Early Activation Research Articles

LITERASI ANAK USIA DINI: OPTIMALISASI PENGGUNAAN PERPUSTAKAAN TAMAN KANAK-KANAK

Early childhood literacy is essential to children's cognitive and social development. A literacy environment helps build children's interests, including reading and writing. Reading readiness is very important so young children can develop a basic understanding of letters and sounds before formal learning at school. One practical approach to increasing early childhood literacy is to utilize kindergarten libraries. They are optimizing Kindergarten Libraries as a form of accommodating Early Childhood literacy. This research uses descriptive qualitative so that the author can describe in detail and interpret the data or symptoms obtained during the study, which was carried out at Kindergarten Pelita Hati Jember. Data collection techniques include interviews, observation, and documentation, with purposive determination of informants. So the informants chosen were the Principal, Class Teacher, Student Teacher, Library Teacher, and Students. The data analysis technique used is the Miles and Huberman data analysis technique. The research results show two developments in the optimization of the kindergarten library at Kindergarten Pelita Hati Jember, namely the development of book collections that are relevant to early childhood development and the development of new learning models. The library at Kindergarten Pelita Hati Jember is based on the tasks and functions of the library, including being a place for early childhood literacy activities. The room design and arrangement of books and other supporting equipment are very neatly arranged, with unique colours and a lovely study table.

Comparison of Early Fungicidal Activity and Mortality Between Daily Liposomal Amphotericin B and Daily Amphotericin B Deoxycholate for Cryptococcal Meningitis

Abstract Background Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet noninferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin B among persons with human immunodeficiency virus (HIV)–related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day. Methods We analyzed data from 3 clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (n = 94) or amphotericin B deoxycholate at 0.7–1.0 mg/kg/day with flucytosine (n = 404) as induction therapy. We compared participant baseline characteristics, cerebrospinal fluid (CSF) early fungicidal activity (EFA), and 10-week mortality. Results We included 498 participants in this analysis, of whom 201 had available EFA data (n = 46 liposomal amphotericin B; n = 155 amphotericin B deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA, 0.495 [95% confidence interval {CI}, .355–.634] log10 colony-forming units [CFU]/mL/day) differ from amphotericin B deoxycholate (mean EFA, 0.402 [95% CI, .360–.445] log10 CFU/mL) (P = .13). Mortality at 10 weeks trended lower for liposomal amphotericin B (28.2%) versus amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted hazard ratio, 0.74 [95% CI, .44–1.25]; P = .26). Conclusions Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis.

Literasi Anak Usia Dini: Optimalisasi Perpustakaan Taman Kanak-Kanak

Early childhood literacy is essential to children's cognitive and social development. A literacy environment helps build children's interests, including reading and writing. Reading readiness is very important so young children can develop a basic understanding of letters and sounds before formal learning at school. One practical approach to increasing early childhood literacy is to utilize kindergarten libraries. They are optimizing Kindergarten Libraries as a form of accommodating Early Childhood literacy. This research uses descriptive qualitative so that the author can describe in detail and interpret the data or symptoms obtained during the study, which was carried out at Kindergarten Pelita Hati Jember. Data collection techniques include interviews, observation, and documentation, with purposive determination of informants. So the informants chosen were the Principal, Class Teacher, Student Teacher, Library Teacher, and Students. The data analysis technique used is the Miles and Huberman data analysis technique. The research results show two developments in the optimization of the kindergarten library at Kindergarten Pelita Hati Jember, namely the development of book collections that are relevant to early childhood development and the development of new learning models. The library at Kindergarten Pelita Hati Jember is based on the tasks and functions of the library, including being a place for early childhood literacy activities. The room design and arrangement of books and other supporting equipment are very neatly arranged, with unique colours and a lovely study table.

