bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the molecular subtypes of breast cancer using nomograms based on three-dimensional ultrasonography characteristics
Authors: Xu Xiaojing , Lu Liren , Zhu Luoxi , Tan Yanjuan , Yu Lifang , Bao Lingyun 
Published: August 2022

BackgroundMolecular subtyping of breast cancer is commonly doneforindividualzed cancer management because it may determines prognosis and treatment. Therefore, preoperativelyidentifying different molecular subtypes of breast cancery can be significant in clinical practice.Thisretrospective study aimed to investigate characteristic three-dimensional ultrasonographic imaging parameters of breast cancer that are associated with the molecular subtypes and establish nomograms to predict the molecular subtypes of breast cancers.MethodsA total of 309 patients diagnosed with breast cancer between January 2017and December 2019 were enrolled. Sonographic features were compared between the different molecular subtypes. A multinomial logistic regression model was developed, and nomograms were constructed based on this model.ResultsThe performance of the nomograms was evaluated in terms of discrimination and calibration.Variables such as maximum diameter, irregular shape, non-parallel growth, heterogeneous internal echo, enhanced posterior echo, lymph node metastasis, retraction phenomenon, calcification, and elasticity score were entered into the multinomial model.Three nomograms were constructed to visualize the final model. The probabilities of the different molecular subtypes could be calculated based on these nomograms. Based on the receiver operating characteristic curves of the model, the macro-and micro-areaunder the curve (AUC) were0.744, and 0.787. The AUC was 0.759, 0.683, 0.747 and 0.785 for luminal A(LA), luminal B(LB), human epidermal growth factor receptor 2-positive(HER2), and triple-negative(TN), respectively.The nomograms for the LA, HER2, and TN subtypes provided good calibration.ConclusionsSonographic features such as calcification and posterior acoustic features were significantly associated with the molecular subtype of breast cancer. The presence of the retraction phenomenon was the most important predictor for the LA subtype. Nomograms to predict the molecular subtype were established, and the calibration curves and receiver operating characteristic curves proved that the models had good performance.
Respiratory system toxicity induced by immune checkpoint inhibitors: A real-world study based on the FDA adverse event reporting system database
Authors: Cui Chanjuan , Deng Lei , Wang Wenqing , Ren Xiayang , Wang Yanfeng , Cui Wei 
Published: August 2022

BackgroundImmune checkpoint inhibitors (ICIs), the treatment of multiple cancer types, can be associated with respiratory system adverse events (AEs). The aim of this study is to quantify the association of respiratory system AEs and ICIs and to characterize the profiles of ICI-related respiratory system complications from Food and Drug Administration Adverse Event Reporting System (FAERS) data.MethodsThe disproportionality of respiratory system AE-related ICIs based on FAERS data from January 2014 to September 2021 was analyzed using the reporting odds ratio (ROR) and information component (IC) as measures of potential risk increase.ResultsA total of 38,415,849 records were involved; among these, 36,923 records related to respiratory system AEs after ICI treatment were identified. In the first 3 months, the cumulative proportion of respiratory system AEs was 75.40%. Men had a slightly higher reporting frequency than that of women (ROR = 1.74, 95% CI: 1.70–1.78). Death cases had a slightly higher reporting frequency in ICI-associated respiratory system AEs than that of other drug-associated respiratory system AEs (ROR = 1.40, 95% CI: 1.38–1.41). Anti-programmed cell death 1 (PD-1) drugs and anti-programmed cell death ligand 1 (PD-L1) drugs were significantly associated with respiratory system toxicities. However, anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drugs did not demonstrate an association with respiratory system toxicities. Interstitial lung disease and pneumonitis were found to be significantly associated with all eight types of ICIs. In addition, 7 in 10 class-specific respiratory system AEs (lower respiratory tract disorders, pleural disorders, pulmonary vascular disorders, respiratory disorders not elsewhere classified (NEC), respiratory tract infections, respiratory tract neoplasms, and thoracic disorders) were associated with ICIs. The signal values of IC025 were from 0.08 to 2.66.ConclusionsOverall, this study showed a high reporting frequency of respiratory system toxicities caused by ICIs. Early recognition and management of ICI-related respiratory system AEs are of vital importance in practice. Maximizing the benefit while reducing potential respiratory system toxicities of ICIs should become a priority.
Prognostic role of the platelet to lymphocyte ratio (PLR) in the clinical outcomes of patients with advanced lung cancer receiving immunotherapy: A systematic review and meta-analysis
Authors: Zhou Ke , Cao Jie , Lin Huahang , Liang Linchuan , Shen Zhongzhong , Wang Lei , Peng Zhiyu , Mei Jiandong 
Published: August 2022

