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Generative Artificial Intelligence is set to revolutionize healthcare delivery by transforming traditional patient care into a more personalized, efficient, and proactive process. Chatbots, serving as interactive conversational models, will probably drive this patient-centered transformation in healthcare. Through the provision of various services, including diagnosis, personalized lifestyle recommendations, dynamic scheduling of follow-ups, and mental health support, the objective is to substantially augment patient health outcomes, all the while mitigating the workload burden on healthcare providers. The life-critical nature of healthcare applications necessitates establishing a unified and comprehensive set of evaluation metrics for conversational models. Existing evaluation metrics proposed for various generic large language models (LLMs) demonstrate a lack of comprehension regarding medical and health concepts and their significance in promoting patients’ well-being. Moreover, these metrics neglect pivotal user-centered aspects, including trust-building, ethics, personalization, empathy, user comprehension, and emotional support. The purpose of this paper is to explore state-of-the-art LLM-based evaluation metrics that are specifically applicable to the assessment of interactive conversational models in healthcare. Subsequently, we present a comprehensive set of evaluation metrics designed to thoroughly assess the performance of healthcare chatbots from an end-user perspective. These metrics encompass an evaluation of language processing abilities, impact on real-world clinical tasks, and effectiveness in user-interactive conversations. Finally, we engage in a discussion concerning the challenges associated with defining and implementing these metrics, with particular emphasis on confounding factors such as the target audience, evaluation methods, and prompt techniques involved in the evaluation process.

Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Signaling through the Ras-MAPK pathway can exhibit switch-like activation, which has been attributed to the underlying positive feedback and bimodality in the activation of RasGDP to RasGTP by SOS. SOS contains both catalytic and allosteric Ras binding sites, and a common assumption is that allosteric activation selectively by RasGTP provides the mechanism of positive feedback. However, recent single-molecule studies have revealed that SOS catalytic rates are independent of the nucleotide state of Ras in the allosteric binding site, raising doubt about this as a positive feedback mechanism. Here, we perform detailed kinetic analyses of receptor-mediated recruitment of full-length SOS to the membrane while simultaneously monitoring its catalytic activation of Ras. These results, along with kinetic modeling, expose the autoinhibition release step in SOS, rather than either recruitment or allosteric activation, as the underlying mechanism giving rise to positive feedback in Ras activation.

Apart from northern and central China, the fossil record of the latest Miocene and Early Pliocene of Asia is not well documented and the record of South China during this interval is especially poor. Shuitangba, a site in Yunnan Province, offers a rare window into the paleoenvironment of the latest Miocene in southwestern China. Over 2400 vertebrate and macrobotanical specimens have been recovered from the site. The faunal assemblage is dominated by aquatic avian taxa and many of the mammalian taxa are those that indicate densely vegetated, water-margin habitats. Pollen and carpological remains indicate a temperate to subtropical, broad-leaved/coniferous forest around standing water, with more open areas containing grasses and herbs. Analyses of clay minerals, chemical weathering, and enamel stable isotopes suggest that Shuitangba was warmer and more humid than today, possibly with more pronounced seasonality. Results of community structure analysis indicate that the Shuitangba mammalian community was different from those of other Late Miocene Chinese sites in the high proportions of aquatic-dependent mammalian taxa. While Shuitangba shared mammalian faunal elements with other Late Miocene sites in Yunnan, it was still faunally distinct. Further, Shuitangba was depauperate in its mammalian fauna, which may have been a result of the depositional setting rather than a true reflection of regional faunal diversity.

The direction of individual B8 solar neutrinos has been reconstructed using the SNO+ liquid scintillator detector. Prompt, directional Cherenkov light was separated from the slower, isotropic scintillation light using time information, and a maximum likelihood method was used to reconstruct the direction of individual scattered electrons. A clear directional signal was observed, correlated with the solar angle. The observation was aided by a period of low primary fluor concentration that resulted in a slower scintillator decay time. This is the first time that event-by-event direction reconstruction in high light-yield liquid scintillator has been demonstrated in a large-scale detector.

Populations composed of individuals descended from multiple distinct genetic lineages often feature significant differences in phenotypic frequencies. We considered hatchery production of steelhead, the migratory anadromous form of the salmonid species Oncorhynchus mykiss, and investigated how differences among genetic lineages and environmental variation impacted life history traits. We genotyped 23,670 steelhead returning to the four California Central Valley hatcheries over 9 years from 2011 to 2019, confidently assigning parentage to 13,576 individuals to determine age and date of spawning and rates of iteroparity and repeat spawning within each year. We found steelhead from different genetic lineages showed significant differences in adult life history traits despite inhabiting similar environments. Differences between coastal and Central Valley steelhead lineages contributed to significant differences in age at return, timing of spawning, and rates of iteroparity among programs. In addition, adaptive genomic variation associated with life history development in this species varied among hatchery programs and was associated with the age of steelhead spawners only in the coastal lineage population. Environmental variation likely contributed to variations in phenotypic patterns observed over time, as our study period spanned both a marine heatwave and a serious drought in California. Our results highlight evidence of a strong genetic component underlying known phenotypic differences in life history traits between two steelhead lineages.

