Science Progress最新文献

Cell division cycle-associated (CDCA) genes are dysregulated in carcinomas. Our study aims to identify similarities and differences of the clinical roles of CDCAs in breast cancer (BRCA) and to explore their potential mechanisms. In GEPIA, compared to normal tissues, expressions of CDCAs were higher in BRCA and sub-types. In addition, CDCAs were significantly positively related to stages and predicted worse survival in BRCA. In CancerSEA, expression levels of most CDCAs were strongly positively related to cell cycle, DNA damage, DNA repair, and proliferation. In TIMER, CDCAs were linked with immune infiltration levels of BRCA, including Dendritic cell, B cell and so on, and were positively related to most of the common markers of immune cells, especially CD38 of B cell and IL12RB2 of Th1. In GeneMANIA, there were complex interactions and co-expression relationships between CDCAs and cell division-associated genes. In addition, CDCA1, CDCA3, CDCA5, CDCA6 and CDCA8 had a high proportion of amplification in BRCA, and CDCA1, CDCA2, CDCA5, CDCA7 and CDCA8 had high levels of body DNA methylation. Among 11 transcription factors possibly combining promoters of all CDCAs, FOXP3 and YY1 were significantly higher in BRCA in comparison to normal tissues, and both had a positive relationship with all CDCAs in GEPIA and IHC. In addition, silencing FOXP3 or YY1 decreased levels of CDCAs in MDA-MB-231. In summary, CDCAs have various similarities in clinical functions, functional states, immune infiltration, and mechanisms, and they may become novel potential biomarkers for BRCA.

Ensuring the integrity of shipping containers is crucial for maintaining product quality, logistics efficiency, and safety in the global supply chain. Damaged containers can lead to significant economic losses, delays, and safety hazards. Traditionally, container inspections have been manual, which are labor-intensive, time-consuming, and error-prone, especially in busy port environments. This study introduces an automated solution using the YOLO-NAS model, a cutting-edge deep learning architecture known for its adaptability, computational efficiency, and high accuracy in object detection tasks. Our research is among the first to apply YOLO-NAS to container damage detection, addressing the complex conditions of seaports and optimizing for high-speed, high-accuracy performance essential for port logistics. Our method showcases YOLO-NAS's superior efficacy in detecting container damage, achieving a mean average precision (mAP) of 91.2%, a precision rate of 92.4%, and a recall of 84.1%. Comparative analyses indicate that YOLO-NAS consistently outperforms other leading models like YOLOv8 and Roboflow 3.0, which showed lower mAP, precision, and recall values under similar conditions. Additionally, while models such as Fmask-RCNN and MobileNetV2 exhibit high training accuracy, they lack the real-time assessment capabilities critical for port applications, making YOLO-NAS a more suitable choice. The successful integration of YOLO-NAS for automated container damage detection has significant implications for the logistics industry, enhancing port operations with reliable, real-time inspection solutions that can seamlessly integrate into predictive maintenance and monitoring systems. This approach reduces operational costs, improves safety, and lessens the reliance on manual inspections, contributing to the development of "smart ports" with higher efficiency and sustainability in container management.

A backtracking heuristic algorithm (BHA) was proposed for a two-dimensional rectangular strip packing problem with rotations and without guillotine cutting, which has many applications. An improved fitness strategy was used to select the fittest rectangle to be packed on a strip with a certain height. Next, a backtracking constructive heuristic was repeatedly used at a higher height until all the rectangles were packed. A multi-start improvement procedure then found the best solution by taking a different rectangle as the first rectangle, whereas the sequence of the other rectangles remained unchanged. Finally, in order to further expand the scope of the solution, a simple randomized local search procedure based on random sequences of rectangles with the first rectangle unchanged was applied to search for the optimal solution. BHA has only two parameters; it is simple and effective. Computational results on benchmark problems (zero-waste instances and non-zero-waste instances) with different scales (from 10 to 75,032 rectangles) indicate the following: (1) though it is non-deterministic, the difference between the results after each running is tiny and (2) the proposed algorithm outperforms most of the other algorithms under comparison on the whole, especially for large-scale instances with more than 1000 rectangles, which is further verified by statistical analysis and greatly meaningful in mass industrial production like metal cutting.

