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The sustainable performance of the endek ikat weaving business is essential for the growth of small and medium enterprises and the local economy of Bali (Indonesia). This study intends to examine the direct effects of green entrepreneurial orientation and sustainable leadership on endek weaving SME performance, as well as their indirect effects through the mediation of green digital innovation. This analysis was conducted on endek ikat weaving SMEs in the province of Bali. The population included 1,391 management personnel. Using the proportional random sampling, the study selected 311 respondents. The research hypotheses were tested using a questionnaire distributed among SME management in Bali. Research data were analyzed using the PLS-SEM method and SmartPLS 3 as the analytical tool. The results revealed that sustainable leadership affects green digital innovation (β = 0.483, t-statistic = 5.968). Green entrepreneurial orientation affects sustainable performance and green digital innovation (β = 0.240, 0.445; t-statistic = 2.858, 5.457). Moreover, green digital innovation has the potential to mediate the effect of sustainable leadership and green entrepreneurial orientation toward sustainable performance (β = 0.317, 0.292; t-statistic = 4.184, 4.645). By integrating leadership strategies with a green entrepreneurial approach, as well as innovating through digital media, Balinese endek weaving SMEs can improve their performance to achieve business sustainability. AcknowledgmentsThis is independent research that has not been funded by any institution. We would like to thank all parties who have provided immaterial support for this investigation.

Riset ini bertujuan untuk menganalisis pengaruh kepuasan kerja terhadap turnover intention dengan komitmen organisasional sebagai mediasi (studi pada Karyawan Beachwalk Shopping Center). Riset ini menggunakan sampel sejumlah 78 karyawan. Metode yang digunakan dalam riset ini adalah metode survei dengan teknik kuesioner dan wawancara dengan alat analisis statistik inferensial Structural Equation Modeling (SEM) berbasis PLS. Hasil riset menunjukkan bahwa kepuasan kerja berpengaruh negatif dan signifikan terhadap turnover intention. Kepuasan kerja berpengaruh positif dan signifikan terhadap komitmen organisasional, komitmen organisasional bepengaruh negatif dan signifikan terhadap turnover intention, dan komitmen organisasional memediasi pengaruh kepuasan kerja terhadap turnover intention. Implikasi riset ini adalah membuktikan traditional turnover theory serta kaitannya dengan variabel penelitian. Riset ini juga menawarkan manfaat komitmen organisasional, pengelolaan kepuasan kerja terhadap turnover intention.

Background: Previous studies have reported that the imbalance of occlusion, cervical spine, length of the limb, and asymmetric leg length are related to the presence of muscle compensation. These issues influence some strategies in orthodontic diagnosis for developing an updated stomatognathic system over multidisciplinary care issues. Purpose: This study aimed to obtain orthodontic findings and an orthopedic relationship between foot posture/function and dental malocclusion based on cross-sectional studies. Review: Some findings about postural system disequilibrium in static and dynamic foot postural related to occlusal changes have been reported following the mixed dentition phase. From 248 articles, 5 articles were selected and assessed with the Joanna Briggs Institute critical appraisal cross-sectional checklist and analyzed. Conclusions: Although the selected eligible articles demonstrated a low risk of bias in agreement (p > 0.05) among authors, the evaluation of those cross-sectional studies is still limited and requires further longitudinal studies with precise diagnostic parameters. Those parameters for evaluating the relationship between foot posture and malocclusion should encompass both static and dynamic approaches, including those related to mandibular position, tongue posture and function, bad habits, and temporomandibular disorder.

Background We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥65-years.Research design and methods We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model.Results XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65–79-year-olds and in ≥80-year-olds, respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time.Conclusion Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥65.

ABSTRACT: Background: Vibration amplification of sound energy at resonance (VASER) liposuction is an innovative technique that allows surgeons to selectively remove fat and shape desired areas of the body, resulting in more precise and controlled outcomes compared to traditional liposuction techniques. VASER liposuction offers several advantages, including targeted action that reduces trauma to the surrounding tissues, limiting pain, swelling and recovery time. Purpose: This study compared the complication rates among patients who underwent VASER liposuction in relation to their body mass index (BMI) and the amount of fat aspirated. Methods: The authors reviewed the medical records of all patients who underwent VASER liposuction at Scalera Clinic in Naples, dividing them into two groups: the first with BMI < 24.9 kg/m2 and second with BMI >25.0 kg/m2. Results: The authors examined 117 patients who were operated on within a year (2022/2023), with 48 of them having BMIs < 24.9 kg/m2 and 69 showing BMIs >25.0 kg/m2. In patients with a BMI >25 kg/m2, the most common complications were contusion, hematomas and abnormal skin retraction, whereas no complications were observed in the patients with normal-weight. Conclusions: To minimise post-operative complications and maximise results, it is advisable to select patients based on their BMI assessment, the anatomy of the treated body area and the volume of fat to be removed. This approach aims to ensure that the patients are suitable for the procedure and the achieved results align with their aesthetic expectations.

Abstract The common tern (Sterna hirundo) is a migratory seabird experiencing a decline in breeding pairs across several European populations due to various threats, including habitat destruction and human disturbance. This study investigates the population genetic structure and diversity of common terns sampled extensively across three European areas—Northern, Southern Inland and Southern Marine—during the breeding seasons, using 18 microsatellite markers and a mitochondrial DNA control region fragment. High genetic diversity was found in both types of markers, with the Southern Marine group showing the lowest overall diversity, although signals of possible population bottlenecks were detected in all groups. Various analyses indicated that population genetic structure was weak or absent, suggesting high gene flow among groups. The low genetic differentiation is likely influenced by distinct migration patterns, particularly between Southern Inland and Marine groups. Our results suggest that geographical distance between breeding colonies had minimal effect on population genetic structure. Further studies with tracking devices are needed to clarify how migration dynamics impacts genetic structure in common terns, while conservation efforts should focus on securing multiple breeding sites and currently unoccupied areas to increase options for habitat selection, supporting the species’ genetic diversity and long-term resilience.

Abstract Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma. We generated personalized sequencing panels targeting 10 tumor-specific single nucleotide variants (SNVs) for each patient and performed ctDNA analysis of 136 plasma samples collected longitudinally in 13 children with neuroblastoma. ctDNA was detected using ultra-deep next generation sequencing with unique molecular identifiers to eliminate polymerase-induced errors. We found that the levels of ctDNA at diagnosis correlated with risk group and decreased gradually during effective treatment. All samples collected during follow-up in patients without disease relapse were ctDNA-negative. All four relapses were associated with elevated ctDNA levels, and a majority of the analyzed SNVs were detected at time of relapse. In one case, ctDNA became positive 78 days before the relapse was diagnosed with routine assessment and increased by over a thousandfold before the start of additional treatment. Overall, ctDNA was more uniformly elevated at diagnosis, showed less putative false positive results, and was more sensitive for detection of relapse compared to five serum or urine tumor markers used in clinical routine. In conclusion, personalized ctDNA analysis is suitable for clinical monitoring of tumor burden and may be used in all neuroblastoma patients regardless of risk group or tumor genetics.

