bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability and electronic properties of XO (X = Be, Mg, Zn, Cd) biphenylene and graphenylene networks: A first-principles study
Authors: Abdullahi Yusuf Zuntu , Ersan Fatih
Published: December 2023

The ultrawide bandgap semiconducting property of materials is key to the development of advanced optoelectronic nanodevices with potential applications in flexible and transparent electronics and high-power radio frequency electronics. Here, a series of nonmagnetic porous XO (X = Be, Mg, Zn, and Cd) biphenylene- and graphenylene-type structures are predicted using the first-principles calculations based on the density functional theory (DFT). DFT results proved that XO monolayers exhibit excellent energetic, mechanical, dynamic, and thermal stabilities. The Heyd–Scuseria–Ernzerhof calculations show that the XO-biphenylene and graphenylene structures exhibit narrow, wide, ultra-wide, and insulating semiconducting electronic properties. We then investigated the bandgaps dependent on the thickness of the XO layer and found that the bandgaps decrease uniformly as the number of XO-biphenylene and -graphenylene layers increases. These remarkable electronic properties of XO structures expand the potential of porous oxide materials for the development of practical optoelectronic and thermoelectric nanodevices.
Saturable absorption and third-order nonlinear refraction of 2D CdSe nanoplatelets resonant with heavy-hole excitonic transitions
Authors: Gonçalves Igor M. , Medda Anusri , Bautista Jessica E. Q. , Campos Cecília L. A. V. , Ghosh Soubhik , Patra Amitava , Gomes Anderson S. L.
Published: December 2023

We report on the nonlinear optical response of CdSe nanoplatelets and CdSe/CdS core/shell nanoplatelets in the heavy-hole resonant excitonic transition spectral regions with femtosecond pulses. The nonlinear refraction and saturable absorption coefficients were obtained using the Z-scan technique, and the results were explained theoretically. The nonlinear optical response under nonresonant excitation has been previously examined; comparing with the results presented in this work, at least a one order of magnitude increase in the nonlinear refraction coefficient is evident.
Circular dichroism of pseudo-two-dimensional metal nanostructures: Rotational symmetry and reciprocity
Authors: Endo Kensaku , Hashiyada Shun , Narushima Tetsuya , Togawa Yoshihiko , Okamoto Hiromi
Published: December 2023

Circular dichroism (CD) spectra for pseudo-two-dimensional chiral nanomaterials were systematically investigated and analyzed in relation to the rotational symmetry of the nanomaterials. Theoretically, an ideal two-dimensional chiral matter is CD inactive for light incident normal to the plane if it possesses threefold or higher rotational symmetry. If the matter has two- or onefold rotational symmetry, it should exhibit CD activity, and the CD signal measured from the back side of the matter is expected to be inverted from that measured from the front side. For pseudo-two-dimensional chiral gold nanostructures fabricated on glass substrates using electron beam lithography, matter with fourfold rotational symmetry is found to be CD active, even when special care is taken to ensure that the optical environments for the front and back sides of the sample are equivalent. In this case, the CD signal measured from the back side is found to be almost exactly the same as that measured from the front side. It is revealed that the observed chiro-optical behavior arises from three-dimensional chiral characteristics due to differences in the surface shape between the front and back sides of the structures. For matter that is two- or onefold rotationally symmetric, the CD signal measured from the back side is not coincident with that from the front side. For certain wavelength regions, the CD signals measured from the front side and back side are observed to be similar, while at other wavelengths, the inverted component of the CD signals is found to dominate. The observed CD spectral behavior for reciprocal optical measurement configurations is considered to be determined by a balance between the in-plane isotropic and anisotropic components of the chiral permittivity.
Synthesis, characterization, and first-principles analysis of Mo2NiB2-type high-entropy boride ceramic
Authors: Wang Jie , Shangguan Dongyu , Zheng Shaohui , Jiang Xianquan , Liu Huake , Wang Guangrui
Published: December 2023

A Mo2NiB2-type high-entropy boride ceramic with the nominal formula of (Mo0.5W0.5)2(Fe0.3Co0.35Ni0.35)B2 (abbreviated as X3B2) was synthesized by vacuum sintering. The phase structure, crystalline construction, bonding, and hardness properties were clarified in detail by first-principles calculations and experiment. The results show that the as-synthesized sample exhibits single phase and satisfied compositional homogeneity. Moreover, it can be obtained that both Mo–B bonds and W–B bonds in X3B2 exhibit the covalent characteristics, while the binding of Mo–B is stronger than the other. Initial property assessments show that the Vickers hardness of X3B2 is generally more than 20% higher than the reported Mo2NiB2. These results suggest an idea to achieve high hard and high-performance materials via exploring high-entropy ternary-boride ceramic.
Hole diffusion effect on the minority trap detection and non-ideal behavior of NiO/β-Ga2O3 heterojunction
Authors: Labed Madani , Alotaibi Saud , Min Ji Young , Almalki Abdulaziz , Henini Mohamed , Rim You Seung
Published: December 2023

