utilizing audio signals captured by piezoelectric sensors. The signals were recorded 24/7 for 19 consecutive days. A subset of the raw data was chosen, and events were labeled in two classes, feed-pecking and non-pecking (including singing, anomaly, and silence samples). Next, the labeled data were preprocessed through a noise removal algorithm and a band-pass filter. Then, the spectrogram and the signal envelope were extracted from each signal and fed as inputs to a VGG-16-based convolutional neural network (CNN) with two branches for 1D and 2D feature extraction followed by a binary classification head to classify feed-pecking and non-pecking events. The model achieved 92% accuracy in feed-pecking vs. non-pecking events classification with an f1-score of 91%. Finally, the entire raw dataset was processed utilizing the developed model, and the resulting feed intake estimation was compared with the ground truth data from scale measures. The estimated feed consumption showed an 8 ± 7% mean percent error on daily feed intake estimation with a 71% R2 score and 85% Pearson product moment correlation coefficient (PPMCC) on hourly intake estimation. The results demonstrate that the proposed system estimates broiler feed intake at each feeder and has the potential to be implemented in commercial farms.

The distribution of adipose tissue plays a crucial role in the progression of lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH). This study was performed to explore the longitudinal association between the lipid accumulation product index (LAPI) and LUTS/BPH. Based on logistic and restricted cubic spline (RCS) regressions, data from the China Health and Retirement Longitudinal Study were used to evaluate the odds ratio (OR) and non-linear correlation between LAPI and LUTS/BPH. Subgroup and interactive analyses were adopted to determine the interactive effects of covariates. In addition, a 7-year retrospective cohort from 2011–2018 was constructed to investigate the longitudinal association. After data cleansing, this study included 3967 males aged >40 years in 2011. In the full model, high LAPI was significantly associated with prevalent LUTS/BPH (OR = 1.007; 95% CI (confidence interval): 1.001–1.013, p = 0.016). Furthermore, as a categorical variable, the ORs were 1.21 (95% CI = 0.91–1.62, p = 0.197) and 1.56 (95% CI = 1.09–2.23, p = 0.014) for the second and third tertile groups, respectively. No significant interactive effects were detected (all p for interaction > 0.05). The RCS regression revealed a linear association between LAPI and prevalent LUTS/BPH in the overall population (p for overall < 0.05) and an L-shaped association in males aged ≥60 years (p for non-linear = 0.006). In the 2011–2018 cohort, the ORs for the second and third tertile groups were 1.51 (95% CI = 1.11–2.04, p = 0.008) and 1.74 (95% CI = 1.21–2.50, p = 0.003) in the full models, respectively. All the sensitivity analyses supported similar findings. In conclusion, aging males with high LAPI have a higher risk of developing LUTS/BPH than their counterparts.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p

Abstract Background The number of migrant older adults with children (MOAC) in China has been increasing in recent years, and most of them are women. This study aimed to explore the mediating effect of social support between social integration and loneliness among the female MOAC in Jinan, China. Methods In this study, 418 female MOAC were selected using multi-stage cluster random sampling in Jinan, Shandong Province, China. Loneliness was measured by the eight-item version of the University of California Los Angeles Loneliness Scale (ULS-8), and social support was measured by The Social Support Rating Scale (SSRS). Descriptive analyses, t-tests, ANOVA, and structural equation modeling (SEM) were used to illustrate the relationship between social integration, social support, and loneliness. Results The average scores of ULS-8 and SSRS were 12.9 ± 4.0 and 39.4 ± 5.9 among female MOAC in this study. Social integration and social support were found to be negatively related to loneliness, and the standardized direct effect was -0.20 [95% CI: -0.343 to -0.068] and -0.39 [95% CI: -0.230 to -0.033], respectively. Social support mediated the relationship between social integration and loneliness, and the indirect effect was -0.16 [95% CI: -0.252 to -0.100]. Conclusion The female MOAC’s loneliness was at a relatively lower level in this study. It was found that social integration was negatively associated with loneliness, and social support mediated the relationship between them. Helping female MOAC integrate into the inflow city and improving their social support could be beneficial for alleviating their loneliness.

