bluuebunny/crossref_metadata_2025 huggingface dataset:
Driving mechanisms and multi-scenario simulation of land use change based on National Land Survey Data: a case in Jianghan Plain, China
Authors: Zhou Heng , Tang Mingdong , Huang Jun , Mei Xiaoxia , Zhao Haijuan
Published: July 2024

The Jianghan Plain is simultaneously responsible for ecological protection, food security and urbanization, and land use conflicts are prominent. Revealing the driving mechanism of land use/cover change (LUCC) and simulating the land use pattern can help to coordinate the land use conflicts in the future. Utilizing the National Land Survey Data (NLSD) of Jiangling County in Jianghan Plain (2011–2020) and the patch-generating land use simulation (PLUS) model, this paper analyzed the characteristics of land use evolution, applied the random forest classification (RFC) to analyze the driving mechanism, simulated the 2035 land use pattern under three scenarios of natural development, planning guidance and ecological protection through Markov and Cellular Automaton based on multiple random seeds (CARS) models, and proposed several countermeasures. The study found that: 1) From 2011 to 2020, town construction land increased, village construction land, agricultural land and ecological land decreased. 2) The factors driving LUCC were socio-economic factors, spatial factors, and natural factors in descending order. 3) In the three scenarios, the trend of construction land expansion, agricultural land and ecological land encroachment is inevitable by 2035. 4) It is imperative to actively advocate for large-scale mechanization and informatization of agricultural production, encourage the repurposing of idle and inefficiently used construction land, facilitate multi-purpose land utilization, and implement a policy of locally balancing occupation and compensation for cultivated and ecological land. 5) When employing the PLUS model to simulate LUCC, using continuous NLSD yielded more accurate results than remote sensing image interpretation data. This study offers a theoretical basis for the coordinated development of land use in Jianghan Plain, and presents a method to enhance the simulation accuracy of the PLUS model.
Causal associations between sleep traits and temporomandibular disorders: a bidirectional mendelian randomization analysis
Authors: Xu Lihan , Zhou Haojing
Published: July 2024

Objectives

This study aims to investigate the relationship between five sleep traits (insomnia, sleep duration, getting up in morning, snoring, and daytime nap) and temporomandibular disorders (TMD) using bi-directional Mendelian randomization.

Methods

The bi-directional Mendelian randomization study was conducted in two stages. Initially, sleep traits were examined as exposures while TMD was evaluated as an outcome, whereas the second step was reversed. The inverse variance weighted (IVW) method and other Mendelian randomization methods were used for analysis. Furthermore, we performed the MR-Egger intercept, MR-PRESSO, Cochran’s Q test, and “Leave-one-out” to assess the levels of pleiotropy and heterogeneity.

Results

The IVW method indicates that getting up in the morning reduces the risk of developing TMD (OR = 0.50, 95% CI 0.30–0.81, p = 0.005), while insomnia may increase the risk of TMD (OR = 2.05, 95% CI 1.10–3.85, p = 0.025). However, other sleep traits are not associated with the risk of TMD, and having TMD does not alter an individual’s sleep traits. After removing outliers, the results remained robust, with no pleiotropy detected.

Conclusion

Genetically determined difficulty in getting up in the morning and insomnia can increase the risk of TMD. By optimizing sleep, the risk of developing TMD can be reduced. This underscores the importance of sleep in preventing TMD.
Proposal of a novel cardiovascular risk prediction score in lupus nephritis
Authors: Molnár Adél , Juha Márk , Bulajcsík Klaudia , Tabák Ádám Gy. , Tislér András , Ledó Nóra
Published: July 2024

Introduction

Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality.

Methods

We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations.

Results

91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE – Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence.

Conclusion

This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.
Human stem cell–derived neurons and astrocytes to detect novel auto-reactive IgG response in immune-mediated neurological diseases
Authors: Mathias Amandine , Perriot Sylvain , Jones Samuel , Canales Mathieu , Bernard-Valnet Raphaël , Gimenez Marie , Torcida Nathan , Oberholster Larise , Hottinger Andreas F. , Zekeridou Anastasia , Theaudin Marie , Pot Caroline , Du Pasquier Renaud
Published: July 2024

Background and objectives

Up to 46% of patients with presumed autoimmune limbic encephalitis are seronegative for all currently known central nervous system (CNS) antigens. We developed a cell-based assay (CBA) to screen for novel neural antibodies in serum and cerebrospinal fluid (CSF) using neurons and astrocytes derived from human-induced pluripotent stem cells (hiPSCs).

