bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlocking the potential: unveiling tyrphostins with Michael-reactive cyanoacrylate motif as promising inhibitors of human 5-lipoxygenase
Authors: Molitor Maximilian , Menge Amelie , Mandel Sebastian , George Sven , Müller Susanne , Knapp Stefan , Hofmann Bettina , Steinhilber Dieter , Häfner Ann-Kathrin 
Published: September 2024

AbstractHuman 5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes, mediators of the innate immune system that also play an important role in inflammatory diseases and cancer. In this study, we present compounds, containing a Michael-reactive cyanoacrylate moiety as potent inhibitors of 5-LO. Representatives of the tyrosine kinase inhibitor family called tyrphostins, structurally related to known 5-LO inhibitors, were screened for their 5-LO inhibitory properties using recombinant human 5-LO, intact human PMNL (polymorphonuclear leukocytes), and PMNL homogenates. Their mode of action was characterized by the addition of glutathione, using a fourfold cysteine 5-LO mutant and mass spectrometry analysis. SAR studies revealed several members of the tyrphostin family containing a Michael-reactive cyanoacrylate to efficiently inhibit 5-LO. We identified degrasyn (IC50 0.11 µM), tyrphostin A9 (IC50 0.8 µM), AG879 (IC50 78 nM), and AG556 (IC50 64 nM) as potent 5-LO inhibitors. Mass spectrometry analysis revealed that degrasyn and AG556 covalently bound to up to four cysteines, including C416 and/or C418 which surround the substrate entry site. Furthermore, the 5-LO inhibitory effect of degrasyn was remarkably impaired by the addition of glutathione or by the mutation of cysteines to serines at the surface of 5-LO. We successfully identified several tyrphostins as potent inhibitors of human 5-LO. Degrasyn and AG556 were able to covalently bind to 5-LO via their cyanoacrylate moiety. This provides a promising mechanism for targeting 5-LO by Michael acceptors, leading to new therapeutic opportunities in the field of inflammation and cancer.
Neurological sequelae after childhood bacterial meningitis
Authors: Lempinen Laura , Saat Riste , Niemelä Sakke , Laulajainen-Hongisto Anu , Aarnisalo Antti A. , Nieminen Tea , Jero Jussi 
Published: September 2024

AbstractThe purpose of this study is to evaluate childhood bacterial meningitis (BM): incidence, clinical presentation, causative pathogens, diagnostics, and outcome (neurological sequelae, hearing loss, and death). A retrospective review of all children aged ≤ 16 years and 1 month diagnosed with BM at a tertiary children’s centre in the period 2010–2020. The Glasgow Outcome Scale (GOS) was used to assess outcome, with a GOS score of 1–4 considered to be an unfavourable outcome. Logistic regression univariate analysis was used to determine predefined risk factors for death, unfavourable outcome, and long-term neurological sequelae. Seventy-four patients (44 males) with a median age of 8.0 months (range 1 day to 16 years and 1 month) and 77 BM episodes were included in the study. The average incidence rate of BM was 2.2/100,000/year, the majority (91%) being community-acquired BM. Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens 12/77 (16%) each. Neurological sequelae at discharge were present in 24 (34%) patients, unfavourable outcome in 19 (25%), and hearing loss (deafness) in two (3%) survivors of BM. Seven (9%) patients died. Long-term neurological sequelae were observed in 19/60 (32%), aphasia/dysphasia being the most common in 10 (17%) BM children. No independent risk factors were identified for long-term neurological sequelae in univariate analysis. Conclusion: The risk for a fatal course of BM is still remarkable. Neurological sequelae persisted in a substantial proportion of BM survivors in long-term follow-up, aphasia/dysphasia being the most common. Hearing loss (deafness) occurred in 3%. However, no specific risk factors predicting the long-term sequelae were found.

What is Known:• Streptococcus pneumonia and Neisseria meningitidis were the most common pathogens causing bacterial meningitis.• Risk for fatal course of bacterial meningitis (BM) remains remarkable despite advances in modern medicine.

