bluuebunny/crossref_metadata_2025 huggingface dataset:
The terrestrial end-Permian mass extinction in the paleotropics postdates the marine extinction
Authors: Wu Qiong , Zhang Hua , Ramezani Jahandar , Zhang Fei-fei , Erwin Douglas H. , Feng Zhuo , Shao Long-yi , Cai Yao-feng , Zhang Shu-han , Xu Yi-gang , Shen Shu-zhong
Published: January 2024

The end-Permian mass extinction was the most severe ecological event during the Phanerozoic and has long been presumed contemporaneous across terrestrial and marine realms with global environmental deterioration triggered by the Siberian Traps Large Igneous Province. We present high-precision zircon U-Pb geochronology by the chemical abrasion–isotope dilution–thermal ionization mass spectrometry technique on tuffs from terrestrial to transitional coastal settings in Southwest China, which reveals a protracted collapse of the Cathaysian rainforest beginning after the onset of the end-Permian marine extinction. Integrated with high-resolution geochronology from coeval successions, our results suggest that the terrestrial extinction occurred diachronously with latitude, beginning at high latitudes during the late Changhsingian and progressing to the tropics by the early Induan, spanning a duration of nearly 1 million years. This latitudinal age gradient may have been related to variations in surface warming with more degraded environmental conditions at higher latitudes contributing to higher extinction rates.
Coherent spore dispersion via drop-leaf interaction
Authors: Wu Zixuan , Basu Saikat , Kim Seungho , Sorrells Mark , Beron-Vera Francisco J. , Jung Sunghwan
Published: January 2024

The dispersion of plant pathogens, such as rust spores, is responsible for more than 20% of global crop yield loss annually. However, the release mechanism of pathogens from flexible plant surfaces into the canopy is not well understood. In this study, we investigated the interplay between leaf elasticity and rainfall, revealing how a flexible leaf structure can generate a lateral flow stream, with embedded coherent structures that enhance transport. We first modeled the linear coupling between drop momentum, leaf vibration, and the stream flux from leaf surfaces. With Lagrangian diagnostics, we further mapped out the nested coherent structures around the fluttering profile, providing a dynamical description for local spore delivery. We hope the mechanistic details extracted here can facilitate the construction of physically informed analytical models for local crop disease management.
Rescuing lung development through embryonic inhibition of histone acetylation
Authors: Stokes Giangela , Li Zhuowei , Talaba Nicole , Genthe William , Brix Maria B. , Pham Betty , Wienhold Mark D. , Sandok Gracia , Hernan Rebecca , Wynn Julia , Tang Haiyang , Tabima Diana M. , Rodgers Allison , Hacker Timothy A. , Chesler Naomi C. , Zhang Pan , Murad Rabi , Yuan Jason X. -J. , Shen Yufeng , Chung Wendy K. , McCulley David J.
Published: January 2024

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator geneSIN3Ain two patients with complex CDH. Tissue-specific deletion ofSin3ain mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonicSin3amutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in theSin3amouse model of CDH.
Type IV pili of
Enterobacteriaceae
species
Authors: Little Janay I. , Singh Pradip K. , Zhao Jinlei , Dunn Shakeera , Matz Hanover , Donnenberg Michael S.
Published: January 2024

Type IV pili (T4Ps) are surface filaments widely distributed among bacteria and archaea. T4Ps are involved in many cellular functions and contribute to virulence in some species of bacteria. Due to the diversity of T4Ps, different properties have been observed for homologous proteins that make up T4Ps in various organisms. In this review, we highlight the essential components of T4Ps, their functions, and similarities to related systems. We emphasize the unique T4Ps of enteric pathogens within the
Enterobacteriaceae
family, which includes pathogenic strains of
Escherichia coli
and
Salmonella
. These include the bundle-forming pilus (BFP) of enteropathogenic
E. coli
(EPEC), longus (Lng) and colonization factor III (CFA/III) of enterotoxigenic
E. coli
(ETEC), T4P of
Salmonella enterica
serovar Typhi, Colonization Factor Citrobacter (CFC) of
Citrobacter rodentium
, T4P of
Yersinia pseudotuberculosis
, a ubiquitous T4P that was characterized in enterohemorrhagic
E. coli
(EHEC), and the R64 plasmid thin pilus. Finally, we highlight areas for further study.
Utilization of nanopore direct RNA sequencing to analyze viral RNA modifications
Authors: Tan Lu , Guo Zhihao , Wang Xiaoming , Kim Dal Young , Li Runsheng
Published: January 2024

