Desarrollo de la comprensión emocional. ¿Qué tipo de tecnología para qué alumno con trastorno del espectro autista? Revisión sistemática / Development of emotional understanding. What type of technology for which student with autism spectrum disorder? Systematic review

La falta de información sobre el uso de la tecnología en niños con trastorno del espectro autista (TEA) de diferentes perfiles puede dificultar que docentes y alumnos se estén beneficiando del apoyo tecnológico más eficaz y ajustado a sus necesidades. El objetivo de esta revisión fue analizar y sintetizar la evidencia científica sobre la eficacia de los recursos tecnológicos en la mejora de la comprensión emocional de estudiantes con TEA con perfiles de alto y bajo funcionamiento. Para ello se realizó una revisión sistemática de las publicaciones científicas indexadas en algunas de las bases de datos de mayor relevancia siguiendo los criterios establecidos en la declaración PRISMA. En total se analizaron 38 artículos que cumplieron con los criterios de inclusión preestablecidos. Los resultados muestran la importancia de diseñar sistemas versátiles que puedan personalizarse y adaptarse en tiempo real y en contextos naturales con un enfoque claramente inclusivo. Pero también sugieren que la tecnología puede no ser una herramienta de intervención complementaria adecuada para todos los niños con TEA. Lo que subraya la necesidad de ensayos adicionales bien controlados sobre las características que permitan identificar qué estudiantes podrían o no beneficiarse de diferentes modalidades de tecnología. (AU)

The lack of information on the use of technology in children with autism spectrum disorder (ASD) of different profiles can make it difficult for teachers and students to benefit from the most effective technology support tailored to their needs. The aim of this review was to analyze and synthesize scientific evidence on the effectiveness of technological resources in improving the emotional understanding of students with high and low functioning ASD profiles. A systematic review of the scientific publications indexed in some of the most relevant databases was carried out following the criteria established in the PRISMA declaration. A total of 38 articles that met the pre-established inclusion criteria were analyzed. The results show the importance of designing versatile systems that can be customized and adapted in real time and in natural contexts with a clearly inclusive approach. But they also suggest that technology may not be an appropriate complementary intervention tool for all children with ASD. This underlines the need for additional well-controlled tests on the characteristics that would allow identifying which students might or might not benefit from different technology modalities. (AU)

'The way to obtain freedom and equality': Experiences and needs of Thai adolescent mothers in terms of the use smartphone applications for breastfeeding support.

BACKGROUND: Breastfeeding brings about a positive impact on both child and maternal health in the short and long terms. However, adolescent mothers have a lower breastfeeding initiation rate and a shorter breastfeeding duration than adult mothers. Although mobile applications have been found to be the most widely used platform for breastfeeding support, there is still a lack of design specific for adolescents. AIM: To explore the experiences, perspectives and needs of adolescent mothers and professional nurses using smartphone applications for breastfeeding support and the influence of this technology on healthcare in Thailand. METHODS: This formative qualitative research of the 'Development of smartphone application for promoting breastfeeding and learning of infant responsiveness for Thai teenage pregnant women' study intends to design a smartphone application and develop an implementation plan. A purposive sample was used to elicit experiences from adolescent mothers and nurses. Data were collected from 48 adolescent mothers through in-depth interviews with six focus group discussions and 12 nurses, following the data saturation principle. Thematic analysis was conducted, and potential factors and needs were mapped to the capability, opportunity, and motivation model of behaviour change (COM-B). RESULTS: Most adolescent mothers perceived the usefulness of smartphone apps as breastfeeding support resources. The qualitative findings of adolescent mothers were grouped into the following three themes: a friendly breastfeeding tool; allows them to manage their breastfeeding activities; and enhances the accessibility and equality of breastfeeding support. The professional nurses perceived the benefits of using smartphone applications in their work, which included the following three themes: reducing workload and making their work easier; preparation is always better; and increasing the standards of breastfeeding support. CONCLUSION: Adolescent mothers and professional nurses showed favourable attitudes toward smartphone apps for breastfeeding support. These smartphone apps should be tailored to these groups to achieve optimal BF outcomes.