What is New:• In long-term follow-up, 1/3 of BM children suffered from neurological sequelae in the 2010s, aphasia and dysphasia being the most common sequelae.• Hearing loss was diagnosed in only two (3%) children, whom of both were deaf.
Rare homozygous cilia gene variants identified in consanguineous congenital heart disease patients
Authors: Baird Daniel A. , Mubeen Hira , Doganli Canan , Miltenburg Jasmijn B. , Thomsen Oskar Kaaber , Ali Zafar , Naveed Tahir , Rehman Asif ur , Baig Shahid Mahmood , Christensen Søren Tvorup , Farooq Muhammad , Larsen Lars Allan 
Published: September 2024

AbstractCongenital heart defects (CHD) appear in almost one percent of live births. Asian countries have the highest birth prevalence of CHD in the world. Recessive genotypes may represent a CHD risk factor in Asian populations with a high degree of consanguineous marriages. Genetic analysis of consanguineous families may represent a relatively unexplored source for investigating CHD etiology. To obtain insight into the contribution of recessive genotypes in CHD we analysed a cohort of forty-nine Pakistani CHD probands, originating from consanguineous unions. The majority (82%) of patient’s malformations were septal defects. We identified protein altering, rare homozygous variants (RHVs) in the patient’s coding genome by whole exome sequencing. The patients had a median of seven damaging RHVs each, and our analysis revealed a total of 758 RHVs in 693 different genes. By prioritizing these genes based on variant severity, loss-of-function intolerance and specific expression in the developing heart, we identified a set of 23 candidate disease genes. These candidate genes were significantly enriched for genes known to cause heart defects in recessive mouse models (P < 2.4e−06). In addition, we found a significant enrichment of cilia genes in both the initial set of 693 genes (P < 5.4e−04) and the 23 candidate disease genes (P < 5.2e−04). Functional investigation of ADCY6 in cell- and zebrafish-models verified its role in heart development. Our results confirm a significant role for cilia genes in recessive forms of CHD and suggest important functions of cilia genes in cardiac septation.
Effect of preoperative liraglutide 3.0 mg on incidence of intraoperative adhesions in laparoscopic sleeve gastrectomy
Authors: Martines G. , Giove C. , Carlucci B. , Dezi A. , Ranieri C. , Rotelli M. T. , De Fazio M. , Tomasicchio G. 
Published: September 2024

Abstract
Introduction
Liraglutide has shown promising results in the field of bariatric surgery, preparing patients for surgery. However, chronic therapy is often correlated with gastrointestinal disorders, such as subclinical pancreatitis. The aim of this study was to evaluate the incidence of intraoperative adhesions and post-operative complications in patients undergoing laparoscopic sleeve gastrectomy (LSG) with or without prior therapy with liraglutide.

Methods
Clinical records of patients affected by obesity who underwent LSG between March 2017 and October 2022 were retrospectively reviewed using a prospectively maintained database. Patients were separated into two groups: those managed with preoperative liraglutide for 24 weeks prior to LSG, and those without prior medical therapy. Demographic data, operative time, intraoperative adhesions, and postoperative complications were reported and compared between two groups.

Results
Ninety-three patients underwent LSG without prior medical therapy, while 87 were treated with liraglutide before surgery. There were no significant differences in terms of gender, age, and comorbidities. After treatment with liraglutide, weight (117 vs 109 kg) and BMI (45 vs 42.2 kg/m2) were statistically lower than the group with no prior treatment to surgery. Thirty-two (37%) patients of the group treated with liraglutide had intraoperative adhesion vs nine (10%) patients of the control group (p < 0.005). There were no differences recorded between the two groups concerning post-operative complications.

