bluuebunny/crossref_metadata_2025 huggingface dataset:
Short Proof for the Riemann Hypothesis
Authors: Vega Frank
Published: November 2023

The Riemann hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. It is considered by many to be the most important unsolved problem in pure mathematics. Let $\Psi(n) = n \cdot \prod_{q \mid n} \left(1 + \frac{1}{q} \right)$ denote the Dedekind $\Psi$ function where $q \mid n$ means the prime $q$ divides $n$. Define, for $n \geq 3$; the ratio $R(n) = \frac{\Psi(n)}{n \cdot \log \log n}$ where $\log$ is the natural logarithm. Let $N_{n} = 2 \cdot \ldots \cdot q_{n}$ be the primorial of order $n$. There are several statements equivalent to the Riemann hypothesis. We state that if for each large enough prime number $q_{n}$, there exists another prime $q_{n'} > q_{n}$ such that $R(N_{n'}) \leq R(N_{n})$, then the Riemann hypothesis is true. In this note, using our criterion, we prove that the Riemann hypothesis is true.
Perspectives on Mental Health Digital Platforms: A Usability Study with Ergonomics Design Students
Authors: Ngabo-Woods Harold
Published: November 2023

The prevalence of mental health issues has reached alarming levels globally. In response, the integration of technology in mental health care, particularly through mental health apps, has emerged as a promising frontier for delivering scalable and accessible therapeutic interventions. However, the effectiveness of these apps is contingent upon their usability. This study explores the critical link between the usability of mental health apps and their efficacy in managing mental health symptoms. Focusing on university students, the research investigates how usability influences user experience, engagement, and adherence to mental health interventions. It also examines the role of usability in reducing barriers to seeking professional help and the variations in usability perceptions. Through a usability study of a mental health app pilot platform, this research seeks to provide actionable insights for future design and development, emphasizing the need for user-friendly interfaces that effectively support mental health outcomes. The findings aim to contribute to the broader understanding of digital mental health interventions and their role in addressing the escalating mental health crisis.
Perkembangan Berbagi Pengetahuan Pada Pendidikan Jarak Jauh
Authors: Munir Syaiful
Published: November 2023

The development of knowledge sharing in distance education has become a significant topic in the era of globalization, supported by innovation and technological advancements. Open University (UT) is an educational institution that adopts a distance education model and utilizes information technology as a learning medium. UT employs various forms of e-learning, such as online tutorials, television programs, web resources, digital libraries, and more, to facilitate interaction among students, course materials, tutors, and fellow students. This article delves into how knowledge sharing management is crucial in the context of distance education, drawing insights from UT's instructional model and knowledge management theory. Knowledge management is considered essential for enhancing student performance during the learning process and in their future careers. The article also outlines how information technology serves as a tool to facilitate knowledge sharing in distance education. This research offers valuable insights into how knowledge management and knowledge sharing can be applied within the realm of distance education, particularly at institutions like Open University. It serves as a guide for other educational organizations seeking to enhance the effectiveness of their distance learning programs by implementing principles of knowledge management and information technology.
Small heat shock proteins as modulators of cell death in Plasmodium falciparum parasites and its human host
Authors: Timothy Francisca Magum , Zininga Tawanda
Published: November 2023

Plasmodium falciparum, the predominant cause of severe malaria, thrives within both poikilotherm mosquitoes and homeotherm humans, navigating challenging temperature shifts during its life cycle. Survival in such varying environments necessitate the development of robust mechanisms, including a sophisticated protein folding system to mitigate proteopathy. The parasite needs to control the survival of its host cells which affects its chances of development and propagation. Central to this system are heat shock proteins (Hsps), among which small Hsps (sHsps) play pivotal roles in maintaining proteostasis (protein homeostasis). In both humans and P. falciparum, numerous sHsps have been identified, making them attractive candidates as biomarkers for diagnostic and drug development strategies. Evidence is accumulating suggesting that these sHsps participate in cell death processes, potentially influencing disease pathogenesis. Despite their significance, the precise functions of sHsps in P. falciparum’s adaptation to stress conditions remains largely unknown. Comparative structural analysis of sHsps between human and P. falciparum reveals species-specific variations. Despite conserved tertiary structures, unique motifs are found in parasite sHsps which may modulate specialised chaperone functions. This review discusses the conserved and distinctive motifs of sHsps from the human host and the parasite, offering insights into shared and unique attributes. These findings illuminate the potential for species-specific targeting of sHsps, as players in cell death processes that may foster innovative biomarker identification approaches. As malaria continues to ravage Sub-Saharan Africa, understanding the molecular intricacies guiding parasite survival are essential in the development of interventions with heightened efficacy against this global health crisis.
In silico studies on cytotoxicity and antitumoral activity of acetogenins from Annona muricata L
Authors: Fallon Adido Houéfa Egidia , Silva Chagas Cristian Kallahan , Ferreira Gleison Gonçalves , Carmo Bastos Mírian Letícia , Dolabela Maria Fâni
Published: November 2023

