bluuebunny/crossref_metadata_2025 huggingface dataset:
What If Nice Terrorist Attack Would Have Happened in Milan? Drawing a Disaster Plan for Mass Casualty Incidents Involving the Pediatric Population
Authors: Difino Margherita , Stucchi Riccardo , Weinstein Eric S. , De Pellegrin Maurizio , Zoli Alberto , Sechi Giuseppe Maria , Faccincani Roberto
Published: May 2024

Terrorist attacks involving children raised concern regarding the preparedness to treat pediatric trauma patients during mass casualty incidents (MCIs). The purpose of this project was to assess the resources available in Milan to respond to MCIs as the 2016 Bastille Day attack in Nice. Literature and guidelines were reviewed and minimal standard requirements of care of pediatric trauma patients in MCIs were identified. The hospitals that took part in the study were asked to answer a survey regarding their resource availability. An overall surge capability of 40-44 pediatric trauma patients was identified, distributed based on age and severity, hospital resources, and expertise. The findings showed that adult and pediatric hospitals should work in synergy with pediatric trauma centers, or offer an alternative if there is none, and should be included in disaster plans for MCIs. Simulations exercises need to be carried out to evaluate and validate the results.
Sums of squares, Hankel index and almost real rank
Authors: Blekherman Grigoriy , Chen Justin , Jung Jaewoo
Published: May 2024

The Hankel index of a real variety X is an invariant that quantifies the difference between nonnegative quadrics and sums of squares on X. In [5], the authors proved an intriguing bound on the Hankel index in terms of the Green–Lazarsfeld index, which measures the ‘linearity’ of the minimal free resolution of the ideal of X. In all previously known cases, this bound was tight. We provide the first class of examples where the bound is not tight; in fact, the difference between Hankel index and Green–Lazarsfeld index can be arbitrarily large. Our examples are outer projections of rational normal curves, where we identify the center of projection with a binary form F. The Green–Lazarsfeld index of the projected curve is given by the complex Waring border rank of F [16]. We show that the Hankel index is given by the almost real rank of F, which is a new notion that comes from decomposing F as a sum of powers of almost real forms. Finally, we determine the range of possible and typical almost real ranks for binary forms.
Explaining the politicization of EU trade agreement negotiations over the past 30 years
Authors: Cabras Luca
Published: May 2024

Although the Transatlantic Trade and Investment Partnership with the USA and the Comprehensive Economic and Trade Agreement with Canada have elicited considerable domestic contestation in Europe, several other agreements have been negotiated into public and media indifference. What explains this difference? In this article, I put forward a number of arguments on the structural causes of the politicization of European Union (EU) trade policy over the past 30 years and test them against a newly collected dataset covering 19 preferential trade agreements. The qualitative comparative analysis suggests that the politicization of EU trade negotiations is determined by the co-occurrence of several, well-defined conditions. More specifically, it tells us that: (1) the Lisbon Treaty's reform of EU trade policymaking is the main driver of politicization, (2) the level of public support for the EU is of particular relevance when it comes to ‘deep and comprehensive’ agreements that touch on sensitive domestic issues, and that (3) high adjustment costs expected from trade liberalization can lead to the politicization of trade negotiations.
‘This you may NNNNNNEVER have heard before’: initial lengthening of accented negative items as vocal-entangled gestures
Authors: Harrison Simon
Published: May 2024

Movement scientists have proposed to ground the relation between prosody and gesture in ‘vocal-entangled gestures’, defined as biomechanical linkages between upper limb movement and the respiratory–vocal system. Focusing on spoken language negation, this article identifies an acoustic profile with which gesture is plausibly entangled, specifically linking the articulatory behaviour of onset consonant lengthening with forelimb gesture preparation and facial deformation. This phenomenon was discovered in a video corpus of accented negative utterances from English-language televised dialogues. Eight target examples were selected and examined using visualization software to analyse the correspondence of gesture phase structures (preparation, stroke, holds) with the negation word’s acoustic signal (duration, pitch and intensity). The results show that as syllable–onset consonant lengthens (voiced alveolar /n/ = 300 ms on average) with pitch and intensity increasing (e.g. ‘NNNNNNEVER’), the speaker’s humerus is rotating with palm pronating/adducing while his or her face is distorting. Different facial distortions, furthermore, were found to be entangled with different post-onset phonetic profiles (e.g. vowel rounding). These findings illustrate whole-bodily dynamics and multiscalarity as key theoretical proposals within ecological and enactive approaches to language. Bringing multimodal and entangled treatments of utterances into conversation has important implications for gesture studies.
Digital war diaries: Witnessing the 2022 Russian War against Ukraine
Authors: Kot Svitlana , Mozolevska Alina , Polishchuk Olha
Published: May 2024

