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Direct identification of Mycobacterium species from liquid medium (MGIT) using FastPrep-2 bead beating system and MALDI-TOF mass spectrometry technology: a comparison with solid media and PCR-based method
No full textBackground: Mycobacterial infections present significant global health challenges. Traditional diagnostic methods are inadequate for the identification of Mycobacterium species, highlighting the need for more efficient techniques. Matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) technology offers potential advantages in rapid and accurate pathogen identification.
Objective: This study evaluates the accuracy and precision of the MALDI-TOF using the FastPrep-2 bead beating system and VITEK MS version 3.2 for identifying Mycobacterium species directly from Mycobacteria Growth Indicator Tube (MGIT), liquid medium, compared to MALDI-TOF (VITEK MS) based on the traditional solid medium (Lowenstein-Jensen). We also compared the result of the MALDI-TOF from MGIT to M tuberculosis results by PCR-based method.
Methods: The study included 16 mycobacterium tuberculosis (MTB) and 37 nontuberculous mycobacteria (NTM). Isolates were grown in LJ solid medium and MGIT liquid medium, and lysed using the FastPrep-2 bead beating system. Identification was performed using VITEK MS version 3.2 from liquid.
Results: NTM comprised 70 % (37/53) of the total isolates evaluated. Of these, 92 % (34/37) were successfully identified using VITEK MS from MGIT liquid medium. Overall, the method achieved 88.6 % accuracy for identifying Mycobacterium species from liquid medium, compared to 96.2 % from solid medium. The agreement between both methods was moderate (Kappa = 0.470, p < 0.001). MTB isolates were identified with 100 % accuracy, and the approach demonstrated excellent reproducibility with 100 % intra-assay and inter-day consistency.
Conclusion: Using VITEK MS version 3.2 to directly identify MTB and NTM from MGIT liquid medium provides a rapid, cost-effective, and reliable method for identifying Mycobacterium species. Further optimization and database expansion are recommended to enhance accuracy for rare and less common mycobacterial species
Human and vector behavioural determinants of malaria transmission in the Nandi highlands, western Kenya
No full textBackground: Malaria transmission, characterized by spatial and temporal heterogeneity and complex vector behaviours, persists in Kenya's highlands despite widespread use of long-lasting insecticidal nets (LLINs). The role of human activity in exposure risk remains underexplored. Identifying vulnerable times and locations is crucial for designing and optimizing targeted control strategies that address the intricate interplay between human activity and local vector behaviour that results in transmission. This study examined human-mosquito interactions in three different ecological settings in Nandi highlands in western Kenya.
Methods: Malaria vector biting rates were monitored both indoors and outdoors from 18:00 to 06:00 over five consecutive nights in ten houses per village in three different ecological settings namely site close to the forest (Kipsamoite), neutral site neither close to forest nor swamp (Kebulonik), site close to the swamp and with past high malaria prevalence (Kapsisywa) using human landing catches (HLC) during the long (May 2018) and short (October 2018) rainy seasons. Concurrently, hourly human behaviour observations (HBOs) were conducted to assess indoor versus outdoor presence, sleeping patterns and LLINs use. All Anopheles mosquitoes were first identified morphologically using standard anopheline keys and subsequently confirmed to species level through molecular sequencing of the internal transcribed spacer 2 (ITS2) region and cytochrome c oxidase subunit 1 (CO1) gene.
Results: High Anopheles species diversity was observed, with site-specific dominance: Anopheles arabiensis in Kipsamoite, Anopheles christyi in Kebulonik, and the novel Anopheles spp. 14 BSL-2014 in multiple sites. The majority of specimens were collected indoors in Kipsamoite (67%) and Kebulonik (52.9%), while most specimen were collected outdoors in Kapsisywa (58.3%) were outdoors. Mosquito exposure peaked outdoors in the early evening (1800-2100 h) and indoors during the first half of the night (1900-0100 h), coinciding with periods when people were awake or transitioning to or from sleep, with low LLIN use. Human behaviour-adjusted exposure was highest outdoors in the early evening (1800-2100 h) and indoors during the first half of the night (1900-0100 h). Overall, most exposure occurred indoors for unprotected sleepers and individuals awake (53-55%), followed by outdoor exposure in the early evening and late morning (16-44%). LLINs prevented 24.5% (long rains) and 44.9% (short rains) of bites in Kipsamoite, 24.6 to 37% in Kebulonik, and 35.8% in Kapsisywa (short rains).