Methods

Human iPSC-derived astrocytes or neurons were incubated with serum/CSF from 99 patients [42 with inflammatory neurological diseases (IND) and 57 with non-IND (NIND)]. The IND group included 11 patients with previously established neural antibodies, six with seronegative neuromyelitis optica spectrum disorder (NMOSD), 12 with suspected autoimmune encephalitis/paraneoplastic syndrome (AIE/PNS), and 13 with other IND (OIND). IgG binding to fixed CNS cells was detected using fluorescently-labeled antibodies and analyzed through automated fluorescence measures. IgG neuronal/astrocyte reactivity was further analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were used as CNS-irrelevant control target cells. Reactivity profile was defined as positive using a Robust regression and Outlier removal test with a false discovery rate at 10% following each individual readout.

Results

Using our CBA, we detected antibodies recognizing hiPSC-derived neural cells in 19/99 subjects. Antibodies bound specifically to astrocytes in nine cases, to neurons in eight cases, and to both cell types in two cases, as confirmed by microscopy single-cell analyses. Highlighting the significance of our comprehensive 96-well CBA assay, neural-specific antibody binding was more frequent in IND (15 of 42) than in NIND patients (4 of 57) (Fisher’s exact test, p = 0.0005). Two of four AQP4+ NMO and four of seven definite AIE/PNS with intracellular-reactive antibodies [1 GFAP astrocytopathy, 2 Hu+, 1 Ri+ AIE/PNS)], as identified in diagnostic laboratories, were also positive with our CBA. Most interestingly, we showed antibody-reactivity in two of six seronegative NMOSD, six of 12 probable AIE/PNS, and one of 13 OIND. Flow cytometry using hiPSC-derived CNS cells or PBMC-detected antibody binding in 13 versus zero patients, respectively, establishing the specificity of the detected antibodies for neural tissue.

Conclusion

Our unique hiPSC-based CBA allows for the testing of novel neuron-/astrocyte-reactive antibodies in patients with suspected immune-mediated neurological syndromes, and negative testing in established routine laboratories, opening new perspectives in establishing a diagnosis of such complex diseases.
IL-2 based cancer immunotherapies: an evolving paradigm
Authors: Rokade Sushama , Damani Anita Mehta , Oft Martin , Emmerich Jan
Published: July 2024

Discovered over 4 decades ago in the supernatants of activated T cells, interleukin-2 (IL-2) is a potent pleiotropic cytokine involved in the regulation of immune responses. It is required for effector T cell expansion and differentiation as well as for peripheral tolerance induced by regulatory T cells. High-dose IL-2 treatment was the first FDA-approved immunotherapy for renal cell carcinoma and melanoma, achieving single agent complete and durable responses, albeit only in a small proportion of patients. The therapeutic potential of wild type IL-2 is clinically limited by its short half-life and severe vascular toxicity. Moreover, the activation of regulatory T cells and the terminal differentiation of effector T cells on IL-2 pose additional restrictions. To overcome the toxicity of IL-2 in order to realize its full potential for patients, several novel engineering strategies are being developed and IL-2 based immunotherapy for cancer has emerged as a burgeoning field of clinical and experimental research. In addition, combination of IL-2 with PD-1/L1 pathway blockade shows vastly improved anti-tumor efficacy over either monotherapy in preclinical tumor models. In this review we discuss the biological characteristics of IL-2 and its receptors, as well as its efficacy and treatment limiting toxicities in cancer patients. We also explore the efforts aimed at developing novel and safer IL-2 therapies to harness the full therapeutic potential of this cytokine.
Behavioral response of megafauna to boat collision measured via animal-borne camera and IMU
Authors: Chapple Taylor K. , Cade David E. , Goldbogen Jeremy , Massett Nick , Payne Nicholas , McInturf Alexandra G.
Published: July 2024