A NiO/β-Ga2O3 heterojunction was fabricated by sputtering a highly p-doped NiO layer onto β-Ga2O3. This heterojunction showed a low leakage current and a high turn-on voltage (Von) compared to a Ni/β-Ga2O3 Schottky barrier diode. The extracted Von from the NiO/β-Ga2O3 heterojunction's forward current–voltage characteristics was ∼1.64 V, which was lower than the extracted built-in potential voltage (Vbi) obtained from the capacitance–voltage curve. To explain this difference, deep level transient spectroscopy and Laplace-deep level transient spectroscopy were employed to study majority and minority traps in β-Ga2O3 films. A minority trap was detected near the surface of β-Ga2O3 under a reverse bias of −1 V but was not observed at −4 V, indicating its dependence on hole injection density. Using Silvaco TCAD, the hole diffusion length from P+-NiO to β-Ga2O3 was determined to be 0.15 μm in equilibrium, which is increased with increasing forward voltage. This finding explained why the trap level was not detected at a large reverse bias. Moreover, hole diffusion from NiO into β-Ga2O3 significantly affected the β-Ga2O3 surface band bending and impacted transport mechanisms. It was noted that the energy difference between the conduction band minimum (CBM) of β-Ga2O3 and the valence band maximum (VBM) of NiO was reduced to 1.60 eV, which closely matched the extracted Von value. This supported the dominance of direct band-to-band tunneling of electrons from the CBM of β-Ga2O3 to the VBM of NiO under forward bias voltage.
Diffusion-controlled annealing kinetics of interstitial H in SnO2
Authors: Venzie Andrew , Stavola Michael , Fowler W. Beall , Boatner Lynn A.
Published: December 2023

SnO2 is a prototypical transparent conducting oxide that finds widespread applications as transparent electrodes, gas sensors, and transparent thin-film devices. Hydrogen impurities in SnO2 give rise to unintentional n-type behavior and unexpected changes to conductivity. Interstitial H (Hi) and H at an oxygen vacancy (HO) are both shallow donors in SnO2. An O–H vibrational line at 3155 cm−1, that can be produced by a thermal anneal at 500 °C followed by a rapid quench, has been assigned to the Hi center and is unstable at room temperature on a timescale of weeks. An IR absorption study of the decay kinetics of the 3155 cm−1 O–H line has been performed. The disappearance of Hi upon annealing has been found to follow second-order kinetics. Measurements of the decay rate for a range of temperatures have determined an activation energy for the diffusion of interstitial H in SnO2. These results provide fundamental information about how unintentional hydrogen impurities and their reactions can change the conductivity of SnO2 device materials in processes as simple as thermal annealing in an inert ambient.
Ian McDougall 1935–2018
Authors: Phillips David
Published: December 2023

Ian McDougall was a renowned Earth scientist who gained worldwide distinction for his research in the fields of K-Ar and 40Ar/39Ar geochronology. He was born in Hobart, Tasmania and obtained a BSc (Hons) at the University of Tasmania and a PhD at the Australian National University in Canberra. Following his PhD, he was introduced to the emerging field of K-Ar geochronology during a postdoctoral year at the University of Berkeley in 1961. On his return to Australia, Ian accepted a position in the newly established K-Ar laboratory at the Australian National University. He pioneered the application of the K-Ar dating method to young volcanic rocks and played a pivotal role in developing the geomagnetic timescale. These findings provided crucial evidence in support of the ‘hot spot’ (mantle plume) model and the emerging theory of plate tectonics. He subsequently established the 40Ar/39Ar geochronology method at the Australian National University and gained an international reputation for meticulous experimental work. In the 1980s, he resolved a significant controversy with regard to the age of hominin fossils and artefacts in the Turkana Basin, Kenya. Over the following four decades, he developed a comprehensive geochronological framework for volcanism across the Turkana Basin, providing the basis for current interpretations of early human evolution in the region. Other notable collaborative accomplishments include the application of the 40Ar/39Ar method to thermal history studies and noble gas geochemistry studies of volcanic glasses and mantle material, which provided insights into the evolution of Earth’s atmosphere and interior. Ian’s scientific contributions were recognised with numerous honours and awards, including being elected a Fellow of the American Geophysical Union, a Fellow of the Australian Academy of Science, and receiving the Jaeger Medal from the Australian Academy of Science and the Centenary Medal for ‘service to Australian society and science in geochronology’.
Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis
Authors: Song Da , Hu Fuqing , Huang Changsheng , Lan Jingqin , She Xiaowei , Zhao Chongchong , Wu Hong , Liu Anyi , Wu Qi , Chen Yaqi , Luo Xuelai , Feng Yongdong , Yang Xiangping , Xu Chuan , Hu Junbo , Wang Guihua
Published: December 2023