A forecast-driven stochastic optimization method for proactive activation of manual reserves

Reducing operating balancing costs is paramount for an affordable transition towards renewable-dominated power systems. In European balancing markets, operating balancing costs are driven by the activation of automatic and manual frequency restoration reserves, respectively aFRR and mFRR. An inadequate combination of both products for resolving grid imbalances may result in economic inefficiencies where, e.g., saturated aFRR can lead to balancing price spikes. To avoid such situation, we propose a proactive activation policy of manual reserves, aiming at an optimal trade-off between aFRR and mFRR products via a stochastic optimization method. The tool is fed with 1-min time trajectories of system imbalances covering the next quarter hour. The one minute temporal granularity allows modeling the ramping phenomena of mFRR products, while keeping track of the faster activation of aFRR products. The proposed balancing energy activation methodology is tested on Belgian market data, which currently adopts a reactive balancing strategy. Ex-post comparisons of the proposed balancing strategy with a reactive one show that our methodology allows a decrease of the balancing activation costs. This is expected as early activation of mFRR, when appropriately provided, allows avoiding the activation of extremely high aFRR bids.

Unravelling the Biochemical and Molecular Priming Effect of a New Yeast-Derived Product: New Perspectives towards Disease Management

Plants constantly face the environment that surrounds them and fight for survival against biotic and abiotic stress factors. To deal with harmful conditions, plants have developed a multilayer defence system, making them capable of recognising threats and promptly recovering from them. This phenomenon, which takes advantage of the “memory effect”, is referred to as bio-priming and represents a new frontier in terms of crop protection. Here, we investigated the “indirect” protective mechanisms of a new yeast extract formulate in Vitis vinifera cv. Sangiovese plants at both the biochemical and genic levels. The formulate was applied once a week for three consecutive weeks, and grapevine leaves were sampled from the first to the fifth day after treatment (dat) at every week of the experiment. Increased levels of jasmonic acid (every week at 2 dat; +70% as average) and abscisic acid (at 1 dat of the first week, more than 1.7-fold higher than the control) and the underproduction of salicylic acid (from 2 dat; −18%) confirmed that these signalling molecules/”specialised compounds” are actively involved in the early activation of defence pathways in treated vines. In addition, pr2 and chit1b, two genes involved in regulating hormonal crosstalk, were significantly up-regulated (both in the first and second week of the trial) and were also found to underlie upstream molecular activation. The results obtained by this investigation confirm the use of this new product to prime and protect grapevines from a wide range of fungal and fungal-like plant pathogens through the induction of defence responses.

Female Adolescents’ Experiences with Contraceptive Method Decision-Making, Access, and Continuation: Qualitative Research

Objective: Because of early sexual activity that starts in adolescence, critical problems such as unwanted pregnancies arise. The aim of this study was to examine the experiences of female adolescents in decision making, accessing, and maintaining contraception. Methods: The study was conducted as a case study with a phenomenological design and a qualitative approach. The study included adolescents who had contraception experience and were present in the gynecology clinic(s) of the hospital to receive any care service. Participants (n=22) was selected through purposive sampling. Semi-structured in-depth interviews were conducted, transcribed, and analyzed using the approach, content, and descriptive analysis. Results: Through the analysis of in-depth interview data with female adolescents examining their experiences related to contraceptive method use, four themes were identified: "reasons for using and deciding on pregnancy prevention methods, accessibility to pregnancy prevention methods, experiences during the use of pregnancy prevention methods, and continuity of pregnancy prevention method use." Conclusion: In this study, it was determined that female adolescents faced some difficulties in deciding on, accessing, and maintaining contraceptive methods. In this context, units such as youth centers where adolescents can apply can be established. Unwanted pregnancies can be prevented by regulations regarding the provision of counseling and contraceptive services to adolescents.

Fermi GBM Observations of the Galactic Magnetar SGR 1935+2154 during Its 2022 January Activity

The X-ray and radio burst-emitting soft gamma-ray repeater SGR 1935+2154 has been the most active magnetar during the past decade, with at least one active episode each year since 2019. We report on the 2022 January activity as observed by the Fermi Gamma-Ray Burst Monitor and present the temporal and time-integrated spectral properties of the observed 112 X-ray bursts. No radio bursts were reported during the activity. The mean burst duration is comparable to most of the previous activities but is shorter than that of 2020, during which the magnetar emitted radio bursts. The mean burst spectrum is softer than the earlier activities and a long-term softening trend since 2016 is evident and is accompanied by a rise in the mean burst fluence and blackbody emission radii. The power-law indices of the RBB2−kTBB correlation also show an evolution during 2019–2022, where the soft component started becoming steeper, whereas the hard component shows a less steep trend. The burst properties show no significant evolution within the activity, which lasted for ∼ 45 days, and none of the observed bursts showed properties reminiscent of those of the hard, long X-ray counterpart to the 2020 fast radio burst FRB 200428 from the source. We discuss the results comparatively with the 8 yr history of the source since its discovery in 2014.