Overlap between marine megafauna and maritime activities is a topic of global concern. Basking sharks (Cetorhinus maximus; CM) are listed as Globally Endangered under the IUCN, though reported sightings appear to be increasing in Ireland. While such trends in the region are welcome, increasing spatiotemporal overlap between CM and numerous water users poses an increased risk of boat strikes to the animals. To demonstrate the risk and impact of boat strikes on marine megafauna, we present camera-enabled animal-borne inertial measurement unit (IMU) data from a non-lethal boat strike on a CM within a proposed National Marine Park in Ireland. We tagged a ~7-m female CM in County Kerry, Ireland, which was struck by a boat ~6 h after tag deployment. Comparison of pre-strike data with 4 h of video and ~7.5 h of IMU data following the boat strike provides critical insight into the animal’s response. While the CM reacted momentarily with an increase in activity and swam to the seafloor, it quickly reduced its overall activity (i.e., overall dynamic body acceleration, tailbeat cycles, tailbeat amplitude, and vertical velocity) for the remainder of the deployment. Notably, the animal also ceased feeding for the duration of the video and headed towards deep offshore waters, which is in stark contrast to the pre-strike period where the animal was consistently observed feeding along the surface in shallow coastal water. This work provides insight into a CM’s response to acute injury and highlights the need for appropriate protections to mitigate risks for marine megafauna.
Comparison of sevoflurane and propofol in combination with remifentanil on the quality of postoperative recovery in patients undergoing laparoscopic bariatric surgery
Authors: Shu Zhuolin , Lin Tiancheng , Xu Dingchen , Zheng Shuyuan
Published: July 2024

Objective

This study aimed to evaluate and compare the effects of sevoflurane + remifentanil (Sev + Rem) and propofol + remifentanil (Pro + Rem) on the postoperative recovery quality of patients undergoing laparoscopic bariatric surgery to determine which anesthesia regimen provides a better overall recovery experience.

Methods

Sixty patients were divided into two groups based on the treatments they underwent: Sev + Rem (n = 30) and Pro + Rem (n = 30). The Sev + Rem group received sevoflurane inhalation (0.5%, increasing to 0.5–4%) and remifentanil via target-controlled infusion. The Pro + Rem group received propofol [4–8 mg/(kg·h)] and remifentanil via target-controlled infusion. Anesthesia depth was maintained at a bispectral index of 40–60 in both groups. Perioperative data, hemodynamic parameters, and postoperative recovery quality were assessed.

Results

Compared to the Pro + Rem group, the dose of remifentanil in the Sev + Rem group was significantly lower (1693.67 ± 331.75 vs. 2,959 ± 359.77, p < 0.001), the proportion of patients used norepinephrine was markedly higher [16 (53.33) vs. 8 (26.67), p = 0.035], and the time of extubation was earlier (356.33 ± 63.17 vs. 400.3 ± 50.11, p = 0.004). The Hemodynamic results showed the HR in the Sev + Rem group was faster than that in the Pro + Rem group at the beginning of surgery and 1 h post-surgery (67.37 ± 4.40 vs. 64.33 ± 4.44, p = 0.010, 69.07 ± 4.23 vs. 66.40 ± 5.03, p = 0.030). In regard to the assessment of postoperative recovery quality, the emotional state scores in the Sev + Rem group were significantly lower than the Pro + Rem group (36.83 ± 2.79 vs. 39.50 ± 4.64, p = 0.009).

Conclusion

The two anesthesia modalities (Sev + Rem and Pro + Rem) have their advantages and disadvantages for patients undergoing laparoscopic bariatric surgery and have comparable effects on postoperative recovery quality.
A robust ensemble deep learning framework for accurate diagnoses of tuberculosis from chest radiographs
Authors: Sun Xin , Xing Zhiheng , Wan Zhen , Ding Wenlong , Wang Li , Zhong Lingshan , Zhou Xinran , Gong Xiu-Jun , Li Yonghui , Zhang Xiao-Dong
Published: July 2024

Introduction

Tuberculosis (TB) stands as a paramount global health concern, contributing significantly to worldwide mortality rates. Effective containment of TB requires deployment of cost-efficient screening method with limited resources. To enhance the precision of resource allocation in the global fight against TB, this research proposed chest X-ray radiography (CXR) based machine learning screening algorithms with optimization, benchmarking and tuning for the best TB subclassification tasks for clinical application.

