bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel chemical entity, that reverses Warburg metabolism by disrupting VDAC1/HK2 interaction through “Toposteric Effect” in Cancer
Authors: Herzberg Max , Becker Oren M. , Behar Vered , Yosef Reut , Dor-On Eyal , Pahima Hadas , de Conto Veronique , Maubon Nathalie , Sagiv Yuval 
Published: May 2024

Abstract

Background
Acidic pH and low oxygen levels Due to the Warburg effect have been shown to impart resistance to certain anti-cancer therapies for solid tumors, such as radiation and a variety of chemotherapeutic drugs. Cancer immunotherapy represents one of the most exciting advancements in recent cancer therapy. However, despite these achievements, the numbers of patients with effective cure are very low for patients with solid tumors. Recent studies pointed out that the main cause for this low efficiency is the Tumor microenvironment (TME), with metabolic changes, and immune evasion that renders solid tumor eradication a real challenge. Drugs targeting the inhibitory TME are urgently needed in combination with Immunotherapy, as well as other conventional therapies like chemotherapy and cancer targeted growth blockers.
Methods
In this study we used an inhibitor of Hexokinase-2 binding to the mitochondrial VDAC1 channel (VDA-1275), that is shown to block cancer cell proliferation, induce apoptosis in cancer cells, and change TME from a protumor to a pro-immunological environment. Our studies demonstrate a significant tumor growth inhibition and survival prolongation, combined with a strong safety profile in-vivo. In addition, a powerful synergistic anti-cancer effect was demonstrated, using a 3D cell culture with human hepatic cancer cell organoids, when VDA-1275 was combined with low levels of Cisplatin or Sorafenib, as examples for chemotherapy and targeted therapy treatments, respectively.
Results
Our results suggest that VDA-1275 is a novel compound that effect cancer cells directly and indirectly by changing the TME to a pro-immunogenic environment.
Conclusion
VDA-1275 may be used as a standalone drug, or in combination therapy that will allow more effective and safe treatment of patients with solid tumors. We coined the word and concept of “Toposteric” effect as the use of small molecules or peptides which interact with a receptor or ligand binding site avoiding the possibility of a pro-pathological harmful anchoring without affecting its active site.
Blood mercury and depressive symptoms: a longitudinal study combining metabolomics
Authors: Li Xinyuan , Ma Yang , Qiao Lingyan , Feng Mingyu , Sun Shengjun , Wen Shuo , Yang Liu , Yan Lailai , Ye Tingting , Wang Jianyu , Xu Ping , Li Shanshan , Fan Shijie , Guo Yuming , Lu Peng 
Published: May 2024

Abstract

Mercury exposure may increase the risk of depression. This study aimed to examine the association between blood mercury and depressive symptoms in Chinese young adults. We collected 477 fasting venous blood samples and questionnaire data from the Chinese undergraduate cohort study in 2019 and 2021. Patient Health Questionnaire-9 was used to estimate depressive symptoms. Blood mercury levels and metabolomic levels were measured using inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography-mass spectrometry. Using linear mixed-effects models and ANOVAs based on baseline blood samples (N = 468) to examine metabolomic changes associated with mercury exposure. Our study found for every 2-fold increase in blood mercury levels, the depression scale score increased by 0.50 [95% confidence interval (CI): 0.14, 0.86]. And in males, a 2-fold increase in blood mercury levels was associated with a 0.87 (95% CI: 0.12, 1.61) increase in depression scale scores, while it wasn’t observed in females. Individuals consuming fish ≥ once a month shows similar negative correlation. Metabolomic analysis identified 10 differential metabolites enriched in 4 metabolic pathways. Blood mercury may deteriorate depressive symptoms. Males and those who consume more fish are susceptible subjects. Mercury exposure may affect depressive symptoms through neurotransmitter, energy and inflammation-related pathways.
Predicting Long-Term Patency of Radiocephalic Arteriovenous Fistulas with Machine Learning and the PREDICT-AVF Web App
Authors: Fitzgibbon James J. , Ruan Mengyuan , Heindel Patrick , Appah-Sampong Abena , Dey Tanujit , Khan Ali , Hentschel Dirk M. , Ozaki C. Keith , Hussain Mohamad A. 
Published: May 2024

