bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Toxicity of 6PPD-Quinone to Early Life Stage Juvenile Chinook (Oncorhynchus tshawytscha) and Coho (Oncorhynchus kisutch) Salmon
Authors: Lo Bonnie P. , Marlatt Vicki L. , Liao Xiangjun , Reger Sofya , Gallilee Carys , Ross Andrew R.S. , Brown Tanya M. 
Published: January 2023

Abstract
The breakdown product of the rubber tire antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD)-6-PPD-quinone has been strongly implicated in toxic injury and death in coho salmon (Oncorhynchus kisutch) in urban waterways. Whereas recent studies have reported a wide range of sensitivity to 6PPD-quinone in several fish species, little is known about the risks to Chinook salmon (Oncorhynchus tshawytscha), the primary prey of endangered Southern Resident killer whales (Orcinus orca) and the subject of much concern. Chinook face numerous conservation threats in Canada and the United States, with many populations assessed as either endangered or threatened. We evaluated the acute toxicity of 6PPD-quinone to newly feeding (~3 weeks post swim-up) juvenile Chinook and coho. Juvenile Chinook and coho were exposed for 24 h under static conditions to five concentrations of 6PPD-quinone. Juvenile coho were 3 orders of magnitude more sensitive to 6PPD-quinone compared with juvenile Chinook, with 24-h median lethal concentration (LC50) estimates of 41.0 and more than 67 307 ng/L, respectively. The coho LC50 was 2.3-fold lower than what was previously reported for 1+-year-old coho (95 ng/L), highlighting the value of evaluating age-related differences in sensitivity to this toxic tire-related chemical. Both fish species exhibited typical 6PPD-quinone symptomology (gasping, increased ventilation, loss of equilibrium, erratic swimming), with fish that were symptomatic generally exhibiting mortality. The LC50 values derived from our study for coho are below concentrations that have been measured in salmon-bearing waterways, suggesting the potential for population-level consequences in urban waters. The higher relative LC50 values for Chinook compared with coho merits further investigation, including for the potential for population-relevant sublethal effects. Environ Toxicol Chem 2023;42:815–822. © 2023 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.
Deep learning identified genetic variants for COVID‐19‐related mortality among 28,097 affected cases in UK Biobank
Authors: Liu Zihuan , Dai Wei , Wang Shiying , Yao Yisha , Zhang Heping 
Published: January 2023

AbstractAnalysis of host genetic components provides insights into the susceptibility and response to viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19). To reveal genetic determinants of susceptibility to COVID‐19 related mortality, we train a deep learning model to identify groups of genetic variants and their interactions that contribute to the COVID‐19 related mortality risk using the UK Biobank data (28,097 affected cases and 1656 deaths). We refer to such groups of variants as super variants. We identify 15 super variants with various levels of significance as susceptibility loci for COVID‐19 mortality. Specifically, we identify a super variant (odds ratio [OR] = 1.594, p = 5.47 × 10−9) on Chromosome 7 that consists of the minor allele of rs76398985, rs6943608, rs2052130, 7:150989011_CT_C, rs118033050, and rs12540488. We also discover a super variant (OR = 1.353, p = 2.87 × 10−8) on Chromosome 5 that contains rs12517344, rs72733036, rs190052994, rs34723029, rs72734818, 5:9305797_GTA_G, and rs180899355.
In vivo characterization of magnetic resonance imaging‐based T1w/T2w ratios reveals myelin‐related changes in temporal lobe epilepsy
Authors: Jiang Yuchao , Li Wei , Qin Yingjie , Zhang Le , Tong Xin , Xiao Fenglai , Jiang Sisi , Li Yunfang , Gong Qiyong , Zhou Dong , An Dongmei , Yao Dezhong , Luo Cheng 
Published: January 2023

AbstractTemporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains unclear how the myelination network changes in TLE. This study developed a novel method in characterization of myelination structural covariance network (mSCN) by T1‐weighted and T2‐weighted magnetic resonance imaging (MRI). The mSCNs were estimated in 42 left TLE (LTLE), 42 right TLE (RTLE) patients, and 41 healthy controls (HCs). The topology of mSCN was analyzed by graph theory. Voxel‐wise comparisons of myelination laterality were also examined among the three groups. Compared to HC, both patient groups showed decreased myelination in frontotemporal regions, amygdala, and thalamus; however, the LTLE showed lower myelination in left medial temporal regions than RTLE. Moreover, the LTLE exhibited decreased global efficiency compared with HC and more increased connections than RTLE. The laterality in putamen was differently altered between the two patient groups: higher laterality at posterior putamen in LTLE and higher laterality at anterior putamen in RTLE. The putamen may play a transfer station role in damage spreading induced by epileptic seizures from the hippocampus. This study provided a novel workflow by combination of T1‐weighted and T2‐weighted MRI to investigate in vivo the myelin‐related microstructural feature in epileptic patients first time. Disconnections of mSCN implicate that TLE is a system disorder with widespread disruptions at regional and network levels.
Ischemic stroke on SARS‐CoV2 vasculitis in a healthy young girl
Authors: Petat Hortense , Hassani Adnan , Dabaj Ivana , Tzaroukian Lucile , Goujard Barbara , Michelet Isabelle , More Rebecca 
Published: January 2023

AbstractBackground and AimsIn France, we noted the fifth wave of SARS‐CoV2 pandemic, characterized by presence of Omicron variant. This variant is very contagious, but less often aggressive, especially in pediatric population.MethodsWe report a case of a 10‐year‐old girl, previously healthy, not yet vaccinated for SARS‐CoV2, presented to our emergency department for left hemiparesis associated with headache and vomiting, without any signs of respiratory tract infection.ResultsCerebral CT and MRI showed an ischemic stroke of right sylvian artery. Magnetic resonance angiography performed upon resurgence of new symptoms was in favor of vasculitis on the right internal carotid and right sylvian artery. PCR SARS‐CoV2 was positive for Omicron variant. She fully recovered after few days and was treated with acetylsalicylic acid and intravenous corticosteroids.ConclusionWe report this case to raise awareness on the possible complications related to SARS‐CoV2 infection and we highly recommend vaccination in this age group.
Potential clinical benefits of warfarin in end‐stage cancers: A retrospective analysis
Authors: Imataki Osamu , Arai Takeshi , Uemura Makiko 
Published: January 2023

AbstractBackground and AimsCoagulopathy and thromboembolism are common comorbidities in cancer, and anticoagulants, such as warfarin, are needed in specific situations. This study aimed to determine the clinical relevance of prothrombin time (PT) monitoring and the clinical usefulness of warfarin in patients with malignancy.MethodsWe retrospectively investigated patients with PT lower than 10% treated in our hospital between April 2006 and March 2013. Cases of false coagulopathy, including those due to technical errors during blood sampling, were excluded. The cause of coagulopathy was determined or estimated by physicians.ResultsThis study included 338 cases comprising 155 females and 183 males with a median age was 68 (0–97) years. Among them, 89 (26.3%) had cancer, and 163 (48.2%) received warfarin at a median dose of 2.23 (0.5–8.0) mg/day. PT prolongation caused by warfarin overdose and malignancy exacerbation were observed in 75 (22.2%) and 64 (18.9%) patients, respectively. The leading reasons for warfarin administration were arterial fibrillation, chronic heart failure, and deep vein thrombosis. Univariate analysis revealed that the overall survival was higher in the warfarin and nononcology groups than in the nonwarfarin and oncology groups (both p < 0.001). In multivariate analysis, survival was significantly decreased in older adults (p = 0.049), those with malignancy (p < 0.001), and those without warfarin therapy (p < 0.001). Early mortality (within 3 days after PT prolongation) was observed in 65 patients and was mostly related to emergent diseases (36.9%, 24/65) and end‐stage malignancy (32.3%, 21/65).ConclusionPatients with malignancy may experience subclinical PT prolongation upon disease progression. Warfarin treatment mitigates panic PT values in patients with malignancy. Conversely, those not treated with warfarin have poor survival, suggesting that coagulopathy without warfarin treatment can lead to death. Warfarin enhances hemostatic conditions, thereby preventing malignancy‐related lethal hemorrhagic or thromboembolic events.
Managing an extension of screening intervals: Avoiding boom and bust in health care workloads
Authors: Pesola Francesca , Rebolj Matejka , Sasieni Peter 
Published: January 2023