Attitudes, motivators, and barriers toward influenza vaccination for children: a study from a conflict-ridden country.

BACKGROUND: Despite the increased recommendations for influenza vaccination, particularly among high-risk groups such as young children, Yemen lacks an influenza vaccination program, and the influenza vaccine is not included in the national immunization regime. This is exacerbated by the country's fragile infrastructure, as well as the devastating consequences of the ongoing conflict, which include child undernutrition and strained healthcare resources. Thus, the objective of the current study is to assess the public attitudes and perceptions toward vaccinating children against influenza in Yemen. METHODS: A cross-sectional study was conducted by distributing a validated survey questionnaire to potential participants using convenience sampling. Descriptive statistics were used to summarize sociodemographic data, knowledge of influenza vaccines, and attitudes and perceptions regarding vaccinating children against influenza. Logistic regression analysis was employed to identify associations between independent variables and the acceptance of vaccines for children. RESULTS: A total of 853 eligible individuals, parents and non-parents, successfully completed the survey. The uptake of the influenza vaccine among the participants was notably low as the majority (69.2%) had not previously received the vaccine, although the majority expressed a willingness to get vaccinated in the future (59.4%). The majority (68.5%) were willing to vaccinate children. The largest percentage of the participants who expressed hesitancy toward children's vaccination cited multiple reasons to reject the vaccine (39.7%), with concerns regarding the safety of the vaccine being the predominant barrier to its acceptance for children (29.6%). On the other hand, motivating factors for vaccinating children included the validation of the vaccine's safety and efficacy, endorsement of the vaccine by the government and physicians, integration of the vaccine into the national immunization program, and the provision of the vaccine free of charge and through schools. Significant predictors for vaccine acceptance in children included male gender, knowledge of the protective effect of the influenza vaccine, previous receipt of the vaccine, and a willingness to receive the vaccine in the future. CONCLUSIONS: The study highlights the need for educational health campaigns to raise awareness and remove misconceptions regarding influenza and the role, benefits, and availability of its vaccine. These findings can serve as a robust foundation for the future design and implementation of an influenza vaccination program for children in Yemen.

Operationalizing the Consolidated Framework for Implementation Research to build and support the lived experience workforce in direct health service provision.

BACKGROUND: The involvement of people with lived experience (LEX) workers in the development, design, and delivery of integrated health services seeks to improve service user engagement and health outcomes and reduce healthcare gaps. Yet, LEX workers report feeling undervalued and having limited influence on service delivery. There is a need for systematic improvements in how LEX workforces are engaged and supported to ensure the LEX workforce can fully contribute to integrated systems of care. OBJECTIVE: This study aimed to operationalize the Consolidated Framework for Implementation Research (CFIR) using a rigorous scoping review methodology and co-creation process, so it could be used by health services seeking to build and strengthen their LEX workforce. SEARCH STRATEGY: A systematic literature search of four databases was undertaken to identify peer-reviewed studies published between 2016 and 2022 providing evidence of the inclusion of LEX workers in direct health service provision. DATA EXTRACTION AND SYNTHESIS: A descriptive-analytical method was used to map current evidence of LEX workers onto the CFIR. Then, co-creation sessions with LEX workers (n = 4) and their counterparts-nonpeer workers (n = 2)-further clarified the structural policies and strategies that allow people with LEX to actively participate in the provision and enhancement of integrated health service delivery. MAIN RESULTS: Essential components underpinning the successful integration of LEX roles included: the capacity to engage in a co-creation process with individuals with LEX before the implementation of the role or intervention; and enhanced representation of LEX across organizational structures. DISCUSSION AND CONCLUSION: The adapted CFIR for LEX workers (CFIR-LEX) that was developed as a result of this work clarifies contextual components that support the successful integration of LEX roles into the development, design, and delivery of integrated health services. Further work must be done to operationalize the framework in a local context and to better understand the ongoing application of the framework in a health setting. PATIENT OR PUBLIC CONTRIBUTION: People with LEX were involved in the operationalization of the CFIR, including contributing their expertise to the domain adaptations that were relevant to the LEX workforce.

