Rethinking pulmonary toxicity in advanced non-small cell lung cancer in the era of combining anti-PD-1/PD-L1 therapy with thoracic radiotherapy.

The combination of programmed cell death 1/programmed cell death ligand 1 blockade and thoracic radiotherapy has become the new standard of care in the treatment of locally advanced non-small-cell lung cancer. The information regarding the pulmonary safety of such therapy remains limited to mostly retrospective studies and case reports with a small portion of data from prospective clinical trials. By analyzing the underlying mechanisms of interactions between radiation and immunotherapy from preclinical data and summarizing safety data from relevant clinical studies with pulmonary toxicity, we believe that longer and rigorous follow-up is warranted, to determine if the combination of such modalities is appropriate for patients without risking undue toxicity

Composition of Rumen Bacterial Community in Dairy Cows With Different Levels of Somatic Cell Counts

Mastitis is an inflammatory disease, affects the dairy industry and has a severe economic impact. During subclinical mastitis, milk production and milk quality deteriorates. Recently, rumen microbial composition has been linked to rumen health, but few studies have investigated the effect of rumen microbiota on mammary health in cows. This study was undertaken to identify the rumen microbial composition and associated microbial fermentation in cows with different somatic cell counts (SCC), with the speculation that cows with different health statuses of the mammary gland have different rumen bacterial composition and diversity. A total of 319 Holstein dairy cows fed the same diet and under the same management were selected and divided into four groups as SCC1 (N = 175), SCC2 (N = 49), SCC3 (N = 49), and SCC4 (N = 46) with < 200,000, 200,001–500,000, 500,001–1,000,000, and >1,000,000 somatic cells/mL, respectively. Further, 20 cows with the lowest SCC and 20 cows with the highest SCC were identified. The rumen microbial composition was profiled using 16S rRNA sequencing, along with measurement of rumen fermentation parameters and milking performance. Compared to low SCC, cows with high SCC showed poorer milk yield, milk composition, and rumen volatile fatty acids concentration, but higher rumen bacterial diversity. Although the predominant rumen bacterial taxa did not vary among the SCC groups, the relative abundance of phyla SR1 and Actinobacteria, unclassified family Clostridiales and genus Butyrivibrio were significantly different. In addition, Proteobacteria and family Succinivibrionaceae were enriched in cows with low SCC. Our results suggest that specific rumen microbes are altered in cows with high SCC

Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy: Meta-Analysis

Introduction:The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect.Methods:We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy.Results:Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively.Conclusion:Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC

Exogenous testosterone decreases men’s sensitivity to vocal cues of male dominance

Assessing dominance is important for effective social interactions, and prior research suggests that testosterone is associated with men's dominance perceptions. The present study tested for a causal effect of exogenous testosterone on men's sensitivity to vocal cues of other men's dominance, an important parameter in male-male competition across species. One hundred and thirty-nine Chinese men received a single dose (150 mg) of testosterone or placebo gel in a double-blind, placebo-controlled, between-participant design. Participants reported their own dominance and judged other men's dominance from voices. Men's dominance sensitivity was significantly weaker in the testosterone group compared to those in the placebo group. Moreover, men's dominance sensitivity was negatively associated with their self-reported dominance in our Chinese sample, consistent with findings from Western populations. These results indicate that exogenous testosterone has a causal effect in decreasing men's dominance sensitivity, consistent with the Challenge Hypothesis, suggesting that the fluctuation of testosterone concentration mediates individuals' behaviors. Additionally, the present study could motivate further work on vocal assessment in the context of competition in humans and other species

