bluuebunny/crossref_metadata_2025 huggingface dataset:
GPMeta: a GPU-accelerated method for ultrarapid pathogen identification from metagenomic sequences
Authors: Wang Xuebin , Wang Taifu , Xie Zhihao , Zhang Youjin , Xia Shiqiang , Sun Ruixue , He Xinqiu , Xiang Ruizhi , Zheng Qiwen , Liu Zhencheng , Wang Jin’An , Wu Honglong , Jin Xiangqian , Chen Weijun , Li Dongfang , He Zengquan
Published: March 2023

Metagenomic sequencing (mNGS) is a powerful diagnostic tool to detect causative pathogens in clinical microbiological testing owing to its unbiasedness and substantially reduced costs. Rapid and accurate classification of metagenomic sequences is a critical procedure for pathogen identification in dry-lab step of mNGS test. However, clinical practices of the testing technology are hampered by the challenge of classifying sequences within a clinically relevant timeframe. Here, we present GPMeta, a novel GPU-accelerated approach to ultrarapid pathogen identification from complex mNGS data, allowing users to bypass this limitation. Using mock microbial community datasets and public real metagenomic sequencing datasets from clinical samples, we show that GPMeta has not only higher accuracy but also significantly higher speed than existing state-of-the-art tools such as Bowtie2, Bwa, Kraken2 and Centrifuge. Furthermore, GPMeta offers GPMetaC clustering algorithm, a statistical model for clustering and rescoring ambiguous alignments to improve the discrimination of highly homologous sequences from microbial genomes with average nucleotide identity >95%. GPMetaC exhibits higher precision and recall rate than others. GPMeta underlines its key role in the development of the mNGS test in infectious diseases that require rapid turnaround times. Further study will discern how to best and easily integrate GPMeta into routine clinical practices. GPMeta is freely accessible to non-commercial users at https://github.com/Bgi-LUSH/GPMeta.
METTL3 promotes proliferation of goat endometrial epithelial cells by regulating CTGF in an m6A-dependent manner
Authors: Sun Ya , Zhang Xin-Cheng , Li Meng-Die , Bu Li-Ge , Wang Bo , Li Ting-Yue , Ding Nai-Zheng , Ni Hua
Published: March 2023

N6-methyladenosine (m6A), an epigenetic modification on RNAs, plays an important role in many physiological and pathological processes. However, the involvement of m6A in goat uterus during early pregnancy remains largely unknown. In this study, we found that the total m6A level was increasing in goat uterus as early pregnancy progressed. Methyltransferase-like 3 (METTL3) is a core catalytic subunit of the m6A methyltransferase. We thus determined the expression and regulation of METTL3 in goat uterus. METTL3 was highly expressed in the luminal and glandular epithelia from day 16 (D16) to D25 of pregnancy, and it could be up-regulated by estrogen and progesterone in goat uterus and primary endometrial epithelial cells (EECs). In EECs, knockdown or overexpression of METTL3 resulted in a significant decrease or increase of cell proliferation, respectively. METTL3 knockdown reduced the m6A level of not only total RNA but also connective tissue growth factor (CTGF) mRNA. Luciferase assay suggested that METTL3 might target the potential m6A sites in the 3’untranslated region (3’UTR) of CTGF mRNA. Moreover, METTL3 positively regulated CTGF expression, and CTGF knockdown significantly counteracted the promoting effect of METTL3 overexpression on EEC proliferation. Collectively, METTL3 is dynamically expressed in goat uterus and can affect EEC proliferation by regulating CTGF in an m6A-dependent manner. Our results will lay a foundation for further studying the crucial mechanism of METTL3-mediated m6A modification in goat uterus during early pregnancy.
Clinical features and prognostic factors in adults with viral meningitis
Authors: Petersen Pelle Trier , Bodilsen Jacob , Jepsen Micha Phill Grønholm , Larsen Lykke , Storgaard Merete , Hansen Birgitte Rønde , Helweg-Larsen Jannik , Wiese Lothar , Lüttichau Hans Rudolf , Andersen Christian Østergaard , Nielsen Henrik , Brandt Christian Thomas ,   for the Danish Study Group of Infections of the Brain (DASGIB)
Published: March 2023

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined.

This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1–4) 30 days after discharge were examined by modified Poisson regression.