Mustafa Arici,1 Saeed MG Al-Ghamdi,2 Alain G Assounga,3 Ahmed F El-Koraie,4 Abigail McMillan,5 Lucinda J Camidge,5 Budiwan Sumarsono,6 Martin Blogg,7 Daniel Bin Ng,6 Elvira P Lansang6 1Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Türkiye; 2Department of Medicine, Nephrology Section, King Abdulaziz University and King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia; 3Department of Nephrology, Division of Medicine, University of KwaZulu-Natal, Durban, South Africa; 4Nephrology Unit, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Adelphi Real World, Bollington, UK; 6Astellas Pharma Singapore Pte. Ltd, Singapore, Singapore; 7Astellas Pharma Europe Ltd, Addlestone, UKCorrespondence: Mustafa Arici, Hacettepe University Faculty of Medicine, Department of Nephrology, Sihhiye, Ankara, 06100, Türkiye, Tel +90-312-324 3109, Fax +90-312-311 3958, Email marici@hacettepe.edu.tr, aricim@gmail.comIntroduction: Limited data exist regarding treatment patterns and symptom burden of patients with anemia of chronic kidney disease (CKD) in the Middle East, South Africa, and Türkiye.Methods: This real-world study explored clinical characteristics, symptom burden, and treatment patterns of patients with anemia of CKD living in the Middle East, South Africa, and Türkiye. Physician and patient perceptions of treatment were captured via cross-sectional surveys; patients’ clinical characteristics were recorded by retrospective review of medical records.Results: Data were collected from 1788 patients and 217 physicians. A high proportion of patients had never received treatment for their anemia (n = 701, 39.2%); the most common treatment was erythropoietin-stimulating agents (ESAs) + intravenous iron (n = 457, 50.3%). High symptom burden was reported, with lack of energy being the most common symptom (n = 394, 75.6% treated and n = 133, 59.9% non-treated patients). Patients’ self-reported symptom burden was higher than physician-reported burden; less agreement was seen for non-dialysis-dependent (NDD) patients (kappa = 0.193, standard deviation [SD]: 0.081) than dialysis-dependent (DD) patients (kappa = 0.442, SD: 0.103). Median hemoglobin thresholds that physicians reported using for initiating treatment (NDD: < 10.5 [interquartile range, 9.5– 12.0] g/dL; DD: < 9.3 [9.0– 10.0] g/dL) were higher than actual test levels at treatment initiation (NDD: 9.2 [8.7– 10.0] g/dL; DD: 9.0 [8.1– 10.0] g/dL).Conclusion: Treatment inertia is apparent despite high symptom burden in the Middle East, South Africa, and Türkiye, and disagreement was seen in physician and patient perspectives on symptomology. Improved awareness of this disagreement may help facilitate physician–patient dialogue to improve patient experience.Plain Language Summary: A survey to understand the experiences of people living with anemia and kidney disease in the Middle East, South Africa, and TürkiyeBackgroundPeople living with kidney disease can have a low number of red blood cells (anemia).This can cause heart problems, make kidney disease worse, and lead to death.Not much is known about the experiences of people living with kidney disease and anemia in the Middle East, South Africa, and Türkiye.For example, what symptoms do they experience, and which treatments do they receive for their anemia?What we didWe carried out surveys in the Middle East, South Africa, and Türkiye between June and September 2022.We surveyed 1788 people living with kidney disease and anemia, and 217 of their doctors.We asked about symptoms experienced by people living with kidney disease and anemia, and which treatments they received for their anemia.What we foundPeople living with kidney disease and anemia experienced many different symptoms.Lack of energy was the most common.People living with kidney disease and anemia mentioned symptoms more frequently than their doctors.Almost 40% of people living with kidney disease did not receive any treatment for their anemia.The most common treatment was iron combined with drugs that increase production of red blood cells (erythropoietin-stimulating agents).What does this mean?To improve communication and care, doctors should be made aware of how much the symptoms of anemia affect the lives of people living with kidney disease.Disclaimer: This plain language summary represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, and copyright information, please see the full text online.Keywords: anemia, chronic kidney disease, treatment patterns, treatment satisfaction, symptom burden, real-world evidence