Conclusion: This study demonstrates that human exposure to malaria vectors is shaped by the interplay between temporal and spatial human and vector behaviours, with the highest biting rates indoors for unprotected sleepers and awake individuals, and outdoor exposure peaking in the early evening and late morning. It also reveals diverse, behaviourally adaptable vector populations, including cryptic species, sustaining indoor and outdoor transmission. While LLINs use provide partial protection, significant gaps in protection remained during periods and in spaces where nets are not effective, highlighting persistent residual transmission and the need for vector characterization, behaviour-informed interventions (e.g., spatial repellents and larviciding), community engagement, and strengthened entomological surveillance to guide effective malaria control
Navigating Serious Illness: The Role of Palliative Care Consultations in Nursing Homes
No full textPalliative care (PC) consultations in nursing homes (NHs) are recognized for enhancing the quality of life for residents living with serious illness. Despite their benefits, the accessibility of PC consultations remains variable and inconsistent across NHs. This study aimed to develop a framework to explain PC consultation implementation and utilization in NHs from the perspective of PC and NH key partners. A constructivist grounded theory approach was employed, using semi-structured and group interviews with PC and NH administrators, nursing directors, social workers, nurses, primary care providers, and PC specialist nurse practitioners. Participants (N = 33) were purposively sampled from three PC agencies with relationships in 14 NHs to capture variability in PC implementation and utilization. Data were analyzed through open, process, and theoretical coding to develop a theoretical framework. The central issue influencing PC consultations in NHs was the need to navigate resident and family uncertainty and complexity in serious illness care, especially for residents living with dementia. NH staff used PC consultations to guide residents and families during unpredictable disease trajectories, mediate family and institutional expectations by “bridging the gap”, and reframe PC as integrated support rather than only for end-of-life care. PC consultations facilitated better sensemaking, improved communication, and led to more effective care planning. PC consultations serve as strategic tools for NH staff to manage the complexities of serious illness care. Understanding and supporting the practical applications of PC consultations within NHs can lead to more effective integration and utilization of these services, ultimately enhancing resident care
Elevated tumor mutation burden in patients with cancer with underlying HIV infection: data from the Oncology Research Information Exchange Network (ORIEN)
No full textBackground: People living with HIV (PWH) have improved life expectancy because of effective human immunodeficiency virus (HIV) therapy but still experience immune impairment (e.g., altered CD4/CD8 T cells). We hypothesized that tumors diagnosed in PWH would have distinct molecular features.
Methods: We utilized whole-exome sequencing of paired tumor and germline DNA and RNA from 229 patients with cancer enrolled into the Oncology Research Information Exchange Network to classify total tumor mutation burden (TMB), MHC class I neoantigen count, and MHC class II neoantigen count.
Results: Specimens from 229 patients with cancer (110 PWH and 119 without HIV) were evaluated. Average TMB for tumors diagnosed in PWH was 249, compared with 172 for those without HIV. After adjustment for age, sex, race, smoking, and cancer site, the association between HIV and TMB remained statistically significant (OR = 1.72; 95% confidence interval (CI), 1.26-2.43). We further observed an association between HIV and higher putative class I neoantigen count (OR = 1.62; 95% CI, 1.10-2.41) but no association with putative class II neoantigens. When considering cancer sites separately in unadjusted analyses, average TMB was elevated in PWH for thyroid (P < 0.01) and bladder cancers (P = 0.03) and sarcoma (P = 0.04). Similarly, putative class I neoantigen count was elevated in PWH for head and neck (P < 0.01) and thyroid (P = 0.01) cancers, as well as sarcoma (P = 0.04).
