bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling multivariate extreme value distributions via Markov trees
Authors: Hu Shuang , Peng Zuoxiang , Segers Johan
Published: November 2023

Multivariate extreme value distributions are a common choice for modeling multivariate extremes. In high dimensions, however, the construction of flexible and parsimonious models is challenging. We propose to combine bivariate max‐stable distributions into a Markov random field with respect to a tree. Although in general not max‐stable itself, this Markov tree is attracted by a multivariate max‐stable distribution. The latter serves as a tree‐based approximation to an unknown max‐stable distribution with the given bivariate distributions as margins. Given data, we learn an appropriate tree structure by Prim's algorithm with estimated pairwise upper tail dependence coefficients as edge weights. The distributions of pairs of connected variables can be fitted in various ways. The resulting tree‐structured max‐stable distribution allows for inference on rare event probabilities, as illustrated on river discharge data from the upper Danube basin.
How fear of Covid‐19 predicts differential attitudes between nonphysician healthcare workers and other essential occupations
Authors: Ng Gary Ting Tat , Chow Dawn Yi Lin
Published: November 2023

We examine two competing hypotheses about how individual differences in fear of Covid‐19 influence attitudes toward nurses, hospital janitors and garbage collectors. On one hand, fear of Covid‐19 can predict less warmth toward nurses because fear may lead to avoidance and contempt. On the other hand, fear of Covid‐19 can predict greater warmth toward nurses because greater fear of Covid‐19 could alternatively imply greater cognizance of the contribution that nurses make, and the risk they undertake. Also, we hypothesize that fear of Covid‐19 does not predict greater warmth toward hospital janitors or garbage collectors. Findings of two studies (cross‐sectional and longitudinal) generally showed that increased fear of Covid‐19 (mainly on the psychological dimension) predicted greater warmth toward nurses, but not toward hospital janitors and garbage collectors. In the pandemic context, it appears that healthcare workers directly involved in patient care are not so much stigmatized, as appreciated, for their risk and contribution. However, other essential workers that are not involved in direct patient care appear less valued.
Monoclonal antibody cetuximab impairs matrix metalloproteinases 2 and 9, epithelial–mesenchymal transition and cell migration in feline oral squamous cell carcinoma in vitro
Authors: Altamura Gennaro , Martano Manuela , Matrone Anna , Corteggio Annunziata , Borzacchiello Giuseppe
Published: November 2023

Feline oral squamous cell carcinoma (FOSCC) is characterised by invasive and metastatic behaviour and is poorly responsive to current treatments, hence the need for new therapeutic strategies. FOSCC shares molecular targets with human head and neck squamous cell carcinoma (HNSCC), among these the epidermal growth factor receptor. Cetuximab is an anti‐epidermal growth factor receptor monoclonal antibody employed in the therapy of HNSCC and, interestingly, previous work in vitro suggested that it displays cytostatic and cytotoxic properties also against FOSCC. With the present study, we aimed at further investigating the effects of cetuximab on invasion and metastasis pathways proven to be relevant in human patients. To this purpose, FOSCC cell lines SCCF1, SCCF2 and SCCF3 were treated with cetuximab for 48/72 h and subjected to Western blot for matrix metalloproteinases‐2/9 (MMP‐2/9) and epithelial–mesenchymal transition markers vimentin, E‐, P‐ and N‐cadherin. Treatment with cetuximab resulted in downregulation of MMP‐2/‐9 in all of the three cell lines in a dose‐dependent manner. Moreover, cetuximab downregulated vimentin and P‐cadherin in SCCF1, upregulated E‐cadherin whilst downregulating P‐/N‐cadherins in SCCF2, and impaired P‐/N‐cadherins in SCCF3. An in vitro scratch test also demonstrated that cetuximab delayed cell migration in SCCF3. These data suggest that cetuximab mitigates invasion and metastasis processes by impairing MMPs and epithelial–mesenchymal transition pathways in FOSCC, indicating that this monoclonal antibody may help to counteract malignant progression and improve the management of locally invasive disease.
Behaviour of the Extrapolated Implicit IMR and ITR With and Without Compensated Summation
Authors: Ismail Amira , Gorgey Annie
Published: November 2023

Extrapolation involves taking a certain linear combination of the numerical solutions of a base method applied with different stepsizes to obtain greater accuracy. This linear combination is done so as to eliminate the leading error term. The technique of extrapolation in accelerating convergence has been successfully in numerical solution of ordinary differential equations. In this study, symmetric Runge-Kutta methods for solving linear and nonlinear stiff problem are considered. Symmetric methods admit asymptotic error expansion in even powers of the stepsize and are therefore of special interest because successive extrapolations can increase the order by two at time. Although extrapolation can give greater accuracy, due to the stepsize chosen, the numerical approximations are often destroy due to the accumulated round off errors. Therefore, it is important to control the rounding errors especially when applying extrapolation. One way to minimize round off errors is by applying compensated summation. In this paper, the numerical results are given for the symmetric Runge-Kutta methods Implicit Midpoint and Implicit Trapezoidal Rule applied with and without compensated summation. The result shows that symmetric methods with higher level extrapolation using compensated summation gives much smaller errors. On the other hand, symmetric methods without compensated summation when applied with extrapolation, the errors are affected badly by rounding errors
Implicit Runge-Kutta Methods Based on Gauss-Kronrod-Lobatto Quadrature Formulae
Authors: Yuan Ying Teh , Yaacob Nazeeruddin
Published: November 2023