Abstract When applying data mining or machine learning techniques to large and diverse datasets, it is often necessary to construct descriptive and predictive models. Descriptive models are used to discover relationships between the attributes of the data while predictive models identify the characteristics of the data that will be collected in the future. Bioinformatics data is high-dimensional, making it practically impossible to apply the majority of “classical” algorithms for classification and clustering. Even if the algorithms are useful, training with large multidimensional data significantly increases processing time. The algorithms specialized for working with high-dimensional data often cannot process data containing large data sets with several thousand dimensions (features). Dimension reduction methods (such as PCA) do not provide satisfactory results, and also obscure the meaning of the original attributes in the data. For the constructed models to be usable, they must fulfill the requirement of scalability, as the amount of bioinformatics data is increasing rapidly. Furthermore, the significance of individual data features can differ from source to source. This paper describes an attribute selection method for efficient classification of high-dimensional (30,698) transcriptomics data collected from different sources. The proposed method was tested with 22 classification algorithms. The classification results for the selected attribute sets are comparable to the results for the complete attribute set.

Literary texts of different genres can be the starting point for intra-curricular and intercurricular connections. Our research, that included a sample of 225 primary school teachers, was conducted to establish the following: 1) how practitioners evaluate the potential of different types of literary texts as a starting point for integration in teaching and 2) what attitudes they have about how the application of a literary text as a starting point for integration affects the class organisation and dynamics. The obtained results show that teachers most positively evaluate the possibilities provided by prose literature as a starting point for integration, primarily the tales written by authors and folktales. When it comes to the class organisation and dynamics, the largest number of teachers agree (completely or mostly) on the following: all lower grades of primary school are suitable for using a literary text as a starting point for integration; the literary text can be used as a starting point for integration even beyond Serbian language classes; the application of the literary text as a starting point for integration affects the greater dynamics of teaching. A considerable number also agrees with the fact that in teaching practice the process of integration makes it difficult to choose an adequate literary text, but there are quite a few who are undecided when it comes to this issue. The obtained results show that primary school teachers positively evaluate the potential of literary texts as a starting point for integration in teaching, but they also raise the issue of an insufficient application in practice of this form of work and the need for additional support for practitioners in performing integration.

The topic of the research is the spontaneous speech of the children of preschool age, aged three to seven years. The corpus consists of a total of 400 children’s statements, one hundred each from the children of ages 3.0‒3.11, 4.0‒4.11, 5.0‒5.11 and 6.0‒6.11. The statements were collected using the technique of anecdotal notes in kindergartens in Jagodina. In the analysis, the lists of nouns, pronouns, verbs, adjectives, numbers, adverbs, prepositions, conjunctions, exclamations, and words that appear in children’s speech were extracted. The research provides a significant insight into the speech development of the children aged three to seven and indicates the aspects of speech development that should be given more attention. Speech is acquired through imitation, so the teacher should use the carefully selected vocabulary in his/her speech, taking care that the statement is understandable to the children, but that the children have opportunities every day to hear a new word from the teacher. Our study showed that certain word classes are absent in children’s spontaneous speech. The use of adjectives, adverbs, exclamations, and particles should be encouraged in preschool children’s speech.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

PYTA is demonstrated to rapidly and stably complex 225Ac, 177Lu, 111In, and 44Sc, a “superfecta” of complementary but chemically distinct radiometals for targeted theranostic applications.

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc)-a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST)-as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders-and how this relationship is mediated by alterations in the EAc-could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant-inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.