Computational approaches utilizing Oxford Nanopore Technologies Direct RNA Sequencing data were almost exclusively designed to map eukaryotic epitranscriptomes. Therefore, extra caution must be exercised when using these tools to detect vRNA modifications, as in most cases, vRNA modification profiles should be regarded as unknown epitranscriptomes without prior knowledge. Here, we comprehensively evaluated the performance of 10 computational tools in detecting vRNA modification sites. All tested single-mode methods failed to differentiate native and
in vitro-
transcribed samples. Using optimized cutoff values, seven tested comparative tools generated very different predictions. An integrated analysis showed significant enrichment of Tombo_com and xPore predictions against the background. A pipeline for vRNA modification detection was proposed accordingly and applied to Sindbis virus RNAs. In conclusion, our study underscores the need for the careful application of computational tools to analyze viral epitranscriptomics. It also offers insights into alphaviral RNA modifications, although further validation is required.
Global epidemiology of asymptomatic colonisation of methicillin-resistantStaphylococcus aureusin the upper respiratory tract of young children: a systematic review and meta-analysis
Authors: Yang Liuyue , Dharmaratne Priyanga , Zhu Chendi , Sapugahawatte Dulmini Nanayakkara , Rahman Nannur , Barua Nilakshi , Li Carmen , Kwok Kin On , Luo Mingjing , Liyanapathirana Veranja , Ip Margaret
Published: January 2024

Objective

To estimate the global prevalence of asymptomatic colonisation, and determine the associated risk factors, antibiotic resistance and genotypes of methicillin-resistantStaphylococcus aureus(MRSA) in the upper respiratory tract of young children.

Design

Four bibliometric databases were searched for publications between 2010 and 2022 according to the protocol registered in PROSPERO. Cross-sectional or cohort studies describing the prevalence of asymptomatic colonisation ofS. aureusand MRSA in young children were included. Data extraction and analysis were carried out by two reviewers independently according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Pooled prevalence was estimated using a random effects model.

Setting and studies

We included studies where children without respiratory tract infection or Staphylococcal infection were recruited from the community, children’s institutions (ie, nurseries, kindergartens, daycare centres and preschools) and healthcare centre visits and assessed for asymptomatic colonisation withS. aureusand MRSA.

Main outcome measures

The pooled prevalence of asymptomatic colonisation ofS. aureusand MRSA of young children globally.

Results

In this systematic review and meta-analysis of 21 416 young children, the pooled global prevalence of asymptomaticS. aureuscolonisation was 25.1% (95% CI 21.4 to 28.8) and MRSA colonisation was 3.4% (95% CI 2.8 to 4.1). The clones of MRSA strains included healthcare-associated MRSA, community-associated MRSA and livestock-associated MRSA.

Conclusion

This study provides evidence of increased MRSA colonisation globally among young children, underlining the critical role of asymptomatic carriers in MRSA transmission and the need for control measures.

PROSPERO registration number

CRD 42022328385.
Intrathoracic Ewing’s sarcoma in an adult masquerading as lung abscess
Authors: Lahiri Raja , Rawat Shubham Singh , Srikant Kandhala , Rao Shalinee
Published: January 2024

Intrathoracic extraskeletal Ewing’s sarcoma (EES) is a relatively uncommon malignant tumour. Here, we present a scenario involving an adult man in his 20s with a large intrathoracic EES that manifested as a lung abscess. Preoperative diagnostic tests were inconclusive; hence, the patient underwent an exploratory thoracotomy for the excision of the mass. Histopathology revealed a small round blue cell tumour, and immunohistochemistry, along with fluorescence in situ hybridisation, confirmed the diagnosis of Ewing’s sarcoma. Adjuvant chemoradiotherapy was recommended, but the patient did not comply. A year later, he presented with a recurrence of the intrathoracic mass and subsequently received adjuvant chemotherapy. Currently, he is in remission.
Case of postoperative mitral and tricuspid valve repair with large vessel occlusion ischaemic stroke: successfully treated with mechanical thrombectomy extracting subocclusive thrombus containing foreign material
Authors: Bah Momodou G , Vollhaber Daniel , Lin Leanne , Wilseck Zachary , Gemmete Joseph J , Conyers Frank G , Carrera Joseph F , Chaudhary Neeraj
Published: January 2024

A woman in her 60s with a history of prior ischaemic stroke developed acute onset slurring of speech, left-sided facial droop and left-sided weakness and was found on CT angiography to have a subocclusive thrombus multiple days after undergoing mitral and tricuspid valve repair surgery. A stent retriever and aspiration catheter were used to successfully remove the subocclusive material which was identified as ‘foreign material’ on histology. Ultimately, the patient demonstrated clinical improvement.