Methods

This investigation delves into the development and evaluation of a robust ensemble deep learning framework, comprising 43 distinct models, tailored for the identification of active TB cases and the categorization of their clinical subtypes. The proposed framework is essentially an ensemble model with multiple feature extractors and one of three fusion strategies-voting, attention-based, or concatenation methods-in the fusion stage before a final classification. The comprised de-identified dataset contains records of 915 active TB patients alongside 1,276 healthy controls with subtype-specific information. Thus, the realizations of our framework are capable for diagnosis with subclass identification. The subclass tags include: secondary tuberculosis/tuberculous pleurisy; non-cavity/cavity; secondary tuberculosis only/secondary tuberculosis and tuberculous pleurisy; tuberculous pleurisy only/secondary tuberculosis and tuberculous pleurisy.

Results

Based on the dataset and model selection and tuning, ensemble models show their capability with self-correction capability of subclass identification with rendering robust clinical predictions. The best double-CNN-extractor model with concatenation/attention fusion strategies may potentially be the successful model for subclass tasks in real application. With visualization techniques, in-depth analysis of the ensemble model's performance across different fusion strategies are verified.

Discussion

The findings underscore the potential of such ensemble approaches in augmenting TB diagnostics with subclassification. Even with limited dataset, the self-correction within the ensemble models still guarantees the accuracies to some level for potential clinical decision-making processes in TB management. Ultimately, this study shows a direction for better TB screening in the future TB response strategy.
A Mendelian randomization analysis reveals the multifaceted role of the skin microbiota in liver cancer
Authors: Wang Xiaoxue , Zhu Zexin
Published: July 2024

Background

Hepatocellular carcinoma (HCC, or hepatic cancer, HC) and cholangiocarcinoma (CCA, or hepatic bile duct cancer, HBDC) are two major types of primary liver cancer (PLC). Previous studies have suggested that microbiota can either act as risk factors or preventive factors in PLC. However, no study has reported the relationship between skin microbiota and PLC. Therefore, we conducted a two-sample Mendelian randomization (MR) study to assess the causality between skin microbiota and PLC.

Methods

Data from the genome-wide association study (GWAS) on skin microbiota were collected. The GWAS summary data of GCST90018803 (HBDC) and GCST90018858 (HC) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was utilized as the principal method in our MR study. The MR-Egger intercept test, Cochran's Q-test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis were conducted to identify the heterogeneity and pleiotropy.

Results

The results showed that Veillonella (unc.) plays a protective role in HBDC, while the family Neisseriaceae has a positive association with HBDC risk. The class Betaproteobacteria, Veillonella (unc.), and the phylum Bacillota (Firmicutes) play a protective role in HC. Staphylococcus epidermidis, Corynebacterium (unc.), the family Neisseriaceae, and Pasteurellaceae sp. were associated with an increased risk of HC.

Conclusion

This study provided new evidence regarding the association between skin microbiota and PLC, suggesting that skin microbiota plays a role in PLC progression. Skin microbiota could be a novel and effective way for PLC diagnosis and treatment.
Eight challenges in developing theory of intelligence
Authors: Huang Haiping
Published: July 2024

A good theory of mathematical beauty is more practical than any current observation, as new predictions about physical reality can be self-consistently verified. This belief applies to the current status of understanding deep neural networks including large language models and even the biological intelligence. Toy models provide a metaphor of physical reality, allowing mathematically formulating the reality (i.e., the so-called theory), which can be updated as more conjectures are justified or refuted. One does not need to present all details in a model, but rather, more abstract models are constructed, as complex systems such as the brains or deep networks have many sloppy dimensions but much less stiff dimensions that strongly impact macroscopic observables. This type of bottom-up mechanistic modeling is still promising in the modern era of understanding the natural or artificial intelligence. Here, we shed light on eight challenges in developing theory of intelligence following this theoretical paradigm. Theses challenges are representation learning, generalization, adversarial robustness, continual learning, causal learning, internal model of the brain, next-token prediction, and the mechanics of subjective experience.
Screening of preoperative obstructive sleep apnea by cardiopulmonary coupling and its risk factors in patients with plans to receive surgery under general anesthesia: a cross-sectional study
Authors: Hou Shujie , Zhu Guojia , Liu Xu , Wang Chuan , Liang Junchao , Hao Wei , Kong Lili
Published: July 2024

Objective

Preoperative obstructive sleep apnea (OSA) is supposed to be the abnormally high occurrence of OSA the night before surgery under general anesthesia. This study aimed to evaluate the prevalence preoperative OSA using cardiopulmonary coupling (CPC) and its correlation with imbalance of sympathetic/parasympathetic nervous system.