Combined PIVKA II and Vimentin-Guided EMT Tracking in Pancreatic Adenocarcinoma Combined Biomarker-Guided EMT Tracking in PDAC.

"Background/Aim": the current inability to diagnose Pancreatic Cancer Adenocarcinoma (PDAC) at an early stage strongly influences therapeutic strategies. Protein Induced by Vitamin K Absence (PIVKA II) showed an accurate diagnostic performance for PDAC. Since circulating PIVKA II has been recently associated with pancreatic origin cells with Vimentin, an epithelial-to-mesenchymal transition (EMT) early activation marker, the aim of this study was to investigate in vivo the combination between the two proteins. "Materials and Methods": we assayed the presence of PIVKA II and Vimentin proteins by using different diagnostic methods. A total of 20 PDAC patients and 10 healthy donors were tested by Western Blot analysis; 74 PDAC patient and 46 healthy donors were assayed by ECLIA and Elisa. "Results": Western Blot analysis showed the concomitant expression of PIVKA II and Vimentin in PDAC patient sera. Immunometric assay performed on a larger cohort of patients demonstrated that 72% of PIVKA II-positive PDAC patients were Vimentin-positive. Additionally, in a group of PDAC patients with PIVKA II levels ≥2070 ng/mL, the percentage of Vimentin-positive subjects reached 84%. "Conclusion": the association between PIVKA II protein and the EMT suggests that this molecule could be considered a marker of the acquisition of an aggressive phenotype.

Prognostic significance of nadir platelet count in patients with heatstroke: A multi-center retrospective study

BackgroundHeatstroke (HS), associated with the early activation of the coagulation system and frequently presenting with thrombocytopenia, poses a significant healthcare challenge. Understanding the relationship of nadir platelet count (PLT) within 24 h for adverse outcomes in HS patients is crucial for optimizing management strategies. MethodsThis retrospective cohort study, conducted in six tertiary care hospitals, involved patients diagnosed with HS and admitted to the emergency departments. The primary and secondary outcomes included in-hospital mortality and various acute complications, respectively, with logistic regression models utilized for assessing associations between nadir PLT and outcomes. The PLT count change curve was described using a generalized additive mixed model (GAMM), with additional analyses involving body temperature (BT) at 2 h also conducted. ResultsOf the 152 patients included, 19 (12.5%) died in-hospital. The median nadir PLT within 24 h was 99.5 (58.8–145.0)*10^9/L. Notably, as a continuous variable (10*10^9/L), nadir PLT was significantly associated with in-hospital mortality (OR 0.76; 95% CI 0.64–0.91; P = 0.003) and other adverse outcomes like acute kidney and liver injury, even after adjustment for confounders. GAMM revealed a more rapid and significant PLT decline in the non-survival group over 24 h, with differential PLT dynamics also observed based on BT at 2 h. ConclusionsNadir PLT within 24 h were tied to in-hospital mortality and various adverse outcomes in HS patients. Early effective cooling measures demonstrated a positive impact on these associations, underscoring their importance in patient management.

Inferring occluded projectile motion changes connectivity within a visuo-fronto-parietal network

Anticipating the behaviour of moving objects in the physical environment is essential for a wide range of daily actions. This ability is thought to rely on mental simulations and has been shown to involve frontoparietal and early visual areas. Yet, the connectivity patterns between these regions during intuitive physical inference remain largely unknown. In this study, participants underwent fMRI while performing a task requiring them to infer the parabolic trajectory of an occluded ball falling under Newtonian physics, and a control task. Building on our previous research showing that when solving the physical inference task, early visual areas encode task-specific and perception-like information about the inferred trajectory, the present study aimed to (i) identify regions that are functionally coupled with early visual areas during the physical inference task, and (ii) investigate changes in effective connectivity within this network of regions. We found that early visual areas are functionally connected to a set of parietal and premotor regions when inferring occluded trajectories. Using dynamic causal modelling, we show that predicting occluded trajectories is associated with changes in effective connectivity within a parieto-premotor network, which may drive internally generated early visual activity in a top-down fashion. These findings offer new insights into the interaction between early visual and frontoparietal regions during physical inference, contributing to our understanding of the neural mechanisms underlying the ability to predict physical outcomes.