BackgroundIt remains controversial whether the platelet to lymphocyte ratio (PLR) serves as a potential indicator for the efficacy of immunotherapy in advanced lung cancer. This meta-analysis aimed to address this concern.MethodsUp to March 2022, we searched PubMed, Embase, Web of Science and the Cochrane Library to retrieve potentially eligible articles. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the relationship between PLR and progression-free survival (PFS) as well as overall survival (OS), while the combined odds ratios (ORs) and 95% CIs were estimated to evaluate the relationship between PLR and the objective response rate (ORR) as well as the disease control rate (DCR). Subgroup analyses were further performed to detect the source of heterogeneity and potential predictive value of PLR in different groups in terms of OS and PFS.ResultsA total of 21 included studies involving 2312 patients with advanced lung cancer receiving immunotherapy were included. The combined results suggested that elevated PLR was associated with poorer OS (HR=2.24; 95% CI: 1.87-2.68; I² =44%; P=0.01) and PFS (HR=1.66; 95% CI: 1.36-2.04; I² =64%; P&lt;0.01). Furthermore, elevated PLR showed a lower ORR (OR= 0.61; 95% CI: 0.43-0.87, I²=20%; P=0.29) and DCR (OR= 0.44; 95% CI: 0.27-0.72, I²=61%; P=0.02). In subgroup analyses, pretreatment PLR was significantly associated with adverse OS and PFS. The same results were observed in different PLRs in terms of cutoff value (&gt;200 vs. ≤200). Furthermore, high PLR was significantly associated with poor OS and PFS in advanced non-small cell lung cancer (NSCLC); however, PLR was not associated with OS and PFS in advanced small cell lung cancer (SCLC). In addition, PLR predicted poor OS irrespective of regions and types of immune checkpoint inhibitors (ICIs).ConclusionOn the whole, patients with low PLR had better OS and PFS, as well as higher ORR and DCR when receiving immunotherapy in advanced lung cancer especially for advanced NSCLC. And further investigations are warranted to confirm the prognostic value of PLR in advanced SCLC.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022315976.
Postnatal probiotic supplementation can prevent and optimize treatment of childhood asthma and atopic disorders: A systematic review of randomized controlled trials
Authors: Uwaezuoke Samuel N. , Ayuk Adaeze C. , Eze Joy N. , Odimegwu Chioma L. , Ndiokwelu Chibuzo O. , Eze Ikenna C. 
Published: August 2022

BackgroundAlthough several randomized controlled trials (RCTs) published over the past 5 years show that prenatal or postnatal probiotics may prevent or optimize the treatment of childhood asthma and atopic disorders, findings from the systematic reviews and meta-analyses of these studies appear inconsistent. More recent RCTs have focused on postnatal probiotics, and linked specific probiotic strains to better disease outcomes.ObjectiveThis systematic review aimed to determine if postnatal probiotics are as effective as prenatal probiotics in preventing or treating childhood asthma and atopic disorders.MethodsWe searched the PubMed, Medline, Google Scholar, and EMBASE databases for RCTs published within the past 5 years (from 2017 to 2022). We included only full-text RCTs on human subjects published in or translated into the English language. We retrieved relevant data items with a preconceived data-extraction form and assessed the methodological quality of the selected RCTs using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. We qualitatively synthesized the retrieved data to determine any significant differences in study endpoints of the probiotic and placebo groups.ResultsA total of 1,320 participants (688 and 632 in the probiotic and placebo groups) from six RCTs were investigated. One RCT showed that early Lactobacillus rhamnosus GG (LGG) led to a reduction in the cumulative incidence rate of asthma. Another study demonstrated that mixed strains of Lactobacillus paracasei and Lactobacillus fermentum could support clinical improvement in children with asthma while one trial reported a significant reduction in the frequency of asthma exacerbations using a mixture of Ligilactobacillus salivarius and Bifidobacterium breve. Three trials showed that a combination of LGG and Bifidobacterium animalis subsp lactis, Lactobacillus rhamnosus alone, and a probiotic mixture of Lactobacillus ŁOCK strains improved clinical outcomes in children with atopic dermatitis and cow-milk protein allergy.ConclusionsPostnatal strain-specific probiotics (in single or mixed forms) are beneficial in preventing and treating atopic dermatitis and other allergies. Similarly, specific strains are more effective in preventing asthma or improving asthma outcomes. We recommend more interventional studies to establish the most useful probiotic strain in these allergic diseases.
Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability
Authors: Mantov Nikola , Zrounba Mathilde , Brollo Marion , Grassin-Delyle S , Glorion Matthieu , David Mélanie , Naline Emmanuel , Devillier Philippe , Salvator Hélène 
Published: August 2022

