bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recording ten-fold larger IKr conductances with automated patch clamping using equimolar Cs+ solutions
Authors: Bloothooft Meye , Verbruggen Bente , Seibertz Fitzwilliam , Heyden Marcel A. G. van der , Voigt Niels , de Boer Teun P. 
Published: January 2024

Background: The rapid delayed rectifier potassium current (IKr) is important for cardiac repolarization and is most often involved in drug-induced arrhythmias. However, accurately measuring this current can be challenging in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes because of its small current density. Interestingly, the ion channel conducting IKr, hERG channel, is not only permeable to K+ ions but also to Cs+ ions when present in equimolar concentrations inside and outside of the cell.Methods: In this study, IhERG was measured from Chinese hamster ovary (CHO)-hERG cells and hiPSC-CM using either Cs+ or K+ as the charge carrier. Equimolar Cs+ has been used in the literature in manual patch-clamp experiments, and here, we apply this approach using automated patch-clamp systems. Four different (pre)clinical drugs were tested to compare their effects on Cs+- and K+-based currents.Results: Using equimolar Cs+ solutions gave rise to approximately ten-fold larger hERG conductances. Comparison of Cs+- and K+-mediated currents upon application of dofetilide, desipramine, moxifloxacin, or LUF7244 revealed many similarities in inhibition or activation properties of the drugs studied. Using equimolar Cs+ solutions gave rise to approximately ten-fold larger hERG conductances. In hiPSC-CM, the Cs+-based conductance is larger compared to the known K+-based conductance, and the Cs+ hERG conductance can be inhibited similarly to the K+-based conductance.Conclusion: Using equimolar Cs+ instead of K+ for IhERG measurements in an automated patch-clamp system gives rise to a new method by which, for example, quick scans can be performed on effects of drugs on hERG currents. This application is specifically relevant when such experiments are performed using cells which express small IKr current densities in combination with small membrane capacitances.
An auditory perspective on phonological development in infancy
Authors: Hegde Monica , Nazzi Thierry , Cabrera Laurianne 
Published: January 2024

IntroductionThe auditory system encodes the phonetic features of languages by processing spectro-temporal modulations in speech, which can be described at two time scales: relatively slow amplitude variations over time (AM, further distinguished into the slowest &lt;8–16 Hz and faster components 16–500 Hz), and frequency modulations (FM, oscillating at higher rates about 600–10 kHz). While adults require only the slowest AM cues to identify and discriminate speech sounds, infants have been shown to also require faster AM cues (&gt;8–16 Hz) for similar tasks.MethodsUsing an observer-based psychophysical method, this study measured the ability of typical-hearing 6-month-olds, 10-month-olds, and adults to detect a change in the vowel or consonant features of consonant-vowel syllables when temporal modulations are selectively degraded. Two acoustically degraded conditions were designed, replacing FM cues with pure tones in 32 frequency bands, and then extracting AM cues in each frequency band with two different low-pass cut- off frequencies: (1) half the bandwidth (Fast AM condition), (2) &lt;8 Hz (Slow AM condition).ResultsIn the Fast AM condition, results show that with reduced FM cues, 85% of 6-month-olds, 72.5% of 10-month-olds, and 100% of adults successfully categorize phonemes. Among participants who passed the Fast AM condition, 67% of 6-month-olds, 75% of 10-month-olds, and 95% of adults passed the Slow AM condition. Furthermore, across the three age groups, the proportion of participants able to detect phonetic category change did not differ between the vowel and consonant conditions. However, age-related differences were observed for vowel categorization: while the 6- and 10-month-old groups did not differ from one another, they both independently differed from adults. Moreover, for consonant categorization, 10-month-olds were more impacted by acoustic temporal degradation compared to 6-month-olds, and showed a greater decline in detection success rates between the Fast AM and Slow AM conditions.DiscussionThe degradation of FM and faster AM cues (&gt;8 Hz) appears to strongly affect consonant processing at 10 months of age. These findings suggest that between 6 and 10 months, infants show different developmental trajectories in the perceptual weight of speech temporal acoustic cues for vowel and consonant processing, possibly linked to phonological attunement.
An app-based training for adolescents with problematic digital-media use and their parents (Res@t digital): protocol for a cluster-randomized clinical trial
Authors: Paschke Kerstin , Diestelkamp Silke , Zapf Antonia , Busch Katharina , Arnaud Nicolas , Prehn-Kristensen Alexander , Reis Olaf , Stark Maria , Cloes Jan-Ole , Schulz Anna-Lena , Brauer Hannah , Krömer Thomas , Thomasius Rainer ,   the Res@t Consortium
Published: January 2024