Digital media have changed the ways people mobilise and act collectively in times of crisis. During the Russian aggression against Ukraine, they have been at the forefront of war coverage giving users the possibility to share experiences of wartime reality. To critically engage in the mediatisation of the current war in the context of war witnessing, this article aims at studying the war diaries shared on media during the Russo-Ukrainian war. More precisely, this study focuses on the analysis of Facebook and MyWar platform digital war diaries that were triggered by Russia's full-fledged invasion of Ukraine 2022. The article seeks to understand the main tools for experiencing and constructing wartime reality and war trauma. The experimental work presented here provides one of the first investigations into how wartime witnessing of Russian aggression is happening and how it is shared in the contemporary space of digital media and fosters intellectual discussion about the dynamics of digital participation while witnessing and narrating war experiences.
Further expansion of morphological variability in the Porinaceae (Ascomycota, Ostropales) with the placement of the enigmatic genus Gallaicolichen
Authors: Lebreton Elise , Ertz Damien , Lücking Robert , Simon Antoine , Smith Clifford , Sérusiaux Emmanuël
Published: May 2024

The foliicolous lichen Gallaicolichen pacificus exhibits unique goniocystangia-like structures named peltidiangia and peltidia. Its taxonomic classification within the Ascomycota has been unclear due to the absence of ascomata and lack of molecular data. Here we clarify the phylogenetic affinities of Gallaicolichen pacificus by analyzing mitochondrial small subunit ribosomal RNA (mtSSU) sequences obtained from specimens collected in New Caledonia. Ascomata and ascospores of G. pacificus, previously unknown, are described and illustrated for the first time. The results from the molecular and morphological analyses clearly indicate that Gallaicolichen pacificus belongs to the Porinaceae and is closely related to Porina guianensis. This is a remarkable extension of the already known, wide morphological diversity of thalli and diaspores produced within this family.
The association of adverse childhood experiences with long-term outcomes of psychosis: a 21-year prospective cohort study after a first episode of psychosis
Authors: Peralta Victor , García de Jalón Elena , Moreno-Izco Lucía , Peralta David , Janda Lucía , Sánchez-Torres Ana M. , Cuesta Manuel J. ,   SEGPEPs group
Published: May 2024

Background

Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.

Methods

Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications.

Results

There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (ΔR2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (ΔR2 between 0.040 and 0.066). A dose–response relationship was observed between levels of CA and severity of outcome domains.

Conclusion

Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions.
Impacts of soil and water conservation measures on farm technical efficiency in the semi-arid tropics of central India
Authors: Singh Priyanka , Choudhary Bishwa Bhaskar , Sharma Purushottam , Kumar Sunil , Dev Inder , Singh Ramesh , Garg Kaushal K , Chand Khem , Ram Asha , Kumar Naresh , Arunachalam A
Published: May 2024

Natural resources such as soil and water are essential to agriculture, especially in arid and semi-arid rain-fed areas, yet the impacts of managing these crucial natural resources on farm technical efficiency are little known. Using data from 400 households with 1031 plots, we examined the impacts of soil and water conservation measures (SWCMs) on the technical efficiency of farmers in the semi-arid Bundelkhand (central India). We estimated stochastic production frontiers, considering potential self-selection bias stemming from both observable and unobservable factors in the adoption of SWCMs at the farm level. The farm technical efficiency for adopters of SWCMs ranged from 0.68 to 0.72, and that for non-adopters ranged from 0.52 to 0.65, depending on how biases were controlled for. As the average efficiency is consistently higher for adopter farmers than the control group, promoting SWCMs could help to increase input use efficiency, especially in resource-deprived rain-fed systems in the semi-arid tropics.
Egalitarian greetings: the social spread of the handshake in urbanizing Britain, 1700–1850
Authors: Corfield Penelope J.
Published: May 2024

Handshaking has a long multi-cultural history. This article focuses upon its diffusion in Britain 1700–1850. Two networks boosted the handshaking salutation. One was a mercantile network, extending across Europe’s urban/commercial regions. The other featured ‘middling sort’ Quaker men and women, who shook hands on principle. Gradually, the salutation became widely diffused – and acquired a range of egalitarian meanings. Handshaking was not an elite practice which ‘trickled down’ to the masses. Instead, it spread by social negotiation both ‘upwards’ and ‘downwards’ from middle-class society. Traditional hierarchy was yielding to an urbanizing and internationalizing world – with multiple individual options.
Transcatheter balloon angioplasty of internal pulmonary artery bands to improve pulmonary blood flow: a case series
Authors: Srivatsav Ashwin , Eilers Lindsay , Khan Asra , Stapleton Gary
Published: May 2024

