bluuebunny/crossref_metadata_2025 huggingface dataset:
SLGC: Identifying influential nodes in complex networks from the perspectives of self-centrality, local centrality, and global centrality
Authors: Ai 艾 Da 达 , Liu 刘 Xin-Long 鑫龙 , Kang 康 Wen-Zhe 文哲 , Li 李 Lin-Na 琳娜 , Lü 吕 Shao-Qing 少卿 , Liu 刘 Ying 颖
Published: August 2023

Identifying influential nodes in complex networks and ranking their importance plays an important role in many fields such as public opinion analysis, marketing, epidemic prevention and control. To solve the issue of the existing node centrality measure only considering the specific statistical feature of a single dimension, a SLGC model is proposed that combines a node’s self-influence, its local neighborhood influence, and global influence to identify influential nodes in the network. The exponential function of e is introduced to measure the node’s self-influence; in the local neighborhood, the node’s one-hop neighboring nodes and two-hop neighboring nodes are considered, while the information entropy is introduced to measure the node’s local influence; the topological position of the node in the network and the shortest path between nodes are considered to measure the node’s global influence. To demonstrate the effectiveness of the proposed model, extensive comparison experiments are conducted with eight existing node centrality measures on six real network data sets using node differentiation ability experiments, susceptible–infected–recovered (SIR) model and network efficiency as evaluation criteria. The experimental results show that the method can identify influential nodes in complex networks more accurately.
Dynamical behavior of memristor-coupled heterogeneous discrete neural networks with synaptic crosstalk
Authors: Ma 马 Minglin 铭磷 , Xiong 熊 Kangling 康灵 , Li 李 Zhijun 志军 , He 贺 Shaobo 少波
Published: August 2023

Synaptic crosstalk is a prevalent phenomenon among neuronal synapses, playing a crucial role in the transmission of neural signals. Therefore, considering synaptic crosstalk behavior and investigating the dynamical behavior of discrete neural networks are highly necessary. In this paper, we propose a heterogeneous discrete neural network (HDNN) consisting of a three-dimensional KTz discrete neuron and a Chialvo discrete neuron. These two neurons are coupled mutually by two discrete memristors and the synaptic crosstalk is considered. The impact of crosstalk strength on the firing behavior of the HDNN is explored through bifurcation diagrams and Lyapunov exponents. It is observed that the HDNN exhibits different coexisting attractors under varying crosstalk strengths. Furthermore, the influence of different crosstalk strengths on the synchronized firing of the HDNN is investigated, revealing a gradual attainment of phase synchronization between the two discrete neurons as the crosstalk strength decreases.
Reconstruction of baryon number distributions*
Authors: Huang 黄 Chuang 闯 , Tan 谈 Yang-yang 阳阳 , Wen 温 Rui 睿 , Yin 尹 Shi 诗 , Fu 付 Wei-jie 伟杰
Published: August 2023

The maximum entropy method (MEM) and Gaussian process (GP) regression, which are both well-suited for the treatment of inverse problems, are used to reconstruct net-baryon number distributions based on a finite number of cumulants of the distribution. Baryon number distributions across the chiral phase transition are reconstructed. It is deduced that with the increase of the order of cumulants, distribution in the long tails, i.e., far away from the central number, would become increasingly important. We also reconstruct the distribution function based on the experimentally measured cumulants at the collision energy

GeV. Given the sizable error of the fourth-order cumulant measured in the experiments, the calculation of MEM shows that with the increasing fourth-order cumulant, there is another peak in the distribution function developed in the region of the large baryon number. This unnaturalness observed in the reconstructed distribution function could in turn be used to constrain the cumulants measured in the experiments.
Search for two-neutrino double-beta decay of 136Xe to the
excited state of 136Ba with the complete EXO-200 dataset*
Authors: Al Kharusi S. , Anton G. , Badhrees I. , Barbeau P.S. , Beck D. , Belov V. , Bhatta T. , Breidenbach M. , Brunner T. , Cao G.F. , Cen W.R. , Chambers C. , Cleveland B. , Coon M. , Craycraft A. , Daniels T. , Darroch L. , Daugherty S.J. , Davis J. , Delaquis S. , Der Mesrobian-Kabakian A. , DeVoe R. , Dilling J. , Dolgolenko A. , Dolinski M.J. , Echevers J. , Fairbank Jr. W. , Fairbank D. , Farine J. , Feyzbakhsh S. , Fierlinger P. , Fu Y.S. , Fudenberg D. , Gautam P. , Gornea R. , Gratta G. , Hall C. , Hansen E.V. , Hoessl J. , Hufschmidt P. , Hughes M. , Iverson A. , Jamil A. , Jessiman C. , Jewell M.J. , Johnson A. , Karelin A. , Kaufman L.J. , Koffas T. , Krücken R. , Kuchenkov A. , Kumar K.S. , Lan Y. , Larson A. , Lenardo B.G. , Leonard D.S. , Li G.S. , Li S. , Li Z. , Licciardi C. , Lin Y.H. , MacLellan R. , McElroy T. , Michel T. , Mong B. , Moore D.C. , Murray K. , Njoya O. , Nusair O. , Odian A. , Ostrovskiy I. , Perna A. , Piepke A. , Pocar A. , Retière F. , Robinson A.L. , Rowson P.C. , Runge J. , Schmidt S. , Sinclair D. , Skarpaas K. , Soma A.K. , Stekhanov V. , Tarka M. , Thibado S. , Todd J. , Tolba T. , Totev T.I. , Tsang R. , Veenstra B. , Veeraraghavan V. , Vogel P. , Vuilleumier J.-L. , Wagenpfeil M. , Watkins J. , Weber M. , Wen L.J. , Wichoski U. , Wrede G. , Wu S.X. , Xia Q. , Yahne D.R. , Yang L. , Yen Y.-R. , Zeldovich O.Ya. , Ziegler T.
Published: August 2023