Electrophilic proximity-inducing synthetic adapters enhance universal T cell function by covalently enforcing immune receptor signaling

Proximity-induction of cell-cell interactions via small molecules represents an emerging field in basic and translational sciences. Covalent anchoring of these small molecules represents a useful chemical strategy to enforce proximity; however, it remains largely unexplored for driving cell-cell interactions. In immunotherapeutic applications, bifunctional small molecules are attractive tools for inducing proximity between immune effector cells like Tcells and tumor cells to induce tumoricidal function. We describe a two-component system composed of electrophilic bifunctional small molecules and paired synthetic antigen receptors (SARs) that elicit Tcell activation. The molecules, termed covalent immune recruiters (CIRs), were designed to affinity label and covalently engage SARs. We evaluated the utility of CIRs to direct anti-tumor function of human Tcells engineered with three biologically distinct classes of SAR. Irrespective of the electrophilic chemistry, tumor-targeting moiety, or SAR design, CIRs outperformed equivalent non-covalent bifunctional adapters, establishing a key role for covalency in maximizing functionality. We determined that covalent linkage enforced early Tcell activation events in a manner that was dependent upon each SARs biology and signaling threshold. These results provide a platform to optimize universal SAR-T cell functionality and more broadly reveal new insights into how covalent adapters modulate cell-cell proximity-induction.

The location of pain in cluster headache: Data from the International Cluster Headache Questionnaire.

To identify the most common locations of cluster headache pain from an international, non-clinic-based survey of participants with cluster headache, and to compare these locations to other cluster headache features as well as to somatotopic maps of peripheral, brainstem, thalamic, and cortical areas. Official criteria for cluster headache state pain in the orbital, supraorbital, and/or temporal areas, yet studies have noted pain extending beyond these locations, and the occipital nerve appears relevant, given the effectiveness of suboccipital corticosteroid injections and occipital nerve stimulation. Furthermore, cranial autonomic features vary between patients, and it is not clear if the trigeminovascular reflex is dermatome specific (e.g., do patients with maxillary or V2 division pain have more rhinorrhea?). Finally, functional imaging studies show early activation of the posterior hypothalamus in a cluster headache attack. However, the first somatosensory area to be sensitized is unclear; the first area can be hypothesized based on the complete map of pain locations. The International Cluster Headache Questionnaire was an internet-based cross-sectional survey that included a clickable pain map of the face. These data were compared to several other datasets: (1) a meta-analysis of 22 previous publications of pain location in cluster headache (consisting of 6074 patients); (2) four cephalic dermatome maps; (3) participants' survey responses for demographics, autonomic features, and effective medications; and (4) previously published somatotopic maps of the brainstem, thalamus, primary somatosensory cortex, and higher order somatosensory cortex. One thousand five hundred eighty-nine participants completed the pain map portion of the survey, and the primary locations of pain across all respondents was the orbital, periorbital, and temporal areas with a secondary location in the lower occiput; these primary and secondary locations were consistent with our meta-analysis of 22 previous publications. Of the four cephalic dermatomes (V1, V2, V3, and a combination of C2-3), our study found that most respondents had pain in two or more dermatomes (range 85.7% to 88.7%, or 1361-1410 of 1589 respondents, across the four dermatome maps). Dermatomes did not correlate with their respective autonomic features or with medication effectiveness. The first area to be sensitized in the canonical somatosensory pathway is either a subcortical (brainstem or thalamus) or higher order somatosensory area (parietal ventral or secondary somatosensory cortices) because the primary somatosensory cortex (area 3b) and somatosensory area 1 have discontinuous face and occipital regions. The primary pain locations in cluster headache are the orbital, supraorbital, and temporal areas, consistent with the official International Classification of Headache Disorders criteria. However, activation of the occiput in many participants suggests a role for the occipital nerve, and the pain locations suggest that somatosensory sensitization does not start in the primary somatosensory cortex.