Dan Liu, Li-Jun Chi Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Li-Jun Chi, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Postal Street, Nangang District, Harbin, Heilongjiang Province, People’s Republic of China, Email clj3751@163.comPurpose: Vascular cognitive impairment(VCI) ranks as the second most prevalent type of dementia.Increasing evidence has shown that inflammation and multi-faceted neuro-immune interactions integrate systemic and central inflammatory pathways, thereby inducing vascular tissue injury and contributing to the development of vascular cognitive impairment (VCI).V-type immunoglobulin-like suppressor of T cell activation (VISTA) is an Negative checkpoint regulators(NCR) that is associated with CNS homeostasis, interactions with peripheral immunity and CNS inflammation.The primary objective of this study was to seek the correlation between VISTA and VCI in patients with cardiovascular risk factors.Our secondary objective was to explore the potential of VISTA as a biomarker for VCI.Patients and Methods: We enrolled individuals with cardiovascular risk factors in this cross-sectional study research and categorized them into two groups: without cognitive impairment (control) and with cognitive impairment (VCI). VISTA expression in peripheral blood mononuclear cells (PBMCs) was analyzed using relative quantitative polymerase chain reaction. VISTA expression was identified in monocyte subsets using flow cytometry. We use Enzyme linked immunosorbent assay to detect inflammatory factors in serum.Results: In PBMC in patients with VCI, the expression of VSIR was significantly reduced. In contrast to controls, fasting glucose, fibrosis, and the levels of interleukin 6 (IL-6) in VCI patients were noticeably higher, and uric acid levels were significantly lower. Vsir mRNA expression in PBMCs correlated negatively with IL-6 levels, Trail Making Test B scores, and Hachinski scores and positively with Boston Naming Test scores. In intermediate monocytes, flow cytometry showed reduced Vsir expression, which was connected with VCI. The percentage of intermediate monocytes, uric acid, and the VISTA mean fluorescence intensity on intermediate monocytes were shown to be independent factors to VCI by multivariate logistic regression analysis.Conclusion: Decreased VISTA promotes the occurrence of VCI in patients with cardiovascular risk factors by promoting monocytes toward the proinflammatory intermediate monocyte subset. VISTA may serve as a potential biomarker for distinguishing VCI in individuals with cardiovascular risk factors.Keywords: neuroinflammation, intermediate monocyte, biomarker, flow cytometry

Chantal Emade Nkwelle,1,2 Smith B Babiaka,3,4 Clovis S Metuge,2,3 Kimberly Liang,5 Unique Stephens,5 Seraphine Nkie Esemu,1 David S Zuzga,5 Kristy Shuda McGuire,5 Luis J Montaner,5 Roland N Ndip,1 Ian Tietjen,5 Fidele Ntie-Kang2,3,6 1Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon; 2Center for Drug Discovery, Faculty of Science, University of Buea, Buea, Cameroon; 3Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon; 4Department of Microbial Bioactive Compound, University of Tübingen, Tübingen, Germany; 5Drug Discovery, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA; 6Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle, GermanyCorrespondence: Ian Tietjen, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA, Tel +1-215-898-3938, Email itietjen@wistar.org Fidele Ntie-Kang, Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon, Tel +237-673872475, Email fidele.ntie-kang@ubuea.cmBackground: Croton oligandrus Pierre & Hutch is a tropical tree that grows in West and Central Africa, used in ethnomedicine to treat cancer, diabetes, headaches, convulsions, urinary diseases, and inflammatory diseases. As other Croton species have been observed to possess chemical compounds that target HIV latency-reversal, we hypothesized that this species may have similar properties.Aim of the Study: The identification of extracts and compounds of this species, which have HIV-1 latency-reversing activity in J-Lat T cell lines.Methods: The stem bark was obtained, air-dried, powdered, and extracted using dichloromethane. In vitro flow cytometry was used to monitor GFP expression, a marker of HIV latency reversal, following treatment of J-Lat T cells with extracts and compounds.Results: Four extracts were found to reverse HIV latency, the most active extract showing better activity (ie, latency reversal in 69.7 ± 7.1% [mean ± s.e.m.] of J-Lat 10.6 cells at 1 μg/mL) than control agents prostratin (46.2 ± 9.5% at 1.2 μg.mL) and the “Mukungulu” (Croton megalobotrys) extract (34.9 ± 24.2% at 1 μg/mL). Extracts reversed HIV latency through mechanisms over and above protein kinase C (PKC) activation and distinct from histone deacetylase (HDAC) inhibition. The most active extract also synergized with the control HDAC inhibitor romidepsin but did not synergize with other extracts. Isolated compounds (β-Stigmasterol and lupeol) had limited but consistent latency reversal on their own.Conclusion: The plant extracts and compounds reverse HIV latency through mechanisms additional to PKC activation and/or synergize with romidepsin in vitro. Extracts and compounds from this plant may enhance the activity of current HIV latency-reversing agents being assessed in HIV cure studies.Keywords: antiviral, compounds, extracts, HIV-1, latency reversal, screening