A new search for two-neutrino double-beta (2νββ) decay of 136Xe to the

excited state of 136Ba is performed with the full EXO-200 dataset. A deep learning-based convolutional neural network is used to discriminate signal from background events. Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two. With the addition of the Phase II dataset taken with an upgraded detector, the median 90% confidence level half-life sensitivity of 2νββ decay to the

state of 136Ba is

yr using a total 136Xe exposure of 234.1 kg yr. No statistically significant evidence for 2νββ decay to the

state is observed, leading to a lower limit of

yr at 90% confidence level, improved by 70% relative to the current world's best constraint.
Nuclear photonics: Laser-driven nuclear physics
Authors: Ong J. F. , Koh Meng-Hock , Hashim I. H.
Published: August 2023

High-power lasers can produce high-energy gamma rays, charged particles, and neutrons and induce various types of nuclear reactions. In Extreme Light Infrastructure Nuclear Physics (ELI-NP), Romania, high-power lasers are entering a new realm of 10 PW peak power, capable of obtaining a focused intensity of 1023 Wcm–2. Such an intense laser pulse will be used for studies relevant to nuclear physics, high-field physics, and quantum electrodynamics, or the combination of laser gamma experiments. Here, we describe how a laser is used to drive high-energy photons and accelerate electrons and protons. These particles can be used for secondary interactions in nuclear physics. Laser-driven nuclear physics can be a source of nuclear isomers for applications in medicine and astrophysics.
Gamma radiation shielding simulation for thermoplastic elastomer and silicon rubber/alloy dopant with functional nanoparticle
Authors: Ful Chai Chan , Sazali Muhammad Arif , Jamaluddin Khairulnadzmi , Mohd Ali Nur Syazwani , Sarkawi Muhammad Syahir
Published: August 2023

With the global energy crisis worsening, the research and application of new energy have become a strategic objective for the major countries’ long-term development in the twenty-first century. Nuclear energy technology development and application have become central to new energy development. Numerous types of high-energy radiation (such as X-rays, gamma rays, and neutron rays) produced by nuclear materials not only impose stricter requirements on the radiation-resistant materials used in the reactor but also risk causing significant environmental pollution (nuclear pollution) and serious harm to human life and health if a leak does not form. As a result, the prudent control and protection of nuclear radiation have become critical issues in the development of nuclear energy. With the rapid development of nuclear power today, it is necessary to seek new nuclear radiation protection materials, particularly those with high energy, penetrating ability, and other neutron-protective material characteristics. This is a new type of nuclear power design and construction of critical materials. In this study, WinXCom software is used to simulate the shielding properties of the used functional shielding element, compounds of metal oxide, and the mixture of RTV and TPE with the functional nanoparticle and observe the K-edge absorption of the material used. Based on the simulation, the shielding performance of the selected element of Sm was observed to have the smallest weak gap absorption zone of 40-47 MeV in common medical radiation of 30-150 KeV. Different sets of combinations of shielding material were simulated and found that the combination of WO3 with Sm2O3 gave the most pronounced radiation shielding performance with two strong absorption peaks at 46.8 KeV and 69.5 KeV. RTV composite (Sm2O3+RTV+ WO3) with WO3 as matrix gave the best shielding performance and was used as a reference for the manufacture of the new type of shielding materials.
Preliminary study on radiation shielding properties of sulfur concrete on Mars
Authors: Nazrif Zamani Muhammad , Syahir Sarkawi Muhammad , Arif Abu Bakar Asyraf , Rahim Sapizah , Ahmad Shah Mohamad Shazwan , Umar Sarehati , Md Noor Norhazilan
Published: August 2023

The hypothetical human exploration and inhabitation on Mars would certainly be difficult as the planet itself is vulnerable to the outer space radiation. The outer space radiation consists of the solar particle events (SPEs) that could easily penetrate the very thin atmospheric layers on Mars. Since sulfur concrete is identified as the feasible in situ building material on Mars, its radiation shielding capability is yet to be clarified. Here we report the preliminary radiation shielding properties of the Martian sulfur concrete composed of elemental sulfur and silica with the latter identified on Mars and incorporated by previous related studies upon irradiation with gamma rays generated from the Iridium-192. It is found that the Martian sulfur concrete demonstrated an approximately 50% efficiency upon irradiation. Martian sulfur concrete demonstrated a high potential in radiation shielding capability as well as the structural integrity post irradiation.
Assessment and sources identification of air quality pollution in Klang Valley, Kuala Lumpur, Malaysia
Authors: Elias Md Suhaimi , Hashim Azian , Bahrudin Nurul Fairuz Dyana , Sapiee Nur Aqilah , Paulus Wilfred , Azman Muhammad Azfar , Raduian Nor Jawahir , Abdullah Intan Masayu
Published: August 2023

