bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically relevant fluorescent assay for identification of 17β‐hydroxysteroid dehydrogenase type 10 inhibitors
Authors: Schmidt Monika , Vaskova Michaela , Rotterova Aneta , Fiandova Pavlina , Miskerikova Marketa , Zemanova Lucie , Benek Ondrej , Musilek Kamil 
Published: July 2023

AbstractMitochondrial enzyme 17β‐hydroxysteroid dehydrogenase type 10 (HSD10) is a potential molecular target for treatment of mitochondrial‐related disorders such as Alzheimer's disease (AD). Its over‐expression in AD brains is one of the critical factors disturbing the homeostasis of neuroprotective steroids and exacerbating amyloid beta (Aβ)‐mediated mitochondrial toxicity and neuronal stress. This study was focused on revalidation of the most potent HSD10 inhibitors derived from benzothiazolyl urea scaffold using fluorescent‐based enzymatic assay with physiologically relevant substrates of 17β‐oestradiol and allopregnanolone. The oestradiol‐based assay led to the identification of two nanomolar inhibitors (IC50 70 and 346 nM) differing from HSD10 hits revealed from the formerly used assay. Both identified inhibitors were found to be effective also in allopregnanolone‐based assay with non‐competitive or uncompetitive mode of action. In addition, both inhibitors were confirmed to penetrate the HEK293 cells and they were able to inhibit the HSD10 enzyme in the cellular environment. Both molecules seem to be potential lead structures for further research and development of HDS10 inhibitors.image
Patent foramen ovale in carcinoid heart disease: The potential role for and risks of percutaneous closure prior to cardiothoracic surgery
Authors: Douglas Sasha , Oelofse Tessa , Shah Tahir , Rooney Stephen , Arif Sayqa , Steeds Richard P. 
Published: July 2023

AbstractNeuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right‐sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right‐sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left‐sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.
Implementation of precision medicine in healthcare—A European perspective
Authors: Stenzinger Albrecht , Moltzen Ejner K. , Winkler Eva , Molnar‐Gabor Fruzsina , Malek Nisar , Costescu Alexandru , Jensen Brigitte Nybo , Nowak Frédérique , Pinto Carmine , Ottersen Ole Petter , Schirmacher Peter , Nordborg Jenni , Seufferlein Thomas , Fröhling Stefan , Edsjö Anders , Garcia‐Foncillas Jesus , Normanno Nicola , Lundgren Bettina , Friedman Mikaela , Bolanos Natacha , Tatton‐Brown Katrina , Hill Sue , Rosenquist Richard 
Published: July 2023

AbstractThe technical development of high‐throughput sequencing technologies and the parallel development of targeted therapies in the last decade have enabled a transition from traditional medicine to personalized treatment and care. In this way, by using comprehensive genomic testing, more effective treatments with fewer side effects are provided to each patient—that is, precision or personalized medicine (PM). In several European countries—such as in England, France, Denmark, and Spain—the governments have adopted national strategies and taken “top‐down” decisions to invest in national infrastructure for PM. In other countries—such as Sweden, Germany, and Italy with regionally organized healthcare systems—the profession has instead taken “bottom‐up” initiatives to build competence networks and infrastructure to enable equal access to PM. In this review, we summarize key learnings at the European level on the implementation process to establish sustainable governance and organization for PM at the regional, national, and EU/international levels. We also discuss critical ethical and legal aspects of implementing PM, and the importance of access to real‐world data and performing clinical trials for evidence generation, as well as the need for improved reimbursement models, increased cross‐disciplinary education and patient involvement. In summary, PM represents a paradigm shift, and modernization of healthcare and all relevant stakeholders—that is, healthcare, academia, policymakers, industry, and patients—must be involved in this system transformation to create a sustainable, non‐siloed ecosystem for precision healthcare that benefits our patients and society at large.
Melatonin targets MoIcl1 and works synergistically with fungicide isoprothiolane in rice blast control
Authors: Bi Ruiqing , Li Renjian , Xu Zhenyi , Cai Huanyu , Zhao Juan , Zhou Yaru , Wu Bangting , Sun Peng , Yang Wei , Zheng Lu , Chen Xiao‐Lin , Luo Chao‐Xi , Teng Huailong , Li Qiang , Li Guotian 
Published: July 2023

