Mentorship and sponsorship play pivotal roles in career development, yet disparities in access to these opportunities persist among medical trainees. This report describes a structured alumni engagement programme for pulmonary, critical care and sleep medicine fellows, aimed at fostering mentorship, professional development and equitable career opportunities. Conducted within a university-based fellowship programme, the intervention comprised seven themed virtual sessions featuring alumni from diverse career trajectories, including academia, industry and private practice. Thematic analysis of session transcripts identified ten key themes across four domains: career development, personal fulfilment, professional relationships and adaptability. Postsession feedback indicated high participant satisfaction, with 53% of fellows reporting subsequent mentorship or career opportunities with alumni. Limitations include the small sample size, short follow-up period and lack of full characterisation of baseline features. This initiative highlights the scalability and potential impact of alumni engagement on career development, emphasising the importance of mentorship and sponsorship. Broader implementation could enhance networking opportunities across medical disciplines, addressing long-standing disparities in access to professional growth resources. Future studies should focus on longitudinal outcomes to assess the influence of such programmes on trainees' career trajectories. This innovative model offers a replicable framework to strengthen professional networks and support leadership development among trainees.
Cervical cancer is a leading cause of cancer mortality among Ghanaian women, yet screening uptake is under 5%. The Cervical Cancer Prevention and Training Centre (CCPTC) partnered with Rotary Clubs across the country to implement the first-ever nationally representative cervical precancer screening project and to demonstrate the feasibility of an integrated nationwide screening program. We conducted a cross-sectional analysis of 1,636 asymptomatic women aged 25 years and above screened at 29 government and private facilities across all 16 regions of Ghana (January-February 2025). Eligible women underwent concurrent hr-HPV genotyping (Sansure MA-6000 platform) and VIA by CCPTC-trained alumni, with immediate thermal ablation for eligible VIA-positive lesions (TZ type 1 or 2). Multivariable logistic regression (backward stepwise elimination, P < 0.25 retention threshold) identified factors associated with hr-HPV positivity and VIA positivity. Analyses were performed in Stata v17.0. Among 1,636 women, the overall hr-HPV prevalence was 26·6% (95% CI, 24·5-28·8) and the VIA 'positivity' was 4·0% (95% CI, 3·1-5·0). Predominant genotypes were HPV52 (5·3%), HPV58 (4·4%), and HPV51 (3·6%); HPV16 and HPV18 together accounted for <5% of infections. Independent factors associated with hr-HPV infection were HIV infection (aOR=5·77; 95% CI, 2·07-16·13, P = 0.001) and having a steady partner (aOR=2·02; 95% CI, 1·22-3·36, P = 0.006); being married/cohabiting (aOR=0·51; 95% CI, 0·38-0·69, P < 0.001) or widowed (aOR=0·43; 95% CI, 0·23-0·82, P = 0.011), and prior screening (aOR=0·67; 95% CI, 0·48-0·92, P = 0.014) were protective. VIA 'positivity' was independently associated with HIV infection (aOR 7.49, 95% CI 1.99-28.19, P = 0.003). Regional hr-HPV prevalence varied from 10·0% to 39·2%. Thirty-five percent of VIA-positive women received same-visit thermal ablation. This decentralized alumni-driven model integrating off-site HPV testing, task-shifted VIA, and immediate thermal ablation proved operationally feasible across Ghana's diverse health system and revealed a substantial hr-HPV burden. The approach offers a scalable blueprint for national cervical cancer control and informs Ghana's transition toward HPV-based screening.
