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Abstract Background Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation. Methods A total of 4487 mother–newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into “any” versus “no”. DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed. Results Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P

La investigación tiene como objetivo explorar cómo la ingeniería de software puede facilitar o limitar la inclusión a través del diseño y desarrollo de tecnologías accesibles. Para lograr esto, se aplicó una encuesta a 176 desarrolladores de software de Guayaquil y Quito, con el fin de conocer sus conocimientos, prácticas y percepciones en torno al diseño de tecnologías accesibles. Los resultados de la encuesta revelaron que, aunque la mayoría de los encuestados reconoce la importancia de desarrollar un software basado en principios de inclusión, existen barreras significativas, como la falta de formación en principios de diseño inclusivo y herramientas adecuadas. En cuanto a las mejores prácticas, se identificaron enfoques como la utilización de guías de accesibilidad y la implementación de pruebas de usabilidad con usuarios diversos, lo cual puede ser adoptado para mejorar la inclusión. Estos hallazgos sugieren no solo un interés en mejorar las prácticas actuales, sino también una clara oportunidad para fomentar una cultura de accesibilidad entre los desarrolladores desde el inicio del diseño del software, atendiendo al impacto que tiene la ingeniería de software en los procesos inclusivos.

Evaluation of land suitability is carried out to perceive the potential and limitation factors of an area as an agricultural development area. Air Putih Village is one of the potential area for watermelon development area. This research was conducted to perceive the level of actual and potential land suitability for watermelon cultivation in Air Putih Village, Tuah Madani District, Pekanbaru City in the form of a semi-detailed map scale of 1:25.000. The method used in this study was a purposive sampling survey based on a map of land units. There were 7 units of land covering an area of 330.56 ha with a total of 21 sample points. Data were sourced from field observation, analysis of chemistry and physics of soil samples at the laboratory and secondary data from climate data. Land suitability assessment was carried out using the limiting factor matching method. The actual land suitability was in class S3 and N with effective soil depth (rc), base saturation (nr), slope (eh) and soil texture (rc) as limiting factors. The class of the potential land suitability for watermelon cultivation were S2, S3 and N.

Abstract The plasticity of cancer cells facilitates their ability to adopt heterogeneous differentiation states, posing a significant challenge to therapeutic interventions. Specific gene expression programs, driven in part by super-enhancers (SEs), underlie cancer cell states. Here we successfully inhibit SE-driven transcription in phenotypically distinct metastatic melanoma cells using next-generation synthetic ecteinascidins. Through functional genomic methodologies, we demonstrate that these compounds inhibit the expression of genes encoding lineage-specific or ubiquitous transcription factors/coactivators by selectively targeting the CpG-rich sequences within their promoters and/or enhancers. This prevents the formation of transcription factor/coactivator condensates necessary for SE-dependent gene expression. Consequently, these compounds exhibit cytotoxic activity across distinct subpopulations of metastatic melanoma cells and inhibit tumor proliferation, including those resistant to current therapies. These findings extend to other cancers, like small cell lung cancer, recently approved for ecteinascidin-based treatment. Overall, our study provides preclinical proof that pan-inhibition of SE-dependent genes with synthetic ecteinascidins is a promising therapeutic approach for tumors with heterogeneous transcriptional landscapes.

Objective: The study aimed to optimize protocols for the joint extraction of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from 0.025 × 106 CFU of Candida albicans, targeting to overcome the challenges in the extraction of these genetic materials. Materials and methods: From this, treated silicon carbide (SiC) granules were added to fungal samples from methods 1, 2, and 3 obtained from aliquots of BHI or Sabouraud medium to cause cell lysis and enable the isolation of these macromolecules by phenol and chloroform. The concentration and integrity of the extracted nucleic acids were analyzed, respectively, by spectrophotometry using the A260/A280 ratios and 1% agarose gel electrophoresis. Results: Therefore, method 3 is the one that most comprises samples considered pure of both DNA and RNA, simultaneously. Furthermore, the presence of intact RNAs corresponding to the base pair size such as 5.8 S rRNA and tRNA was verified during electrophoresis, considering the particularities of RNA, which makes it very unstable and easily degraded. Conclusions: Thus, it results in a faster and simpler method in addition to obtain promising results using minimal amounts of biological sample and offering a valuable alternative for small laboratories to work with molecular biology.

Abstract A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.