Abstract

The goal of this study was to expand our previously created prediction tool (PREDICT-AVF) and web app by estimating long-term primary and secondary patency of radiocephalic AVFs. The data source was 911 patients from PATENCY-1 and PATENCY-2 randomized controlled trials, which enrolled patients undergoing new radiocephalic AVF creation with prospective longitudinal follow up and ultrasound measurements. Models were built using a combination of baseline characteristics and post-operative ultrasound measurements to estimate patency up to 2.5 years. Discrimination performance was assessed, and an interactive web app was created using the most robust model. At 2.5 years, the unadjusted primary and secondary patency (95% CI) was 29% (26%-33%) and 68% (65%-72%). Models using baseline characteristics generally did not perform as well as those using post-operative ultrasound measurements. Overall, the Cox model(4-6 weeks ultrasound) had the best discrimination performance for primary and secondary patency, with an integrated Brier score of 0.183 (0.167, 0.199) and 0.106 (0.085, 0.126). Expansion of the PREDICT-AVF web app to include prediction of long-term patency can help guide clinicians in developing comprehensive end-stage kidney disease Life-Plans with hemodialysis access patients.
Lipid accumulation product Index is more Closely related to Hyperuricemia than other Obesity Indices or Lipid Parameters: a population-based study
Authors: Li Lusha , Cai Xixuan , Xu Mingying , Chen Jieru , Huang Yilin , Shen Keqing , Pan Jianjiang , Zhu Yue , Chen Liying 
Published: May 2024

Abstract

Background
Both obesity and dyslipidemia are associated with hyperuricemia (HUA). However, it is unclear which obesity indices or lipid parameters are strongly associated with HUA. Therefore this study aims to analyze and compare the associations of HUA with the obesity indices, lipid parameters, and its discriminative power. To provide early guidance on risk predictors of HUA in the Chinese population.
Methods
This study was a cross-sectional survey including 60,516 participants. Investigators conducted face-to-face interview surveys and physical examinations. Automated biochemical methods were used to detect biochemical indicators. Logistic regression was used to analyze the relationship between obesity indices, lipid parameters, and HUA. The odds ratio (OR) value and 95% confidence interval (95%CI) were used to reflect the strength of their association. Receiver operating characteristic (ROC) curve was used for assessing the predictive ability of different indices of HUA.
Results
Multivariate logistic regression analysis showed that compared with other obesity indices and lipid parameters, the LAP index has a significant association with HUA, especially in females (total participants, OR 7.143, 95% CI 6.669-7.652, P<0.001; males, OR 5.831, 95% CI 5.353-6.352, P<0.001; females, OR 8.178, 95% CI 7.209-9.277, P<0.001). Except for Hdlc, all other indices could predict the occurrence of HUA. For males, the area under the curve (AUC) of the LAP index was the largest (AUC 0.665, 95% CI 0.659-0.671, P < 0.001), with a cut-off value of 33.135. In females, the LAP index also showed a maximum AUC value of 0.701 (95%CI 0.712-0.730, P < 0.001), with a cut-off value of 20.465.
Conclusions
The LAP index was significantly associated with HUA and had better power to discriminate HUA compared with other obesity indices or lipid parameters in the Chinese population.
Trial registration
Not applicable.
Thoracoabdominal aortic replacement in a 6-year-old boy with Loeys-Dietz syndrome
Authors: Zhen Jianfan , Sun Tucheng , Yu Changjiang 
Published: May 2024

Abstract

Connective tissue disorders such as Marfan- and Loeys-Dietz syndrome (LDS) can lead to aortic aneurysms and aortic dissections in children. Patients with LDS often necessitating multiple aortic surgeries throughout their lives to extend their lifespan. A boy underwent Bentall procedure at the age of three for aortic aneurysm. On August 4, 2023, this boy was referred to the hospital again due to severe abdominal pain. CTA indicates aortic dissection (DeBakey Type III, Stanford Type B). After a multidisciplinary team discussion, a successful thoracoabdominal aortic replacement was performed.
Assessing the causal relationship between serum urate and the risk of lung cancer: a bidirectional Mendelian randomization study
Authors: Cheng Zewen , Wu Jian , Xu Chun , Yan Xiaokun 
Published: May 2024