As life expectancy increases, the number of people affected by cancer is increasing. The available drugs still cause several adverse reactions, and it is important to look for less toxic drugs that act on resistant cancers. The present study evaluated the antitumor potential of acetogenins. Through a literature review, 44 acetogenins isolated from Annona muricata were selected and subjected to in silico studies to predict the physicochemical properties, pharmacokinetics (Preadmet and Admet lab), toxicity (Preadmet and Protox II) and molecular docking in caspase 3 (DockThor). For muricatacin, a literature review was carried out for antitumor activity and cytotoxicity. Only muricatacin met all physicochemical criteria, while all compounds showed high cutaneous and intestinal absorption (HIA), moderate permeability in Madin-Darby canine kidney and Caco2 cells, strongly bound plasma proteins, freely crossed the blood-brain barrier, inhibited CYP2C19, CYP2C9 and CYP3A4 and have an affinity for CYP3A4, being metabolized by it, an undesirable characteristic for antitumor drugs. All compounds were toxic in at least one model, while compound 28 was not carcinogenic in rats and mice. Compounds 13, 14, 15, 16, 17 and 28 were selected for molecular docking into Caspase 3. Docking showed hydrophobic interactions, hydrogen and covalent bonds performed to maintain the stability of caspase 3, and cis-uvariamicin IV stood out more through the energies and chemical bonds of this parameter. The chloroform fraction from the methanolic extract of the seeds showed activity against triple-negative breast cancer, both in vitro and in vivo, and only muricatacin has studies in which the antitumor activity was evaluated in vitro and showed to be very promising. In summary, muricatacin and cis-uvariamicin IV appear to be very promising as antitumors, especially cis-uvariamicin IV.
Development and validation of a nomogram to predict the five-year risk of revascularization for non-culprit lesion progression in STEMI patients after primary PCI
Authors: Dai Feng , Xu Xianzhi , Zhou Chunxue , Li Cheng , Tian Zhaoxuan , Wang Zhaokai , Yang Shuping , Liao Gege , Shi Xiangxiang , Wang Lili , Li Dongye , Hou Xiancun , Chen Junhong , Xu Tongda
Published: November 2023

Background

Acute ST-segment elevation myocardial infarction (STEMI) patients after primary PCI were readmitted for revascularization due to non-culprit lesion (NCL) progression.

Objective

To develop and validate a nomogram that can accurately predict the likelihood of NCL progression revascularization in STEMI patients following primary PCI.

Methods

The study enrolled 1,612 STEMI patients after primary PCI in our hospital from June 2009 to June 2018. Patients were randomly divided into training and validation sets in a 7:3 ratio. The independent risk factors were determined by LASSO regression and multivariable logistic regression analysis. Multivariate logistic regression analysis was utilized to develop a nomogram, which was then evaluated for its performance using the concordance statistics, calibration plots, and decision curve analysis (DCA).

Results

The nomogram was composed of five predictors, including age (OR: 1.007 95% CI: 1.005–1.009, P < 0.001), body mass index (OR: 1.476, 95% CI: 1.363–1.600, P < 0.001), triglyceride and glucose index (OR: 1.050, 95% CI: 1.022–1.079, P < 0.001), Killip classification (OR: 1.594, 95% CI: 1.140–2.229, P = 0.006), and serum creatinine (OR: 1.007, 95% CI: 1.005–1.009, P < 0.001). Both the training and validation groups accurately predicted the occurrence of NCL progression revascularization (The area under the receiver operating characteristic curve values, 0.901 and 0.857). The calibration plots indicated an excellent agreement between prediction and observation in both sets. Furthermore, the DCA demonstrated that the model exhibited clinical efficacy.

Conclusion

A convenient and accurate nomogram was developed and validated for predicting the occurrence of NCL progression revascularization in STEMI patients after primary PCI.
Application of machine learning algorithms to construct and validate a prediction model for coronary heart disease risk in patients with periodontitis: a population-based study
Authors: Wang Yicheng , Ni Binghang , Xiao Yuan , Lin Yichang , Jiang Yu , Zhang Yan
Published: November 2023

Background

The association between periodontitis and cardiovascular disease is increasingly recognized. In this research, a prediction model utilizing machine learning (ML) was created and verified to evaluate the likelihood of coronary heart disease in individuals affected by periodontitis.