Foreign material embolism is a rare but serious complication that can occur during or after mitral and tricuspid valve repair surgery. It can cause ischaemic stroke and prompt recognition and immediate intervention are necessary to prevent serious complications.

The case report highlights the successful use of stent retriever-mediated suction thrombectomy to remove a foreign material embolism in a patient. It emphasises the importance of timely intervention to prevent serious complications and shows the potential benefits of this technique.
Exploring Online Health Information Seeking Behaviour (OHISB) among young adults: A scoping review protocol
Authors: Bratland Kristine Moksnes , Wien Charlotte , Sandanger Torkjel M
Published: January 2024

Introduction

In recent years, information technology and social media have experienced unprecedented growth, particularly in the Nordic countries. However, there is a noticeable lack of comprehensive understanding regarding the latest research findings on online health information seeking behaviour (OHISB) among young adults (18 to >30). There is a need to conduct an updated review to identify knowledge gaps in where young adults find health information and their user interface preferences and to provide research-based guidance and recommendations to governments, health organisations and social media platforms on how to facilitate this prominent pattern. The scoping review protocol outlines a study that will systematically map the existing literature on young adults’ preferences for digital platforms and platform characteristics in relation to OHISB, enabling the identification of promising areas for further research and the development of more effective interventions to promote healthy and informed choices. Conducting a scoping review is imperative to gain a comprehensive understanding of young adults’ OHISB and support the next generation of dissemination that promotes accurate and reliable digital health information.

Methods and analysis

The scoping review will use Arksey and O’Malley’s methodological framework (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)) and employ the citation pearl method and the Sample, Phenomenon of Interest, Design, Evaluation, Research type model to design the search strategy. To identify relevant literature, three databases will undergo a search: Scopus, Web of Science and EMBASE. Additionally, a subsidiarily grey literature search will be conducted in Google Scholar. The data charting process will conform to the PRISMA-ScR standard and will be further structured with EndNote. Qualitative and quantitative analyses of the extracted data will be developed using EndNote and Excel.

Ethics and dissemination

Conducting a scoping review involves secondary data analysis of publicly available sources and does not require an ethical review. The protocol will be published to ensure transparency. The scoping review results will be disseminated through open-access peer-reviewed publications, national and international conferences, social media platforms, newspapers and YouTube to service users and stakeholders.
Measuring and predicting the effect of remyelinating therapy in multiple sclerosis: a randomised controlled trial protocol (RESTORE)
Authors: Hof Sam , van Rijn Laurentius J , Uitdehaag Bernard M J , Nij Bijvank Jenny A , Petzold Axel
Published: January 2024

Introduction

Remyelination failure hampers symptomatic recovery in multiple sclerosis (MS), underlining the importance of developing remyelinating therapies. Optic neuritis is currently the most established method of measuring remyelination in MS trials. Complementary more generalisable methods of measuring remyelination are required to confirm treatment efficacy. Measuring internuclear ophthalmoplegia (INO) with infrared oculography provides such a method. Moreover, this method can be expanded with a test for selecting likely treatment responders by using fampridine. The aim of this trial is to investigate the (long-term) remyelinating effects of clemastine fumarate in patients with MS and INO and to evaluate if treatment response can be predicted using fampridine.

Methods and analysis

RESTORE is a single-centre double-blind randomised placebo-controlled trial of clemastine fumarate versus placebo. Prior to clemastine treatment improvement in oculographic features of INO after a single 10 mg dose of fampridine is measured in all participants and used to predict the treatment response to clemastine. Eighty individuals with MS and INO will be 1:1 randomised to 4 mg of clemastine fumarate two times a day for 6 months or equivalent placebo. Our primary outcome is improvement in the Versional Dysconjugacy Index-area under the curve, measured by infrared oculography after 6 months of treatment. Participants are assessed for persistent treatment effects 6, 18 and 30 months after end of treatment. Secondary outcome measures include other oculography parameters including double-step saccades, retinal imaging, visual acuities, physical disability, cognition and patient-reported outcomes.

Ethics and dissemination

Clemastine is a registered and very well-established drug with well-known safety and side effects. The protocol was approved by the medical ethical committee of the Amsterdam UMC, location VUMC and the Dutch Central Committee on Research Involving Human Subject. Written informed consent is obtained from all participants. The results will be published in peer-reviewed medical scientific journals.