In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27–44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3–7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60–358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95–1.88) for enteroviruses, 1.55 (95% CI 1.00–2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98–2.33) for varicella-zoster virus and 1.37 (95% CI 0.61–3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03–1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
Current understanding of the chronic stress response to burn injury from human studies
Authors: Osborne Tyler , Wall Bradley , Edgar Dale W , Fairchild Timothy , Wood Fiona
Published: March 2023

There is a marked inflammatory and hypermetabolic response following a burn injury. The interlinked responses are more pronounced than for other forms of trauma and can persist for ≥3 years post-injury in burned patients. After a burn, patients have an increased risk of diseases of ageing including cancer, diabetes and cardiovascular disease, highlighting the need for effective long-term strategies to ameliorate the stress response post-burn. Current therapeutic strategies for post-burn recovery include removal of damaged tissue with surgical excision and wound repair, nutritional supplementation and rehabilitative exercise. These strategies aim to minimize the hypermetabolic and inflammatory responses, as well as reducing the loss of lean body mass. This review briefly summarises the inflammatory and hypermetabolic responses and provides an update on the current therapeutic strategies for burned patients. The review examines the persistent nutritional challenge of ensuring sufficient energy intake of each macronutrient to fuel the hypermetabolic and counteract the catabolic response of burn injury, whilst reducing periods of hyperglycaemia and hypertriglyceridemia. Patients require individualized treatment options tailored to unique systemic responses following a burn, facilitated by a precision medicine approach to improve clinical and physiological outcomes in burned patients. Thus, this review discusses the utility of metabolic flexibility assessment to aid clinical decision making and prescription relating to nutritional supplementation and rehabilitative exercise in the burned patient.
Current landscape of clinical trials for vitiligo: improving outcome standardization and trial diversity
Authors: Mulligan Kathleen M , O’Connell Katie A , Coleman Madeline S , da Silva Alexandra , Reddy Minal , Kim Lori , Bazzi Nagham , Afrin Antara , Dellavalle Robert P
Published: March 2023

We assessed interventional clinical trials for vitiligo from 2015 to 2021 noting patient demographics, intervention types and reported outcomes. We discuss that across studies, more consistent documentation of patient characteristics as well as more variable intervention types may broaden trial generalizability and provide benefit to more patients.
Early motor skill acquisition in healthy older adults: brain correlates of the learning process
Authors: Durand-Ruel Manon , Park Chang-hyun , Moyne Maëva , Maceira-Elvira Pablo , Morishita Takuya , Hummel Friedhelm C
Published: March 2023

Motor skill learning is a crucial process at all ages. However, healthy aging is often accompanied by a reduction in motor learning capabilities. This study characterized the brain dynamics of healthy older adults during motor skill acquisition and identified brain regions associated with changes in different components of performance. Forty-three subjects participated in a functional magnetic resonance imaging study during which they learned a sequential grip force modulation task. We evaluated the continuous changes in brain activation during practice as well as the continuous performance-related changes in brain activation. Practice of the motor skill was accompanied by increased activation in secondary motor and associative areas. In contrast, visual and frontal areas were less recruited as task execution progressed. Subjects showed significant improvements on the motor skill. While faster execution relied on parietal areas and was inversely associated with frontal activation, accuracy was related to activation in primary and secondary motor areas. Better performance was achieved by the contribution of parietal regions responsible for efficient visuomotor processing and cortical motor regions involved in the correct action selection. The results add to the understanding of online motor learning in healthy older adults, showing complementary roles of specific networks for implementing changes in precision and speed.
The cortical hypogyrification pattern in antipsychotic-naive first-episode schizophrenia
Authors: Gao Xin , Yao Li , Li Fei , Yang Chengmin , Zhu Fei , Gong Qiyong , Lui Su
Published: March 2023

Schizophrenia is thought to be a neurodevelopmental disease with high genetic heritability, and evidence from neuroimaging studies has consistently shown widespread cortical local gyrification index (LGI) alterations; however, genes accounting for LGI alterations in schizophrenia remain unknown. The present study examined the LGI alterations in first-episode antipsychotic-naive schizophrenia compared with controls (235 patients and 214 controls); transcription-neuroimaging association analysis was used to evaluate the relationship between LGI deficits and specific risk genes. The expression profiles of 232 schizophrenia risk genes were extracted from six donated normal brains from the Allen Human Brain Atlas database. The correlation between LGI alterations and clinical symptoms was also tested. We found lower LGI values involved in frontotemporal regions and limbic systems. Nonparametric correlation analysis showed that 83 risk genes correlated with the hypogyrification pattern in schizophrenia. These identified risk genes were functionally enriched for the development of the central nervous system. The LGI in the left superior temporal gyrus was negatively associated with Positive and Negative Syndrome Scale negative symptoms. In summary, the present study provides a set of risk genes possibly related to the hypogyrification pattern in antipsychotic-naive first-episode schizophrenia, which could help to unveil the neurobiological underpinnings of cortical impairments in early-stage schizophrenia.
Opioid Injection-Associated Bacterial Infections in England, 2002–2021: A Time Series Analysis of Seasonal Variation and the Impact of Coronavirus Disease 2019
Authors: Lewer Dan , Brothers Thomas D , Croxford Sara , Desai Monica , Emanuel Eva , Harris Magdalena , Hope Vivian D
Published: March 2023

Background

Bacterial infections cause substantial pain and disability among people who inject drugs. We described time trends in hospital admissions for injecting-related infections in England.

