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Learning loss pertains to the decline or regression in knowledge and abilities, as well as setbacks in academic advancement. This phenomenon typically arises from prolonged interruptions or gaps in the pupil's educational journey. Learning loss can be observed in diverse manifestations due to many factors. One example that can be illustrated is the disruption of formal education due to the COVID-19 pandemic that struck the world in 2019. As a result, this phenomenon has impacted students' academics, whether at the school level or higher education institutions, especially primary school students, thus causing learning poverty. This scoping review aims to identify the degree of reading literacy among primary school students and to investigate the factors that contribute to the learning losses of primary school students from the reading aspect. Four databases, including Scopus, Education Resources Information Center (ERIC), Bielefeld Academic Search Engine (BASE), and Directory of Open Access Journals (DOAJ), were used in this research, which found 40 articles for eligibility. Only 20 articles are eligible for analysis and reference after the exclusion and inclusion process for data collection. The findings show that learning losses have impacted the education sector, leading to poverty, especially among primary school children.

Special education in Singapore has evolved considerably during the past two decades with greater enrollments of students with special educational needs in regular mainstream schools. This progressive transformation in Singapore's education towards the inclusion of students with special needs in mainstream classes has been accompanied by concomitant changes in teacher preparation programs for both general and special education teachers and professionals. This article situates and describes special education in Singapore and its increasing role in partnering with mainstream education within Singapore's socio-historical context and evolvement as a nation since independence. Current issues related to special education and its expanding role in preparing teachers and related professionals for working with students with special educational needs in both mainstream and special schools are discussed with implications raised for future directions.

The rapid advancement of technology in recent years has brought about profound changes in every aspect of our lives. Such technological advancement has impacted children in a digital age where technology permeates every facet of their existence, from education to entertainment and communication to socialization. The younger generations today appear deficient in motor, emotional, and social abilities. They appear to exhibit higher levels of aggression, anxiety, dependency, and reduced creativity. Integrating non-formal education into children's learning aims to maximize enjoyment and engagement by capturing children's interest and inspiring them to continue learning. Thus, non-formal education encompasses a spectrum of curricular activities in the natural environment outside of the school area. This scoping review aims to identify the focus skills development among primary school learners and how non-formal educational activities could boost learners' learning ability. Four databases, including Scopus, web of science (WoS), Education Resources Information Center (ERIC), and ScienceDirect, were used in this research, which found 36 articles for eligibility. Only 15 articles are eligible for analysis and reference after the exclusion and inclusion process for data collection. The findings show that non-formal education offers learners the opportunity to explore a multitude of interests beyond the structured confines of the classroom.

Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation). We therefore analyzed genomic, transcriptomic, and proteomic data to characterize prostate cancer radioresistance in cells treated with both conventionally fractionated and hypofractionated radiotherapy. Independent of fractionation schedule, resistance to radiotherapy involved massive genomic instability and abrogation of DNA mismatch repair. Specific prostate cancer driver genes were modulated at the RNA and protein levels, with distinct protein subcellular responses to radiotherapy. Conventional fractionation led to a far more aggressive biomolecular response than hypofractionation. Testing preclinical candidates identified in cell lines, we revealed POLQ (DNA Polymerase Theta) as a radiosensitizer. POLQ-modulated radioresistance in model systems and was predictive of it in large patient cohorts. The molecular response to radiation is highly multimodal and sheds light on prostate cancer lethality.SignificanceRadiation is standard of care in prostate cancer. Yet, we have little understanding of its failure. We demonstrate a new paradigm that radioresistance is fractionation specific and identified POLQ as a radioresistance modulator.

Introduction: Paediatric patients admitted to the inpatient units from the emergency department (ED) are increasing, but the mean length of stay has fallen significantly. We aimed to determine the reasons behind paediatric one-day admissions in Singapore and to assess their necessity. Methods: A retrospective study involving paediatric patients who were admitted from a general ED of an adult tertiary hospital to a paediatric tertiary hospital between 1 August 2018 and 30 April 2020. One-day admission was defined as an inpatient stay of less than 24 h from the time of admission to discharge. An unnecessary admission was defined as one with no diagnostic test ordered, intravenous medication administered, therapeutic procedure performed or specialty review made in the inpatient unit. Data were captured in a standardised form and analysed. Results: There were 13,944 paediatric attendances — 1,160 (8.3%) paediatric patients were admitted. Among these, 481 (41.4%) were one-day admissions. Upper respiratory tract infection (62, 12.9%), gastroenteritis (60, 12.5%) and head injury (52, 10.8%) were the three most common conditions. The three most common reasons for ED admissions were inpatient treatment (203, 42.2%), inpatient monitoring (185, 38.5%) and inpatient diagnostic investigations (32, 12.3%). Ninety-six (20.0%) one-day admissions were unnecessary. Conclusion: Paediatric one-day admissions present an opportunity to develop and implement interventions targeted at the healthcare system, the ED, the paediatric patient and their caregiver, in order to safely slow down and perhaps reverse the trend of increased hospital admissions.

