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BACKGROUND: Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. METHODS: Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. DISCUSSION: This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

Sotigalimab is an agonistic anti-CD40 monoclonal antibody that can modulate anti-tumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer with the primary outcome of efficacy as measured by pathologic complete response (pCR) rate, the combination induced pCR in 38% of treated patients. We investigated the mechanism of action of sotigalimab in samples obtained from this clinical trial. Tumor biopsies and peripheral blood samples were collected at baseline, following an initial dose of sotigalimab, and at the time of surgery after CRT completion from six patients. High dimensional single cell techniques were used, including combined single cell RNA sequencing and proteomics (CITEseq) and multiplexed ion beam imaging (MIBI), to analyze immune responses. Sotigalimab dramatically re-modeled the immune compartment in the periphery and within the tumor microenvironment (TME), increasing expression of molecules related to antigen processing and presentation and altering metabolic pathways in myeloid cells. Concomitant with these changes in myeloid cells, sotigalimab treatment primed new T cell clonotypes and increased the density and activation of T cells with enhanced cytotoxic function. Sotigalimab treatment also induced a decrease in the frequency of Tregs in the TME. These findings indicate that a single dose of sotigalimab leads to enhanced antigen presentation that can activate T cells and induce new T cell clones. This restructuring of the TME provides elements which are critical to the development of effective antitumor immune responses and improved clinical outcomes.

Abstract Chronic obstructive pulmonary disease (COPD) is an etiologically complex disease characterized by acute exacerbations and stable phases. We aimed to identify biological functions modulated in specific COPD conditions, using whole blood samples collected in the AERIS clinical study (NCT01360398). Considered conditions were exacerbation onset, severity of airway obstruction, and presence of respiratory pathogens in sputum samples. With an integrative multi-network gene community detection (MNGCD) approach, we analyzed expression profiles to identify communities of correlated genes. The approach combined different layers of gene interactions for each explored condition/subset of samples: gene expression similarity, protein-protein interactions, transcription factors, and microRNAs validated regulons. Heme metabolism, interferon-alpha, and interferon-gamma pathways were modulated in patients at both exacerbation and stable-state visits, but with the involvement of distinct sets of genes. An important gene community was enriched with G2M checkpoint, E2F targets, and mitotic spindle pathways during exacerbation. Targets of TAL1 regulator and hsa−let−7b − 5p microRNA were modulated with increasing severity of airway obstruction. Bacterial infections with Moraxella catarrhalis and, particularly, Haemophilus influenzae triggered a specific cellular and inflammatory response in acute exacerbations, indicating an active reaction of the host to infections. In conclusion, COPD is a complex multifactorial disease that requires in-depth investigations of its causes and features during its evolution and whole blood transcriptome profiling can contribute to capturing some relevant regulatory mechanisms associated with this disease. In this work, we explored multi-network modeling that integrated diverse layers of regulatory gene networks and enhanced our comprehension of the biological functions implicated in the COPD pathogenesis.

Abstract While existing literature describing the use of co-design has focused on its application within individual-level or group-level health interventions, the use of co-design to plan and support the implementation of mental health and substance use health stepped care (MHSUH) models and other MHSUH system transformation initiatives is more limited. In this commentary, the authors describe the Populating the Model Series, a co-design-based, system-level planning intervention specifically developed for sites implementing the Stepped Care 2.0 (SC2.0) model of care. The use of co-design, which is a core component of the SC2.0 model, distributes risk through engagement across the community, broadens the system of care to include and acknowledge informal and formal options, creates person-centricity, and incorporates access points and care modalities that are tailored to the intervention site’s context. Seven steps are identified within the Populating the Model Series including assessing intervention site readiness, understanding site context, planning and adjusting engagement of key groups for co-design, learning through workshop sessions and co-design, validation with key groups, understanding findings, and application of findings. This guidance provides an actionable process framework for the application of co-design in the planning and implementation of SC2.0 and other stepped care models.