Background: Fatigue is one of the common symptoms in patients with chronic medical conditions like kidney failure that require hemodialysis. It is also associated with bad quality of life. Therefore, it is crucial to evaluate it using tools like Fatigue Severity Scale (FSS). Aim: The purpose of this study was to evaluate the reliability and validity of the translated FSS. Methods: FSS was performed on 41 chronic kidney patients undergoing dialysis. The FSS used in the study was translated from English to Bahasa Indonesia by the team. The questionnaire was assessed for its reliability and validity using Cronbach’s Alpha (CA) and Pearson Validity Test, respectively. Reliability for each item was also evaluated using the corrected item-total correlation. The scale is reliable if its CA value >0.6 and valid if the r-value is higher than the expected r on Pearson's table. Results: The scale was perceived as reliable based on the CA values from both respondent groups: 0.968 for HD and 0.952 for the CAPD group. All nine items were also deemed reliable based on the corrected item-total correlation score. Based on both r and Sig values, the translated FSS was valid for all groups: r>0.433 for HD, r>0.444 for CAPD, and Sig value

Abstract Frustration is a complex emotional phenomenon subject to various triggers and manifested through multifaceted behavioral and affective responses. This study investigates the relationship between distinct frustration-inducing situations encountered during driving and the corresponding affective responses, focusing on the mediating role of behavioral dimensions. A total of 2244 participants answered a questionnaire on driving behavior, the likelihood of experiencing frustration in various driving situations, and affective responses in frustrating situations. Latent factors and triggers of frustration were determined using Exploratory Factor Analysis, and their relationship to driving behavior was assessed using Multiple Regression Analysis. We identified four primary clusters of situations that could trigger frustration in drivers: Unpredictable Experiences, Achievement Obstacles, Distress Elicitors and External Distractions. The emotions accompanying driver frustration clustered into four distinct dimensions: Irritation, Anxiety, Boredom, and Embarrassment. While anxiety-related emotions were central in all frustrating responses (i.e., all four clusters), the other emotion dimensions were specifically related to some of the frustration clusters. Additionally, different types of frustrating situations were characterized by different emotional responses. Furthermore, having more lapses was related to heightened frustration levels. Unraveling the complexities of frustration may aid in the further further development of traffic safety by attempting to eliminate frequent frustration triggers in driving situations.

Abstract Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains. Additionally, we generate a mouse model replicating the patients’ phenotypic defects, including retinal dystrophy and behavioral abnormalities. Our results reveal a subcellular localization of GPATCH11 characterized by a diffuse presence in the nucleoplasm, as well as centrosomal localization, suggesting potential functions in RNA and cilia metabolism. Transcriptomic analysis performed on mouse retina detect dysregulation in both gene expression and splicing activity, impacting key processes such as photoreceptor light responses, RNA regulation, and primary cilia-associated metabolism. Proteomic analysis of mouse retina confirms the roles GPATCH11 plays in RNA processing, splicing, and transcription regulation, while also suggesting additional functions in synaptic plasticity and nuclear stress response. Our research provides insights into the diverse roles of GPATCH11 and identifies that the mutations affecting this protein are responsible for a recently characterized described syndrome.

Abstract Introduction The delineation of organs-at-risk and lymph node areas is a crucial step in radiotherapy, but it is time-consuming and associated with substantial user-dependent variability in contouring. Artificial intelligence (AI) appears to be the solution to facilitate and standardize this work. The objective of this study is to compare eight available AI software programs in terms of technical aspects and accuracy for contouring organs-at-risk and lymph node areas with current international contouring recommendations. Material and methods From January–July 2023, we performed a blinded study of the contour scoring of the organs-at-risk and lymph node areas by eight self-contouring AI programs by 20 radiation oncologists. It was a single-center study conducted in radiation department at the Lorraine Cancer Institute. A qualitative analysis of technical characteristics of the different AI programs was also performed. Three adults (two women and one man) and three children (one girl and two boys) provided six whole-body anonymized CT scans, along with two other adult brain MRI scans. Using a scoring scale from 1 to 3 (best score), radiation oncologists blindly assessed the quality of contouring of organs-at-risk and lymph node areas of all scans and MRI data by the eight AI programs. We have chosen to define the threshold of an average score equal to or greater than 2 to characterize a high-performing AI software, meaning an AI with minimal to moderate corrections but usable in clinical routine. Results For adults CT scans: There were two AI programs for which the overall average quality score (that is, all areas tested for OARs and lymph nodes) was higher than 2.0: Limbus (overall average score = 2.03 (0.16)) and MVision (overall average score = 2.13 (0.19)). If we only consider OARs for adults, only Limbus, Therapanacea, MVision and Radformation have an average score above 2. For children CT scan, MVision was the only program to have a average score higher than 2 with overall average score = 2.07 (0.19). If we only consider OARs for children, only Limbus and MVision have an average score above 2. For brain MRIs: TheraPanacea was the only program with an average score over 2, for both brain delineation (2.75 (0.35)) and OARs (2.09 (0.19)). The comparative analysis of the technical aspects highlights the similarities and differences between the software. There is no difference in between senior radiation oncologist and residents for OARs contouring. Conclusion For adult CT-scan, two AI programs on the market, MVision and Limbus, delineate most OARs and lymph nodes areas that are useful in clinical routine. For children CT-scan, only one IA, MVision, program is efficient. For adult brain MRI, Therapancea,only one AI program is efficient. Trial registration: CNIL-MR0004 Number HDH434.

I denne artikkelen undersøker vi forhandlinger mellom minoritetsnorske ungdommer og deres foreldre om romantiske relasjoner. I en flerkulturell kontekst med ulike normer og verdier knyttet til seksualitet, kjønn og ungdomstid, utgjør romantiske relasjoner en form for vitale veiskiller («vital conjuncture») (Johnson-Hanks, 2002) hvor potensielle fremtider og identiteter er oppe til forhandling, noe som gir rom for både usikkerhet og nye muligheter. Med utgangspunkt i intervjuer med minoritetsnorske kvinner og menn som i ungdomstiden inngikk i kjæresteforhold som brøt med familiens normer for akseptable parforhold, analyserer vi forhandlinger om hva som er et akseptabelt parforhold, hvem som er en akseptabel partner, og hvordan et akseptabelt forhold skal inngås. De generasjonelle forhandlingene synliggjør hvordan de unge utforsker og utvider rommet for å etablere romantiske relasjoner. Gjennom forhandlinger legges nye premisser for pardannelser. Dette gjøres på måter som både viderefører og utfordrer foreldregenerasjonens tradisjoner, og innebærer en omdefinering snarere enn svekking av relasjonene til foreldrene. Dette peker mot nye fremtidshorisonter for minoritetsnorske ungdommer og deres familier. I tillegg til å gi en bredere forståelse av ungdomsliv og unges familierelasjoner i Norden er artikkelen et bidrag til diskusjonen om minoritetsungdom, selvbestemmelse og sosial kontroll.