Methods

A total of 550 patients with plans to receive surgery under general anesthesia were enrolled. All patients were assigned to wear CPC on the night before surgery until the next day. Sleep quality characteristics, heart rate variation parameters, and apnea-hypopnea index were acquired. The diagnosis of pre-existing OSA was not considered in the current study.

Results

According to apnea-hypopnea index, 28.4%, 32.2%, 26.2%, and 13.3% patients were assessed as no, mild, moderate, and severe operative OSA, respectively. Multivariate logistic regression model revealed that higher age [p < 0.001, odds ratio (OR) = 1.043] was independently and positively associated with preoperative OSA; heart rate variation parameters representing the imbalance of sympathetic/parasympathetic nervous system, such as higher low-frequency (p < 0.001, OR = 1.004), higher low-frequency/high-frequency ratio (p = 0.028, OR = 1.738), lower NN20 count divided by the total number of all NN intervals (pNN20; p < 0.001, OR = 0.950), and lower high-frequency (p < 0.001, OR = 0.998), showed independent relationships with a higher probability of preoperative OSA. Higher age (p = 0.005, OR = 1.024), higher very-low-frequency (p < 0.001, OR = 1.001), and higher low-frequency/high-frequency ratio (p = 0.003, OR = 1.655) were associated with a higher probability of moderate-to-severe preoperative OSA, but higher pNN10 (p < 0.001, OR = 0.951) was associated with a lower probability of moderate-to-severe preoperative OSA.

Conclusion

Preoperative OSA is prevalent. Higher age and imbalance of sympathetic/parasympathetic nervous system are independently and positively associated with a higher occurrence of preoperative OSA. CPC screening may promote the management of preoperative OSA.
Efficacy of cannabinoids compared to the current standard treatments on symptom relief in persons with multiple sclerosis (CANSEP trial): study protocol for a randomized clinical trial
Authors: Zertal Amel , Alami Marrouni Kanza , Arbour Nathalie , Jutras-Aswad Didier , Pomey Marie-Pascale , Rouleau Isabelle , Prat Alexandre , Larochelle Catherine , Beaulieu Pierre , Chamelian Laury , Sylvestre Marie-Pierre , Morin Danielle , Ouellette Jean-Sylvain , Fréjeau Nathalie , Duquette Pierre
Published: July 2024

Background

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions.

Methods

A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l’Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7 days. The main outcome will be the difference in this score at 4 weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments.

Discussion

Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS.

Clinical trial registration

ClinicalTrials.Gov, NCT05092191.
Based on machine learning, CDC20 has been identified as a biomarker for postoperative recurrence and progression in stage I & II lung adenocarcinoma patients
Authors: Miao Rui , Xu Zhi , Han Tao , Liu Yafeng , Zhou Jiawei , Guo Jianqiang , Xing Yingru , Bai Ying , He Zhonglei , Wu Jing , Wang Wenxin , Hu Dong
Published: July 2024

Objective

By utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets.

Methods

To begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment.

Results

First, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway.

Conclusion

CDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.
Comparative cost-effectiveness analysis of CDK4/6 inhibitors in the first-line treatment of HR-positive and HER2-negative advanced breast cancer: a Markov's model-based evaluation
Authors: Elazzazy Shereen , Al-Ziftawi Nour Hisham , Mohamed Ibrahim Mohamed Izham , Bujassoum Salha , Hamad Anas
Published: July 2024

Introduction

CDK4/6 inhibitors are the first-line treatment for HR+/HER2- advanced breast cancer. Despite their clinical benefit, they can increase healthcare expenditure. To date, there is no thorough comparison among the three approved CDK4/6 inhibitors in terms of their cost-effectiveness.