AbstractMelatonina natural harmless molecule—displays versatile roles in human health and crop disease control such as for rice blast. Rice blast, caused by the filamentous fungus Magnaporthe oryzae, is one devastating disease of rice. Application of fungicides is one of the major measures in the control of various crop diseases. However, fungicide resistance in the pathogen and relevant environmental pollution are becoming serious problems. By screening for possible synergistic combinations, here, we discovered an eco‐friendly combination for rice blast control, melatonin, and the fungicide isoprothiolane. These compounds together exhibited significant synergistic inhibitory effects on vegetative growth, conidial germination, appressorium formation, penetration, and plant infection by M. oryzae. The combination of melatonin and isoprothiolane reduced the effective concentration of isoprothiolane by over 10‐fold as well as residual levels of isoprothiolane. Transcriptomics and lipidomics revealed that melatonin and isoprothiolane synergistically interfered with lipid metabolism by regulating many common targets, including the predicted isocitrate lyase‐encoding gene MoICL1. Furthermore, using different techniques, we show that melatonin and isoprothiolane interact with MoIcl1. This study demonstrates that melatonin and isoprothiolane function synergistically and can be used to reduce the dosage and residual level of isoprothiolane, potentially contributing to the environment‐friendly and sustainable control of crop diseases.
Medical competence as a multilayered construct
Authors: ten Cate Olle , Khursigara‐Slattery Natasha , Cruess Richard L. , Hamstra Stanley J. , Steinert Yvonne , Sternszus Robert 
Published: July 2023

AbstractBackgroundThe conceptualisation of medical competence is central to its use in competency‐based medical education. Calls for ‘fixed standards’ with ‘flexible pathways’, recommended in recent reports, require competence to be well defined. Making competence explicit and measurable has, however, been difficult, in part due to a tension between the need for standardisation and the acknowledgment that medical professionals must also be valued as unique individuals. To address these conflicting demands, a multilayered conceptualisation of competence is proposed, with implications for the definition of standards and approaches to assessment.The modelThree layers are elaborated. This first is a core layer of canonical knowledge and skill, ‘that, which every professional should possess’, independent of the context of practice. The second layer is context‐dependent knowledge, skill, and attitude, visible through practice in health care. The third layer of personalised competence includes personal skills, interests, habits and convictions, integrated with one's personality. This layer, discussed with reference to Vygotsky's concept of Perezhivanie, cognitive load theory, self‐determination theory and Maslow's ‘self‐actualisation’, may be regarded as the art of medicine.We propose that fully matured professional competence requires all three layers, but that the assessment of each layer is different.ImplicationsThe assessment of canonical knowledge and skills (Layer 1) can be approached with classical psychometric conditions, that is, similar tests, circumstances and criteria for all. Context‐dependent medical competence (Layer 2) must be assessed differently, because conditions of assessment across candidates cannot be standardised. Here, multiple sources of information must be merged and intersubjective expert agreement should ground decisions about progression and level of clinical autonomy of trainees. Competence as the art of medicine (Layer 3) cannot be standardised and should not be assessed with the purpose of permission to practice. The pursuit of personal excellence in this level, however, can be recognised and rewarded.
Introduction: Nation promotion and the crisis of neoliberal globalisation
Authors: Jiménez‐Martínez César , Mihelj Sabina , Sage Daniel 
Published: July 2023