Air quality pollution increases a research interest due to its importance in
influencing weather and temperature, restricting visibility and causing harmful effects on human health. Samples of airborne particulate matter (APM) were collected weekly during the period from 2018 to 2020 at Klang Valley, Kuala Lumpur. The samples were collected using a Gent stacked filter sampler in two fractions particulate matter PM2.5 (PM2.5 – size of particulate < 2.5 μm) and particulate matter PM10 (PM10 – size of particulate 2.5 – 10 μm). 100 pairs of APM samples were analysed by Energy Dispersive X-Ray Fluorescence (EDXRF) for their elemental composition. The analysis result of air quality in Klang Valley, Kuala Lumpur, for an average mass concentration of PM2.5 (26.8 μg/m3) and PM10 (44.8 μg/m3) were higher compared to the interim value of Malaysian ambient air quality standard 2020 (MAAQS-2020) (PM2.5 = 15.0 μg/m3; PM10 = 40.0μg/m3). The results showed the possible sources of air pollution in the Klang Valley contributed by biomass burning/smoke (31.6%), soil dust (10.3%), industries (8.4%), motor vehicles (7.1%), sea spray (6.3%) and secondary sulphate (5.5%).
Three factors make bulk high-entropy alloys as effective electrocatalysts for oxygen evolution
Authors: Zhang Tao , Zhao Hui-Feng , Wang Ke-Yan , Chen Zhen-Jie , Li Li , Peng Jing , Peng Xu , Huang Yong-Jiang , Yu Hai-Bin
Published: August 2023

Even in their bulk forms, complex alloys like high-entropy alloys (HEAs) exhibit favorable activity and stability as electrocatalysts for the oxygen evolution reaction (OER). However, the underlying reasons are not yet fully understood. In a family of Mo-doped CrFeCoNi-based HEAs, we have identified three crucial factors that govern their performance: (i) homogeneous solid solution phase of HEAs helps to maintain high-valence states of metals; (ii) surface reconstruction results in a hybrid material comprising amorphous domains and percolated crystalline structures; (iii) diversity of active intermediate species (M–O, M–OOH, and, notably, the abundance of superoxide μ–OO), which display stronger adsorption capacity on the reconstructed surface. These results are revealing due to their resemblance to findings in other families of electrocatalysts for OER, as well as their unique features specific to HEAs. In line with these factors, a CrFeCoNiMo0.2 bulk integrated electrode displays a low overpotential of 215 mV, rapid kinetics, and long-term stability of over 90 d. Bulk HEAs hold great potential for industrial applications.
Molecular insights on the origin and development of waxy genotypes in major crop plants
Authors: Gaur Vikram S , Sood Salej , Guzmán Carlos , Olsen Kenneth M
Published: August 2023

Starch is a significant ingredient of the seed endosperm with commercial importance in food and industry. Crop varieties with glutinous (waxy) grain characteristics, i.e. starch with high amylopectin and low amylose, hold longstanding cultural importance in some world regions and unique properties for industrial manufacture. The waxy character in many crop species is regulated by a single gene known as GBSSI (or waxy), which encodes the enzyme Granule Bound Starch Synthase1 with null or reduced activity. Several allelic variants of the waxy gene that contribute to varying levels of amylose content have been reported in different crop plants. Phylogenetic analysis of protein sequences and the genomic DNA encoding GBSSI of major cereals and recently sequenced millets and pseudo-cereals have shown that GBSSI orthologs form distinct clusters, each representing a separate crop lineage. With the rapidly increasing demand for waxy starch in food and non-food applications, conventional crop breeding techniques and modern crop improvement technologies such as gene silencing and genome editing have been deployed to develop new waxy crop cultivars. The advances in research on waxy alleles across different crops have unveiled new possibilities for modifying the synthesis of amylose and amylopectin starch, leading to the potential creation of customized crops in the future. This article presents molecular lines of evidence on the emergence of waxy genes in various crops, including their genesis and evolution, molecular structure, comparative analysis and breeding innovations.
COWID: an efficient cloud-based genomics workflow for scalable identification of SARS-COV-2
Authors: Lim Hendrick Gao-Min , Fann Yang C , Lee Yuan-Chii Gladys
Published: August 2023

Implementing a specific cloud resource to analyze extensive genomic data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a challenge when resources are limited. To overcome this, we repurposed a cloud platform initially designed for use in research on cancer genomics (https://cgc.sbgenomics.com) to enable its use in research on SARS-CoV-2 to build Cloud Workflow for Viral and Variant Identification (COWID). COWID is a workflow based on the Common Workflow Language that realizes the full potential of sequencing technology for use in reliable SARS-CoV-2 identification and leverages cloud computing to achieve efficient parallelization. COWID outperformed other contemporary methods for identification by offering scalable identification and reliable variant findings with no false-positive results. COWID typically processed each sample of raw sequencing data within 5 min at a cost of only US$0.01. The COWID source code is publicly available (https://github.com/hendrick0403/COWID) and can be accessed on any computer with Internet access. COWID is designed to be user-friendly; it can be implemented without prior programming knowledge. Therefore, COWID is a time-efficient tool that can be used during a pandemic.
ML-PLIC: a web platform for characterizing protein–ligand interactions and developing machine learning-based scoring functions
Authors: Zhang Xujun , Shen Chao , Wang Tianyue , Deng Yafeng , Kang Yu , Li Dan , Hou Tingjun , Pan Peichen
Published: August 2023