Trial registration number

EudraCT: 2021-003677-66, ClinicalTrials.gov:NCT05338450.
Predicting response to iron supplementation in patients with active inflammatory bowel disease (PRIme): a randomised trial protocol
Authors: Loveikyte Roberta , Duijvestein Marjolijn , Mujagic Zlatan , Goetgebuer Rogier L , Dijkstra Gerard , van der Meulen-de Jong Andrea E
Published: January 2024

Introduction

Iron deficiency anaemia (IDA) is the most common systemic manifestation of inflammatory bowel disease (IBD) that has detrimental effects on quality of life (QoL) and disease outcomes. Iron deficiency (ID), with or without anaemia, poses a diagnostic and therapeutic challenge in patients with IBD due to the multifactorial nature of ID(A) and its frequent recurrence. Elevated hepcidin—a systemic iron regulator that modulates systemic iron availability and intestinal iron absorption—has been associated with oral iron malabsorption in IBD. Therefore, hepcidin could assist in therapeutic decision-making. In this study, we investigate whether hepcidin can predict response to oral and intravenous iron supplementation in patients with active IBD undergoing anti-inflammatory treatment.

Methods and analysis

PRIme is an exploratory, multicentre, open-label and randomised trial. All adult patients with active IBD and ID(A) will be assessed for eligibility. The participants (n=90) will be recruited at five academic hospitals within the Netherlands and randomised into three groups (1:1:1): oral ferrous fumarate, oral ferric maltol or intravenous iron. Clinical and biochemical data will be collected at the baseline and after 6, 14 and 24 weeks. Blood samples will be collected to measure hepcidin and other biomarkers related to iron status. In addition, patient-reported outcomes regarding QoL and disease burden will be evaluated. The primary outcome is the utility of hepcidin as a predictive biomarker for response to iron therapy, which will be assessed using receiver operating curve analysis.

Ethics and dissemination

The study has been approved by the Institutional Review Board at the Leiden University Medical Center (IRB No. P21.109) and other study sites. All participants will provide written informed consent to enrol in the study. The findings will be published in a peer-reviewed journal and disseminated at scientific conferences; the dataset will be available on reasonable request.

Trial registration

Prospectively registered in thehttps://clinicaltrials.gov/and the Eudra registries. First submitted on 10 May 2022 to the ClinicalTrials.gov (ID:NCT05456932) and on 3 March 2022 to the European Union Drug Regulating Authorities Clinical Trials Database (ID: 2022-000894-16).
Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study
Authors: Hopkins Rhian , Young Katherine G , Thomas Nicholas J , Godwin James , Raja Daniyal , Mateen Bilal A , Challen Robert J , Vollmer Sebastian J , Shields Beverley M , McGovern Andrew P , Dennis John M
Published: January 2024

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.
Exploring important service characteristics of telephone cancer information and support services for callers: protocol for a systematic review of qualitative research
Authors: Livingstone Ann , Murphy April , Bucholc Jessica , Engel Lidia , Lane Katherine , Spence Danielle , McCaffrey Nikki
Published: January 2024

Introduction

As cancer incidence continues to rise, challenges remain in how to communicate accurate, timely information to people with cancer, their families and healthcare professionals. One option is to provide support and comprehensive, tailored information via a telephone cancer information and support service (CISS). This systematic review aims to summarise the service characteristics of telephone CISS and identify what aspects of services are important from callers’ perspectives.

Methods and analysis

A comprehensive literature search will be conducted for articles published from database inception to 30 March 2023 (OVID MEDLINE, EMBASE, CINAHL, PsycINFO and SocINDEX). Published, peer-reviewed, articles reporting qualitative research on the service characteristics of telephone CISS important to callers in any language will be included. One researcher will complete the searches, two researchers will independently screen results for eligible studies and a third researcher will resolve any disagreement. A narrative and thematic synthesis of studies will be provided. Study characteristics will be independently extracted by one researcher and checked by a second. Included studies’ methodological quality will be evaluated independently by two researchers using the 2022 Critical Appraisal Skills Programme Qualitative Studies Checklist. Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research tool will assess the confidence of the review findings.

Ethics and dissemination

Ethics approval is not required for this research as it is a planned systematic review of published literature. Findings will be presented at leading cancer, health economic and supportive care conferences, published in a peer-reviewed journal, and disseminated via websites and social media.