Pulmonary artery banding (PAB) is used to restrict pulmonary blood flow in select patients with large left-to-right intracardiac shunts or unrestrictive pulmonary blood flow prior to eventual surgical repair or palliation. More recently, surgical placement of an internal or intraluminal PAB (IPAB) has been used to restrict pulmonary circulation. Here we present two patients who underwent balloon angioplasty of the IPAB to treat cyanosis and improve pulmonary blood flow.
Indian Myth, Korean Wave, and ‘Thainess’: Politics of Hybridity in Thai Literature in the 21st Century
Authors: Boonhok Saranpat
Published: May 2024

‘Thainess’ [khwam-pen-Thai] or Thai identity has long been a state-constructed ideology linked to nationalist sentiment. However, in the 21st century, internal politics and globalisation have come to challenge its monopoly. Against this backdrop, reinventing classical literature and folklore has emerged as a way to reimagine and rethink ‘Thainess’ in Thai literature. This holds particular relevance since transnational cultures, ranging from classical Indian mythology to the contemporary Korean wave, continue to be hybridised and reconstructed. This paper examines the hybridity of Thainess in contemporary Thai literature, focusing on two different genres: fantasy and fanfiction. Firstly, I explore the fantasy novel series ‘Nawa Himmaphan’ [New Himmaphan] (2013–2018), depicting an apocalypse and creating a new world inspired by the Indian mythical forest named Himavanta. The novel adapts and reinterprets the roles and meanings of Deva (the god) and Asura (the demon) in an upside-down future. Secondly, I examine an adaptation of the Ramakien, the Thai version of the Indian Ramayana, published on the internet and transformed into Boys Love (BL) fanfiction referencing Korean idols called ‘Huachai Thotsakan KAIHUN’ [The Heart of Thotsakan KAIHUN] (2016–2017). It reconstructs the Ramakien, challenging its traditional meaning while asserting the aesthetics of K-pop fans. Through the lens of the hybridity framework, this paper argues that these texts not only illustrate cross-regional cultural hybridisation but also challenge the top-down construction of Thainess. Hybridity creates a ‘liminal space’ for Thainess, establishing a new power structure that highlights the significance of marginalised voices against the backdrop of political polarisation and the influence of transnational flows.
Local‐Scale Controls Over Leaf N and P Stoichiometry of 121 Plant Species in the Inner Mongolia Grassland
Authors: Zhu Jianjun , Yan Qiyao , Zhang Bin , Cheng Junhui , Li Chao , Wang Xiaoliang , Yang Yang , Pan Qingmin
Published: May 2024

Nitrogen (N) and phosphorus (P) stoichiometry in plant leaves plays an important role in linking plant physiological processes with community assemblage and species distribution. Studies have revealed that temperature is a major driver of leaf stoichiometry, however, whether current global warming will alter leaf N and P stoichiometry on a local scale remain poorly understood. Taking advantage of an unique data set on leaf element concentrations of 122 plant species in the Xilingol Grassland National Reserve (established in 1979), we addressed this issue by resampling plant leaves of the same 121 species in 2018, and compared the leaf N, P, and N:P ratio between the 2 years. We found that leaf N, P, and N:P ratio of the 121 species all exhibited large variation, with a magnitude of 4.5‐fold for N, 5.8‐fold for P, and 6.3‐fold for N:P ratio, respectively. However, the mean leaf N, P, and N:P ratio of the 121 species, as well as for each family, each life form and each habitat type, did not significantly change over 40 years (1979 vs. 2018), though a 2°C increase in annual mean temperature occurred. We identified that taxonomic difference was the primary driver for variations in leaf N, P, and N:P ratio in this grassland reserve, which is different from those on the regional and global scales. These results suggest that controls over leaf stoichiometry are likely scale‐dependent. Thus, using leaf stoichiometry to explain community assemblage and species distribution should take into account the scale‐dependent drivers.
Prevalence and network structure of depression, insomnia and suicidality among mental health professionals who recovered from COVID-19: a national survey in China
Authors: Sun He-Li , Chen Pan , Bai Wei , Zhang Ling , Feng Yuan , Su Zhaohui , Cheung Teris , Ungvari Gabor S. , Cui Xi-Ling , Ng Chee H. , An Feng-Rong , Xiang Yu-Tao
Published: May 2024