Conclusion
Liraglutide has introduced a new way to treat obesity, improving weight loss and comorbidities. Gastrointestinal disorders, such as subclinical pancreatitis, associated with GLP-1 analogue could explain the elevated incidence of intraoperative adhesions during bariatric surgery.
Optimisation and monotonicity of the second Robin eigenvalue on a planar exterior domain
Authors: Krejčiřík David , Lotoreichik Vladimir 
Published: September 2024

AbstractWe consider the Laplace operator in the exterior of a compact set in the plane, subject to Robin boundary conditions. If the boundary coupling is sufficiently negative, there are at least two discrete eigenvalues below the essential spectrum. We state a general conjecture that the second eigenvalue is maximised by the exterior of a disk under isochoric or isoperimetric constraints. We prove an isoelastic version of the conjecture for the exterior of convex domains. Finally, we establish a monotonicity result for the second eigenvalue under the condition that the compact set is strictly star-shaped and centrally symmetric.
Quantitative isoperimetric inequalities for classical capillarity problems
Authors: Pascale Giulio , Pozzetta Marco 
Published: September 2024

AbstractWe consider capillarity functionals which measure the perimeter of sets contained in a Euclidean half-space assigning a constant weight $$\lambda \in (-1,1)$$

λ
∈
(
-
1
,
1
)

to the portion of the boundary that touches the boundary of the half-space. Depending on $$\lambda $$
λ
, sets that minimize this capillarity perimeter among those with fixed volume are known to be suitable truncated balls lying on the boundary of the half-space. We first give a new proof based on an ABP-type technique of the sharp isoperimetric inequality for this class of capillarity problems. Next we prove two quantitative versions of the inequality: a first sharp inequality estimates the Fraenkel asymmetry of a competitor with respect to the optimal bubbles in terms of the energy deficit; a second inequality estimates a notion of asymmetry for the part of the boundary of a competitor that touches the boundary of the half-space in terms of the energy deficit. After a symmetrization procedure, the quantitative inequalities follow from a novel combination of a quantitative ABP method with a selection-type argument.
Suspended Particulate Organic Matter Supports Mesopredatory Fish Across a Tropical Seascape
Authors: Moustaka Molly , Bassett Tahlia J. , Beltran Leah , Cuttler Michael V. W. , Evans Richard D. , Gorman Daniel , Grimaldi Camille M. , Gruber Renee K. , Hyndes Glenn A. , Kendrick Gary A. , Travaglione Natalie , Wilson Shaun K. 
Published: September 2024

AbstractUnderstanding the sources of primary production supporting marine food webs is important for conserving critical habitats. However, the importance of allochthonous versus autochthonous production is often unclear. We identify the sources of primary production supporting three species of predatory fish (Lutjanus carponotatus, Lutjanus fulviflamma, and Lethrinus punctulatus) in the Dampier Archipelago, Western Australia. The proportions of mangrove, seagrass, macroalgae, and suspended particulate organic matter (SPOM) assimilated by fish of different life-history stages and from different habitats were determined using stable isotopes and Bayesian mixing models. While contributions of sources varied among species and habitats, we found that SPOM was an important energetic resource for both adults and juveniles of all three fish species. Juvenile L. carponotatus and L. punctulatus inhabiting macroalgal habitats assimilated more seagrass- and macroalgae-derived material than fish from coral or mangrove habitats, while reliance on mangrove carbon was generally limited overall. Assimilation of macrophyte-derived material decreased throughout ontogeny for L. carponotatus, while L. fulviflamma relied on a combination of SPOM and seagrass into adulthood. The contribution of macroalgae and SPOM to the diets of juvenile L. punctulatus and L. carponotatus from macroalgal habitats varied spatially but was unrelated to seascape configuration, habitat quality, or hydrodynamic conditions. While mixing models suggested a modest degree of trophic connectivity, cross-habitat trophic subsidies provided by macrophytes play a minor role in supporting the studied fish of either life-history stage. Instead, microalgal production predominantly fuels the productivity of predatory fish in this turbid, macrotidal system.
Predicting undergraduate OSCE performance using traditional and construct-driven situational judgment tests at admission
Authors: Mielke Ina , Breil Simon M. , Hissbach Johanna , Ehrhardt Maren , Knorr Mirjana 
Published: September 2024