AbstractThis themed section seeks to initiate a debate about the changing nature of what we call nation promotion. That is, promotional practices aimed at creating, communicating and managing versions of national identity to advance economic or political goals. These practices—badged as ‘nation branding’, ‘public diplomacy’, ‘country branding’ or ‘soft power—emerged more than two decades ago, in a context characterised by the proliferation of digital communication technologies, the intensification of globalisation and international cooperation, and the shift in the balance of power from states to market forces. However, as we outline in this introduction, nation promotion operates today in a very different environment, marked by a crisis of neoliberal globalisation, the changing communication environment and mounting global challenges. The three articles that make up this themed section tackle the changing practices of nation promotion by focusing on the impact of at least one of these structural shifts, offering conceptual and analytical tools for making sense of these transformations.
TIM‐3/Galectin‐9 and CD160 expression in salivary adenoid cystic carcinoma
Authors: Li Mao , Wan Zi‐xin , Tang Yue‐yang , Liang Xin‐hua , Tang Ya‐ling 
Published: July 2023

AbstractObjectiveInvestigating T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3), Galectin 9 (Gal‐9), CD160 expression and tumor‐infiltrating lymphocytes (TILs) and correlation with clinicopathological characteristics of salivary adenoid cystic carcinoma (SACC).MethodsSixty cases of SACC were detected by immunohistochemical staining to evaluate TIM‐3, Gal‐9, and CD160 expression and analyze the correlation between TIM‐3, Gal‐9, CD160 expression and clinicopathologic features by rank‐sum test. The association of TILs with TIM‐3, Gal‐9, and CD160 expression in SACC stromal was done by Chi‐square test.ResultsTIM‐3 and CD160 overexpression were correlated with recurrence of SACC (p = 0.029, p = 0.007, respectively). High Gal‐9 expression was correlated with pathological classification (p = 0.018). The average percentage of TILs was 18.2% in SACC and most of TILs were more likely to occur in minor salivary glands (p = 0.038). Pairwise positive correlations were observed between the expression of TIM‐3, Gal‐9, and CD160 in tumor cells as well as in TILs, respectively.ConclusionLow density of TILs was characteristic of the SACC microenvironment, with upregulation of TIM‐3, Gal‐9, and CD160 all occurring. However, TIM‐3, Gal‐9, and CD160 expression in the stromal dependent on the number of TILs represent potential therapeutic targets in SACC.
Patient and clinician perspectives of information needs concerning oral epithelial dysplasia
Authors: Alsoghier Abdullah , Riordain Richeal Ni , Fedele Stefano , Porter Stephen 
Published: July 2023

AbstractObjectivesIndividuals diagnosed with a chronic oral disease that increase the risk of mouth cancer, such as oral epithelial dysplasia (OED), require appropriate knowledge to make informed decisions. The present study aimed to assess whether patient information needs of a group of patients concerning dysplasia were met and to what degree clinicians agree with patients on ‘important’ topics.Subjects and MethodsThis represented secondary analyses of a cross‐sectional study to assess the information needs of 86 patients diagnosed with dysplasia compared with those of 77 clinicians using the validated OED Information Needs Questionnaire. Descriptive, concordance and regression analyses were performed for the collected data.ResultsThe mean and median total scores for all items in the amount of information received subscale were 2.33 and 2.44, indicating overall unmet needs concerning dysplasia. Clinicians were generally able to predict topics of greatest importance to patients, although their scores were mainly lower than those of patients (k = 0.06). There was a higher agreement between patients (k = 0.25) than clinicians (k = 0.09).ConclusionClinicians are encouraged to assess a patient's information needs to ensure tailored and patient‐centred communication concerning OED during all clinical consultations.
Short‐term use of Lacticaseibacillus rhamnosusSD11 and the oral microbiome: Low caries RCT study
Authors: Teanpaisan Rawee , Surachat Komwit , Wonglapsuwan Monwadee , Piwat Supatcharin , Pahumunto Nuntiya 
Published: July 2023