Summary: Background: Physiological-based cord clamping (PBCC) in preterm infants is beneficial for cardiovascular transition at birth and may optimize placental transfusion. Whether PBCC can improve clinical outcomes is unknown. The aim of the Aeration, Breathing, Clamping (ABC3) trial was to test whether PBCC results in improved intact survival in very preterm infants. Methods: The ABC3 trial was a parallel-group, multicentre, randomised, controlled superiority clinical trial conducted in all Dutch tertiary referral centers for perinatal care involving infants born before 30 weeks of gestation. Infants were randomised to either PBCC or time-based delayed cord clamping (TBCC), stratified by gestational age and treatment center. Infants receiving PBCC were stabilised with umbilical cord intact, which was clamped after reaching cardiorespiratory stability (heart rate >100 bpm and SpO2 >85% while supplemental oxygen

Background The neonatal Sequential Organ Failure Assessment (nSOFA) score is an organ dysfunction score developed for predicting mortality risk in preterm neonates with proven late-onset neonatal sepsis (LONS) and necrotising enterocolitis. However, the utility of the nSOFA score in determining the risk of retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) or mortality in patients with suspected LONS is unknown.Methods We performed a dual-centre retrospective cohort study of preterm (gestational age

Abstract BackgroundNeonatal intensive care unit admissions of newborns are emotional and stressful for parents, influencing their mental and physical well-being and resulting in high rates of psychological morbidities. Significant research has been undertaken to understand and quantify the burden of a newborn’s medical journey on parents’ well-being. Simultaneously, an increase has been observed in the development and implementation of telemedicine interventions, defined as the remote delivery of health care. Telemedicine is used as an overarching term for different technological interventions grouped as real-time audio-visual communication, remote patient monitoring, and asynchronous communication. Various telemedicine interventions have been proposed and developed but scarcely with the primary goal of improving parental well-being during their newborn’s medical journey. ObjectiveThis study aims to identify telemedicine interventions with the potential to improve parents’ well-being and to present the methods used to measure their experience. MethodsA scoping review was conducted, including empirical studies evaluating telemedicine in neonatal care that either measured parental well-being or included parents in the evaluation. Abstract and title screening, full-text screening, and data extraction were performed by three researchers. Two researchers were needed to reach decisions on both the inclusion and extraction of articles. ResultsThe review included 50 out of 737 screened articles. Telemedicine interventions focused mainly on daily visits at the neonatal intensive care unit and discharge preparedness for parents. Surveys were the primary tool used for outcome measurement (36/50, 72%). Aspects of parents’ well-being were evaluated in 62% (31/50) of studies. Telemedicine interventions developed to provide education and support showed a potential to improve self-efficacy and discharge preparedness and decrease anxiety and stress when they included a real-time telemedicine component. ConclusionsThis scoping review identified specific telemedicine interventions, such as real-time audio-visual communication and eHealth apps, that have the potential to improve parental well-being by enhancing self-efficacy and discharge preparedness, and reducing anxiety and stress. However, more insights are needed to understand how these interventions affect well-being. Parents should be included in future research in both the development and evaluation stages. It is important to not only measure parents’ perceptions but also focus on the impact of a telemedicine intervention on their well-being.

Moringa oleifera (“moringa”) seeds are sources of fixed oil with a composition of fatty acids important for their biological properties. This work aimed to verify the fixed oil of seed, regarding chemical composition, antibacterial activity alone and in association with antibiotics against standard and multidrug resistant bacterial strains. In the chemical composition of the fixed oil, the unsaturated fatty acids (78.26 %) predominated in relation to saturated fatty acids (17.34 %). The palmitic acid (5.88 %), behenic acid (4.27 %), stearic acid (4.17 %) and oleic acid (74.15 %) were the main constituents. Physicalchemical analyzes for moisture, acidity, pH, relative density, peroxide index and refractive index indicated chemical quality of the oil. We performed docking calculation to prioritize low affinity major molecules present in the chemical composition. The docking result of the all compounds showed that highest binding energy type Hydrogen bond, water hydrogen bond and hydrophobic interaction. The fixed oil did not show antibacterial activity alone with a minimum inhibitory concentration (MIC ≥ 1024 μg/mL) for the analyzed bacterial strains. Synergistic effects were verified in the association of the fixed oil with gentamicin, ofloxacin and penicillin against multiresistant strains, with reductions in MICs.

The majority of AI literacy studies have designed and developed self-reported questionnaires to assess AI learning and understanding. These studies assessed students' perceived AI capability rather than AI literacy because self-perceptions are seldom an accurate account of true measures. International assessment programs that use objective measures to assess science, mathematical, digital, and computational literacy back up this argument. Furthermore, because AI education research is still in its infancy, the current definition of AI literacy in the literature may not meet the needs of young students. Therefore, this study aims to develop and validate an AI literacy test for school students within the interdisciplinary project known as AI4future. Engineering and education researchers created and selected 25 multiple-choice questions to accomplish this goal, and school teachers validated them while developing an AI curriculum for middle schools. 2390 students in grades 7 to 9 took the test. We used a Rasch model to investigate the discrimination, reliability, and validity of the items. The results showed that the model met the unidimensionality assumption and demonstrated a set of reliable and valid items. They indicate the quality of the test items. The test enables AI education researchers and practitioners to appropriately evaluate their AI-related education interventions.