Metastasis is a major cause of cancer therapy failure and mortality. However, targeting metastatic seeding and colonization remains a significant challenge. In this study, we identified NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, as being overexpressed in metastatic tumors. Our findings suggest that NSD2 overexpression enhances tumor metastasis both in vitro and in vivo. Further analysis revealed that NSD2 promotes tumor metastasis by activating Rac1 signaling. Mechanistically, NSD2 combines with and activates Tiam1 (T lymphoma invasion and metastasis 1) and promotes Rac1 signaling by methylating Tiam1 at K724. In vivo and in vitro studies revealed that Tiam1 K724 methylation could be a predictive factor for cancer prognosis and a potential target for metastasis inhibition. Furthermore, we have developed inhibitory peptide which was proved to inhibit tumor metastasis through blocking the interaction between NSD2 and Tiam1. Our results demonstrate that NSD2-methylated Tiam1 promotes Rac1 signaling and cancer metastasis. These results provide insights into the inhibition of tumor metastasis.
Drift on holey landscapes as a dominant evolutionary process
Authors: Dochtermann Ned A. , Klock Brady , Roff Derek A. , Royauté Raphaël
Published: December 2023

An organism’s phenotype has been shaped by evolution but the specific processes have to be indirectly inferred for most species. For example, correlations among traits imply the historical action of correlated selection and, more generally, the expression and distribution of traits is expected to be reflective of the adaptive landscapes that have shaped a population. However, our expectations about how quantitative traits—like most behaviors, physiological processes, and life-history traits—should be distributed under different evolutionary processes are not clear. Here, we show that genetic variation in quantitative traits is not distributed as would be expected under dominant evolutionary models. Instead, we found that genetic variation in quantitative traits across six phyla and 60 species (including both Plantae and Animalia) is consistent with evolution across high-dimensional “holey landscapes.” This suggests that the leading conceptualizations and modeling of the evolution of trait integration fail to capture how phenotypes are shaped and that traits are integrated in a manner contrary to predictions of dominant evolutionary theory. Our results demonstrate that our understanding of how evolution has shaped phenotypes remains incomplete and these results provide a starting point for reassessing the relevance of existing evolutionary models.
Instructor positioning as participants in a transnational EMI program
Authors: Shea Kate , Vu Truong , Sokol Geoff
Published: December 2023

The simultaneous global growth in higher education’s student population and demand for English-medium instruction
(EMI) have created various models of transnational education (TNE) partnerships that use EMI to recruit students and increase
opportunities for international collaboration. Inevitably, in transnational collaborative efforts, stakeholders have far more
conflicting considerations as they navigate multiple countries’ academic policies and norms, diverse student, staff and faculty
expectations, and the myriad of linguistic and cultural differences. In response to these concerns, this qualitative case study
analyzed instructor discursive positioning in a TNE partnership between a US and a Vietnamese institution. Using a collaborative
action research approach, this article features the experience of two instructors teaching in a TNE partnership using an EMI model
in Vietnam. Using identity and positioning theory as guiding theoretical frameworks, instructors’ and students’ discourses were
thematically analyzed. The findings reflect dominant discourses and language ideologies surrounding the “Englishization” of higher
education, in addition to highlighting stakeholders’ challenges of working between two institutions and having
conflicting responsibilities as both instructors and administrative staff. Similarly, the students’ interview data reflected their
navigation of being participants at two universities with different academic systems and norms.
A four-year trajectory of development from student to published researcher
Authors: Shahri Naseh Nasrollahi
Published: December 2023

This case study tracks a multilingual writer’s academic writing, in particular her engagement in the research article (RA) genre, over the course of four years as she moved along a trajectory from a novice graduate student to a confident disciplinary writer. The theoretical framework draws from academic literacies (Barton & Hamilton, 1998), highlighting practice and disposition (Bourdieu, 1990) as a way of understanding engagement with the RA genre. The findings, based on an analysis of interviews conducted with the participant, reveal three stages of the participant’s development in her disposition toward the RA genre, all interspersed with affect. Each stage is illustrated through examples from the interviews. The study’s longitudinal design provides a novel perspective that brings out a dynamic picture of thedevelopmentof a graduate student writer. The findings are discussed in light of previous research and pedagogical implications are set out.
Japanese scientists’ English for research publication purposes
Authors: McDowell Leigh
Published: December 2023