Abstract Background Radiotherapy is the primary treatment modality for most head and neck cancers (HNCs). Despite the addition of chemotherapy to radiotherapy to enhance its tumoricidal effects, almost a third of HNC patients suffer from locoregional relapses. Salvage therapy options for such recurrences are limited and often suboptimal, partly owing to divergent tumor and microenvironmental factors underpinning radioresistance. In this study, we utilized a combinatorial functionomics approach, the Quadratic Phenotypic Optimization Platform (QPOP), to rationally design drug pairings that exploit the molecular fingerprint and vulnerability of established in vitro isogenic radioresistant (RR)-HNC models. Methods A QPOP-specific protocol was applied to RR-HNC models to rank and compare all possible drug combinations from a 12-drug set comprising standard chemotherapy, small molecule inhibitors and targeted therapies specific to HNC. Drug combination efficacy was evaluated by computing combination index scores, and by measuring apoptotic response. Drug targeting was validated by western blot analyses, and the Comet assay was used to quantify DNA damage. Enhanced histone deacetylase inhibitor (HDACi) efficacy in RR models was further examined by in vivo studies, and genetic and chemical inhibition of major Class I/II HDACs. Regulatory roles of HDAC6/SP1 axis were investigated using immunoprecipitation, gel shift and ChIP-qPCR assays. Comparative transcriptomic analyses were employed to determine the prognostic significance of targeting HDAC6. Results We report the therapeutic potential of combining panobinostat (pan-HDAC inhibitor) with AZD7762 (CHK1/2 inhibitor; AstraZeneca) or ionizing radiation (IR) to re-sensitize RR-HNC cells and showed increased DNA damage underlying enhanced synergy. We further refined this RR-specific drug combination and prioritized HDAC6 as a targetable dependency in reversing radioresistance. We provide mechanistic insights into HDAC6-mediated regulation via a crosstalk involving SP1 and oncogenic and repair genes. From two independent patient cohorts, we identified a four-gene signature that may have discriminative ability to predict for radioresistance and amenable to HDAC6 inhibition. Conclusion We have uncovered HDAC6 as a promising molecular vulnerability that should be explored to treat RR-HNC.

Abstract Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways. Despite significant inter-cell type heterogeneity of their transcriptomic profiles, 18 common dysregulated genes (5 upregulated and 13 downregulated) were identified across the 4 models, including the overexpression of bromo-adjacent homology domain containing 1 (BAHD1) gene, which is involved in heterochromatin formation. Interestingly, this coincided with our observation of increased histone 3 lysine 9 trimethylation (H3K9me3) and histone 3 lysine 27 trimethylation (H3K27me3) expression post-irradiation in our radioresistant cells. The dependency between BAHD1 and heterochromatin formation was confirmed by siRNA knockdown of BAHD1, indicating preferential reduction of H3K9me3 and H3K27me3 expression in the radioresistant cells, but not the wild-type parentals, and confirmed by clonogenic assays showing reversal of radioresistance post-siBAHD1 treatment. We further showed that inhibition of the BAHD1-heterochromatin formation axis led to reduced DNA double-strand break repair. Finally, analyses of treatment outcomes in 4 prostate and head and neck cancer radiotherapy cohorts suggested an increased risk of failures in tumours of high heterochromatin activity. Taken together, our results support a new model implicating BAHD1-dependent modulation of the heterochromatin in acquired radioresistance of prostate and head and neck cancers.

This study identified research trends, intellectual connections, and social connections in the field of museum visitor experiences. It also outlines future research to understand existing scientific research and shed light on key areas of research. The study reviewed 407 articles published in peer-reviewed journal articles, which were generated from the Scopus database. Bibliometric analysis software VOSviewer and Harzing POP were used. Citation analysis, co-authorship analysis, bibliometric coupling, and co-occurrence analysis have been employed. Findings highlight the need for increased representation from scholars in the Global South to ensure a more inclusive and comprehensive understanding of museum visitors’ experiences worldwide. Nine key research areas for future studies were identified: sustainability, mixed reality, social media, accessibility, emotion, co-creation, interpretation, exhibition, and museum visitors’ experience and engagement. The results benefit stakeholders and researchers by allowing them to stay informed about the latest developments and breakthroughs in the global academic landscape and visitors’ experiences in museums.