Abstract Background Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults. This streamlined MSI is comprised of constructive memory supports that will be applied to a broader range of treatment content. The platform for this study is the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C). We will focus on midlife and older adults who are low income and experiencing mobility impairments. Methods Participants (N = 178) will be randomly allocated to TranS-C + MSI or TranS-C alone. Both intervention arms include eight 50-min weekly sessions. Assessments will be conducted at pre-treatment, post-treatment, 6-, and 12-month follow-up (6FU and 12FU). Aim 1 will compare the effects of TranS-C + MSI versus TranS-C alone on sleep and circadian functioning, daytime functioning, well-being, and patient memory. Aim 2 will test whether patient memory for treatment mediates the relationship between treatment condition and patient outcomes. Aim 3 will evaluate if previously reported poor treatment response subgroups will moderate the relationship between treatment condition and (a) patient memory for treatment and (b) treatment outcome. Exploratory analyses will compare treatment condition on (a) patient adherence, patient-rated treatment credibility, and patient utilization of treatment contents, and (b) provider-rated acceptability, appropriateness, and feasibility. Discussion This study has the potential to provide evidence for (a) the efficacy of a new simplified version of the MSI for maintaining health, well-being, and functioning, (b) the wider application of the MSI for midlife and older adults and to the treatment of sleep and circadian problems, and (c) the efficacy of the MSI for sub-groups who are likely to benefit from the intervention. Trial registration ClinicalTrials.gov NCT05986604. Registered on 2 August 2023.

Students with Autism Spectrum Disorder (ASD) are one of the fastest growing groups at the community college, and supporting faculty members who teach students with ASD is a challenge for college leaders. Faculty members need a knowledge base about these students as well as the pedagogical practices that lead to their success. There have been no instruments, however, specifically designed to explore community college faculty members knowledge about students with ASD and the instructional methods to support them. This paper presents the development of an instrument assessing faculty members knowledge about students with ASD and the pedagogical practices to help them succeed. The instrument also addresses faculty members preferences for professional development to enhance ASD student success. Implications for community college leaders are presented, including the using instrument to develop systematic professional development plans -- involving both full-time and adjunct faculty -- to improve instruction for ASD students.

A promising solution for reducing costs for students, especially textbook costs, is Open Educational Resources (OER). We explored community college faculty members' perceptions of using OER compared with publisher textbooks. In this comparative context, we investigated how OER impacted faculty, their instructional decisions, and their students as well as other aspects of OER faculty considered beneficial. The data is from a larger mixed-methods research study conducted in one large community college with multiple campuses in the Virginia Community College System (VCCS). Interviews were conducted with four faculty members who taught both an OER and non-OER section of the same course in the same semester. Three interconnected themes emerged from faculty responses. The first theme was the customizable content and format of OER facilitated access to and for diversity. The second theme was the ease of access with OER supported student engagement with the content and with each other. The third theme was faculty engagement with OER promoted transformative and reflective pedagogies. Findings provide important insight into the contribution of OER materials to equity, diversity, and inclusion beyond the barrier of financial costs. Practitioners should be encouraged by OER's potential benefits to students and instructors.

This study analyzes the economic factors affecting public health expenditure in Türkiye from 2002 to 2022. The main objective is to identify the economic reasons for the decreasing share of public health expenditure in Gross Domestic Product (GDP). It examines macroeconomic variables such as GDP per capita, unemployment rate, labor force participation rate, consumer price index, tax revenue, and exchange rate using principal component analysis (PCA). The results show that GDP per capita, exchange rate, and tax revenue significantly impact public health expenditure, indicating a direct relationship between economic growth and health spending. The unemployment rate does not directly affect public health expenditure, while an increase in labor force participation rate can reduce it. This study underscores the importance of macroeconomic stability and effective economic policies for sustainable health financing in Türkiye. By using long-term data, it provides a comprehensive analysis of how economic factors impact health expenditure, distinguishing it from other studies in the literature. The findings emphasize that a healthy economy leads to increased public investment in health services.

Aim: In recent years, physicians practicing in Turkey have started to face various legal processes such as patient complaints, medical malpractise,administrative disciplinary proceedings, criminal cases, and compensation lawsuits more frequently. This study aimed to evaluate the experiences and opinions of physicians on the subject. Materials and Methods: The study was conducted in the form of a questionnaire, and the questions directed to the participants were created through the application called Google Forms and were requested to be filled in electronically. Results: The age range of 30-35 years (32.6%) and 1-5 years of professional experience (34.4%) had the highest participation rate. Among the physicians who participated in the survey, 80.2% stated that they had complained at least once, 81.5% stated that they had testified at least once in judicial institutions, and 46.8% stated that they had attended a hearing in court. Of the physicians, 21.8% received administrative penalties and 7.9% received judicial penalties. According to the results of our study, general practitioners and emergency medicine specialists were the most frequently complained about physicians who were prosecuted in judicial courts for assault,insult, and assault. Conclusion: Efforts should be made to reduce the forensic concerns of physicians, and a common perspective on the issue should be developed by creating platforms where medical and legal sciences come together.