In this paper, four new implicit Runge-Kutta methods which based on 7-point Gauss-Kronrod-Lobatto quadrature formula were developed. The resulting implicit methods were 7-stage tenth order Gauss-Kronrod-Lobatto III (GKLM(7,10)-III), 7-stage tenth order Gauss-Kronrod-Lobatto IIIA (GKLM(7,10)-IIIA), 7-stage tenth order Gauss-Kronrod-Lobatto IIIB (GKLM(7,10)-IIIB) and 7-stage tenth order Gauss-Kronrod-Lobatto IIIC (GKLM(7,10)-IIIC). Each of these methods required 7 function of evaluations at each integration step and gave accuracy of order 10. Theoretical analyses showed that the stage order for GKLM(7,10)-III, GKLM(7,10)-IIIA, GKLM(7,10)-IIIB and GKLM(7,10)-IIIC are 6, 7, 3 and 4, respectively. GKLM(7,10)-IIIC possessed the strongest stability condition i.e. L-stability, followed by GKLM(7,10)-IIIA and GKLM(7,10)-IIIB which both possessed A-stability, and lastly GKLM(7,10)-III having finite region of absolute stability. Numerical experiments compared the accuracy of these four implicit methods and the classical 5-stage tenth order Gauss-Legendre method in solving some test problems. Numerical results revealed that, GKLM(7,10)-IIIA was the most accurate method in solving a scalar stiff problem. All the proposed methods were found to have comparable accuracy and more accurate than the 5-stage tenth order Gauss-Legendre method in solving a two-dimensional stiff problem.
Super-Continuous Maps, Feebly-Regular and Completely Feebly-Regular Spaces
Authors: Kharbhih John Paul , Dutta Sanghita
Published: November 2023

In this paper properties of super-continuous are further studied. In addition, two new separation axioms for a topological space viz. feebly-regular space and completely feebly-regular spaces are introduced and their basic properties are studied.Keywords super-closed; super-open; super-continuity; feebly-regular; completely feebly-regular
Stability Analysis of a Three Species Syn-Eco-System with Mortality Rate for Commensal
Authors: Prasad B.Hari
Published: November 2023

The main objective of the present paper is to examine the stability of three species syn-eco-system. The system comprises of a commensal (S1) common to two hosts S2 and S3 with mortality rate for commensal. Further S2 is a commensal of S3 and S3 is a host of both S1, S2. Here all three species are having limited resources. The mathematical model equations constitute a set of three first order non-linear simultaneous coupled differential equations in the strengths N1, N2, N3 of S1, S2, S3 respectively. Criteria for the asymptotic stability of all the eight equilibrium points are established. Trajectories of the perturbations over the equilibrium points are illustrated. Further the global stability of a three species syneco system is established with the aid of suitably constructed Liapunov’s functionpair. Also the growth rates of the species are numerically estimated using RungeKutta fourth order scheme.Key words Commensal; Equilibrium state; Global stability; Host; Mortality rate; Stable; Trajectories.
Parallel Localized Differential Quadrature Approach in Boundary Value Problem
Authors: Cheong Hui Ting
Published: November 2023

In this paper, we need to developed a numerical strategy by implementing FORTRAN programming and OpenMP parallelization in Localized Differential Quadrature method in boundary value problem. Localized Differential Quadrature method is developed from the DQ method which used to improve the accuracy of the results by increasing the number of grid points. In order to reduce the execution time for sequential algorithm in solving value boundary problem using LDQ method, parallel programming of shared memory architecture (OpenMP) is introduced. With the introduction of share memory architecture, the computational time can be further speed up using parallel approach.
Supercobalancing Numbers
Authors: Davala Ravi Kumar , Panda G. K.
Published: November 2023

A natural number n is called cobalancing number (with cobalancer r) if it satisfies the Diophantine equation 1+2+·· ·+n = (n+1)+(n+2)+·· ·+(n+r). However, if for some pair of natural numbers (n, r), 1+2+· · ·+n > (n+1)+(n+2)+· · ·+(n+r) and equality is achieved after adding a natural number D to the right hand side then we call n a D-supercobalancing number with D-supercobalaner number r. In this paper, such numbers are studied for certain values of D.
3-total edge product cordial labeling of wheel related graphs
Authors: Hasni Roslan , Azaizeh Almothana
Published: November 2023

For a graph G = (V (G), E(G)), an edge labeling function f : E(G) → {0, 1, · · · , k − 1} where k is an integer, 2 ≤ k ≤ |E(G)|, induces a vertex labeling function f*: V (G) → {0, 1, · · · , k − 1} such that f*(v) is the product of the labels of the edges incident to v (mod k). This function f is called k-total edge product cordial (or simply k-TEPC) labeling of G if |(vf (i) + ef (i)) − (vf (j) + ef (j))| ≤ 1 for all i, j ϵ {0, 1, · · · , k−1}. In this paper, 3-total edge product cordial labeling for wheel related graphs is determined.
A new paradigm of fuzzy control point in space curve
Authors: Wahab Abd Fatah , Husain Mohd Sallehuddin , Zulkifly Mohammad Izat Emir
Published: November 2023