Covid 19 patients often present with elevated D-dimer levels. The purpose of this study is to evaluate the role of D-Dimer levels in Covid 19 patients to predict mortality and venous thromboembolism (VTE) events. This is a retrospective chart review study from 1 April 2020 to 30 June 2020, during the peak Covid pandemic. A total of 350 patients were enrolled in this study; 69 (19.7%) patients died; 12 (3.4%) had a deep venous thrombosis; and 8 (2.3%) had a pulmonary embolism outcome. Peak D-dimer levels were collected with median levels of 765 ng/ml (266, 3135). Patients with VTE outcomes had significantly higher levels of peak D-dimers than patients in the non-VTE group (4876 vs 680, p < 0.0001). Patients who died had higher peak D-dimer levels than those who survived (4690 vs 501, p < 0.0001). The optimal cutoff point in peak D-dimer in predicting VTE events was 1437, yielding a sensitivity of 84.2% and a specificity of 65.0%. The optimal cutoff point in peak D-dimer in predicting mortality was 2004, yielding a sensitivity of 71.0% and a specificity of 77.9%. This study suggests that D-dimer levels can be elevated in Covid 19 hospitalized patients and can serve as indicators for mortality and VTE events.

The thick glutenite formed in the Linhe Depression of the Hetao Basin during the Early Cretaceous offers notable exploration potential. However, the sediment comprises a rapidly stacked succession of glutenite featuring poor sortability, with the individual sedimentary layers reaching up to 120 m in thickness. However, the limited core variations coupled with the "dentate box" shape of the well logging curves pose challenges in identifying the sedimentary microfacies of the study area, thereby hindering its exploration and development. This study selected the Jihua-2 block in the Linhe Depression as the study area and attempted to identify the sedimentary microfacies in the thick glutenite formed in this region. Results indicate that under arid and shallow-water conditions, the Langshan Fault continued to move, and a set of thick-bedded glutenite masses was deposited in the downthrown block. Detailed core observations revealed seven lithofacies and five lithofacies combinations. The study area is mainly characterized by a fan-delta front, which is further subdivided into the main part of underwater distributary channels, lateral margins of underwater distributary channels, and interdistributary bays. By integrating probabilistic distribution statistics with single well analysis, a quantitative standard for identifying well logging facies based on cored wells was established. Kriging interpolation was performed to clarify the spatial distribution of the sedimentary microfacies across the study area, enabling the establishment of a depositional model of fan-delta facies for the study area. The influence of faults on sedimentary facies and the relation between depositional patterns and hydrocarbon distribution in the study area were also discussed. The findings of this study can contribute to the development of improved methods for identifying sedimentary microfacies in glutenite fan deltas, with implications for guiding exploration and development.

ObjectiveThe sensitivity of immune checkpoint inhibitors (ICIs) as monotherapy is low in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins). This study aims at investigating the effectiveness of the combination of ICI and chemotherapy (ICI-combined regimen) in a real-world population of NSCLC patients harboring near-loop insertions of EGFR exon 20.MethodsWe conducted a retrospective study of advanced NSCLC with EGFR ex20ins from April 2016 to March 2021 at Guangdong Provincial People's Hospital, Southern Medical University, China. A total of 126 cases of EGFR ex20ins were screened from 1610 patients with advanced NSCLC harboring EGFR mutations and 62 cases were further analyzed for different therapeutic efficacy.ResultsThe first-line ICI-combined regimen showed marked efficacy for near-loop insertions of EGFR exon 20, with an ORR of 71.4% and a mPFS of 11.5 months, compared to ORRs of 12.5% for traditional targeted therapy (P = .003) and 18.8% for chemotherapy (P = .013). The first-line mPFS of traditional EGFR-TKIs and chemotherapy were only 5.6 and 5.8 months, respectively. Similar results were observed for any-line therapy of ICI-combined regimen, with an ORR of 80%. The median progression-free survival (PFS) of any-line therapy of ICI-combined regimen was 11.5 months, which were significantly longer than that of traditional targeted therapy (4.5 months, P = .026) and chemotherapy (5.0 months, P = .013).ConclusionsICI-combined regimen may be superior compared to targeted therapy and chemotherapy for advanced NSCLC with near-loop insertions of EGFR exon 20. Further exploration is warranted to confirm the efficacy of ICI-combined regimen.

Objective: To study the impact of kinetic glomerular filtration rate (kGFR) on clinical decision making and its implications on drug dosing compared to that of estimated GFR (eGFR) using chronic kidney disease epidemiology collaboration (CKD-EPI) equation in critically ill patients with acute kidney injury (AKI) admitted in a tertiary level intensive care unit (ICU).

Methods: Cross-sectional, prospective, observational study design. All patients admitted to Medical ICU, Fortis Hospital, Bangalore with AKI defined as per AKI network (AKIN) criteria. Patients were recruited after approval from the scientific and institutional ethics committee, with written informed consent. Serum creatinine values at admission and further values were noted. GFR was calculated using both formulas (CKD-EPI and kGFR) and documented at all intervals of creatinine sampling. Drugs requiring renal dose modification along with the dosing were documented. Sample size was calculated after a pilot study and a total of 107 patients were analyzed.