Building capacity through training and education is recommended to support meaningful engagement of patient partners in health research. The Patient and Community Engagement Research (PaCER) programme is a 12-month initiative that enables patients and community members to co-design and conduct qualitative health research projects. Learners are sponsored by clinician researchers, community organisations, and/or jurisdictional health organisations. This study aimed to assess the experiences and impact of the PaCER programme on: (1) past learners' personal development and engagement in health research; and (2) sponsors' research programmes. We conducted a qualitative impact evaluation involving past learners (alumni) and sponsors of the PaCER programme from 2019 to 2024. A purposive sampling strategy was used, whereby selected alumni and sponsors from the 2019-2024 cohorts were invited to participate in an online semi-structured interview. Sponsors and alumni with diverse characteristics, including variation in age, ethnicity, educational attainment, and geographic location were invited. The interview guide included questions on the experiences in the PaCER programme, post-programme research activities, and perceptions of the programme's impact. Data were analysed using a reflexive thematic analysis approach. Eighteen participants (12 PaCER alumni and 6 sponsors) were interviewed, and four main themes were identified: (1) seeing the value of the training programme; (2) Diverse people and groups working together; (3) Learner readiness and capacity; (4) Academic opportunities for learners and career growth. Alumni described significant personal impact, empowerment, academic contributions, and increased access to meaningful patient partner opportunities. Alumni reported co-authoring publications and presenting their work at academic conferences and to various stakeholders, including health system leadership. Many alumni had no prior experience with qualitative participatory research, and participation in the programme supported the development of these research skills. Sponsors also noted impacts on their research programmes, such as securing additional funding informed by PaCER project findings. The findings demonstrate that structured, experiential training for patients and community members supports meaningful engagement in health research, contributes to sustained capacity development, and positively influences the patient-oriented research landscape. Patient partners were involved in the design and conduct of the study (data collection), analysis and interpretation of the data, and in the preparation of this manuscript.
Background: Allergy/immunology (A/I) fellowship recruitment occurs within a competitive match environment, with most interviews conducted virtually. Program web sites play a critical role in informing applicants and shaping program perception. Despite established literature that demonstrates the importance of program web sites across specialties, the comprehensiveness of A/I fellowship web sites has not been systematically evaluated. Objective: The purpose of this study was to evaluate existing A/I fellowship program web sites with the intent to identify opportunities for improvement. Methods: A list of 91 A/I fellowship programs was obtained from the American Academy of Allergy, Asthma & Immunology web site. Eighty-nine programs with accessible web sites were included. Each web site was evaluated for the presence of 24 predefined metrics derived from previous residency and fellowship web site studies. Sixteen programs affiliated with World Allergy Organization (WAO) Centers of Excellence in the United States were analyzed as a subgroup. Mean metric counts were compared by using a two-sample t-test. Results: Web sites contained a mean ± standard deviation (SD) of 13.7 ± 4.9 of 24 metrics. WAO-affiliated programs contained a mean ± SD of 13.2 ± 4.6 metrics, with no statistically significant difference when compared with all the programs (p = 0.70). Although most web sites listed program leadership, curriculum, and training sites, fewer included alumni information (40%), job placement (38%), or wellness initiatives (18%). Conclusion: A/I fellowship program web sites vary widely in content and may lack information, particularly with regard to wellness, alumni outcomes, and trainee demographics. Enhancing web site comprehensiveness represents an opportunity to improve recruitment, branding, and applicant engagement in a competitive application environment.
Primary care continues to face pressure to improve clinical outcomes with limited resources. Point-of-care ultrasound (POCUS) offers potential value by improving diagnostic efficiency and procedural safety; yet early adoption in family medicine has been limited by faculty expertise, time constraints, and infrastructure barriers. In 2014, we developed a structured POCUS curriculum to address resident demand and programmatic gaps in family medicine training. We implemented a 4-week required postgraduate year (PGY) one ultrasound rotation designed to function with limited faculty availability. The curriculum integrates asynchronous learning, simulation, supervised scanning with standardized patients and sonographers, structured image review, and competency assessment. Residents complete a defined number of scans in high-yield applications including cardiac, lung, abdominal aorta, venous thrombosis, musculoskeletal/soft tissue, and obstetric ultrasound. Longitudinal reinforcement was later added through quarterly hands-on sessions and a PGY-3 advanced ultrasound rotation emphasizing competency reassessment and near-peer teaching. Over 10 years, faculty capacity expanded primarily through training program graduates. An alumni survey (2015-2022 graduates; 58% response rate) demonstrated continued POCUS use in 44% of respondents, with higher utilization among rural physicians and billing rates exceeding national primary care averages. Common barriers included time constraints and equipment access, while skin/soft tissue, musculoskeletal, and procedural applications were most frequently used. A scalable, longitudinal POCUS curriculum in family medicine is feasible despite limited protected faculty time. Tailoring training to anticipated practice settings, emphasizing ambulatory-relevant applications, and addressing workflow and billing education may improve long-term adoption and sustainability.