Cracking the entangling code of protein–ligand interaction (PLI) is of great importance to structure-based drug design and discovery. Different physical and biochemical representations can be used to describe PLI such as energy terms and interaction fingerprints, which can be analyzed by machine learning (ML) algorithms to create ML-based scoring functions (MLSFs). Here, we propose the ML-based PLI capturer (ML-PLIC), a web platform that automatically characterizes PLI and generates MLSFs to identify the potential binders of a specific protein target through virtual screening (VS). ML-PLIC comprises five modules, including Docking for ligand docking, Descriptors for PLI generation, Modeling for MLSF training, Screening for VS and Pipeline for the integration of the aforementioned functions. We validated the MLSFs constructed by ML-PLIC in three benchmark datasets (Directory of Useful Decoys-Enhanced, Active as Decoys and TocoDecoy), demonstrating accuracy outperforming traditional docking tools and competitive performance to the deep learning-based SF, and provided a case study of the Serine/threonine-protein kinase WEE1 in which MLSFs were developed by using the ML-based VS pipeline in ML-PLIC. Underpinning the latest version of ML-PLIC is a powerful platform that incorporates physical and biological knowledge about PLI, leveraging PLI characterization and MLSF generation into the design of structure-based VS pipeline. The ML-PLIC web platform is now freely available at http://cadd.zju.edu.cn/plic/.
Horses for courses: Plato’s vocabulary and authority in the Onomasticon
Authors: Zadorojnyi Alexei V
Published: August 2023

The Onomasticon by Julius Pollux is more than just a word-hoard: Pollux’s work actively mediates, through lexicographic appraisal, the cultural assets and anxieties of the Second Sophistic. In the light of the ongoing debate among the Imperial intellectuals and specifically Platonists about the value of style and diction as ingredients of the Platonic text, the numerous references to Plato’s vocabulary from across the Onomasticon bespeak an essentially coherent yet ambivalent attitude. Pollux cites Platonic words both appreciatively (at times, demonstrating reasonable awareness of the philosophical content) and critically; there is a tendency to characterize Plato’s lexical choices as strained and cavalier. As a case study of how Pollux deals with a famous Platonic passage that was held dear by the Middle Platonists and Imperial pepaideumenoi at large, his handling of the epithets used in the description of the two horses in the Chariot Allegory (Phdr. 253d–e) is examined.
An advanced protocol for profiling RNA-binding proteins in Arabidopsis using plant phase extraction
Authors: Zhang Yong , Xu Ye , Skaggs Todd H , Ferreira Jorge F S , Chen Xuemei , Sandhu Devinder
Published: August 2023

RNA-binding proteins (RBPs) are key players in regulating cell fate and essential developmental processes. Systematic profiling of the RNA-binding proteome (RBPome) is thus indispensable for researchers aiming to understand the mechanisms of post-transcriptional gene regulation. RBPome identification methods developed in humans, mice, and bacteria have successfully identified RBPomes in these organisms. However, the biochemical and genetic complexities of plant tissues have greatly hindered the effectiveness of these methods in plants. Moreover, plant RBPs have been predominantly discovered through oligo d(T) based affinity purification (RNA-interactome capture). Since polyadenylated RNA only accounts for less than 5% of the total RNA population in eukaryotic cells, there is a pressing need to develop a comprehensive, yet unbiased, method to capture the full spectrum of RBPs in plants. Here, we describe a detailed protocol of Plant Phase Extraction (PPE), a recently developed method to identify RBPs in Arabidopsis (Zhang Y, Xu Y, Skaggs TH, et al. Plant phase extraction: a method for enhanced discovery of the RNA-binding proteome and its dynamics in plants. Plant Cell 2023; 35: 2750–72.) [1]. The PPE method enables the efficient enrichment of both poly(A) and non-poly(A) RBPs from various tissues quickly and reproducibly. Most importantly, PPE allows for unveiling dynamic RBP–RNA interactions under various abiotic and biotic stress conditions and during different plant developmental stages. This provides a much broader and more accurate understanding of plant RBPs, marking a significant advancement in plant molecular biology.
Changes in public health-seeking behaviours for self-limiting respiratory tract infections across England during the COVID-19 pandemic
Authors: Read Brieze , McLeod Monsey , Tonkin-Crine Sarah , Ashiru-Oredope Diane , Quigley Anna , Brown Colin S , Lecky Donna M
Published: August 2023

Background

National Health Service (NHS) guidance for acute respiratory tract infections (RTIs) advocates self-care, encourages utilization of local pharmacies and recommends consulting general practitioners (GPs) primarily for the vulnerable or those with persistent symptoms. Coronavirus disease 2019 exerted substantial strain on the English NHS, affecting public access to primary care services.

Methods

For 3 years, public surveys assessed RTI incidences in the previous 12 months and associated health-seeking behaviours. Telephone surveys of 1676 respondents across England were conducted in March 2021 and 1663 respondents in March 2022. Findings were compared with a face-to-face baseline survey of 2022 respondents from March 2020. Key demographics were representative of the population.