Background: Post streptococcal acute glomerulonephritis (PSAGN) patients have favorable prognosis, in which most patients showed full recovery in terms of kidney function. However, there is a slight chance ranging from 3 to 6% that PSAGN patients develop chronic kidney diseasewhich may progress into end-stage kidney disease in later life. It is important to identify the factors that can predict the development of chronic glomerulonephritis following PSAGN. Therefore, early intervention can be performed to halt the progression of chronic kidney disease. This study aimed to determine the predictive factors of chronic glomerulonephritis in pediatric patients with PSAGN. Methods: This study was an analytical observational study with retrospective cohort design. The accessible population was children within the age of 2–18 years old who were admitted with PSAGN between January 2015 and December 2020 in Dr. Sardjito General Hospital Yogyakarta. All anonymized patient data were evaluated for demographic variables, clinical features, laboratory profiles and outcome. Multivariate analysis was performed with multivariate logistic regression method. Results: A total of 124 patients with PSAGN were obtained from medical record data. There were 65 patients (52.4%) with chronic glomerulonephritis. Bivariate analysis was performed on assumed predictive factors with the results indicating massive proteinuria with hypoalbuminemia (OR 1.670, 95%CI 1.199–2.326; p = 0.003), oliguria (OR 1.517, 95%CI 1.101–2.089; p = 0.028) and macroscopic hematuria (OR 1.647, 95%CI:1.061–2.555; p = 0.013) were significantly higher in the PSAGN group with chronic glomerulonephritis compared to those without. Results of the multivariate logistic regression analysis showed massive proteinuria with hypoalbuminemia (OR 2.896, 95%CI 1.177–7.123, p = 0.021) and macroscopic hematuria (OR 2.457, 95%CI ,1.018–5.933, p = 0.046) would highly predict chronic glomerulonephritis in subjects with PSAGN. Conclusion: We concluded that massive proteinuria with hypoalbuminemia and macroscopic hematuria are the predictive factors which highly predict chronic glomerulonephritis in PSAGN.

This community service activity aims to increase the community's knowledge and skills in using chopping machines, which is a basic skill in managing litter and agricultural waste into compost and processing livestock forage into silage. Service activities were carried out in Tempurejo village, Kediri Regency with a total of 36 partners. The method used in this service is an empowerment based on collaborative participation. The activity stages follow the community empowerment implementation model, namely ODSIMED (Observation, Development, Socialisation, Implementation, Monitoring, Evaluation and Desemination). The instrument used to measure community knowledge and skills is a questionnaire and the data is analyzed quantitatively. The results of this service show that partners (1) are able to determine chopped materials for making compost or silage, achieving an average skill score of 3.27, (2) are able to differentiate the function of each part of the machine, achieving an average skill score of 3.30, (3) able to turn on and turn off the machine with a partner skill score reaching 3.20, (4) able to produce various forms of shreds both for compost and silage making purposes achieving an average score of 3.50, (5) able to calculate production capacity reaching the average skill score is 3.40, and (6) being able to carry out maintenance on machines reaches an average skill score of 2.80.

Packaging during the transportation process greatly influences the damage to horticultural products. Harvest apples are usually packed in wooden boxes or bamboo baskets and stacked until they reach maximum capacity. This makes the fruit easily damaged by bruising due to high piles. Based on these conditions, it is necessary to handle horticultural products in the form of apples to reduce damage to the fruit during transportation to maintain the quality of the apples until they reach consumers and extend the shelf life of the fruit. This research aims to design protective packaging for apples from a combination of water hyacinth and coconut fiber. The experimental method was carried out in this research with 2 factors consisting of 3 levels; factor one the combination of packaging materials, and factor two was the pressure of the packaging printer. Nine experimental units were obtained from the combination of the two treatments, namely K1T1 (E 90% + S 10%) with a pressing pressure of 400 psi, K1T1 (E 90% + S 10%) with a pressing pressure of 700 psi, K1T1 (E 90% + S 10% ) with a pressing pressure of 1000 psi, K2T1 (E 60% + S 40%) with a pressing pressure of 400 psi, K2T2 (E 60% + S 40%) with a pressing pressure of 700 psi, K2T3 (E 60% + S 40%) with pressing pressure 1000 psi, K3T1 (E 30% + S 70%) with pressing pressure 400 psi, K3T2 (E 30% + S 70%) with pressing pressure 700 psi, K3T3 (E 30% + S 70%) with pressing pressure 1000 psi. The results showed that the combination treatment of K2T2 with a pressing pressure of 700 psi provided the best protective quality for apples with the lowest percentage of mechanical damage and reduction in apple mass, at 5.556%, 2.55%, respectively. The springiness and texture values for apples were the highest with values respectively 3.17 mm, 16.7335N. Meanwhile, the highest packaging compressive strength value was obtained in the K3T3 treatment with a value of 26.164N.

Abstract Objective The influence of different faecal collection methods on metagenomic analyses remains under discussion, and there is no general agreement on which collection method is preferable for gut microbiome research. We compared faecal samples collected in tubes without preservatives with those containing 10 mL of 96% ethanol for gut microbiome research when the timeframe from defecation to freezing at – 80 °C was up to 24 h. We aimed to compare the collection methods on faeces from participants with inflammatory and non-inflammatory gastrointestinal disorders and healthy controls to investigate the most suitable method when considering data yield, human fraction of sequencing reads, and ease of use. We also examined the faecal sample homogeneity. Results Faeces collected in tubes without preservatives resulted in more sequencing reads compared to faeces collected in tubes with 96% ethanol and were also easier to handle. The human fraction of total reads in faeces collected in ethanol from participants with inflammatory bowel disease was higher than all other samples. DNA extraction and sequencing from two different locations in the same faecal sample gave similar results and showed sample homogeneity.