L Jay Katz,1,2 Jonathan S Myers,1 Leon W Herndon Jnr,3 Yocheved Shira Kresch,4 Fritz H Hengerer5,6 1Wills Eye Hospital, Philadelphia, PA, USA; 2Glaukos Corporation, Aliso Viejo, CA, USA; 3Duke University Eye Center, Durham, NC, USA; 4Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 5Department of Ophthalmology, Buergerhospital, Frankfurt, Germany; 6University Eye Hospital, University of Heidelberg, Heidelberg, GermanyCorrespondence: L Jay Katz, Glaukos Corporation, One Glaukos Way, Aliso Viejo, CA, 92656, USA, Tel +01 949-367 9600, Fax +01 949 367 9984, Email jkatz@glaukos.comAbstract: Glaucoma treatment is beginning to undergo an evolution, moving away from topical medication-based therapies toward more proactive minimally invasive interventions. This shift towards an “interventional glaucoma” treatment paradigm has been shown to benefit patients, providers, and society. A key component of effectively implementing this approach is education about the importance of glaucoma diagnosis and treatment, as well as the various treatment modalities available. Such education is relevant not only for patient but also patients’ support networks, ophthalmologists, optometrists, third-party payers, and policy-makers. Education can occur both within and outside the clinical setting. The present article provides an overview of the diverse educational methods available for glaucoma patients, including those based on patient-provider interactions and those based on internet and printed material. Examples of the former could include general and specific verbal instruction, motivational interviewing, or community-based educational workshops, while examples of the latter could include office-based movies or printed materials, virtual reality headset educational videos, artificial intelligence-assisted education, or self-directed internet videos and articles. By empowering patients with knowledge and an up-to-date awareness of treatment options, effective education can be a valuable part of making an interventional glaucoma treatment paradigm possible.Keywords: MIGS, education, intervention/interventional, glaucoma, surgery

Hong-Da Zhang,&ast; Lei Ding,&ast; Li-Jie Mi, Ai-Kai Zhang, Yuan-Dong Liu, Xiang-Nan Li, Xin-Xin Yan, Yu-Jing Shen, Min Tang State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Tang; Yu-Jing Shen, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email doctortangmin@yeah.net; shenyj0328@126.comBackground: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in critically ill patients and significantly impacts mortality. This study sought to evaluate the impact of new-onset AF on mortality in a critically ill population.Methods: This study identified 48018 adult patients admitted to the ICU from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were categorized as no AF, pre-existing AF, or new-onset AF. We analyzed mortality at 3 months, 6 months, and 1 year.Results: Overall, 31,562 (65.73%) patients had no AF, 4877 (10.16%) had pre-existing AF, and 11,579 (24.11%) had new-onset AF. Median ages were 61.47 years (no AF), 76.12 years (pre-existing AF), and 75.26 years (new-onset AF). New-onset AF was associated with the highest mortality rates: 25.16% at 3 months, 29.23% at 6 months, and 34.04% at 1 year, compared to 17.94%, 22.55%, and 28.52% for pre-existing AF, and 14.54%, 17.25%, and 20.69% for no AF respectively (p < 0.001 for all). Multivariate Cox regression indicated that new-onset AF significantly increased the risk of 1-year mortality by 15.5% compared to no AF (HR: 1.155, 95% CI: 1.101– 1.212; p < 0.001) and by 23.9% compared to pre-existing AF (HR: 1.239, 95% CI: 1.164– 1.318; p < 0.001). Kaplan-Meier analysis confirmed lower survival probabilities for new-onset AF over one year compared to the other groups (p < 0.001).Conclusion: In patients with critical illness, new-onset AF is associated with an increased risk of mortality compared with pre-existing AF or no AF.Keywords: atrial fibrillation, mortality, intensive care unit

Shuang Wu,1,2,&ast; Xing-chen Zhou,1,2,&ast; Tao Li,1,2,&ast; Jia-yu Sun,1,2 Long-hao Chen,1,2 Zi-cheng Wei,1,2 Kai-zheng Wang,1,2 Shuang-wei Hong,1,2 Hui-nan Xu,1,2 Zhi-zhen Lv,1,2 Li-jiang Lv1,2 1The Third Affiliated Hospital of Zhejiang, Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, People’s Republic of China; 2The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-zhen Lv; Li-jiang Lv, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, People’s Republic of China, Tel +86-13750821128; +86-13958107858, Email lvzhizhen1992@163.com; lvlijiang0288@163.comBackground: Previous metabolomics studies have indicated a close association between blood metabolites and pain. However, the causal relationship between blood metabolites and spinal pain (SP) remains unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 452 blood metabolites and SP.Methods: We used bidirectional two-sample MR analysis to assess the causal relationship between blood metabolites and SP, including neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). Genome-wide association studies (GWAS) data for 452 metabolites (7,824 participants) were used as exposure variables. Summary data for NP were obtained from the UK Biobank, for TSP from the FinnGen Biobank, and for LBP from both the UK Biobank and the FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. Inverse-variance weighting (IVW) was used to estimate the causal relationships between metabolites and SP, complemented by various sensitivity analyses to account for pleiotropy and heterogeneity, ensuring robust results.Results: The IVW analysis identified 155 metabolites associated with SP risk and 142 metabolites influenced by SP. No significant heterogeneity or horizontal pleiotropy was observed through other analytical methods.Conclusion: This study demonstrates potential causal effects between blood metabolites and SP, providing new insights into the pathogenesis of SP. These findings lay a theoretical foundation for preventing and treating SP through targeted interventions on specific blood metabolites, potentially elucidating underlying biological mechanisms.Keywords: spinal pain, neck pain, thoracic spine pain, low back pain, back pain, blood metabolites, Mendelian randomization, causality