AbstractExtending screening intervals in ongoing cancer screening programmes can lead to challenging year‐on‐year variations in the number of screening tests. We explored how such variation could be diminished with a managed transition to the extended interval. We defined three extension scenarios: immediate extension for the entire target population; stepped transition by birth cohort; and gradual transition by reducing the number of available screening appointments. These were compared to a situation in which the interval remains unchanged in a demographic model covering a 15‐year period. The model was populated with observed parameters from England, a real‐world setting recommending cervical screening with 3‐year intervals at age 25‐49 and 5‐year intervals at age 50‐64. Informed by typical changes currently considered by several European programmes including the programme in England, we explored the effect on screening test numbers of an extension of the 3‐year interval to 5 years for women younger than 50. All three extension scenarios resulted in similar cumulative numbers of screening tests, which were about 30% lower compared to a situation in which the interval would remain unchanged. However, the year‐on‐year variation in the number of screening tests varied between the scenarios. This variation was around 4‐fold for the immediate scenario. In the stepped scenario, the yearly numbers could differ by around 20%, whereas in the gradual scenario they were virtually constant. A managed interval extension, transitioning different groups of the target population at different times, can substantially reduce the yearly variation in screening workload without increasing the total number of screening tests in the long term.
Molnupiravir is effective in patients with haematological malignancies
Authors: Bołkun Łukasz , Pula Bartosz , Kołkowska‐Leśniak Agnieszka , Morawska Marta , Cichocka Edyta , Charlinski Grzegorz , Garus Bartosz , Giebel Sebastian , Piszcz Jaroslaw , Drozd‐Sokolowska Joanna , Kwiatkowski Jacek , Biernat Monika , Hus Iwona , Lech‐Maranda Ewa , Długosz‐Danecka Monika , Giannopoulos Krzysztof , Wróbel Tomasz 
Published: January 2023

AbstractPatients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS‐CoV‐2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS‐CoV‐2 less effective than in immunocompetent individuals. Molnupiravir is one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death in COVID‐19 in the general population. In this context, 175 haematology patients with diagnosed COVID‐19, and treated with MOL between January and April 2022, came under our scrutiny with a view to defining their clinical characteristics and outcomes. The most common underlying conditions were lymphomas (45%), multiple myelomas (21%) and acute leukaemias or myelodysplastic syndrome (35%). Of all, 77% of the patients were vaccinated, and half of them received a booster. At 28 days after the breakthrough COVID‐19 diagnosis, 35 (20%) subjects required hospital admission. Out of those patients, seven (4%) died during the follow‐up due to the progression of COVID. Our results corroborate what has been established to date with regard to the positive clinical and safety outcomes of MOL in haematology patients with mild or moderate COVID‐19.
Lipid raft protein flotillin‐1 is important for the interaction between SOS1 and H‐Ras/K‐Ras, leading to Ras activation
Authors: Jin Hao , Koh Minsoo , Lim Hyesol , Yong Hae‐Young , Kim Eun‐Sook , Kim Sun Young , Kim Kyoungmee , Jung Joohee , Ryu Won‐Ji , Choi Kang‐Yell , Moon Aree 
Published: January 2023