Abstract Background Within the contemporary policy turn towards co-production and co-research in Sweden, older people, practitioners and researchers alike have expressed uncertainty about how to undertake co-research. Moreover, scepticism persists about the merits and contributions of co-research and co-production to research and service development. In this paper, we aim to describe a co-research model developed with older care-experienced lay co-researchers and explore the utility of our model’s outcomes to social care research and practice. Method In a Participatory Action Research project, we established a team of three co-researchers by professional experience and eight lay co-researchers by lived experience who were over age 75. Our team undertook a complete study cycle from inception and funding through to knowledge exchange and dissemination. Our process lasted one year and comprised three phases: the group alone establishing collective knowledge, testing knowledge in peer interviews with acquaintances, exchanging knowledge in events with multi-sector actors. We generated and analysed data concurrently in fortnightly workshops and round-table meetings using procedures inspired by framework analysis to produce themes illustrated by vignettes. Findings We highlight our co-research model’s utility to social research, policy and practice under three themes. Expressly, how our approach (1) reaches and engages older people who are isolated at home, (2) generates out-of-the box thinking and innovative solutions for service development and research, (3) recognizes and benefits from older people’s authentic experience and knowledge. We critically reflect upon these three themes and the conditions that lead towards or away from the adoption of key co-research principles. Conclusions Public services and research and development units working in the interests of older people can take inspiration from our co-research model when seeking to meet the challenges brought by new reforms towards closer community involvement. Despite messiness in the process, integrating and embedding principled co-research and co-production can bring clarity and structure to the issues that matter most to older people, and draw organisations closer to the communities they serve.

Introdução: A desnutrição afeta tanto a condição clínica do paciente como também aumenta o risco de complicações em idosos, sendo responsável por contribuir com o aumento do tempo de hospitalização e a taxa de morbimortalidade dessa faixa etária. Objetivo: Estudar a associação do risco nutricional e desfechos clínicos em idosos internados em unidade de clínica médica em hospital privado do Rio de Janeiro. Materiais e métodos: Estudo longitudinal prospectivo, com 116 pacientes idosos. Nas primeiras 72 horas após a admissão hospitalar foi aplicado o questionário Triagem de Risco Nutricional (NRS-2002), coletados dados antropométricos, como peso e altura e diagnóstico clínico, e dados de desfechos clínicos no final da internação (óbito, infecção e tempo de internação). Os dados foram avaliados em programa estatístico SPSS e foi considerada significância 13 dias) apresentam chance três vezes maior de desenvolver infecção e ir a óbito. Conclusão: Os pacientes em risco nutricional tiveram maior risco de complicações e maior tempo de internação, infecção e óbito.

Abstract Introduction Women are more likely than men to experience interpersonal trauma, with 1 in 3 women affected globally. This paper aims to give a 2-year report of the demographics, trauma history [i.e., non-interpersonal and interpersonal including adverse childhood event (ACEs)] and psychiatric disorders endorsed by premenopausal women screened for our cardiovascular research study. Methods Premenopausal women were recruited from the Twin-Cities area using flyers. Interested participants were screened for this study via REDCap. Age, race, history of psychiatric disorders, menopausal status, contraceptives, and current medications were collected. Participants who met the eligibility criteria were enrolled and completed additional questionnaires focusing on trauma exposure and mental health. Results The first 2 years our study was open to accrual, a total of 447 premenopausal women were screened. The majority (~ 71%) of our participants were between 18 and 30 years old. Among the 447 women, 35% reported a diagnosis of posttraumatic stress disorder (PTSD), while 46% reported depression and 53% an anxiety disorder, according to DSM-5. Further, we found that women between the ages of 21–25 years reported the most (23%) psychiatric disorders, mainly PTSD. The main type of trauma reported was interpersonal trauma (~ 62%), of which 76% were ACEs. Conclusion Among the trauma-exposed women enrolled in our study, the age group between 21 and 25 years old endorsed the most psychiatric disorders, possibly stemming from ACEs. Our findings shed the light on the rising rate of psychiatric disorders in premenopausal women and support the growing public health burden of trauma exposure, particularly in childhood.

Abstract The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26–27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.

Abstract It has been shown recently, without an explanation of the possible molecular mechanisms involved, that 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic (EPPS) acid effectively protects from the neurotoxicity induced by oligomers and plaques formed by the protein amyloid-β protein. Here we report the same protective effect, obtained in vitro (HT22-diff cell line) and ex vivo (hippocampal slices) models, against amyloid neurotoxicity induced by oligomers of salmon Calcitonin (sCT), which has been shown to be a good model for the study of neurodegenerative diseases. Based on biophysical studies focusing on the protein aggregation kinetic and the interaction of the aggregates with model membranes, we propose a possible molecular mechanism underlying the protective effects. Taken together, our results indicate that EPPS is able to counteract the direct association (primary aggregation) of harmless low-molecular weight aggregates (dimers and trimers) or their aggregation catalysed by surfaces present in the solution (secondary aggregation). Thus, EPPS stabilizes harmless aggregates and hinders the formation of toxic and metastable prefibrillar oligomers. Overall, our data demonstrate that EPPS is an excellent drug candidate for the treatment of neurodegeneration due to misfolded proteins, such as Alzheimer’s or Parkinson’s disease.

Abstract Background In mucopolysaccharidosis type III (MPS III, also known as Sanfilippo syndrome), a pediatric neurodegenerative disorder, accumulation of abnormal glycosaminoglycans (GAGs) induces severe neuroinflammation by triggering the microglial pro-inflammatory cytokines production via a TLR4-dependent pathway. But the extent of the microglia contribution to the MPS III neuropathology remains unclear. Extracellular vesicles (EVs) mediate intercellular communication and are known to participate in the pathogenesis of adult neurodegenerative diseases. However, characterization of the molecular profiles of EVs released by MPS III microglia and their effects on neuronal functions have not been described. Methods Here, we isolated EVs secreted by the microglial cells after treatment with GAGs purified from urines of Sanfilippo patients (sfGAGs-EVs) or from age-matched healthy subjects (nGAGs-EVs) to explore the EVs’ proteins and small RNA profiles using LC–MS/MS and RNA sequencing. We next performed a functional assay by immunofluorescence following nGAGs- or sfGAGs-EVs uptake by WT primary cortical neurons and analyzed their extensions metrics after staining of βIII-tubulin and MAP2 by confocal microscopy. Results Functional enrichment analysis for both proteomics and RNA sequencing data from sfGAGs-EVs revealed a specific content involved in neuroinflammation and neurodevelopment pathways. Treatment of cortical neurons with sfGAGs-EVs induced a disease-associated phenotype demonstrated by a lower total neurite surface area, an impaired somatodendritic compartment, and a higher number of immature dendritic spines. Conclusions This study shows, for the first time, that GAGs from patients with Sanfilippo syndrome can induce microglial secretion of EVs that deliver a specific molecular message to recipient naive neurons, while promoting the neuroinflammation, and depriving neurons of neurodevelopmental factors. This work provides a framework for further studies of biomarkers to evaluate efficiency of emerging therapies. Graphical Abstract

Abstract Nervous system cancers exhibit diverse transcriptional cell states influenced by normal development, injury response, and growth. However, the understanding of these states’ regulation and pharmacological relevance remains limited. Here we present “single-cell regulatory-driven clustering” (scregclust), a method that reconstructs cellular regulatory programs from extensive collections of single-cell RNA sequencing (scRNA-seq) data from both tumors and developing tissues. The algorithm efficiently divides target genes into modules, predicting key transcription factors and kinases with minimal computational time. Applying this method to adult and childhood brain cancers, we identify critical regulators and suggest interventions that could improve temozolomide treatment in glioblastoma. Additionally, our integrative analysis reveals a meta-module regulated by SPI1 and IRF8 linked to an immune-mediated mesenchymal-like state. Finally, scregclust’s flexibility is demonstrated across 15 tumor types, uncovering both pan-cancer and specific regulators. The algorithm is provided as an easy-to-use R package that facilitates the exploration of regulatory programs underlying cell plasticity.