Methods

We conducted a comprehensive analysis of data obtained from the National Health and Nutrition Examination Survey (NHANES) database, encompassing the period between 2009 and 2014.This dataset comprised detailed information on a total of 3,245 individuals who had received a confirmed diagnosis of periodontitis. Subsequently, the dataset was randomly partitioned into a training set and a validation set at a ratio of 6:4. As part of this study, we conducted weighted logistic regression analyses, both univariate and multivariate, to identify risk factors that are independent predictors for coronary heart disease in individuals who have periodontitis. Five different machine learning algorithms, namely Logistic Regression (LR), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Classification and Regression Tree (CART), were utilized to develop the model on the training set. The evaluation of the prediction models’ performance was conducted on both the training set and validation set, utilizing metrics including AUC (Area under the receiver operating characteristic curve), Brier score, calibration plot, and decision curve analysis (DCA). Additionally, a graphical representation called a nomogram was created using logistic regression to visually depict the predictive model.

Results

The factors that were found to independently contribute to the risk, as determined by both univariate and multivariate logistic regression analyses, encompassed age, race, presence of myocardial infarction, chest pain status, utilization of lipid-lowering medications, levels of serum uric acid and serum creatinine. Among the five evaluated machine learning models, the KNN model exhibited exceptional accuracy, achieving an AUC value of 0.977. The calibration plot and brier score illustrated the model's ability to accurately estimate probabilities. Furthermore, the model's clinical applicability was confirmed by DCA.

Conclusion

Our research showcases the effectiveness of machine learning algorithms in forecasting the likelihood of coronary heart disease in individuals with periodontitis, thereby aiding healthcare professionals in tailoring treatment plans and making well-informed clinical decisions.
Long-term hydrological monitoring of soils in the terraced environment of Cinque Terre (north-western Italy)
Authors: Fiorucci Matteo , Pepe Giacomo , Marmoni Gian Marco , Pecci Massimo , Di Martire Diego , Guerriero Luigi , Bausilio Giuseppe , Vitale Enza , Raso Emanuele , Raimondi Luca , Cevasco Andrea , Calcaterra Domenico , Scarascia Mugnozza Gabriele
Published: November 2023

Terraced landscapes represent one of the most widespread human-induced/man-made transformations of hilly-mountainous environments. Slope terracing produces peculiar morphologies along with unusual soil textures and stratigraphic features, which in turn strongly influence slope hydrology. The investigation of the hydrological features of terraced soils is of fundamental importance for understanding the hydrological dynamics occurring in these anthropogenic landscapes, especially during rainfall events. To this purpose, the availability of extensive field monitoring data series and of information on subsoil properties and structure is essential. In this study, multi-sensor hydrological data were acquired over a period longer than 2 years in the experimental site of Monterosso al Mare, in the Cinque Terre National Park (Liguria region, Italy), one of the most famous examples of terraced landscape worldwide. Monitoring data were coupled with accurate engineering-geological investigations to achieve the hydro-mechanical characterization of backfill soils and to investigate their hydrological response at both the seasonal and the single rainstorm scale. The results indicated that the coarse-grained, and anthropically remolded texture of the soils favors the rapid infiltration of rainwater, producing sharp changes in both soil volumetric water content and pore water pressure. Furthermore, the pattern of hydrological parameters showed seasonal trends outlined by alternating phases of slow drying and fast wetting. The study outcomes provide useful insights on the short and long-term evolution of hydrological factors operating in agricultural terraces. These findings represent a useful basis for a better understanding of the time-dependent processes that guide water circulation in terraced systems, which have a key role in controlling the occurrence of erosion and landslide processes.
A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022
Authors: Luo Qin , Tang Zhenchu , Wu Panyun , Chen Zhangling , Fang Zhenfei , Luo Fei
Published: November 2023

Background

Since the approval of the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for marketing in 2015, PCSK9 inhibitors have attracted significant interest in the field of cardiovascular endocrinology. A large number of clinical trials have confirmed the efficacy and safety of PCSK9 inhibitors in reducing cholesterol and the risk of cardiovascular events. No bibliometric analysis of PCSK9 inhibitors has been performed as of yet. This study aims to analyze the research trends and hotspots of PCSK9 inhibitors through bibliometric analysis.

Methods

We searched the Web of Science Core Collection (WoSCC) database for PCSK9 inhibitor-related publications from 2007 to 2022. Data visualization analysis was performed using CiteSpace software. Microsoft Excel and Graphpad software were used for the drawing of some tables and figures.

Results

A total of 1072 pieces of literature were retrieved between 2007 and 2022. The number of publications concerning PCSK9 inhibitors is growing annually. The top five countries with the most articles published were the United States, England, Canada, Italy, and France. Harvard University, Amgen, Brigham & Women’s Hospital, Harvard Medical School, and Imperial College London are the five institutions with the highest output. The Journal of Clinical Lipidology is the most popular journal in this field. The most frequently cited journal is the New England Journal of Medicine. As for authors, Sabatine MS and Giugliano RP from Brigham & Women’s Hospital have the highest number of published articles. Amgen is the funding agency for most of the research. According to keyword analysis, “low density lipoprotein”, “familial hypercholesterolemia”, “PCSK9 inhibitor”, “PCSK9”, and “efficacy” are the five keywords with the highest frequency of co-occurrence.