Error Analysis was developed by early Second Language Acquisition (SLA) researchers as a way to investigate
interlanguage and better understand the second-language learning processes. While it is no longer an active branch of research in
SLA, it remains a useful tool for those concerned with accuracy in language use. Given the elevated importance of accuracy in
English for Research and Publication Purposes (ERPP), this may be one area where Error Analysis may continue to inform research
and praxis. The high degree of language precision demanded in ERPP contexts can be a source of frustration for many engaged in
scholarly publication, especially those for whom English is an additional language, such as the Japanese scientists studied in
this paper. For Japanese scientists and possibly others, an empirical profile of their most frequent error patterns may help them
to better deal with accuracy in research writing. With this motivation, this study applies a corpus-assisted error analysis
framework to quantify sentence-level grammar errors and identify the most frequent error patterns in the research article
manuscripts of Japanese scientists. A corpus of 53 research article manuscripts with 4,495 errors comprises the primary data.
Additionally, two raters and a comparison of errors from scientists from six different L1 backgrounds are employed to triangulate
the data and investigate the reliability and generalizability of the findings. Findings reveal that the top ten most frequent
errors comprise 52.9%, or half of all errors in the corpus, and are dominated by errors with determiners and prepositions.
Torso articulation in sign languages
Authors: Napoli Donna Jo , Sutton-Spence Rachel
Published: December 2023

Torso articulation in sign languages is mentioned variably in the linguistic analysis of sign languages but is
often ignored. The prevailing idea seems to be that detailed study of movement of the parts of the torso will yield little insight
into linguistic matters – so mentions can be general and brief. The result is that torso articulations are an unmined area –
perhaps one that holds treasures, particularly regarding the appreciation of creative sign language. We draw together the findings
of other research regarding torso articulation, then give an inventory of possible torso articulations, exemplified with signs
from dozens of the world’s named sign languages, and a brief overview of how annotation systems have approached torso movement in
signs. We end with suggestions for how the study of torso articulation can open new avenues of sign language research.
Evaluate Emotional State Based on Temperature Readings
Authors: Uddin Jashim
Published: December 2023

Infrared thermography (IRT) allows visualization of temperature changes within the body system of animals due to emotional changes in a fearful situation such as facing an unknown person in their flight distance. Infrared thermography is becoming popular in the research of animal emotions as an objective measure. Stress stimulants activate the autonomic nervous system to secrete adrenaline, which causes the blood vessels to tighten and increase blood flow throughout the body. Infrared thermography quantifies the heat radiation emitted from the body’s surface, which fluctuates depending on the flow of blood below the skin. It has been discovered through a number of studies that IRT of the eyes of lactating dairy cows can more accurately predict their emotional responses than the commonly used rectal temperature and/or other behavioural measures. The IRT of eyes showed the potential to predict negative emotional responses in association with laterality testing, flight speed, waiting time, and other behaviours such as sniffing. The IRT of the eye was a repeatable measure, while rectal temperature was not.

Information

© The Author 2023
Dengue virus: Epidemiology, clinical aspects, diagnosis, prevention and management of disease in Pakistan: Review
Authors: Muhammad Usman , Ahmad Maqsood , Abbas Sohail , Arif Muhammad Zahid Ehsan , Jan Misbah , Sarwar Muhammad Farhan , Aziz Mariam , Alam Aleena , Sumbal Ghulam Ahmad Khan , Hameed Muhammad Salman
Published: December 2023

Worldwide, the dengue virus (DENV) is a common cause of infections. The disease can range from a minor flu-like illness to a serious complex ailment that kills the sufferer. Both the morbidity and fatality rates associated with dengue fever (DF) are high in Pakistan and other Asian nations. Through a mosquito bite, the DENV is spread. DENV was isolated to specific regions of the tropics and subtropics until the middle of the 20th century. Global distribution of DF is influenced by a number of variables, including changing climate, rising international travel and urban population, poor vector management techniques, lack of safe and effective antiviral medications and a lack of vaccines to prevent the disease. In over 100 nations, DF poses a major threat to the lives of over 2.5 billion people. Today, DF is endemic to the Caribbean, South America, Africa and Asia. In actuality, 40% of the world’s population currently resides in nations where there is a significant risk of DF transmission. It has grown to be a significant health issue in Pakistan and is predicted to get worse over the next few years. In Pakistan, dengue cases increase in the rainfall season, especially during monsoon season. In Pakistan, the mosquito species
Aedes aegypti
is the main carrier of this disease. This review article summarizes the epidemiology, clinical aspects of DF and DHF, diagnosis, prevention and management of disease in Pakistan.
Dual-frequency transmitter configuration for shallow surface electromagnetic detection
Authors: Liu Weiyu , Yu Shengbao , Zhang Xinhao
Published: December 2023

In shallow surface electromagnetic detection, the square wave scheme is generally used in conventional transmission systems. Based on frequency-domain electromagnetic sounding theory, high-frequency measurement helps to improve vertical resolution. However, long grounded cable inductance produces severe reactive power suppression at high frequency transmission frequencies, which will reduce detection. To further improve detection accuracy and efficiency, a dual-frequency transmitter configuration is proposed in this article for shallow surface detection. The transmitter simultaneously powers two LC series resonant circuits for the detection of shallow and deep area. Dual-frequency control strategy is adopted, with both bridge arms being provided with constant switching frequency operation. According to the equivalent model of the transmission system, the control of the load branches is independent of each other. The LC series resonant circuit guarantees a wide passband to match long cable inductance that cannot be accurately estimated in advance. Simulations and experimental tests were carried out using this transmitter configuration and control technique. The simulation and experimental results are in general agreement, verifying the feasibility and effectiveness of the proposed dual-band transmitter configuration.
Half-wavelength velocity bunching: non-adiabatic temporal focusing of charged particle beams
Authors: Opanasenko Anatoliy , Perosa Giovanni , Ribbing Johan , Goryashko Vitaliy
Published: December 2023