Sunitinib-mediated inhibition of STAT3 in skeletal muscle and spinal cord does not affect the disease in a mouse model of ALS

Variability in disease onset and progression is a hallmark of amyotrophic lateral sclerosis (ALS), both in sporadic and genetic forms. Recently, we found that SOD1-G93A transgenic mice expressing the same amount of mutant SOD1 but with different genetic backgrounds, C57BL/6JOlaHsd and 129S2/SvHsd, show slow and rapid muscle wasting and disease progression, respectively. Here, we investigated the different molecular mechanisms underlying muscle atrophy. Although both strains showed similar denervation-induced degradation of muscle proteins, only the rapidly progressing mice exhibited early and sustained STAT3 activation that preceded atrophy in gastrocnemius muscle. We therefore investigated the therapeutic potential of sunitinib, a tyrosine kinase inhibitor known to inhibit STAT3 and prevent cancer-induced muscle wasting. Although sunitinib treatment reduced STAT3 activation in the gastrocnemius muscle and lumbar spinal cord, it did not preserve spinal motor neurons, improve neuromuscular impairment, muscle atrophy and disease progression in the rapidly progressing SOD1-G93A mice. Thus, the effect of sunitinib is not equally positive in different diseases associated with muscle wasting. Moreover, given the complex role of STAT3 in the peripheral and central compartments of the neuromuscular system, the present study suggests that its broad inhibition may lead to opposing effects, ultimately preventing a potential positive therapeutic action in ALS.

Effects of a monthly unconditional cash transfer starting at birth on family investments among US families with low income.

How does unconditional income for families in poverty affect parental investments for their young children? Mothers in four US metropolitan areas were randomized to receive a monthly unconditional cash transfer of either $333 per month (high) or $20 per month (low) for the first several years after childbirth. During the first 3 years, high-cash gift households spent more money on child-specific goods and more time on child-specific early learning activities than the low-cash gift group. Few changes were evident in other core household expenditures. Compared with low-cash gift families, high-cash gift families reported lower rates of public benefit receipt and fewer were residing in poverty, although mean income and wealth remain low for the majority of families by year 3. No statistically significant differences were evident in mothers' participation in paid work, children's time in childcare or mothers' subjective wellbeing.

Abstract PO-008: Phase I/II study of VIP152 (enitociclib), venetoclax, and prednisone (VVIP) in relapsed/refractory (R/R) lymphoid malignancies