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen. Methods: Experiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, stimulated Raman scattering (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy. Main findings: 1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to low density lipoprotein (LDL) density; 3) Both in vitro and in vivo, when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress. Conclusion: The results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be an important factor in the partitioning of TG between cytosolic LDs and VLDL particles.

Pectobacterium chrysanthemi es el agente causal de la pudrición blanda que comúnmente afecta los cultivos de banano orgánico de todo el planeta. Las políticas actuales de control fitosanitario se basan en la sintomatología causada por la enfermedad. Sin embargo, al existir otras especies que causan síntomas similares, se recurre a pruebas de patogenicidad a las que se debe adicionar pruebas bioquímicas para llegar a identificar la bacteria, prescindiendo de ensayos moleculares que, en contraste, permitirían obtener resultados más específicos y en menor tiempo. Este artículo presenta una metodología alternativa en el diagnóstico rápido y específico de la pudrición blanda causada por Pectobacterium chrysanthemi en cultivos de banano orgánico del Perú. La detección mediante virulencia de la bacteria en tejido hospedante de Solanum tuberosum y la PCR del espaciador transcrito interno (ITS) del ADNr 16S/23S, permite el manejo oportuno de la enfermedad. Los resultados demuestran que en el complejo entre la prueba de patogenicidad y el ensayo PCR- ITS 16S/23S es posible detectar a Pectobacterium chrysanthemi en un periodo de 8 días, 3 horas y 15 minutos, demostrando que este método es más eficiente que las pruebas bioquímicas usualmente empleadas para el diagnóstico de la pudrición blanda en Musa sp.

Abstract Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk.

Fire caterpillars (Sethotosea asigna, Lepidoptera: Limacodidae) are a major pest of oil palms and cause harvesting losses. Natural enemies such as Sycanus sp. are reported to control fire caterpillars. The biological of Sycanus sp. were observed in the laboratory when fed using the alternative feed, maggot Black Soldier Fly (Hermetia illucens L.). Variables observed were egg, nymph, imago stadia, and the life cycle of Sycanus sp. The data were calculated, displayed as figures and tables, and given descriptive analysis. The results showed that predatory insects, Sycanus sp., can thrive well by providing alternative feed, such as Black Soldier Fly (BSF) (Hermetia illucens) maggots. Based on the results, it was known that one female Sycanussp. Could produce 101 eggs after being fed BSF maggots, with an incubation period of 17 days. The duration of the nymph stage was around 64.16 days, with a relatively low mortality rate (2-12%). Morphologically, Sycanus sp. grew and developed well. The body length was about twice the width of the body. The age of the male was shorter than that of the female, as was the body size. The sex ratio also showed fewer males than females (2:3).

IntroductionWeekly head circumference (HC) measurements using a measuring tape is the current standard for longitudinal brain growth monitoring of preterm infants. The MONITOR3D (M3D) 3D scanner has been developed to measure both HC and cranial volume (CrV) of preterm infants within incubators. The M3D’s usability, accuracy and precision were validated in a simulated setting in a neonatal intensive care unit (NICU).Materials and methodsDuring a simulated routine care moment, NICU nurses conducted M3D scans of a preterm doll simulating an extreme low birthweight preterm (ELBW; BW < 1,000 g) infant, followed by manual HC measurements using a measuring tape. Usability was quantified by percentage of successful HC and CrV measurements from scans. HC and CrV were calculated by marking anatomical landmarks on the 3D image. Measurements were compared to the real, ground truth (GT) values of the doll’s head, defined by an accurate medical scanner. Measurement accuracy was assessed using mean or median absolute measurement error (ME), and precision by the spread of ME, represented by the 95% interval of the ME range. ME intervals were compared with preterm weekly growth increases to assess clinical usability.ResultsRegarding usability, 56 M3D scan sessions resulted in 25 successful (44.6%) HC and CrV measurements, with incomplete 3D data being the primary cause of unsuccessful scans. Accuracy of the measuring tape for HC was 0.2 cm (proportional 0.9% of GT), and precision was 1.6 cm (6.3%). M3D’s accuracy of HC was 0.4 cm (1.5%), and precision was 0.7 cm (2.9%). For CrV, M3D’s accuracy was 8.0 mL (3.8%) and precision 22.6 mL (10.8%).ConclusionThe M3D scanner is suitable for measuring HC and CrV in ELBW infants. However, current scan success rate is too low for practical usability. The M3D’s accuracy and precision are clinically sufficient, while the precision of the current measuring tape method is inadequate for preterm infants. This makes the M3D a promising alternative for HC, offering less disturbance to the infant. In the future, the M3D technique could facilitate the creation of CrV growth reference charts for ELBW infants, enhancing the accuracy of clinical growth monitoring for preterm infants.