The INSPIRE project, funded by the European Marie Skłodowska-Curie Action (MSCA) program, was a doctoral network designed to train early-stage researchers (ESRs) and stimulate exploratory research in cardiovascular safety pharmacology (SP). From 2020 until 2024, INSPIRE trained 15 doctoral candidates hosted by a consortium of academic and industrial partners. The current publication summarizes the outcomes of INSPIRE and reflects on the impact to the field. As part of INSPIRE, ESRs were engaged in individual research projects covering a range of topics, yet grounded in 4 thematic clusters to facilitate collaboration. The first cluster focused on human induced pluripotent stem cells-derived cardiomyocyte (hiPSC-CM) assays and explored additional readouts such as morphological profiling, miRNAs panels and artificial intelligence assisted analyses. The second cluster aimed to develop a new telemetry platform with integrated positioning system, but technical drawbacks required initiation of alternative plans still aligned with the mission to refine in vivo SP studies. A third cluster explored new concepts for hemodynamic assessment, such as arterial stiffness and in silico modelling. Finally, the fourth cluster involved mechanistic research in cardio-oncology. Some ESR projects, especially those hosted by industry partners, delivered tangible prototype products or services with potential for commercialization. Alternative outcomes included optimized experimental workflows, datasets with reference compounds and mechanistic insights. Overall, INSPIRE delivered on its mission to initiate explorative research in SP, although many results will require further development, standardization and establishment of their context of use. This highlights the difficulty of achieving regulatory relevance within PhD timelines. For the latter, sustained engagement from industry beyond the duration of the doctoral program seems essential. Educationally, 8 ESRs have successfully defended their PhD thesis and a few ESRs have transitioned into permanent roles in drug R&D. Mobility of ESRs was a crucial, mandatory element of the training resulting in 23 secondments. The close interaction with industrial partners significantly enhanced trainee awareness of regulatory thinking, experimental robustness, and translational constraints. A yearly summer school was organized to facilitate mutual learning and build group cohesion. Meanwhile, the INSPIRE summer school has become a legacy with close to 100 alumni and offers a mix of theoretical lectures and broader sessions on career development. Looking ahead, ongoing revisions of international SP guidance (ICH S7A) and increasing interest in new approach methodologies (NAMs) create opportunities for a next-generation training network. In this context, we propose a roadmap for initiating INSPIRE v2.0 and have launched a call for input and participation to help shaping the future of SP.
Early exposure to research is essential for developing evidence-based practitioners and academic leaders in dentistry. To this end, University of Mississippi School of Dentistry established the Undergraduate and Professional Student Training in Advanced Research Techniques (UPSTART) program to integrate research, mentoring, and professional development. Since 2008, the UPSTART program has provided a structured curriculum comprising team-science mentoring, hands-on laboratory research, professional development seminars, and oral research presentations. Program data from 2008 to 2022 were analyzed to evaluate outcomes related to student and mentor participation, skills provided by research projects, and after-graduation outcomes for the participant students. Over 15 years, 244 students (132 dental, 81 undergraduate, 31 postbaccalaureate) completed the UPSTART program. Out of the 194 projects conducted during that time, 37% projects were categorized as being "closer to clinic" and 63% projects were categorized as being "closer to bench." With continuous mentoring that involved teams of dental and undergraduate students mentored by graduate students and faculty, the UPSTART participants produced more than 50 peer-reviewed publications, 200 presentations, and received over 50 research awards. Among dental students, 65% successfully matched into postgraduate residency programs-more than double the rate of non-participants. Undergraduate alumni also demonstrated strong advancement into graduate (36%) and clinical (32%) programs. The UPSTART program demonstrates that structured research training with personalized mentoring and professional development enhances students' research engagement and postgraduate competitiveness. Such a program can serve as a scalable model for dental schools seeking to strengthen research scholarship and prepare future clinician-scientists.