Conclusion

The past 15 years have witnessed a rapid and fruitful development of PCSK9 inhibitors. The research trend and focus for PCSK9 inhibitors are from the mechanism of reducing low-density lipoprotein cholesterol to related clinical trials. Developed countries such as the United States have contributed prominently in this area. Coronary artery and inflammation are currently at the forefront of research in the field and are in an explosion period.
Causal relationship between rheumatoid arthritis and hypothyroidism or hyperthyroidism: a bidirectional two-sample univariable and multivariable Mendelian randomization study
Authors: Lai Rui , Deng Xinmin , Lv Xiaofeng , Liu Qian , Zhou Kun , Peng Dezhong
Published: November 2023

Objective

The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR).

Method

We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency.

Results

The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01–1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15–1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05–1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83–1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05).

Conclusion

Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA.
Association between high serum blood glucose lymphocyte ratio and all-cause mortality in non-traumatic cerebral hemorrhage: a retrospective analysis of the MIMIC-IV database
Authors: Yang Shiqiang , Liu Yanwei , Wang Shiqiang , Cai Zhonghai , Yang Anqiang , Hui Xuhui
Published: November 2023

Background

This study aimed to evaluate the association between the glucose-to-lymphocyte ratio (GLR) and all-cause mortality in intensive care unit (ICU) patients with Non-traumatic cerebral hemorrhage.

Methods

This is a retrospective cohort study. Baseline data and in-hospital prognosis from patients with non-traumatic cerebral hemorrhage admitted to the intensive care unit. Multivariate COX regression analysis was applied and adjusted hazard ratios (HR) and 95% predictive values with confidence intervals (CI) were calculated. Survival curves for the two groups of cases were plotted using K-M curves, and subgroup analyses were performed in one step. Using restricted cubic spline curves, we analyzed the potential linear relationship between GLR and outcome indicators.

Results

In the Medical Information Mart for Intensive Care IV (MIMIC-IV database), we extracted 3,783 patients with nontraumatic intracerebral hemorrhage, and 1,806 patients were finally enrolled in the study after exclusion of missing values and patients with a short hospital stay. The overall ICU mortality rate was 8.2% (148/1806) and the in-hospital mortality rate was 12.5% (225/1806). The use of curve fitting yielded a significant linear relationship between GLR and both ICU mortality and in-hospital mortality. It also suggested a reference point at GLR=3.9. These patients were categorized into high and low subgroups based on the median value of their GLR (GLR = 3.9). Model comparisons based on multivariate COX regression analysis showed that in-hospital mortality was higher in the high GLR group after adjusting for all confounders (HR = 1.31, 95% CI: 1.04-1.47), while the ICU mortality in the high GLR group was (HR = 1.73, 95% CI: 1.18-2.52). Stratified analyses based on age, gender, race, GCS, BMI, and disease type showed stable correlations between the high GLR group and in-hospital and ICU mortality.

Conclusion

Based on our retrospective analysis, it is known that as the GLR increased, the in-hospital mortality rate and ICU mortality rate of patients with nontraumatic cerebral hemorrhage also increased progressively in the United States in a clear linear relationship. However, further studies are needed to confirm these findings.
Osteocalcin has a muscle-protective effect during weight loss in men without metabolic syndrome: a multicenter, prospective, observational study
Authors: Xiang Yi , Lu Wenyi , Mao Xiaomeng , Zou Jing , Wang Jialu , Xu Renying , Tang Qingya
Published: November 2023

Objective

Weight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS).

Measures

We enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss.

Results

Following weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (β=0.089, p=0.017).

Conclusion

High-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males.
Mechanisms of carbon dioxide detection in the earthworm Dendrobaena veneta
Authors: Smith Emily Jordan , Ryan Jennifer L. , Lopresti Sofia A. , Haghnazari Dastan B. S. , Anderson Karleigh A. S. , Lipson Sarah J. , Johnson Erik C. , Silver Wayne L. , Saunders Cecil J.
Published: November 2023

Introduction

Carbon dioxide (CO2) is a critical biological signal that is noxious to many animals at high concentrations. The earthworm Dendrobaena veneta lives in subterranean burrows containing high levels of CO2 and respires through its skin. Despite the ecological and agricultural importance of earthworms, relatively little is known about how they make decisions in their environment, including their response to elevated levels of CO2.