Abstract Background: Relapsed/refractory (R/R) aggressive lymphomas, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma double-hit (HGBCL-DH), and peripheral T-cell lymphoma (PTCL), have poor outcomes with standard therapy. VIP152 (enitociclib) leads to rapid depletion of short-lived mRNA transcripts such as MYC and MCL1 through CDK9 inhibition. Preclinical studies have identified BCL2 overexpression as a mechanism of resistance to CDK9 inhibition, and synergistic cytotoxicity has been shown with venetoclax (BCL2 inhibitor), steroids, and CDK9 inhibitors in DLBCL. Based on this preclinical data, we hypothesized that the combination of VIP152 with venetoclax and prednisone (VVIP) would result in acceptable safety and improved efficacy in R/R lymphoid malignancies. Methods: R/R non-GCB DLBCL, MYC-rearranged DLBCL/HGBCL-DH, and PTCL pts after 2 prior systemic therapies are eligible. In phase I, pts are treated at 4 dose levels (DL) of VIP152 and venetoclax in combination with fixed-dose prednisone to identify the recommended phase II dose (RP2D). VIP152 (15mg, 22.5mg, or 30mg) is given IV on days 2 and 9 in combination with venetoclax (600mg or 800mg) PO and prednisone 100 mg PO on days 1-10 every 21 days. Phase II expansion cohorts are included at the RP2D. VVIP x 12 cycles is given for pts who achieve complete response (CR), with a max of 24 cycles for pts not in CR. TLS, G-CSF, and PCP prophylaxis are given to all pts. Baseline CT, PET, and BM are performed with CT after cycles 1 and 2 then every 2 cycles and PET after cycles 6 and 12. CT is then performed q3m x 1y, q4m x 1y, q6m x 1y, then q12m x 2y post-therapy. Results: As of March 26, 2024, 5 pts were enrolled (3 at DL1 and 2 at DL2), including 3 PTCL, 1 non-GCB DLBCL, and 1 HGBCL-DH. Median (range) age was 56 (55-77) yrs, with stage 3/4 disease in 100%, >/=2 extranodal sites in 100%, IPI >/=3 in 80%, and elevated LDH in 40%. Median (range) prior therapies were 3 (3-6), with prior ASCT, allo-HSCT, and CAR-T in 1 (20%) pt each, and 80% of pts refractory per SCHOLAR-1 criteria. All 5 pts completed the dose-limiting toxicity (DLT) window with no DLTs observed. The most common adverse events (AEs) (% pts) included hypokalemia (100%), thrombocytopenia (80%), neutropenia (80%), and anemia (80%). Two (40%) pts had G3-4 neutropenia and 1 (20%) pt had G3 hypokalemia, with no other >/=G3 AEs observed. No dose reductions occurred and only 1 pt required a dose delay due to infection. Tumor reduction was observed in 80% (4/5) of pts, with an overall response rate of 60% (3/5). Partial responses include 1 HGBCL-DH pt refractory to both CAR-T and epcoritamab (71% tumor reduction) and 2 PTCL pts refractory to CHOP and targeted therapy (86% and 91% tumor reduction). Four pts have progressed, and no pts have died. Conclusions: Preliminary results show VVIP to be safe and well tolerated with no DLTs observed. Early activity is noted in pts with HGBCL-DH and PTCL. Enrollment continues to identify the RP2D and to further assess the safety and efficacy of VVIP in R/R aggressive lymphomas. Citation Format: Christopher Melani, Max Gordon, Rahul Lakhotia, Stefania Pittaluga, Jillian Simard, Jagan Muppidi, James D. Phelan, Svetlana Pack, Amynah Pradhan, Candis Morrison, Atekelt Tadese, Anna M. Juanitez, Amy J. Johnson, Melanie M. Frigault, Ahmed Hamdy, Mark Roschewski, Louis M. Staudt, Wyndham H. Wilson. Phase I/II study of VIP152 (enitociclib), venetoclax, and prednisone (VVIP) in relapsed/refractory (R/R) lymphoid malignancies [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-008.

From Ponds to Pine Plantations in 9000 Years: The Environmental Archaeology of Beck Burn, Solway Moss, Cumbria

ABSTRACT This article explores the evidence for environmental change at Beck Burn, Solway Moss, on the English/Scottish border. The analysed pollen, non-pollen palynomorphs (NPP) and microscopic charcoal particles permit several palaeoenvironmental events to be interpreted, supported by radiocarbon dating. These and previously published data suggest the presence of very early Mesolithic water-edge activity, later Mesolithic woodland management, clearance and small-scale cultivation during the early Neolithic period, followed by low-level disturbance for pastoral farming in the early Bronze Age. Woodland clearance and cereal cultivation are dated to the middle Bronze Age, with significant clearance and cultivation identified during the late Iron Age or early Roman period. The medieval period is characterised by evidence for a mixed subsistence economy, with reduced activity possibly coincident with the Wars of Scottish Independence, famines and the Black Death of the fourteenth century, as well as the Little Ice Age. Renewed activity, with evidence for both arable and pastoral farming, is dated to the late medieval to early post-medieval period. Pine plantations were then created, possibly in the eighteenth century or later. The data reveal the importance of palaeoenvironmental archaeology, in the absence of significant finds or features, in creating a link with the past.

예비유아교사들이 유아 과학 활동 장면을 떠올리며 그린 그림(drawings)

Objectives The purpose of this study was to analyze the drawings and interviews of pre-service early childhood teachers on early childhood science activities and to orient them on the educational contents and methods to be taught in early childhood science education. Methods For this purpose, 34 students from the Department of Early Childhood Education at a 4-year university located in City A were asked to draw scenes of early childhood science activities during an early childhood science education class, and then interviews were conducted with 9 of them. The content of the drawings drawn by pre-service early childhood teachers was classified according to the content of early childhood science education to examine trends, and the interview data was read repeatedly and categorized based on major keywords and main content. Results In this study, pre-service early childhood teachers’ drawings were analyzed and found that the most common scenes were ‘growing and observing plants’ and ‘raising and observing animals’. But ‘experimenting with the teacher’, ‘doing science in play’, ‘experiencing plants and animals in outdoor learning’ were relatively rare. Through these research results, it was found that pre-service early childhood teachers have biased ideas about early childhood science activities, topics related to ‘animals and plants’, ‘life and the natural environment’, and the types of science activities that take place indoors. The interviews also revealed that pre-service early childhood teachers have negative experiences and feelings related to science, which makes them feel uncomfortable and have difficulty with science. Conclusions These findings suggest that it is necessary for instructors to reflect more diverse contents of science education in early childhood science education courses and to experience science activities directly with pre-service early childhood teachers. In addition, this suggests that there is a need to reduce pre-service early childhood teachers’ indifference to science and their vague fear of science.