Background: Stereotactic body radiation therapy (SBRT) is effective for hepatocellular carcinoma (HCC). Its role as a bridging therapy before deceased-donor liver transplantation (DDLT) remains unclear. Methods: Our institution conducted a prospective study on SBRT before DDLT for 32 HCC patients within University of California, San Francisco (UCSF) criteria as the first cohort, staged with gadoxetate disodium-enhanced MRI and 11C-acetate (ACC) and 18F-fluorodeoxyglucose (FDG) (dual-tracer) positron-emission tomography with computed tomography (PET-CT), followed by SBRT of 35–50 Gy in 5 fractions. They were followed up with the same imaging modalities afterwards while awaiting DDLT. The results were published in June 2024. In view of the encouraging treatment outcomes, SBRT before DDLT has become a routine clinical practice in our institution and the study has been carried on without dual-tracer PET-CT imaging for all subsequent patients recruited prospectively for another 39 patients following revised sample size estimation. Co-primary end points were progression-free survival (PFS) and objective response rates (ORRs) by RECIST 1.1 and mRECIST. Secondary end points were overall survival (OS), safety, and others. The trial is registered with clinicaltrials.gov, NCT04186234. Findings: Between July 1, 2015 until October 31, 2023, 71 patients with 118 HCC lesions were recruited with a median follow-up duration of 62.9 months (IQR 36.5–95.0). The median dose of SBRT was 45Gy (IQR 37.5–50). Both the median PFS and OS were not reached. The 5-year PFS and OS were 57.2% (95% CI 44.3%–70.1%) and 62.3% (95% CI 49.8%–74.8%), respectively. In terms of number of patients, ORRs were in 73.2% (53 patients) by RECIST 1.1 and 77.5% (55 patients) by mRECIST. In terms of number of lesions, ORRs were 78.0% (92 lesions) by RECIST 1.1 and 82.2% (97 lesions) by mRECIST. Thirty-four patients (47.9%) with 54 lesions (45.8%) received DDLT, of whom 14 patients (41.1%) with 31 lesions (57.4%) exhibited pathologic complete response. Univariable analyses revealed ≤2 lesions (vs 3) (p=0.046), partial response (PR) by either RECIST 1.1 or mRECIST after SBRT (p=0.001), and DDLT (p=0.001) were prognostic of PFS, while tumours within Milan’s criteria (p=0.004), PR after SBRT (p=0.013) and DDLT (p

Introduction Despite the global prevalence of low fertility rates, male contributions to fertility and reproductive health outcomes have been understudied. This study aims to investigate the male contribution to fertility and explore the underlying biological mechanisms. Specifically, we aim to (1) identify male factors associated with successful pregnancy, (2) develop a fertility index incorporating modifiable factors for both males and females to predict pregnancy rate and (3) explore the relationship of male modifiable factors with semen parameters and molecular characteristics.Methods and analysis We will conduct an unmatched case-control study involving 240 couples with impaired male fertility (cases) and 240 couples with normal male fertility (controls). Between July 2024 and June 2026, we will recruit 480 eligible couples from KK Women’s and Children’s Hospital, Singapore. Male and female participants will complete questionnaires on sociodemographics, general health and lifestyle factors, and their anthropometry and body fat composition will be measured. Blood and semen samples from the male participants will be collected for biochemical, molecular and semen analyses. Predictive male factors will be identified using the least absolute shrinkage and selection operator method, accounting for female factors. We will construct a logistic regression model incorporating both male and female factors to derive a fertility index, which will be evaluated using cross-validation on subsets of the study population. Multivariable linear regression will be used to explore relationships between male modifiable exposures and semen parameters.Ethics and dissemination The study protocol has received approval from the Centralised Institutional Review Board of SingHealth (2024/2120), Singapore. Participants will provide written informed consent. Study results will be disseminated through conferences and peer-reviewed scientific journals.Trial registration number NCT06293235.

