Central Event Research Articles

Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Observation of the Electromagnetic Field Effect via Charge-Dependent Directed Flow in Heavy-Ion Collisions at the Relativistic Heavy Ion Collider

The deconfined quark-gluon plasma (QGP) created in relativistic heavy-ion collisions enables the exploration of the fundamental properties of matter under extreme conditions. Noncentral collisions can produce strong magnetic fields on the order of 1018 G, which offers a probe into the electrical conductivity of the QGP. In particular, quarks and antiquarks carry opposite charges and receive contrary electromagnetic forces that alter their momenta. This phenomenon can be manifested in the collective motion of final-state particles, specifically in the rapidity-odd directed flow, denoted as v1(y). Here, we present the charge-dependent measurements of dv1/dy near midrapidities for π±, K±, and p(p¯) in Au+Au and isobar (Ru4496+Ru4496 and Zr4096+Zr4096) collisions at sNN=200 GeV, and in Au+Au collisions at 27 GeV, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The combined dependence of the v1 signal on collision system, particle species, and collision centrality can be qualitatively and semiquantitatively understood as several effects on constituent quarks. While the results in central events can be explained by the u and d quarks transported from initial-state nuclei, those in peripheral events reveal the impacts of the electromagnetic field on the QGP. Our data put valuable constraints on the electrical conductivity of the QGP in theoretical calculations. Published by the American Physical Society 2024

Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study.

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol's adverse effects. Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18-11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84-9.28), and 3.25 (95% CI 1.78-5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.

A Novel Perspective on PCSK9 in Alzheimer's Disease: A Focus on Amyloid Beta.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) belongs to a member of the proprotein convertase (PC) family, which is mainly secreted by the liver and plays a central role in lipid metabolism. Furthermore, PCSK9 plays a multifunctional role in promoting the inflammatory response, inducing cell apoptosis and pyroptosis and affecting tumor homeostasis. The brain is the organ with the richest lipid content. Incidentally, PCSK9 increased in many brain diseases, including brain injury and Alzheimer's disease (AD). Consequently, the relationship between PCSK9 and brain diseases has attracted increasing research interest. Amyloid beta (Aβ) accumulation is the central and initial event in the pathogenesis of AD. This study focuses on the effects of PCSK9 on Aβ accumulation in the brain via multiple modalities to explore the potential role of PCSK9 in AD, which is characterized by progressive loss of brain cells by increasing Aβ accumulation. The study also explores the new mechanism by which PCSK9 is involved in the pathogenesis of AD, providing interesting and innovative guidance for the future of PCSK9-targeted therapy for AD.

The Prevalence of Sentinel Central Events (SCent) During Drug-Induced Sleep Endoscopy.

With the recent addition of airflow and respiratory effort channels, our group has observed central and mixed apnea events during drug-induced sleep endoscopy (DISE). We measured the frequency and timing of sentinel central and/or mixed events (SCents), as well as assessed for differences in velum, oropharynx, tongue, and epiglottis (VOTE) classification compared to obstructive events. Prospective single-cohort study. Tertiary Care Academic Medical Center. Patients underwent DISE between June 2020 and November 2022. Nasal airflow, thoracoabdominal effort belt signals, and videoendoscopy were simultaneously captured. Demographics, sleep study, and DISE data were compared among patients with and without SCents using Student's T tests or χ2 tests. On average, the cohort (n = 103) was middle-aged (53.5 ± 12.1 years), overweight (body mass index of 29.7 ± 5.3 kg/m2), and had severe obstructive sleep apnea (apnea-hypopnea index of 30.7 ± 18.7 events/h). Forty-seven patients (46%) were found to have at least 1 SCent. Among those with SCent, 45 (95.7%) transitioned to obstructive pathology after an average of 7.91 ± 2.74minutes, with at least 95% of patients expected to do so within 12.57minutes. Twenty-nine out of 47 patients (61.2% [95% confidence interval: 46.4.9%, 75.5%]) with SCent had meaningful differences between central/mixed and obstructive VOTE scores. Central events were present in almost half of our cohort. At least 95% of patients were expected to transition to obstructive events within 12 to 13minutes of propofol initiation. In addition, over half of patients demonstrate significantly different VOTE scores between central and obstructive events. These factors should raise awareness of central events and scoring passive apneas during DISE and consider delaying VOTE scoring.