Background: The Janus kinase (JAK) 1/2 inhibitor ruxolitinib has been approved in an indication of myelofibrosis and is a candidate for the treatment of a number of inflammatory or autoimmune diseases. We assessed the effects of ruxolitinib on lipopolysaccharide (LPS)- and poly (I:C)-induced cytokine production by human lung macrophages (LMs) and on the LMs’ phagocytic activity.Methods: Human LMs were isolated from patients operated on for lung carcinoma. The LMs were cultured with ruxolitinib (0.5 × 10−7 M to 10–5 M) or budesonide (10–11 to 10–8 M) and then stimulated with LPS (10 ng·ml−1) or poly (I:C) (10 μg·ml−1) for 24 h. Cytokines released by the LMs into the supernatants were measured using ELISAs. The phagocytosis of labelled bioparticles was assessed using flow cytometry.Results: Ruxolitinib inhibited both the LPS- and poly (I:C)-stimulated production of tumor necrosis factor alpha, interleukin (IL)-6, IL-10, chemokines CCL2, and CXCL10 in a concentration-dependent manner. Ruxolitinib also inhibited the poly (I:C)- induced (but not the LPS-induced) production of IL-1ß. Budesonide inhibited cytokine production more strongly than ruxolitinib but failed to mitigate the production of CXCL10. The LMs’ phagocytic activity was not impaired by the highest tested concentration (10–5 M) of ruxolitinib.Conclusion: Clinically relevant concentrations of ruxolitinib inhibited the LPS- and poly (I:C)-stimulated production of cytokines by human LMs but did not impair their phagocytic activity. Overall, ruxolitinib’s anti-inflammatory activities are less intense than (but somewhat different from) those of budesonide—particularly with regard to the production of the corticosteroid-resistant chemokine CXCL-10. Our results indicate that treatment with a JAK inhibitor might be a valuable anti-inflammatory strategy in chronic obstructive pulmonary disease, Th1-high asthma, and both viral and non-viral acute respiratory distress syndromes (including coronavirus disease 2019).
Qu-Du-San-Jie decoction induces growth inhibition and vascular normalization in NF2-associated vestibular schwannoma
Authors: Lin Jie , Li Shi-Wei , Zhang Jing , Chu Fu-Hao , Li Cheng-Ze , Bie Zhi-Xu , Tang Han-Lu , Gao Shan , Li Ping , Liao Meng-Ting , Xin Tian-Xi , Zhao Fu , Liu Pi-Nan , Ding Xia 
Published: August 2022