"Athlete's heart" refers to the physiological cardiac hypertrophy observed in competitive athletes, which reverts to normal after retirement from competition. However, few studies have examined long-term follow-up. This study investigated whether former college athletes with a history of an athlete's heart have a higher risk of developing heart disease later in life and examined its association with angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms. A total of 980 participants (mean age, 52.0 ± 15.7 years) from the Juntendo University Alumni Study were analyzed. Information on Athlete's heart during college and subsequent heart disease, including left ventricular hypertrophy, was obtained through self-administered questionnaires in 2018. The ACE I/D genotype was determined based on the rs4341 C/G polymorphism. Of all participants, 177 (18.1%) reported Athlete's heart during college, and 15 (1.5%) were diagnosed with left ventricular hypertrophy later in life. Former athletes with Athlete's heart had a 7.3-fold higher prevalence of left ventricular hypertrophy than those without such a history. Moreover, carriers of the D allele showed a further increased risk (odds ratio, 13.63; 95% confidence interval, 1.31-142.41). These findings suggest that regular cardiac monitoring may be warranted to identify potential late-onset cardiac remodeling in former athletes with Athlete's heart carrying the ACE D allele.
Tactile sensing can provide a critical function in advanced interactive systems by emulating the human sense of touch to detect stimuli. Vision-based tactile sensors are promising for providing multimodal capabilities and high robustness, yet existing technologies still have limitations in sensitivity, spatial resolution and the high computational demands of deep learning-based image processing. This paper presents a comprehensive approach combining a novel microstructure-based sensor design and efficient image processing, demonstrating that carefully engineered microstructures can significantly enhance performance while reducing computational load. Without traditional tracking markers, our sensor incorporates a surface with micromachined trenches, as an example of microstructures which can modulate light transmission and amplify the visual response to applied force. The amplified image features can be extracted by an ultra-lightweight convolutional neural network to accurately infer contact location, displacement, and applied force with high precision. Through theoretical analysis, we demonstrate that the micro trenches significantly amplify the visual effects of surface deformation. Using only a commercial webcam, the sensor system effectively detected forces below 5 mN and achieved a millimetre-level single-point spatial resolution. Using a model with only one convolutional layer, a mean absolute error below 0.05 mm was achieved. The compliant sensor body and optical readout design make the system inherently compatible with soft robotic integration and immune to electrical crosstalk or electromagnetic interference that often affects electronic tactile arrays. These characteristics highlight its potential for reliable operation in complex human-machine environments.
To evaluate the short- and mid-term volume reduction rate(VRR) after percutaneous ethanol injection(PEI), at 1,3 and 6 months, in patients with cystic or predominantly cystic thyroid nodules(CNs/pCNs, respectively), conducting a systematic review and meta-analysis of published data on VRR outcomes across these intervals. A systematic search of articles published up to October 30,2025 identified studies reporting PEI treatment for CNs/pCNs.Characteristics of the study design, CNs/pCNs cohorts, and outcomes of interest(VRR at 1,3 and 6 months of follow up)were extracted.Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression and subgroup analyses to explore potential sources of heterogeneity. Six studies comprising 431 CNs/pCNs were included.The pooled VRRs at 1,3 and 6 months post-PEI were 85.18%(95% CI: 80.72-89.64),91.50%(95% CI: 88.88-94.12) and 93.11%(95% CI: 90.91-95.31),respectively. Stratifying by nodule cystic composition, the VRR at consecutive follow-up time points was significantly different between the 1- and 3-month intervals in both subgroups [CN: VRRs at 1, 3 and 6 months were 91.16% (88.38-93.93), 95.69% (94.16-97.22) and 96.02% (94.16-97.87), respectively; pCN: VRRs at 1,3 and 6 months were respectively 80.19% (77.04-83.33), 87.08% (84.95-89.2) and 90.01%(88.83-91.19)].A secondary meta-regression analysis with baseline mean volume as covariate demonstrated a significant inverse association with VRR at 1 and 3 months in pCN(p = 0.02). By providing pooled VRRs for the short- and mid-term follow-up, this meta-analysis should be regarded as an initial step, paving the way for larger, high-quality studies aimed at standardizing the PEI procedure and supporting its incorporation into future dedicated guidelines.