Abstract

Background: Serum urate levels have been associated with a lower risk of lung carcinogenesis in observational studies but the causality from serum urate levels on lung cancer has yet to determined. We conducted a bidirectional Mendelian randomization(MR) study to evaluate the causal effect of these associations.
Methods: Summary-level data for serum urate were obtained from 288,649 CKDGen participants of European ancestry. We drew summary statistics of lung cancer from the TRICL (29,266 cases and 56,450 controls), the ILCCO (11,348 cases and 15,861 controls) and the FinnGen study (1,627 cases and 174,006 controls). The inverse-variance-weighted method was applied to estimate the causal effects, whereas weighted median, MR-Egger, and MR pleiotropy residual sum and outlier were performed in the sensitivity analyses. Analyses were conducted per outcome database and were subsequently meta-analyzed using a fixed-effects model.
Results: Genetically determined serum urate levels were associated with lung adenocarcinoma (LUAD) [odds ratio(OR), 0.89; 95% confidence interval (CI), 0.82–0.97; P = 0.007] and overall lung cancer (OR, 0.94; 95% CI, 0.89-0.99; P = 0.014). The main results remained robust in most of the sensitivity analyses. The association pattern remained for the combined results of the three databases[(OR, 0.90; 95% CI, 0.84-0.96; P = 0.002); (OR, 0.94; 95% CI, 0.90-0.98; P = 0.006)]. No consistent evidence was found for the causal effect of lung cancer on serum urate levels.
Conclusions: Our MR estimates provide consistent evidence for the independent effect of serum urate levels on lung cancer, particularly LUAD, which may be mediated by urate metabolic process, but not the reverse effect of lung cancer. Urate-elevating therapy may be of pulmonary benefit in the prevention of lung cancer.
Deep Learning-Assisted Segmentation of X-ray Images for Rapid and Accurate Assessment of Foot Arch Morphology and Plantar Soft Tissue Thickness
Authors: Ning Xinyi , Ru Tianhong , Zhu Jun , Chen Li , Ma Xin , Huang Ran 
Published: May 2024

Abstract

The morphological characteristics of the foot arch and the plantar soft tissue thickness are pivotal in assessing foot health, which is associated with various foot and ankle pathologies. By applying deep learning image segmentation techniques to lateral weight-bearing X-ray images, this study investigates the correlation between foot arch morphology (FAM) and plantar soft tissue thickness (PSTT), examining influences such as age, gender, health status, physical activity, and footwear habits. Specifically, we use the DeepLab V3 + network model to accurately delineate the boundaries of the first metatarsal, talus, calcaneus, navicular bones, and overall foot, enabling rapid and automated measurements of FAM and PSTT. A retrospective dataset containing 1,497 X-ray images is analyzed to explore associations between FAM, PSTT, and various demographic factors. Our findings contribute novel insights into foot morphology, offering robust tools for clinical assessments and interventions. The enhanced detection and diagnostic capabilities provided by precise data support facilitate population-based studies and the leveraging of big data in clinical settings.
Periodic fever syndromes in Chinese children and adolescents: a single-centre cohort study
Authors: Chen Xiongbin , Li Yulu , Yang Mengyang , Shu Zhou , Mao Huawei 
Published: May 2024

Abstract

Objective: Periodic fever syndromes (PFS) are a broad group of autoinflammatory diseases characterised by recurrent episodes of fever in the absence of microbial, autoimmune or malignant conditions. We aimed to evaluate the clinical and genetic characteristics of patients with periodic fever syndrome. And to evaluate the safety and efficacy of colchicine in the treatment of PFS.
Methods: This study included patients diagnosed with PFS between April 2021 and January 2024 at Bei Jing Children's Hospital, Immunology Department. We retrospectively analyzed the clinical data (clinical features, laboratory findings and genetic features). The onset of the disease and adverse events following the use of colchicine were also analysed.
Results: A total of 130 patients were included in this study, with a male to female ratio of 1.2:1. The mean (95% CI) ages at symptom onset and diagnosis were 3.59(3.06-4.11) years and 5.33(4.79-5.87) years, respectively. The average duration of the febrile episode is 3.92 days and the average frequency of the febrile episode is 3.44 weeks. During PFS flares, leukocytes, neutrophils, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than in inter-episode periods. The most frequently detected gene mutation is MEFV. Thirty-five patients were free of clinical symptoms 5 month after taking colchicine.
Conclusion: We present a cohort of children and adolescence with periodic fever syndrome. The most common PFS is PFAPA and the most common gene mutation in PFS patients is MEFV. Colchicine is a safe and effective drug for the treatment of PFS.
Prevalence and risk factors for falls among the elderly in communities of Chongqing municipality, China: a cross-sectional survey
Authors: Yang Xianxian , Li Wanhua , He Jitong , Zhang Guiting , Tan Qiang , Tan Bin , Ding Xianbin 
Published: May 2024