Background: Neurofibromatosis type 2 (NF2) is a rare genetic syndrome that predisposes individuals to develop bilateral vestibular schwannomas (VSs) causing a high risk of life-threatening neurological complications. Traditional treatment options for NF2-associated VS usually cause neurological damage, and to date, there are no FDA-approved pharmacotherapies for NF2. The aim of this study was to evaluate the antitumor efficacy of Qu-Du-San-Jie (QDSJ) decoction, a traditional Chinese medicine formula, on NF2-associated VS and to investigate the potential underlying mechanisms.Methods: Ultra high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) analysis was performed to identify the components of QDSJ and their targets. To determine the relationships between the putative targets of QDSJ and the differential genes of NF2-associated VS, the drug-disease crossover genes were screened using the UHPLC-MS data combined with our previous gene expression profiling data. The differentially expressed genes were imported into the STRING database to generate a PPI network. Differentially expressed gene targets and pathways were identified using GO and KEGG pathway enrichment analyses. The in vitro and in vivo drug efficacy of QDSJ decoction was tested using a patient-derived schwannoma cell line and a patient-derived xenograft mouse model, respectively. H&amp;E staining, immunochemistry, and immunofluorescence staining were used to evaluate the cell proliferation and tumor vessels.Results: A total of 133 compounds were identified in QDSJ decoction using UHPLC-MS analysis. Network pharmacology showed that the regulation of necroptosis, apoptosis, cell cycle, angiogenesis, adherens junction, and neuroactive ligand-receptor interaction could be associated with the efficacy of QDSJ in treating NF2-associated VS. Treatment with QDSJ induced necrotic cell death and apoptosis of schwannoma cells in vitro and suppressed the tumor growth in vivo. Histopathological analysis revealed areas of cell necrosis and enlarged tumor blood vessels in the QDSJ-treated tumors. The numbers of cells positive for Cyclin D1 and Ki-67 were significantly reduced in QDSJ-treated tumors compared to control tumors. Immunofluorescence staining of CD31 and αSMA showed a decreased number and density of tumor vessels and normalized vessel structure in QDSJ-treated tumors.Conclusion: Our study demonstrates that QDSJ decoction shows significant antitumor activity against NF2-associated schwannoma and is a possible candidate for future clinical trials.
A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects
Authors: Hu Xingjiang , Zhang Qiao , Zheng Yunliang , Zhai You , Xu Nana , Zhao Qingwei , Liu Jian , Wan Longyan , Luo Jindan 
Published: August 2022

Leuprolide acetate microspheres developed by Shanghai Livzon Pharmaceutical Co., Ltd. (T) have been marketed in China for more than 10 years, benefiting a large number of patients, and will continue to play an important role in China. However, as a generic drug, it is unclear whether there is a difference in efficacy between T and the original product Enantone® (R). This study compared the differences in efficacy and safety of two 1-month depot formulations in 48 healthy Chinese male subjects by comparing multiple pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The main research indicators were the PK parameters of leuprolide (Cmax, AUC0-t, AUC0-D7, and AUCD7-t) and the PD parameters of testosterone (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) after 42 days of administration. The Cmax, AUC0-t, AUC0-D7 and AUCD7-t of leuprolide were slightly higher in the T group than in the R group with 90% confidence intervals (CIs) of 94.43–118.53%, 109.13–141.88%, 109.53–139.54%, and 105.17–145.74%, respectively. No significant differences in the PD parameters (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) existed between the T and R groups, and 90% CIs were 62.80–93.57%, 88.17–110.55, 95.72%–118.50%, and 79.77–105.63, respectively. At 672 h (D28), the castration rate of T was 91.30% (21/23) and that of R was 60.87% (14/23). The PK characteristics were consistent and the inhibitory effects on testosterone levels were similar in both T and R groups; further, clinical safety was observed for both T and R formulations, suggesting that these two products can replace each other in clinical practice.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20200641.
Postponement of the opacification of lentoid bodies derived from human induced pluripotent stem cells after lanosterol treatment—the first use of the lens aging model in vitro in cataract drug screening
Authors: Zhang Lifang , Qin Zhenwei , Lyu Danni , Lu Bing , Chen Zhijian , Fu Qiuli , Yao Ke 
Published: August 2022