Unusual Atrophic Nervus Intermedius in a Patient with Refractory Nervus Intermedius Neuralgia and History of Ipsilateral Sudden-Onset Central Facial Palsy and Sensorineural Hearing Loss: Cadaveric-Clinical Images with Surgical Video

Nervus intermedius (NI) arises from the superior salivary nucleus, solitary nucleus, and the trigeminal tract. It leaves the pons as one to five roots and then travels between the facial and vestibulocochlear nerves before merging with the facial nerve within the internal auditory canal. The mastoid segment of the facial nerve then gives rise to a sensory branch that supplies the posteroinferior wall of the external auditory meatus and inferior pina. This complex pathway renders the nerve susceptible to various pathologies, leading to NI neuralgia. Here, the authors present an unusual intraoperative finding of an atrophic NI in a patient with refractory NI neuralgia and a history of ipsilateral sudden-onset central facial palsy and microvascular decompression for trigeminal neuralgia. The patient underwent NI sectioning via the previous retrosigmoid window and achieved partial ear pain improvement. The gross size of the NI is compared to a cadaveric specimen. This case highlights the potential role of subtle central ischemic events and subsequent atrophy of NI in the pathogenesis of NI neuralgia, as well as the ongoing need to investigate NI sectioning therapeutic efficacy.

Automated scoring of the autobiographical interview with natural language processing.

The autobiographical interview has been used in more than 200 studies to assess the content of autobiographical memories. In a typical experiment, participants recall memories, which are then scored manually for internal details (episodic details from the central event) and external details (largely non-episodic details). Scoring these narratives requires a significant amount of time. As a result, large studies with this procedure are often impractical, and even conducting small studies is time-consuming. To reduce scoring burden and enable larger studies, we developed an approach to automatically score responses with natural language processing. We fine-tuned an existing language model (distilBERT) to identify the amount of internal and external content in each sentence. These predictions were aggregated to obtain internal and external content estimates for each narrative. We evaluated our model by comparing manual scores with automated scores in five datasets. We found that our model performed well across datasets. In four datasets, we found a strong correlation between internal detail counts and the amount of predicted internal content. In these datasets, manual and automated external scores were also strongly correlated, and we found minimal misclassification of content. In a fifth dataset, our model performed well after additional preprocessing. To make automated scoring available to other researchers, we provide a Colab notebook that is intended to be used without additional coding.

Measurements of inclusive J/ψ production at midrapidity and forward rapidity in Pb–Pb collisions at [formula omitted] = 5.02 TeV

The measurements of the inclusive J/ψ yield at midrapidity (|y|<0.9) and forward rapidity (2.5 <y< 4) in Pb–Pb collisions at sNN=5.02 TeV with the ALICE detector at the LHC are reported. The inclusive J/ψ production yields and nuclear modification factors, RAA, are measured as a function of the collision centrality, J/ψ transverse momentum (pT), and rapidity. The J/ψ average transverse momentum and squared transverse momentum (〈pT〉 and 〈pT2〉) are evaluated as a function of the centrality at midrapidity. Compared to the previous ALICE publications, here the entire Pb–Pb collisions dataset collected during the LHC Run 2 is used, which improves the precision of the measurements and extends the pT coverage. The pT-integrated RAA shows a hint of an increasing trend towards unity from semicentral to central collisions at midrapidity, while it is flat at forward rapidity. The pT-differential RAA shows a strong suppression at high pT with less suppression at low pT where it reaches a larger value at midrapidity compared to forward rapidity. The ratio of the pT-integrated yields of J/ψ to those of D0 mesons is reported for the first time for the central and semicentral event classes at midrapidity. Model calculations implementing charmonium production via the coalescence of charm quarks and antiquarks during the fireball evolution (transport models) or in a statistical approach with thermal weights are in good agreement with the data at low pT. At higher pT, the data are well described by transport models and a model based on energy loss in the strongly-interacting medium produced in nuclear collisions at the LHC.