Results

In 2021, the proportion of respondents who reported an RTI (51%) significantly declined from 2020 (70%, P < 0.05), then returned to pre-pandemic rates in 2022 (67%). Respondents reported more proactive symptom management in both 2021 and 2022 from 2020: there were greater reports of seeking over-the-counter treatments (55%, 55% vs. 35%, P < 0.05) and use of alternative remedies (38%, 38% vs. 21%, P < 0.05). 2022 observed a reduction in those who reported consulting their GP for their most recent RTI (15%) compared to 2021 (25%, P < 0.05) and 2020 (23%), which was not accounted for through greater consultation rates with other healthcare services.

Conclusions

Public health bodies should consider how pandemic-related changes may have facilitated increased self-care for self-limiting infections such as RTIs. Resources and support must include safety-netting advice to safeguard against unintentional consequences of increased self-care.
Participation in Community Gathering Places and Subsequent Health and Well-Being: An Outcome-Wide Analysis
Authors: Ide Kazushige , Nakagomi Atsushi , Tsuji Taishi , Yamamoto Takafumi , Watanabe Ryota , Yokoyama Meiko , Shirai Kokoro , Kondo Katsunori , Shiba Koichiro
Published: August 2023

Background and Objectives

Evidence remains inadequate regarding the benefits of participation in community gathering places, which is Japan’s primary strategy for preventing functional disability in older adults, in other domains of health and well-being. This longitudinal study examined the associations of participation in community gathering places with an array of subsequent health and well-being outcomes among older adults.

Research Design and Methods

We used 3-wave data (2013, 2016, and 2019) from Japan Gerontological Evaluation Study (n = 5 879 or 4 232 depending on the outcome). Our exposure was participation in community gathering places in 2016. We assessed 34 health/well-being outcomes in 2019 across 6 domains. We adjusted for pre-baseline covariates including prior outcome values in 2013.

Results

Compared with nonparticipation, participation in community gathering places was associated with some outcomes in the following 3 domains: physical/cognitive health (better higher-level functional capacity), social well-being (more frequent participation in hobby groups, senior citizens clubs, learning or cultural groups, and seeing more friends within a month), and prosocial/altruistic behaviors (more frequent participation in volunteering; after Bonferroni correction as p < .0015, .05/34).

Discussion and Implications

Evidence was mixed and more modest for the outcomes in three other domains, mental health, psychological well-being, and health behaviors. Promoting participation in community gathering places may not only fulfill its original goal (ie, preventing functional disability) but also enhance other domains of human well-being, potentially by increasing social interactions.
Digital applications as a means for promotion of healthy behaviours among Albanian children
Authors: Vasil Suela , Xinxo Sonela , Alia Albano , Muça Kliton , Tresa Eni , Burazeri Genc
Published: August 2023

Digital applications can be effective tools for strengthening school-based health education programs as they can provide valuable health information to children through interactive videos, quizzes and games. We aimed at assessing the change in the prevalence of healthy behaviours among children exposed to digital applications (intervention) employed for promoting healthy behaviours. We conducted a cross-sectional study before the intervention in March 2022 including a representative sample of 1500 Albanian schoolchildren (≈54% girls) aged 12–15 years. In June 2022, after 4-month exposure to digital applications aimed at promoting healthy behaviours (intervention), we carried out a second cross-sectional study in the same sample of schoolchildren. In both survey rounds, an anonymous and structured self-administered questionnaire inquired children about a range of behavioural practices including nutrition, oral health, physical activity and hygiene practices. After the intervention, overall, there was evidence of a significant increase in the prevalence of all healthy behavioural practices measured: ~9% for breakfast consumption and/or environmental protection, 12% for toothbrushing, 14% for handwashing, 15% for leisure time physical exercise and 24% for adequate fruit and vegetable intake (all p < 0.001). Engagement in healthy behaviours only after the intervention was higher among rural children (from 18% for breakfast consumption to 37% for handwashing and/or adequate fruit and vegetable intake) and especially those pertinent to Roma/Egyptian communities (from 18% for breakfast consumption to 46% for adequate fruit and vegetable intake), except for engagement in safe environmental protection which was more prevalent among urban residents (28% vs. 15% among rural children) and ethnic Albanian children (24% vs. 13% among Roma/Egyptian children). Our findings from Albania indicate that digital applications can be useful for strengthening school-based health promotion programs.
Cryptic splice mutation in the fumarate hydratase gene in patients with clinical manifestations of Hereditary Leiomyomatosis and Renal Cell Cancer
Authors: Crooks Daniel R , Cawthon Geetha Mariah , Fitzsimmons Christina M , Perez Minervo , Ricketts Christopher J , Vocke Cathy D , Yang Ye , Middelton Lindsay , Nielsen Debbie , Schmidt Laura S , Tandon Mayank , Merino Maria J , Ball Mark W , Meier Jordan L , Batista Pedro J , Linehan William Marston
Published: August 2023