AbstractRas mutations have been frequently observed in human cancer. Although there is a high degree of similarity between Ras isomers, they display preferential coupling in specific cancer types. The binding of Ras to the plasma membrane is essential for its activation and biological functions. The present study elucidated Ras isoform‐specific interactions with the membrane and their role in Ras‐mediated biological activities. We investigated the role of a lipid raft protein flotillin‐1 (Flot‐1) in the activations of Ras. We found that Flot‐1 was co‐localized with H‐Ras, but not with N‐Ras, in lipid rafts of MDA‐MB‐231 human breast cells. The amino‐terminal hydrophobic domain (1‐38) of Flot‐1 interacted with the hypervariable region of H‐Ras. The epidermal growth factor‐stimulated activation of H‐Ras required Flot‐1 which was not necessary for that of N‐Ras in breast cancer cells. Flot‐1 interacted with son of sevenless (SOS)‐1, which promotes the conversion of Ras‐bound GDP to GTP. Notably, Flot‐1 was crucial for the interaction between SOS1 and H‐Ras/K‐Ras in breast and pancreatic cancer cells. Stable knockdown of Flot‐1 reduced the in vivo metastasis in a mouse xenograft model with human breast carcinoma cells. A tissue microarray composed of 61 human pancreatic cancer samples showed higher levels of Flot‐1 expression in pancreatic tumor tissues compared to normal tissues, and a correlation between K‐Ras and Flot‐1. Taken together, our findings suggest that Flot‐1 may serve as a membrane platform for the interaction of SOS1 with H‐Ras/K‐Ras in human cancer cells, presenting Flot‐1 as a potential target for Ras‐driven cancers.
Deep distributional time series models and the probabilistic forecasting of intraday electricity prices
Authors: Klein Nadja , Smith Michael Stanley , Nott David J. 
Published: January 2023

SummaryRecurrent neural networks (RNNs) with rich feature vectors of past values can provide accurate point forecasts for series that exhibit complex serial dependence. We propose two approaches to constructing deep time series probabilistic models based on a variant of RNN called an echo state network (ESN). The first is where the output layer of the ESN has stochastic disturbances and a Bayesian prior for regularization. The second employs the implicit copula of an ESN with Gaussian disturbances, which is a Gaussian copula process on the feature space. Combining this copula process with a nonparametrically estimated marginal distribution produces a distributional time series model. The resulting probabilistic forecasts are deep functions of the feature vector and marginally calibrated. In both approaches, Markov chain Monte Carlo methods are used to estimate the models and compute forecasts. The proposed models are suitable for the complex task of forecasting intraday electricity prices. Using data from the Australian market, we show that our deep time series models provide accurate short‐term probabilistic price forecasts, with the copula model dominating. Moreover, the models provide a flexible framework for incorporating probabilistic forecasts of electricity demand, which increases upper tail forecast accuracy from the copula model significantly.
Promoting engagement with self‐guided digital therapeutics for mental health: Insights from a cross‐sectional survey of end‐users
Authors: Gan Daniel Z. Q. , McGillivray Lauren , Larsen Mark E. , Torok Michelle 
Published: January 2023

AbstractBackgroundPoor engagement has hindered the dissemination of self‐guided digital therapeutics for mental health. Evidence on the efficacy of technology‐supported strategies designed for increasing engagement with these interventions is currently inconclusive. Few studies have examined user perceptions of such strategies, which could yield key insights for enhancing their effectiveness.MethodsTwo hundred and eleven participants completed a cross‐sectional online survey. All participants were aged 18 years and above, living in Australia, fluent in English, and self‐reported prior use of digital therapeutics for mental health needs. Survey items elicited participants' views on factor(s) contributing to their engagement/disengagement with digital therapeutics, and perceptions of engagement strategies, including: automated electronic reminders, fun facts, quizzes, and social media platforms. χ2 tests of independence were used to analyse nominal data. Inductive thematic analysis was used to analyse free‐text data.ResultsFactors facilitating engagement included digestible content, assurance of confidentiality, and esthetically appealing design. Factors hindering engagement included lack of time, forgetfulness, and lack of perceived intervention efficacy. Participants had mixed views over the feasibility and acceptability of the strategies explored toward promoting engagement.ConclusionsRegardless of strategy type, succinct and easily applicable content was identified as an important feature for promoting engagement. Conversely, content that could trigger psychological distress among intervention users should be avoided. Overall, the diverse range of user perspectives highlighted that engagement strategies for any specific digital intervention should be co‐designed with individuals with lived experience of mental health difficulties.
Intuition and meaning in life in persons with varying level of depressive symptoms and impairments in personality functioning
Authors: Remmers Carina , Zürn Michael , Anoschin Albert , Topolinski Sascha , Zimmermann Johannes 
Published: January 2023