BackgroundDigital media-use disorders (DMUD) in adolescents are a rising phenomenon associated with psychological distress, comorbid mental disorders, and high burden on affected families. Since the ICD-11 introduced criteria for gaming disorder, these can now be transferred to describe additional DMUD associated with social media platforms and streaming services. Most evidence for effective treatments comes from cognitive-behavioral therapy (CBT). However, interventions based on theoretical models for adolescents and their parents are widely missing, leading to a significant clinical gap.MethodsRes@t digital (Resource-Strengthening Training for Adolescents with Problematic Digital-Media Use and their Parents) is the app-based translation of the first model-based digital intervention for adolescents with DMUD and their parents based on CBT. It comprises separate but content-related modules for adolescents (Res@t–A) and parents (Res@t–P), applying multimodal techniques. The effectiveness of Res@t will be evaluated within a multicenter cluster-randomized controlled evaluator-blinded pre–post follow-up trial with the waitlist control group (CG). In addition to the Res@t program in the intervention group, both groups will receive treatment as usual within primary child and adolescent psychiatric/psychotherapeutic healthcare. The primary outcome addresses DMUD symptom reduction after 10 weeks. Secondary outcomes are related to a reduction in psychological and family-related problems and an increase in parental self-efficacy. All outcomes will be assessed using standardized self-report measures. A total of 1,334 participating adolescent–parent dyads from a large clinical network throughout Germany are planned to be included in the primary analyses based on an intention-to-treat approach, applying linear mixed models.DiscussionAssuming superiority of Res@t over the control condition, the intervention has the potential to provide evidence-based treatment for a significant number of help-seeking families, supporting local healthcare structures and resources. It is a promising program for practicable implementation and flexible use in different settings.Clinical trial registrationhttps://drks.de, DRKS00031043.
Maternal dietary intake of fish and child neurodevelopment at 3 years: a nationwide birth cohort—The Japan Environment and Children's Study
Authors: Inoue Mariko , Matsumura Kenta , Hamazaki Kei , Tsuchida Akiko , Inadera Hidekuni 
Published: January 2024

BackgroundResults on the association between fish intake during pregnancy and a reduction in neurodevelopmental delays in children have been inconsistent, with some reports finding an association and others finding none. Because neurodevelopmental delays are more pronounced at the age of 3 years, their association needs to be examined at this age.MethodsAfter exclusion and multiple imputation from a dataset comprising 104,057 records from the Japan Environment and Children's Study, logistic regression analysis was conducted in quintiles to evaluate the association between maternal fish intake during pregnancy and child neurodevelopment at age 3 years in 91,909 mother–child pairs. The Food Frequency Questionnaire (FFQ), validated in the Japan Public Health Center-Based Prospective Study for the Next Generation, was used to assess maternal fish intake during pregnancy. The Ages and Stages Questionnaires-3 was used to assess children's neurodevelopment in five domains: communication, gross motor, fine motor, problem-solving, and personal-social.ResultsConsistently lower odds were found for the highest vs. lowest quintile for the domains of communication, fine motor, problem-solving, and personal-social but not gross motor skills, with adjusted odd ratios (95% confidence intervals) of 0.89 (0.80–0.998), 0.90 (0.83–0.97), 0.86 (0.80–0.94), 0.87 (0.77–0.98), and 1.04 (0.94–1.16), respectively. The trend for lower odds of symptoms of neurodevelopmental delays across quintiles of higher maternal fish intake were significant for fine motor, problem-solving, and personal-social but not communication or gross motor.ConclusionsFish consumption during pregnancy may be associated with a reduced risk of neurodevelopmental delay in 3-year-olds, particularly in the fine motor, problem-solving, and personal-social domains. Continued investigation after the age of 3 could further clarify the association.
How do socioeconomic determinants of health affect the likelihood of living with HTLV-1 globally? A systematic review with meta-analysis
Authors: Ramesh Nydile , Cockbain Beatrice , Taylor Graham P. , Rosadas Carolina 
Published: January 2024