The control point is the most important element in the production of spline curve or surface model. This is because any changes of control points in the spline model affect the shape of the resulting curve or surface. Wahab and colleagues have introduced fuzzy control points to solve the problem of uncertainty prevailing in the spline modeling. However, based on this concept, this paper will discusses a new type of fuzzy control point that can generates a spline space curve model in 3-dimensional. This is because the generated control point is a 3-dimensional that satisfies the basic concepts of fuzzy set was introduced by Zadeh. However, this paper only taking a B-Spline model as a numerical example in the discussed model.
US-China Strategic Competition Amidst the Paradox of Decoupling
Authors: Park Yong Soo
Published: November 2023

Propelled by its remarkable economic growth, China has emerged as a significant player in the global arena, challenging the traditional dominance of the United States. Leveraging its economic prowess, China has strategically advanced its interests not only in the Indo-Pacific context but also on a global scale. This strategy has prompted the United States, starting with the Trump administration, to transition from engagement to comprehensive containment, aiming to counter China's influence and uphold American leadership. This shift signifies a new era, resembling a modern-day Cold War, distinct from the previous engagement-oriented policies. Intriguingly, amidst the calls within Washington to decouple the US economy from that of China, trade and investment data hint at a nuanced revival of bilateral ties between these global superpowers, prompting a re-evaluation of conventional wisdom. Despite the strong rhetoric advocating decoupling, its tangible implementation remains uncertain. Economic indicators suggest a trend toward recoupling, underscoring the intricate interplay between strategic competition and economic interdependence. This complexity generates a paradoxical situation in the new Cold War era, in which intense strategic rivalry and crucial economic cooperation coexist.
Predicting the Mechanical Behavior of Additively Manufactured Mechanical Metamaterials Using Point Cloud Representation Learning
Authors: Ye Zehao , Liu Xin , Peng Bo , Kan Chen
Published: November 2023

Additive manufacturing (AM) has been widely adopted to produce mechanical metamaterials for load bearing, energy absorption, and other applications in various industries such as aerospace, automotive, and healthcare. However, geometric imperfections largely exist in AM. Since the mechanical behavior of metamaterials is primarily dependent on their geometries, it is critical to evaluate how process-induced geometric imperfections affect the mechanical behavior of fabricated metamaterials. Most of the existing approaches for AM quality control concentrate on the detection of defects and are limited in their ability to assess defect-altered mechanical behavior of finished builds. Some studies leverage destructive tests or numerical methods for mechanical behavior assessment, which are costly and time-consuming, and impractical for high-throughput routine quality control. In this paper, a new machine learning framework is developed to predict the mechanical behavior of fabricated metamaterials based on their as-built geometries (represented as high-resolution point clouds). Specifically, the point cloud is first converted into an image profile, which preserves detailed geometric patterns. then, a deep neural network is constructed to encode salient features of the image profile and associate them with the load-deflection curve of the fabricated metamaterial. The effectiveness of the developed framework is experimentally validated through a case study with auxetic mechanical metamaterial. This work has great potential to be extended for in-process prediction of AM builds’ mechanical behavior based on layer-wise point cloud scanning.
Convolutional Dimension-Reduction With Knowledge Reasoning for Reliability Approximations of Structures Under High-Dimensional Spatial Uncertainties
Authors: Shi Luojie , Zhou Kai , Wang Zequn
Published: November 2023

Along with the rapid advancement of additive manufacturing technology, 3D-printed structures and materials have been successfully employed in various applications. Computer simulations of these structures and materials are often characterized by a vast number of spatial-varied parameters to predict the structural response of interest. Direct Monte Carlo methods are infeasible for uncertainty quantification and reliability assessment of such systems as they require a large number of forward model evaluations to obtain convergent statistics. To alleviate this difficulty, this paper presents a convolutional dimension-reduction method with knowledge reasoning-based loss regularization for surrogate modeling and uncertainty quantification of structures with high-dimensional spatial uncertainties. To manage the inherent high-dimensionality, a deep convolutional dimension-reduction network (ConvDR) is constructed to transform the spatial data into a low-dimensional latent space. In the latent space, knowledge reasoning is formulated as a form of loss regularization, and evolutionary algorithms are employed to train both the ConvDR network and a linear regression model as surrogate models for predicting the response of interest. 2D structures with spatial-variated material compositions are used to demonstrate the performance of the proposed approach.
Egeoglandula subgen. nov.: a new subgenus of Neumania Lebert, 1879 (Acari: Hydrachnidia: Unionicolidae) from China
Authors: Ding ZhuHui , Gu Xinyao , Yi Tianci , Guo Jianjun , Jin Daochao
Published: November 2023

A new subgenus Egeoglandula subgen. nov., has been erected within the water mite genus Neumania Lebert, 1879. This subgenus includes the following four species: Neumania disetus Jin, 1997, Neumania cercalis Jin, 1997, Neumania dolichotricha Jin, 1997 and Neumania navina Cook, 1967. The latter species is recorded for the first time from China. Additionally, three new species of the new subgenus are described: Neumania segrega sp. nov., Neumania palosa sp. nov., Neumania secara sp. nov. These new findings contribute to the knowledge of the genus Neumania from China.
A new species and two new records of Stigmaeidae (Acari: Prostigmata) from Russia
Authors: Khaustov Alexander A.
Published: November 2023