X-ray free-electron lasers (XFELs) and megaelectronvolt ultrafast electron diffractometers (MeV UEDs) are revolutionary scientific instruments that allow visualizing the dynamics of elementary excitations in a wide range of systems from atoms and molecules to phonons, magnons and plasmons. Femtosecond (fs) electron beams are at the heart of XFELs and MeV UEDs, and the formation of fs electron beams with ultrahigh brightness is the subject of active research. We report an interesting regime of non-adiabatic temporal compression of electron beams by two orders of magnitude. Via analytical calculations and numerical simulations, we show that few MeV electron bunches can be trapped and compressed by a strong electromagnetic field within a half of the field wavelength. Furthermore, in a multi-cell accelerating cavity, the bunch is first compressed and then accelerated, thus allowing one to preserve very short bunch duration. For example, a 3 ps 16 pC 1 MeV electron bunch is compressed to 21 fs rms and accelerated to 12 MeV in a TESLA superconducting cavity. Another example is the production of 1.2 fs 16 fC 3.3 MeV bunches with a coherence length of 20 nm and and an energy spread less than 3 keV. The discovered mechanism of compression, which is another mode of velocity bunching, opens the door for obtaining very high electron brightness.
Predict the last closed-flux surface evolution without physical simulation
Authors: Wan Chenguang , Bai Shuhang , Yu Zhi , Yuan Qiping , Huang Yao , Liu Xiaojuan , Hu Yemin , Li Jiangang
Published: December 2023

One of the main challenges in developing effective control strategies for the magnetic control system in tokamaks has been the difficulty in obtaining the last closed-flux surface (LCFS) evolution results from control commands. We have developed a data-driven model that combines a predictive model and a surrogate model for physics simulation programs. This model is capable of predicting the LCFS without relying on physical simulation codes. Addressing the data characteristics of LCFS, we have proposed a specialized discretization approach to achieve dimensionality reduction. Furthermore, we have excluding the control references, the model can be seamlessly integrated into the control system, providing real-time LCFS prediction. Following comprehensive testing and multifaceted evaluation, our model has demonstrated highly satisfactory results of 95% or above, meeting practical requirements.
Power Brownian motion
Authors: Eliazar Iddo
Published: December 2023

Brownian motion (BM) is the archetypal model of regular diffusion. BM is a Gaussian and Markov process, whose increments are stationary, and whose non-overlapping increments are independent. Elevating from regular diffusion to anomalous diffusion, fractional Brownian motion (FBM) and scaled Brownian motion (SBM) are arguably the two most popular Gaussian anomalous-diffusion models. Each of these two models maintains some BM properties, abandons other, and displays certain anomalous behaviors. This paper explores a Gaussian anomalous-diffusion model—Power Brownian Motion (PBM)—that is attained by a coupled amplitudal and temporal ‘tinkering’ with BM. The PBM model combines ‘the better of FBM and SBM’. Indeed, as FBM, PBM displays the anomalous behaviors of persistence and anti-persistence. And, as SBM, PBM is a Markov process that displays the anomalous behaviors of aging and anti-aging. On their own, neither FBM nor SBM can provide the ‘features package’ that PBM provides. The PBM ‘features package’ on the one hand, and its simple construction on the other hand, render PBM a compelling anomalous-diffusion model.
On some Lie-theoretic solutions of the tt*-Toda equations with integer Stokes data
Authors: Hateruma Yudai , Kaneko Yoshiki
Published: December 2023

We describe some solutions of the tt*-Toda equations with integer Stokes data, based on a Lie-theoretic approach. In particular, we find all such solutions in a certain 1-parameter family. For general solutions, we compare the results of Guest–Its–Lin (based on solving the equations) with the original classification of Cecotti–Vafa (based on braid group orbits of Stokes matrices for hypothetical solutions), and find that these agree in low dimensions.
Unraveling viral drug targets: a deep learning-based approach for the identification of potential binding sites
Authors: Popov Petr , Kalinin Roman , Buslaev Pavel , Kozlovskii Igor , Zaretckii Mark , Karlov Dmitry , Gabibov Alexander , Stepanov Alexey
Published: December 2023