IntroductionHuman T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity.MethodsA systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence.Results42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34–2.57]; p &lt; 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant.ConclusionFewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).
Effects of a Delayed Harvest and Additives on the Fermentation Quality of Corn Stalk Silage
Authors: Wang Li-Li , Li Yan-Fen , Yu Young-Sang , Kim Hak-Jin , Lee Won-Jin , Kim Jong-Geun 
Published: January 2024

This study investigated the effects of harvest time, cellulase, lactic acid bacteria, and ensiling with alfalfa hay on the chemical parameters, bacterial community composition, and fermentation of corn stalk silage. Corn stalks were ensiled after the ear harvest at 0 days (D0) and 20 days (D20). Each harvest was treated with alfalfa hay [AL, 5% of fresh matter (FM)], Lactobacillus plantarum (Lp) (1 × 106 CFU/g of FM), Trichoderma cellulase (TC) (100 mg/kg of FM), or both Lp and TC (Lp+TC). The silos were opened after 60 days of fermentation. The dry matter (DM) content of raw materials increased from 18.79% to 28.32% with the harvest time. The acid detergent fiber (ADF) content also significantly increased (p < 0.05), while water-soluble carbohydrates (WSCs) and in vitro dry matter digestibility (IVDMD) significantly decreased (p < 0.05). After 60 days, the neutral detergent fiber (NDF) and ADF contents increased, and all chemical composition and fermentation state parameters of silages had significant differences (p < 0.05) with the harvest time. Compared with the control group, the AL treatment resulted in higher (p < 0.05) DM and crude protein (CP) contents, and the Lp+TC treatment resulted in a lower NDF (p < 0.05) content. For D0, the TC and Lp+TC treatments resulted in a higher WSC content and lower NDF and ADF contents than in D20. Meanwhile, the ammonia-nitrogen (NH3-N) content in each treatment was less than 10% of the DM. The pH values were all approximately 3.70. The AL treatment significantly increased the lactic acid (LA) content and lactic/acetic acid ratio (LA/AA). Additionally, the silages had a similar microbial environment before and after fermentation. We recommend harvesting corn stalks for silage immediately after the corn ear harvest. Adding cellulase improved the corn stalk feed value, and ensiling with alfalfa hay improved its fermentation quality.
The Impact of Heterologous Regulatory Genes from Lipodepsipeptide Biosynthetic Gene Clusters on the Production of Teicoplanin and A40926
Authors: Zhukrovska Kseniia , Binda Elisa , Fedorenko Victor , Marinelli Flavia , Yushchuk Oleksandr 
Published: January 2024