A better understanding of environmental exposure to agricultural pesticides is crucial for public health, regulatory and management purposes. Residents in close vicinity to agricultural fields are likely to be more exposed to pesticides. In that context, an innovative geospatial approach for mapping estimates of agricultural pesticide exposure was developed in this study. Data on pesticide application rates, high-resolution annual datasets of the geographic distribution of crops, and the 100 × 100m grid population dataset were utilized to complete this analysis in Wallonia (Belgium) over the period 2015–2019. Pesticide exposure metrics were estimated using a buffer-based exposure model by conducting neighborhood analysis within a 1000m buffer radius. Subsequently, a population weighted method was used to ‘up-scale’ the exposure data to administrative levels. In a limited validation effort, model estimates were compared with pesticide measurements in air collected at 12 stations during the period 2015–2016. The results present the first modeling map of environmental exposure to agricultural pesticides for the whole of the Walloon region. The northern part of the Sambre-Meuse axis demonstrates more intensive agriculture and the highest pesticide weighted exposure indices. The majority of the population resides near agricultural areas, with only 4 % living in regions that lack crops within a 1000m radius, primarily in the central areas of large cities. A positive trend association between pesticide measures in air and the index was observed at the different stations, nevertheless further validation efforts are needed to accurately compare the same active ingredients. This work gives a valuable basis for research and environmental health actions in Belgium. Maps highlight areas where human biomonitoring and epidemiological studies should be implemented to investigate the impact of potential environmental exposure to pesticides. This information helps policy-makers to take measures to control and reduce the load of agricultural pesticides in the environment.

The Qinling Mountains, the so-called “central water tower,” are extremely important water resource hubs in China. The influence of the forest ecological environment on water quality is complicated. Therefore, to investigate the spatiotemporal variations in water quality, we employed a random forest model to integrate multiple key water quality indicators into one overall ranking value. Monthly monitoring data of surface runoff and atmospheric precipitation events (2003–2022) for the Huodigou stream in the Qinling Mountains were used. The results revealed that after atmospheric precipitation entered the forest ecosystem, the coefficients of variation of surface runoff for most of the selected indicators decreased, but there were significant differences among the six indicators (NO3−, Mg2+, Na+, pH, K+, Ca2+). Most of the indicators within surface runoff were positively correlated, such as those in atmospheric precipitation. However, some indices of surface runoff were negatively correlated with those of atmospheric precipitation, and there was a significant negative correlation between Ca2+ in atmospheric precipitation and Ca2+ in surface runoff and between NO3−in atmospheric precipitation and K+ and Na+ in surface runoff (p Mg2+ > Na+ > pH > K+ > Ca2+. Overall, our assessment revealed that from 2003 to 2022, the water quality grade in the Huodigou stream improved and was more stable. In summary, the forest ecosystem in the Huodigou stream has a significant water quality purification effect on the atmospheric precipitation it receives. Our novel criterion-based approach for categorizing the water quality of atmospheric precipitation and surface runoff offers a new tool for examining spatiotemporal stream water quality variations in the Qinling region and other mountainous areas.

Colorectal cancer patients with ≤10 unresectable metastases were treated with single-fraction sub-ablative radiotherapy in addition to standard of care systemic therapy in a single-arm, open-label, multicenter, pilot study (SIRIUS) to assess feasibility and safety. Results indicate that radiotherapy combined with systemic therapy is feasible and safe in this population.

Plasmodium falciparum infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in ten Ugandan adults before and after local reduction of P. falciparum transmission. After a median of 1.7 years without P. falciparum infections, the percentage of antigen-specific activated B cells declined, but long-lived antigen-specific B cells were still detectable in all individuals. The majority of MSP1/AMA1-specific B cells were CD95+CD11c+ memory B cells, which are primed for rapid differentiation into antibody-secreting cells, and FcRL5-T-bet- atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95-CD11c- memory B cells. CIDRα1-specific B cells were also enriched among a subset of atypical B cells that seem poised for antigen presentation. These results point to differences in how these antigens are recognized or processed by the immune system and how P. falciparum-specific B cells will respond upon re-infection.