Methods

We analyzed hospital admissions in England between January 2002 and December 2021. We included patients with infections commonly caused by drug injection, including cutaneous abscesses, cellulitis, endocarditis, or osteomyelitis, and a diagnosis of opioid use disorder. We used Poisson regression to estimate seasonal variation and changes associated with coronavirus disease 2019 (COVID-19) response.

Results

There were 92 303 hospital admissions for injection-associated infections between 2002 and 2021. Eighty-seven percent were skin, soft-tissue, or vascular infections; 72% of patients were male; and the median age increased from 31 years in 2002 to 42 years in 2021. The rate of admissions reduced from 13.97 per day (95% confidence interval [CI], 13.59–14.36) in 2003 to 8.94 (95% CI, 8.64–9.25) in 2011, then increased to 18.91 (95% CI, 18.46–19.36) in 2019. At the introduction of COVID-19 response in March 2020, the rate of injection-associated infections reduced by 35.3% (95% CI, 32.1–38.4). Injection-associated infections were also seasonal; the rate was 1.21 (95% CI, 1.18–1.24) times higher in July than in February.

Conclusions

This incidence of opioid injection-associated infections varies within years and reduced following COVID-19 response measures. This suggests that social and structural factors such as housing and the degree of social mixing may contribute to the risk of infection, supporting investment in improved social conditions for this population as a means to reduce the burden of injecting-related infections.
Seasonal, environmental and individual effects on hypoxia tolerance of eastern sand darter (Ammocrypta pellucida)
Authors: Firth Britney L , Craig Paul M , Drake D Andrew R , Power Michael
Published: March 2023

Metabolic rate and hypoxia tolerance are highly variable among individual fish in a stable environment. Understanding the variability of these measures in wild fish populations is critical for assessing adaptive potential and determining local extinction risks as a result of climate-induced fluctuations in temperature and hypoxic conditions. We assessed the field metabolic rate (FMR) and two hypoxia tolerance metrics, oxygen pressure at loss of equilibrium (PO2 at LOE) and critical oxygen tolerance (Pcrit) of wild-captured eastern sand darter (Ammocrypta pellucida), a threatened species in Canada, using field trials (June to October) that encompassed ambient water temperatures and oxygen conditions typically experienced by the species. Temperature was significantly and positively related to hypoxia tolerance but not FMR. Temperature alone explained 1%, 31% and 7% of the variability observed in FMR, LOE, and Pcrit, respectively. Environmental and fish-specific factors such as reproductive season and condition explained much of the residual variation. Reproductive season significantly affected FMR by increasing it by 159–176% over the tested temperature range. Further understanding the impact of reproductive season on metabolic rate over a temperature range is crucial for understanding how climate change could impact species fitness. Among-individual variation in FMR significantly increased with temperature while among-individual variation in both hypoxia tolerance metrics did not. A large degree of variation in FMR in the summer might allow for evolutionary rescue with increasing mean and variance of global temperatures. Findings suggest that temperature may be a weak predictor in a field setting where biotic and abiotic factors can act concurrently on variables that affect physiological tolerance.
The Silk roads: phylogeography of Central Asian dice snakes (Serpentes: Natricidae) shaped by rivers in deserts and mountain valleys
Authors: Jablonski Daniel , Mebert Konrad , Masroor Rafaqat , Simonov Evgeniy , Kukushkin Oleg , Abduraupov Timur , Hofmann Sylvia
Published: March 2023

Influenced by rapid changes in climate and landscape features since the Miocene, widely distributed species provide suitable models to study the environmental impact on their evolution and current genetic diversity. The dice snake Natrix tessellata, widely distributed in the Western Palearctic is one such species. We aimed to resolve a detailed phylogeography of N. tessellata with a focus on the Central Asian clade with 4 and the Anatolia clade with 3 mitochondrial lineages, trace their origin, and correlate the environmental changes that affected their distribution through time. The expected time of divergence of both clades began at 3.7 Mya in the Pliocene, reaching lineage differentiation approximately 1 million years later. The genetic diversity in both clades is rich, suggesting different ancestral areas, glacial refugia, demographic changes, and colonization routes. The Caspian lineage is the most widespread lineage in Central Asia, distributed around the Caspian Sea and reaching the foothills of the Hindu Kush Mountains in Afghanistan, and Eastern European lowlands in the west. Its distribution is limited by deserts, mountains, and cold steppe environments. Similarly, Kazakhstan and Uzbekistan lineages followed the Amu Darya and the Syr Darya water systems in Central Asia, with ranges delimited by the large Kyzylkum and Karakum deserts. On the western side, there are several lineages within the Anatolia clade that converged in the central part of the peninsula with 2 being endemic to Western Asia. The distribution of both main clades was affected by expansion from their Pleistocene glacial refugia around the Caspian Sea and in the valleys of Central Asia as well as by environmental changes, mostly through aridification.
Association of accompanying dyspnoea with diagnosis and outcome of patients presenting with acute chest discomfort
Authors: Boeddinghaus Jasper , Nestelberger Thomas , Koechlin Luca , Lopez-Ayala Pedro , Wussler Desiree , Mais Maximilian , Zwimpfer Luca , Zimmermann Tobias , Wildi Karin , Giménez Maria Rubini , Strebel Ivo , Miró Òscar , Martin-Sanchez F Javier , Parenica Jiri , Keller Dagmar I , Gualandro Danielle M , Nickel Christian H , Bingisser Roland , Christ Michael , Mueller Christian ,   for the APACE investigators
Published: March 2023