Abstract Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity. In vivo, the selected bispecific antibody BiA9*2_HF loaded with peptide cargos induces improved antigen-specific proliferation of CD8+ (10-15 fold) and CD4+ T cells (2-7 fold) over control in draining lymph nodes. In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.

Abstract Background Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12 months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care. Methods Employed individuals aged 18–59 years on sick leave (2 to 12 weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12 months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression. Results One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04). Conclusions A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context. Trial registration NCT3346395, registration date 2017–11-17.

Telah banyak dilakukan penelitian mengenai Moodle, LMS terkenal, dan pengaruhnya terhadap berbagai aspek pendidikan. Akan tetapi, terdapat kekurangan yang signifikan dalam literatur mengenai penggunaan Moodle secara spesifik untuk meningkatkan kemampuan menulis teks eksposisi. Penelitian ini untuk mengetahui bagaimana pemahaman dan kemampuan siswa menulis teks eksposisi dan bagaimana penggunaan Moodle dalam meningkatkan kemampuan menulis teks eksposis. Melalui metode penelitian literatur review, penulis memilih 2 artikel dari 19 artikel terkait Moodle dan memilih 6 artikel dari 18 artikel terkait penulisan teks eksposisi untuk dianalisa. Dari hasil penelitian ini, siswa mampu menulis teks eksposisi dengan baik dengan pemahaman yang baik juga. Di samping itu, penggunaan Moodle dapat meningkatkan kemampuan menulis siswa bahasa Inggris. Penggunaa Moodle lebih efektif daripada metode konvensional dalam meningkatkan kemampuan menulis siswa, dengan hasil yang menguntungkan kelompok eksperimen. Implikasinya adalah peneliti lain bisa meneliti dampak penggunaan Moodle untuk meningkatkan kemampuan teks eksposisi di sekolah dasar.

Introduction: Individuals with traumatic brain injury (TBI) experience long-term consequences of the injury and need long-term support from health care services. The consequences are complex and heterogeneous and may limit physical, cognitive, emotional, and social activities. Goal-oriented and individualized home-based rehabilitation is an appropriate approach for individuals living at home with long-term activity limitations after TBI. Main part: Based on a recently completed research project, this article describes a SMART-goal and action planning approach based on patient-reported problem areas for home dwelling individuals with ongoing activity limitations in the chronic phase of TBI. Collaboration with municipal health-resources and other outside collaborators was established for 53% of the participants. Acceptability was high for both participants and family members. The research project has shown that goal-oriented and individualized home-based rehabilitation improves health-related quality of life and reduces symptom burden and anxiety in the chronic phase of TBI. Sum up: This article has exemplified how individualized goal-oriented rehabilitation can be carried out for individuals living at home with long-term activity limitations after TBI. Even after several years, the physical, cognitive, emotional and social activity limitations can be improved by individualized and goal-oriented evidence-based rehabilitation. The SMART-goal and action planning approach is well suited to strengthen the collaboration between the municipality and the specialist health care service.

Abstract Patients with phenylketonuria (PKU) have a highly restrictive diet, which involves restriction of phenylalanine (Phe) intake and daily use of Phe‐free metabolic formula. However, little is known about the potential impact of this diet on chemical senses. The present study aimed to evaluate the olfactory and gustatory perceptions of patients with PKU. A cross‐sectional controlled study which included patients with PKU on dietary treatment and healthy controls was performed. Olfactory perception was assessed using the 12‐item Sniffin’ Sticks test, and taste perception using the Taste Strips test. Twenty‐five patients (mean age 19.3 ± 4.7 years; 13 females) and 25 controls (mean age 19.9 ± 4.9 years, p = 0.676; 13 females) were included. The mean age at treatment onset was 52.8 ± 29.7 days. The mean scores for olfactory and gustatory perceptions, and for bitter and salty flavors, were lower in patients than in controls (p = 0.039, p = 0.004, p = 0.008, and p = 0.020, respectively). Among patients, Phe levels at diagnosis correlated negatively with bitter taste (r = −0.493, p = 0.006). The lower olfaction and gustation scores found in patients may be related to understimulation caused by the highly restrictive PKU diet and the deprivation of flavors from breast milk.

Introduction: Environmental temperature conditions might influence the composition of secondary metabolites in certain medicinal plants. This study aimed to examine how some of the phytochemicals and anticancer properties of Carpobrotus edulis may be impacted by temperature conditions. Methods: The plant specimens were kept in growth chambers at 15/10 °C and 45/35 °C (day/night), and harvested at 48-hour intervals (48, 96, and 144 hours). Control conditions were maintained at 25/15 °C. Standard phytochemical colour tests were used to determine the presence of eight phytochemicals. The anticancer activity against cervical cancer cell lines was determined using cell viability assay, cell morphology, Hoechst staining, and wound healing assays. Results: The phytochemical screening showed the presence of all tested phytochemicals (phenolics, flavonoids, terpenoids, saponins, tannins, steroids, and cardiac glycosides) in all treatments except for saponins in the 96- and 144-hour temperature treatments. A noteworthy IC50 value of 284.9 µg/mL was determined from the methanolic leaf extract exposed to high temperatures for 144 hours against cervical cancer. Treatment with this extract suggested changes in cancer cell morphology, signs of apoptosis, and cell migration inhibition. Conclusion: The preliminary results obtained suggest that the C. edulis methanolic extract has potential anticancer properties against cervical cancer. These observations may have implications for the indigenous plant use in treating various ailments and broaden the type of anticancer research involving this plant.