Objective

To investigate and compare the cost-effectiveness of CDK4/6 inhibitors in combination with letrozole as a first-line treatment for advanced breast cancer with hormonal-receptor-positivity and HER-2-negativity versus one another and versus letrozole monotherapy.

Methods

A 10-year within-cycle-corrected Markov’s model was employed from the healthcare payer perspective. Costs were obtained from the National Center for Cancer Care and Research (NCCCR) in Qatar. Utilities and transition probabilities were calculated from published landmark trials of PALOMA-2, MONALEESA-2, MONARCH-3, PO25, and other relevant literature. Costs, measured in Qatari Riyal (QAR), and effectiveness, measured in quality-adjusted-life-years (QALYs), were incremented and the incremental cost-effectiveness ratio (ICER) was compared to a willingness-to-pay threshold (WTP) of 1.5 Qatari GDP (448,758 QAR). A deterministic sensitivity analysis was implemented to account for uncertainties.

Results

Ribociclib was the most effective option, generating 4.420 QALYs, followed by palbociclib (4.406 QALYs), abemaciclib (4.220 QALYs), then letrozole monotherapy (2.093 QALYs). As for cost-effectiveness, ribociclib dominated palbociclib. However, it was not cost-effective compared to abemaciclib (ICER=1,588,545 QAR/QALY). Ribociclib remained dominant over palbociclib with all uncertainties. The base-case conclusion of ribociclib versus abemaciclib remained robust over all uncertainties.

Conclusion

From the healthcare payer perspective in Qatar, ribociclib is the most effective CDK4/6 inhibitor. It was dominant over palbociclib in terms of cost-effectiveness; however, it was not cost-effective compared to abemaciclib at current prices.
Reading for life-long health
Authors: Shulman Kaiulani , Baicker Karen , Mayes Linda
Published: July 2024

There is a strong, positive relationship between childhood literacy and physical and mental health outcomes in adulthood. Through primary care-based literacy interventions, pediatricians reach children and their families long before they enter traditional education venues. In so doing, pediatricians play a key role in children's school readiness and in turn health outcomes. The current state of childhood literacy in United States defines an increasingly urgent platform for the healthcare profession generally, and pediatricians specifically, to embrace. Through reviewing the existing literature on the impact of childhood literacy on physical, mental, and social-emotional health outcomes, we hope to highlight the need for increased collaboration between the education and medical fields to further promote the literacy interventions in pediatric healthcare settings.
Low gain avalanche diodes for photon science applications
Authors: Centis Vignali Matteo , Paternoster Giovanni
Published: July 2024

Low Gain Avalanche Diodes (LGADs) are silicon sensors designed to achieve an internal gain in the order of 10 through the impact ionization process. The development of LGADs was pushed forward by their application in High Energy Physics (HEP) experiments, where they will be employed to provide measurements of the time of arrival of minimum ionizing particles with a resolution of around 30  ps. The initial technological implementation of the sensors constrains their minimum channel size to be larger than 1 mm2, in order to reduce inefficiencies due to the segmentation of the gain structure. The gain of the sensors is kept in the order of 10 to limit the sensor shot noise and their power consumption. In photon science, the gain provided by the sensor can boost the signal-to-noise ratio of the detector system, effectively reducing the x-ray energy threshold of photon counting detectors and the minimum x-ray energy where single photon resolution is achieved in charge integrating detectors. This can improve the hybrid pixel and strip detectors for soft and tender x-rays by simply changing the sensor element of the detector system. Photon science applications in the soft and tender energy range require improvements over the LGADs developed for HEP, in particular the presence of a thin entrance window to provide a satisfactory quantum efficiency and channel size with a pitch of less than 100 μm. In this review, the fundamental aspects of the LGAD technology are presented, discussing also the ongoing and future developments that are of interest for photon science applications.
Flow-mediated modulation of the endothelial cell lipidome
Authors: Hong Soon-Gook , Kennelly John P. , Williams Kevin J. , Bensinger Steven J. , Mack Julia J.
Published: July 2024

The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 h. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 h. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.
Changes in the growth and physiological property of tea tree after aviation mutagenesis and screening and functional verification of its characteristic hormones
Authors: Jia Miao , Chen Yiling , Zhang Qi , Wang Yuhua , Li Mingzhe , Pang Xiaomin , Hong Lei , Lin Shaoxiong , Jia Xiaoli , Ye Jianghua , Wang Haibin
Published: July 2024