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant condition characterized by the development of cutaneous and uterine leiomyomas and risk for development of an aggressive form of papillary renal cell cancer. HLRCC is caused by germline inactivating pathogenic variants in the fumarate hydratase (FH) gene, which encodes the enzyme that catalyzes the interconversion of fumarate and L-malate. We utilized enzyme and protein mobility assays to evaluate the FH enzyme in a cohort of patients who showed clinical manifestations of HLRCC but were negative for known pathogenic FH gene variants. FH enzyme activity and protein levels were decreased by 50% or greater in three family members, despite normal FH mRNA expression levels as measured by quantitative PCR. Direct Nanopore RNA sequencing demonstrated 57 base pairs of retained intron sequence between exons 9 and 10 of polyadenylated FH mRNA in these patients, resulting in a truncated FH protein. Genomic sequencing revealed a heterozygous intronic alteration of the FH gene (chr1: 241498239 T/C) resulting in formation of a splice acceptor site near a polypyrimidine tract, and a uterine fibroid obtained from a patient showed loss of heterozygosity at this site. The same intronic FH variant was identified in an unrelated patient who also showed a clinical phenotype of HLRCC. These data demonstrate that careful clinical assessment as well as biochemical characterization of FH enzyme activity, protein expression, direct RNA sequencing, and genomic DNA sequencing of patient-derived cells can identify pathogenic variants outside of the protein coding regions of the FH gene.
Male reproductive ageing: a radical road to ruin
Authors: Aitken R John
Published: August 2023

In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about the intersection of age and male reproduction. Our current understanding is that advancing age brings forth a progressive decline in male fertility accompanied by a reduction in circulating testosterone levels and the appearance of age-dependent reproductive pathologies including benign prostatic hypertrophy and erectile dysfunction. Paternal ageing is also associated with a profound increase in sperm DNA damage, the appearance of multiple epigenetic changes in the germ line and an elevated mutational load in the offspring. The net result of such changes is an increase in the disease burden carried by the progeny of ageing males, including dominant genetic diseases such as Apert syndrome and achondroplasia, as well as neuropsychiatric conditions including autism and spontaneous schizophrenia. The genetic basis of these age-related effects appears to involve two fundamental mechanisms. The first is a positive selection mechanism whereby stem cells containing mutations in a mitogen-activated protein kinase pathway gain a selective advantage over their non-mutant counterparts and exhibit significant clonal expansion with the passage of time. The second is dependent on an age-dependent increase in oxidative stress which impairs the steroidogenic capacity of the Leydig cells, disrupts the ability of Sertoli cells to support the normal differentiation of germ cells, and disrupts the functional and genetic integrity of spermatozoa. Given the central importance of oxidative stress in defining the impact of chronological age on male reproduction, there may be a role for antioxidants in the clinical management of this process. While animal studies are supportive of this strategy, carefully designed clinical trials are now needed if we are to realize the therapeutic potential of this approach in a clinical context.
An integrated end-to-end deep neural network for automated detection of discarded fish species and their weight estimation
Authors: Sokolova Maria , Cordova Manuel , Nap Henk , van Helmond Aloysius , Mans Michiel , Vroegop Arjan , Mencarelli Angelo , Kootstra Gert
Published: August 2023

Sustainable management of aquatic resources requires efficient acquisition and processing of vast amounts of information to check the compliance of fishing activities with the regulations. Recent implementation of the European Common Fisheries Policy Landing Obligation implies the declaration of all listed species and sizes at the harbour. To comply with such regulation, fishers need to collect and store all discards onboard the vessel, which results in additional processing time, labour demands, and costs. In this study, we presented a system that allowed image-based documentation of discards on the conveyor belt. We presented a novel integrated end-to-end simultaneous detection and weight prediction pipeline based on the state-of-the-art deep convolutional neural network. The performance of the network was evaluated per species and under different occlusion levels. The resulting model was able to detect discards with a macro F1-score of $94.10\%$ and a weighted F1-score of $93.88\%$. Weight of the fish could be predicted with mean absolute error, mean absolute percentage error, and root squared error of 29.74 (g), $23.78\%$, and 44.69 (g), respectively. Additionally, we presented a new dataset containing images of fish, which, unlike common object detection datasets, also contains weight measurements and occlusion level per individual fish.
Aromatase Inhibition and Electroconvulsive Seizures in Adolescent Rats: Antidepressant and Long-Term Cognitive Sex Differences
Authors: Ledesma-Corvi Sandra , García-Fuster M Julia
Published: August 2023

Background

We recently showed sex differences in the antidepressant-like potential of electroconvulsive seizures (ECS) in adolescent rats; whereas it worked for male rats, it was inefficacious in females. Because sex steroids might be important modulators of these sex disparities, we evaluated the role of estrogens in the differential response induced by adolescent ECS. Moreover, given the literature suggesting certain cognitive sequelae from ECS exposure, we aimed at evaluating its long-term safety profile in adulthood.

Methods

Adolescent Sprague-Dawley rats were pretreated with letrozole (1 mg/kg/day) or vehicle (1 mL/kg/day) for 8 days (i.p.) and treated during the last 5 days (3 hours later) with ECS (95 mA, 0.6 s, 100 Hz) or SHAM. Antidepressant-like responses were measured in the forced swim test, and long-term cognitive performance was assessed in the Barnes maze.