Indonesia, as the country with the largest Muslim population globally, faces challenges in implementing religious moderation to maintain harmony and peace amidst diversity. One such challenge is the rejection of constructing non-Muslim places of worship in several regions, indicating ongoing resistance to religious pluralism. This study aims to analyze Quranic verses related to religious moderation and the construction of non-Muslim places of worship through a comparative study between Tafsir Al-Azhar by Buya Hamka and Tafsir Juz 'Amma by Firanda Andirja, focusing on Surah Al-Hajj verse 40, Al-Baqarah verse 256, Al-An'am verse 108, and Al-Kafirun verses 1–6. The research employs a qualitative method with a literature study approach, analyzing the interpretations of both scholars on these verses. The findings indicate that Buya Hamka in Tafsir Al-Azhar*emphasizes the importance of tolerance and respecting the rights of non-Muslims to worship and build places of worship, while affirming that there is no compromise in matters of faith and monotheism. In contrast, Firanda Andirja in Tafsir Juz 'Amma emphasizes a stance of disengagement regarding the welfare of non-Muslims and tends not to support the construction of non-Muslim places of worship, although still advocating for tolerance. Abstrak: Indonesia, sebagai negara dengan populasi Muslim terbesar di dunia, menghadapi tantangan dalam menerapkan moderasi beragama untuk menjaga kerukunan dan perdamaian di tengah keberagaman. Salah satu tantangan tersebut adalah penolakan terhadap pembangunan tempat ibadah non-Muslim di beberapa wilayah, yang menunjukkan masih adanya resistensi terhadap pluralitas agama. Penelitian ini bertujuan untuk menganalisis ayat-ayat Al-Qur'an terkait moderasi beragama dan pembangunan tempat ibadah non-Muslim melalui studi komparatif antara Tafsir Al-Azhar karya Buya Hamka dan Tafsir Juz 'Amma karya Firanda Andirja, dengan fokus pada Surah Al-Hajj ayat 40, Al-Baqarah ayat 256, Al-An'am ayat 108, dan Al-Kafirun ayat 1–6. Metode penelitian yang digunakan adalah studi kepustakaan dengan pendekatan kualitatif deskriptif, menganalisis penafsiran kedua mufasir terhadap ayat-ayat tersebut. Hasil penelitian menunjukkan bahwa Buya Hamka dalam Tafsir Al-Azhar menekankan pentingnya toleransi dan menghargai hak non-Muslim untuk beribadah dan mendirikan tempat ibadah, sambil tetap menegaskan bahwa dalam akidah dan tauhid tidak ada kompromi. Sementara itu, Firanda Andirja dalam Tafsir Juz 'Amma lebih menekankan sikap berlepas diri dalam hal kemaslahatan non-Muslim dan cenderung tidak mendukung pembangunan tempat ibadah non-Muslim, meskipun tetap menganjurkan sikap toleransi.

Objectives Disorders of amino acid metabolism fall under the category of inborn errors of metabolism that can be managed with a protein-restricted diet. However, adherence to such a diet often poses challenges, leading to low treatment engagement. Consequently, there is a pressing need for new resources to aid in dietary self-monitoring. The goal is to develop and implement “AminoApp,” an application tailored for dietary self-monitoring in patients with inborn errors of metabolism who are on a low-protein diet. Methods The design and development of the application adhered to the user-centered design method. This approach emphasizes active participation and collaboration between users and designers/researchers throughout all stages of product development, including requirement gathering, prototype development, and evaluation. Usability was evaluated using the System Usability Scale, which has been validated in Portuguese. Results The application’s features include a food diary, a food consultation area, exam records, a recipe calculator, and reports on diet composition and metabolic control. The usability test included four patients on a low-protein diet, three caregivers, and three healthcare professionals. The average usability score was 84.9, with averages of 77.5 for patients, 85.8 for caregivers, and 91.6 for professionals, indicating that the application is user-friendly. Conclusions AminoApp is the first application developed in Brazil designed to assist in managing inborn errors of metabolism that require a protein-restricted diet. It was found to be easy to use, and the initial results are promising. Further research is necessary to evaluate the impact of the application on metabolic control and treatment adherence.

Abstract Background Few studies describe the use of the Post-Stroke Checklist (PSC) as a tool for longitudinal stroke follow-up in clinical practice. We mapped the prevalence of stroke-related health problems and targeted interventions at 3 and 12 months post-stroke by using the PSC. Methods Patients with acute stroke discharged home in 2018–2019 at Skåne University Hospital, Sweden, were invited to participate in a comprehensive nurse-led follow-up based on a 14-item PSC 3 and 12 months post-stroke. We measured time consumption, screened for stroke-related health problems, compared the findings, and recorded targeted healthcare interventions. Problems at 12 months were grouped into new, persistent, or none compared to the 3-month evaluation. Results Of 200 consecutively included patients, 146 (77%) completed both the 3- and 12-month follow-ups. At 12-month follow-up, 36% of patients reported no stroke-related health problems, 24% reported persistent problems, and 40% reported new problems since the 3-month evaluation. New problems at 12 months were most common within the domains: secondary prevention (23%) and life after stroke (10%). Stroke recurrence rate was 7.5%, 43% had high blood pressure, and few smokers had quit smoking. At 12 months, 53% received at least one new healthcare intervention, compared to 84% at 3 months. Conclusions Stroke-related health problems decreased beyond 3 months but were still present in two-thirds of patients at 1 year. This emphasizes the relevance of continuous structured follow-up using the PCS. However, the follow-up alone was insufficient to adequately achieve treatment targets for secondary prevention, which require intensified focus. Trial registration ClinicalTrials.gov ID NCT04295226, (04/03/2020)

Abstract Background Classical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD. Method Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE). Results The median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates). Conclusion Our results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Abstract Background Erector spinae plane block (ESPB) is a novel analgesic technique that can reduce post-operative pain and postoperative opioid consumption in laparoscopic surgeries. Methods We searched PubMed, Scopus, and Web of Science on November 17th, 2023 for clinical trials comparing ESPB with other analgesic techniques or placebo for laparoscopic surgeries. We meta-analyzed post-operative pain at rest, postoperative opioid consumption, time to first rescue analgesic request, and postoperative nausea and vomiting using a random effects model. Results ESPB significantly reduced opioid consumption compared to placebo (SMD, (95CI), p-value; -1.837, (-2.331, -1.343),

Abstract Background The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Abstract Background Phenylketonuria (PKU) is a rare genetic disorder characterized by a deficiency in the metabolism of the essential amino acid phenylalanine, which has a neurotoxic effect at high concentrations. The available treatment for PKU involves limiting the intake of phenylalanine through a restrictive diet. Strict adherence to treatment is essential for a child’s proper development. Owing to their rare and chronic condition, PKU patients and their caregivers need to address many specific challenges, which can affect their quality of life (QoL). Purpose This review aimed to identify, characterize, map, and summarize existing knowledge about the quality of life of PKU patients and their primary caregivers. Methods A scoping review was conducted following the PRISMA-ScR guidelines. The PubMed, PsycINFO, EMBASE, Scopus, CINAHL, and BVS databases were searched, and articles published between January 2000 and February 2023 were included. Results The search resulted in 3249 articles, 29 of which were selected for analysis. Most studies were cross-sectional, and the highest concentration of publications ranged between 2011 and 2021. Generic self-report questionnaires were the tools most commonly used to assess patients’ and their caregivers’ QoL. A significant negative impact on QoL was found in most studies with pediatric patients and caregivers. High current and lifetime blood Phe levels were associated with worse QoL in several domains, and higher tolerance of ingested phenylalanine was associated with a lower impact on QoL. Among caregivers, psychosocial variables such as stress, anxiety, depression, and child behavior problems were associated with poorer QoL. Higher perceived social and emotional support was a protective factor of QoL in caregivers. Conclusion Patients of pediatric age and their caregivers, younger caregivers, and female patients and caregivers seem to be especially vulnerable to QoL impairments. The social and emotional dimensions were the most affected. These results emphasize the importance of combining generic and disease-specific assessment tools to achieve a comprehensive assessment. Despite the growing interest in this topic, the longitudinal literature is limited, and there is a lack of interventional studies on this population. Future interventions addressing diet management and providing psychosocial support may benefit the QoL of the PKU population.