The vaccination against COVID-19 is being carried out, and observing the aging process and changes in the face of the pandemic in the older adults, studies are needed to better understand these changes. The purpose of this study was to compare immune response, inflammation, physical-functional performance, and gait at one and nine months after the fourth dose of the COVID-19 vaccine between physically active and insufficiently active older adults. Prospective cohort study. Thirty older adults were evaluated and divided into two groups: the Experimental Group ‒ physically active (EG, n = 15) and the Control Group ‒ insufficiently active (CG, n = 15). Assessments were baseline, one and nine months, post-vaccination and regular exercise practice. Immunological and inflammatory markers and physical-functional variables: questionnaires (FRAQ, Baecke), physical tests (Step Test, Floor Transfer Test, Timed Up and Go, six-minute walk test, hand grip strength), and gait analysis using a pressure platform. The EG showed increased IgA and decreased IgG levels over time. Regarding inflammation, EG demonstrated modulation of the inflammatory response, characterized by increased IL-10 levels, significant changes in IL-12p70 and IP-10 concentrations, and improved pro-/anti-inflammatory cytokine ratios (e.g., IL-6/IL-10), indicating a more regulated immune profile. Additionally, EG improved physical performance in the Step Test, Floor Transfer Test, and six-minute walking test, along with reduced plantar load in the midfoot and rearfoot regions. In contrast, the CG showed reductions in IL-10 and IP-10 levels over time, without consistent improvement in inflammatory modulation or physical-functional performance. In inter-group comparisons at nine months, EG exhibited higher IL-10 levels and a more favorable pro-/anti-inflammatory balance compared with CG, suggesting a controlled and effective immune activation following vaccination. The practice of regular physical exercise was associated with more favorable immune, inflammatory, physical-functional, and gait outcomes at one and nine months after the fourth dose of the COVID-19 vaccine in physically active older adults compared with insufficiently active peers. These findings suggest that long-term regular physical exercise was associated with modulation of the immune-inflammatory profile, marked by a balanced increase in both Th1-associated cytokines (IL-12p70, IP-10) and the regulatory cytokine IL-10 and increased IgA levels and a reduction in IgG over time, suggesting a controlled and effective immune activation following vaccination against COVID-19 and regular exercise practice compared with CG (insufficiently active) and better physical-functional performance with reduction plantar overloading during gait.
Malignant phyllodes tumor of the breast (MPTB) is rare but aggressive fibroepithelial neoplasms. This study aimed to compare long-term survival outcomes between Breast-conserving therapy (BCT) and mastectomy in patients with stage T1‑3N0M0 MPTB and to develop a prognostic nomogram. We identified 683 female patients with stage T1‑3N0M0 MPTB from the SEER database (2010‑2017). Overall survival (OS) and breast cancer‑specific survival (BCSS) were analyzed using Kaplan‑Meier and Cox regression. A nomogram predicting 3‑ and 5‑year OS was constructed and validated. After matching, 282 patients remained in each group. In unadjusted Kaplan‑Meier analysis, BCT was associated with significantly better BCSS (P = 0.0048) and OS (P = 0.017) compared with mastectomy. However, multivariate Cox regression revealed that BCT was not an independent predictor of BCSS (P = 0.355) or OS (P = 0.789). Independent adverse prognostic factors for OS included age ≥ 50 years and T3 stage. The nomogram showed moderate discrimination, with a C‑index of 0.706 (95% CI: 0.524-0.888) in the training cohort and 0.764 (95% CI: 0.543-0.984) in the validation cohort. Although overall prediction error was low in both cohorts, calibration drift was observed in the validation cohort. After adjusting for confounding factors, BCT was not independently associated with inferior long-term survival compared with mastectomy. When negative margins can be achieved, BCT is a reasonable surgical option. The proposed nomogram may assist in individualized risk assessment, but requires further external validation before clinical implementation.