Psychiatric syndromes are common following recovery from Coronavirus Disease 2019 (COVID-19) infection. This study investigated the prevalence and the network structure of depression, insomnia, and suicidality among mental health professionals (MHPs) who recovered from COVID-19. Depression and insomnia were assessed with the Patient Health Questionnaire (PHQ-9) and Insomnia Severity Index questionnaire (ISI7) respectively. Suicidality items comprising suicidal ideation, suicidal plan and suicidal attempt were evaluated with binary response (no/yes) items. Network analyses with Ising model were conducted to identify the central symptoms of the network and their links to suicidality. A total of 9858 COVID-19 survivors were enrolled in a survey of MHPs. The prevalence of depression and insomnia were 47.10% (95% confidence interval (CI) = 46.09–48.06%) and 36.2% (95%CI = 35.35–37.21%), respectively, while the overall prevalence of suicidality was 7.8% (95%CI = 7.31–8.37%). The key central nodes included “Distress caused by the sleep difficulties” (ISI7) (EI = 1.34), “Interference with daytime functioning” (ISI5) (EI = 1.08), and “Sleep dissatisfaction” (ISI4) (EI = 0.74). “Fatigue” (PHQ4) (Bridge EI = 1.98), “Distress caused by sleep difficulties” (ISI7) (Bridge EI = 1.71), and “Motor Disturbances” (PHQ8) (Bridge EI = 1.67) were important bridge symptoms. The flow network indicated that the edge between the nodes of “Suicidality” (SU) and “Guilt” (PHQ6) showed the strongest connection (Edge Weight= 1.17, followed by “Suicidality” (SU) - “Sad mood” (PHQ2) (Edge Weight = 0.68)). The network analysis results suggest that insomnia symptoms play a critical role in the activation of the insomnia-depression-suicidality network model of COVID-19 survivors, while suicidality is more susceptible to the influence of depressive symptoms. These findings may have implications for developing prevention and intervention strategies for mental health conditions following recovery from COVID-19.
ProMENDA: an updated resource for proteomic and metabolomic characterization in depression
Authors: Pu Juncai , Yu Yue , Liu Yiyun , Wang Dongfang , Gui Siwen , Zhong Xiaogang , Chen Weiyi , Chen Xiaopeng , Chen Yue , Chen Xiang , Qiao Renjie , Jiang Yanyi , Zhang Hanping , Fan Li , Ren Yi , Chen Xiangyu , Wang Haiyang , Xie Peng
Published: May 2024

Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available athttps://menda.cqmu.edu.cn.
Bioprinting salivary gland models and their regenerative applications
Authors: Klangprapan Jutapak , Souza Glauco R. , Ferreira João N.
Published: May 2024

Objective

Salivary gland (SG) hypofunction is a common clinical condition arising from radiotherapy to suppress head and neck cancers. The radiation often destroys the SG secretory acini, and glands are left with limited regenerative potential. Due to the complex architecture of SG acini and ducts, three-dimensional (3D) bioprinting platforms have emerged to spatially define these in vitro epithelial units and develop mini-organs or organoids for regeneration. Due to the limited body of evidence, this comprehensive review highlights the advantages and challenges of bioprinting platforms for SG regeneration.

Methods

SG microtissue engineering strategies such as magnetic 3D bioassembly of cells and microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes have been proposed to replace the damaged acinar units, avoid the use of xenogeneic matrices (like Matrigel), and restore salivary flow.

Results

Replacing the SG damaged organ is challenging due to its complex architecture, which combines a ductal network with acinar epithelial units to facilitate a unidirectional flow of saliva. Our research group was the first to develop 3D bioassembly SG epithelial functional organoids with innervation to respond to both cholinergic and adrenergic stimulation. More recently, microtissue engineering using coaxial 3D bioprinting of hydrogel microfibers and microtubes could also supported the formation of viable epithelial units. Both bioprinting approaches could overcome the need for Matrigel by facilitating the assembly of adult stem cells, such as human dental pulp stem cells, and primary SG cells into micro-sized 3D constructs able to produce their own matrix and self-organize into micro-modular tissue clusters with lumenized areas. Furthermore, extracellular vesicle (EV) therapies from organoid-derived secretome were also designed and validated ex vivo for SG regeneration after radiation damage.

Conclusion

Magnetic 3D bioassembly and microfluidic coaxial bioprinting platforms have the potential to create SG mini-organs for regenerative applications via organoid transplantation or organoid-derived EV therapies.
Saudi dental students’ perceptions on sustainable development goals and sustainable dental practice
Authors: Haque Sanjida , Nurunnabi Mohammad , Haque Tahsinul
Published: May 2024

Objectives

This study utilised a cross-sectional survey design to assess the levels of knowledge and awareness among 841 undergraduate dental students from Saudi Arabia regarding sustainable development goals (SDGs) and sustainable dental practices (SDP).

Materials and methods

A self-administered online questionnaire was distributed to adults aged between 18 and 35 years of both genders, from November 2022 to November 2023. The study has obtained appropriate ethical approval.

Results

Participants exhibited a moderate level of knowledge and awareness regarding the SDGs, while demonstrating a high level of awareness specifically related to the SDP. The presence of a correlation between gender-associated beliefs and pro-environmental behaviours is apparent. Additionally, it has been observed that participants who engage in clinical activities exhibit a heightened level of awareness concerning SDP.