This study investigates the mechanical properties of cementitious composites with 3D-printed auxetic lattices, featuring negative Poisson’s ratios (auxetic behavior) in multiple directions. These lattices were fabricated using vat photopolymerization 3D printing, and three base materials with varying stiffness and deformation capacities were analyzed to determine their impact on the composites’ mechanical behavior. To unravel the reinforcing mechanisms of multidirectional auxetic lattices, which exhibit auxetic behavior in both planar and out-of-plane directions, X-ray computed tomography (X-ray CT) was utilized to analyze composite damage evolutions under different strain levels. The micro-CT characterization reveals that auxetic lattices more effectively constrain crack growth and dissipate energy by distributing stress evenly within the cement matrix. In contrast, due to lack of lateral confinement, the non-auxetic lattice reinforced composites primarily dissipate energy through extensive crack propagation and interfacial damage, leading to lower peak strength. When strain exceeding 5%, although the confinement from the auxetic behavior diminished with crack propagation, the lattice can still maintain the composite’s structural integrity, resulting in 1.7 times higher densification energy than conventional cement-based materials. These findings provide valuable insights for designing auxetic lattice-reinforced cementitious composites with enhanced load-bearing capacity and improved dissipation capabilities.

Background: We sought to investigate the epidemiology of epilepsy in Wulu County (Lakes State, South Sudan), and document the onchocerciasis transmission status in the study villages. Methods: In February 2024, a community-based epilepsy study was conducted Wulu County and participants were surveyed via a door-to-door approach in five villages, namely: Kombi, Makundi Center, Tonjo, War-Pac, and Woko. All village residents were asked about ivermectin intake during the 2023 round of community-directed treatment with ivermectin (CDTI). In addition, children aged 3–9 years were tested for Ov16 antibodies using a rapid diagnostic test. Epilepsy diagnosis in screened individuals was confirmed by a physician. Results: We surveyed 1355 persons in the five study sites. The overall CDTI coverage in 2023 was 67.4 %. Fifty-five persons with epilepsy (PWE) were identified (prevalence 4.1 %) and a history of nodding seizures was noted in 11/55 (20 %) PWE. The mean age of PWE was 21.5 ± 9.6 years, with 32 (58.2 %) being males. Epilepsy onset frequently occurred under 5 years of age (38.6 % of cases). In two PWE, seizure onset occurred during the past 12 months (annual incidence: 147.6 per 100,000 persons). Twenty-nine PWE (52.7 %) were taking anti-seizure medicines, but only five were taking them daily. Overall, Ov16 seroprevalence in children aged 3–9 years (n = 119) was 15.1 % and differed across villages, peaking at 30.9 % in Woko village where epilepsy prevalence was also highest (7.1 %). Of the 35 recorded deaths during the past two years, 9 (25.7 %) occurred in PWE. Annual estimates for epilepsy mortality and fatality rates were 323.7 per 100,000 persons and 7031.3 per 100,000 PWE, respectively. Conclusion: High epilepsy prevalence was found in Wulu, particularly in villages with persistent onchocerciasis transmission. Frequent epilepsy onset among under-fives suggests that perinatal/early childhood etiologies are common. Appropriate measures should be instituted to prevent and treat epilepsy in Wulu villages.