History of the Children of Israel Between the Noble Qur’an and the Book of Exodus

The second book of the Pentateuch is called Exodus, from the Greek word for “departure,” because its central event was understood by the Septuagint’s translators to be the departure of the Israelites from Egypt. Its Hebrew title, Shemoth (“Names”), is from the book’s opening phrase, “These are the names….” Continuing the history of Israel from the point where the Book of Genesis leaves off, Exodus recounts the Egyptian oppression of Jacob’s ever-increasing descendants and their miraculous deliverance by God through Moses, who led them across the Red Sea to Mount Sinai where they entered. This article attempts to study the historical aspect of the Book of Exodus compared to the Noble Qur’an, adopting the comparative historical methodology.

War and women: An analysis of Ukrainian refugee women staying in the Czech Republic.

In addition to the loss of life, Russian aggression against Ukraine, which began in February 2022, also brings interpersonal losses resulting from the need to emigrate. Parallel to the fighting men, women bear most of the burden of caring for the family. Using in-depth interviews supplemented by questions about adverse childhood experiences and administration of The Centrality of Events Scale and the PTSD Checklist - PCL-5 with 43 Ukrainian women (18-60years old), we analyzed adaptation to the situation of emigration and the association of their war and earlier experiences with the level of traumatization. Women were interviewed shortly after emigration to the Czech Republic (3-42week afterward). High levels of adverse childhood experiences and post-traumatic stress symptoms were found. The war was perceived as a currently negative central event associated with traumatic stress symptoms, and 79% of the sample expressed the opinion that the war had changed them. The results of this study suggest an intertwining of previous life experiences with the current need and ability to adapt.

Fast Window-Based Event Denoising with Spatiotemporal Correlation Enhancement.

Previous deep learning-based event denoising methods mostly suffer from poor interpretability and difficulty in real-time processing due to their complex architecture designs. In this paper, we propose window-based event denoising, which simultaneously deals with a stack of events while existing element-based denoising focuses on one event each time. Besides, we give the theoretical analysis based on probability distributions in both temporal and spatial domains to improve interpretability. In temporal domain, we use timestamp deviations between processing events and central event to judge the temporal correlation and filter out temporal-irrelevant events. In spatial domain, we choose maximum a posteriori (MAP) to discriminate real-world event and noise and use the learned convolutional sparse coding to optimize the objective function. Based on the theoretical analysis, we build Temporal Window (TW) module and Soft Spatial Feature Embedding (SSFE) module to process temporal and spatial information separately, and construct a novel multi-scale window-based event denoising network, named WedNet. The high denoising accuracy and fast running speed of our WedNet enables us to achieve real-time denoising in complex scenes. Extensive experimental results verify the effectiveness and robustness of our WedNet. Our algorithm can remove event noise effectively and efficiently and improve the performance of downstream tasks.

A candidate for central tidal disruption event in the broad line AGN SDSS J1605 with double-peaked broad H β

ABSTRACT In this letter, motivated by double-peaked broad Balmer emission lines probably related to tidal disruption events (TDEs), a potential TDE candidate is reported in Sloan Digital Sky Survey (SDSS) J160536+134838 (=SDSS J1605) at z ∼ 0.44 having quasar-like spectrum but with double-peaked broad H β. The long-term Catalina Sky Survey (CSS) light curve can be naturally described by a main-sequence star of $2.82_{-0.19}^{+0.20}{\rm M_\odot }$ disrupted by the central black hole (BH) of $144_{-21}^{+26} \times 10^6{\rm M_\odot }$ in SDSS J1605. Meanwhile, the All-Sky Automated Survey for SuperNovae light curves afterwards show none apparent trend variability, indicating the bright CSS flare in SDSS J1605 unique and different enough from variability of normal active galactic nuclei (AGN). Furthermore, there is a consistency between the TDE model determined sizes of debris with the sizes of emission regions for the double-peaked broad H β described by the accretion disc model, supporting the disc-like broad emission line regions (BLRs) probably related to a central TDE in SDSS J1605. And the virial BH mass ∼7 times higher than the TDE model determined value can be naturally explained by R–L relation determined BLRs sizes very larger than the actual distance of emission regions related to TDEs debris in SDSS J1605. Although no clear conclusion on double-peaked broad lines absolutely related to TDEs, the results here provide clues to detect potential TDEs in AGN with double-peaked broad lines.