PROSPERO registration number

CRD42023413897.
Opt-in versus universal codeine provision for medical abortion up to 10 weeks of gestation at British Pregnancy Advisory Service: a cross-sectional evaluation
Authors: Taghinejadi Neda , McCulloch Hannah , Krassowski Michał , McInnes-Dean Amelia , Whitehouse Katherine C , Lohr Patricia A
Published: January 2024

Objective

To assess patient experiences of pain management during medical abortion up to 10 weeks’ gestation with opt-in versus universal codeine provision.

Methods

We invited patients who underwent medical abortion up to 10 weeks of gestation to participate in an online, anonymous, English-language survey from November 2021 to March 2022. We performed ordinal regression analyses to compare satisfaction with pain management (5-point Likert scale) and maximum abortion pain score (11-point numerical rating scale) in the opt-in versus universal codeine provision groups.

Results

Of 11 906 patients invited to participate, 1625 (13.6%) completed the survey. Participants reported a mean maximum pain score of 6.8±2.2. A total of 1149 participants (70.7%) reported using codeine for pain management during their abortion. Participants in the opt-in codeine provision group were significantly more likely to be satisfied with their pain management than those in the universal group (aOR 1.48, 95% CI 1.12 to 1.96, p<0.01). Maximum abortion pain scores were lower on average among the opt-in codeine provision group (OR 0.80, 95% CI 0.66 to 0.96, p=0.02); however, this association was not statistically significant in the model adjusted for covariates (aOR 0.85, 95% CI 0.70 to 1.03, p=0.09).

Conclusion

Our findings suggest that patients have a better experience with pain management during medical abortion when able to opt-in to codeine provision following counselling versus receiving this medication routinely.
MicroRNA-451a is a candidate biomarker and therapeutic target for major depressive disorder
Authors: Hu Panpan , Cao Qiuchen , Feng Hu , Liu Yun , Chen Yan , Xu Jingfan , Feng Weixi , Sun Huaiqing , Ding Huachen , Wang Chun , Gao Junying , Xiao Ming
Published: January 2024

Background

Increasing evidence supports the role of microRNAs (miRNAs) in major depressive disorder (MDD), but the pathophysiological mechanism remains elusive.

Aims

To explore the mechanism of microRNA-451a (miR-451a) in the pathology and behaviours of depression.

Methods

Abnormal miRNAs such as miR-451a reported previously in the serum of patients with MDD were screened and then confirmed in a mouse model of depression induced by chronic restraint stress (CRS). Eight-week-old male C57BL/6 mice had miR-451a overexpression in the medial prefrontal cortex (mPFC) via adeno-associated virus serotype 9 vectors encoding a pri-mmu-miR-451a-GFP fusion protein followed by behavioural and pathological analyses. Finally, molecular biological experiments were conducted to investigate the potential mechanism of miR-451a against depression.

Results

The serum levels of miRNA-451a were significantly lower in patients with MDD, with a negative correlation with the Hamilton Depression Scale scores. Additionally, a negative association between serum miR-451a and behavioural despair or anhedonia was observed in CRS mice. Notably, miR-451a expression was significantly downregulated in the mPFC of CRS-susceptible mice. Overexpressing miR-451a in the mPFC reversed the loss of dendritic spines and the depression-like phenotype of CRS mice. Mechanistically, miR-451a could inhibit CRS-induced corticotropin-releasing factor receptor 1 expression via targeting transcription factor 2, subsequently protecting dendritic spine plasticity.

Conclusions

Together, these results highlighted miR-451a as a candidate biomarker and therapeutic target for MDD.
Echocardiographic artificial intelligence for pulmonary hypertension classification
Authors: Hirata Yukina , Tsuji Takumasa , Kotoku Jun'ichi , Sata Masataka , Kusunose Kenya
Published: January 2024

Objective

The classification of pulmonary hypertension (PH) is crucial for determining the appropriate therapeutic strategy. We investigated whether machine learning (ML) algorithms may assist in echocardiographic PH prediction, where current guidelines recommend integrating several different parameters.

Methods

We obtained physical and echocardiographic data from 885 patients who underwent right heart catheterisation (RHC). Patients were classified into three groups: non-PH, precapillary PH and postcapillary PH, based on values obtained from RHC. Using 24 parameters, we created predictive models employing four different classifiers and selected the one with the highest area under the curve. We then calculated the macro-average classification accuracy for PH on the derivation cohort (n=720) and prospective validation data set (n=165), comparing the results with guideline-based echocardiographic assessment obtained from each cohort.