Aerospace breeding is a breeding technique that utilizes a spacecraft to position plants in a space environment for mutagenesis, which is conducive to rapid mutagenesis for the screening of superior plant varieties. In this study, tea trees with aviation mutagenesis (TM) and those without aviation mutagenesis (CK) were selected as research subjects to analyze the effects of aviation mutagenesis on the growth, physiological properties, and hormone metabolism of tea trees, and to further screen the characteristic hormones and validate their functions. The results showed that the leaf length, leaf width, and leaf area of TM tea trees were significantly larger than those of CK. The growth indexes, the photosynthetic physiological indexes (i.e., chlorophyll content, intercellular CO2 concentration, stomatal conductance, transpiration rate, and photosynthetic rate), and the resistance physiological indexes (i.e., superoxide dismutase, peroxidase, catalase, and soluble sugar) were significantly higher in TM than in CK. Hormone metabolome analysis showed that four characteristic hormones distinguished CK from TM, namely, l-tryptophan, indole, salicylic acid, and salicylic acid 2-O-β-glucoside, all of which were significantly more abundant in TM than in CK. These four characteristic hormones were significantly and positively correlated with the growth indexes, tea yield, and the photosynthetic and resistance physiological indexes of tea trees. The leaf area, chlorophyll content, photosynthetic rate, and superoxide dismutase activity of tea tree seedlings after spraying with the four characteristic hormones were significantly increased, in which salicylic acid and salicylic acid 2-O-β-glucoside were more favorable to increase the leaf area and superoxide dismutase activity, while l-tryptophan and indole were more favorable to increase the leaf chlorophyll content and photosynthetic rate. It can be observed that aviation mutagenesis improves the accumulation of the characteristic hormones of tea trees, enhances their photosynthetic capacity, improves their resistance, promotes their growth, and then improves the tea yield.
Sport anxiety and subjective happiness of college athletes: a self-determination theory perspective
Authors: Zhang Zhiwen , Chen Xiaoyu , Xu Liyu , Qin Xiao , Veloo Arsaythamby
Published: July 2024

Introduction

Sport anxiety not only impacts the performance of college athletes but also influences their psychological well-being. The psychological well-being of sports students is crucial for both academic performance and competition, as they need to balance their academic performance with professional athletic training.

Method

Based on self-determination theory, this study examines the relationship between various factors in sport anxiety (somatic anxiety, worry, and concentration disruption) and subjective happiness, as well as the mediating role of need satisfaction in this relationship. A total of 835 college athletic students participated in the study, completing the Sport Anxiety Scale-2, Basic Psychological Needs Satisfaction Scale-in General, and Subjective Happiness Scale.

Results

An analysis of gender differences revealed that female participants scored significantly higher on somatic anxiety (t= −2.21,df= 833,p= 0.028, Cohen’sd= −0.155) and worry (t= −3.17,df= 833,p= 0.002, Cohen’sd= −0.223) compared to males. In the analysis by sport type, participants engaged in team sports scored significantly higher on somatic anxiety (t= 2.70,df= 833,p= 0.007, Cohen’sd= 0.187), Worry (t= 1.97,df= 833,p= 0.049, Cohen’sd= 0.136), and concentration disruption (t= 2.73,df= 833,p= 0.007, Cohen’sd= 0.189) than those in individual sports. Additionally, in the analysis by grade level, freshman college athletes exhibited significantly lower sport anxiety compared to sophomore athletes [F(4, 830) = 4.06,p= 0.003,ηp2=0.019]. The mediation analysis revealed that concentration disruption in sport anxiety is significantly and negatively related to subjective happiness. Additionally, need satisfaction (competence, autonomy, and relatedness) mediates the relationship between worry, as well as concentration disruption in sport anxiety and subjective happiness.