The coronavirus disease 2019 (COVID-19) pandemic has spurred a wide range of approaches to control and combat the disease. However, selecting an effective antiviral drug target remains a time-consuming challenge. Computational methods offer a promising solution by efficiently reducing the number of candidates. In this study, we propose a structure- and deep learning-based approach that identifies vulnerable regions in viral proteins corresponding to drug binding sites. Our approach takes into account the protein dynamics, accessibility and mutability of the binding site and the putative mechanism of action of the drug. We applied this technique to validate drug targeting toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein S. Our findings reveal a conformation- and oligomer-specific glycan-free binding site proximal to the receptor binding domain. This site comprises topologically important amino acid residues. Molecular dynamics simulations of Spike in complex with candidate drug molecules bound to the potential binding sites indicate an equilibrium shifted toward the inactive conformation compared with drug-free simulations. Small molecules targeting this binding site have the potential to prevent the closed-to-open conformational transition of Spike, thereby allosterically inhibiting its interaction with human angiotensin-converting enzyme 2 receptor. Using a pseudotyped virus-based assay with a SARS-CoV-2 neutralizing antibody, we identified a set of hit compounds that exhibited inhibition at micromolar concentrations.
KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling
Authors: Ren Qun , Qu Ning , Sun Jingjing , Zhou Jingyi , Liu Jin , Ni Lin , Tong Xiaochu , Zhang Zimei , Kong Xiangtai , Wen Yiming , Wang Yitian , Wang Dingyan , Luo Xiaomin , Zhang Sulin , Zheng Mingyue , Li Xutong
Published: December 2023

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.
StabJGL: a stability approach to sparsity and similarity selection in multiple-network reconstruction
Authors: Lingjærde Camilla , Richardson Sylvia
Published: December 2023

Motivation

In recent years, network models have gained prominence for their ability to capture complex associations. In statistical omics, networks can be used to model and study the functional relationships between genes, proteins, and other types of omics data. If a Gaussian graphical model is assumed, a gene association network can be determined from the non-zero entries of the inverse covariance matrix of the data. Due to the high-dimensional nature of such problems, integrative methods that leverage similarities between multiple graphical structures have become increasingly popular. The joint graphical lasso is a powerful tool for this purpose, however, the current AIC-based selection criterion used to tune the network sparsities and similarities leads to poor performance in high-dimensional settings.

Results

We propose stabJGL, which equips the joint graphical lasso with a stable and well-performing penalty parameter selection approach that combines the notion of model stability with likelihood-based similarity selection. The resulting method makes the powerful joint graphical lasso available for use in omics settings, and outperforms the standard joint graphical lasso, as well as state-of-the-art joint methods, in terms of all performance measures we consider. Applying stabJGL to proteomic data from a pan-cancer study, we demonstrate the potential for novel discoveries the method brings.

Availability and implementation

A user-friendly R package for stabJGL with tutorials is available on Github https://github.com/Camiling/stabJGL.
ENTRAIN: integrating trajectory inference and gene regulatory networks with spatial data to co-localize the receptor–ligand interactions that specify cell fate
Authors: Kyaw Wunna , Chai Ryan C , Khoo Weng Hua , Goldstein Leonard D , Croucher Peter I , Murray John M , Phan Tri Giang
Published: December 2023

Motivation

Cell fate is commonly studied by profiling the gene expression of single cells to infer developmental trajectories based on expression similarity, RNA velocity, or statistical mechanical properties. However, current approaches do not recover microenvironmental signals from the cellular niche that drive a differentiation trajectory.

Results

We resolve this with environment-aware trajectory inference (ENTRAIN), a computational method that integrates trajectory inference methods with ligand-receptor pair gene regulatory networks to identify extracellular signals and evaluate their relative contribution towards a differentiation trajectory. The output from ENTRAIN can be superimposed on spatial data to co-localize cells and molecules in space and time to map cell fate potentials to cell-cell interactions. We validate and benchmark our approach on single-cell bone marrow and spatially resolved embryonic neurogenesis datasets to identify known and novel environmental drivers of cellular differentiation.

Availability and implementation

ENTRAIN is available as a public package at https://github.com/theimagelab/entrain and can be used on both single-cell and spatially resolved datasets.
Shipwreck ecology: Understanding the function and processes from microbes to megafauna
Authors: Paxton Avery B , McGonigle Christopher , Damour Melanie , Holly Georgia , Caporaso Alicia , Campbell Peter B , Meyer-Kaiser Kirstin S , Hamdan Leila J , Mires Calvin H , Taylor J Christopher
Published: December 2023