Female and male of the new species, Stigmaeus burjaticus sp. nov. (Acari: Stigmaeidae), collected from soil in Buryatia are described. Females of Stigmaeus fidelis Kuznetsov and Eustigmaeus parakauaiensis Kapaxidi, Stathakis and Papadoulis, collected from soil and moss, are recorded from Russia for the first time and redescribed based on materials from Kabardino-Balkaria (North Caucasus).
Nesting chinstrap penguins accrue large quantities of sleep through seconds-long microsleeps
Authors: Libourel P.-A. , Lee W. Y. , Achin I. , Chung H. , Kim J. , Massot B. , Rattenborg N. C.
Published: November 2023

Microsleeps, the seconds-long interruptions of wakefulness by eye closure and sleep-related brain activity, are dangerous when driving and might be too short to provide the restorative functions of sleep. If microsleeps do fulfill sleep functions, then animals faced with a continuous need for vigilance might resort to this sleep strategy. We investigated electroencephalographically defined sleep in wild chinstrap penguins, at sea and while nesting in Antarctica, constantly exposed to an egg predator and aggression from other penguins. The penguins nodded off >10,000 times per day, engaging in bouts of bihemispheric and unihemispheric slow-wave sleep lasting on average only 4 seconds, but resulting in the accumulation of >11 hours of sleep for each hemisphere. The investment in microsleeps by successfully breeding penguins suggests that the benefits of sleep can accrue incrementally.
Penguins snatch seconds-long microsleeps
Authors: Harding Christian D. , Vyazovskiy Vladyslav V.
Published: November 2023

Chinstrap penguins fall asleep thousands of times per day in the wild
A low-mass star with a large-mass planet
Authors: Masset Frédéric
Published: November 2023

A large planet orbiting a very low-mass star challenges theories of planet formation
Surtsey at 60
Eat, Poop, Die: How Animals Make Our World
Joe Roman
Little, Brown Spark, 2023. 288 pp.
Authors: Roman Joe
Published: November 2023

A volcanic island off the coast of Iceland celebrates six decades as a living laboratory
In Other Journals
Authors: Vignieri Sacha , Jiang Di , Ross Sarah H. , Smith H. Jesse , Lopez Bianca , Stajic Jelena , Funk Michael A.
Published: November 2023

Editors’ selections from the current scientific literature
Maize has an unexpected wild ancestor
Authors: Wade Lizzie
Published: November 2023

Genes from second wild grass may have helped propel its success—but scientists don’t know how
Structural characterization of M8C10, a neutralizing antibody targeting a highly conserved prefusion-specific epitope on the metapneumovirus fusion trimerization interface
Authors: Xiao Xiao , Wen Zhiyun , Chen Qing , Shipman Jennifer M. , Kostas James , Reid John C. , Warren Christopher , Tang Aimin , Luo Bin , O’Donnell Gregory , Fridman Arthur , Chen Zhifeng , Vora Kalpit A. , Zhang Lan , Su Hua-Poo , Eddins Michael J.
Published: November 2023

Human metapneumovirus (hMPV) is a major respiratory pathogen worldwide. Here, we report the crystal structure of a neutralizing antibody M8C10 isolated from human B cells that targets the viral fusion protein (hMPV-F) trimerization interface. This is a novel prefusion-specific epitope that is highly conserved across hMPV strains and other related viruses. The interactions between M8C10 and hMPV-F are largely driven by residues on the light chain with most hypermutated light chain residues on or near the interface. This highlights the immune recognition of a buried trimerization interface during the
in vivo
affinity maturation process. In addition,
in vivo
cotton rat challenge studies were performed that show M8C10 provides strong lung protection against hMPV A viral challenge. The hMPV-F:M8C10 Fab structure reported reveals a class of hMPV antibodies in the human immune repertoire with a novel neutralization mechanism, targeting the trimerization interface of hMPV-F antigen.

IMPORTANCE

Human metapneumovirus (hMPV) is a common pathogen causing lower respiratory tract infections worldwide and can develop severe symptoms in high-risk populations such as infants, the elderly, and immunocompromised patients. There are no approved hMPV vaccines or neutralizing antibodies available for therapeutic or prophylactic use. The trimeric hMPV fusion F protein is the major target of neutralizing antibodies in human sera. Understanding the immune recognition of antibodies to hMPV-F antigen will provide critical insights into developing efficacious hMPV monoclonal antibodies and vaccines.
A live-cell ergosterol reporter for visualization of the effects of fluconazole on the human fungal pathogen
Candida albicans
Authors: Serrano Antonio , Basante-Bedoya Miguel A. , Bassilana Martine , Arkowitz Robert A.
Published: November 2023

Ergosterol, an essential plasma membrane amphipathic lipid, is a major component of the fungal plasma membrane. Most fungal pathogens are susceptible to azole drugs that target ergosterol biosynthesis, and resistance/tolerance to azoles is increasingly problematic.
Candida albicans
is the most prevalent etiology of candidiasis, and, in this fungal pathogen, ergosterol-rich sub-domains are likely to include sphingolipids, as well as specific membrane proteins, such as multidrug transporters. To investigate the dynamics of ergosterol during the cell cycle and whether drug treatment affects these dynamics in this opportunistic pathogen, we adapted the D4H (domain 4 of the perfringolysin O bacterial toxin) reporter for studying sterol-rich membrane domains. We show that D4H provides a direct readout for the cellular effects of fluconazole and that highly polarized ergosterol is not critical for budding or filamentous growth.