Aims

The presence of accompanying dyspnoea is routinely assessed and common in patients presenting with acute chest pain/discomfort to the emergency department (ED). We aimed to assess the association of accompanying dyspnoea with differential diagnoses, diagnostic work-up, and outcome.

Methods and results

We enrolled patients presenting to the ED with chest pain/discomfort. Final diagnoses were adjudicated by independent cardiologists using all information including cardiac imaging. The primary diagnostic endpoint was the final diagnosis. The secondary diagnostic endpoint was the performance of high-sensitivity cardiac troponin (hs-cTn) and the European Society of Cardiology (ESC) 0/1h-algorithms for the diagnosis of myocardial infarction (MI). The prognostic endpoints were cardiovascular and all-cause mortality at two years. Among 6045 patients, 2892/6045 (48%) had accompanying dyspnoea. The prevalence of acute coronary syndrome (ACS) in patients with vs. without dyspnoea was comparable (MI 22.4% vs. 21.9%, P = 0.60, unstable angina 8.7% vs. 7.9%, P = 0.29). In contrast, patients with dyspnoea more often had cardiac, non-coronary disease (15.3% vs. 10.2%, P < 0.001). Diagnostic accuracy of hs-cTnT/I concentrations was not affected by the presence of dyspnoea (area under the curve 0.89–0.91 in both groups), and the safety of the ESC 0/1h-algorithms was maintained with negative predictive values >99.4%. Accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death at two years [hazard ratio 1.813 (95% confidence intervals, 1.453–2.261, P < 0.01)].

Conclusion

Accompanying dyspnoea was not associated with a higher prevalence of ACS but with cardiac, non-coronary disease. While the safety of the diagnostic work-up was not affected, accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587
Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure
Authors: Kvandová Miroslava , Rajlic Sanela , Stamm Paul , Schmal Isabella , Mihaliková Dominika , Kuntic Marin , Bayo Jimenez Maria Teresa , Hahad Omar , Kollárová Marta , Ubbens Henning , Strohm Lea , Frenis Katie , Duerr Georg Daniel , Foretz Marc , Viollet Benoit , Ruan Yue , Jiang Subao , Tang Qi , Kleinert Hartmut , Rapp Steffen , Gericke Adrian , Schulz Eberhard , Oelze Matthias , Keaney John F , Daiber Andreas , Kröller-Schön Swenja , Jansen Thomas , Münzel Thomas
Published: March 2023

Aims

Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment.

Methods and results

Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting.

Conclusion

Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.
“It was a very awkward consultation because I didn’t know”—general practice staff experiences and challenges in providing healthcare to gender and sexual minority youth in Aotearoa New Zealand
Authors: Carroll Rona , Morgan Sonya J , Ker Alex , Garrett Susan M , Rose Sally B , Gardiner Tracey , McKinlay Eileen M
Published: March 2023

Background

Rainbow young people (RYP; people of diverse genders, sexualities, and variations in sex characteristics) face barriers accessing primary care, often report negative experiences and the need to educate clinicians on rainbow-specific issues. This study explores general practice staff views and experiences of providing care to RYP.

Methods

Three focus groups were held with staff from 5 general practices in an urban area of Aotearoa New Zealand (25 participants in total). Practices were purposively selected to include some known to be more “rainbow-friendly” seeing larger numbers of RYP and some with no particular focus on RYP. All members of each practice were invited to participate, including administration and reception staff. Focus groups were audio-recorded, transcribed, and analysed in NVivo using inductive thematic analysis.

Results

Four main themes were identified: (i) Practice experience, (ii) Feeling awkward, (iii) Knowledge and training, and (iv) Structural barriers. Differences were apparent in health provider knowledge, comfort, and experience in providing care to RYP. Participants identified a lack of knowledge and training and wanted more resources and education. Systems limitations were common (e.g. with IT systems for recording gender) and often contributed to awkward clinical encounters.