Molecular docking and MD simulations reveal protease inhibitors block the catalytic residues in Prp8 intein of Aspergillus fumigatus: a potential target for antimycotics

Resistance to azoles and amphotericin B especially in Aspergillus fumigatus is a growing concern towards the treatment of invasive fungal infection. At this critical juncture, intein splicing would be a productive, and innovative target to establish therapies against resistant strains. Intein splicing is the central event for the activation of host protein, essential for the growth and survival of various microorganisms including A. fumigatus. The splicing process is a four-step protease-like nucleophilic cascade. Thus, we hypothesise that protease inhibitors would successfully halt intein splicing and potentially restrict the growth of the aforementioned pathogen. Using Rosetta Fold and molecular dynamics simulations, we modelled Prp8 intein structure; resembling classic intein fold with horse shoe shaped splicing domain. To fully comprehend the active site of Afu Prp8 intein, C1, T62, H65, H818, N819 from intein sequences and S820, the first C-extein residue are selected. Molecular docking shows that two FDA-approved drugs, i.e. Lufotrelvir and Remdesivir triphosphate efficiently interact with Prp8 intein from the assortment of 212 protease inhibitors. MD simulation portrayed that Prp8 undergoes conformational change upon ligand binding, and inferred the molecular recognition and stability of the docked complexes. Per-residue decomposition analysis confirms the importance of F: block R802, V803, and Q807 binding pocket in intein splicing domain towards recognition of inhibitors, along with active site residues through strong hydrogen bonds and hydrophobic contacts. However, in vitro and in vivo assays are required to confirm the inhibitory action on Prp8 intein splicing; which may pave the way for the development of new antifungals for A. fumigatus. Communicated by Ramaswamy H. Sarma

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning.

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Challenges and adverse events in pediatric hypoglossal nerve stimulation

IntroductionHypoglossal nerve stimulation was recently FDA approved for use in children with Down Syndrome and persistent obstructive sleep apnea. Although there is a robust experience in hypoglossal nerve stimulation in adults, we observed several challenges that are unique to providing this therapy to a complex pediatric population with a high rate of sensory processing disorders. We sought to review the adverse events and challenges to inform clinicians as hypoglossal nerve stimulation becomes a more accessible option for this complex population. MethodsRetrospective case series of children with Down Syndrome and persistent OSA who underwent hypoglossal nerve stimulation. Inclusion and exclusion criteria included Down Syndrome, age 10–22 years, persistent severe OSA after adenotonsillectomy (AHI>10 with <25 % central or mixed events), inability to tolerate positive airway pressure, and absence of concentric palatal collapse on sleep endoscopy. Patients were identified and their charts were reviewed. Adverse events and their subsequent management were recorded. The major outcome variable was the total number of adverse events. ResultsA total of 53 patients underwent implantation of a hypoglossal nerve stimulator; 35 (66 %) patients were male and the average age at implantation was 15.1 years (standard deviation 3.0y). A total of 30 adverse events were noted, including 17 nonserious and 13 serious. The most common nonserious complications included temporary tongue discomfort, rash at the surgical site, and cellulitis. Serious complications included readmission (for cellulitis, pain, and device extrusion), reoperation (most commonly for battery depletion) and pressure ulcer formation. ConclusionHypoglossal nerve stimulation provides a much-needed therapy for children with DS and persistent OSA after adenotonsillectomy. Although there is a robust experience in providing this treatment to adults, many considerations must be made when adapting this technology to a pediatric population with a high rate of sensory processing disorders.