IMPORTANCE

Ergosterol is a critical membrane lipid in fungi. In
Candida albicans
, this essential plasma membrane amphipathic lipid is important for interactions with host cells, in particular, host immune responses. Here, we use a live-cell reporter for specifically visualizing ergosterol and show that apical enrichment of this sterol is not critical for budding and filamentous growth in this human fungal pathogen. Our results highlight that this live-cell reporter is likely to be a useful tool in the analyses of azole resistance and tolerance mechanisms, including alterations in drug targets and upregulation of efflux activities.
Diversity and Evolution of Mitochondrial Translation Apparatus
Authors: Baleva Mariya V. , Piunova Ulyana E. , Chicherin Ivan V. , Levitskii Sergey A. , Kamenski Piotr A.
Published: November 2023

The evolution of mitochondria has proceeded independently in different eukaryotic lines, which is reflected in the diversity of mitochondrial genomes and mechanisms of their expression in eukaryotic species. Mitochondria have lost most of bacterial ancestor genes by transferring them to the nucleus or eliminating them. However, mitochondria of almost all eukaryotic cells still retain relatively small genomes, as well as their replication, transcription, and translation apparatuses. The dependence on the nuclear genome, specific features of mitochondrial transcripts, and synthesis of highly hydrophobic membrane proteins in the mitochondria have led to significant changes in the translation apparatus inherited from the bacterial ancestor, which retained the basic structure necessary for protein synthesis but became more specialized and labile. In this review, we discuss specific properties of translation initiation in the mitochondria and how the evolution of mitochondria affected the functions of main factors initiating protein biosynthesis in these organelles.
Fracture of the fabella with radiologic and MRI
Authors: Buruian Alexei , Pinheiro Vitor , Fonseca Fernando , Matos Pedro
Published: November 2023

The fabella is an inconstant sesamoid bone. A handful of cases have been reported so far describing fabella fracture, usually involving high energy mechanism or stress fractures after total knee arthroplasty. This paper presents a fabella fracture in a man in his 40s after suffering a car crash, the clinical and radiographic presentation, treatment and complete recovery at 4-months follow-up.
Skene’s gland duct cyst: three cases in female newborns
Authors: Neto Joana Afonso , Carmo Beatriz , Rodrigues Alexandra M , Silva Jorge Santos
Published: November 2023

Skene’s gland duct cysts are benign, asymptomatic bulging interlabial masses that are rarely identified in female newborns. The aetiology is unknown, but it is commonly associated with in utero maternal oestrogen exposure or obstruction or stenosis of the gland duct. We report three unrelated cases of neonatal Skene’s gland duct cysts that resolved spontaneously without the need for surgical intervention.
Unusual case of sodium valproate-induced hyperammonaemia encephalopathy
Authors: Ranjith Shristhi , Abeysundera Hesitha , Jeyaranjan Hilary
Published: November 2023

There is limited information about sodium valproate-induced hyperammonaemia encephalopathy (VPAIHE). The aim of this case report is to provide medical practitioners with a greater awareness of the possible development of hyperammonaemia due to sodium valproate use and its associated complications.

This paper describes a middle-aged man with a history of bipolar affective disorder who was admitted with a manic relapse secondary to medication non-compliance. His admission was complicated by an intensive care unit admission to manage medical compromise in the context of sodium VPAIHE.
Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study
Authors: Lycke Kathrine Dyhr , Kahlert Johnny , Petersen Lone Kjeld , Damgaard Rikke Kamp , Cheung Li C , Gravitt Patti E , Hammer Anne
Published: November 2023

Objective

To describe the long term risk of cervical cancer in women with untreated (that is, undergoing active surveillance) or immediately treated cervical intraepithelial neoplasia grade 2 (CIN2).

Design

Nationwide population based historical cohort study.

Setting

Danish healthcare registries.

Participants

Women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis, who had either active surveillance or immediate treatment with large loop excision of the transformation zone (LLETZ). Women with a previous record of CIN2 or worse or LLETZ were excluded.

Main outcome measure

A Weibull survival model for interval censored time-to-event data was used to estimate the cumulative risk of cervical cancer. Inverse probability treatment weighting was used to adjust estimates for age, index cytology, calendar year, and region of residence.

Results

The cohort included 27 524 women with CIN2, of whom 12 483 (45%) had active surveillance and 15 041 (55%) had immediate LLETZ. During follow-up, 104 cases of cervical cancer were identified—56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. The cumulative risk of cervical cancer was comparable across the two groups during the active surveillance period of two years. Thereafter, the risk increased in the active surveillance group, reaching 2.65% (95% confidence interval 2.07% to 3.23%) after 20 years, whereas it remained stable in the LLETZ group at 0.76% (0.58% to 0.95%).