Results

During adolescence, whereas ECS alone exerted an antidepressant-like response in male rats, its combination with letrozole permitted ECS to also induce efficacy in females. Moreover, adolescent ECS treatment improved cognitive performance in adulthood although exclusively in male rats.

Conclusions

Adolescent ECS demonstrated an antidepressant-like potential together with certain long-term beneficial cognitive effects but exclusively in male rats. For females, efficacy was restricted to a situation in which the biosynthesis of estrogens was reduced. Therefore, estrogens and/or testosterone levels play a crucial role in the sex disparities induced by ECS in Sprague-Dawley rats. Based on this study and on the literature supporting its safety, ECS should be encouraged for use in cases of treatment-resistant depression during adolescence, while adhering to sex-specific considerations.
Interpreting the Results of Trials of BCG Vaccination for Protection Against COVID-19
Authors: Noble Christie C A , Messina Nicole L , Pittet Laure F , Curtis Nigel
Published: August 2023

BCG vaccination has beneficial off-target (“nonspecific”) effects on nonmycobacterial infections. On this premise, trials set out to investigate whether BCG provides off-target protection against coronavirus disease 2019 (COVID-19). A literature search identified 11 randomized “BCG COVID-19” trials, with conflicting results. These trials and the differences in their study design are discussed using the PICOT (participants, intervention, control, outcome, and timing) framework to highlight the factors that likely explain their inconsistent findings. These include participant age, sex and comorbid conditions, BCG vaccination strain and dose, outcome measure and duration of follow-up. Understanding how to control these factors to best exploit BCG's off-target effects will be important in designing future trials and intervention strategies.
Sequence Data From a Travel-Associated Case of Microcephaly Highlight a Persisting Risk due to Zika Virus Circulation in Thailand
Authors: Marquine Solène , Durand Guillaume André , Modenesi Gabriela , Khouadhria Siham , Piorkowski Géraldine , Badaut Cyril , Canivez Thomas , De Lamballerie Xavier , Grard Gilda , Klitting Raphaëlle
Published: August 2023

Zika virus has been circulating in Thailand since 2002 through continuous but likely low-level circulation. Here, we describe an infection in a pregnant woman who traveled to Thailand and South America during her pregnancy. By combining phylogenetic analysis with the patient's travel history and her pregnancy timeline, we confirmed that she likely got infected in Thailand at the end of 2021. This imported case of microcephaly highlights that Zika virus circulation in the country still constitutes a health risk, even in a year of lower incidence.

Main points

Here we trace the origin of travel-acquired microcephaly to Thailand, providing additional evidence that pre-American lineages of Zika virus can harm the fetus and highlighting that Zika virus constitutes a health threat even in a year of lower incidence.
Real-world Effectiveness of Molnupiravir and Nirmatrelvir/Ritonavir as Treatments for COVID-19 in Patients at High Risk
Authors: Paraskevis Dimitrios , Gkova Maria , Mellou Kassiani , Gerolymatos Gerasimos , Psalida Naya , Gkolfinopoulou Kassiani , Kostaki Evangelia-Georgia , Loukides Stylianos , Kotanidou Anastasia , Skoutelis Athanasios , Thiraios Eleftherios , Saroglou Georgios , Zografopoulos Dimitrios , Filippou Dimitrios , Mossialos Elias , Zaoutis Theoklis , Gaga Mina , Tsiodras Sotirios , Antoniadou Anastasia
Published: August 2023

Background

Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable.

Methods

The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy.

Results

Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence.

Conclusions

Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations.
Threat Conceptions in Global Security Discourse: Analyzing the Speech Records of the United Nations Security Council, 1990–2019
Authors: Sakamoto Takuto
Published: August 2023

Since the end of the Cold War, the notion of global security, and presumed threats to it, has undergone considerable expansion and diversification. This process has been led by the United Nations Security Council (UNSC), where active deliberations concerning “threat(s) to the peace” have taken place among major international actors. Despite a sizable accumulation of scholarly arguments, however, the defining features of the structure and dynamics of the post-Cold War security discourse remain ambiguous. To address these ambiguities, this study investigates the entire body of Council deliberations over the past three decades. Based on an original dataset consisting of policy statements delivered at the UNSC, the study employs quantitative text analysis tools, including word embedding, to examine how council members have conceived the notion of security threat in terms of the various issues and entities discussed. It shows the security discourse at the UNSC to be highly stratified and reveals the persistent and pervasive influence of terrorism and the proliferation of weapons of mass destruction, which constitute the limited common grounds shared by the Council’s permanent members. These findings caution against the unconstrained use of certain theoretical constructs widely employed in other works, most notably, “securitization” and “interpretative community.”
Foundational domains and competencies for baccalaureate health informatics education
Authors: Khairat Saif , Feldman Sue S , Rana Arif , Faysel Mohammad , Purkayastha Saptarshi , Scotch Matthew , Eldredge Christina
Published: August 2023

Background

Foundational domains are the building blocks of educational programs. The lack of foundational domains in undergraduate health informatics (HI) education can adversely affect the development of rigorous curricula and may impede the attainment of CAHIIM accreditation of academic programs.

Objective

This White Paper presents foundational domains developed by AMIA’s Academic Forum Baccalaureate Education Committee (BEC) which include corresponding competencies (knowledge, skills, and attitudes) that are intended for curriculum development and CAHIIM accreditation quality assessment for undergraduate education in applied health informatics.