AbstractObjectivesThe objective of the study was to investigate the effect of short‐term lozenges containing Lacticaseibacillus rhamnosus SD11 on cariogenic pathogens and on oral microbiota.Materials and MethodsThis double‐blind, randomized, controlled trial included 121 subjects and was randomly divided into the control and probiotic group. All subjects were blindly administered to receive the control‐ or probiotic L. rhamnosus SD11 lozenges every day for 4 weeks and then followed up for another 4 weeks.ResultsAfter probiotic consumption, the probiotic group had significantly lower levels of Streptococcus mutans and significantly higher levels of total lactobacilli at 4 and 8 weeks compared with the baseline. The 16S rRNA sequencing revealed an increase in bacterial diversity and beneficial bacteria in the Firmicutes phylum, Bacilli class, and a reduction in the mutans streptococci group in the probiotic group. The opposite results were found in the control group. This study did not find any caries increment, nor did the subjects have any side effects after product consumption.ConclusionWith the limitation of a short‐time study in low caries children, it showed that L. rhamnosus SD11 could increase beneficial bacteria in the Firmicutes phylum and Bacilli class that might support good oral health in children.
Molly Dewson, the women's division, and grassroots presidential campaigning during the New Deal
Authors: Blair Melissa E. 
Published: July 2023

AbstractIn the 1930s, Molly Dewson built the Women's Division of the Democratic National Committee into a central cog of FDR's presidential campaigns. She leveraged her personal friendship with the Roosevelts to develop a connected, national network of women who became the foot soldiers of the Democratic Party. By designing structures that made women the eyes and ears of the New Deal at the local level, the tactics and organizations she established persisted after her retirement and were copied by Republicans. Dewson ushered in a 30‐year period when women were at the center of presidential campaigns
Effects of selection regimes on state supreme court opinion writing
Authors: Shieh Marcy 
Published: July 2023

AbstractBackgroundJudicial reformers have long debated the merits of different types of judicial selection methods.ObjectivesWhile many of the debates center on how selection methods impact decision making, I argue that selection methods may also affect how justices approach opinion writing.MethodsUsing opinion data from 1953 to 2014 in 21 states and opinion data from 1953 to 2019 in five states, this article investigates whether selection methods influence the clarity of the opinions.ResultsThe results show that selection methods do not have a substantive impact on opinion clarity. What does have an effect on opinion clarity is when justices are ideologically distant from their constituents. Opinion clarity increases when nonpartisan justices are ideologically distant from their constituents, indicating that justices may use written opinions to demonstrate support for public opinion on specific issues, even if they do not generally vote in line with public opinion. In contrast, opinions in states that changed from partisan to nonpartisan are less clear, indicating that when a court changes its selection method, opinion authors may purposefully obfuscate their views and rely on their incumbency advantage to hold on to power.ConclusionThe findings suggest that judicial selection methods only influence opinion clarity in certain contexts.
Numerical constraints on the one‐stage and two‐stage Greater India collision models
Authors: Li Qian , Li Zhong‐Hai , Huangfu Pengpeng 
Published: July 2023

AbstractIndia‐Asia collision is generally believed to have collided since 55 ± 5 Ma, with a total amount of convergence of 2900–4400 km. Besides the overriding Tibetan lithospheric shortening, a large amount of convergence has to be accommodated by the subducting plate of Greater India. Three typical India‐Asia collision models have been proposed, including the Greater Indian Continent (GIC) model, Intra‐Oceanic Arc model and Greater Indian Oceanic Basin model. In this study, a large‐scale 2D numerical model, driven by the reconstruction‐based India‐Asia convergence rate, have been conducted to evaluate these three major models. The model results indicate that the one‐stage GIC model favours later initial collision at ≤50 Ma. For the two‐stage collision, the large amount of convergence can be easily accommodated by modifying the length of oceanic subduction after the first stage of continental collision. This study provides systematic numerical constraints for the favourable conditions of each model.
Wood–Ljungdahl pathway found in novel marine Korarchaeota groups illuminates their evolutionary history
Authors: Pan Jie , Zhang Xinxu , Xu Wei , Liu Yang , Liu Lirui , Luo Zhuhua , Li Meng 
Published: July 2023