Success in vaccination programming through community health workers: a qualitative analysis of interviews and focus group discussions from Nepal, Senegal and Zambia.

OBJECTIVES: Community health workers are essential to front-line health outreach throughout low-income and middle-income countries, including programming for early childhood immunisation. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunisation coverage would support evidence-based policy guidance across contexts. DESIGN: We employed a multiple case study design using qualitative research methods. SETTING: We conducted research in Nepal, Senegal and Zambia. PARTICIPANTS: We conducted 207 interviews and 71 focus group discussions with 678 participants at the national, regional, district, health facility and community levels of the health systems of Nepal, Senegal and Zambia, from October 2019 to April 2021. We used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunisation within each country and across contexts. RESULTS: Implementation of vaccination programming relied principally on the (1) organisation, (2) motivation and (3) trust of community health workers. Organisation was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on their work. CONCLUSION: Improvements in immunisation coverage was facilitated by community health worker organisation, motivation and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to underserved populations. Although improvements in vaccination programming were seen in all three countries-including government commitment to addressing human resource deficits, training and remuneration; workload, inconsistency in compensation, training duration and scope, and supervision remain major challenges to immunisation programming. Health decision-makers should consider organisation, motivation and trust of community health workers to improve the implementation of immunisation programming.

Elucidating the Cell Surfaceome to Accelerate Cancer Drug Development.

SUMMARY: Cell surface proteins represent ideal therapeutic targets because of their accessibility to antibodies, T cell-directed therapies, and radiotherapies, but there are only 25 therapeutically relevant cell surface targets for which cancer therapies are approved in the United States or European Union. This commentary calls for intensified research into mapping the universe of cell surface proteins - the cell surfaceome - in order to accelerate cancer drug development.

The Digital Navigator: Standardizing Human Technology Support in App-Integrated Clinical Care.

Background: Mental health apps offer scalable care, yet clinical adoption is hindered by low user engagement and integration challenges into clinic workflows. Human support staff called digital navigators, trained in mental health technology, could enhance care access and patient adherence and remove workflow burdens from clinicians. While the potential of this role is clear, training staff to become digital navigators and assessing their impact are primary challenges. Methods: We present a detailed manual/framework for implementation of the Digital Navigator within a short-term, cognitive-behavioral therapy-focused hybrid clinic. We analyze patient engagement, satisfaction, and digital phenotyping data quality outcomes. Data from 83 patients, for the period spanning September 2022 to September 2023, included Digital Navigator satisfaction, correlated with demographics, mindLAMP app satisfaction, engagement, and passive data quality. Additionally, average passive data across 33 clinic patients from November 2023 to January 2024 were assessed for missingness. Results: Digital Navigator satisfaction averaged 18.8/20. Satisfaction was not influenced by sex, race, gender, or education. Average passive data quality across 33 clinic patients was 0.82 at the time this article was written. Digital Navigator satisfaction scores had significant positive correlation with both clinic app engagement and perception of that app. Conclusions: Results demonstrate preliminary support and patient endorsement for the Digital Navigator role and positive outcomes around digital engagement and digital phenotyping data quality. Through sharing training resources and standardizing the role, we aim to enable clinicians and researchers to adapt and utilize the Digital Navigator for their own needs.

Implementation of Endoscopic Minimally Invasive Mitral Valve Replacement Surgery With Automated Suturing Technology.