Methods

To examine CO2 detection in this species, we designed the exudate assay, in which we placed an earthworm in a sealed container, exposed it to varying concentrations of CO2 for one minute, and recorded the amount of exudate secreted. Because earthworms excrete exudate in response to noxious stimuli, we hypothesized that the amount of exudate produced was proportional to the amount of irritation. We repeated these experiments after treatment with several blockers for molecules with potential involvement in CO2 detection, including carbonic anhydrases, guanylate cyclase, TRPA1, ASICs, and OTOP channels. We also confirmed the presence of homologous transcripts for each of these gene families in an epithelial transcriptome for D. veneta. Additionally, since organisms often detect CO2 levels indirectly by monitoring the conversion to carbonic acid (a weak acid), we used the exudate assay to evaluate aversion to additional weak acids (formic acid, acetic acid, and propionic acid).

Results

Earthworms excreted significantly more exudate in response to CO2 in a dosage-dependent manner, and this response was muted by the general carbonic anhydrase inhibitor acetazolamide, the carbonic anhydrase IX/XII inhibitor indisulam, the calcium channel blocker ruthenium red, the sodium channel blocker amiloride, and the acid-sensing ion channel blocker diminazene aceturate.

Discussion

These data provide evidence of the role of carbonic anhydrase and epithelial sodium channels in earthworm CO2 detection, establish that, similar to other subterranean-dwelling animals, earthworms are extremely tolerant of CO2, and contribute to our understanding of the mechanisms used by earthworms to detect and react to weak acids in their environment.
Stacking-ac4C: an ensemble model using mixed features for identifying n4-acetylcytidine in mRNA
Authors: Lou Li-Liang , Qiu Wang-Ren , Liu Zi , Xu Zhao-Chun , Xiao Xuan , Huang Shun-Fa
Published: November 2023

N4-acetylcytidine (ac4C) is a modification of cytidine at the nitrogen-4 position, playing a significant role in the translation process of mRNA. However, the precise mechanism and details of how ac4C modifies translated mRNA remain unclear. Since identifying ac4C sites using conventional experimental methods is both labor-intensive and time-consuming, there is an urgent need for a method that can promptly recognize ac4C sites. In this paper, we propose a comprehensive ensemble learning model, the Stacking-based heterogeneous integrated ac4C model, engineered explicitly to identify ac4C sites. This innovative model integrates three distinct feature extraction methodologies: Kmer, electron-ion interaction pseudo-potential values (PseEIIP), and pseudo-K-tuple nucleotide composition (PseKNC). The model also incorporates the robust Cluster Centroids algorithm to enhance its performance in dealing with imbalanced data and alleviate underfitting issues. Our independent testing experiments indicate that our proposed model improves the Mcc by 15.61% and the ROC by 5.97% compared to existing models. To test our model’s adaptability, we also utilized a balanced dataset assembled by the authors of iRNA-ac4C. Our model showed an increase in Sn of 4.1%, an increase in Acc of nearly 1%, and ROC improvement of 0.35% on this balanced dataset. The code for our model is freely accessible at https://github.com/louliliang/ST-ac4C.git, allowing users to quickly build their model without dealing with complicated mathematical equations.
The role of m6A demethylases in lung cancer: diagnostic and therapeutic implications
Authors: Yu Mengjiao , Ji Wenqian , Yang Xu , Tian Kai , Ma Xinyi , Yu Shali , Chen Lin , Zhao Xinyuan
Published: November 2023

m6A is the most prevalent internal modification of eukaryotic mRNA, and plays a crucial role in tumorigenesis and various other biological processes. Lung cancer is a common primary malignant tumor of the lungs, which involves multiple factors in its occurrence and progression. Currently, only the demethylases FTO and ALKBH5 have been identified as associated with m6A modification. These demethylases play a crucial role in regulating the growth and invasion of lung cancer cells by removing methyl groups, thereby influencing stability and translation efficiency of mRNA. Furthermore, they participate in essential biological signaling pathways, making them potential targets for intervention in lung cancer treatment. Here we provides an overview of the involvement of m6A demethylase in lung cancer, as well as their potential application in the diagnosis, prognosis and treatment of the disease.
Trophic ecology shapes spatial ecology of two sympatric predators, the great hammerhead shark (Sphyrna mokarran) and bull shark (Carcharhinus leucas)
Authors: Lubitz Nicolas , Abrantes Kátya , Crook Kevin , Currey-Randall Leanne M. , Chin Andrew , Sheaves Marcus , Fitzpatrick Richard , Barbosa Martins Ana , Bierwagen Stacy , Miller Ingo B. , Barnett Adam
Published: November 2023