Los deportes alternativos se caracterizan por estar cargados de motivación, disfrute e implicación práctica. Se utilizan en las clases de educación física por su capacidad de adaptación y facilidad de adecuación a las habilidades del alumnado, fomentando además la igualdad entre género. Consecuentemente, el objetivo de este estudio fue realizar una propuesta didáctica sobre un deporte alternativo, "el balonkorf", para trabajar de manera lúdica la cooperación. Fue diseñada de acuerdo con la instrucción 12/2022 del 23 de junio, para 6º grado de Educación Primaria con un total de 26 estudiantes. La propuesta incluyó una secuencia de siete sesiones: La sesión 1 se centra en los pases y recepciones. La sesión 2 introduce los pases, recepciones y la ocupación del espacio. La sesión 3 incorpora los pases, recepciones, la ocupación del espacio y los lanzamientos. La sesión 4 aborda las tácticas defensivas y ofensivas. Las sesiones 5 y 6 integran los pases, recepciones, la ocupación del espacio y las tácticas. Finalmente, la sesión 7 presenta una competición formal para aplicar las tácticas y técnicas desarrolladas en las sesiones anteriores.

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with > 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information. Plain language summary Many babies with epilepsy continue to have seizures (‘fits’), despite taking medicines. These babies are unlikely to make the same developmental progress as babies without epilepsy. Ketogenic diets are high in fat and low in carbohydrate and have been shown to reduce seizures in older children and adults. Babies (age 1–24 months) with epilepsy, who still had seizures despite having tried medicines, either started a ketogenic diet or another medicine. They then stayed on this treatment for 8 weeks. We wanted to know whether there was a difference in the number of seizures in the last 2 weeks of treatments compared to before. Seventy-eight babies started a ketogenic diet and 58 started another medicine. Overall, the number of seizures babies had every day was similar in both groups. A similar number of babies in both groups either had to go to hospital for some reason or stay in hospital for longer. This was mostly because of seizures. Two babies suffered ‘sudden unexpected death in epilepsy’ and another died during a planned surgery. These deaths were not thought to be related to the ketogenic diet. Both the ketogenic diet and the medicines helped to reduce the number of seizures in the babies. Babies in both groups had similar side effects. Doctors could consider starting a ketogenic diet in babies who continue to have seizures even though they have tried medicines to stop their seizures. Scientific summary Background Many infancy-onset epilepsies are poorly responsive to antiseizure medicines (ASMs) with poor prognosis for neurodevelopmental outcome. Ketogenic diets (KDs), which are high-fat, low-carbohydrate diets, have been shown to reduce seizures in older children with drug-resistant epilepsy. No high-quality evidence is available for infants. Objectives In this open-label randomised controlled trial, we compared the efficacy of the classical KD to a further appropriate ASM in infants with drug-resistant epilepsy. The primary outcome was the number of seizures recorded during weeks 6–8, accounting for the baseline rate and randomised group. Secondary outcomes at 8 weeks were the number of infants seizure-free in weeks 6–8 of the intervention period, responder rate (defined as the number showing more than a 50% improvement in seizure frequency compared to baseline), tolerance to KD and relationship between medium-chain fatty acids and seizure control. Secondary outcomes at 12 months were retention on treatment, quality of life and neurodevelopmental outcome. Adverse events were recorded throughout the trial. Serious adverse events were reported to the study sponsor. Methods Infants (age 1–24 months) with epilepsy, with an average ≥ 4 seizures/week and previous trials of ≥ 2 ASMs were recruited from 19 hospitals in the UK. Following a 1- or 2-week observation period, during which there were no changes to regular ASMs (emergency seizure treatments continued as required), participants were randomised to receive a classical KD or a further ASM for 8 weeks, using a computer-generated schedule without stratification. An allocation ratio of 1 : 1.35 was used to account for the therapist effect in the KD group only. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The following assessments were performed in all infants prior to randomisation: medical history, physical examination, administration of the Infant Toddler Quality of Life Questionnaire™ (ITQOL-97; © HealthActCHQ Inc. 2013) and Vineland Adaptive Behaviour Scales (Vineland™-II), and clinical laboratory assessments. Food diaries required for diet calculation were returned from parents/guardians of all participants a maximum of 1 week into the observation period. Parents/carers were asked to keep daily seizure diaries throughout the 8-week treatment periods for participants in both arms. Thereafter, they were requested to reduce seizure recording to at least 1–2 days per week, as clinically indicated, until 28 days before the final 12-month visit, when daily seizure recording recommenced. Follow-up visits were arranged at 4 weeks, 8 weeks, and 6, 9 and 12 months. Assessments included clinical review, physical examination, documentation of seizure frequency from seizure diaries, review of adverse events and concomitant medication, clinical laboratory assessments (8 weeks, and 6 and 12 months) and completion of tolerability questionnaire by parents/carers together with research nurses, the ITQOL-97 (8 weeks and 12 months) and Vineland-II (12 months). After the 8-week assessment, according to the infant’s clinical response to treatment (seizure outcome and tolerability), KD or ASM was then continued or changed; those randomised to the ASM arm then had the opportunity to start KD. Results Of 136 eligible infants, 78 were randomised to KD and 58 to ASM. Of 78 infants who started KD, 67 (86%) continued to 8 weeks, of which 61 (78%) had primary outcome data available; 53 (91% of those randomised to ASM group) started a further ASM, 49 (84%) continued to 8 weeks and 47 (81%) had primary outcome data available. The median number of daily seizures was not significantly different in both groups at 8 weeks [KD 5 (1, 16); ASM 3 (2, 11), incidence rate ratio (IRR) 1.33, 95% confidence interval (CI) 0.84 to 2.11; p = 0.22]. The odds ratio (OR) of achieving ≥ 50% seizure reduction was 1.21 (95% CI 0.55 to 2.65) and 0.88 (0.27 to 2.80) for seizure freedom. A total of 7/63 infants (11%) in the KD group were seizure-free, compared with 6/48 (13%) in the ASM group (OR 0.88, 95% CI 0.27 to 2.80). A higher proportion of infants in the ASM group changed the number or dose of concurrent ASMs during the intervention period [24/48 (50%)] compared to KD [9/66 (14%)]. The side-effect score at 8 weeks was similar in both groups [KD median 40; interquartile range (IQR) 38–42; ASM median 41 IQR 39‒44) and there were no clinically significant differences other than those expected in clinical or laboratory parameters between groups. At 8 weeks, median scores within the ITQOL-97 were numerically higher (suggesting better health) in the KD group for 7 of the 12 concepts. The infant’s pain, its global behaviour, impact on parental time and family cohesion were equal between the two groups, although general perceptions of the infant’s health were numerically higher in the ASM arm. A numerically larger proportion of parents/guardians of infants in the KD group perceived their child’s health to be ‘much better than a year ago’ (10/40, 25%) compared to those in the ASM group (3/32, 9%); numerically more parents/guardians of infants in the ASM group perceived their child’s health to be ‘much worse than a year ago’ (8/32, 25%) compared to those in the KD group (2/40, 5%). Of 66 infants randomised to KD > 12 months before the study end date, 31 (47%) continued the diet to 12 months; of 47 randomised to further ASM > 12 months before the study end date, 21 (45%) continued the ASM to 12 months. For those who reported data, there were no differences between groups for any concept within the ITQOL-97 at 12 months, except for the infant’s temperament and mood (coefficient −6.09, 95% CI −11.63 to −0.54) and the infant getting along with others (coefficient −6.79, 95% CI −12.97 to −0.60), which favoured the ASM group. A similar proportion of parents/guardians of infants in both groups perceived their child’s health to be ‘much better than a year ago’ (12/24 50% ASM; 11/30 37% KD) or ‘much worse than a year ago’ (0/24, 0% ASM; 1/30, 3% KD). Within the Vineland-II there were neither significant differences between groups in the overall standardised score nor domain standard scores at 12 months. The Daily living domain sum of v-scale scores was nominally improved in the ASM group (coefficient 2.23, 95% CI −4.22 to −0.25). A total of 73 serious adverse events (SAEs) were reported in the ASM group and 161 in the KD group. A similar proportion of infants in both groups reported at least 1 SAE (43% ASM; 51% KD) – most commonly seizures. Three infants died in the KD arm, all considered unrelated to treatment. Conclusions There was no evidence that KD was better than further ASM in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and KD appeared safe to use in infants with epilepsy. KD could be a treatment option in infants whose seizures continue despite trial of two standard ASMs. Further trials are needed with larger cohorts at 12-month follow-up and beyond, particularly to look at quality of life and neurodevelopment, perhaps with alternative study design. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Es fundamental conocer los niveles de actividad física de cada grupo poblacional, así como los factores que los condicionan. De esta forma, se pueden identificar grupos donde priorizar las actuaciones de promoción de la actividad física y conseguir que estas sean más eficaces. El estudio tuvo como objetivos: 1) Describir los niveles de práctica de actividad física moderada-vigorosa y de apoyo social de los adolescentes de zonas rurales en función de la ubicación del municipio; 2) Analizar las relaciones entre la práctica de actividad física moderada-vigorosa y el apoyo social percibido; 3) Identificar las variables de apoyo social predictoras de los niveles de actividad física moderada-vigorosa de los jóvenes de zonas rurales. Participaron estudiantes de municipios rurales de Soria (edad media 14,13±1,29 años). Se administraron Four by one-day Physical Activity Questionnaire, Parent Support Scale y Peer Support Scale. Los jóvenes de zonas rurales próximas realizan 62,80±43,27 minutos/día de actividad física moderada-vigorosa y los de zonas remotas 63,86±45,43 minutos/día. Además, la mayoría de las relaciones entre la actividad física y el apoyo social son significativas, independientemente del tipo de municipio rural. Se concluye afirmando que el apoyo de familiares y amigos influye sustancialmente en los niveles de actividad física moderada-vigorosa de los jóvenes. Igualmente, la realización de actividad física junto a amigos predice el 12,7% de la actividad física de los adolescentes de zonas próximas y el 29,7% de los de zonas remotas. Palabras clave: apoyo social; municipio rural; actividad física moderada-vigorosa; factores; salud. Abstract. It is important to know the level of physical activity of each population group and the factors that determine it. In this way, it is possible to identify groups in which physical activity interventions should be prioritised and made them more effective. The aims of the study were: 1) describe the levels of moderate-vigorous physical activity and social support of rural adolescents according to the location of the municipality; 2) analyse the relationships between moderate-vigorous physical activity and perceived social support; 3) identify the social support variables that predict moderate-vigorous physical activity levels of rural adolescents. Students from rural communities in Soria (mean age 14.13±1.29 years) participated. Four one-day physical activity questionnaires, parent support scale and peer support scale were administered. Young people from nearby rural areas performed 62.80±43.27 minutes/day of moderate-vigorous physical activity and those from remote areas 63.86±45.43 minutes/day. Furthermore, most of the relationships between physical activity and social support are significant, regardless of the type of rural community. It can be concluded that the support of family and friends has a significant impact on young people's levels of moderate-to-vigorous physical activity. Similarly, being physically active with friends predicts 12.7% of the physical activity of adolescents in nearby areas and 29.7% of those in remote areas. Keywords: Social support; Rural regions; Moderate to vigorous physical activity; Factors; Health.