ABSTRACT: This study evaluated the welfare and behaviors of Cobb 700 broilers as affected by growth rate (GR) and stocking density (SD). Slower-growth (weight gain < 50 g/d) and medium-growth (weight gain = 50–60 g/d) broilers were produced by providing 57.1% and 78.6% of the feed intake listed in the Cobb 700 production manual for standard (fed ad libitum) broilers (weight gain > 60 g/d). Broilers at all 3 GRs were reared at 2 SDs of 30 and 40 kg/m2. Broiler welfare indicators, including gait score, tibia strength, feather coverage, and footpad condition were evaluated when birds reached 1, 2, and 3 kg of body weight. The activity index was determined by overhead cameras and image processing, and the time spent at feeders was recorded using the radio-frequency identification (RFID) systems. The results show that it took 45 d for standard, 52 d for medium-growth, and 62 d for slower-growth broilers to reach a 3 kg market body weight. Feed conversion ratios (FCR, kg/kg) were 1.57 for standard, 1.67 for medium-growth, and 1.80 for slower-growth broilers. Growth rate and SD had an interaction effect on feather cleanliness (P = 0.03), and belly feather coverage (P = 0.02). Slower-growth broilers were more active and had better feather coverage and gait scores than medium-growth and standard broilers (all P < 0.01) but may feel hungry and depressed, medium-growth broilers spent the most time at the feeder among the 3 growth groups (P = 0.02), and standard broilers showed the best production performance. Broilers at 30 kg/m2 showed better bone strength (P = 0.04), and footpad condition (P < 0.01) compared to those at 40 kg/m2. In conclusion, reducing GR and SD may slightly improve broiler leg health at the high expense of compromised production performance and prolonged production cycles.

ROS proto‐oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non‐small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions from 134 Chinese NSCLC patients using next‐generation sequencing (NGS). The fusions were categorized into common and uncommon based on their incidence. Our study revealed, for the first time, a unique distribution preference of breakpoints within ROS1, with common fusions occurring in introns 31–33 and uncommon fusions occurring in introns 34 and 35. Additionally, we identified previously unknown breakpoints within intron 28 of ROS1. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on ROS1, providing important insights into the molecular landscape of ROS1 fusions. We also confirmed the presence of inconsistent breakpoints in ROS1 fusions between DNA‐based NGS and RNA‐based NGS through rigorous validation methods. These inconsistencies were attributed to alternative splicing resulting in out‐of‐frame or exonic ROS1 fusions. These findings significantly contribute to our understanding of the molecular characteristics of ROS1 fusions, which have implications for panel design and the treatment of NSCLC patients with ROS1 rearrangements.

Abstract Transcriptome sequencing technologies have revolutionized the field of phylogenomics by facilitating the identification of homologous genes for species without whole genome sequences. To infer complex evolution relationship among eukaryotes, it is essential to obtain complete sequences of protein‐coding genes to provide informative mutations. However, transcriptomes in eukaryotes often consist of a large number of duplicated genes and alternative isoforms, bringing great challenges for developing effective tools to obtain complete coding gene sequences. Here, we present a net‐flow based assembler TransMCL, which aims to assemble fragmented transcripts into complete sequences while eliminating redundant isoforms during homologue clustering. By employing Markov clustering strategies and homologous gene guidance, TransMCL can accurately assemble genes for multiple organisms in an affordable time frame, making it well‐suited for phylogenomic studies based on transcriptomic data. Our results demonstrate that TransMCL can assemble 89.95%–92.95% of the total expressed genes into near‐complete transcripts on benchmark plant/animal datasets. Furthermore, applying TransMCL to multiple transcriptomes in a single run enhances the completeness of genes, even in the absence of guidance homologues from closely related species. These findings highlight the potential of TransMCL in phylogenomic studies, enabling the comprehensive characterization of gene families at the whole genome scale. By overcoming the challenges of complex gene contents in eukaryotes, TransMCL can significantly enhance our understanding of evolution of gene families across species.