Conclusions

Participants recognized shortcomings in their training, knowledge, and level of confidence providing care to RYP and expressed a desire to improve their competency. Further work is needed to identify and trial practical strategies that help improve communication skills, knowledge, and the delivery of more equitable healthcare to RYP.
A Social Exergame Intervention to Promote Physical Activity, Social Support, and Well-Being in Family Caregivers
Authors: Lin Xin Yao , Zhang Lin , Yoon Saiyeon , Zhang Ruoying , Lachman Margie E
Published: March 2023

Background and Objectives

Family caregivers often experience a high level of stress, social isolation, a sedentary lifestyle, and poor mental and physical health. An exergame intervention was developed to promote physical activity and well-being in family caregivers and to test social support as a mechanism for behavior change.

Research Design and Methods

The current study was a randomized pilot trial (N = 76) to compare the effectiveness of Go&Grow (social vs nonsocial exergame) to promote well-being through increased social support and physical activity for family caregivers over a 6-week intervention.

Results

The treatment group increased significantly more than the control group in well-being (management of distress) and social support (satisfaction with contact quality). Social support served as a mechanism (mediator and moderator): The treatment group increased more than the control group in satisfaction with social contact quality, which led to more positive affect and less loneliness. Moreover, those in the treatment group who increased more in overall social support and knowing others’ experiences increased their steps more than those with less support, whereas the change in steps for the control group was not related to a support level. Those in the treatment group who used more social features of the app had a greater increase in steps compared with those who used it less.

Discussion and Implications

Social support in technology interventions is a promising direction to promote caregivers’ well-being and physical activity. Social support served as a mechanism of behavior change that can inform more engaging, sustainable, portable, and scalable interventions in the future for sedentary and socially isolated family caregivers.

Clinical Trial Registration Number: NCT05032872
Looking at the Data Governance Act and Beyond: How to Better Integrate Data Intermediaries in the Market Order for Data Sharing
Authors: Richter Heiko
Published: March 2023

This article enquires into the current prospects for data intermediaries in the context of competition and innovation policies. It asks what the conditions for and means to fulfil these promises are. This requires looking at the evolving legal framework – including the recently enacted Regulation (EU) 2022/686 ‘Data Governance Act’, which affects the incentives of data intermediaries and market actors. In particular, this article explores the obstacles for the establishment of data intermediaries, the context for their activities and the necessary conditions to be set, and complimentary measures to be taken to make them work. The overall goal is to discuss how the findings would translate into viable policy options to advance the regulatory framework that would contribute to an effective market design for data sharing.**
Critical thinking in musicians’ health education. Findings from four workshops with experts (Part I)
Authors: Matei Raluca , Phillips Keith
Published: March 2023

Health education encompasses building health knowledge, but also training skills such as critical thinking, that guide individuals’ ability to access, understand and use health information to take care of their own health (WHO, 1998). This study aimed to document expert discussions on the content of an ideal health education curriculum for higher music education (HME) students in the UK, integrating critical thinking. Four interdisciplinary workshops were conducted, where 67 experts in relevant fields discussed the content of four lists created based on literature reviews (cognitive biases, logical fallacies, critical appraisal tools and health topics). Notes taken during the discussions were thematically analysed. Most of the participants thought that the topics and tools were relevant. Two of four identified themes are reported in this paper, which represents the first of a two-part series: (1) critical thinking applied to health; and (2) misconceptions. This is the first attempt to document conversations aimed at using the applied knowledge of key stakeholders to discuss the content of an ideal health education curriculum integrating critical thinking, for conservatoire students.
Scaling from eDNA to biomass: controlling allometric relationships improves precision in bycatch estimation
Authors: Urban P , Bekkevold D , Degel H , Hansen B K , Jacobsen M W , Nielsen A , Nielsen E E
Published: March 2023