Significant efforts have been made to characterize the biophysical properties of proteins. Small proteins have received less attention because their annotation has historically been less reliable. However, recent improvements in sequencing, proteomics, and bioinformatics techniques have led to the high-confidence annotation of small open reading frames (smORFs) that encode for functional proteins, producing smORF-encoded proteins (SEPs). SEPs have been found to perform critical functions in several species, including humans. While significant efforts have been made to annotate SEPs, less attention has been given to the biophysical properties of these proteins. We characterized the distributions of predicted and curated biophysical properties, including sequence composition, structure, localization, function, and disease association of a conservative list of previously identified human SEPs. We found significant differences between SEPs and both larger proteins and control sets. In addition, we provide an example of how our characterization of biophysical properties can contribute to distinguishing protein-coding smORFs from noncoding ones in otherwise ambiguous cases.

A-kinase anchor protein 12 (AKAP12), a scaffold protein, has been implicated in the central nervous system, including blood-brain barrier (BBB) function. Although its expression level in the corpus callosum is higher than in other brain regions, such as the cerebral cortex, the role of AKAP12 in the corpus callosum remains unclear. In this study, we investigate the impact of AKAP12 deficiency by transcriptome analysis using RNA-sequencing (RNA-seq) on the corpus callosum of AKAP12 knockout (KO) mice. We observed minimal changes, with only 13 genes showing differential expression, including Akap12 itself. Notably, Klf2 and Sgk1 , genes potentially involved in BBB function, were downregulated in AKAP12 KO mice and expressed in vascular cells similar to Akap12 . These changes in gene expression may affect important biological pathways that may be associated with neurological disorders. Our findings provide an additional data set for future research on the role of AKAP12 in the central nervous system.