Abstract

Background The aging population is associated with an increasing burden of falls worldwide. However, the epidemiological features of falls in Chongqing, China are not well understood. Objective To assess the prevalence and factors associated with falls in an elderly population aged 60 years or older in Chongqing municipality, China. Design, setting, and subjects This cross-sectional study was conducted from April 2022 to December 2022. A random sample of individuals aged 60 years or older, representative of both urban and rural areas of Chongqing were enrolled, with a 100% participation rate. Methods The weighted prevalence of and risk factors associated with falls by age, sex, and urban vs rural residence were determined by electronic questionnaire. Results A total of 3 072 participants were included in this study (1 534 women [49.93%]; mean [SD] age, 53 [13] years) who had a free medical examination and completed the questionnaire. The prevalence of falls among those aged 60 years or older was 20.28%, 14.83% (95% CI, 13.06%-16.61%) among men and 25.94% (95% CI, 23.74%-28.13%) among women, 15.95% (95% CI, 14.12%-17.78%) in urban and 24.78% (95% CI, 22.62%-26.94%) in rural, and the 80-year-old age group had the highest fall rate (25.78%). According to the multivariable logistic regression analysis, self-rated health status is poor (OR = 2.24, 95% CI 1.65–3.04), afraid of falling (OR = 1.78, 95% CI 1.43–2.20), even if not injured, one should not tell family or doctor after a fall (OR = 1.68, 95% CI 1.32–2.14), and female gender (OR = 1.60, 95% CI 1.32–1.95) were the top four risk factors. Conclusionsand RelevanceIn this cross-sectional study of the elderly population in Chongqing municipality, China, the prevalence of falls was high in men and women. Fall prevention health education and behavior intervention should be focused on the elderly and women to reduce the prevalence and mitigate the harm of falls.
Microbiology and predictors of mortality in haematological malignancy patients with gram-negative bacterial bloodstream infections
Authors: Zheng Jing , Li Jinlian , xu Xuejun , Li Yuqing , Guo Ya , Hu Jing , Wang Ling 
Published: May 2024

Abstract

Background: Bloodstream infection (BSI) in haematological malignancy patients caused by gram-negative bacteria (GNB) poses a clinical challenge, which is exacerbated by the increased dissemination of carbapenem-resistant GNB (CRGNB). In this study, we investigated the prevalence and factors for GNB BSI and mortality in this population.
Methods: This retrospective study included haematological malignancy patients who developed GNB BSI between 2015 and 2023 at a tertiary teaching hospital in southern China. Risk factors for CRGNB BSI and mortality of GNB BSI were identified by using multivariate logistic analyses. The patients were randomly divided into training and validation cohorts at a ratio of 7:3 to establish the model of 30-day mortality. C-indices, calibration plots, and decision curve analyses were generated to evaluate the model. A nomogram of the model was established.
Results: Among the 351 patients with GNB BSIs, acute myeloid leukaemia (51.3%) was the most common. Escherichia coli (28.8%) and Klebsiella pneumoniae (29.7%) were the most common pathogens of GNB BSI and CRGNB BSI, respectively. The risk factors for CRGNB BSI were chronic liver disease, previous exposure to carbapenems, a platelet count < 30×109/l and an albumin concentration < 30 g/l before BSI. The model for 30-day mortality of GNB BSI included neutropenia and an albumin concentration < 30 g/l before BSI, as well as septic shock and mechanical ventilation after BSI. The C-indices were 0.942 and 0.931 in the training and validation cohorts, respectively. The calibration plots and decision curves indicated that the model had good performance.
Conclusions: The identified factors allow for the stratification of patients at greatest risk for CRGNB BSI and poor prognosis for GNB BSI, which could help in facilitating timely effective intervention.
Simulation and experimental study on the effects of annular groove design on the inner surface of behind-armor damage
Authors: Zhou Peng , Li Rujiang 
Published: May 2024