Results: Incidence of AKI was 12.84%. The mean (±SD) eGFR was 37.25 (±29.4) and kGFR was 42.5 (±33.2), (p-value .003). 70 (65.42%) patients required drug dose change when kGFR was used. Dosing changes from Day 1 to Day 5 are 53/104 (50.9%), 39/81 (48.1%), 12/26 (46.1%), 2/9 (28.5%), 1/2 (50%). Predominant dose changes were for antimicrobials: vancomycin (35.7%), acyclovir (23.1%), and meropenem (23%).

Discussion: Drug dosing using different methods of GFR calculation showed a difference in the dosing in 65.42% of patients with AKI. Accounting for change in creatinine over time using kinetic GFR may lead to better drug dosing in critically ill patients with AKI.

Conclusion: Our study shows that calculating GFR using kGFR formula instead of CKD-EPI may change drug dosages among patients with AKI admitted in ICU. By replacing conventional GFR estimation formulas with kGFR we may reduce the drug dosing inaccuracies that are currently prevalent in this cohort of patients.

Delusional misidentification, a rare syndrome in which a patient displays persistent delusional misidentification of individuals or objects, occurs in several types of dementia. However, the pathology of delusional misidentification is still unclear, and there was no data pertaining to striate-frontal projection. Here, we report a case of delusional misidentification following frontotemporal dementia in which complex striate-frontal and some specific frontal gyrus dysfunction were observed. In our presented case, delusional misidentification progressed following frontal atrophy. Believing that her actual daughter had been replaced by her niece, her symptoms of delusional misidentification and frontal atrophy progressed in the short term, and social arrangement was necessary three months after the onset. There were no abnormal neurological findings including parkinsonism and general cognitive function test scores were preserved. Validated by dopamine transporter single-photon emission computed tomography, right unilateral striatal uptake decreased significantly without parkinsonism or Parkinson's disease. In addition, of specific concern, functional magnetic resonance images showed left opercular inferior frontal gyrus and right superior frontal gyrus dysfunctions. Our case study highlights complex striate-frontal projection and specific frontal gyrus dysfunctions associated with the pathology of delusional misidentification syndrome.

Objectives: Data regarding the long-term outcomes of patients with thromboangiitis obliterans (TAO) after drug therapy (DT) alone and endovascular procedure (EP)+ drug therapy (DT) are limited. In this study, we compared the long-term outcomes and prognostic factors of major amputation in TAO patients treated with DT alone and those treated with EP+ DT.

Methods: Consecutive patients with TAO treated at Ganzhou People's Hospital between 2012 and 2022 were included in this real-world study. All patients were administered DT. Some patients were treated with EP in addition to DT. The patients were classified into two groups: the DT group and the EP+ DT group. Long-term follow-up was sustained for all patients after treatment, and limb events were documented throughout the follow-up period. Cox regression analyses were used to analyze the factors associated with major amputation of the TAO.

Results: A total of 150 TAO patients with 175 lower limb lesions were included in the study and the number of patients in DT group and EP+ DT group was 81 and 69, respectively. The technical success rate in the EP group was 82.6%. The major amputation was performed in 19 and 21 patients in the respective groups, accounting for 26.7% of the total patients. The Kaplan-Meier curves for major amputation did not significantly differ between the two groups. Cox regression analysis revealed that disease duration (hazard ratio (HR), 0.865; 95% confidence interval (CI) [0.783-0.979], p = 0.005), wound grade (HR, 2.240; 95% CI 1.565-3.207], p < 0.001) and current smoking (HR, 3.075; 95% CI 1.317-7.812], p = 0.009) were independent factors for major amputation in patients with TAO.

Conclusion: In terms of long-term outcomes, major amputation in TAO patients did not seem to be related to the treatment methods despite a higher immediate patency rate observed after endovascular procedures. Additionally, we identified independent factors for major amputation.

Hearing loss is the third most significant cause of disability globally and is associated with anxiety, depression, loneliness, and cognitive decline. For those unable to utilize conventional hearing aids due to conditions such as ear canal atresia, eczema, recurrent external otitis or extensive ear surgery, implantable hearing aids provide an alternative. This narrative review provides an overview of available bone conduction devices and active middle ear implants. The rapid advancements in implantable hearing aid technology necessitate ongoing education of healthcare professionals to enable informed patient decisions.