In the evolving landscape of cardiac surgery, this article explores the potential of minimally invasive mitral valve replacement procedures as a viable alternative to conventional surgical techniques. Leveraging advancements in automated suturing devices and video endoscopy, our work aims to demonstrate that minimally invasive approaches can be applied across a broad spectrum of surgical scenarios. Herein we highlight preoperative diagnostics and operative techniques, with a focus on infra-axillary anterolateral minithoracotomy as the access point. Our technique utilizes technology from LSI SOLUTIONS® (Victor, NY, USA), including the RAM® Device for automated suturing, which has an ergonomic design and safety features. The device's capabilities are further enhanced by the SEW-EASY® Device, the RAM® RING, and the COR-KNOT MINI® Device, which streamline suture management and securement. This work outlines how these technological advancements can mitigate concerns about technical complexity and learning curves, thereby encouraging wider adoption of minimally invasive techniques. Clinical benefits may include reduced surgical trauma, quicker recovery, and cost-effectiveness, making it a compelling option in an era of aggressively promoted transcatheter interventions.

Simultaneous Screening of 172 Veterinary Drugs by Modified QuEChERS-LC-MS/MS in TCM Galli Gigerii Endothelium Corneum.

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 µm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation-LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2-20 µg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines.

A Historical Perspective on RSV Prevention: A Journey Spanning Over Half a Century from the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.

The efforts to prevent RSV infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV naïve children, when subsequently exposed to natural RSV infection from wild type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants.

"It's Like A Partnership": Exploring the Primary Care Experiences and Patient-Defined Goals of People Who Use Drugs.

BACKGROUND: Primary care is an important yet underutilized resource in addressing the overdose crisis. Previous studies have identified important aspects of primary care for people who use drugs (PWUD) and have found patient involvement in healthcare decisions and goal-setting to be especially critical. However, there has been limited research describing the primary care goals of PWUD. In harm reduction settings, where it is imperative that PWUD set their own goals, this research gap becomes especially relevant. OBJECTIVE: To explore how PWUD navigate primary care with a focus on understanding their primary care goals. DESIGN: A qualitative study using semi-structured interviews. PARTICIPANTS: PWUD currently engaged in primary care at the Respectful and Equitable Access to Comprehensive Healthcare (REACH) Program, a harm reduction-based primary care program in New York City. APPROACH: Between June 2022 and August 2022, we conducted 17 semi-structured interviews. Informed by phenomenology, transcripts were coded using both inductive and deductive codes and themes were developed using thematic analysis approaches. KEY RESULTS: Phenomenological analysis identified four core components that, together, created an experience that participants described as "a partnership" between patient and provider: (1) patient-provider collaboration around patient-defined healthcare goals; (2) support provided by harm reduction-based approaches to primary care anchored in incrementalism and flexibility; (3) care teams' ability to address healthcare system fragmentation; and (4) the creation of social connections through primary care. This holistic partnership fostered positive primary care experiences and supported participants' self-defined care goals, thereby facilitating meaningful care outcomes. CONCLUSIONS: To best meet the primary care goals of PWUD, these findings underscore the importance of primary care providers and programs facilitating such partnerships through organizational-level support anchored in harm reduction. Future research should explore how these experiences in primary care affect patient health outcomes, ultimately shaping best practices in the provision of high-quality primary care for PWUD.

HPV-specific antibodies in female genital tract secretions captured via first-void urine retain their neutralizing capacity.

Human papillomavirus (HPV) vaccines, primarily relying on neutralizing antibodies, have proven highly effective. Recently, HPV-specific antibodies have been detected in the female genital tract secretions captured by first-void urine (FVU), offering a minimally invasive diagnostic approach. In this study, we investigated whether HPV16-specific antibodies present in FVU samples retain their neutralizing capacity by using pseudovirion-based neutralization assays. Paired FVU and serum samples (vaccinated n = 25, unvaccinated n = 25, aged 18-25) were analyzed using two orthogonal pseudovirion-based neutralization assays, one using fluorescence microscopy and the other using luminescence-based spectrophotometry. Results were compared with HPV16-specific IgG concentrations and correlations between neutralizing antibodies in FVU and serum were explored. The study demonstrated the presence of neutralizing antibodies in FVU using both pseudovirion-based neutralization assays, with the luminescence-based assay showing higher sensitivity for FVU samples, while the fluorescence microscopy-based assay exhibited better specificity for serum and overall higher reproducibility. High Spearman correlation values were calculated between HPV16-IgG and HPV16-neutralizing antibodies for both protocols (rs: 0.54-0.94, p < .001). Significant Spearman correlations between FVU and serum concentrations were also established for all assays (rs: 0.44-0.91, p < .01). This study demonstrates the continued neutralizing ability of antibodies captured with FVU, supporting the hypothesis that HPV vaccination may reduce autoinoculation and transmission risk to the sexual partner. Although further protocol optimizations are warranted, these findings provide a foundation for future research and larger cohort studies that could have implications for the optimal design, evaluation, and implementation of HPV vaccination programs.