Abstract Background Neuroinflammation and Alzheimer’s disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to clarify whether a different pattern of neuroinflammation, such as alteration in microglial and astroglial morphology and distribution, is present in DLB cases with and without AD co-pathology. Methods The morphology and load (% area of immunopositivity) of total (Iba1) and reactive microglia (CD68 and HLA-DR), reactive astrocytes (GFAP) and proteinopathies of alpha-synuclein (KM51/pser129), amyloid-beta (6 F/3D) and p-tau (AT8) were assessed in a cohort of mixed DLB + AD (n = 35), pure DLB (n = 15), pure AD (n = 16) and control (n = 11) donors in limbic and neocortical brain regions using immunostaining, quantitative image analysis and confocal microscopy. Regional and group differences were estimated using a linear mixed model analysis. Results Morphologically, reactive and amoeboid microglia were common in mixed DLB + AD, while homeostatic microglia with a small soma and thin processes were observed in pure DLB cases. A higher density of swollen astrocytes was observed in pure AD cases, but not in mixed DLB + AD or pure DLB cases. Mixed DLB + AD had higher CD68-loads in the amygdala and parahippocampal gyrus than pure DLB cases, but did not differ in astrocytic loads. Pure AD showed higher Iba1-loads in the CA1 and CA2, higher CD68-loads in the CA2 and subiculum, and a higher astrocytic load in the CA1-4 and subiculum than mixed DLB + AD cases. In mixed DLB + AD cases, microglial load associated strongly with amyloid-beta (Iba1, CD68 and HLA-DR), and p-tau (CD68 and HLA-DR), and minimally with alpha-synuclein load (CD68). In addition, the highest microglial activity was found in the amygdala and CA2, and astroglial load in the CA4. Confocal microscopy demonstrated co-localization of large amoeboid microglia with neuritic and classic-cored plaques of amyloid-beta and p-tau in mixed DLB + AD cases. Conclusions In conclusion, microglial activation in DLB was largely associated with AD co-pathology, while astrocytic response in DLB was not. In addition, microglial activity was high in limbic regions, with prevalent AD pathology. Our study provides novel insights into the molecular neuropathology of DLB, highlighting the importance of microglial activation in mixed DLB + AD.

Abstract Background We (1) examined the effects of evaluative labels and visual aids on people’s understanding, evaluation, and use of the COVID-19 reproduction number (or “r-number”), (2) examined whether people’s perceived susceptibility and (intended) adherence to preventive measures changed after being exposed to the r-number, and (3) explored whether these effects and changes depended on people’s numeracy skills. Methods In an online experiment, participants from a large Dutch representative sample (N = 1,168) received information about the COVID-19 r-number displayed on the corona dashboard of the Dutch Ministry of Health, Welfare and Sport. The r-number was either presented with or without a categorical line display (i.e., evaluative label) and with or without an icon-based tree diagram (i.e., visual aid) explaining how the number works. Regarding people’s use of the statistic, we measured perceived susceptibility to COVID-19 and adherence (intention) to five preventive measures before and after exposure to the r-number. After exposure, we also measured participants’ understanding, perceived usefulness, affective and cognitive evaluation, and objective numeracy. Results About 56% of participants correctly interpreted the r-number, with highly numerate people having better understanding than less numerate people. Information about the r-number was perceived as more useful when presented with a visual aid. There were no differences across experimental conditions in people’s understanding, affective, and cognitive evaluations. Finally, independent of experimental conditions, intention to adhere to preventive measures was higher after seeing the r-number, but only among highly numerate people. Conclusions Although evaluative labels and visual aids did not facilitate people’s understanding and evaluation of the r-number, our results show that the statistic is perceived as useful and may be used to stimulate adherence to preventive measures. Policy makers and public health communicators are advised to clearly explain why they are giving these numbers to – especially – the less numerate people, but also how people could use them for behavior change to combat the spread of virus during a pandemic.

Numeracy ability is one of the abilities that students need to have to be able to overcome problems related to mathematical logic. The results of the PISA survey stated that Indonesia is classified as a country with the numeracy ability of students that has not been maximized. Meanwhile, to be more specific, the numeracy ability of students in areas spread throughout Indonesia is not clearly known. This research method is quantitative research, with a survey type. The subjects in this study were 364 students from elementary schools spread across Kupang City. Data collection was carried out using test techniques with a total of 15 numeracy test questions. The collected data was analyzed using descriptive statistics so that the average and distribution of the frequency of numeracy skills of students in elementary schools in Kupang City was known based on the level of their levels. The results showed that as many as 157 students or 45.35% had numeracy skills at level 3, namely being able to choose and apply simple problem-solving strategies; 143 respondents or 41.33% have numeracy skills at level 2, namely being able to use formulas, carry out procedures or agreements in solving problems; and the remaining 46 respondents or 13.29% have numeracy skills in Level 1 is being able to identify information and complete routine procedures according to clear instructions for the situation