Introduction/purpose: The aim of this paper is to obtain quantitative and qualitative indicators of vehicle condition and reliability based on operational data which can be used to determine the optimal periodicity of preventive maintenance for special purpose vehicles, and to more accurately manage the maintenance process and the operational readiness of these vehicles. Methods: Based on operational failure data and statistical methods, a mathematical model of the reliability of special purpose vehicles was determined. Using this model and operational data, the periodicity of preventive maintenance for the vehicles was determined through multicriteria optimization, considering both readiness and minimum maintenance costs. The same methodology was applied to determine the optimal preventive maintenance periodicity for 15 components of the mechanical system of special purpose vehicles. A group analysis was conducted using Minitab 15 statistical software, based on the theory of similarity in preventive maintenance periodicity for the 15 components, and a statistical analysis of the conducted research was performed using Minitab 16 statistical software. Results: Models for preventive maintenance of special purpose vehicles were developed based on the recorded vehicle failures and the failures of fifteen vital components. A group analysis grouped the fifteen components into optimal maintenance groups, similar in terms of working time between failures. The statistical analysis of the research determined a functional relationship for the optimal periodicity of preventive maintenance for special purpose vehicles. Conclusion: The maintenance periodicity obtained through multi-criteria analysis is optimal, as it achieves satisfactory vehicle readiness with optimal maintenance costs. The statistical analysis of the research concluded that the maintenance periodicities of the vehicle components are different. In both fleets, the engine and the transmission block have the longest maintenance intervals. The research results can be used to rationalize the existing preventive maintenance concept.

Qiu-Xia Jiang,1 Li-Jing Shi,1 Xiu-Yang Hong,2 Yu-Qin Zhu,3 Qiu-Ling Guo,1 Wen Xie,1 Guo-Rong Lyu4 1Department of Ultrasound, Quan-Zhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 2Department of Women Health Care, Quan-Zhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 3Department of Pathology, Quan-Zhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 4Department of Ultrasound, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of ChinaCorrespondence: Guo-Rong Lyu, Email lgr_feus@sina.comAbstract: Primary breast Burkitt lymphoma (PB-BL) is an exceedingly rare form of primary breast lymphoma. Ultrasonography is the preferred modality for diagnosing breast diseases; however, the ultrasonic features of Burkitt lymphoma have rarely been reported. Herein, we report a case of ultrasonically diagnosed bilateral PB-BL in a lactating patient and present a literature review. A 28-year-old female patient experienced bilateral breast engorgement starting more than a month after childbirth. At three months postpartum, the patient experienced extreme bilateral breast engorgement, with the skin appearing dark purple and jaundiced. Based on the imaging diagnosis, pathological, immunohistochemical, and molecular biological findings, she was diagnosed with Burkitt lymphoma involves bilateral breasts, right adrenal glands, uterus, and multiple bones. After 4 cycles of combination chemotherapy, the tumor basically disappeared, and then after autologous stem cell transplantation and one cycle of combination chemotherapy, the patient is generally in good condition and is under follow-up. We found that the ultrasonic characteristics of PB-BL are different from those of common breast cancer or lactation mastitis. PB-BL lesions are often multiple, large masses, and even involve the whole breast. The characteristic reticular structures are common in lesions, and irregular hyperechoic masses can be seen around it. The mass has abundant peripheral and internal blood flow signals, but internal calcification and attenuated posterior echoes of masses are rarely observed. Thus, the ultrasonic features of breast Burkitt lymphoma are somewhat specific and understanding these features is conducive to its early identification.Keywords: Burkitt lymphoma, ultrasonography, case report