Inflammatory bowel disease (IBD) is a complex group of chronic intestinal diseases, the cause of which has not yet been clarified, but it is widely believed that the disorder of the intestinal microenvironment and its related functional changes are key factors in the development of the disease. Houttuynia cordata thunb. is a traditional plant with abundant resources and long history of utilization in China, which has attracted widespread attention in recent years due to its potential in the treatment of IBD. However, its development and utilization are limited owing to the aristolochic acid alkaloids contained in it. Therefore, based on the relationship between the intestinal microenvironment and IBD, this article summarizes the potential mechanisms by which the main active ingredients of Houttuynia cordata thunb., such as volatile oils, polysaccharides, and flavonoids, and related traditional Chinese medicine preparations, such as Xiezhuo Jiedu Formula, alleviate IBD by regulating the intestinal microenvironment. At the same time, combined with current reports, the medicinal and edible safety of Houttuynia cordata thunb. is explained for providing ideas for further research and development of Houttuynia chordate thunb. in IBD disease, more treatment options for IBD patients, and more insights into the therapeutic potential of plants with homology of medicine and food in intestinal diseases, and even more diseases.

Background: Rituximab combined with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R–CHOP) regimen has improved the survival of diffuse large B-cell lymphoma (DLBCL) patients worldwide, compared with CHOP alone. Several limitations were seen in previous studies of Chinese DLBCL patients treated with R–CHOP or R-CHOP-like regimens. This study aimed to investigate the clinical characteristics and treatment outcomes of Chinese DLBCL patients treated with the standard first-line treatment. Methods: Clinical data were collected from DLBCL patients who received frontline R–CHOP or R-CHOP–like regimens at the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College (CHCAMS) between January 1, 2005, and December 31, 2018. The treatment outcomes were compared with those of patients diagnosed with DLBCL between 2004 and 2017 and who received immunochemotherapy from the United States Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis of progression-free survival (PFS) and overall survival (OS) was performed using Cox proportional hazard regression. Results: Overall, 1084 patients from the CHCAMS and 4013 patients from the SEER database were included in the study. As of April 30, 2022, the median follow-up period for the CHCAMS group was 87.3 (range: 0.5–195.4) months. For the CHCAMS group, the 5-year PFS and OS rates were 61.7% (95% confidence interval [CI]: 58.8–64.7%) and 70.6% (95% CI: 67.8–73.4%), respectively. For the SEER group, the 5-year OS rate was 66.5% (95% CI: 65.0–68.0%), which was inferior to that of the CHCAMS group (P ​

BackgroundLittle is known about the association between frailty level and medical financial hardship among older adults with cancer. This study aims to describe the prevalence of frailty and to identify its association with medical financial hardship among older cancer survivors in the United States.MethodsThe National Health Interview Survey (NHIS; 2019–2020) was used to identify older cancer survivors (n = 3,919). Both the five-item (Fatigue, Resistance, Ambulation, Illnesses, and Low weight-for-height) FRAIL and the three-domain (Material, Psychological, and Behavioral) medical financial hardship questions were constructed based on the NHIS questionnaire. Multivariable logistic models were used to identify the frailty level associated with financial hardship and its intensity.ResultsA total of 1,583 (40.3%) older individuals with cancer were robust, 1,421 (35.9%) were pre-frail, and 915 (23.8%) were frail. Compared with robust cancer survivors in adjusted analyses, frail cancer survivors were more likely to report issues with material domain (odds ratio (OR) = 3.19, 95%CI: 2.16–4.69; p < 0.001), psychological domain (OR = 1.47, 95%CI: 1.15–1.88; p < 0.001), or behavioral domain (ORs ranged from 2.19 to 2.90, all with p < 0.050), and greater intensities of financial hardship.ConclusionBoth pre-frail and frailty statuses are common in the elderly cancer survivor population, and frail cancer survivors are vulnerable to three-domain financial hardships as compared with robust cancer survivors. Ongoing attention to frailty highlights the healthy aging of older survivors, and efforts to targeted interventions should address geriatric vulnerabilities during cancer survivorship.