ABSTRACT
Korarchaeota, due to its rarity in common environments, is one of the archaeal phyla that has received the least attention from researchers. It was previously thought to consist solely of strict thermophiles. However, our study provides genetic evidence for the presence of korarchaeal members in temperate subsurface seawater. Furthermore, a systematic reclassification of the Korarchaeota based on 16S rRNA genes and genomes has revealed three novel marine groups (Kor-6 to Kor-8) at the root of the Korarchaeota branch. Kor-6 contains microbes that are present in moderate temperatures. All three novel marine phyla possess genes for the Wood–Ljungdahl pathway, and Kor-7 and Kor-8 possess fewer genes encoding oxygen resistance traits than other korarchaeal groups, suggesting a distinct lifestyle for these novel phyla. Our results, together with estimations of Korarchaeota divergence times, suggest that oxygen availability may be one of the important factors that have influenced the evolution of Korarchaeota.

IMPORTANCE
Korarchaeota were previously thought to inhabit exclusively high-temperature environments. However, our study provides genetic evidence for their unexpected presence in temperate marine waters. Through analysis of publicly available korarchaeal reference data, we have systematically reclassified Korarchaeota and identified the existence of three previously unknown marine groups (Kor-6, Kor-7, and Kor-8) at the root of the Korarchaeota branch. Comparative analysis of their gene content revealed that these novel groups exhibit a lifestyle distinct from other Korarchaeota. Specifically, they have the ability to fix carbon exclusively via the Wood–Ljungdahl (WL) pathway, and the genomes within Kor-7 and Kor-8 contain few genes encoding antioxidant enzymes, indicating their strictly anaerobic lifestyle. Further studies suggest that the genes related to methane metabolism and the WL pathway may have been inherited from a common ancestor of the Korarchaeota and that oxygen availability may be one of the important evolutionary factors that shaped the diversification of this archaeal phylum.
Alcohol septal ablation in patients aged 75 years or older with hypertrophic obstructive cardiomyopathy
Authors: Lawin Dennis , Stellbrink Christoph , Stellbrink Ekaterina , Buck Benjamin , Poudel Madan Raj , Tego Andi , Marx Kristin , Lawrenz Thorsten 
Published: July 2023

ObjectiveOutcome data for patients ≥75 years with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA) are lacking. Therefore, a retrospective single-centre analysis was conducted.MethodsThe data of all consecutive ASAs, that were performed at our institution between 1 September 1997 and 31 July 2021 in patients with HOCM with left ventricular outflow tract gradients (LVOTG) ≥50 mm Hg, were collected from patient reports. ASA was performed per institutional standards with 95% ethanol infused into a feasible septal branch. Differences regarding echocardiographic, procedural and clinical parameters at baseline and after 6 months between patients ≥75 years and <75 years were assessed.ResultsWe found 208 ASAs in patients ≥75 years (85.1% female; age 78.0 years (IQR 76.0–80.0)) and 1430 ASAs in patients <75 years (42.0% female; age 56.0 years (IQR 46.0–65.0)). Patients ≥75 years had lower distances in 6 min walk test (baseline: 317.0 m (IQR 242.0–389.0) vs 438.0 m (IQR 353.3–504.0); p<0.0001). Exercise-induced LVOTG calculated at follow-up was lower in patients ≥75 years (29.5 mm Hg (IQR 18.0–54.0) vs 39.5 mm Hg (IQR 23.0–73.8); p=0.0007). There were more high-degree AV blocks after ASA in patients ≥75 years (25.5% vs 13.6%; p<0.0001). The in-hospital mortality did not differ between the groups (age ≥75 years: 1.0%; age <75 years: 0.6%; p=0.6580).ConclusionASA had similar efficacy and intrahospital mortality in patients ≥75 years compared with younger patients. Higher rates of AV block with need for permanent pacemaker implantation were observed in patients ≥75 years of age.