StrR-like pathway-specific transcriptional regulators (PSRs) function as activators in the biosynthesis of various antibiotics, including glycopeptides (GPAs), aminoglycosides, aminocoumarins, and ramoplanin-like lipodepsipeptides (LDPs). In particular, the roles of StrR-like PSRs have been previously investigated in the biosynthesis of streptomycin, novobiocin, GPAs like balhimycin, teicoplanin, and A40926, as well as LDP enduracidin. In the current study, we focused on StrR-like PSRs from the ramoplanin biosynthetic gene cluster (BGC) in Actinoplanes ramoplaninifer ATCC 33076 (Ramo5) and the chersinamycin BGC in Micromonospora chersina DSM 44151 (Chers28). Through the analysis of the amino acid sequences of Ramo5 and Chers28, we discovered that these proteins are phylogenetically distant from other experimentally investigated StrR PSRs, although all StrR-like PSRs found in BGCs for different antibiotics share a conserved secondary structure. To investigate whether Ramo5 and Chers28, given their phylogenetic positions, might influence the biosynthesis of other antibiotic pathways governed by StrR-like PSRs, the corresponding genes (ramo5 and chers28) were heterologously expressed in Actinoplanes teichomyceticus NRRL B-16726 and Nonomuraea gerenzanensis ATCC 39727, which produce the clinically-relevant GPAs teicoplanin and A40926, respectively. Recombinant strains of NRRL B-16726 and ATCC 39727 expressing chers28 exhibited improved antibiotic production, although the expression of ramo5 did not yield the same effect. These results demonstrate that some StrR-like PSRs can “cross-talk” between distant biosynthetic pathways and might be utilized as tools for the activation of silent BGCs regulated by StrR-like PSRs.
Numerical Approximation for a Stochastic Fractional Differential Equation Driven by Integrated Multiplicative Noise
Authors: Hoult James , Yan Yubin 
Published: January 2024

We consider a numerical approximation for stochastic fractional differential equations driven by integrated multiplicative noise. The fractional derivative is in the Caputo sense with the fractional order α∈(0,1), and the non-linear terms satisfy the global Lipschitz conditions. We first approximate the noise with the piecewise constant function to obtain the regularized stochastic fractional differential equation. By applying Minkowski’s inequality for double integrals, we establish that the error between the exact solution and the solution of the regularized problem has an order of O(Δtα) in the mean square norm, where Δt denotes the step size. To validate our theoretical conclusions, numerical examples are presented, demonstrating the consistency of the numerical results with the established theory.
Screening as a stage in the prevention of oral mucosal diseases in patients undergoing chemotherapy for malignant growths
Authors: Makedonova Yu. А. , Shkarin V. V. , Emelyanova O. S. , Chizhikova T. V. , Venskel I. V. , Devyatchenko L. A. 
Published: January 2024

Relevance. The incidence of malignant growths in the maxillofacial area has consistently increased over the years. Chemotherapy stands out as one of the most effective treatments for cancerous tumors. Chemotherapeutic drugs possess the capability to either inhibit the proliferation of malignant cells or cause damage to them. However, while acting on abnormal cells, cytostatic drugs also impact actively dividing cells in normal tissues, including the mucous membranes in the oral cavity. As a result, various complications are observed in every patient undergoing treatment for malignant neoplasms (MN), particularly chemotherapy (CT). The nature and severity of side effects undergo changes based on the specific drugs and cytostatic treatment regimen employed. Adverse reactions and side effects inherent to each drug category manifest at different points throughout a chemotherapy course and its aftermath. Oral mucosal (OM) complications, such as oral mucositis, may ensue as a consequence of CT side effects.Materials and methods. In order to assess the effectiveness of screening for OM disorders arising as side effects of chemotherapy, a study involving 37 patients undergoing chemotherapy for an underlying condition was conducted. The screening study comprised two stages: Stage I involved a quality-of-life assessment utilizing questionnaires developed by the authors, while Stage II entailed a clinical examination of the oral mucosa. The obtained data were subjected to statistical analysis methods. Variation statistics were employed to assess the likelihood of data errors.Results. Comprehensive OM diagnostics in patients undergoing chemotherapy for an underlying oncology condition enable the early identification of oral mucosal diseases and the prevention of complications. It is recommended to conduct a thorough clinical examination and employ toluidine blue staining during each follow-up visit. Any observed clinical or stained tissue changes, the emergence of new erythematous lesions, erosions, or ulcers may serve as indicators of malignant transformation.Conclusion. It is advisable to incorporate screening diagnostics into each patient's dental visit to proactively prevent the onset of various pathological conditions.
Predictors of atrial fibrillation recurrence after simultaneous Maze-V procedure and coronary artery bypass grafting
Authors: Revishvili A. Sh. , Popov V. A. , Malyshenko E. S. , Anishchenko M. M. , Popova N. V. , Kadyrova M. W. , Aminov V. V. , Svetkin M. A. 
Published: January 2024