Summary: Background: Existing studies have not provided robust evidence about the CVD risk of non-smoking patients with restrictive spirometric pattern (RSP) or airflow obstruction (AFO), and how the risk is modified by body shape. We aimed to bridge the gap. Methods: We used never-smokers' data from the China Kadoorie Biobank (CKB) and performed Cox models by sex (278,953 females and 50,845 males). Spirometry was used to assess the baseline spirometric pattern. CVD outcomes were captured through multiple sources. Findings: Females’ results were presented primarily, though males' results were similar. During a median 12-year (maximum 14.5 years) follow-up, both RSP and AFO patients had increased risks of acute myocardial infarction (AMI), other ischaemic heart disease (other IHD), heart failure, pulmonary heart disease, arrhythmia, and intracerebral haemorrhage (ICH). RSP was also associated with ischaemic stroke (IS). The HRs (95% CIs) for AFO in females ranged from 1.29 (1.15–1.45) for ICH to 8.84 (7.79–10.03) for pulmonary heart disease, while those for RSP ranged from 1.11 (1.08–1.15) for IS to 3.17 (2.80–3.59) for pulmonary heart disease. These risks increased with the severity of AFO and reduced FVC. RSP/AFO was more strongly associated with other IHD, heart failure, and pulmonary heart disease in underweight females than in normal and obese counterparts, respectively. Interpretation: With the confounding of smoking fully controlled, both RSP and AFO were associated with higher risks of various CVD outcomes, which further increased with the severity of AFO and reduced FVC. These associations were even stronger in underweight individuals. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Ministry of Science and Technology of the People's Republic of China, Kadoorie Charitable Foundation, UK Wellcome Trust, UK Medical Research Council, Cancer Research UK, and British Heart Foundation.

Aim: Elder abuse may result in serious injuries with significant psychological consequences, leading to increased use of emergency department (ED) for trauma-related presentations. We aimed to describe the utilization of healthcare resources by victims of elder abuse. Materials and Methods: This retrospective study was conducted. Victims of elder abuse that were 65 years or older and presented between August 2018 and December 2020 were included. Information on demographics, mode of arrival, place and mechanism of injury, sustained injuries, injury severity score (ISS), disposition, and length of stay were collected and analyzed. Results: There were 33 (0.3%) victims of elder abuse. The median age was 69-year old (interquartile range: 66 to 76) and 23 (68.8%) participants were female. Majority (n=32, 97.0%) of patients sustained blunt injuries, with contusions to the limbs and head being the most common. The injuries were mostly minor to moderate in severity (ISS 8 or less: n=32, 97.0%). The utilization of healthcare resources was low: only two (6.1%) required ambulance transport to the ED, one (3.0%) required activation of the trauma team, one (3.0%) required surgery, and one (3.0%) required transfusion of blood products. However, 12 (36.4%) patients were admitted to the hospital, and five (15.2%) were admitted to the observation unit of the ED. Conclusion: Utilization of healthcare resource for injuries related to elder abuse was low. However, identification remains a challenge, and it is crucial for teams in the ED to be cognizant of elder abuse, as management should go beyond treating the injuries by including case notification, psychosocial assessment, and caregiver support.

Traditional optical waveguides or mediums are often silica-based materials, but their applications in biomedicine and healthcare are limited due to the poor biocompatibility and unsuitable mechanical properties. In term of the applications in human body, a biocompatible hydrogel system with excellent optical transparency and mechanical flexibility could be beneficial. In this review, we explore the different designs of hydrogel-based optical waveguides derived from natural and synthetic sources. We highlighted key developments such as light emitting contact lenses, implantable optical fibres, biosensing systems, luminating and fluorescent materials. Finally, we expand further on the challenges and perspectives for hydrogel waveguides to achieve clinical applications.

Background: Chest compressions are life-saving in cardiac arrest but concern by layperson of causing unintentional injury to patients who are not in cardiac arrest may limit provision and therefore delay initiation when required. Aim: To perform a systematic review of the evidence to identify if; among patients not in cardiac arrest outside of a hospital, does provision of chest compressions from a layperson, compared to no use of chest compressions, worsen outcomes. Method: We searched Medline (Ovid), Web of Science Core Collection (clarivate) and Cinahl (Ebsco). Outcomes included survival with favourable neurological/functional outcome at discharge or 30 days; unintentional injury (e.g. rib fracture, bleeding); risk of injury (e.g. aspiration). ROBINS-I was used to assess for risk of bias. Grading of Recommendations, Assessment, Development and Evaluation methodology was used to determine the certainty of evidence. (PROSPERO registration number: CRD42023476764). Results: From 7832 screened references, five observational studies were included, totaling 1031 patients. No deaths directly attributable to chest compressions were reported, but 61 (6 %) died before discharge due to underlying conditions. In total, 9 (