Information on how the trophic ecology of predators shapes their movement patterns and space-use is fundamental to understanding ecological processes across organisational levels. Despite this, studies combining spatial and trophic ecology to determine how prey preference and/or resource availability shape space use are lacking in marine predators as these can occur at low density and are often difficult to track over extended periods. Furthermore, many exhibit behavioural variability within species and among closely related, sympatric species adding further complexity. We applied a context-focused, multi-method approach to the understudied great hammerhead shark (Sphyrna mokarran) to test if movement and home ranges relate to prey preference and availability. Movement data from satellite and acoustic telemetry in Queensland, Australia, were combined with stable-isotope analysis, drone surveys, and videos of hunting behaviour. Limited dispersal, and small home ranges in S. mokarran were linked to trophic specialisation on stingray prey. Drone surveys and videos showed predation events on stingrays and demonstrated high, year-round availability of this prey in shallow, inshore habitats, which may allow the majority of S. mokarran to remain resident. This affinity for inshore habitats suggests that critical life-history requirements are performed over local or regional scales, although some larger movements were evident. These results were interpreted in comparison to the well-studied bull shark (Carcharhinus leucas), which showed reliance on pelagic food webs. Carcharhinus leucas had high individual variability in movement, with both large-scale migrations and residency. This could indicate that only some individuals are locally sustained on dynamic, pelagic food webs, while others undergo large-scale excursions over distant habitats. The specialised foraging of S. mokarran indicates they play an apex predator role in shallow, inshore habitats, potentially shaping space-use, and foraging behaviour of batoids. As inshore habitats are disproportionately affected by anthropogenic stressors, S. mokarran’s trophic specialisation and limited demographic connectivity may make the species particularly vulnerable to anthropogenic threats.
Comparative effectiveness of explainable machine learning approaches for extrauterine growth restriction classification in preterm infants using longitudinal data
Authors: Cho Kee Hyun , Kim Eun Sun , Kim Jong Wook , Yun Cheol-Heui , Jang Jae-Won , Kasani Payam Hosseinzadeh , Jo Heui Seung
Published: November 2023

Introduction

Preterm birth is a leading cause of infant mortality and morbidity. Despite the improvement in the overall mortality in premature infants, the intact survival of these infants remains a significant challenge. Screening the physical growth of infants is fundamental to potentially reducing the escalation of this disorder. Recently, machine learning models have been used to predict the growth restrictions of infants; however, they frequently rely on conventional risk factors and cross-sectional data and do not leverage the longitudinal database associated with medical data from laboratory tests.

Methods

This study aimed to present an automated interpretable ML-based approach for the prediction and classification of short-term growth outcomes in preterm infants. We prepared four datasets based on weight and length including weight baseline, length baseline, weight follow-up, and length follow-up. The CHA Bundang Medical Center Neonatal Intensive Care Unit dataset was classified using two well-known supervised machine learning algorithms, namely support vector machine (SVM) and logistic regression (LR). A five-fold cross-validation, and several performance measures, including accuracy, precision, recall and F1-score were used to compare classifier performances. We further illustrated the models’ trustworthiness using calibration and cumulative curves. The visualized global interpretations using Shapley additive explanation (SHAP) is provided for analyzing variables’ contribution to final prediction.

Results

Based on the experimental results with area under the curve, the discrimination ability of the SVM algorithm was found to better than that of the LR model on three of the four datasets with 81%, 76% and 72% in weight follow-up, length baseline and length follow-up dataset respectively. The LR classifier achieved a better ROC score only on the weight baseline dataset with 83%. The global interpretability results revealed that pregnancy-induced hypertension, gestational age, twin birth, birth weight, antenatal corticosteroid use, premature rupture of membranes, sex, and birth length were consistently ranked as important variables in both the baseline and follow-up datasets.

Discussion

The application of machine learning models to the early detection and automated classification of short-term growth outcomes in preterm infants achieved high accuracy and may provide an efficient framework for clinical decision systems enabling more effective monitoring and facilitating timely intervention.
Repurposing of Rutan showed effective treatment for COVID-19 disease
Authors: Salikhov Shavkat I. , Abdurakhmonov Ibrokhim Y. , Oshchepkova Yuliya I. , Ziyavitdinov Jamolitdin F. , Berdiev Nodir Sh. , Aisa Haji Akber , Shen Jingshan , Xu Yechun , Xu H. Eric , Jiang Xiangrui , Zhang Leike , Vypova Natalia L. , Allaberganov Dilshod Sh. , Tagayalieva Nigora A. , Musabaev Erkin I. , Ibadova Gulnara A. , Rajabov Ilxom B. , Lokteva Lyubov M.
Published: November 2023

Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent RNA polymerase (RdRp). There was no drug accumulation in experimental animals’ organs and tissues. A clinical study demonstrated a statistically significant decrease in the C-reactive protein and a reduction of the viremia period. In patients receiving Rutan 25 mg (children) and 100 mg (adults), the frequency of post-COVID-19 manifestations was significantly less than in the control groups not treated with Rutan tablets. Rutan, having antiviral activity, can provide safe treatment and prevention of COVID-19 in adults and children.