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

Abstract Background This study aimed to propose a new user-friendly, cost effective and robust risk model to facilitate risk stratification for diffuse large B-cell lymphoma (DLBCL) treated with frontline R-CHOP regimens. Methods Data on 998 patients with de novo DLBCL diagnosed between Jan 1st, 2005 and Dec 31st, 2018 at our center, who received frontline R-CHOP or R-CHOP-like regimens, were retrospectively collected. Patients were randomly divided into the training cohort (n = 701) and the validation cohort (n = 297). A new prognostic model for overall survival (OS) was built based on the training cohort. The performance of the new model was compared with International prognostic index (IPI), revised IPI (R-IPI) and National Comprehensive Cancer Network (NCCN)-IPI (NCCN-IPI). The new model was validated in the validation cohort. Results The multivariate analysis of the training cohort showed that the IPI, β2-microglobulin, platelet count and red blood cell distribution width were independent factors for OS, which were incorporated into the new prognostic model. Patients were stratified into low risk, low-intermediate risk, high-intermediate risk, high risk and very high risk groups, with distinct survival outcomes. The new model achieved good C-indexes for 5-year OS prediction of 0.750 (95%CI 0.719–0.781) and 0.733 (95%CI 0.682–0.784) in the training and validation cohorts, respectively, and displayed well-fitted calibration curves. The C-index and the time-dependent ROC analysis demonstrated better performance of the new model than the IPI, R-IPI and NCCN-IPI in both training and validation cohorts. The integrated Brier score for predicting 5-year OS of the new model was lower than that of the IPI, R-IPI and NCCN-IPI in both cohorts, and decision curve analysis also showed a higher net benefit, indicating the superiority of the new model over the conventional models. Conclusion The new prognostic model might be a useful predictive tool for DLBCL treated with R-CHOP regimens. Further external validation is warranted.

Abstract Prussian Blue (PB) is an excellent electrochromic (EC) material, possessing many praiseworthy advantages such as proper redox potential, large transmittance, environmental benignity, neutral colored state, and low cost. However, the co‐influence of weak interaction force and low electrical conductivity results in poor cyclic stability and slow switching speed. In this work, the novel Pt/Au and Au/PB films are prepared by electrodeposition to improve the EC properties of PB. The introduction of Au and Pt nanoparticles not only enhances the conductivity and inhibits polarization, but also increases the contact area and alleviates the stress and strain caused by volume expansion during ion insertion/extraction. Furthermore, the Pt/PB and Au/PB heterojunction with a strong inner electronic field promote the separation of electrons and holes and quicken charge transfer. In consideration of the better electrical conductivity, higher transmittance and strong local plasma resonance effect of Au nanoparticles, the Au/PB film shows ultrastable EC cyclic stability (96.4% after 2000), fast coloration/bleaching switching time (1.36/2.32 s), small charge transfer resistance (38.2 Ω), and high coloration efficiency (131.3 cm2 C−1). In addition, the EC iris devices are designed and assembled using Au/PB film as an EC layer to confirm the feasibility of the material in digital cameras and mobile phones.

Sediment transport modeling for flows with cylinders is very challenging owing to the complicated flow–cylinder–sediment interactions, especially under the combined wave-current flows. In this paper, an improved formulation for incipient sediment suspension considering the effect of cylinder density (i.e., solid volume fraction) is employed to simulate the bottom sediment flux in the flow with cylinders. The proposed model is calibrated and validated using laboratory measurements under unidirectional and combined wave-current flows in previous studies. It is proved that the effects of cylinders on sediment suspension can be accounted for through a modified critical Shields number, and the proposed model is capable of simulating sediment suspension under both unidirectional and combined wave–current flows reasonably well with the average the coefficients of determination and model skills greater than 0.8 and 0.64.