Abstract

The continual pursuit of enhanced destructive effects in contemporary military endeavors has fostered in-depth research aimed at enhancing warhead performance. This study focuses on improving the lateral killing efficacy of shaped charge explosives, employing Smoothed Particle Hydrodynamics (SPH) methodology for simulation. Keeping charge height and warhead diameter constant, the investigation analyzes the impact of varying depths and spacings of annular grooves on post-destruction effects. Research findings indicate that, contingent upon groove depth and spacing, there are distinct patterns of change in both front and rear perforation areas. Particularly noteworthy is the observed increase in front perforation area by 66.14% and rear perforation area by 17.8% under the conditions of a 2mm spacing and 0.3mm depth of grooves, significantly surpassing the ungrooved scenario. Aluminum plate perforation analysis reveals that, in the majority of cases, annular grooved warhead shells result in larger primary perforation areas and a greater number of secondary perforations compared to ungrooved counterparts. Experimental and numerical simulation results demonstrate highly consistent penetration effects of annular grooved warhead shells within different spacings, with errors consistently below 5%. Particularly in the case of annular grooves with a depth of 0.3mm, the expansion area varies with spacing, while experiments and simulation results with a 2mm spacing exhibit pronounced front and rear perforation areas, reflecting effectiveness in diffusion-based killing effects. Overall, the design of annular grooves on the inner surface of warhead shells significantly enhances lateral diffusion effects, with the consistency between experimental and simulation data reinforcing this assertion.
A Centralised Control Approach to Compliant Aerial Manipulation on Overhangs
Authors: Brummelhuis Martijn Bernard Johan , Smeur Ewoud Jan Jacob , Hamaza Salua 
Published: May 2024

Abstract

Aerial physical interaction opens the door for many operations at height to be automated using flying robots. This research presents a novel manipulator design mounted on a traditional quadrotor, which employs both mechanical and software compliance to perform physical interaction on vertical walls and overhanging surfaces, such as those found under bridges. A centralised control scheme paired with an impedance filter enables direct control of the end-effector pose in the task space, without the need for separate control modes for the free-flight and contact phases. A spring-loaded prismatic joint on the manipulator provides mechanical compliance, while doubling as a force-feedback for the impedance filter by measuring the spring displacement. Flight experiments validate our approach for exerting high forces at height with varying wall inclinations, with a total of 43 successful experiments carried out in four different settings. In these flight experiments an average maximum force of 5.66 N, or 19.3% of the system's weight was sustained.
Experimental results of a 330 GW impedance-matched Marx generator
Authors: Damideh Vahid , Btaiche J. C. , Ho Alex , Spielman R. B. , Lehr Jane M. , Mehlhorn T. A. , Hassen Isaac , Akoulov Alexei , Aranfar Elahe , McDonald Alex , Tochon Pierre , Choudhury Ayan , Beaulieu Emile , Tan Hao Xian , Faliero Sophie , Tetreault Richard , Breault Gael , Tetreault Rodrigue , Hosseiny Negar , Smith Edward 
Published: May 2024

Abstract

Impedance-Matched Marx Generators (IMGs) are considered next generation pulsed-power drivers because of their long lifetime (> 10,000 shots), repeatability (> 0.1-Hz), fast rise time (~ 100-ns), and high-energy-delivery efficiency (~ 90%). “TITAN” is a 14-stage IMG designed to deliver 1-TW to a 2-Ω matched load. In this paper, design, simulation, and experimental results for six stages of TITAN including its triggering system, air delivery system, and pulse shaping are presented. To achieve efficiency over 85% and maximize the capability of an IMG, synchronized triggering, reduced pre-fire rate, and pulse shaping ability are crucial. In this paper, novel engineering solutions are introduced, tested, and proven to overcome those challenges. 6-stage TITAN, powered by 102 identical bricks and 102 field-distortion-triggered gas switches, could generate ~ 600-kA and ~ 700-kV across a ~ 0.9-Ω matched load when fully charged to +/- 100-kV. In these experiments, 6-stage TITAN is tested up to +/- 70-kV charge voltage which delivers a peak power of 330-GW to a 1.2-Ω resistive load.