Manajemen perusahaan bertanggung jawab dalam mengelola bisnis untuk mencapai keberlanjutan dan meningkatkan nilai perusahaan. Penelitian ini bertujuan untuk mengetahui peran environmental performance dalam memoderasi hubungan profitabilitas dan gross domestic product (GDP) terhadap nilai perusahaan. Populasi dalam penelitian ini adalah perusahaan yang terdaftar PROPER di Bursa Efek Indonesia periode 2019 – 2023. PROPER adalah program penilaian peringkat kinerja perusahaan dalam pengelolaan lingkungan hidup. Teknik pengambilan sampel yang digunakan adalah teknik sampling jenuh, yaitu meneliti seluruh populasi, dengan jumlah sampel sebanyak 84 perusahaan. Teknik analisis data dalam penelitian ini menggunakan teknik moderated regression analysis (MRA). Berdasarkan hasil analisis penelitian ini menunjukkan bahwa profitabilitas berpengaruh positif signifikan terhadap nilai perusahaan, gross domestic product berpengaruh negatif signifikan terhadap nilai perusahaan, environmental performance tidak mampu memoderasi pengaruh profitabilitas terhadap nilai perusahaan, dan environmental performance tidak mampu memoderasi pengaruh gross domestic product terhadap nilai perusahaan. Hasil penelitian ini diharapkan dapat menjadi bahan pertimbangan bagi manajemen perusahaan maupun investor.

Los recientes adelantos de la genómica y el acelerado desarrollo de las llamadas “ciencias ómicas” han permitido diagnosticar incontables enfermedades poco frecuentes (EPF). La inteligencia artificial (IA) ha permitido sistematizar los conocimientos de la genómica y de los informes clínicos y epidemiológicos. Sin embargo, la preservación y resguardo del anonimato y el eventual uso inadecuado de la información obtenida, se presentan como un gran desafío ético, jurídico y social. Las EPF además de constituir un problema de salud pública y un desafío en materia de justicia social y no discriminación, generan vulnerabilidades. El presente trabajo tiene por objeto reflexionar sobre la doble vulnerabilidad de las personas que viven con EPF: la enfermedad misma, y cómo preservar su integridad física, psíquica, social y espiritual cuando el uso de la IA para el diagnóstico o registro podría revelar su identidad, imagen y datos sensibles, mediante el uso de algoritmos.

Abstract The Citarum River revitalization program through the “Citarum Harum” program, focuses on integrated cooperation between multi-sector actors in managing the Citarum Watershed sustainably and improving the quality of life around the river. Such as ministries (central government) acting as policy and regulation providers and as the leading sector, local governments acting as program supervisors and monitors, academics/universities acting as knowledge creators and program management innovations, the private sector acting as important partners, communities acting as program supporters and participants, and the Indonesian National Army (Tentara National Indonesia, TNI) acting as initiators, law enforcers, and field supervisors. This article outlines some of the challenges faced by Citarum Watershed, as well as important findings regarding collaborative sustainable and resilient watershed management, particularly in the context of the Citarum River, Indonesia. In this commentary, we underscore the importance of collaborative efforts, effective policy frameworks, and adaptive management strategies in addressing the environmental challenges faced by the Citarum River, while highlighting the need for ongoing commitment from all stakeholders during program implementation and post-program. The implications of these findings suggest a holistic, inclusive, and adaptive approach to sustainable management of watersheds and the environment that can be applied to other regions facing similar challenges such as Pollution; Environmental Degradation; Critical Land and Sedimentation; Inadequate Infrastructure; Population Growth and Urbanization; Climate Change, Weak Law Enforcement, and Lack of Coordination Among Stakeholders.

Abstract Background Breast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important. Methods This real-world cohort study is based on electronic health records from Capital Region of Denmark. All women with metastatic breast cancer initiating first-line treatment with CDK4/6 inhibitor between May 2017 and October 2022 were included. Results A total of 546 patients were eligible for inclusion in the 12-week landmark analysis and 192 (35%) experienced dose reduction. These patients were older, had worse ECOG PS, more received prior adjuvant endocrine treatment, and more received fulvestrant as the endocrine backbone. Dose reduction was associated with reduced overall survival (39.9 vs. 54.3 months) and shorter treatment duration (18.0 vs. 26.9 months). Adjusted hazard ratio for death was 1.38 (95% CI: 1.01–1.89). Conclusions Dose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with significantly higher mortality and shorter treatment duration. These findings contrast with previous analyses showing no effect of dose reduction, likely due to considering immortal time bias in this study.

Abstract Background Primary healthcare, the first line of care in many countries, treats patients with diverse health problems. High workload, time pressure, poor job control and negative interpersonal experiences with supervisors have been documented in primary healthcare. The work environment in primary healthcare is also affected by several types of changes. Aim We aimed to explore the levels of job satisfaction, turnover intention, social support, leadership climate and change fatigue according to physicians in Swedish primary healthcare. We also aimed to identify and characterize physicians exhibiting both high turnover intention and low job satisfaction, i.e., “discontent with current job”. Methods A cross-sectional survey based on a random sample of physicians working in Swedish primary healthcare. Results Approximately one-quarter of the respondents were discontented with their current job. Discontent was negatively associated with poor general health and change fatigue among the respondents; social support from colleagues and a favorable leadership climate showed positive associations in terms of reducing the levels of discontent with current job. Conclusions The findings of this study highlight the association between low levels of job satisfaction and high levels of turnover intention (i.e., discontent with current job) among physicians in primary healthcare. Moreover, these variables exhibited a strong association with physicians’ general health; poor health significantly increased the likelihood of discontent with current job. Our findings also show that experiencing change fatigue is associated with discontent with current job among physicians in primary healthcare. This knowledge can help identify and improve shortcomings within the psychosocial work environment in Swedish primary healthcare.

Abstract We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.