Conclusions

By assessing dental students’ current knowledge and awareness of the SDGs and SDP, we can inform stakeholders in the dental industry about how to enhance sustainability competence and develop dental policy curricula. This will better prepare students to serve as educators as well as professionals, aligning with their commitment to integrating the principles and objectives of various SDGs and SDP into dental education and practice.
Three-year outcomes of post-acute sequelae of COVID-19
Authors: Cai Miao , Xie Yan , Topol Eric J. , Al-Aly Ziyad
Published: May 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 years but still contributed 9.6 (95% confidence interval (CI): 0.4–18.7) disability-adjusted life years (DALYs) per 1,000 persons in the third year. Among hospitalized individuals, risk of death declined but remained significantly elevated in the third year after infection (incidence rate ratio: 1.29 (95% CI: 1.19–1.40)). Risk of incident PASC declined over the 3 years, but substantial residual risk remained in the third year, leading to 90.0 (95% CI: 55.2–124.8) DALYs per 1,000 persons. Altogether, our findings show reduction of risks over time, but the burden of mortality and health loss remains in the third year among hospitalized individuals.
Nf1 mutation disrupts activity-dependent oligodendroglial plasticity and motor learning in mice
Authors: Pan Yuan , Hysinger Jared D. , Yalçın Belgin , Lennon James J. , Byun Youkyeong Gloria , Raghavan Preethi , Schindler Nicole F. , Anastasaki Corina , Chatterjee Jit , Ni Lijun , Xu Haojun , Malacon Karen , Jahan Samin M. , Ivec Alexis E. , Aghoghovwia Benjamin E. , Mount Christopher W. , Nagaraja Surya , Scheaffer Suzanne , Attardi Laura D. , Gutmann David H. , Monje Michelle
Published: May 2024

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4–24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects in activity-dependent oligodendrogenesis and harbor focal OPC hyperdensities with disrupted homeostatic OPC territorial boundaries. These OPC hyperdensities develop in a cell-intrinsic Nf1 mutation-specific manner due to differential PI3K/AKT activation. OPC-specific Nf1 loss impairs oligodendroglial differentiation and abrogates the normal oligodendroglial response to neuronal activity, leading to impaired motor learning performance. Collectively, these findings show that Nf1 mutation delays oligodendroglial development and disrupts activity-dependent OPC function essential for normal motor learning in mice.
Real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for detection of cassava brown streak viruses
Authors: Munguti Florence M. , Kilalo Dora C. , Yegon Hillary K. , Macharia Isaac , Seal Susan E. , Mwango’mbe Agnes W. , Nyaboga Evans N. , Silva Gonçalo
Published: May 2024

Cassava brown streak disease (CBSD) caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) is the most economically important viral disease of cassava. As cassava is a vegetatively propagated crop, the development of rapid and sensitive diagnostics would aid in the identification of virus-free planting material and development of effective management strategies. In this study, a rapid, specific and sensitive real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed for real-time detection of CBSV and UCBSV. The RT-RPA was able to detect as little as 2 pg/µl of purified RNA obtained from infected cassava leaves, a sensitivity equivalent to that obtained by quantitative real-time reverse transcription PCR (qRT-PCR), within 20 min at 37 °C. Further, the RT-RPA detected each target virus directly from crude leaf and stem extracts, avoiding the tedious and costly isolation of high-quality RNA. The developed RT-RPA assay provides a valuable diagnostic tool that can be adopted by cassava seed certification and virus resistance breeding programs to ensure distribution of virus-free cassava planting materials to farmers. This is the first report on the development and validation of crude sap-based RT-RPA assay for the detection of cassava brown streak viruses (UCBSV and CBSV) infection in cassava plants.
Automated machine learning for predicting liver metastasis in patients with gastrointestinal stromal tumor: a SEER-based analysis
Authors: Liu Luojie , Zhang Rufa , Shi Ying , Sun Jinbing , Xu Xiaodan
Published: May 2024