This comment critiques the concept of "sensory horizon" for focussing narrowly on vision, overlooking aquatic animals' rich multisensory integration. Aquatic vertebrates possess sophisticated auditory, mechanosensory, olfactory, and tactile systems that support essential behaviours. Evidence indicates that multisensory integration evolved in water, challenging visual-centric views. We thus urge replacing "sensory horizon" with "multisensory horizon" to more accurately reflect ecological and evolutionary realities.
Plant-pollinator communities are critical for biodiversity, ecosystem function and human well-being. Yet our ability to predict divergent species responses to environmental change, the risk of abrupt collapse, or the potential for recovery in plant-pollinator systems remains limited. Here, we argue that individual variation within species may play a critical but underappreciated role in shaping the sensitivity, robustness and resilience of animal pollinators and plant-pollinator communities. We explore processes by which individual variation may influence responses to perturbation, highlighting parallels with existing niche theory at the species level (e.g. the biodiversity-ecosystem function literature). We suggest that individual variation-as a key but distinct component of total intraspecific variation-may generate more gradual (rather than abrupt) responses to environmental stress than predictions based on species means in many cases, but that these effects will depend on how traits underlying performance, interaction frequency, stress sensitivity and pollination efficacy covary among individuals. Finally, we highlight critical knowledge gaps and open questions in the structure and dynamics of plant-pollinator interactions at the individual scale and conclude by outlining a roadmap for integrating individual variation into studies of plant-pollinator communities under global change. Comunidades de plantas e polinizadores são fundamentais para a biodiversidade, o funcionamento dos ecossistemas e o bem‐estar humano. No entanto, nossa capacidade de prever respostas divergentes das espécies às mudanças ambientais, o risco de colapsos abruptos ou o potencial de recuperação em sistemas planta–polinizador ainda é limitada. Neste trabalho, argumentamos que a variação individual dentro das espécies desempenha um papel crítico, embora ainda subestimado, na determinação da sensibilidade, robustez e resiliência tanto dos polinizadores quanto das comunidades planta–polinizador. Exploramos os processos pelos quais a variação individual pode influenciar as respostas a perturbações, destacando paralelos com a teoria de nicho já estabelecida em nível de espécie (por exemplo, a literatura sobre biodiversidade e funcionamento dos ecossistemas—biodiversity–ecosystem function). Sugerimos que a variação individual—como um componente‐chave, mas distinto, da variação intraespecífica total—pode gerar respostas mais graduais (em vez de abruptas) ao estresse ambiental do que aquelas previstas com base nas médias das espécies. No entanto, esses efeitos dependem de como os traços que determinam desempenho, frequência de interação, sensibilidade ao estresse e eficácia da polinização covariam entre os indivíduos. Por fim, destacamos lacunas críticas de conhecimento e questões em aberto sobre a estrutura e a dinâmica das interações planta–polinizador em escala individual e concluímos delineando um roteiro sobre como integrar a variação individual aos estudos de comunidades planta–polinizador sob cenários de mudança global.