Purpose: Our previous study observed that human induced pluripotent stem cell (HiPSC)-derived lentoid bodies (LBs) became cloudy with extended culture time, partially mimicking the progress of human age-related cataracts (ARCs) in a dish. In the present study, lanosterol, a potential anticataract drug, was used to further verify the value of this model in drug screening for cataract treatment.Methods: Mature LBs on day 25, which were differentiated from HiPSCs using the “fried egg” method, were continually cultured and treated with either dimethyl sulfoxide (control) or lanosterol. The LBs’ shape and opacity alterations were examined using light microscopy and mean gray value evaluation. The soluble and insoluble proteins were examined through SDS-PAGE gel electrophoresis combined with Coomassie blue staining. The protein aggregations were examined with immunofluorescence.Results: The mature LBs became cloudy with an extended culture time, and the opacification of the LBs was partially prevented by lanosterol treatment. There was less increase in insoluble proteins in the lanosterol-treated LBs than in the control group. There were also fewer cells containing aggregated protein (αA‐crystallin and αB‐crystallin) puncta in the lanosterol-treated LBs than in the control LBs.Conclusion: It was found that the opacification of LBs could be delayed by lanosterol treatment, which could be achieved by reducing protein aggregation, suggesting a promising HiPSC-derived drug-screening model for Age-related cataract.
Cysteamine affects skeletal development and impairs motor behavior in zebrafish
Authors: Chen Chao , Zheng Yongliang , Li Xue , Zhang Li , Liu Kangyu , Sun Sujie , Zhong Zilin , Hu Hongmei , Liu Fasheng , Xiong Guanghua , Liao Xinjun , Lu Huiqiang , Bi Yanlong , Chen Jianjun , Cao Zigang 
Published: August 2022

Cysteamine is a kind of feed additive commonly used in agricultural production. It is also the only targeted agent for the treatment of cystinosis, and there are some side effects in clinical applications. However, the potential skeletal toxicity remains to be further elucidated. In this study, a zebrafish model was for the first time utilized to synthetically appraise the skeletal developmental defects induced by cysteamine. The embryos were treated with 0.35, 0.70, and 1.05 mM cysteamine from 6 h post fertilization (hpf) to 72 hpf. Substantial skeletal alterations were manifested as shortened body length, chondropenia, and abnormal somite development. The results of spontaneous tail coiling at 24 hpf and locomotion at 120 hpf revealed that cysteamine decreased behavioral abilities. Moreover, the level of oxidative stress in the skeleton ascended after cysteamine exposure. Transcriptional examination showed that cysteamine upregulated the expression of osteoclast-related genes but did not affect osteoblast-related genes expression. Additionally, cysteamine exposure caused the downregulation of the Notch signaling and activating of Notch signaling partially attenuated skeletal defects. Collectively, our study suggests that cysteamine leads to skeletal developmental defects and reduces locomotion activity. This hazard may be associated with cysteamine-mediated inhibition of the Notch signaling and disorganization of notochordal cells due to oxidative stress and apoptosis.
Traceability of optical frequency to SI second via UTC(NIM)
Authors: Wang Yuzhuo , Lin Yige , Gao Yuan , Zhang Aimin 
Published: August 2022

Absolute frequency measurement of an optical clock is a milestone towards the redefinition of second in the International System of Units. This work summarizes briefly the measurement of frequency ratio between an optical clock and the second, applying the frequency comparison link from UTC(NIM) to International Atomic Time. Some strategies and suggestions are proposed to reduce the uncertainty introduced by the measurement system and dead time, which guided the frequency measurement of three optical clocks at 10−16 level in the past 3 years.
High-Isolation wideband MIMO antenna with offset T-Shaped slots for 5G/WLAN applications
Authors: Chen Shuyi , Lu Na , Sun Jiaxing , Zhou Changfei , Li Changxian , Wu Di 
Published: August 2022

A broadband multiple-input multiple-output (MIMO) antenna with high isolation operating in 3.14–5.42 GHz (2.28 GHz, 53.3%) is proposed for 5G smartphones. An offset T-shaped slot with dual functions is employed to improve the bandwidth of one antenna element and enhance the isolation. Then, the double L-shaped stubs are loaded to improve the impedance matching of the other antenna in the MIMO antenna. Finally, the 2 × 2 MIMO antenna is constructed by four T-shaped monopole antennas, two double L-shaped stubs, and two offset T-shaped slots. The proposed MIMO antenna is first simulated and then experimentally tested with a good agreement. High isolation of greater than 15 dB, high antenna efficiency of more than 54%, and low envelope correlation coefficient (ECC) of smaller than 0.08 are realized within 3.14–5.42 GHz. These good performances indicate that the proposed antenna can be applied for MIMO applications in smartphones.