Gastrointestinal stromal tumors (GISTs) are a rare type of tumor that can develop liver metastasis (LIM), significantly impacting the patient's prognosis. This study aimed to predict LIM in GIST patients by constructing machine learning (ML) algorithms to assist clinicians in the decision-making process for treatment. Retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database, and cases from 2010 to 2015 were assigned to the developing sets, while cases from 2016 to 2017 were assigned to the testing set. Missing values were addressed using the multiple imputation technique. Four algorithms were utilized to construct the models, comprising traditional logistic regression (LR) and automated machine learning (AutoML) analysis such as gradient boost machine (GBM), deep neural net (DL), and generalized linear model (GLM). We evaluated the models' performance using LR-based metrics, including the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), as well as AutoML-based metrics, such as feature importance, SHapley Additive exPlanation (SHAP) Plots, and Local Interpretable Model Agnostic Explanation (LIME). A total of 6207 patients were included in this study, with 2683, 1780, and 1744 patients allocated to the training, validation, and test sets, respectively. Among the different models evaluated, the GBM model demonstrated the highest performance in the training, validation, and test cohorts, with respective AUC values of 0.805, 0.780, and 0.795. Furthermore, the GBM model outperformed other AutoML models in terms of accuracy, achieving 0.747, 0.700, and 0.706 in the training, validation, and test cohorts, respectively. Additionally, the study revealed that tumor size and tumor location were the most significant predictors influencing the AutoML model's ability to accurately predict LIM. The AutoML model utilizing the GBM algorithm for GIST patients can effectively predict the risk of LIM and provide clinicians with a reference for developing individualized treatment plans.
Explaining the impact of mutations on quantification of SARS-CoV-2 in wastewater
Authors: Endo Noriko , Nihei Yoshiaki , Fujita Tomonori , Yasojima Makoto , Daigo Fumi , Takemori Hiroaki , Nakamura Masafumi , Matsuda Ryo , Sovannrlaksmy Sorn , Ihara Masaru
Published: May 2024

Wastewater surveillance is an effective tool for monitoring community spread of COVID-19 and other diseases. Quantitative PCR (qPCR) analysis for wastewater surveillance is more susceptible to mutations in target genome regions than binary PCR analysis for clinical surveillance. The SARS-CoV-2 concentrations in wastewater estimated by N1 and N2 qPCR assays started to diverge around July 2022 in data from different sampling sites, analytical methods, and analytical laboratories in Japan. On the basis of clinical genomic surveillance data and experimental data, we demonstrate that the divergence is due to two mutations in the N1 probe region, which can cause underestimation of viral concentrations. We further show that this inaccuracy can be alleviated if the qPCR data are analyzed with the second derivative method or the Cy0 method instead of the crossing point method.
Machine learning models for predicting blood pressure phenotypes by combining multiple polygenic risk scores
Authors: Hrytsenko Yana , Shea Benjamin , Elgart Michael , Kurniansyah Nuzulul , Lyons Genevieve , Morrison Alanna C. , Carson April P. , Haring Bernhard , Mitchell Braxton D. , Psaty Bruce M. , Jaeger Byron C. , Gu C. Charles , Kooperberg Charles , Levy Daniel , Lloyd-Jones Donald , Choi Eunhee , Brody Jennifer A. , Smith Jennifer A. , Rotter Jerome I. , Moll Matthew , Fornage Myriam , Simon Noah , Castaldi Peter , Casanova Ramon , Chung Ren-Hua , Kaplan Robert , Loos Ruth J. F. , Kardia Sharon L. R. , Rich Stephen S. , Redline Susan , Kelly Tanika , O’Connor Timothy , Zhao Wei , Kim Wonji , Guo Xiuqing , Ida Chen Yii-Der ,   The Trans-Omics in Precision Medicine Consortium, Sofer Tamar
Published: May 2024

We construct non-linear machine learning (ML) prediction models for systolic and diastolic blood pressure (SBP, DBP) using demographic and clinical variables and polygenic risk scores (PRSs). We developed a two-model ensemble, consisting of a baseline model, where prediction is based on demographic and clinical variables only, and a genetic model, where we also include PRSs. We evaluate the use of a linear versus a non-linear model at both the baseline and the genetic model levels and assess the improvement in performance when incorporating multiple PRSs. We report the ensemble model’s performance as percentage variance explained (PVE) on a held-out test dataset. A non-linear baseline model improved the PVEs from 28.1 to 30.1% (SBP) and 14.3% to 17.4% (DBP) compared with a linear baseline model. Including seven PRSs in the genetic model computed based on the largest available GWAS of SBP/DBP improved the genetic model PVE from 4.8 to 5.1% (SBP) and 4.7 to 5% (DBP) compared to using a single PRS. Adding additional 14 PRSs computed based on two independent GWASs further increased the genetic model PVE to 6.3% (SBP) and 5.7% (DBP). PVE differed across self-reported race/ethnicity groups, with primarily all non-White groups benefitting from the inclusion of additional PRSs. In summary, non-linear ML models improves BP prediction in models incorporating diverse populations.
Reliability and accuracy of intraoperative fluoroscopy assessment of acetabular cup anteversion in supine direct anterior approach total hip arthroplasty
Authors: Li Weihua , Huang Yan , Zou Zehui , Liu Xuqiang , Li Xiaofeng
Published: May 2024