Significant relationships between drought indicators and impacts for the 2018–2019 drought in Germany

Despite the scientific progress in drought detection and forecasting, it remains challenging to accurately predict the corresponding impact of a drought event. This is due to the complex relationships between (multiple) drought indicators and adverse impacts across different places/hydroclimatic conditions, sectors, and spatiotemporal scales. In this study, we explored these relationships by analyzing the impacts of the severe 2018–2019 central European drought event in Germany. We first computed the standardized precipitation index (SPI), the standardized precipitation evaporation index (SPEI), the standardized soil moisture index (SSMI) and the standardized streamflow index (SSFI) over various accumulation periods, and then related these indicators to sectorial losses from the European drought impact report inventory (EDII) and media sources. To cope with the uncertainty associated with both drought indicators and impact data, we developed a fuzzy method to categorize them. Lastly, we applied the method at the region level (EU NUTS1) by correlating monthly time series. Our findings revealed strong and significant relationships between drought indicators and impacts over different accumulation periods, albeit in some cases region-specific and time-variant. Furthermore, our analysis established the interconnectedness between various sectors, which displayed systematically co-occurring impacts. As such, our work provides a new framework to explore drought indicators-impacts dependencies across space, time, sectors, and scales. In addition, it emphasizes the need to leverage available impact data to better forecast drought impacts.

Sleep bruxism and associated physiological events in children with obstructive sleep apnea: a polysomnographic study.

The aim of this study was to evaluate the physiological events associated with sleep bruxism (Sleep Bruxism [SB]; presence of mandibular movement activity) and the control window (4 minutes prior to SB event, where no mandibular movement activity was detected) in a polysomnography study in children with mild sleep apnea. Polysomnography data from children aged 4 to 9 years old diagnosed with mild sleep apnea were analyzed by 2 trained examiners. The mandibular movement activity (bruxism event; SB) was classified into phasic and tonic. The control window was selected 4 minutes prior to the SB event. All physiological events were recorded in both bruxism and control windows, including sleep phase (N1, N2, N3, and rapid eye movement), arousal, leg movements, tachycardia, bradycardia, oxygen desaturation, and number of obstructive and central sleep apnea events. The moment in which those phenomena occurred when associated with SB was also analyzed (before/after). Data were analyzed using 95% confidence intervals (α = 5%). A total of 661 mandibular movements were analyzed and classified as tonic (n = 372) or phasic (n = 289). The mean apnea-hypopnea index was 1.99 (SD = 1.27) events/h. The frequency of leg movements, microarousal, and tachycardia was increased in SB events when compared with the control window (P < .05). There was an increase in bradycardia frequency in the control window when compared with SB (in both tonic and phasic events). The frequency of obstructive and central apnea during SB was lower when compared with the other physiological phenomena. There is a difference in the physiological parameters evaluated in children with mild sleep apnea when comparing the 2 windows (SB and control). Sleep bruxism is associated with other physiological phenomena, such as leg movements, tachycardia, and microarousal. The use of a control window (where no mandibular activity was detected) was representative since it did not show activation of the sympathetic nervous system. Bonacina CF, Soster LMSFA, Bueno C, etal. Sleep bruxism and associated physiological events in children with obstructive sleep apnea: a polysomnographic study. J Clin Sleep Med. 2024;20(4):565-573.