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.

Abstract Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

Background: Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. Methods: In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. Results: Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 109/L (range 18–219) among patients who received rhTPO and 73 × 109/L (range 42–197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count

Background: Almost a year after the outbreak of coronavirus disease 2019 (COVID-19), many hospitalized COVID-19 patients have recovered. However, little is known about the long-term follow-up (> 2 months) of discharged patients. Methods: This study enrolled 527 discharged COVID-19 patients from 05 February to 11 March 2020. Basic characteristics, imaging features, nucleic acid detection results, and antibody levels of these patients were retrospectively reviewed. Results: Of the 527 discharged patients, 32 (6.1%) had re-detectable positive (RP) nucleic acid results for SARS-CoV-2 during follow-up examinations, with 11 and four detections entailing stool samples and anal swabs, respectively, rather than respiratory samples. Juveniles were more susceptible to “infection recurrence” than other age groups, with shorter time spans for re-detectable positive (RP) RNA tests (an average of 8.8 days [6.0–9.0 days]), while the reverse was true for the middle-aged group (17.5 days on average [14.0–17.5 days]). Similar improvements in the imaging features of both RP and no RP (NRP) groups were observed. Negative antibody detections in patients at 3 and 6 months after discharge were 14.2% and 25.0%, respectively. Cases evidencing negative antibodies were more common among juvenile patients (40% vs. 15.6%, P = 0.03) 6 months post-discharge. Conclusions: A total of 6.1% of 527 discharged patients showed RP status, which may be easier to be identified from stool samples than from other samples. Given the dropping rate of SARS-CoV-2 antibodies, reinfection may happen, especially in juvenile patients (aged

Abstract Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to

We report the case of a patient diagnosed with severe pneumonia due to coronavirus disease 2019 (COVID-19). A percutaneous lung biopsy was performed under ultrasound guidance. Morphological and ultrastructural characteristics of the patient’s lungs are presented, along with details of some important changes in inflammatory biological markers, in order to help better understand the disease and provide clues to allow members of the multidisciplinary team to save more people.

Abstract Background Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE. Methods Female BALB/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Some of the SE dams were given L-Carnitine supplementation (1.5 mM in drinking water, SE + LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks). Results At birth, in male offspring, there were increased levels of inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p- NF-κB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p- NF-κB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age. Conclusion Maternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be less affected by the adverse effects of maternal SE.

This paper discusses the optimization of emergency resource scheduling for major railway emergencies under multiple uncertainties while considering the uncertainties in demand, reserve, and transportation costs of resources. We introduce a novel approach that integrates stochastic mathematical programming, interval parameter programming, and fuzzy mathematical programming to study uncertain parameter interactions and coupling. A two-stage interval fuzzy credibility-constrained model is established and solved using an interval interactive algorithm. Finally, through a case study on China Railway Nanchang Group Co., Ltd., the novelty and effectiveness of the proposed method for optimizing emergency resource scheduling strategies under multiple uncertainties are demonstrated.