Guo-Hong Zhao,1 Jin-Da Wang,1 Mei-Rui Liu,2,3 Li-Jun Zhang,4 Yan Sun,5 Kai Cao6 1Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pulmonary Rehabilitation, Emergency General Hospital, Beijing, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, Hebei, People’s Republic of China; 4Department of Obstetrics and Gynecology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 5Department of Ophthalmology, Linyi Hospital of Traditional Chinese Medicine, Linyi, Shandong, People’s Republic of China; 6Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Kai Cao, Email crcteam@163.comObjective: To explore the distribution and influence factors of non-invasive tear film break-up time (NIBUT) in children.Methods: This is a hospital-based cross-sectional study. Spherical equivalent error (SER) was measured with cycloplegia. NIBUT was measured by an ocular surface integrated analyzer.Results: A total of 1269 children (1269 eyes) were included in this study. Participants’ median age was 11 (range 6– 18) years. 47.1% (598/1269) of participants were boys. The median NIBUT of myopic children and non-myopic children were 9.9 seconds (s) (Inter-quartile range, IQR: 6.4 to 16.1) and 10.9 s (IQR: 8.8 to 17.9), respectively, which was statistically significant (p = 0.004). In myopic children, 49.9% (573/1148) were able to achieve NIBUT of 10 s or more, compared to 67.8% (82/121) in non-myopic children, which was statistically significant (p < 0.001). There were 41 (3.57%) children in the myopic group and none (0%) in the non-myopic group with dry eye disease (p = 0.028). There was a positive correlation between NIBUT and age: NIBUT = 9.256 + 0.352&ast;Age. 71.8% (824/1148) of myopic children used electronic products almost every day, compared to 37.2% (45/121) of non-myopic children, which was statistically significant (p < 0.001).Conclusion: The NIBUT of myopic children was significantly shorter than that of non-myopic children. Children with myopia are more likely to have dry eyes. NIBUT increases with age. High frequency of electronic product use may be an important cause to NIBUT shortening in children.Keywords: Tear film break-up time, dry eye, Myopia, ocular surface, children

This article explores the dynamics of inter-generational conversations between queer and trans youth and queer and trans adults through an analysis of a routine segment on the reality show, RuPaul's Drag Race. At the end of each season, the drag queen contestants are asked to give a piece of advice to photos of their younger selves and, by proxy, the young people who may be watching the show from home. This article positions this segment as a pedagogical moment where the queens are forced into the role of teacher. However, like the categories of child and youth, RuPaul's request of the queens is not as innocent as it appears. In turning to address children directly, the queens must reckon with cis-heteronormative expectations of how adults can speak to children, about what topics can be discussed, and the tones such conversation must take. To explore these issues, the article examines this segment alongside scholarship about drag and ballroom cultures to place the show within larger contexts of queer and trans kinship structures. Then, turning to queer and trans studies in education and queer and trans childhood and youth studies, the essay examines the factors impacting how and when queer and trans youth and adults are allowed to be in conversation with youth, if at all.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Background Primary prevention strategies for cardiovascular disease (CVD) conventionally rely on 10-year risk estimates of major adverse cardiovascular events (MACE). However, communicating longer-term total CVD risk may better facilitate informed preventive decisions. Therefore, we aimed to quantify how well 10-year observed incidence reflects 20-year observed incidence and how MACE reflects total CVD events across demographic groups, using observations in long-term prospective data.Methods In individuals aged 40–79 without CVD or diabetes from the population-based EPIC-Norfolk cohort, we compared the first occurrence of 10 and 20 years (1) 3-point MACE events (non-fatal myocardial infarction+non-fatal stroke+fatal CVD) and (2) total CVD events (all non-fatal and fatal CVD events leading to hospitalisation), stratified by sex and age.Results Among 22 569 participants (57% women), incident 10-year and 20-year 3-point MACE was 5.3% and 15.5%, respectively, yielding 20/10 year ratios from 2.2 (in older men) to 4.5 (in younger women). Total CVD increased from 10.5% at 10 years to 26.9% at 20 years, with ratios ranging from 1.9 (older men) to 3.9 (younger women). Ratios between 10-year MACE and 20-year total CVD varied substantially, ranging from 3-fold in (older men) to 10-fold (younger women).Conclusions The observed incidence of CVD roughly triples from 10 to 20 years of follow-up, with 10-year MACE observations underestimating 20-year total CVD burden by a factor ranging from 3 (older men) to 10 (younger women). These findings highlight the limitations of communicating 10-year MACE risk assessments to facilitate informed decisions in longer-term CVD prevention—particularly in younger women.

ABSTRACTInfectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.

Supernova (SN) H0pe was discovered as a new transient in James Webb Space Telescope (JWST) NIRCam images of the galaxy cluster PLCK G165.7+67.0 taken as part of the Prime Extragalactic Areas for Reionization and Lensing Science (PEARLS) JWST GTO program (ID 1176) on 2023 March 30. The transient is a compact source associated with a background galaxy that is stretched and triply imaged by the strong gravitational lensing of the cluster. This paper reports spectra in the 950- 1370 nm observer frame of two of the galaxy images obtained with Large Binocular Telescope (LBT) Utility Camera in the Infrared (LUCI) in long-slit mode two weeks after the JWST observations. The individual and average spectra show the [O′ ¯II] λλ3727,3730 doublet and the Balmer and 4000 Åbreaks at redshift z = 1.783 ± 0.002. The code investigating galaxy emission (CIGALE) best-fit model of the spectral energy distribution indicates that the host galaxy of SN H0pe is massive (Mstar ≃ 6 × 1010 M⊙ after correcting for a magnification factor μ ~ 7) with a predominantly intermediate-age (~2 Gyr) stellar population, moderate extinction, and a magnification-corrected star formation rate ≃13 M⊙ yr-1, consistent with being below the main sequence of star formation. These properties suggest that H0pe might be a type Ia SN. Additional observations of SN H0pe and its host recently carried out with JWST (JWST-DD-4446; PI: B. Frye) will be able to both determine the SN classification and confirm its association with the galaxy analyzed in this work.