Environmental DNA (eDNA) has attracted interest in relation to fisheries, with its possibilities for species identification and promises for species quantification. In the context of fisheries catches, eDNA can be most useful for the estimation of bycatch proportions. The assessment of species mixtures in large catches (>1000 t) is challenging, especially when morphologically similar species are to be differentiated. We used an experimental set-up to simulate industrial sprat fishery catches, and tested two types of water (blood water and discharge water) derived from this simulated fishery for their suitability in reliable species quantification. We analysed nine mixtures of sprat and herring—the main bycatch species. Species-specific quantitative PCR was used for species identification and quantification. Species-to-species weight fractions and eDNA fractions in mixtures showed a strong correlation. Accounting for size-based differences in DNA abundance (allometrically scaled weight) reduced the estimated standard error on weight fraction prediction from 0.064 to 0.054 in blood water, and from 0.080 to 0.075 in discharge water when comparing the weight-based model with the allometrically scaled weight model, respectively. Accounting for allometric scalling in genetic analyses of fisheries process water can serve as a more precise method for the assessment of bycatch, thus in a wider sense improve the quality of fisheries-dependent data.
Blockchain-enabled immutable, distributed, and highly available clinical research activity logging system for federated COVID-19 data analysis from multiple institutions
Authors: Kuo Tsung-Ting , Pham Anh , Edelson Maxim E , Kim Jihoon , Chan Jason , Gupta Yash , Ohno-Machado Lucila ,   The R2D2 Consortium, Anderson David M , Balacha Chandrasekar , Bath Tyler , Baxter Sally L , Becker-Pennrich Andrea , Bell Douglas S , Bernstam Elmer V , Ngan Chau , Day Michele E , Doctor Jason N , DuVall Scott , El-Kareh Robert , Florian Renato , Follett Robert W , Geisler Benjamin P , Ghigi Alessandro , Gottlieb Assaf , Hinske Ludwig C , Hu Zhaoxian , Ir Diana , Jiang Xiaoqian , Kim Katherine K , Kim Jihoon , Knight Tara K , Koola Jejo D , Kuo Tsung-Ting , Lee Nelson , Mansmann Ulrich , Matheny Michael E , Meeker Daniella , Mou Zongyang , Neumann Larissa , Nguyen Nghia H , Nick Anderson , Ohno-Machado Lucila , Park Eunice , Paul Paulina , Pletcher Mark J , Post Kai W , Rieder Clemens , Scherer Clemens , Schilling Lisa M , Soares Andrey , SooHoo Spencer , Soysal Ekin , Steven Covington , Tep Brian , Toy Brian , Wang Baocheng , Wu Zhen R , Xu Hua , Yong Choi , Zheng Kai , Zhou Yujia , Zucker Rachel A
Published: March 2023

Objective

We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.

Materials and Methods

We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain for immutability, transparency, and high availability of research communication. We measured run-time efficiency of contract deployment, network transactions, and confirmed the accuracy of recorded logs compared to a centralized baseline solution.

Results

The smart contract deployment took 4.5 s on an average. The time to record an activity log on blockchain was slightly over 2 s, versus 5–9 s for baseline. For querying, each query took on an average less than 0.4 s on blockchain, versus around 2.1 s for baseline.

Discussion

The low deployment, recording, and querying times confirm the feasibility of our cross-cloud, blockchain-based federated data analysis system. We have yet to evaluate the system on a larger network with multiple nodes per cloud, to consider how to accommodate a surge in activities, and to investigate methods to lower querying time as the blockchain grows.

Conclusion

Blockchain technology can be used to support federated data analysis among multiple institutions.
Aorto-bronchial fistula masquerading as haematemesis: a rare late complication of thoracic aortic vascular grafts
Authors: Peacock Timothy , Limmer Alexandra M , Zahid Assad
Published: March 2023

Aorto-bronchial fistula is an exceedingly rare pathology with high mortality. Late vascular graft infection may occur secondary to haematogenous seeding of bacteria from a distant source such as gastrointestinal infection. We present an unusual case of aorto-bronchial fistula masquerading as haematemesis in a patient with sigmoid diverticulitis, and review the pathophysiology, diagnosis, surgical and endovascular management of aorto-bronchial fistulas.
Insights into the binding of Ag ions with SilE model peptides: an NMR and MS coupled approach
Authors: Zingale Gabriele Antonio , Oliveri Valentina , Grasso Giuseppe
Published: March 2023

The diffuse and renewed use of silver as antimicrobial agent has caused the development of resistance to silver ions in some bacterial strains, posing a serious threat for health systems. In order to cast light on the mechanistic features of resistance, here, we aimed to understand how silver interacts with the periplasmic metal-binding protein SilE which is engaged in bacterial silver detoxification. This aim was addressed by studying two peptide portions of SilE sequence (SP2 and SP3) that contain the putative motifs involved in Ag+ binding. We demonstrate that SP2 model peptide is involved in silver binding through its histidine and methionine residues in the two HXXM binding sites. In particular, the first binding site is supposed to bind the Ag+ ion in a linear fashion, while the second binding site complexes the silver ion in a distorted trigonal planar fashion. We propose a model where the SP2 peptide binds two silver ions when the concentration ratio Ag+/SP2 is ≥10.0. We also suggest that the two binding sites of SP2 have different affinity for silver. This evidence comes from the change in the path direction of the Nuclear Magnetic Resonance (NMR) cross-peaks upon the addition of Ag+. Here, we report the conformational changes of SilE model peptides occurring upon silver binding, monitored at a deep level of molecular details. This was addressed by a multifaceted approach, combining NMR, circular dichroism, and mass spectrometry experiments.
Knockdown of the SELENOK gene induces ferroptosis in cervical cancer cells
Authors: Abdurahman Anwar , Li Yu , Jia Shi-Zheng , Xu Xin-Wen , Lin Shu-Jing , Ouyang Pei , jun He Zhi , Zhang Zhong-Hao , Liu Qiong , Xu Ying , Song Guo-Li
Published: March 2023