Clinical Trial Registration

ClinicalTrials.gov, ID NCT05862883.
Deep learning models for preoperative T-stage assessment in rectal cancer using MRI: exploring the impact of rectal filling
Authors: Tian Chang , Ma Xiaolu , Lu Haidi , Wang Qian , Shao Chengwei , Yuan Yuan , Shen Fu
Published: November 2023

Background

The objective of this study was twofold: firstly, to develop a convolutional neural network (CNN) for automatic segmentation of rectal cancer (RC) lesions, and secondly, to construct classification models to differentiate between different T-stages of RC. Additionally, it was attempted to investigate the potential benefits of rectal filling in improving the performance of deep learning (DL) models.

Methods

A retrospective study was conducted, including 317 consecutive patients with RC who underwent MRI scans. The datasets were randomly divided into a training set (n = 265) and a test set (n = 52). Initially, an automatic segmentation model based on T2-weighted imaging (T2WI) was constructed using nn-UNet. The performance of the model was evaluated using the dice similarity coefficient (DSC), the 95th percentile Hausdorff distance (HD95), and the average surface distance (ASD). Subsequently, three types of DL-models were constructed: Model 1 trained on the total training dataset, Model 2 trained on the rectal-filling dataset, and Model 3 trained on the non-filling dataset. The diagnostic values were evaluated and compared using receiver operating characteristic (ROC) curve analysis, confusion matrix, net reclassification index (NRI), and decision curve analysis (DCA).

Results

The automatic segmentation showed excellent performance. The rectal-filling dataset exhibited superior results in terms of DSC and ASD (p = 0.006 and 0.017). The DL-models demonstrated significantly superior classification performance to the subjective evaluation in predicting T-stages for all test datasets (all p < 0.05). Among the models, Model 1 showcased the highest overall performance, with an area under the curve (AUC) of 0.958 and an accuracy of 0.962 in the filling test dataset.

Conclusion

This study highlighted the utility of DL-based automatic segmentation and classification models for preoperative T-stage assessment of RC on T2WI, particularly in the rectal-filling dataset. Compared with subjective evaluation, the models exhibited superior performance, suggesting their noticeable potential for enhancing clinical diagnosis and treatment practices.
Real-time infrared spectroscopy coupled with blind source separation for nuclear waste process monitoring
Authors: Crouse Steven H. , Kocevska Stefani , Noble Sean , Prasad Rupanjali , Howe Anthony M. , Lambert Dan P. , Rousseau Ronald W. , Grover Martha A.
Published: November 2023

On-line infrared absorbance spectroscopy enables rapid measurement of solution-phase molecular species. Many spectra-to-concentration models exist for spectral data, with some models able to handle overlapping spectral bands and nonlinearities. However, model accuracy is limited by the quality of training data used in model fitting. The process spectra of nuclear waste simulants at the Savannah River Site display incongruity between training and process spectra; the glycolate spectral signature in the training data does not match the glycolate signature in Savannah River National Laboratory process data. A novel blind source separation algorithm is proposed that preprocesses spectral data so that process spectra more closely resemble training spectra, thereby improving model quantification accuracy when unexpected sources of variation appear in process spectra. The novel blind source separation preprocessing algorithm is shown to improve nitrate quantification from an R2 of 0.934 to 0.988 and from 0.267 to 0.978 in two instances analyzing nuclear waste simulants from the Slurry Receipt Adjustment Tank and Slurry Mix Evaporator cycle at the Savannah River Site.
Characterization of garlic oil/β-cyclodextrin inclusion complexes and application
Authors: Li Shangjian , Chen Jiajia , Liu Yuntong , Qiu Honghao , Gao Wei , Che Kundian , Zhou Baogang , Liu Ran , Hu Wenzhong
Published: November 2023

Garlic oil is a liquid extracted from garlic that has various natural antibacterial and anti-inflammatory properties and is believed to be used to prevent and treat many diseases. However, the main functional components of garlic oil are unstable. Therefore, in this study, encapsulating garlic oil with cyclodextrin using the saturated co-precipitation method can effectively improve its chemical stability and water solubility and reduce its characteristic odor and taste. After preparation, the microcapsules of garlic oil cyclodextrin were characterized, which proved that the encapsulation was successful. Finally, the results showed that the encapsulated garlic oil still had antioxidant ability and slow-release properties. The final addition to plant-based meat gives them a delicious flavor and adds texture and mouthfeel. Provided a new reference for the flavor application of garlic cyclodextrin micro-capsules in plant-based meat patties.
Regulatory mechanism and promising clinical application of exosomal circular RNA in gastric cancer
Authors: Han Ming , Zhang Mengyuan , Qi Mei , Zhou Yue , Li Fulong , Fang Shengquan
Published: November 2023