Conclusions

Undergoing active surveillance for CIN2, thereby leaving the lesion untreated, was associated with increased long term risk of cervical cancer compared with immediate LLETZ. These findings show the importance of continued follow-up of women having active surveillance.
Evaluating clinical outcomes and prognosis in patients with cirrhosis and portal hypertension: a retrospective observational cohort study
Authors: Lee Nerissa Hoi Ching , Kiddle Steven J , Chandankhede Shardul , Agrawal Shubh , Bean Daniel M , Hunt Phillip R , Parker Victoria E R , Greasley Peter J , Ambery Philip
Published: November 2023

Objective

Cirrhosis describes the end-stage of chronic liver disease. Irreversible changes in the liver cause portal hypertension, which can progress to serious complications and death. Only a few studies with small sample sizes have investigated the prognosis of cirrhosis with portal hypertension. We used electronic healthcare records to examine liver-related outcomes in patients with diagnosed/suspected portal hypertension.

Design

This retrospective observational cohort study used secondary health data between 1 January 2017 and 3 December 2020 from the TriNetX Network, a federated electronic healthcare records platform. Three patient groups with cirrhosis and diagnosed/suspected portal hypertension were identified (‘most severe’, ‘moderate severity’ and ‘least severe’). Outcomes studied individually and as a composite were variceal haemorrhage, hepatic encephalopathy, complications of ascites and recorded mortality up to 24 months.

Results

There were 13 444, 23 299, and 23 836 patients in the most severe, moderate severity and least severe groups, respectively. Mean age was similar across groups; most participants were white. The most common individual outcomes at 24 months were variceal haemorrhage in the most severe group, recorded mortality and hepatic encephalopathy in the moderate severity group, and recorded mortality in the least severe group. Recorded mortality rate was similar across groups. For the composite outcome, cumulative incidence was 59% in the most severe group at 6 months. Alcohol-associated liver disease and metabolic-associated steatohepatitis were significantly associated with the composite outcome across groups.

Conclusion

Our analysis of a large dataset from electronic healthcare records illustrates the poor prognosis of patients with diagnosed/suspected portal hypertension.
A costing framework to compare tuberculosis infection tests
Authors: Brumwell Amanda , Tso Jade , Pingali Viswanath , Millones Ana Karina , Jimenez Judith , Calderon Roger I , Barreda Nadia , Lecca Leonid , Nicholson Tom , Brooks Meredith
Published: November 2023

Objective

To develop a framework to estimate the practical costs incurred from, and programmatic impact related to, tuberculosis (TB) infection testing—tuberculin skin tests (TST) versus interferon gamma release assay (IGRA)—in a densely populated high-burden TB area.

Methods

We developed a seven-step framework that can be tailored to individual TB programmes seeking to compare TB infection (TBI) diagnostics to inform decision-making. We present methodology to estimate (1) the prevalence of TBI, (2) true and false positives and negatives for each test, (3) the cost of test administration, (4) the cost of false negatives, (5) the cost of treating all that test positive, (6) the per-test cost incurred due to treatment and misdiagnosis and (7) the threshold at which laboratory infrastructure investments for IGRA are outweighed by system-wide savings incurred due to IGRA utilisation. We then applied this framework in a densely populated, peri-urban district in Lima, Peru with high rates of Bacillus Calmette–Guérin (BCG) vaccination.

Findings

The lower sensitivity of TST compared with IGRA is a major cost driver, leading to health system and societal costs due to misdiagnosis. Additionally, patient and staff productivity costs were greater for TST because it requires two patient visits compared with only one for IGRA testing. When the framework was applied to the Lima setting, we estimate that IGRA-associated benefits outweigh infrastructural costs after performing 672 tests.

Conclusions

Given global shortages of TST and concerns about costs of IGRA testing and laboratory capacity building, this costing framework can provide public health officials and TB programmes guidance for decision-making about TBI testing locally. This framework was designed to be adaptable for use in different settings with available data. Diagnostics that increase accuracy or mitigate time to treatment should be thought of as an investment instead of an expenditure.
Decomposing income-related inequality in health-related quality of life in mainland China: a national cross-sectional study
Authors: Yao Qiang , Zhang Xiaodan , Wu Yibo , Liu Chaojie
Published: November 2023

Introduction

Health equity is an important indicator measuring social development and solidarity. However, there is a paucity in nationwide studies into the inequity in health-related quality of life (HRQoL) in mainland China, in particular using the most recent data measuring HRQoL using the EuroQol 5-Dimension-5 Level (EQ-5D-5L). This study aimed to address the gap in the literature by estimating and decomposing income-related inequality of the utility index (UI) of EQ-5D-5L in mainland China.

Methods

Data were extracted from the Psychology and Behaviour Investigation of Chinese Residents (2022), including 19 738 respondents over the age of 18 years. HRQoL was assessed by the UI of the EQ-5D-5L. Concentration index (CI) was calculated to measure the degree of income-related inequality in the UI. The contributions of individual, behavioural and context characteristics to the CI were estimated using the Wagstaff decomposition method.

Results

The CI of the EQ-5D-5L UI reached 0.0103, indicating pro-rich inequality in HRQoL. Individual characteristics made the greatest contribution to the CI (57.68%), followed by context characteristics (0.60%) and health behaviours (−3.28%). The contribution of individual characteristics was mainly attributable to disparities in the enabling (26.86%) and need factors (23.86%), with the chronic conditions (15.76%), health literacy (15.56%) and average household income (15.24%) as the top three contributors. Educational level (−5.24%) was the top negative contributor, followed by commercial (−1.43%) and basic medical insurance (−0.56%). Higher inequality was found in the least developed rural (CI=0.0140) and western regions (CI=0.0134).