Poor implantation positioning of hip prostheses is considered the primary factor affecting postoperative joint wear. Cup anteversion in direct anterior approach (DAA) total hip arthroplasty (THA) is often excessive. Intraoperative fluoroscopy (IF) are effective for improving implant placement accuracy. This study aimed to analyze IF’s reliability and accuracy in assessing intraoperative anteversion. Sixty-two consecutive hips underwent primary THA utilizing DAA alongside IF for cup placement. Intraoperative anteversion was measured using IF images, while postoperative CT and standard anteroposterior (AP) radiographs were used to calculate true anteversion component angles. Differences and correlations between intraoperative and true anteversions were analyzed, and intraclass correlation coefficients (ICC) determined the inter- and intra-observer reliabilities. Excellent intra- and inter-observer reliabilities were observed for all radiographic and CT methods (ICC > 0.9). Strong correlations (PCC > 0.6) existed between anteversion measured on IF image and postoperative CT and AP pelvic measurements. Intraoperative anteversion measured on IF images (16.8 ± 3.2°) was smaller than anteversion measured postoperatively on AP X-rays (21.3 ± 4.7°, P < 0.001) and CT (22.0 ± 4.9°, P < 0.001), with average differences of 4.5°and 5.3°, respectively. Under several influencing factors, the accuracy of IF in assessing cup anteversion in DAA-THA may be limited. However, this still requires large-sample experiments for verification.
L-serine deficiency: on the properties of the Asn133Ser variant of human phosphoserine phosphatase
Authors: Pollegioni Loredano , Campanini Barbara , Good Jean-Marc , Motta Zoraide , Murtas Giulia , Buoli Comani Valeria , Pavlidou Despina-Christina , Mercier Noëlle , Mittaz-Crettol Laureane , Sacchi Silvia , Marchesani Francesco
Published: May 2024

The non-essential amino acid L-serine is involved in a number of metabolic pathways and in the brain its level is largely due to the biosynthesis from the glycolytic intermediate D-3-phosphoglycerate by the phosphorylated pathway (PP). This cytosolic pathway is made by three enzymes proposed to generate a reversible metabolon named the “serinosome”. Phosphoserine phosphatase (PSP) catalyses the last and irreversible step, representing the driving force pushing L-serine synthesis. Genetic defects of the PP enzymes result in strong neurological phenotypes. Recently, we identified the homozygous missense variant [NM_004577.4: c.398A > G p.(Asn133Ser)] in the PSPH, the PSP encoding gene, in two siblings with a neurodevelopmental syndrome and a myelopathy. The recombinant Asn133Ser enzyme does not show significant alterations in protein conformation and dimeric oligomerization state, as well as in enzymatic activity and functionality of the reconstructed PP. However, the Asn133Ser variant is less stable than wild-type PSP, a feature also apparent at cellular level. Studies on patients’ fibroblasts also highlight a strong decrease in the level of the enzymes of the PP, a partial nuclear and perinuclear localization of variant PSP and a stronger perinuclear aggregates formation. We propose that these alterations contribute to the formation of a dysfunctional serinosome and thus to the observed reduction of L-serine, glycine and D-serine levels (the latter playing a crucial role in modulating NMDA receptors). The characterization of patients harbouring the Asn133Ser PSP substitution allows to go deep into the molecular mechanisms related to L-serine deficit and to suggest treatments to cope with the observed amino acids alterations.
A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer
Authors: Kodama Tomoko , Imajima Takashi , Shimokawa Mototsugu , Otsuka Taiga , Kawahira Masahiro , Nakazawa Junichi , Hori Takeshi , Shibuki Taro , Arima Shiho , Ido Akio , Miwa Keisuke , Okabe Yoshinobu , Koga Futa , Ueda Yujiro , Kubotsu Yoshihito , Shimokawa Hozumi , Takeshita Shigeyuki , Nishikawa Kazuo , Komori Azusa , Otsu Satoshi , Hosokawa Ayumu , Sakai Tatsunori , Sakai Kenji , Oda Hisanobu , Kawahira Machiko , Arita Shuji , Honda Takuya , Taguchi Hiroki , Tsuneyoshi Kengo , Kawaguchi Yasunori , Fujita Toshihiro , Sakae Takahiro , Shirakawa Tsuyoshi , Mizuta Toshihiko , Mitsugi Kenji
Published: May 2024

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38–85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64–1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.
Automatic removal of soft tissue from 3D dental photo scans; an important step in automating future forensic odontology identification
Authors: Kofod Petersen Anika , Forgie Andrew , Bindslev Dorthe Arenholt , Villesen Palle , Staun Larsen Line
Published: May 2024