Ammonia-oxidizing nitrifiers (AON) are essential for nitrogen removal in constructed wetlands (CWs). With increasing recognition of the diversity of AON, a reappraisal of the AON community and its relationship with environmental factors in CWs is needed. Here, we investigated the active AON community in inflow and outflow sediments of a landscape CW using amoA (encoding a subunit of ammonia monooxygenase) transcript analysis. Diverse amoA transcript phylotypes of ammonia-oxidizing archaea (AOA), bacteria (AOB), and comammox bacteria (CMX) were identified. Quantitative analysis revealed shifts in the abundances of AOA, AOB, and CMX amoA transcripts between inflow and outflow sediments. AOA amoA transcripts were primarily affiliated with the Nitrosocosmicus, Nitrososphaera, Nitrosotalea, and Nitrosotenuis clusters; AOB amoA transcripts grouped within the Nitrosospira and Nitrosomonas clusters; and CMX amoA transcripts fell into Nitrospira Clade A and B. The amoA transcript abundances of the three AON groups were differentially correlated with potential nitrification rates, ammonia, total nitrogen, pH, organic matter, and nitrate. Canonical correspondence analysis identified ammonia as a factor consistently associated with the community structures of all three AON groups, whereas pH was additionally associated with those of AOB and CMX. This study provides a snapshot of the active AON community in a CW, highlights spatial heterogeneity in abundance and composition, and serves as a reference for future hypothesis-driven investigations into nitrogen removal in wetland systems.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving complex interactions among epithelial, immune, and stromal components. Fibroblasts are key regulators of intestinal inflammation and fibrosis, but their heterogeneity, distribution, and therapeutic potential remain unclear. We systematically identified and characterized intestinal fibroblast subtypes in IBD while exploring the intercellular communication between fibroblasts and immune cells through the integration of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) analyses. Functional gene signatures derived from fibroblast subtypes were applied to bulk RNA-seq datasets to predict therapeutic responses using logistic regression and random forest models. Concurrently, pertinent findings were validated in the intestinal tissues and primary fibroblasts of patients with IBD using multiplex immunohistochemistry (mIHC), western blotting, and quantitative real-time PCR (qPCR). We identified 10 distinct stromal subpopulations comprising two fibroblast subtypes strongly associated with IBD pathology: ICAM1+ inflammatory fibroblasts (iFibro_ICAM1) and FAP+ matrix-producing fibroblasts (mFibro_FAP). These subsets demonstrate distinct transcription factor activity, metabolic reprogramming, and spatial proximity to immune infiltrates, and they undergo remodeling within the inflammatory microenvironment of IBD. Pseudotime trajectory analysis suggested that the iFibro_ICAM1 subset potentially represents a precursor state. CellChat analysis revealed enhanced intercellular communication between fibroblast subsets and immune cells in ileal and colorectal IBD tissues. Furthermore, a machine learning model based on gene expression signatures derived from these fibroblasts effectively predicted poor therapeutic responses to anti-TNF treatments in patients with IBD. This study provides a comprehensive characterization of fibroblast heterogeneity in IBD, highlighting the crucial roles of inflammatory and fibrotic fibroblast subsets as key mediators of immune-stromal interactions and potential predictors of therapeutic responsiveness.
Women are increasingly entering the dementia research workforce, but they frequently fail to attain senior leadership positions in academia. Discrepancies in academic research outputs were investigated to guide equity-focused policy recommendations. Bibliometrics was conducted on 400,482 original research articles (2003-2022) followed by surveying the AD/ADRD research community, to quantitatively and qualitatively evaluate discrepancies in publication and authorship trends. In addition, an unsupervised learning algorithm was developed to analyze underlying relationships between author groups. Male author gender was consistently predictive of better publication and citation metrics across all bibliometrics outcomes, with senior male authors outperforming all other subgroups and fewer senior female authors in most research areas. Female survey respondents reported more barriers, but comparable productivity and citation strategies as male authors. Multi-pronged approaches by stakeholders across institutions, funders, and journals are necessary to provide career support for early-career scientists working to transition to senior research roles.
Swertiamarin (STM), one of the main bioactive compounds of Swertia plants, exerts its potential anti-CLI effects. The objective of this study was to prepare liver-targeting solid lipid nanoparticles (SLNs) with STM, using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA), and evaluate its cholestatic effect on alpha-naphthylisothiocyanate (ANIT)-induced CLI. STM-loaded galactosylated SLN (STM@GalSLN) was prepared using the melt-emulsification-ultrasound method. The influence of STM@GalSLN on liver damage, oxidative stress, hepatocyte apoptosis, and Sirtuin 1 (SIRT1)/NF-E2 p45-related Factor 2 (Nrf2) pathway in ANIT-injured mice was evaluated. Also the cell survival, intracellular ROS, apoptotic rate, expression of SIRT1/Nrf2 pathway ralated proteins in ANIT-induced human liver HepG2 cells were measured. The mean diameter and zeta potential of STM@GalSLN was 167.30 nm and - 13.10 mV respectively. STM@GalSLN (100 mg/kg) alleviated ANIT-induced CLI in vivo, as evidenced by improved histopathology, decreased levels of liver biochemical indicators and cholestatic markers. Also STM@GalSLN (50 µM) notably increased cell survival, reduced ROS overproduction and apoptotic rate in ANIT-injured hepatocytes. Furthermore, STM@GalSLN significantly upregulated the protein expression levels of hepatic SIRT1, pNrf2, HO-1, and NQO1 during CLI. The protective effect of STM@GalSLN in vitro was blocked using EX-527 (10 mM), a selective SIRT1 inhibitor. Taken together, STM@GalSLN alleviated experimental CLI by enhancing the SIRT1/Nrf2 pathway.