Conclusion

Pro-rich inequality in HRQoL is evident in mainland China. Targeted interventions need to prioritise measures that aim at reducing disparities in chronic conditions, health literacy and income.
Designing the global vaccine supply chain: balancing intellectual property rights with post COVID-19 vaccine equity
Authors: Park Sung-Pil , Lee Hye Jin , Yu Yang , Lee Eric Yong Joong , Park Young Soo
Published: November 2023

This article aims to propose practical solutions that coordinate the conflicting interests between the global community and the pharmaceutical industry on the intellectual property (IP) waiver for COVID-19 vaccines and facilitate a more equitable vaccine supply chain in the post-COVID-19 world. We critically conducted a narrative literature review to identify procedural and practical issues in the current vaccine supply chain. The search was conducted across various academic disciplines, including biomedical science, life science, law and social science, using resources such as PubMed, Web of Science, Scopus and Westlaw. After screening 731 articles, 55 studies were selected for review. The narrative review revealed several critical barriers that hinder vaccine supply in less-developed countries (LDCs) as follows: (1) WTO Trade-Related Aspects of Intellectual Property Rights (TRIPs) waiver requests may not be granted due to its stringent consensus rule; (2) the current compulsory license system may not work due to the complexity of IP rights covering COVID-19 vaccine technologies; (3) only a few LDCs have domestic companies capable of manufacturing vaccines, and (4) political and economic tensions among countries exacerbate existing barriers to vaccine distribution in LDCs. Based on these findings, we proposed a comprehensive compulsory license system, which combines TRIPS’s compulsory license system with the third-party beneficiary mechanism under Common Law. This integrated approach offers a balanced solution that ensures fair compensation for vaccine developers while facilitating broader vaccine access.
Application of artificial intelligence in the diagnosis of hepatocellular carcinoma
Authors: Koh Benjamin , Danpanichkul Pojsakorn , Wang Meng , Tan Darren Jun Hao , Ng Cheng Han
Published: November 2023

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. This review explores the recent progress in the application of artificial intelligence (AI) in radiological diagnosis of HCC. The Barcelona Classification of Liver Cancer criteria guides treatment decisions based on tumour characteristics and liver function indicators, but HCC often remains undetected until intermediate or advanced stages, limiting treatment options and patient outcomes. Timely and accurate diagnostic methods are crucial for enabling curative therapies and improving patient outcomes. AI, particularly deep learning and neural network models, has shown promise in the radiological detection of HCC. AI offers several advantages in HCC diagnosis, including reducing diagnostic variability, optimising data analysis and reallocating healthcare resources. By providing objective and consistent analysis of imaging data, AI can overcome the limitations of human interpretation and enhance the accuracy of HCC diagnosis. Furthermore, AI systems can assist healthcare professionals in managing the increasing workload by serving as a reliable diagnostic tool. Integration of AI with information systems enables comprehensive analysis of patient data, facilitating more informed and reliable diagnoses. The advancements in AI-based radiological diagnosis hold significant potential to improve early detection, treatment selection and patient outcomes in HCC. Further research and clinical implementation of AI models in routine practice are necessary to harness the full potential of this technology in HCC management.
Methylglyoxal from gut microbes boosts radiosensitivity and radioimmunotherapy in rectal cancer by triggering endoplasmic reticulum stress and cGAS-STING activation
Authors: Zhou Han , Wang Lei , Lin Zhiwen , Jiang Chenwei , Chen Xingte , Wang Kai , Liu Libin , Shao Lingdong , Pan Jianji , Li Jinluan , Zhang Da , Wu Junxin
Published: November 2023

Background

Preoperative radiation therapy (preRT) is a fundamental aspect of neoadjuvant treatment for rectal cancer (RC), but the response to this treatment remains unsatisfactory. The combination of radiation therapy (RT) and immunotherapy (iRT) presents a promising approach to cancer treatment, though the underlying mechanisms are not yet fully understood. The gut microbiota may influence the response to RT and immunotherapy. Therefore, we aimed to identify the metabolism of gut microbiota to reverse radioresistance and enhance the efficacy of iRT.

Methods

Fecal and serum samples were prospectively collected from patients with locally advanced rectal cancer (LARC) who had undergone pre-RT treatment. Candidate gut microbiome-derived metabolites linked with radiosensitization were screened using 16s rRNA gene sequencing and ultrahigh-performance liquid chromatography-mass coupled with mass spectrometry. In vitro and in vivo studies were conducted to assess the radiosensitizing effects of the metabolites including the syngeneic CT26 tumor model and HCT116 xenograft tumor model, transcriptomics and immunofluorescence. The CT26 abscopal effect modeling was employed to evaluate the combined effects of metabolites on iRT.

Results

We initially discovered the gut microbiota-associated metabolite, methylglyoxal (MG), which accurately predicts the response to preRT (Area Under Curve (AUC) value of 0.856) among patients with LARC. Subsequently, we observed that MG amplifies the RT response in RC by stimulating intracellular reactive oxygen species (ROS) and reducing hypoxia in the tumor in vitro and in vivo. Additionally, our study demonstrated that MG amplifies the RT-induced activation of the cyclic guanosine monophosphate AMP synthase-stimulator of interferon genes pathway by elevating DNA double-strand breaks. Moreover, it facilitates immunogenic cell death generated by ROS-mediated endoplasmic reticulum stress, consequently leading to an increase in CD8+T and natural killer cells infiltrated in the tumor immune microenvironment. Lastly, we discovered that the combination of anti-programmed cell death protein 1 (anti-PD1) therapy produced long-lasting complete responses in all irradiated tumor sites and half of the non-irradiated ones.