Results

Logistic regression with elastic net regularisation had the highest classification accuracy, with areas under the curves of 0.789, 0.766 and 0.742 for normal, precapillary PH and postcapillary PH, respectively. The ML model demonstrated significantly better predictive accuracy than the guideline-based echocardiographic assessment in the derivation cohort (59.4% vs 51.6%, p<0.01). In the independent validation data set, the ML model’s accuracy was comparable to the guideline-based PH classification (59.4% vs 57.8%, p=0.638).

Conclusions

This preliminary study suggests promising potential for our ML model in predicting echocardiographic PH. Further research and validation are needed to fully assess its clinical utility in PH diagnosis and treatment decision-making.
Variant reclassification and clinical implications
Authors: Walsh Nicola , Cooper Aislinn , Dockery Adrian , O'Byrne James J
Published: January 2024

Genomic technologies have transformed clinical genetic testing, underlining the importance of accurate molecular genetic diagnoses. Variant classification, ranging from benign to pathogenic, is fundamental to these tests. However, variant reclassification, the process of reassigning the pathogenicity of variants over time, poses challenges to diagnostic legitimacy. This review explores the medical and scientific literature available on variant reclassification, focusing on its clinical implications.

Variant reclassification is driven by accruing evidence from diverse sources, leading to variant reclassification frequency ranging from 3.6% to 58.8%. Recent studies have shown that significant changes can occur when reviewing variant classifications within 1 year after initial classification, illustrating the importance of early, accurate variant assignation for clinical care.

Variants of uncertain significance (VUS) are particularly problematic. They lack clear categorisation but have influenced patient treatment despite recommendations against it. Addressing VUS reclassification is essential to enhance the credibility of genetic testing and the clinical impact. Factors affecting reclassification include standardised guidelines, clinical phenotype-genotype correlations through deep phenotyping and ancestry studies, large-scale databases and bioinformatics tools. As genomic databases grow and knowledge advances, reclassification rates are expected to change, reducing discordance in future classifications.

Variant reclassification affects patient diagnosis, precision therapy and family screening. The exact patient impact is yet unknown. Understanding influencing factors and adopting standardised guidelines are vital for precise molecular genetic diagnoses, ensuring optimal patient care and minimising clinical risk.
Molecular diagnosis, clinical evaluation and phenotypic spectrum of Townes-Brocks syndrome: insights from a large Chinese hearing loss cohort
Authors: Yan Xiaohong , Wang Jing , Yang Wen , Li Linke , Shen Tian , Geng Jia , Zhang Qian , Zhong Mingjun , Xiong Wenyu , Bu Fengxiao , Lu Yu , Zhao Yu , Cheng Jing , Yuan Huijun
Published: January 2024

Background

Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics.

Methods

We screenedSALL1andDACT1variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS.

Results

We identified five novel and two reported pathogenic/likely pathogenic (P/LP)SALL1variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship betweenSALL1variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring.

Conclusion

This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.
Increased vascular inflammation on PET/CT in psoriatic arthritis patients in comparison with controls
Authors: Kleinrensink Nienke J , Spierings Julia , Vonkeman Harald E , Seddiqi Negina , Herman Amin , Suijkerbuijk Karijn P M , Heijstek Marloes W , Jansen Mylène P , de Jong Pim A , Foppen Wouter
Published: January 2024

Background

Patients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease, possibly due to a chronic inflammatory state.

Objectives

The main objective of this study was to investigate the difference in vascular inflammation, measured with 18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), in PsA patients and controls. We conducted a secondary analysis to assess the association between clinical parameters of disease activity with vascular inflammation in PsA.

Methods

We included a total of 75 PsA patients with active peripheral arthritis (defined as ≥2 tender and swollen joints) from an ongoing clinical trial (EudraCT 2017-003900-28) and a retrospective group of 40 controls diagnosed with melanoma, without distant metastases and not receiving immunotherapy. The main outcome measure was aortic vascular inflammation which was measured on PET/CT scans using target-to-background ratios. Clinical disease activity in PsA was assessed with joint counts, body surface area and the Disease Activity index for PsA. Laboratory assessments included C reactive protein and erythrocyte sedimentation rate.

Results

Vascular inflammation was increased in patients with PsA in comparison with controls (mean target-to-background ratio for entire aorta, respectively, 1.63±0.17 vs 1.49±0.16; p=<0.001). This association remained significant after correction for gender, age, body mass index, mean arterial pressure and aortic calcification (p=0.002). Vascular inflammation was not associated with disease-related parameters.