The Difference in Serum Metabolomic Profiles between the Good and Poor Outcome Groups at 3 Months in the Early and Late Phases of Aneurysmal Subarachnoid Hemorrhage.

We aimed to investigate the characteristics of serum metabolomics in aneurysmal subarachnoid hemorrhage patients (aSAH) with different 3-month outcomes (good = modified Rankin score: 0-3 vs. poor = mRS 4-6). We collected serum samples from 46 aSAH patients at 24 (D1) and 168 (D7) hours after injury for analysis by liquid chromatography-mass spectrometry. Ninety-six different metabolites were identified. Groups were compared using multivariate (orthogonal partial least squares discriminant analysis), univariate, and receiving operator characteristic (ROC) methods. We observed a marked decrease in serum homocysteine levels at the late phase (D7) compared to the early phase (D1). At both D1 and D7, mannose and sorbose levels were notably higher, alongside elevated levels of kynurenine (D1) and increased 2-hydroxybutyrate, methyl-galactoside, creatine, xanthosine, p-hydroxyphenylacetate, N-acetylalanine, and N-acetylmethionine (all D7) in the poor outcome group. Conversely, levels of guanidinoacetate (D7) and several amino acids (both D1 and D7) were significantly lower in patients with poor outcomes. Our results indicate significant changes in energy metabolism, shifting towards ketosis and alternative energy sources, both in the early and late phases, even with adequate enteral nutrition, particularly in patients with poor outcomes. The early activation of the kynurenine pathway may also play a role in this process.

Unveiling the Path: A Qualitative Study on the Initial Sexual Experiences of Cambodian Adolescents.

There still remains a significant gap in understanding the sexual and reproductive health challenges faced by adolescents, particularly in the context of early sexual activity, teenage pregnancy, and sexually transmitted diseases. This study seeks to fill this gap by exploring the initial sexual experiences of Cambodian adolescents, highlighting the complex interplay of cultural, social, and personal influences that shape their sexual health decisions and outcomes. A descriptive qualitative research design was used. Thirty Cambodian adolescents were interviewed from March to June 202 and data were analyzed using thematic analysis. Participants met their sexual partners in school and through friendships and social networking sites. Their motivations for sexual activities ranged from intrinsic desires to influences of inebriation, love, and trust. Consent was crucial but some were influenced by partners. Awareness of sexual protection varied, affecting condom use and information-seeking behaviors. After initial encounters, participants grappled with complex emotions and physical changes. The findings suggest the need for educational interventions that address substance use; promote safe behavior, consensual conduct, open communication, and mutual respect; and provide coping strategies.

CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis

Multiple sclerosis (MS) is characterized by heterogeneity in disease course and prediction of long-term outcome remains a major challenge. Here, we investigate five myeloid markers – CHIT1, CHI3L1, sTREM2, GPNMB and CCL18 – in the cerebrospinal fluid (CSF) at diagnostic lumbar puncture in a longitudinal cohort of 192 MS patients. Through mixed-effects and machine learning models, we show that CHIT1 is a robust predictor for faster disability progression. Integrative analysis of 11 CSF and 26 central nervous system (CNS) parenchyma single-cell/nucleus RNA sequencing samples reveals CHIT1 to be predominantly expressed by microglia located in active MS lesions and enriched for lipid metabolism pathways. Furthermore, we find CHIT1 expression to accompany the transition from a homeostatic towards a more activated, MS-associated cell state in microglia. Neuropathological evaluation in post-mortem tissue from 12 MS patients confirms CHIT1 production by lipid-laden phagocytes in actively demyelinating lesions, already in early disease stages. Altogether, we provide a rationale for CHIT1 as an early biomarker for faster disability progression in MS.