Public health relevance of medicines developed under paediatric legislation in Europe and the USA: a systematic mapping study.

BACKGROUND: Legislation in the European Union (EU) and the USA promoting the development of paediatric medicines has contributed to new treatments for children. This study explores how such legislation responds to paediatric health needs in different country settings and globally, and whether it should be considered for wider implementation. METHODS: We searched EU and US regulatory databases for medicines with approved indications resulting from completed paediatric development between 2007 and 2018. Of 195 medicines identified, 187 could be systematically mapped to the burden of the target disease for six study countries (Australia, Brazil, Canada, Kenya, Russia, South Africa) and globally, using disability-adjusted life years (DALYs). All medicines were also screened for inclusion on the WHO Model List of Essential Medicines (EML) and the EML for children under 13 years (EMLc). RESULTS: The studied medicines were disproportionately focused on non-communicable diseases, which represented 68% of medicines and 21% of global paediatric DALYs. On the other hand, we found 28% of medicines for communicable, maternal, neonatal and nutritional disorders, representing 73% of global paediatric DALYs. Neonatal disorders and malaria were mapped with two medicines, tuberculosis and neglected tropical diseases with none. The gap between medicines and paediatric DALYs was greater in countries with lower income. Still, 34% of medicines are included in the EMLc and 48% in the EML. CONCLUSIONS: Paediatric policies in the EU and the USA are only partially responsive to paediatric health needs. To be considered for wider implementation, paediatric incentives and obligations should be more targeted towards paediatric health needs. International harmonisation of legislation and alignment with global research priorities could further strengthen its impact on child health and support ongoing efforts to improve access to medicines. Furthermore, efforts should be made to ensure global access to authorised paediatric medicines.

Reverse development of vaccines against antimicrobial-resistant pathogens.

Vaccine R&D is typically a lengthy process taking >10 years. However, vaccines still fail in clinical development because of unreliable animal models or absent immunological correlates of protection. Without a correlate of protection, phase-1 and -2 studies of safety and immunogenicity can fail to predict phase-3 efficacy. Indeed, the history of vaccine development is replete with promising phase-1 and -2 results and failed phase-3 efficacy trials. To avoid this misfortune, we present Reverse Vaccine Development for vaccines against antimicrobial-resistant (AMR) pathogens. In this approach, instead of evaluating efficacy in phase 3, proof-of-principle efficacy is evaluated as early as possible in a population with a high incidence of disease, which may differ from the population intended for registration, and can be a controlled human infection population. To identify a correlate of protection in these populations, the vaccine-elicited immune response is compared between protected and unprotected subjects. If a correlate is identified, it can help to refine the vaccine dosage, schedule, and formulation, and facilitate the assessment of vaccine efficacy in other populations with different attack rates, subject characteristics, and disease manifestations. This may be the only way to provide life-saving vaccines to populations affected by AMR-pathogen diseases at incidences that are typically low and unsuited to phase-3 efficacy trials. The availability of a correlate of protection early in clinical development can potentially prevent failures of large phase-3 trials and unnecessary exposures of populations to inefficacious vaccines that have resulted in disinvestment in the development of vaccines against AMR pathogens.

Healthcare providers' perceived barriers to providing breastfeeding support in Northwest rural China.