A hundred years after the discovery of the Merensky Reef in 1924, it is appropriate to present the new mineral andrieslombaardite in honour of Andries Frederik Lombaard who was instrumental in its discovery. Andrieslombaardite, RhSbS, was first described as an unknown mineral from placer deposits associated with the Tulameen Alaskan-Uralian type complex, British Colombia, Canada (Raicevic and Cabri, 1976) but has since been reported from several other deposits including the platiniferous Driekop, Mooihoek, and Onverwacht pipes in the eastern Bushveld Complex, South Africa. The mineral and the name were approved by the Commission on New Minerals Nomenclature and Classification (CNMNC) of the International Mineralogical Association (IMA no. 2022-076) based on data in the co-type samples from Onverwacht and a co-type sample from the Yubdo stream, Birbir River, Ethiopia. Andrieslombaardite in the Onverwacht sample is a single 8 x 20 μm grain attached to laurite in a matrix of altered silicate and Fe-oxyhydroxide minerals. In the Yubdo samples, there are many grains of pale brownish gray andrieslombaardite up to 25 x 55 μm in size, included in Pt-Fe alloys, some associated with erlichmanite, and others attached to bornite and chalcopyrite. The reflectance values (R%) measured in air and in oil at the COM wavelengths are 48.3 and 33.0 (470 nm), 49.3 and 34.0 (546 nm), 51.0 and 35.9 (589 nm), and 51.8 and 36.7 (650 nm). The colour values x, y, Y, λd, and Pe in air are 0.317, 0.322, 50.3, 580, and 3.2, and in oil are 0.319, 0.324, 35.6, 579, and 4.5. The composition of andrieslombaardite is ideally RhSbS, but it contains variable amounts of Fe, Pt, Pd, and Ir that may substitute for Rh. The mineral is cubic with unit-cell dimensions of a = 6.0278(4) Å, V = 219.01(6) Å3 and Z = 4. It was synthesised at 400 and 550°C using stoichiometric elemental amounts. It is a member of the cobaltite group. The mineralisation of the intrusive dunite pipes was probably introduced at high temperatures, under magmatic conditions. The primary assemblages were to a certain degree overprinted and redistributed by low-temperature hydrothermal fluids. The Pt-Fe alloys from Yubdo containing PGM inclusions such as andrieslombaardite in the Yubdo-Alaskan-type complex were formed at some post-magmatic stage owing to PGE remobilisation during hydrothermal or metamorphic episodes.

Background: Detailed spectroscopy of neutron-rich, heavy, deformed nuclei is of broad interest for nuclear astrophysics and nuclear structure. Nuclei in the r-process path and following freeze-out region impact the resulting r-process abundance distribution, and the structure of nuclei midshell in both proton and neutron number helps to understand the evolution of subshell gaps and large deformation in these nuclei. Purpose: We aim to improve the understanding of the nuclear structure of Gd160, specifically the Kπ=4+ bands, as well as study the β decay of Eu160 into Gd160. Methods: High-statistics decay spectroscopy of Gd160 resulting from the β-decay of Eu160 was collected using the GRIFFIN spectrometer at the TRIUMF-ISAC facility. Results: Two new excited states and ten new transitions were observed in Gd160. The β-decaying half-lives of the low- and high-spin isomers in Eu160 were determined, and the low-spin state's half-life was measured to be t1/2=26.0(8) s, ≈16% shorter than previous measurements. Lifetimes of the two Kπ=4+ bandheads in Gd160 were measured for the first time, as well as γ-γ angular correlations and mixing ratios of intense transitions out of those bandheads. Conclusions: Lifetimes and mixing ratios suggest that the hexadecapole phonon model of the Kπ=4+ bandheads in Gd160 is preferred over a simple two-state strong mixing scenario, although further theoretical calculations are needed to fully understand these states. Additionally, the 1999.0-keV state in Gd160 heavily populated in β decay is shown to have positive parity, which raises questions regarding the structure of the high-spin β-decaying state in Eu160.