Can Language Models Pretend Solvers? Logic Code Simulation with LLMs

Transformer-based large language models (LLMs) have demonstrated significant potential in addressing logic problems. capitalizing on the great capabilities of LLMs for code-related activities, several frameworks leveraging logical solvers for logic reasoning have been proposed recently. While existing research predominantly focuses on viewing LLMs as natural language logic solvers or translators, their roles as logic code interpreters and executors have received limited attention. This study delves into a novel aspect, namely logic code simulation, which forces LLMs to emulate logical solvers in predicting the results of logical programs. To further investigate this novel task, we formulate our three research questions: Can LLMs efficiently simulate the outputs of logic codes? What strength arises along with logic code simulation? And what pitfalls? To address these inquiries, we curate three novel datasets tailored for the logic code simulation task and undertake thorough experiments to establish the baseline performance of LLMs in code simulation. Subsequently, we introduce a pioneering LLM-based code simulation technique, Dual Chains of Logic (DCoL). This technique advocates a dual-path thinking approach for LLMs, which has demonstrated state-of-the-art performance compared to other LLM prompt strategies, achieving a notable improvement in accuracy by 7.06% with GPT-4-Turbo.Comment: 12 pages, 8 figure

Decoupled Iterative Refinement Framework for Interacting Hands Reconstruction from a Single RGB Image

Reconstructing interacting hands from a single RGB image is a very challenging task. On the one hand, severe mutual occlusion and similar local appearance between two hands confuse the extraction of visual features, resulting in the misalignment of estimated hand meshes and the image. On the other hand, there are complex spatial relationship between interacting hands, which significantly increases the solution space of hand poses and increases the difficulty of network learning. In this paper, we propose a decoupled iterative refinement framework to achieve pixel-alignment hand reconstruction while efficiently modeling the spatial relationship between hands. Specifically, we define two feature spaces with different characteristics, namely 2D visual feature space and 3D joint feature space. First, we obtain joint-wise features from the visual feature map and utilize a graph convolution network and a transformer to perform intra- and inter-hand information interaction in the 3D joint feature space, respectively. Then, we project the joint features with global information back into the 2D visual feature space in an obfuscation-free manner and utilize the 2D convolution for pixel-wise enhancement. By performing multiple alternate enhancements in the two feature spaces, our method can achieve an accurate and robust reconstruction of interacting hands. Our method outperforms all existing two-hand reconstruction methods by a large margin on the InterHand2.6M dataset.Comment: Accepted to ICCV 2023 (Oral

Hot isostatic pressing of in-situ TiB/Ti-6Al-4V composites with novel reinforcement architecture, enhanced hardness and elevated tribological properties

In this study, titanium borides reinforced Ti-6Al-4V composites have been successfully prepared by hot isostatic pressing (HIPing). The microstructure of the as-fabricated samples was investigated using X-ray diffraction technique, secondary electron microscopy and electron backscatter diffraction and the mechanical properties evaluated through micro-hardness and wear resistance measurements together with nano-indentation. It was found that during HIPing the additive particles TiB2 have transformed into TiB needles which tend to decorate at prior particle boundaries of the consolidated powder particles to form a network structure. Under the same HIPing condition, the needles became increasingly coarser and agglomerated with increased addition of TiB2. The micro-hardness of the synthesized materials increased with increased volume fraction of TiB. Nano-indentation measurement demonstrates that the TiB network structure shows much higher nanohardness than the surrounding matrix regions. The friction coefficient of the synthesized composites decreased continuously with increased volume fraction of TiB, indicating improved wear resistance. High resolution transmission electron microscopy analysis on wear debris revealed the formation of a series of oxides suggesting that chemical reaction between alloy elements and oxygen in air may have happened. It is thus believed that the wearing of the current samples is a result of both friction and chemical reaction

A Systematic Prediction of Multiple Drug-Target Interactions from Chemical, Genomic, and Pharmacological Data