Selenoprotein K (SELENOK) is one of the endoplasmic reticulum (ER) proteins that mainly functions in the regulation of ER stress, calcium flux, and antioxidant defense. Reactive oxygen species (ROS) is one of the key indicators of ferroptosis, and SELENOK inhibition could disrupt ROS balance, and consequently might cause ferroptosis. However, there are no previous studies about the mechanism of SELENOK in ferroptosis by regulating ROS. In this study, we report the effect of SELENOK inhibition on cell proliferation, viability, iron recycling–associated proteins, ROS, antioxidant enzymes, and lipid peroxidation of cervical cancer cells (HeLa cells). The results showed that ROS levels and iron-dependent lipid peroxidation were significantly enhanced, whereas cell viability and proliferation were significantly downregulated, and resulted in marked reductions in tumor size after SELENOK knockdown. SELENOK knockdown also caused steep decreases in glutathione peroxidase 4/glutathione levels and deterioration in ROS scavenging ability, and exacerbated ferroptosis in HeLa cells. Our findings elucidated that SELENOK knockdown could shrink tumor size by regulating ferroptosis, which might provide a theoretical basis for treating cervical cancer.
Tubulovascular protection from protease-activated receptor-1 depletion during AKI-to-CKD transition
Authors: Lok Sarah W Y , Yiu Wai Han , Zou Yixin , Xue Rui , Li Hongyu , Ma Jingyuan , Chen Jiaoyi , Chan Loretta Y Y , Lai Kar Neng , Tang Sydney C W
Published: March 2023

Background

Thromboembolic events are prevalent in chronic kidney disease (CKD) patients due to increased thrombin generation leading to a hypercoagulable state. We previously demonstrated that inhibition of protease-activated receptor-1 (PAR-1) by vorapaxar reduces kidney fibrosis.

Methods

We used an animal model of unilateral ischemia–reperfusion injury-induced CKD to explore the tubulovascular crosstalk mechanisms of PAR-1 in acute kidney injury (AKI)-to-CKD transition.

Results

During the early phase of AKI, PAR-1-deficient mice exhibited reduced kidney inflammation, vascular injury, and preserved endothelial integrity and capillary permeability. During the transition phase to CKD, PAR-1 deficiency preserved kidney function and diminished tubulointerstitial fibrosis via downregulated transforming growth factor-β/Smad signaling. Maladaptive repair in the microvasculature after AKI further exacerbated focal hypoxia with capillary rarefaction, which was rescued by stabilization of hypoxia-inducible factor and increased tubular vascular endothelial growth factor A in PAR-1-deficient mice. Chronic inflammation was also prevented with reduced kidney infiltration by both M1- and M2-polarized macrophages. In thrombin-induced human dermal microvascular endothelial cells (HDMECs), PAR-1 mediated vascular injury through activation of NF-κB and ERK MAPK pathways. Gene silencing of PAR-1 exerted microvascular protection via a tubulovascular crosstalk mechanism during hypoxia in HDMECs. Finally, pharmacologic blockade of PAR-1 with vorapaxar improved kidney morphology, promoted vascular regenerative capacity, and reduced inflammation and fibrosis depending on the time of initiation.

Conclusions

Our findings elucidate a detrimental role of PAR-1 in vascular dysfunction and profibrotic responses upon tissue injury during AKI-to-CKD transition and provide an attractive therapeutic strategy for post-injury repair in AKI.
Practice variation in re-resection for recurrent glioblastoma: A nationwide survey among Dutch neuro-oncology specialists
Authors: van Opijnen Mark P , de Vos Filip Y F , Nabuurs Rob J A , Snijders Tom J , Nandoe Tewarie Rishi D S , Taal Walter , Verhoeff Joost J C , van der Hoeven Jacobus J M , Broekman Marike L D
Published: March 2023

Background

Despite current best treatment options, a glioblastoma almost inevitably recurs after primary treatment. However, in the absence of clear evidence, current guidelines on recurrent glioblastoma are not well-defined. Re-resection is one of the possible treatment modalities, though it can be challenging to identify those patients who will benefit. Therefore, treatment decisions are made based on multidisciplinary discussions. This study aimed to investigate the current practice variation between neuro-oncology specialists.

Methods

In this nationwide study among Dutch neuro-oncology specialists, we surveyed possible practice variation. Via an online survey, 4 anonymized recurrent glioblastoma cases were presented to neurosurgeons, neuro-oncologists, medical oncologists, and radiation oncologists in The Netherlands using a standardized questionnaire on whether and why they would recommend a re-resection or not. The results were used to provide a qualitative analysis of the current practice in The Netherlands.