Conclusions: Our findings indicate that tumors diagnosed in PWH harbor a higher TMB and a higher number of putative class I neoantigens.
Impact: A higher TMB in PWH may portend a more favorable response to certain cancer treatment modalities such as immune checkpoint inhibitors
Targeting Ref-1 in cancer: Progression of advanced generation Ref-1 inhibitors through the drug discovery pipeline
No full textAPE1/Ref-1 (Apurinic endonuclease1 / Redox factor-1, referred to as Ref-1) is a multifunctional
protein with both DNA repair and redox activities. The redox activity of Ref-1 activates
transcription factors such as HIF1a, STAT3, and NFkB that are involved in cancer cell survival
and proliferation. Targeting Ref-1 with specific inhibitors represents a promising therapeutic
strategy across multiple cancer types. This study focuses on screening and characterizing
advanced-generation Ref-1 inhibitors to identify potential candidates for further preclinical
development. As part of this drug discovery pipeline, we evaluated four advanced generation
compounds and compared them to second-generation compound, APX2009. We selected
malignant peripheral nerve sheath tumor (MPNST) cells for evaluation because these tumors
often exhibit elevated oxidative stress and redox signaling, making them more dependent on
Ref-1 activity. Using MPNST cells, I measured inhibition of downstream Ref-1 target, NFκB and
cytotoxicity after treatment. NFκB activity was measured via a luciferase-based reporter assay
and two viability assays were compared: Alamar Blue and Methylene Blue. Luciferase assays
further confirmed on target inhibition of Ref-1–regulated NFκB activity. Both cell viability assays
demonstrated dose-dependent reduction in cellular viability, confirming compound efficacy.
Among the compounds tested, WGK2105 exhibited high potency with an IC₅₀ of ~2 µM.
WGK2110 and WGK2111 demonstrated similar potency and Ref-1 inhibition when compared to
APX2009, while WGK2092 required significantly higher concentrations and will not be prioritized
for further development. These findings support the potential for discovery of more potent Ref-1
inhibitors and identify multiple promising candidates for preclinical advancement. Future efforts
will assess metabolic stability in mouse and human liver microsomes to determine in vivo
suitability. In vivo efficacy studies and full pharmacokinetic profiling (ADME) will follow for top
candidates. Comparative analysis of active versus inactive compounds will inform structure activity relationship (SAR) development, guiding next-generation inhibitor design. These efforts are key steps toward Investigational New Drug (IND) applications and clinical trial readiness
GUIDE and Beyond: Strategies for Comprehensive Dementia Care Integration
No full textThe Centers for Medicare & Medicaid Services' (CMS) Guiding an Improved Dementia Experience (GUIDE) Model represents a landmark opportunity to improve outcomes for persons with dementia and their caregivers and scale comprehensive dementia care through a structured service delivery and alternative payment approach. The National Dementia Care Collaborative (NDCC), a coalition of scientific and clinical leaders in evidence-based dementia care, works to promote comprehensive dementia care. Drawing from the experiences of six previously tested programs-Aging Brain Care, Alzheimer's and Dementia Care, BRI Care Consultation, Care Ecosystem, Integrated Memory Care, and MIND at Home-we describe a four-step approach to enable successful adoption and implementation: identifying key leaders and partners, preparing a tailored value proposition, initiating program start-up, and ensuring sustainable implementation. Our guidance also emphasizes leveraging existing community assets, aligning efforts with organizational priorities, and using both storytelling and data to make the case for change. We highlight practical tools and resources to address operational challenges, including electronic health record integration, reimbursement strategies, and staff training. By focusing on evidence-based models, health systems and other providers can accelerate implementation, reduce costly emergency and institutional care, and deliver high-quality, person-centered support. This approach can help to empower GUIDE participants and others to build effective, durable, scalable comprehensive dementia care systems, ultimately advancing the goal of establishing such care as a permanent Medicare benefit
Protocol for an international multicenter, prospective, observational, non-competitive, study to validate and optimise prediction models of 90-day and 1-year allograft failure after liver transplantation: The global IMPROVEMENT Study