The Popular Ballad, Rumours and Memories as a Special Narrative Format

In principle, the new folksongs or folk ballads of the end of the 19th and beginning of the 20th century telling about dramatic events could also be called versified media news, as their aim was to mediate topical shocking events, in particular accidents or murders, thus serving as rumours, news and entertainment all in one. The popular ballad ‘Saatuse vangis’ (‘Bound by Fate’) tells a sensational story from southern Estonia. The song spread together with hearsay concerning the central event, the circumstances of the making of the song, and the characters involved. Over time, a specific type of story-telling developed, that mingled prose with parts of the song. The ballad together with the pertaining lore allows us to view the events descried from different aspects, creating a broader picture of the development and meaning of a popular text. The rumours, comments and personal memories accompanying the song helped both the contemporary and subsequent generations to understand and interpret the event. The stories spreading in the community by word of mouth addressed various circumstances “beyond the song”, and the narrator’s own emotions and opinions on the matter.

Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites.

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).

Strategies in Recruitment and Retention of Patients with Sickle Cell Disease for a Single-Site Longitudinal Clinical Trial

Background Sickle cell disease (SCD) leads to vaso-occlusive crises (VOCs) and increased healthcare use, disproportionately affecting Black/African Americans. Recruiting and retaining patients with SCD in clinical trials is challenging, with &amp;lt;5% participation rates (Masese et al., 2021) due to complexity, limited awareness, and socio-economic factors (Suarez et al., 2020). Addressing these obstacles to patient recruitment is crucial for advancing SCD research. An estimated 1,695 individuals in various counties in Indiana state are affected by SCD, with 87% being of Black/African American ethnicity (Okolo et al., 2023). The limited number of comprehensive SCD care centers poses significant challenges to recruitment for our ongoing single-site longitudinal trial in Indianapolis to explore the neurobiological mechanisms underlying pain in SCD and the effectiveness of acupuncture. The study consists of 14 in-person visits in 6-8 weeks with 12-month follow-up visits (ClinicalTrials.gov Identifier: NCT05045820). To address these recruitment challenges and ensure meaningful research outcomes, strategic communication, collaboration, and outreach efforts were undertaken to recruit eligible participants and ensure retention. This work aimed to identify factors affecting participant retention rates, including demographic differences between those who completed and those who dropped out. Study Design and Method SCD participants were recruited from either local hospitals, including the Indiana University Affiliated Hospitals and local hospitals (such as Eskenazi Hospital, St. Vincent and the Indiana Hemophilia &amp; Thrombosis Center), or external organizations, such as the Martin Center SCD Initiative and community settings, such as churches and community care centers. Various media platforms and events, such as health fairs, campus center events, and church events, were employed to widen our outreach. Local events suggested by participants further reinforced the study's credibility among prospective participants. Retaining participants was achieved through robust and customized strategies throughout the study, including but not limited to 1) personalized real-time communication with the principal investigator, 2) regular check-ins to address concerns, 3) real-time appointment scheduling, rescheduling and reminding system, and 4) hybrid (remote/in-person) follow-up visits. Moreover, additional complementary strategies, such as motivational incentives, transportation vouchers, education platforms, actively listening to feedback, timely communication, and spiritual support were utilized to ensure our complete dedication to their well-being. Results We achieved high recruitment and retention rates in our study. So far, our retention rate is 87.1%. Of these, 24.19% completed the entire study, including in-person visits and the 12-month follow-up (n=15). 56.45% of participants are still actively enrolled in the study (n=35), while 12.9% have discontinued participation (n=8). Two participants were deceased. Our utilization of effective recruitment and retention strategies yielded continuous success in actively recruiting and retaining patients with SCD. Compared to the group of participants who dropped out from the study (n=8 total, female: n=2), participants who completed all scheduled study visits (n=15, female: n=12) were more likely to be female (p = 0.008, independent samples t-test) and have lower disease severity assessed by the frequency of VOCs in the preceding 12 months (p = 0.007, independent samples t-test). Participants recruited from external facilities/events yielded a significantly lower dropout rate than those recruited from local hospitals (p = 0.036, Chi-Square Tests). These results suggest the impact of gender, disease severity, and recruitment source on the retention rate. Conclusion The success of SCD clinical trials hinges on implementing personalized recruitment and retention strategies. Further efforts are necessary to explore innovative engagement methods targeting gender and disease-specific challenges while continuously forging solid partnerships with external facilities/organizations.