Discussion

Future research should build on the current study by employing longitudinal designs and integrating multiple objective measures to further explore the relationship between sport anxiety and subjective happiness.
Reconsidering the usefulness of long-term high-dose buprenorphine
Authors: Jain Lakshit , Meeks Thomas W. , Blazes Christopher K.
Published: July 2024

Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients’ path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.
Work-related socioeconomic determinants of health: evidence from educational mismatch in Italy
Authors: Abbafati Cristiana , Rosano Aldo
Published: July 2024

Introduction

An educational mismatch is defined as the situation where the education qualifications of an employee do not match the qualifications required for the job they do. A mismatch can be vertical where the level of the employee's qualification is not the one required by the job. This study contributes to the literature on work-related social determinants of health, by carrying out the first assessment of the relationship between educational mismatch and health in Italy.

Methods

Data come from PLUS, a national survey of labor supply. The risk of suffering from bad or very bad health associated with educational mismatch is investigated through a logistic regression model accounting for the socioeconomic context and occupation.

Results

Our findings show women are at greater risk of suffering from bad or very bad health than men, especially if under-educated.

Discussion

Our results show the need to address more research on work-related social determinants of health, which can represent a barrier to achieving health equity.
Path analysis of the awareness status and influencing factors of sarcopenia in older adults in the community: based on structural equation modeling
Authors: Wang Dahui , Zeng Huaying , Wu Peiwen , Zhou Yuchen , Chen Hongkun , Zhao Falin , Liu Shucong
Published: July 2024

Background

Sarcopenia is a progressive geriatric syndrome that impacts older adults’ quality of life. Insufficient focus has been given to sarcopenia among Chinese residents, resulting in low level of sarcopenia awareness. This study aims to investigate awareness of sarcopenia and its influencing factors and the influencing pathways among older adults in Hangzhou.

Methods

A stratified random sample of 942 community-dwelling older adults was evaluated using the SARC-CalF screening tool, along with a questionnaire based on health ecology theory to assess awareness of sarcopenia and its influencing factors and the influencing pathways. Descriptive statistics, linear regression analysis, and path analysis were conducted using SPSS 25.0 and Amos 23.0 to analyze the data.

Results

The mean awareness score for sarcopenia was 60.26 ± 7.31. Self-rated physical health, daily intake of high-quality protein, exercise frequency, smoking status, self-efficacy, religious beliefs, social support, education level, occupation, participation in community free medical examinations, and awareness of nutrition policy were all factors affecting scores for sarcopenia awareness (p < 0.05). Except for negative effects observed in social support, smoking status, and self-rated physical health, all others exhibit positive effects.

Conclusion

Community healthcare institutions should target populations with low awareness of sarcopenia and focus on these key factors. Diverse health education programs and multi-channel screening activities can promote awareness, guide healthy lifestyles and prevent or delay the onset of sarcopenia in the older.
A Mendelian randomization study investigating causal links between gut microbiota or metabolites and chronic hepatitis B
Authors: Xing Tongjing , Wang Xuequan , He Shanshan
Published: July 2024

Objective

This study aimed to explore the potential causal relationship between the gut microbiota and/or its metabolites and the progression of chronic hepatitis B (CHB).

Method

The gut microbiota was used as the exposure factor. The training set exposure data were obtained from the China Nucleotide Sequence Archive (CNSA). Genome-wide association study (GWAS) data from Asia were used as the outcome variables. Outcome data for both the training and validation sets were sourced from the GWAS Catalog database. A dual-sample Mendelian randomization approach was used to analyze the causal relationships, with the inverse variance-weighted method serving as the main analytical strategy. Sensitivity analysis was conducted to assess the robustness of Mendelian randomization analysis results.

Result

In the training set database, analysis using the inverse variance-weighted method revealed a positive correlation between Fusobacterium varium and chronic hepatitis B [OR = 1.122, 95% CI (1.016, 1.240), p = 0.022]. Conversely, Veillonella parvula exhibited a negative correlation with chronic hepatitis B [OR = 0.917, 95% CI (0.852, 0.987), p = 0.021]. Sensitivity analysis revealed no evidence of pleiotropy and heterogeneity. No gut microbiota metabolites with a causal effect on chronic hepatitis B were identified. Additionally, no associations between the gut microbiota and the progression of chronic hepatitis B were found in the validation data from the European cohort.

Conclusion

This study suggests that F. varium may facilitate the progression of chronic hepatitis B, whereas V. parvula may impede it. No causal relationships between gut microbiota metabolites and chronic hepatitis B were established.