Abstract Background Brain metastasis (BM) is a rare but severe complication of head and neck squamous cell carcinoma (HNSCC), with limited knowledge of molecular characteristics and immunogenicity. Methods We analyzed 61 cases of HNSCC-BM from three academic institutions (n = 24) and Foundation Medicine Inc (FMI, n = 37). A subset of cases underwent next-generation sequencing, multiple immunofluorescence, and proximity ligation sequencing. Gene enrichment analysis compared alterations in FMI BM samples (n = 37) with local samples (n = 4082). Results Demographics included: median age of 59 years, 75% male, 55% current/former smokers, 75% oropharyngeal primary, and 67% human papillomavirus (HPV) +. ATM (54%), KMT2A (54%), PTEN (46%), RB1 (46%), and TP53 (46%) were frequently altered in BM samples from academic centers (62% HPV/p16+). Structural rearrangements ranged from 9 to 90 variants by proximity ligation sequencing. BMs had low densities of CD8+, PD-1+, PD-L1+, and FOXP3 + cells, and 92% had PD-L1 combined positive scores

Abstract There is a need to investigate the effect of lifestyle modifications on cardiometabolic health-related issues that occur during menopause. The aim of this study was to compare the effect of resistance and endurance circuit training program alone (exercise group, n = 34) with the effect of time-restricted eating (16:8) combined with a training program (combination group, n = 28) on cardiometabolic health in 62 menopausal women (aged 51.3 ± 4.69 years). Testing was conducted before and after a 12-week period and included an assessment of body composition, glycemic control, lipid panel, blood pressure, and anthropometric measurements. Decreases in body mass index and systolic blood pressure were significantly greater in the combination group than in the exercise group (F(1,60) = 4.482, p = 0.038, η2 = 0.07; F(1,57) = 5.215, p = 0.026, η2 = 0.08, respectively, indicating moderate effects). There were significant decreases in fat mass (p = 0.001, r = 0.654), glucose level (p = 0.017, r = 0.459), insulin level (p = 0.013, r = 0.467), homeostatic model assessment for insulin resistance (p = 0.009, r = 0.499), waist circumference (p = 0.002, r = 0.596), and waist-to-height ratio (p = 0.003, r = 0.588) (indicating moderate effect) in the combination group, while there were no significant changes in the exercise group. There were no changes in lipid panel indicators in either group. This is the first study to investigate the effect of time-restricted eating combined with exercise in menopausal women. The results of the study provide evidence that the combination of time-restricted eating and exercise leads to a greater body mass index reduction than exercise alone in menopausal women. Trial registration: ClinicalTrials.gov, NCT06138015 registered 18 November 2023—Retrospectively registered, https://clinicaltrials.gov/study/NCT06138015 .

Local culture has undergone significant shifts and alienations, leading to the neglect of societal values. This situation underscores the need for teachers to be well-prepared to incorporate local wisdom into science education, supporting Cultured-Based Learning. This study, conducted from January to June 2022, aimed to assess the relevance of items in a teacher readiness instrument for implementing local wisdom-based science learning in Bali. An ex post facto research design was employed to analyze the preparedness of 72 science teachers in Bali through a detailed questionnaire. The collected ordinal data were converted into an interval scale using the Method of Successive Interval (MSI) and analyzed using the Rasch Model with the Jamovi application to assess item relevance. The study's findings highlight the cognitive and emotional readiness of science teachers as being in the high category, while collegial support and instructional tools are in the low category. These results suggest that improving collegial features and instructional tools through lesson studies and workshops could enhance the integration of local wisdom into science education in Bali.

Abstract For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6–77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Abstract Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

Abstract Background Primary ovarian insufficiency (POI) manifests with hormonal imbalances, menstrual irregularities, follicle loss, and infertility. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are emerging as a promising treatment for POI. This systematic review aims to assess the effects of MSC-EVs on follicle number, hormonal profile, and fertility in POI animal models. Methods A systematic search of PubMed, Scopus, and Web of Science databases up to December 14th, 2023 was conducted. Two reviewers independently conducted screening, risk of bias assessment, and data extraction. Meta-analysis was performed to analyze treatment versus control outcomes using a random effects model. Publication bias was assessed using Egger’s regression test and sensitivity analysis was assessed using the leave-one-out method. Subgroup analyses and meta-regressions were conducted based on EV source, induction model, type of animal, study quality, administration route, administration frequency and route, and dose. Results a total of 29 studies were included. MSC-EVs treatment significantly increased total follicle count (SMD, (95CI), p-value; 3.56, (0.91, 6.21),

Abstract Body image disturbance is a key symptom of anorexia nervosa (AN). AN patients report body dissatisfaction and overestimate their own body size in several tasks. This study aimed to clarify whether this overestimation arises from deficits in visual perception. To this end, 36 adolescent restrictive-type AN patients and 42 matched healthy controls performed metric and depictive body size estimation (BSE) tasks. Magneto- and electroencephalography were measured during the size estimation of 66 computer-generated body pictures varying in size from underweight to overweight. AN patients versus controls showed overestimation across self-referential metric and depictive BSE tasks, but similar performance in a depictive BSE task without self-reference and similar early neurophysiological responses. Starting mid-latency (200 ms), AN patients showed relatively more neural activity in response to underweight body pictures and less neural activity in response to higher-weight body pictures in distributed brain regions. A secondary comparison of AN patients with slight vs. distinct overestimation during self-referential BSE uncovered relatively stronger neural responses to body pictures corresponding to the estimated body mass index. These results suggest that body image disturbances in adolescent restrictive-type AN patients depend on self-reference and do not represent a deficit of visual perception, but rather biased emotional attention.

Abstract Venetoclax plus azacitidine treatment is clinically beneficial for elderly and unfit acute myeloid leukemia (AML) patients. However, the treatment is rarely curative, and relapse due to resistant disease eventually emerges. Since no current clinically feasible treatments are known to be effective at the state of acquired venetoclax resistance, this is becoming a major challenge in AML treatment. Studying venetoclax-resistant AML cell lines, we observed that venetoclax induced sublethal apoptotic signaling and DNA damage even though cell survival and growth were unaffected. This effect could be due to venetoclax inducing a sublethal degree of mitochondrial outer membrane permeabilization. Based on these results, we hypothesized that the sublethal apoptotic signaling induced by venetoclax could constitute a vulnerability in venetoclax-resistant AML cells. This was supported by screens with a broad collection of drugs, where we observed a synergistic effect between venetoclax and PARP inhibition in venetoclax-resistant cells. Additionally, the venetoclax-PARP inhibitor combination prevented the acquisition of venetoclax resistance in treatment naïve AML cell lines. Furthermore, the addition of azacitidine to the venetoclax-PARP inhibitor combination enhanced venetoclax induced DNA damage and exhibited exceptional sensitivity and long-term responses in the venetoclax-resistant AML cell lines and samples from AML patients that had clinically relapsed under venetoclax-azacitidine therapy. In conclusion, we mechanistically identify a new vulnerability in acquired venetoclax-resistant AML cells and identify PARP inhibition as a potential therapeutic approach to overcome acquired venetoclax resistance in AML.