An estimated three million shipwrecks exist worldwide and are recognized as cultural resources and foci of archaeological investigations. Shipwrecks also support ecological resources by providing underwater habitats that can be colonized by diverse organisms ranging from microbes to megafauna. In the present article, we review the emerging ecological subdiscipline of shipwreck ecology, which aims to understand ecological functions and processes that occur on shipwrecks. We synthesize how shipwrecks create habitat for biota across multiple trophic levels and then describe how fundamental ecological functions and processes, including succession, zonation, connectivity, energy flow, disturbance, and habitat degradation, manifest on shipwrecks. We highlight future directions in shipwreck ecology that are ripe for exploration, placing a particular emphasis on how shipwrecks may serve as experimental networks to address long-standing ecological questions.
Coexistence of multiple self-healing squamous epithelioma and features of Loeys–Dietz syndrome caused by a pathogenic missense variant in the kinase domain of TGFBR1
Authors: Schirwani Schaida , Suarez Bea , Sommerlad Matthew , Corden Emma , Belgi Geeta , Eccles Diana , Fityan Adam
Published: December 2023

Multiple self-healing squamous epithelioma (MSSE) is characterized by development of multiple self-healing skin tumours that may affect any part of the body. Spontaneous resolution may take several months leaving pitted scars. Most pathogenic variants in patients with MSSE are truncating variants distributed throughout the gene or missense variants in the receptor domain of TGFBR1. Missense variants in the kinase domain of TGFBR1 cause Loeys–Dietz syndrome (LDS), which is a connective tissue disorder associated with increased risk of aortic and arterial aneurysms and dissection. We report the coexistence of MSSE and features of LDS caused by a pathogenic missense variant in the kinase domain of TGFBR1.
Cortical myelin and thickness mapping provide insights into whole-brain tumor burden in diffuse midline glioma
Authors: Zhang Simin , Yang Xibiao , Tan Qiaoyue , Sun Huaiqiang , Chen Di , Chen Yinying , Zhang Hongjing , Yang Yuan , Gong Qiyong , Yue Qiang
Published: December 2023

Systemic infiltration is a hallmark of diffuse midline glioma pathogenesis, which can trigger distant disturbances in cortical structure. However, the existence and effects of these changes have been underexamined. This study aimed to investigate whole-brain cortical myelin and thickness alternations induced by diffuse midline glioma. High-resolution T1- and T2-weighted images were acquired from 90 patients with diffuse midline glioma with H3 K27-altered and 64 patients with wild-type and 86 healthy controls. Cortical thickness and myelin content was calculated using Human Connectome Project pipeline. Significant differences in cortical thickness and myelin content were detected among groups. Short-term survival prediction model was constructed using automated machine learning. Compared with healthy controls, diffuse midline glioma with H3 K27-altered patients showed significantly reduced cortical myelin in bilateral precentral gyrus, postcentral gyrus, insular, parahippocampal gyrus, fusiform gyrus, and cingulate gyrus, whereas diffuse midline glioma with H3 K27 wild-type patients exhibited well-preserved myelin content. Furtherly, when comparing diffuse midline glioma with H3 K27-altered and diffuse midline glioma with H3 K27 wild-type, the decreased cortical thickness in parietal and occipital regions along with demyelination in medial orbitofrontal cortex was observed in diffuse midline glioma with H3 K27-altered. Notably, a combination of cortical features and tumor radiomics allowed short-term survival prediction with accuracy 0.80 and AUC 0.84. These findings may aid clinicians in tailoring therapeutic approaches based on cortical characteristics, potentially enhancing the efficacy of current and future treatment modalities.
Genetic analyses identify brain imaging-derived phenotypes associated with the risk of amyotrophic lateral sclerosis
Authors: Wang Yinan , Shen Ouxi , Xu Qingyun , Sun Lulu , Jia Yiming , Liu Yi , He Yu , Chang Xinyue , Guo Daoxia , Shi Mengyao , Chen Guo-Chong , Zheng Jin , Zhu Zhengbao
Published: December 2023

Brain imaging-derived phenotypes have been suggested to be associated with amyotrophic lateral sclerosis in observational studies, but whether these associations are causal remains unclear. We aimed to assess the potential bidirectional causal associations between imaging-derived phenotypes and amyotrophic lateral sclerosis using bidirectional 2-sample Mendelian randomization analyses. Summary statistics for 469 imaging-derived phenotypes (33,224 individuals) and amyotrophic lateral sclerosis (20,806 cases and 59,804 controls) were obtained from 2 large-scale genome-wide association studies of European ancestry. We used the inverse-variance weighted Mendelian randomization method in the main analysis to assess the bidirectional associations between imaging-derived phenotypes and amyotrophic lateral sclerosis, followed by several sensitivity analyses for robustness validation. In the forward Mendelian randomization analyses, we found that genetically determined high orientation dispersion index in the right cerebral peduncle was associated with the increased risk of amyotrophic lateral sclerosis (odds ratio = 1.30, 95% confidence interval = 1.16–1.45, P = 2.26 × 10−6). In addition, the reverse Mendelian randomization analysis indicated that amyotrophic lateral sclerosis had no effect on 469 imaging-derived phenotypes. Mendelian randomization-Egger regression analysis showed no directional pleiotropy for the association between high orientation dispersion index in the right cerebral peduncle and amyotrophic lateral sclerosis, and sensitivity analyses with different Mendelian randomization models further confirmed these findings. The present systematic bidirectional Mendelian randomization analysis showed that high orientation dispersion index in the right cerebral peduncle might be the potential causal mediator of amyotrophic lateral sclerosis, which may provide predictive guidance for the prevention of amyotrophic lateral sclerosis. Further studies are warranted to replicate our findings and clarify the underlying mechanisms.
The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing (December 2023)
Authors: Hayden Mary K , Hanson Kimberly E , Englund Janet A , Lee Mark J , Loeb Mark , Lee Francesca , Morgan Daniel J , Patel Robin , El Mikati Ibrahim K , Iqneibi Shahad , Alabed Farouk , Amarin Justin Z , Mansour Razan , Patel Payal , Falck-Ytter Yngve , Morgan Rebecca L , Murad M Hassan , Sultan Shahnaz , Bhimraj Adarsh , Mustafa Reem A
Published: December 2023