BACKGROUND: Healthcare providers play important roles in supporting breastfeeding. Although there has been insufficient actual breastfeeding support from healthcare providers in China, little research has been conducted to understand Chinese healthcare providers' perceived barriers to providing breastfeeding support, especially in rural China. This study aims to identify these perceived barriers to providing breastfeeding support in Northwestern rural China. METHODS: This study was conducted during the period from March 2018 to December 2018. Forty-one healthcare providers were recruited through purposive sampling in two rural counties in Northwest China that are in close proximity to each other and share similar demographic features. Participants included obstetrician-gynecologists, midwives, nurses, "village doctors", and township and village maternal and child health workers. Qualitative data were collected through one-on-one in-depth semi-structured interviews and focus group discussions. Transcripts were thematically analyzed. RESULTS: Analysis of interview data resulted in four themes that the participants perceived as barriers to supporting breastfeeding: (1) lack of medical resources, within which inadequate staffing, and lack of financial incentives were discussed, (2) lack of clear and specific responsibility assignment, within which no one takes the lead, and mutual buck-passing were discussed, (3) healthcare providers' lack of relevant expertise, within which lack of knowledge and skills, and low prestige of village healthcare providers were discussed, (4) difficulties in accessing mothers, within which medical equipment shortages reduce services utilization, mothers' housing situation, mothers' mobility, and cultural barriers were discussed. CONCLUSIONS: The study identified HCPs perceived barriers to providing breastfeeding support. Unique to China's Tri-Level Healthcare System, challenges like staffing and financial incentives are hard to swiftly tackle. Recommendations include mHealth enhancement and clarified responsibilities with incentives and tailored training. Further research is crucial to evaluate these strategies in rural Northwestern China and comparable underdeveloped areas nationwide.

Identification of potential drug targets for allergic diseases from a genetic perspective: A mendelian randomization study.

BACKGROUND: Allergic diseases typically refer to a heterogeneous group of conditions primarily caused by the activation of mast cells or eosinophils, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma. Asthma, AR, and AD collectively affect approximately one-fifth of the global population, imposing a significant economic burden on society. Despite the availability of drugs to treat allergic diseases, they have been shown to be insufficient in controlling relapses and halting disease progression. Therefore, new drug targets are needed to prevent the onset of allergic diseases. METHOD: We employed a Mendelian randomization approach to identify potential drug targets for the treatment of allergic diseases. Leveraging 1798 genetic instruments for 1537 plasma proteins from the latest reported Genome-Wide Association Studies (GWAS), we analyzed the GWAS summary statistics of Ferreira MA et al. (nCase = 180,129, nControl = 180,709) using the Mendelian randomization method. Furthermore, we validated our findings in the GWAS data from the FinnGen and UK Biobank cohorts. Subsequently, we conducted sensitivity tests through reverse causal analysis, Bayesian colocalization analysis, and phenotype scanning. Additionally, we performed protein-protein interaction analysis to determine the interaction between causal proteins. Finally, based on the potential protein targets, we conducted molecular docking to identify potential drugs for the treatment of allergic diseases. RESULTS: At Bonferroni significance (p < 3.25 × 10-5), the Mendelian randomization analysis revealed 11 significantly associated protein-allergic disease pairs. Among these, the increased levels of TNFAIP3, ERBB3, TLR1, and IL1RL2 proteins were associated with a reduced risk of allergic diseases, with corresponding odds ratios of 0.82 (0.76-0.88), 0.74 (0.66-0.82), 0.49 (0.45-0.55), and 0.81 (0.75-0.87), respectively. Conversely, increased levels of IL6R, IL1R1, ITPKA, IL1RL1, KYNU, LAYN, and LRP11 proteins were linked to an elevated risk of allergic diseases, with corresponding odds ratios of 1.04 (1.03-1.05), 1.25 (1.18-1.34), 1.48 (1.25-1.75), 1.14 (1.11-1.18), 1.09 (1.05-1.12), 1.96 (1.56-2.47), and 1.05 (1.03-1.07), respectively. Bayesian colocalization analysis suggested that LAYN (coloc.abf-PPH4 = 0.819) and TNFAIP3 (coloc.abf-PPH4 = 0.930) share the same variant associated with allergic diseases. CONCLUSIONS: Our study demonstrates a causal association between the expression levels of TNFAIP3 and LAYN and the risk of allergic diseases, suggesting them as potential drug targets for these conditions, warranting further clinical investigation.