Gastric cancer (GC) is one of the most common malignancies worldwide and the leading cause of cancer-related deaths. Exosomes are nanoscale extracellular vesicles secreted by a variety of cells and play an important role in cellular communication and epigenetics by transporting bioactive substances in the tumor microenvironment (TME). Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a specific structure, which is widely enriched in exosomes and is involved in various pathophysiological processes mediated by exosomes. Exosomal circRNAs play a critical role in the development of GC by regulating epithelial-mesenchymal transition (EMT), angiogenesis, proliferation, invasion, migration, and metastasis of GC. Given the biological characteristics of exosomal circRNAs, they have more significant diagnostic sensitivity and specificity in the clinic and may become biomarkers for GC diagnosis and prognosis. In this review, we briefly describe the biogenesis of exosomes and circRNAs and their biological functions, comprehensively summarize the mechanisms of exosomal circRNAs in the development of GC and chemotherapy resistance, and finally, we discuss the potential clinical application value and challenges of exosomal circRNAs in GC.
Look at the future -perceptions of fertility counseling and decision-making among adolescents and their parents in the context of hematopoietic stem cell transplantation—experience of one major center for pediatric stem cell transplantation
Authors: Barnbrock Anke , Hamannt Fabienne , Salzmann-Manrique Emilia , Rohm Theresa , Lange Sandra , Bader Peter , Jarisch Andrea
Published: November 2023

Introduction

Increasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage of the possibility of fertility preservation, fertility counseling should be provided to patients and their parents prior to gonadotoxic therapies.

Methods

The aim of this survey was to analyze the impact of fertility counseling in pediatric stem cell transplantation in patients and their parents using questionnaires designed for the study questions. Fifty-one parents and 7 adolescent patients were interviewed between February 2019 and October 2021 about the counseling, their perceptions of fertility issues, and the nature of decision- making concerning fertility preservation. The study included patients with malignant (e.g., leukemia, lymphoma, neuroblastoma) and nonmalignant diseases (e.g., thalassemia, sickle cell disease, immunodeficiency) who received counseling on fertility preservation before HSCT based on an in-house standard and analysed the impact for both groups.

Results

Two-thirds of the study participants were concerned about having children and grandchildren respectively; for half of all respondents, the topic of fertility and fertility preservation proved to be hopeful. Forty percent of the study participants were burdened by the risk of possible fertility limitations after HSCT. Concerns about fertility was particularly significant for parents whose children were advised to undergo fertility preservation. Parents of children <12 years found deciding on appropriate measures more difficult. Parents with children >7 years involved their children in the decision. All study participants agreed that fertility counseling had not negatively affected the parent-child relationship. More than 90% of all study participants were in favor of addressing fertility, its potential limitations and fertility preservation measures before HSCT. There was no significant difference between the malignant and the non-malignant cohort in all study questions.

Discussion

Overall, the standardized fertility counseling provided in our center of pediatric stem cell transplantation resulted in high satisfaction among patients and their parents. Multiple counseling on infertility risk, including the younger patients in the decision-making and further options after gonadotoxic therapy may increase the satisfaction of the counseled patients and their parents.
Post-marketing safety surveillance and re-evaluaiton of Shu-Xue-Ning injection: a real-world study based on 30,122 cases
Authors: Xinyao Jin , Yifan Zhang , Keyi Wang , Wentai Pang , Chunyang Wang , Hui Wang , Chunxiang Liu , Yunhua Xue , Wenke Zheng
Published: November 2023

Objective: This study aims to investigate the safety of Shu-Xue-Ning injection (SXNI) in real-world clinical applications.

Methods: A prospective, multi-center, large-sample intensive monitoring method was used to monitor the use of SXNI in several medical institutions across China while collecting patients’ dosing and adverse event information. Patients who suspected as adverse reactions made comparisons with patients who did not report adverse reactions to calculate the correlation between relevant risk factors and suspected adverse reactions. Statistical analysis software SAS 9.1 was used for data analysis.

Results: A total of 48 hospitals participated in this intensive monitoring study of SXNI, and 30,122 patients were monitored from July 2015 to December 2018. A total of 1,908 adverse events were reported during the use of SXNI, with an adverse event rate of 6.33% and a 95% confidence interval (CI) of 6.06%–6.61%. Association assessment showed that 54 cases presented with SXNI-related adverse reactions with an incidence of 0.18% and a 95% CI of 0.13%–0.23%, thereby indicating that the incidence of SXNI-related adverse reactions was occasional. SXNI-related adverse reactions involved 9 systems-organs with 20 clinical manifestations, and the most common adverse reactions were rash, pruritus, and other damages of skin and its appendages. No serious adverse reactions were observed; 27.78% of the adverse reactions occurred within 30 min of drug administration and more than half of them occurred within 2 h of drug administration; 96.3% of the adverse reactions were cured or improved. Causal analysis showed that women, long dispensing time, and slow dripping speed rate were considered as risk factors.

Conclusion: The incidence of SXNI-related adverse reactions in real-world clinical applications is occasional and in a reasonable range with a good prognosis.