Results

The survey was filled out by 56 respondents, of which 15 (27%) were neurosurgeons, 26 (46%) neuro-oncologists, 2 (4%) medical oncologists, and 13 (23%) radiation oncologists. In 2 of the 4 cases, there appeared to be clinical equipoise. Overall, neurosurgeons tended to recommend re-resection more frequently compared to the other specialists. Neurosurgeons and radiation oncologists showed opposite recommendations in 2 cases.

Conclusions

This study showed that re-resection of recurrent glioblastoma is subject to practice variation both between and within neuro-oncology specialties. In the absence of unambiguous guidelines, we observed a relationship between preferred practice and specialty. Reduction of this practice variation is important; to achieve this, adequate prospective studies are essential.
On the biospheric effects of geomagnetic reversals
Authors: Pan Yongxin , Li Jinhua
Published: March 2023

This perspective argues an evolutionary effect of geomagnetic field reversals on life and highlights the urgency of multidisciplinary studies on the linkage between Earth's magnetic field and biosphere.
Chromoblastomycosis Treated With Posaconazole and Adjunctive Imiquimod: Lending Innate Immunity a Helping Hand
Authors: Logan Clare , Singh Manuraj , Fox Natalya , Brown Gordon , Krishna Sreedhar , Gordon Kristiana , Macallan Derek , Bicanic Tihana
Published: March 2023

Chromoblastomycosis (CBM) is a difficult-to-treat, chronic fungal infection of the skin and subcutaneous tissue. The evidence base for treatment is scarce, with no standardized therapeutic approach. Chronicity of CBM infection is postulated to be due in part to a failure of host cell–mediated immunity to generate a proinflammatory response sufficient for fungal clearance. We present a case of a chronic chromoblastomycosis lesion of the hand present for nearly 4 decades, previously refractory to itraconazole monotherapy, that was successfully treated with a combination of posaconazole and adjunctive immunotherapy with topical imiquimod, a Toll-like receptor 7 agonist. Serial biopsies and images demonstrate the clinical and histopathological improvement of the lesion. Randomized trials of antifungal therapy with adjunctive imiquimod are warranted to determine whether a combination of antifungal and host-directed therapy improves outcomes for this neglected tropical mycosis.
Flying cars economically favor battery electric over fuel cell and internal combustion engine
Authors: Liu Ming , Hao Han , Lin Zhenhong , He Xin , Qian Yuping , Sun Xin , Geng Jingxuan , Liu Zongwei , Zhao Fuquan
Published: March 2023

Flying cars, essentially vertical takeoff and landing aircraft (VTOL), are an emerging, disruptive technology that is expected to reshape future transportation. VTOLs can be powered by battery electric, fuel cell, or internal combustion engine, which point to entirely different needs for industry expertise, research & development, supply chain, and infrastructure supports. A pre-analysis of the propulsion technology competition is crucial to avoid potential wrong directions of research, investment, and policy making efforts. In this study, we comprehensively examined the cost competitiveness of the three propulsion technologies. Here we show that battery electric has already become the lowest-cost option for below-200-km VTOL applications, covering intra-city and short-range inter-city travels. This cost advantage can be robustly strengthened in the long term under various technology development scenarios. Battery energy density improvement is the key to reducing cost. In particular, a 600 Wh/kg battery energy density provides battery electric with all-range cost advantage, and promises high return in business. Fuel cell and internal combustion engine, under certain technology development scenarios, can obtain cost advantage in long-range applications, but face intense competition from ground transportation such as high-speed rail. The findings suggest a battery-electric-prioritized VTOL development strategy, and the necessity of developing VTOL-customized high-energy-density batteries.
Management of systemic sclerosis: British Society for Rheumatology guideline scope
Authors: Denton Christopher P , De Lorenzis Enrico , Roblin Elen , Goldman Nina , Alcacer-Pitarch Begonya , Blamont Emma , Buch Maya , Carulli Maresa , Cotton Caroline , del Galdo Francesco , Derrett-Smith Emma , Douglas Karen , Farrington Sue , Fligelstone Kim , Gompels Luke , Griffiths Bridget , Herrick Ariane , Hughes Michael , Pain Clare , Pantano Georgina , Pauling John , Prabu Athiveeraramapandian , O’Donoghue Nuala , Renzoni Elisabetta , Royle Jeremy , Samaranayaka Muditha , Spierings Julia , Tynan Aoife , Warburton Louise , Ong Voon
Published: March 2023

This guideline will provide a practical roadmap for management of SSc that builds upon the previous treatment guideline to incorporate advances in evidence-based treatment and increased knowledge about assessment, classification and management. General approaches to management as well as treatment of specific complications will be covered, including lung, cardiac, renal and gastrointestinal tract disease, as well as RP, digital vasculopathy, skin manifestations, calcinosis and impact on quality of life. It will include guidance related to emerging approved therapies for interstitial lung disease and account for National Health Service England prescribing policies and national guidance relevant to SSc. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence accreditation.