Perspectives on the Performance of the Ethiopian Vaccine Supply Chain and Logistics System after the Last Mile Delivery Initiative: A Phenomenological Study.

Uninterrupted availability of vaccines requires a robust vaccine supply chain and logistics system (VSCLS). With special focus on remote and underserved settings, we assessed the reach and bottlenecks of the Ethiopian VSCLS after the initiation of the last mile transition. We explored the perspectives of key stakeholders using a qualitative phenomenological study. More than 300 in-depth interviews and 22 focus group discussions were conducted. The study was sequentially implemented over two phases to understand the bottlenecks at national and regional (Phase I) and lower (Phase II) levels. After the transition, the Ethiopian Pharmaceutical Supply Service started supplying vaccines directly to health facilities, bypassing intermediaries. The transition reduced supply hiccups and enabled the health sector to focus on its core activities. However, in remote areas, achievements were modest, and health facilities have been receiving supplies indirectly through district health offices. By design, health posts collect vaccines from health centers, causing demotivation of health extension workers and frequent closure of health posts. Challenges of the VSCLS include artificial shortage due to ill forecasting and failure to request needs on time, lack of functional refrigerators secondary to scarcity of skilled technicians and spare parts, and absence of dependable backup power at health centers. Vaccine wastages owing to poor forecasts, negligence, and cold chain problems are common. The VSCLS has not yet sustainably embraced digital logistics solutions. The system is overstrained by frequent outbreak responses and introduction of new vaccines. We concluded that the transition has improved the VSCLS, but the reach remains suboptimal in remote areas.

Revisiting methotrexate and phototrexate Zinc15 library-based derivatives using deep learning in-silico drug design approach.

Introduction: Cancer is the second most prevalent cause of mortality in the world, despite the availability of several medications for cancer treatment. Therefore, the cancer research community emphasized on computational techniques to speed up the discovery of novel anticancer drugs. Methods: In the current study, QSAR-based virtual screening was performed on the Zinc15 compound library (271 derivatives of methotrexate (MTX) and phototrexate (PTX)) to predict their inhibitory activity against dihydrofolate reductase (DHFR), a potential anticancer drug target. The deep learning-based ADMET parameters were employed to generate a 2D QSAR model using the multiple linear regression (MPL) methods with Leave-one-out cross-validated (LOO-CV) Q2 and correlation coefficient R2 values as high as 0.77 and 0.81, respectively. Results: From the QSAR model and virtual screening analysis, the top hits (09, 27, 41, 68, 74, 85, 99, 180) exhibited pIC50 ranging from 5.85 to 7.20 with a minimum binding score of -11.6 to -11.0 kcal/mol and were subjected to further investigation. The ADMET attributes using the message-passing neural network (MPNN) model demonstrated the potential of selected hits as an oral medication based on lipophilic profile Log P (0.19-2.69) and bioavailability (76.30% to 78.46%). The clinical toxicity score was 31.24% to 35.30%, with the least toxicity score (8.30%) observed with compound 180. The DFT calculations were carried out to determine the stability, physicochemical parameters and chemical reactivity of selected compounds. The docking results were further validated by 100 ns molecular dynamic simulation analysis. Conclusion: The promising lead compounds found endorsed compared to standard reference drugs MTX and PTX that are best for anticancer activity and can lead to novel therapies after experimental validations. Furthermore, it is suggested to unveil the inhibitory potential of identified hits via in-vitro and in-vivo approaches.