AbstractSituational Judgement Tests (SJTs) are popular to screen for social skills during undergraduate medical admission as they have been shown to predict relevant study outcomes. Two different types of SJTs can be distinguished: Traditional SJTs, which measure general effective behavior, and construct-driven SJTs which are designed to measure specific constructs. To date, there has been no comparison of the predictive validity of these two types of SJTs in medical admission. With the present research, we examine whether the HAM-SJT, a traditional SJT, and the CD-SJT, a construct-driven SJT with an agentic and a communal scale, administered during undergraduate medical admission can predict OSCE (i.e., objective structured clinical examination) performance in a low-stakes (nLS = 159) and a high-stakes (nHS = 160) sample of medical students. Results showed a moderate positive relation between the communal scale of the CD-SJT and performance in OSCE stations with trained patients in the high-stakes sample (r =.20, p =.009). This SJT had also an incremental value in predicting the OSCE performance above and beyond GPA (i.e., grade point average), a science test (i.e., HAM-Nat), and gender (ß = 0.18, 95% CI [0.03; 0.33], p =.020). That is, individuals who chose more communal behavioral responses in the SJT were rated more favorably in interactions with trained patients in the OSCE. A comparable correlation coefficient was observed for the HAM-SJT when controlling for range restriction due to admission (rraw = 0.14 vs. rcontrolled = 0.20). Our research provides a first indication for the predictive validity of construct-driven SJTs in high-stakes undergraduate medical admission.
Adolescent Girls and Young Women Overcoming Adherence Challenges with Vaginal and Oral PrEP Use: A Longitudinal Qualitative Study from a Crossover Trial in South Africa, Uganda, and Zimbabwe
Authors: Shapley-Quinn Mary Kate , Tenza Siyanda , Jensen Destry , Tauya Thelma , Mampuru Lydia , Etima Juliane , Kemigisha Doreen , Atujuna Millicent , Soto-Torres Lydia , Johnson Sherri , Mpongo Nombeko , Mhlanga Nomsa , Ngure Kenneth , van der Straten Ariane 
Published: September 2024

AbstractRates of HIV acquisition remain high among adolescent girls and young women (AGYW) in sub-Saharan Africa. We explored South African, Ugandan, and Zimbabwean AGYW’s experiences in a crossover trial of two HIV prevention products: Daily oral pre-exposure prophylaxis pills and a monthly dapivirine vaginal ring. A subset of participants (n = 25) across all sites completed up to three serial in-depth interviews (SIDIs). The SIDIs explored barriers to product use, coping strategies, and the resulting outcomes. Coded textual data were analyzed using a product acceptability conceptual framework. Participants in the SIDIs described managing the array of challenges they encountered through formal adherence support, strategic product disclosure, and personally adapted strategies. For both products, perceived discreetness of the product and decision-making around disclosure was an important component of participants’ narratives. Participants tailored their coping strategies based on available personal resources (e.g., cell phone alarms for PrEP reminders, social support through disclosure) or study provided resources (e.g., encouragement from staff, adherence groups). Notably, challenges participants encountered with each product during the crossover period helped inform product selection during the choice period. Our findings suggest that—even in a context where AGYW have access to several options for HIV prevention—challenges to consistent product use remain, but accessible support mechanisms and informed choice can help mitigate these challenges. Enacting that choice may also empower AGYW to reach their short and long-term life goals—including for HIV prevention. (NCT03593655, 20th July 2018).
Promoting sustainability goals: innovation trajectories of Fintech through patent analysis
Authors: Ferraro Giovanna , Iovanella Antonio , Ramponi Alessandro , Rotundo Giulia 
Published: September 2024

AbstractPatents are important sources of technical knowledge because they offer a wealth of information on innovations and technological developments. This paper focuses on Fintech-related patent certificates in order to examine the technical trends in this particular sector and discuss the factors influencing technological advancement. The data were retrieved through the World Intellectual Property Organization database, considering selected keywords. Through the network analysis, we identify five relevant technological clusters that allow us to detect the technological substrate underlying the corresponding cluster. The Bass diffusion model permits the observation of the technological trajectories of each cluster, outlining the diffusion patterns. Furthermore, particular attention is given to the developing technologies defined as "green", and we describe how these trends have changed over time and predict their future technological trajectory. Our findings provide an in-depth analysis of the Fintech patent landscape, highlighting the connections between the different technologies. It also allows us to assess the technological leadership of companies and the technological life cycle that describes the diffusion patterns.
Ticagrelor and Statins: Dangerous Liaisons?
Authors: Rocca Bianca , Bigagli Elisabetta , Cerbai Elisabetta 
Published: September 2024