Abstract Tobacco control policies can protect child health. We hypothesised that the parallel introduction in 2008 of smoke-free restaurants and bars in the Netherlands, a tobacco tax increase and mass media campaign, would be associated with decreases in childhood wheezing/asthma, respiratory tract infections (RTIs), and otitis media with effusion (OME) presenting in primary care. We conducted an interrupted time series study using electronic medical records from the Dutch Integrated Primary Care Information database (2000–2016). We estimated step and slope changes in the incidence of each outcome with negative binomial regression analyses, adjusting for underlying time-trends, seasonality, age, sex, electronic medical record system, urbanisation, and social deprivation. Analysing 1,295,124 person-years among children aged 0–12 years, we found positive step changes immediately after the policies (incidence rate ratio (IRR): 1.07, 95% CI: 1.01–1.14 for wheezing/asthma; IRR: 1.16, 95% CI: 1.13–1.19 for RTIs; and IRR: 1.24, 95% CI: 1.14–1.36 for OME). These were followed by slope decreases for wheezing/asthma (IRR: 0.95/year, 95% CI: 0.93–0.97) and RTIs (IRR: 0.97/year, 95% CI: 0.96–0.98), but a slope increase in OME (IRR: 1.05/year, 95% CI: 1.01–1.09). We found no clear evidence of benefit of changes in tobacco control policies in the Netherlands for the outcomes of interest. Our findings need to be interpreted with caution due to substantial uncertainty in the pre-legislation outcome trends.

The implementation of waste management from upstream (community) by the Yogyakarta City Government has had an impact on the city community, including residents of RW 6 Demangan Sub-district, Gondokusuman District. Communities have limited knowledge and ability to manage inorganic waste independently. Facing these problems, the community needs assistance to increase knowledge and develop the ability to manage inorganic waste. This is important so that the Yogyakarta City Government's goal of achieving zero inorganic waste can be realized. The community service program aims to educate the community through training and workshop in waste management and processing so that it can reduce the production of inorganic waste. Assistance in the form of education, training, and practices in managing and processing inorganic waste needs to be carried out to increase the knowledge and skills of the community so that waste self-management can be realized. The community service results show that the community of RW 06 is able to manage and process waste. However, waste management and processing activities must be carried out consistently so that the target of zero inorganic waste is achieved.

Abstract Coffee professionals have long known that the “roast profile,” i.e., the temperature versus time inside the roaster, strongly affects the flavor and quality of the coffee. A particularly important attribute of brewed coffee is the perceived sourness, which is known to be strongly correlated to the total titratable acidity (TA). Most prior work has focused on laboratory-scale roasters with little control over the roast profile, so the relationship between roast profile in a commercial-scale roaster and the corresponding development of TA to date remains unclear. Here we investigate roast profiles of the same total duration but very different dynamics inside a 5-kg commercial drum roaster, and we show that the TA invariably peaks during first crack and then decays to its original value by second crack. Although the dynamics of the TA development varied with roast profile, the peak TA surprisingly exhibited almost no statistically significant differences among roast profiles. Our results provide insight on how to manipulate and achieve desired sourness during roasting.

Abstract Background Medical cannabis, legalized in many countries, remains illegal in France. Despite an experiment in the medical use of cannabis that began in March 2021 in France, little is known about the factors associated with the use of cannabis for self-medication among adults. Methods Data came from the French TEMPO cohort and were collected between December 2020 and May 2021. Overall, 345 participants aged 27–47 were included. Cannabis for self-medication was defined using the following questions: ‘Why do you use cannabis?’ and ‘In what form do you use cannabis?’. The penalized regression method “Elastic net” was used to determine factors associated with the use of cannabis for self-medication, with the hypothesis that it is mainly used for pain in individuals who have already used cannabis. Results More than half of the participants reported having ever used cannabis (58%). Only 10% used it for self-declared medical reasons (n = 36). All self-medication cannabis users, except one, were also using cannabis for recreational purposes. The main factors associated with cannabis use for self-medication vs. other reasons included cannabis use trajectories, the presence of musculoskeletal disorders, tobacco smoking, and parental divorce. Conclusions Engaging in cannabis use during adolescence or early adulthood may increase the likelihood of resorting to self-medication in adulthood. Due to the propensity of individuals with cannabis use during adolescence to resort to uncontrolled products for self-medication, this population should be more systematically targeted and screened for symptoms and comorbidities that may be associated with cannabis use.

Abstract Background Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. Methods This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBIEIT), Respiratory Rate (RREIT) and Minute Ventilation (MVEIT) were computed on a breath-by-breath basis from stable tidal breathing periods. Results EELI values dropped after the start of the SBT (p

Abstract Background Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. Methods The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. Discussion The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. Trial registration ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Abstract Background Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). Design The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. Trial registration ClinicalTrials.gov NCT04373902 (registered April 2020).