Aim. To identify the predictors of atrial fibrillation (AF) recurrence after simultaneous Maze V procedure in combination with coronary artery bypass grafting.Methods. Medical records of 102 patients with coronary artery disease and concomitant AF were retrospectively reviewed. All patients underwent coronary artery bypass grafting and the combined Maze V procedure. The patients were divided into 2 groups: 51 patients with paroxysmal AF (group I), and 51 patients with non-paroxysmal AF (group II). In group I, 6 cases of AF recurrence were detected (subgroup IA), while 45 patients (subgroup IB) maintained sinus rhythm for the entire follow-up period. Accordingly, in group II, the return of AF was noted in 9 patients (subgroup IIA), sinus rhythm - in 42 patients (subgroup IIB). The follow-up period was 36 months. Clinical and echocardiographic parameters were studied as predictors of AF recurrence.Results. A significant predictor in patients with paroxysmal AF was a recurrence of AF at the hospital stage (odd ratio (OR) 10,25; 95% confidence interval (CI) 1,53-68,20; р=0.032). The duration of the AF history was the main predictor in patients with non-paroxysmal AF (OR 8,8; 95% CI 1,01-76,1; р=0.04). ROC analysis revealed a significant effect on the AF recurrence of left atrium (LA) dimension >48.5 mm, LA volume index >44.4 ml/m2 for patients with paroxysmal AF, and left ventriclular end-diastolic volume > 150 ml for patients with non-paroxysmal AFConclusion. A recurrence of AF at the hospital stage, LA dimension, LA volume index were significant predictors of AF recurrence after coronary artery bypass grafting + Maze V procedure in patients with paroxysmal AF. А long AF history and left ventriclular end-diastolic volume played the role of predictors for patients with non-paroxysmal AF.
Noninvasive activation mapping during the cardiac conductive system pacing
Authors: Medved M. S. , Zubarev S. V. , Chumarnaya T. V. , Bazhutina A. E. , Solovyova O. E. , Lebedev D. S. 
Published: January 2024

Aim. To identify the features of activation of the right and left ventricles during cardiac conductive system pacing.Methods. There are 2 groups of the study. The cardiac conductive pacing carried in patients of first group. The cardiac conductive pacing not carried in patients of second group. Before and after implantation of the pacemaker, all patients underwent ECG, noninvasive activation mapping using the Amycard software and hardware complex, the width of the QRS, the activation time of the left (LVAT) and right (RVAT) ventricles were determined initially and against the background of pacing. The parameter values are presented in the format: median and interquartile range (Me [25; 75]).Results. The study protocol was performed in 30 patients: first group - 20 patients, second group - 10. The age of the patients was 73 [57; 81] and 71 [63; 75] years, respectively. The value of native QRS complexes in first group was 106 [100; 132] msec, in second group - 144 [109; 155] msec; LVAT 70 [60; 93] msec and 88 [75; 115] msec, respectively; RVAT 62 [50; 74] msec and 85 [67; 117] msec, respectively. There were no statistically significant differences between the groups (p > 0.05) in age, values of native QRS, LVAT, RVAT. The implantable electrode model is identical in both groups. The value of the QRS complex during pacing in first group was 117 [109; 125] msec and 160 [145; 173] msec in second group; LVATp 76 [65; 89] msec and 129 [119; 148] msec, respectively; RVAT 67 [60; 80] msec and 108 [90; 128] msec, respectively. The study revealed statistically significant differences between the two groups of all evaluated parameters against the background of pacing: QRS (p = 0.01), LVAT (p = < 0.01), RVAT (p < 0.01). It should be noted that the initial values and values against the background of pacing of the QRS, LVAT, RVAT complex in patients of group No. 1 did not differ (p > 0.05); in patients of the second group, the values of the QRS, LVAT, RVAT complex initially and against the background of stimulation had significant differences (p = 0.11, p < 0.01 and p = 0.038 respectively).Conclusion. Cardiac conductive system paving is a promising method of cardiac pacing, which allows to achieve activation of the myocardium of the left and right ventricles, which does not differ significantly from activation with a sinus rhythm.