Background Adolescent pregnancy is defined as pregnancy occurring in young women between the ages of 10 and 19 years. Adolescent pregnancies, which are among the social healthcare concerns in developed and developing countries, have negative effects on maternal and infant health. Pregnancy in adolescence puts the health of both the mother and child at risk, as adolescent pregnancies have higher rates of eclampsia, systemic infection, low birth weight, and preterm delivery compared to other pregnancies. In this study, the effects of education level, smoking, and marital status on maternal and foetal outcomes in adolescent pregnancies were evaluated.Methods The records of a total of 960 pregnant women (480 pregnant adolescents aged 15–19 years and 480 pregnant adult women aged 20–26 years) were examined retrospectively. The demographic data of the groups and maternal and foetal outcomes of the pregnancies were compared. A logistic regression model was established as a statistical method for reducing confounding effects.Results Unmarried women were statistically significantly more prevalent in the adolescent group (38.3% vs. 7.3%). Among the considered risk factors, preeclampsia (2.9% vs. 0.8%) and smoking (29.8% vs. 9.8%) were statistically significantly more common in the adolescent group. When the groups were compared in terms of risk factors in pregnancy, it was found that pregnancy in adolescence was associated with a 3.04-fold higher risk of smoking, 5.25-fold higher risk of being unmarried, 3.50-fold higher risk of preeclampsia, and 1.70-fold higher risk of intrauterine growth retardation (IUGR).Conclusions This study demonstrates an increased risk of preeclampsia, IUGR, and smoking during pregnancy in adolescent pregnant women. These findings can be used to identify adolescent pregnancies requiring specific assistance and to take measures to reduce the probability of adverse outcomes.

Purpose: Breast cancer is a major cause of cancer-related mortality among African women. The adoption of molecular genomic technologies in the management of cancer cases is limited in Africa. To provide much-needed insights on the feasibility and utility of such precision medicine paradigms in Africa, we conducted a prospective, non-interventional study involving combined tissue and plasma Next-generation sequencing (NGS)-based testing in cancer patients in Ghana. Methods: We recruited 20 newly diagnosed, histologically confirmed, treatment-naïve women with metastatic breast cancer at the Cape Coast Teaching Hospital in Ghana. Tissue (NGS) and cell-free DNA (cfDNA) liquid biopsy analysis were ordered on all 20 patients. Results: All 20/20 (100 %) liquid biopsy samples were acceptable for analysis, whereas only 6/20 (30 %) passed quality control for tissue NGS testing. Liquid biopsy detected 42 cfDNA mutations in 17/20 patients. Of the 17 patients, 3 (17.6 %) had mutations previously associated with African ancestry, including BRCA1 p.K719E, ARAF p.S262I and GATA3 p.G125dup. Eight potentially actionable alterations specific to breast cancer were found in 6/17 (35.3 %) liquid biopsy samples, while potentially actionable mutations non-specific to breast cancer were detected in 12/17 (70.6 %). Tissue biopsy analysis detected mutations in all 6 patients tested, with 3/6 (50 %) patients presenting potentially actionable mutations relevant to breast cancer. Conclusion: Liquid biopsy detected multiple additional actionable variants in Ghanaian women with breast cancer. Plasma cfDNA analysis featured fewer variations in sample preparation which is a key consideration in resource-limited settings. Liquid biopsy presents a great opportunity to improve cancer care in Africa.

Background Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients. Methods and Results Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow‐up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher‐risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III‐IV, or all‐cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor‐3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >−15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area 15, and left atrial reservoir strain

Research on plant-based wound healing agents has been one of the current developing areas in modern biomedical science. This study aimed to assess the effects of ethyl acetate extract of Zingiber zerumbet rhizome (ZZRE) on open wound healing activity in Wistar rats. Ninety male Wistar rats (220–320 g) were divided into three groups treated with phosphate buffered saline (PBS) (negative control), Solcoseryl gel (positive control), and 10 % ZZRE (treatment group), respectively. Six circular full-skin thickness wounds of 6.0 mm in diameter were induced bilaterally on the dorsal surface of each rat. Six rats were sacrificed on Day-1, Day-3, Day-6, Day-10 and Day-14 respectively from each group after wound induction. All data obtained are considered statistically significant at p