Conclusions

Aortic vascular inflammation was significantly increased in patients with active PsA compared with controls. This evidence supports the theory that inflammation in PsA is not limited to the skin and joints but also involves the vascular system.
Delirium pathophysiology in cancer: neurofilament light chain biomarker – narrative review
Authors: Kruize Zita , van Campen Isa , Vermunt Lisa , Geerse Olaf , Stoffels Josephine , Teunissen Charlotte , van Zuylen Lia
Published: January 2024

BackgroundDelirium is a debilitating disorder with high prevalence near the end of life, impacting quality of life of patients and their relatives. Timely recognition of delirium can lead to prevention and/or better treatment of delirium. According to current hypotheses delirium is thought to result from aberrant inflammation and neurotransmission, with a possible role for neuronal damage. Neurofilament light chain (NfL) is a protein biomarker in body fluids that is unique to neurons, with elevated levels when neurons are damaged, making NfL a viable biomarker for early detection of delirium. This narrative review summarises current research regarding the pathophysiology of delirium and the potential of NfL as a susceptibility biomarker for delirium and places this in the context of care for patients with advanced cancer.

ResultsSix studies were conducted exclusively on NfL in patients with delirium. Three of these studies demonstrated that high plasma NfL levels preoperatively predict delirium in older adult patients postoperatively. Two studies demonstrated that high levels of NfL in intensive care unit (ICU) patients are correlated with delirium duration and severity. One study found that incident delirium in older adult patients was associated with increased median NfL levels during hospitalisation.

ConclusionsTargeted studies are required to understand if NfL is a susceptibility biomarker for delirium in patients with advanced cancer. In this palliative care context, better accessible matrices, such as saliva or urine, would be helpful for repetitive testing. Improvement of biological measures for delirium can lead to improved early recognition and lay the groundwork for novel therapeutic strategies.
Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial
Authors: Li Shuya , Wangqin Runqi , Pan Yuesong , Jin Aoming , Li Hao , Schwamm Lee H , Fisher Marc , Campbell Bruce C V , Parsons Mark W , Wang Ziran , Dai Hongguo , Li Deyang , Li Runhui , Wang Junhai , Wang David , Wang Yilong , Zhao Xingquan , Li Zixiao , Zheng Huaguang , Xiong Yunyun , Meng Xia , Wang Yongjun
Published: January 2024

Background

The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks.

Methods

This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0–1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0–90 min, 91–180 min and 181–270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment.

Results

Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0–90 min, 1.23 (95% CI 0.88 to 1.71) for 91–180 min and 1.21 (95% CI 0.88 to 1.65) for 181–270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI −0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI −2.66 to 6.20; p=0.58) for 0–180 min.

Conclusions

In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.
Active particle methods towards a mathematics of living systems
Authors: Bellomo Nicola , Brezzi Franco
Published: January 2024

This editorial paper reviews the articles published in a special issue devoted to the application of active particle methods applied to the study of the collective dynamics of large systems of interacting entities in science and society. The applications presented in this special issue focus on the study of financial markets, cell dynamics in the context of cancer modeling, vehicle and crowd vehicle and crowd dynamics, and classical problems in the kinetic theory of active particles and swarm theory. A critical analysis is proposed to look forward to research. Perspectives with emphasis on the interaction of multiple social dynamics.
Domain Generalization in Time Series Forecasting
Authors: Deng Songgaojun , Sprangers Olivier , Li Ming , Schelter Sebastian , de Rijke Maarten
Published: January 2024

Domain generalization aims to design models that can effectively generalize to unseen target domains by learning from observed source domains. Domain generalization poses a significant challenge for time series data, due to varying data distributions and temporal dependencies. Existing approaches to domain generalization are not designed for time series data, which often results in suboptimal or unstable performance when confronted with diverse temporal patterns and complex data characteristics. We propose a novel approach to tackle the problem of domain generalization in time series forecasting. We focus on a scenario where time series domains share certain common attributes and exhibit no abrupt distribution shifts. Our method revolves around the incorporation of a key regularization term into an existing time series forecasting model:domain discrepancy regularization. In this way, we aim to enforce consistent performance across different domains that exhibit distinct patterns. We calibrate the regularization term by investigating the performance within individual domains and propose thedomain discrepancy regularization with domain difficulty awareness. We demonstrate the effectiveness of our method on multiple datasets, including synthetic and real-world time series datasets from diverse domains such as retail, transportation, and finance. Our method is compared against traditional methods, deep learning models, and domain generalization approaches to provide comprehensive insights into its performance. In these experiments, our method showcases superior performance, surpassing both the base model and competing domain generalization models across all datasets. Furthermore, our method is highly general and can be applied to various time series models.
Understanding the Performance of AI Algorithms in Text-Based Emotion Detection for Conversational Agents
Authors: Kusal Sheetal D. , Patil Shruti G. , Choudrie Jyoti , Kotecha Ketan V.
Published: January 2024