Helpful for human health, omega-3 (n-3)-enriched eggs are preferred by consumers. However, antioxidants should be added to the hen’s diet to prevent n-3 fatty acid oxidation due to their unsaturated bonds. A study was designed to investigate the effects of different antioxidants on performance, egg quality, fatty acid profile, oxidation parameters, gene expression, and magnum morphology. A total of 450 hens were divided into five dietary groups. Wheat–flaxseed was used for the basic diet (control) and supplemented with vitamin E (VE), chlorogenic acid (CA), polyphenol (PF), and lutein (L). The experiment lasted for 10 weeks. The eggs were collected on the 5th week and were analyzed for quality, oxidative stability, and fatty acid (FA) content, being stored for 0 d, 7 d, 14 d, 21 d, 28 d, 35 d, and 42 d. The results showed that supplemental VE, PF, CA, and L improved the egg weight and hen day egg production compared to the control group (p < 0.05). The VE, PF, and L groups significantly (p < 0.05) reduced the malondialdehyde (MDA) and maintained the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in the egg yolk. The albumen height and Haugh unit were maintained in the egg yolk till 35 days of storage by the VE, PF, and L groups, while the CA group reduced the albumen quality after 21 d storage. The VE, PF, CA, and lutein maintained the content of alpha-linolenic acid (ALA), during the whole storage period. The total n-3 FA and docosahexaenoic acid (DHA) were retained in the egg yolk till 35 and 28 days of storage, respectively, and slightly decreased after 35 and 28 days in the L groups. The total n-6 (Tn-6) FA was maintained in the yolk till 28 days of storage in the CA and PF groups, respectively. The VE, PF, and L groups upregulated the expression of Nrf-2, P38MAPK, HO-1, SOD-1, and GSH-Px as compared to the CA and control groups. The VE, PF, and L groups significantly increased the magnum primary folds and epithelium height as compared to CA and the control. Thus, it was concluded that the use of PF and L is better at preventing egg quality deterioration and lipid oxidation, maintaining more than 300 mg/egg n-3 FA during storage, by activating the Nrf-2 pathway through the phosphorylation of P38MAPK, and enhancing the phase-2 antioxidant defense enzymes, namely, SOD, GSH-Px, and HO-1.

Abstract Introduction Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. Materials and Methods We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. Results We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Conclusions Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.

Background: Palliative chemotherapy has been the mainstay treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, little is known about the efficacy and toxicity of nimotuzumab (NTZ) – a monoclonal antibody drug targeting epidermal growth factor receptor – plus chemotherapy (CT) versus CT alone for these patients. Methods: The database at Cancer Hospital of Chinese Academy of Medical Sciences was queried for patients diagnosed with NPC who received CT with or without NTZ between 2004 and 2018. Treatment compliance, survival outcomes, and adverse effects were compared among these groups. Results: Records of 70 patients with R/M-NPC were reviewed: 21 (30%) received NTZ plus CT (NTZ+CT) and 49 (70%) received CT. CT regimens included gemcitabine plus platinum, taxane plus platinum (TP), and fluorouracil plus platinum. Comparing the CT group with NTZ+CT group, the median follow up was 62 months (range = 3–133) versus 59 months (range = 9–117); median progression free survival was 7.5 [95% confidence interval (CI) 6.552–8.381] months versus 8.5 (95% CI 6.091–10.976) months, p = 0.424; median overall survival (OS) was 25.6 (95% CI 18.888–32.379) months versus 48.6 (95% CI 35.619–61.581) months, p = 0.017, respectively. Multivariable analysis established treatment group (CT versus NTZ+CT) as an independent prognostic factor for OS (hazard ratio, 0.5; 95% CI 0.255–0.979; p = 0.043). No significant difference with regard to toxicities was observed between the two groups. Among them, a subgroup analysis was performed in 53 (75.7%) patients who received TP with or without NTZ, which showed similar results. Conclusion: Our findings suggested that NTZ+CT provides a novel treatment option and prolongs survival significantly for R/M-NPC.

Abstract The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (p = 0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (p = 0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses.

In this paper, an HIV infection model including an eclipse stage of infected cells is considered. Some quicker cells in this stage become productively infected cells, a portion of these cells are reverted to the uninfected class, and others will be latent down in the body. We consider CTL-response delay in this model and analyze the effect of time delay on stability of equilibrium. It is shown that the uninfected equilibrium and CTL-absent infection equilibrium are globally asymptotically stable for both ODE and DDE model. And we get the global stability of the CTL-present equilibrium for ODE model. For DDE model, we have proved that the CTL-present equilibrium is locally asymptotically stable in a range of delays and also have studied the existence of Hopf bifurcations at the CTL-present equilibrium. Numerical simulations are carried out to support our main results.