Methods

The AMIA BEC used the previously published master’s foundational domains as a guide to creating a set of competencies for health informatics at the undergraduate level to assess graduates from undergraduate health informatics programs for competence at graduation. A consensus method was used to adapt the domains for undergraduate level course work and harmonize the foundational domains with the currently adapted domains for HI master’s education.

Results

Ten foundational domains were developed to support the development and evaluation of baccalaureate health informatics education.

Discussion

This article will inform future work towards building CAHIIM accreditation standards to ensure that higher education institutions meet acceptable levels of quality for undergraduate health informatics education.
Examining primary care provider experiences with using a clinical decision support tool for pain management
Authors: Mazurenko Olena , McCord Emma , McDonnell Cara , Apathy Nate C , Sanner Lindsey , Adams Meredith C B , Mamlin Burke W , Vest Joshua R , Hurley Robert W , Harle Christopher A
Published: August 2023

Objective

To evaluate primary care provider (PCP) experiences using a clinical decision support (CDS) tool over 16 months following a user-centered design process and implementation.

Materials and Methods

We conducted a qualitative evaluation of the Chronic Pain OneSheet (OneSheet), a chronic pain CDS tool. OneSheet provides pain- and opioid-related risks, benefits, and treatment information for patients with chronic pain to PCPs. Using the 5 Rights of CDS framework, we conducted and analyzed semi-structured interviews with 19 PCPs across 2 academic health systems.

Results

PCPs stated that OneSheet mostly contained the right information required to treat patients with chronic pain and was correctly located in the electronic health record. PCPs used OneSheet for distinct subgroups of patients with chronic pain, including patients prescribed opioids, with poorly controlled pain, or new to a provider or clinic. PCPs reported variable workflow integration and selective use of certain OneSheet features driven by their preferences and patient population. PCPs recommended broadening OneSheet access to clinical staff and patients for data entry to address clinician time constraints.

Discussion

Differences in patient subpopulations and workflow preferences had an outsized effect on CDS tool use even when the CDS contained the right information identified in a user-centered design process.

Conclusions

To increase adoption and use, CDS design and implementation processes may benefit from increased tailoring that accommodates variation and dynamics among patients, visits, and providers.
Exon–intron split analysis reveals posttranscriptional regulatory signals induced by high and low n-6/n-3 polyunsaturated fatty acid ratio diets in piglets
Authors: Manaig Yron Joseph Yabut , Mármol-Sánchez Emilio , Castelló Anna , Esteve-Codina Anna , Sandrini Silvia , Savoini Giovanni , Agazzi Alessandro , Sánchez Armand , Folch Josep M
Published: August 2023

Polyunsaturated fatty acids (PUFA), such as omega-6 (n-6) and omega-3 (n-3), play a vital role in nutrient metabolism, inflammatory response, and gene regulation. microRNAs (miRNA), which can potentially degrade targeted messenger RNAs (mRNA) and/or inhibit their translation, might play a relevant role in PUFA-related changes in gene expression. Although differential expression analyses can provide a comprehensive picture of gene expression variation, they are unable to disentangle when in the mRNA life cycle the regulation of expression is taking place, including any putative functional miRNA-driven repression. To capture this, we used an exon–intron split analysis (EISA) approach to account for posttranscriptional changes in response to extreme values of n-6/n-3 PUFA ratio. Longissimus dorsi muscle samples of male and female piglets from sows fed with n-6/n-3 PUFA ratio of 13:1 (SOY) or 4:1 (LIN), were analyzed in a bidirectional contrast (LIN vs. SOY, SOY vs. LIN). Our results allowed the identification of genes showing strong posttranscriptional downregulation signals putatively targeted by significantly upregulated miRNA. Moreover, we identified genes primarily involved in the regulation of lipid-related metabolism and immune response, which may be associated with the pro- and anti-inflammatory functions of the n-6 and n-3 PUFA, respectively. EISA allowed us to uncover regulatory networks complementing canonical differential expression analyses, thus providing a more comprehensive view of muscle metabolic changes in response to PUFA concentration.
Convenient Frailty: Medical Contestations of Asthma and Hay Fever in African Americans in Late Nineteenth-Century America
Authors: Kola Ijeoma B
Published: August 2023

Post-Emancipation medical and social science scholars extensively theorized Black susceptibility to illness, disease, and death. Most studies of late nineteenth-century medical ideas about the relationship between race and disease have highlighted the construction of medical beliefs that associated Black physical weakness with a proclivity to ill health. This study presents an alternate narrative, one where certain diseases – asthma and hay fever — reflected an opposing racialized understanding of disease that instead centered on White frailty. Based on an examination of turn-of-the-century asthma and hay fever medical literature produced by George Miller Beard, the professionalization of the United States Hay Fever Association, and the publication and dismissal of the first recorded case of asthma in an African American man in 1884, this article argues that late nineteenth-century asthma and hay fever physicians, who themselves often suffered from the conditions, defined the typical asthma patient along racial lines to protect the exclusivity of their own professional and social identities. As a result, asthma and hay fever in Black communities, particularly in the North, where asthma and hay fever scholars primarily lived and worked, remained obscured and untreated until the mid-twentieth century.