Current industry trends demand automation in every aspect, where machines could replace humans. Recent advancements in conversational agents have grabbed a lot of attention from industries, markets, and businesses. Building conversational agents that exhibit human communication characteristics is a need in today's marketplace. Thus, by accumulating emotions, we can build emotionally aware conversational agents. Emotion detection in text-based dialogues has turned into a pivotal component of conversational agents, enhancing their ability to understand and respond to users’ emotional states. This article extensively compares various artificial intelligence techniques adapted to text-based emotion detection for conversational agents. The study covers a wide range of methods, from machine learning models to cutting-edge pre-trained models and deep learning models. We evaluate the performance of these techniques on the benchmark unbalanced Topical-Chat and balanced Empathetic Dialogue datasets. This article offers an overview of the practical implications of emotion detection techniques in conversational systems and their impact on user response. The outcomes of this work contribute to the ongoing development of empathetic conversational agents, emphasizing natural human-machine interactions.
Transmission Line Model of Intercalation Electrode Particle in Lithium-Ion Batteries
Authors: Tibaut Tilen , Zelič Klemen , Katrašnik Tomaž
Published: January 2024

The transmission line model (TLM) is a powerful tool to describe different physicochemical processes and therefore frequently used for the simulation of battery and fuel cell performance. Despite the fact that TLMs exhibit spatial resolution, there still are challenges when applying TLMs to realistic geometries and for modelling arbitrary direct and alternate current operations. To resolve this long-standing challenge, we developed the methodology for designing TLMs, which enables adequate modelling of arbitrary direct and alternate current operations on simplified geometries of active intercalating particles in battery electrodes. The insightful derivation is based on finite volume discretization of the diffusion equation in active particles. The capability of the proposed method to adequately model arbitrary AC and DC operation is demonstrated by comparing the obtained results with the analytic solution. This was validated on the spherical geometry with different solid diffusivity coefficients of active particles.
In Vitro Filaricidal Properties of Aqueous Extracts of Combretum nigricans (Combretaceae) on Onchocerca ochengi (Onchocercidae)
Authors: Ignagali Banserne Brey , Galani Tietcheu Borris Rosnay , Betrosse Theodore , Kamaya Blaise , Ndjonka Dieudonne
Published: January 2024

Aim. Onchocerciasis is an endemic parasitic disease in sub-Saharan Africa that significantly impacts animal and human health. In Northern Cameroon, medicinal plants from the Combretum genus are used for onchocerciasis traditional treatment although there is no scientific evidence of their antifilarial potential. This study evaluates the in vitro macro- and microfilaricidal properties of water extracts from Combretum nigricans in Onchocerca ochengi. Material and Methods. O. ochengi microfilariae and adult male worms were recovered from cowhide fragments. Oxidative stress indicators and motility tests were used to assess the filaricidal impact. Female albino rats were used to test for acute toxicity. The contents of secondary metabolites were quantified. Results. The bark aqueous extract was more active on macrofilariae at 1 mg/mL for 24 h (100%) than the leaf (63.9%) and root (75%) extracts at the same concentration. Likewise, a stronger microfilaricidal effect was found with this extract at 0.5 mg/mL for 1 h (100%) compared to root and leaf extracts. The dose-response effect with the bark extract gave an inhibitory concentration 50 (IC50) of 351 μg/mL vs. 113 μg/mL for flubendazole after 24 h incubation, while the microfilaricidal efficacy revealed an IC50 of 158.7 μg/mL vs. 54.09 μg/mL for ivermectin after one-hour incubation. Examining stress indicators on parasite homogenates showed that macrofilaricidal activity is associated with a significant increase in nitric oxide, glutathione, and malondialdehyde generation and a decrease in catalase activity. At 2000 mg/kg, rats showed no harm. The phytochemical investigation revealed that the barks contained more phenolic acids, condensed tannins, flavonoids, and saponins than the leaves (p<0.001). Conclusion. These findings support C. nigricans’ antifilarial activity and identify oxidative stress indicators as prospective treatment targets in O. ochengi. It would be interesting to conduct in vivo studies to understand their antifilarial activity better.