AbstractPolypharmacy is often necessary in complex, chronic, comorbid and cardiovascular patients and is a known risk factor for potential drug-drug interaction (DDI) that can cause adverse reactions (toxicity or therapeutic failure). Anti-thrombotic drugs (largely low-dose aspirin and a platelet P2Y12 receptor inhibitor) and statins are among the most co-administered drugs in cardiovascular patients. Ticagrelor is a selective antagonist of the platelet P2Y12-receptor, highly effective in inhibiting platelet aggregation and bio-transformed by the CYP3A4 and substrate of transporters, such as the breast cancer resistance protein (BCRP). Statins have different pharmacokinetic profiles; some undergo CYP3A4-mediated metabolism; rosuvastatin is primarily metabolized by the CYP2C9; and they have different affinities for drug transporters. Rhabdomyolysis is a very rare but severe adverse event, which is specific for statins which can be triggered by DDIs that increase statin’s concentrations through blockade of their biotransformation and/or elimination. Large pharmacovigilance and small observational studies reported increased rhabdomyolysis in patients treated with some statins and ticagrelor but not aspirin, clopidogrel or prasugrel. Recent studies in vitro, pharmacokinetic trials and in silico drug modelling identified and validated the BCRP inhibition by ticagrelor, as a mechanism contributing to the DDI with statins, as ‘victim’ drugs, leading to increased rhabdomyolysis. While the clinical impact of this DDI deserves further investigation, a careful evaluation should be advised when ticagrelor is co-prescribed with some statins.
Parent–Child Mealtime Conversations Stimulated with Decorated Tableware
Authors: Kucirkova Natalia , Bubikova-Moan Jarmila 
Published: September 2024

AbstractThis explorative qualitative study investigated how families engage in mealtime conversations supported with decorated plates that were specially designed to promote family conversations. Our aim was to examine the main thematic and discursive patterns that naturally occurred in these conversations. Six Norwegian families of pre-school children aged 3–6 years were provided with five decorated plates and asked to audio-record their conversations during a meal. Transcripts of the audio-recordings were analysed with manifest content-related analysis, followed by an abductive analysis and a mapping of the main discourse types and interactional patterns. We demonstrate that the conversations displayed great thematic heterogeneity and represented a continuum of extended and non-extended talk, ranging from basic labelling and vocabulary recall to narration, explanation and argumentation. Variable engagement levels among the participants were also noted. We argue that decorated tableware can serve as a valuable tool for studying linguistic input and the nature of adult–child conversations during mealtimes at home and beyond.
Self-Regulated Learning Interventions for Pre-service Teachers: a Systematic Review
Authors: Ortube Alazne Fernández , Panadero Ernesto , Dignath Charlotte 
Published: September 2024

AbstractSelf-regulated learning (SRL) is a key competence for pre-service teachers to develop, both for their own activities as learners and for their future activities as teachers. Therefore, it is crucial to understand how pre-service teachers can be supported in acquiring SRL competence in their initial training. To reach this aim, we conducted a systematic review of SRL interventions for pre-service teachers. Sixty-six intervention studies fulfilled the inclusion criteria. We explored three aspects of those SRL interventions, and how they moderate the interventions’ effectiveness: (1) the theoretical and practical underpinnings of SRL, (2) whether the intervention aimed to promote SRL learning and/or teaching of SRL, and (3) the intervention’s pedagogical characteristics and content related to the SRL professional competences. We found that the most effective SRL interventions (1) focused the training on one or two SRL areas (especially cognition and metacognition); (2) when targeted both, SRL learning and teaching of SRL, pre-service teachers’ SRL skills improved as well as their pedagogical skills; and (3) addressed direct and implicit SRL instruction, inside which self-assessment of learning and teaching practices appear as an effective pedagogical method. We derive implications from our findings for designing effective SRL interventions for prospective teachers.