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD.

The oil palm ecosystem is one of the suitable habitats for the order Dermaptera. Several physical factors, especially humidity in the oil palm ecosystem, support these insects' existence. In the oil palm ecosystem, Dermaptera has several functions, including as a predator of oil palm pests, but on the other hand, these insects also prey on Elaeidobius kamerunicus Faust, the primary pollinator of oil palm plants. For that reason, research was conducted to study the structure of the Dermaptera community in the ecosystem of oil palm plantations in the Sitiung sub-district. This research was a survey conducted at three locations- Sitiung, Gunung Medan, and Sungai Duo Villages—the collection of insect samples by hand collection. Identification of insect samples was carried out at the species level according to Burr (1910) and Borror et al. (1996). In this study, 214 individuals of the order Dermaptera were found to consist of three species: Cheslisoches mario, Forficula auricularia, and Vostox brunneipennis. C. mario was the dominant Dermaptera species found with an Importance Value Index (IVI) was 1.27. Based on this research, it is known that the community structure of the order Dermaptera was simple because it has low diversity values.

Microvirin is a lectin molecule known to have monovalent interaction with glycoprotein gp120. A previously reported high-resolution structural analysis defines the mannobiose-binding cavity of Microvirin. Nonetheless, structure does not directly define the energetics of binding contributions of protein contact residues. To better understand the nature of the MVN-Env glycan interaction, we used mutagenesis to evaluate the residue contributions to the mannobiose binding site of MVN that are important for Env gp120 glycan binding. MVN binding site amino acid residues were individually replaced by alanine, and the resulting purified recombinant MVN variants were examined for gp120 interaction using competition Enzyme-Linked Immunosorbent Assay (ELISA), biosensor surface plasmon resonance, calorimetry, and virus neutralization assays. Our findings highlight the role of both uncharged polar and non-polar residues in forming a hydropathic recognition site for the monovalent glycan engagement of Microvirin, in marked contrast to the charged residues utilized in the two Cyanovirin-N (CVN) glycan-binding sites.

Background: Phytol is a diterpene from the long-chain unsaturated acyclic alcohols, known for its diverse biological effects, including antimicrobial and anti-inflammatory activities. Present in essential oils, phytol is a promising candidate for various applications in the pharmaceutical and biotechnological sectors. This study aimed to evaluate the in vitro antibacterial and drug-potentiating effects of phytol against multidrug-resistant bacteria and to evaluate its in silico properties: ADME and molecular docking. Methods: The in vitro antibacterial activity of phytol and the phytol combined with conventional drugs was evaluated by microdilution tests against standard and resistant bacterial strains. Finally, the SwissADME platform was employed to analyse the physicochemical and pharmacokinetic characteristics of phytol. Results: Phytol significantly reduced the Minimum Inhibitory Concentration (MIC) of norfloxacin and gentamicin required to inhibit multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, respectively. Additionally, ADME analysis revealed that phytol exhibits low toxicity and favourable pharmacokinetic properties; in addition, it is revealed through molecular docking that phytol showed a relevant affinity with the proteins 6GJ1 and 5KDR, however, with values lower than the drugs gentamicin and ampicillin. Conclusions: Collectively, these findings suggest that phytol holds potential as an effective adjuvant in combating antimicrobial resistance.

Background/Objectives: This study evaluated the antinociceptive effect of the Ximenia americana L. bark extract (HEXA) and its primary component, caffeic acid (CA), through in vivo assays. Methods: The antinociceptive properties were assessed using abdominal writhing, hot plate, and Von Frey tests. Additionally, the study investigated the modulation of various pain signaling pathways using a pharmacological approach. Results: The results demonstrated that all doses of the HEXA significantly increased latency in the hot plate test, decreased the number of abdominal contortions, reduced hyperalgesia in the Von Frey test, and reduced both phases of the formalin test. Caffeic acid reduced licking time in the first phase of the formalin test at all doses, with the highest dose showing significant effects in the second phase. The HEXA potentially modulated α2-adrenergic (52.99%), nitric oxide (57.77%), glutamatergic (33.66%), vanilloid (39.84%), cyclic guanosine monophosphate (56.11%), and K+ATP channel-dependent pathways (38.70%). Conversely, CA influenced the opioid, glutamatergic (53.60%), and vanilloid (34.42%) pathways while inhibiting nitric oxide (52.99%) and cyclic guanosine monophosphate (38.98%). Conclusions: HEXA and CA exhibit significant antinociceptive effects due to their potential interference in multiple pain signaling pathways. While the molecular targets remain to be fully investigated, HEXA and CA demonstrate significant potential for the development of new analgesic drugs.