In silico prediction of drug-target interactions from heterogeneous biological data can advance our system-level search for drug molecules and therapeutic targets, which efforts have not yet reached full fruition. In this work, we report a systematic approach that efficiently integrates the chemical, genomic, and pharmacological information for drug targeting and discovery on a large scale, based on two powerful methods of Random Forest (RF) and Support Vector Machine (SVM). The performance of the derived models was evaluated and verified with internally five-fold cross-validation and four external independent validations. The optimal models show impressive performance of prediction for drug-target interactions, with a concordance of 82.83%, a sensitivity of 81.33%, and a specificity of 93.62%, respectively. The consistence of the performances of the RF and SVM models demonstrates the reliability and robustness of the obtained models. In addition, the validated models were employed to systematically predict known/unknown drugs and targets involving the enzymes, ion channels, GPCRs, and nuclear receptors, which can be further mapped to functional ontologies such as target-disease associations and target-target interaction networks. This approach is expected to help fill the existing gap between chemical genomics and network pharmacology and thus accelerate the drug discovery processes

Whole brain radiotherapy plus simultaneous in-field boost with image guided intensity-modulated radiotherapy for brain metastases of non-small cell lung cancer

BACKGROUND: Whole brain radiotherapy (WBRT) plus sequential focal radiation boost is a commonly used therapeutic strategy for patients with brain metastases. However, recent reports on WBRT plus simultaneous in-field boost (SIB) also showed promising outcomes. The objective of present study is to retrospectively evaluate the efficacy and toxicities of WBRT plus SIB with image guided intensity-modulated radiotherapy (IG-IMRT) for inoperable brain metastases of NSCLC. METHODS: Twenty-nine NSCLC patients with 87 inoperable brain metastases were included in this retrospective study. All patients received WBRT at a dose of 40 Gy/20 f, and SIB boost with IG-IMRT at a dose of 20 Gy/5 f concurrent with WBRT in the fourth week. Prior to each fraction of IG-IMRT boost, on-line positioning verification and correction were used to ensure that the set-up errors were within 2 mm by cone beam computed tomography in all patients. RESULTS: The one-year intracranial control rate, local brain failure rate, and distant brain failure rate were 62.9%, 13.8%, and 19.2%, respectively. The two-year intracranial control rate, local brain failure rate, and distant brain failure rate were 42.5%, 30.9%, and 36.4%, respectively. Both median intracranial progression-free survival and median survival were 10 months. Six-month, one-year, and two-year survival rates were 65.5%, 41.4%, and 13.8%, corresponding to 62.1%, 41.4%, and 10.3% of intracranial progression-free survival rates. Patients with Score Index for Radiosurgery in Brain Metastases (SIR) >5, number of intracranial lesions <3, and history of EGFR-TKI treatment had better survival. Three lesions (3.45%) demonstrated radiation necrosis after radiotherapy. Grades 2 and 3 cognitive impairment with grade 2 radiation leukoencephalopathy were observed in 4 (13.8%) and 4 (13.8%) patients. No dosimetric parameters were found to be associated with these late toxicities. Patients received EGFR-TKI treatment had higher incidence of grades 2–3 cognitive impairment with grade 2 leukoencephalopathy. CONCLUSIONS: WBRT plus SIB with IG-IMRT is a tolerable and effective treatment for NSCLC patients with inoperable brain metastases. However, the results of present study need to be examined by the prospective investigations

Case Report: Bronchial artery embolization and chemoradiotherapy for central squamous cell lung carcinoma with rapid regression

BackgroundInterventional embolization is a common treatment for hemoptysis, one of the complications of lung cancer. However, there are no official guidelines for the use of this method in antitumor therapy.Case DescriptionHerein, we describe a case of a patient who was pathologically diagnosed as central squamous cell lung cancer. The patient received chemotherapy, interventional embolization and radiotherapy successively. The tumor regressed rapidly within 48 hours of receipt of interventional embolization. Furthermore, the tumor decreased by more than 50% in size within 7 days during radiotherapy. Unfortunately, the patient has since developed lymph node metastases and remains under treatment.ConclusionsThus, finding the suitable blood vessel embolized may be a suitable option to reduce the local tumor load and can be considered as antitumor therapy in combination with other treatments. The patient’s theoretical hypoxia state after interventional therapy still produced a good tumor regression after radiotherapy. However, so far, no related studies have reported the changes of tumor immune microenvironment in human body after intervention and radiotherapy