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.
Artificial intelligence-based identification of left ventricular systolic dysfunction from 12-lead electrocardiograms: external validation and advanced application of an existing model
Authors: König Sebastian , Hohenstein Sven , Nitsche Anne , Pellissier Vincent , Leiner Johannes , Stellmacher Lars , Hindricks Gerhard , Bollmann Andreas
Published: December 2023

Aims

The diagnostic application of artificial intelligence (AI)-based models to detect cardiovascular diseases from electrocardiograms (ECGs) evolves, and promising results were reported. However, external validation is not available for all published algorithms. The aim of this study was to validate an existing algorithm for the detection of left ventricular systolic dysfunction (LVSD) from 12-lead ECGs.

Methods and results

Patients with digitalized data pairs of 12-lead ECGs and echocardiography (at intervals of ≤7 days) were retrospectively selected from the Heart Center Leipzig ECG and electronic medical records databases. A previously developed AI-based model was applied to ECGs and calculated probabilities for LVSD. The area under the receiver operating characteristic curve (AUROC) was computed overall and in cohorts stratified for baseline and ECG characteristics. Repeated echocardiography studies recorded ≥3 months after index diagnostics were used for follow-up (FU) analysis. At baseline, 42 291 ECG-echocardiography pairs were analysed, and AUROC for LVSD detection was 0.88. Sensitivity and specificity were 82% and 77% for the optimal LVSD probability cut-off based on Youden’s J. AUROCs were lower in ECG subgroups with tachycardia, atrial fibrillation, and wide QRS complexes. In patients without LVSD at baseline and available FU, model-generated high probability for LVSD was associated with a four-fold increased risk of developing LVSD during FU.

Conclusion

We provide the external validation of an existing AI-based ECG-analysing model for the detection of LVSD with robust performance metrics. The association of false positive LVSD screenings at baseline with a deterioration of ventricular function during FU deserves a further evaluation in prospective trials.
Surveillance and Self-Control
Authors: Cobb-Clark Deborah A , Dahmann Sarah C , Kamhöfer Daniel A , Schildberg-Hörisch Hannah
Published: December 2023

This paper studies important determinants of adult self-control using population-representative data and exploiting Germany’s division as quasi-experimental variation. We find that former East Germans have substantially more self-control than West Germans and provide evidence for government surveillance as a possible underlying mechanism. We thereby demonstrate that institutional factors can shape people’s self-control. Moreover, we find that self-control increases linearly with age. In contrast to previous findings for children, there is no gender gap in adult self-control and family background does not predict self-control.
Digest: Understanding the evolution of sexual dichromatism also requires a female perspective
Authors: Ottenburghs Jente
Published: December 2023

The study of sexual dichromatism has generally focused on sexual selection for conspicuous males, ignoring the potential role played by selection in females. To address this problem, Price et al. took into account evolutionary changes in both males and females when investigating the evolution of plumage dichromatism across the New World blackbirds (Icteridae). They found that sexual dichromatism was repeatedly and rapidly lost as females evolved male-like plumage traits. The evolutionary dynamics in plumage coloration were drastically different in males and females, highlighting the importance of considering both perspectives in trait evolution.
Including stress relaxation in point-process model for seismic occurrence
Authors: Petrillo Giuseppe , Lippiello Eugenio , Zhuang Jiancang
Published: December 2023

Physics-based and statistic-based models for describing seismic occurrence are two sides of the same coin. In this paper, we compare the temporal organization of events obtained in a spring-block model for the seismic fault with the one predicted by probabilistic models for seismic occurrence. Thanks to the optimization of the parameters, by means of a Maximum Likelihood Estimation, it is possible to identify the statistical model which fits better the physical one. The results show that the best statistical model must take into account the non-trivial interplay between temporal clustering, related to aftershock occurrence, and the stress discharge following the occurrence of high magnitude main shocks. The two mechanisms contribute in different ways according to the minimum magnitude considered in the data fitting catalogue.