The potential of intraoral 3D photo scans in forensic odontology identification remains largely unexplored, even though the high degree of detail could allow automated comparison of ante mortem and post mortem dentitions. Differences in soft tissue conditions between ante- and post mortem intraoral 3D photo scans may cause ambiguous variation, burdening the potential automation of the matching process and underlining the need for limiting inclusion of soft tissue in dental comparison. The soft tissue removal must be able to handle dental arches with missing teeth, and intraoral 3D photo scans not originating from plaster models. To address these challenges, we have developed the grid-cutting method. The method is customisable, allowing fine-grained analysis using a small grid size and adaptation of how much of the soft tissues are excluded from the cropped dental scan. When tested on 66 dental scans, the grid-cutting method was able to limit the amount of soft tissue without removing any teeth in 63/66 dental scans. The remaining 3 dental scans had partly erupted third molars (wisdom teeth) which were removed by the grid-cutting method. Overall, the grid-cutting method represents an important step towards automating the matching process in forensic odontology identification using intraoral 3D photo scans.
AmiA and AliA peptide ligands, found in Klebsiella pneumoniae, are imported into pneumococci and alter the transcriptome
Authors: Lux Janine , Sánchez García Lucía , Chaparro Fernández Patricia , Laloli Laura , Licheri Manon F. , Gallay Clement , Hermans Peter W. M. , Croucher Nicholas J. , Veening Jan-Willem , Dijkman Ronald , Straume Daniel , Hathaway Lucy J.
Published: May 2024

Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins of the ABC transporter Ami-AliA/AliB oligopeptide permease. Exposure to these peptides alters pneumococcal phenotypes such as growth. Using a mutant in which a permease domain of the transporter was disrupted, by growth analysis and epifluorescence microscopy, we confirmed peptide uptake via the Ami permease and intracellular location in the pneumococcus. By RNA-sequencing we found that the peptides modulated expression of genes involved in metabolism, as pathways affected were mostly associated with energy or synthesis and transport of amino acids. Both peptides downregulated expression of genes involved in branched-chain amino acid metabolism and the Ami permease; and upregulated fatty acid biosynthesis genes but differed in their regulation of genes involved in purine and pyrimidine biosynthesis. The transcriptomic changes are consistent with growth suppression by peptide treatment. The peptides inhibited growth of pneumococcal isolates of serotypes 3, 8, 9N, 12F and 19A, currently prevalent in Switzerland, and caused no detectable toxic effect to primary human airway epithelial cells. We conclude that pneumococci take up K. pneumoniae peptides from the environment via binding and transport through the Ami permease. This changes gene expression resulting in altered phenotypes, particularly reduced growth.
Increased incidence and diverse manifestations of multiple evanescent white dot syndrome during the COVID-19 pandemic
Authors: Song Yong Yeon , Kim Jung Tae , Chang Young Suk , Lee Min-Woo , Lee Sung Chul
Published: May 2024

The advent of coronavirus disease 2019 (COVID-19) pandemic has affected the incidence and course of various diseases and numerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. In this study, we compared the incidence of multiple evanescent white dot syndrome (MEWDS) before and during the COVID-19 pandemic at a single center in Korea and analyzed the demographic and clinical features of patients with MEWDS presenting during the COVID-19 pandemic. We categorized patients with MEWDS into two groups according to date of diagnosis. Pre-COVID19 group included patients diagnosed during the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas post-COVID19 group included patients diagnosed during the pandemic period (between March 11, 2020, and March 10, 2023). 6 and 12 patients were included in pre-COVID19 group and post-COVID19 group, respectively. Among all hospital visits during the pre-pandemic and pandemic periods, 0.011% and 0.030% were due to MEWDS, indicating a significant increase during the pandemic (p = 0.029, B = 2.756). The annual incidence of patients with MEWDS in 2017–2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 population, respectively, corresponding to a significant increase (p = 0.039, B = 1.316). Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era.
Transport of non-classical light mediated by topological domain walls in a SSH photonic lattice
Authors: Pérez Gabriel O’Ryan , Dueñas Joaquín Medina , Guzmán-Silva Diego , Torres Luis E. F. Foa , Hermann-Avigliano Carla
Published: May 2024

Advancements in photonics technologies have significantly enhanced their capability to facilitate experiments involving quantum light, even at room temperature. Nevertheless, fully integrating photonic chips that include quantum light sources, effective manipulation and transport of light minimizing losses, and appropriate detection systems remains an ongoing challenge. Topological photonic systems have emerged as promising platforms to protect quantum light properties during propagation, beyond merely preserving light intensity. In this work, we delve into the dynamics of non-classical light traversing a Su-Schrieffer-Heeger photonic lattice with topological domain walls. Our focus centers on how topology influences the quantum properties of light as it moves across the array. By precisely adjusting the spacing between waveguides, we achieve dynamic repositioning and interaction of domain walls, facilitating effective beam-splitting operations. Our findings demonstrate high-fidelity transport of non-classical light across the lattice, replicating known results that are now safeguarded by the topology of the system. This protection is especially beneficial for quantum communication protocols with continuous variable states. Our study enhances the understanding of light dynamics in topological photonic systems and paves the way for high-fidelity, topology-protected quantum communication.