Despite the global shortage of nurses, there is limited literature that comprehensively maps interventions to support, stabilize, and enhance the nursing workforce. This umbrella review aimed to identify structures, interventions, and health system arrangements that healthcare systems have put in place to stabilize, support, and sustain the nursing workforce. The review is guided by the Effective Practice and Organization of Care (EPOC) taxonomy and aimed to synthesize review-level evidence relevant to nursing workforce planning and policy development within a policy-relevant timeframe. Reviews that evaluated one or more interventions to stabilize, support, or enhance the nursing workforce within healthcare systems were considered for inclusion. We conducted academic literature searches in MEDLINE, Embase, CINAHL, and Scopus on March 11, 2024, and conducted grey literature searches in Google from April 11-16, 2024. The search strategy combined controlled vocabulary and keywords related to nurses, recruitment and retention, and review study designs. Searches were limited to sources published between January 2014 and March 11, 2024, and to English and French. Two reviewers independently screened and extracted each identified article.We used the JBI critical appraisal checklist for systematic reviews and research synthesis to appraise the included reviews, applying it pragmatically across the heterogeneous review designs in the sample. This approach was selected to provide a single, transparent review-level appraisal process across the included sample; however, it was used as a pragmatic indicator of methodological and reporting completeness. We categorized the included interventions using the EPOC taxonomy. Following screening, we selected 69 studies for inclusion, the majority of which addressed implementation strategies (n = 60) or delivery arrangements (n = 8). The findings directly addressed the primary objective of identifying interventions used to support nursing workforce sustainability and highlighted important evidence gaps related to rural and remote settings, diversity and representation, population needs, equity, and governance and financial arrangements. The findings of this umbrella review suggest that there is no one-size-fits-all approach for supporting the nursing workforce; rather, a multi-level, multi-pronged approach may be more appropriate to collectively have the most impactful outcomes.Limitations of this review include the heterogeneity of the included review designs and the pragmatic use of a single appraisal approach across those designs, which limits direct cross review quality comparisons. Future studies should incorporate rigorous implementation and evaluation plans, focusing on the long-term impacts of strategies.The targeted grey literature search was designed to identify review-level synthesis.
Nicotine and tobacco products (NTP) and cannabis co-use entail unique risks. However, research on the correlates of co-use is limited, focusing on small samples, subpopulations, or specific correlates, without holistically examining multiple risk behaviors. Using an exploratory, hypothesis-generating approach, this study aimed to identify classifiers of past 30-day co-use of cannabis and NTP using random forest regression in a nationally representative adolescent sample. Data were drawn from the 2023 Youth Risk Behavior Survey (YRBS). Participants were 20,103 US adolescents in grades 9-12. Complete-case analyses included 8263 participants. The sample was 51.9% male and racially and ethnically diverse. The primary outcome was a binary indicator of past 30-day co-use of cannabis and NTPs. Classifiers included demographic, behavioral, and psychosocial factors. Random forest regression, including hyperparameter tuning, importance ranking of classifiers, and model robustness measures, were conducted in complete-case and multiply imputed data. Ten variables emerged as consistent and strongest classifiers of co-use, including past 30-day alcohol use (Mrank=1.00; SD=0.00), ever having had sexual intercourse (Mrank=2.36; SD=0.50), past 30-day binge drinking (Mrank=2.64; SD=0.50), and alcohol or drug use during last sexual intercourse (Mrank=4.00; SD=0.00). Models using imputed data achieved lower OOB error rates compared to the complete-case model. Among US adolescents, alcohol use and sexual behavior were the most salient classifiers of cannabis and NTP co-use. These findings highlight the importance of holistic examinations of multiple health risk behaviors.