AbstractObjectivesThe current research explored the interplay between intuition, meaning in life, and psychopathology. Specifically, we investigated whether experiential and reflective components of meaning in life are associated with depressive symptoms and personality pathology, whether intuition is related to the experience of meaning, and whether psychopathology has disruptive effects on intuition as well as on the link between intuition and the experience of meaning.MethodsWe tested our preregistered hypotheses in two independent studies. In Study 1, N = 448 participants completed self‐report instruments assessing the experiential and the reflective dimensions of meaning in life, depressive symptoms, and impairments in personality functioning. Intuition was operationalized as the ability to intuitively detect semantic coherence in an experimental task. Additionally, self‐reported confidence in intuition was assessed. In Study 2, we aimed to replicate our findings and hypotheses that emerged from Study 1 with a new sample of N = 1189 participants.ResultsIn both studies, participants with more depressive symptoms or higher levels of personality pathology experienced life as less meaningful but reflected significantly more about meaning in life. The intuitive ability to discriminate between coherence and incoherence in the experimental task was neither related to the experience of meaning in life nor to psychopathology, but more confidence in intuition was associated with experiencing life as more meaningful and with less psychopathological symptoms. It was tentatively supported that the association between meaning in life and intuition was moderated by psychopathology.ConclusionThe findings are discussed in terms of their clinical implications and regarding the cognitive‐affective processes potentially underlying people's experience of life being meaningful.
Going the distance: A longitudinal qualitative study of formal youth mentoring relationship development
Authors: Spencer Renée , Drew Alison L. , Gowdy Grace 
Published: January 2023

AbstractMore enduring formal youth mentoring relationships tend to be more effective, but our understanding of how such relationships develop and are sustained remains limited. This prospective, qualitative study examined the development of 67 one‐to‐one, community‐based mentoring relationships over a 2‐year period. Data included interviews with mentors, youth, and the youth's parent/guardian across multiple time‐points and agency case notes. Five developmental trajectories were identified: (a) continued growth, (b) initial growth that plateaued, (c) initial growth followed by decline and then recovery, (d) initial growth followed by decline with no recovery, and (e) little to no growth or connection. Matches in the continued growth and recovery groups were more enduring and experienced by participants as meaningful connections. Factors that appeared to have contributed to these different trajectories were youth interest in the mentoring relationship, mentor empathy, flexibility, and commitment, and program support.
Cocaine perturbs mitovesicle biology in the brain
Authors: D'Acunzo Pasquale , Ungania Jonathan M. , Kim Yohan , Barreto Bryana R. , DeRosa Steven , Pawlik Monika , Canals‐Baker Stefanie , Erdjument‐Bromage Hediye , Hashim Audrey , Goulbourne Chris N. , Neubert Thomas A. , Saito Mariko , Sershen Henry , Levy Efrat 
Published: January 2023

AbstractCocaine, an addictive psychostimulant, has a broad mechanism of action, including the induction of a wide range of alterations in brain metabolism and mitochondrial homeostasis. Our group recently identified a subpopulation of non‐microvesicular, non‐exosomal extracellular vesicles of mitochondrial origin (mitovesicles) and developed a method to isolate mitovesicles from brain parenchyma. We hypothesised that the generation and secretion of mitovesicles is affected by mitochondrial abnormalities induced by chronic cocaine exposure. Mitovesicles from the brain extracellular space of cocaine‐administered mice were enlarged and more numerous when compared to controls, supporting a model in which mitovesicle biogenesis is enhanced in the presence of mitochondrial alterations. This interrelationship was confirmed in vitro. Moreover, cocaine affected mitovesicle protein composition, causing a functional alteration in mitovesicle ATP production capacity. These data suggest that mitovesicles are previously unidentified players in the biology of cocaine addiction and that target therapies to fine‐tune brain mitovesicle functionality may be beneficial to mitigate the effects of chronic cocaine exposure.