Conclusions

Our research indicates that MG shows promise as a radiosensitizer and immunomodulator for RC. Furthermore, we propose that combining MG with iRT has great potential for clinical practice.
Effects of 7-day quercetin intervention on motor unit activity and muscle contractile properties before and after resistance exercise in young adults randomized controlled trials
Authors: Nishikawa Taichi , Hirono Tetsuya , Takeda Ryosuke , Okudaira Masamichi , Ohya Toshiyuki , Watanabe Kohei
Published: November 2023

We investigated whether the alteration of the motor unit recruitment threshold (MURT) caused by quercetin ingestion intervention for 7 days modifies motor unit activation patterns before and after a single session of resistance exercise. Twenty young male and female adults were divided into two groups: ingestion of placebo (PLA) or quercetin glycosides at 200 mg/day (QUE). High-density surface electromyography during submaximal contractions was measured to assess the motor unit firing rate (MUFR) and MURT of the vastus lateralis muscle before (PRE) and after (POST) resistance exercise (DAY1). The same measurements were repeated after 7 days of placebo or quercetin glycoside ingestion (DAY8). In QUE, MURT decreased more from DAY1-PRE to DAY8-PRE (29.1 ± 9.1 to 27.1 ± 9.5% MVC, p < 0.001) but not in PLA (29.8 ± 10.4 to 28.9 ± 9.7% MVC, p < 0.167). For percentage change in MUFR following resistance exercise, there was a significant interaction (day × group, p < 0.001). The degree of changes in MURT from DAY1-PRE to DAY8-PRE was significantly correlated with the percentage change of MUFR from DAY8-PRE to DAY8-POST in QUE ( p = 0.014, r = −0.363) but not in PLA ( p = 0.518). The study suggests that 7-day quercetin ingestion alters the motor unit recruitment pattern, and this may induce changes in motor unit firing patterns during a single session of resistance training (Trial registration: UMIN000052255, R000059650).
Do environmental researchers from marginalized groups experience greater interference? Understanding scientists' perceptions
Authors: Chu Samantha M. , Robertson Manjulika E. , Cloutier Anika , Arif Suchinta , Westwood Alana R.
Published: November 2023

Researchers in the environmental studies and sciences play a critical role in influencing real-world decision-making and policies. However, interference during research and sharing of results has been documented in Canada and around the world. Further, research has shown that workers from marginalized social identitie(s) experience discrimination in the workplace. Whether interference in research is related to social identity has never been examined. Using a mixed-methods design, we surveyed 741 environmental researchers in Canada to understand the relationship between social identity (gender, disability status, 2SLGBTQI+ status, race, and perception of racial identity) and reported experiences of interference. Results found that researchers with marginalized identities experienced worse outcomes across 11 of the 25 quantitative measures. For example, most marginalized groups experienced significantly greater fear of misrepresentation by media and (or) fear of negative career consequences due to public commentary, and racialized and disabled persons reported greater external interference in their work (e.g., from management and workplace policy). Given these findings, we express concern that the experience of interference in research can (1) threaten the personal well-being of marginalized researchers, (2) limit the representativeness of information disseminated, thererby impacting environmental decision-making and policy, and (3) contribute to inequities in representativeness of marginalized researchers in environmental sciences in Canada.
Mathematical analysis of electric signal transmission in semi-conductor materials
Authors: Durur Hülya , Arslantürk Reyhan , Aydın Aleyna
Published: November 2023

This study deals with the Lonngren wave equation, which is used to model the transmission of electrical signals in a type of semiconductor material called a tunnel diode. The aim of this study is to produce dark soliton, singular soliton, trigonometric, complex rational solutions to the Lonngren wave equation by using the sub-equation method. Graphs representing the Lonngren wave are drawn by giving different values to the variables in the solutions obtained. Graphs are presented using a special package program. In the light of the data obtained as a result of the study, it is thought that this new method used in the research of the solution of the Lonngren wave equation will contribute to the literature.
COMPLEXITY-BASED ANALYSIS OF THE CORRELATION OF BRAIN AND HEART ACTIVITY IN YOUNGER AND OLDER SUBJECTS
Authors: PAKNIYAT NAJMEH , VIVEKANANDHAN GAYATHRI , DAWI NORAZRYANA MAT , KREJCAR ONDREJ , FRISCHER ROBERT , NAMAZI HAMIDREZA
Published: November 2023

Studying the activity of organs during aging is a very important research area. On the other hand, simultaneous analysis of the activities of various organs is important to understand how their activities are correlated. For the first time, this research analyzes the brain-heart correlation in younger and older subjects. We analyzed the sample entropy (SampEn) and approximate entropy (ApEn) of EEG and R-R signals (as heart rate variability (HRV)) of younger and older participants while they sat comfortably in an armchair with their eyes open. The results indicated that older subjects’ EEG and R-R signals have greater values of sample and approximate entropies than younger subjects. Therefore, as subjects age, their EEG and R-R signals become more complex. This analysis can be extended to investigate the correlation between other physiological signals among different age groups.