No full textMore liver transplants (LT) are performed worldwide thanks to extended criteria donors (ECD). This is paralleled by a supposed increased risk of allograft failure (AF) at 90 and 365 days. This study has been designed to portray the LT practice worldwide and investigate models of AF prediction and the impact of risk mitigation strategies for further improving graft and patient outcomes. This is a multicenter, international, non-competitive, observational two segment study on consecutive LTs over two periods (2017-2019 and 2022-2024). A steering committee of LT experts defined the study protocol. The prospective segment will enroll 750 patients from 15 high-volume LT centers (50 per center), and the retrospective segment will enrol 4200 patients from 56 LT centers (75 per center). To provide a snapshot of the LT activity globally and to develop new algorithms for the timely prediction of AF at 90 and 365 days post-LT. The study also aims (1) to validate the existing predictive models and (2) to investigate the best time for re-transplantation, paying attention to the differences in AF and Ischemic cholangiopathy according to the donor types and mitigation strategies implemented in the various settings. Since the adoption of machine perfusion has increased in different proportions worldwide, models will be adjusted according to this parameter. Finally, retrospective and prospective data will be available for further stratifications and modelling according to the degree of decompensation at transplant, gender match, postoperative complications and their management. This protocol was approved by Fondazione Policlinico Universitario Agostino Gemelli IRCCS Ethics Committee (study ID: 4571) and the Institutional Review Board of the University of California, Los Angeles. The provisional study protocol was submitted to the main scientific international societies in the transplant field. Results will be published in international peer-reviewed journals and presented at congresses
Identification of Long Noncoding RNA Candidate Disease Genes Associated With Clinically Reported Copy Number Variants in Congenital Heart Disease
No full textBackground: Copy number variants (CNVs) contribute to 3% to 10% of isolated congenital heart disease (CHD) cases, yet their pathogenic roles remain unclear. Diagnostic efforts have focused on protein-coding genes, largely overlooking long noncoding RNAs (lncRNAs), which play key roles in development and disease.
Methods and results: We systematically analyzed lncRNAs overlapping clinically validated CNVs in 743 patients with CHD from the Cytogenomics of Cardiovascular Malformations Consortium. We identified heart-expressed lncRNAs, constructed a gene regulatory network using weighted gene coexpression network analysis, and identified gene modules associated with heart development. Functional enrichment and network analyses were used to identify lncRNAs that may be involved in heart development and potentially contribute to CHD. The code is stably archived at https://doi.org/10.5281/zenodo.13799779. We identified 18 lncRNA candidate genes within modules significantly correlated with heart tissue, highlighting their potential involvement in CHD pathogenesis. Notably, lncRNAs such as lnc-STK32C-3, lnc-TBX20-1, and CRMA demonstrated strong associations with known CHD genes. Strikingly, although only 7.6% of known CHD genes were affected by a CNV, 68.8% of the CNVs contained a lncRNA expressed in the heart.
Conclusions: Using weighted gene coexpression network analysis, we identified CNV-associated lncRNAs with potential relevance to CHD, underscoring the complexities of noncoding regions in disease pathogenesis. These findings suggest that lncRNAs may play a greater role in CHD than previously recognized, highlighting the need for broader genomic analyses that extend beyond protein-coding genes. This study provides a foundation for further exploration of lncRNAs in CHD, with potential implications for improved genetic characterization and diagnosis
Variability in the utilization of preventive dental services among the underserved population of Indiana
No full textObjectives: To explore the variability of utilization patterns of preventive dental services among diverse demographic groups in the state of Indiana.
Methods: This study utilizes a retrospective data analysis approach to examine the preventive dental services utilization among patients treated by senior-year dental students (D4 students) during their community-based clinical rotations at Federally Qualified Health Centers and private practices, affiliated with Indiana University School of Dentistry. The data were extracted from daily patient reports submitted by D4 students for every patient they examined during their rotations, via RedCap. Descriptive statistics and generalized linear modeling using main effects were performed to identify the utilization of different preventive services across urbanization stratification and demographic variables among the included participants.
Results: There was a statistically significant (p < 0.001) distribution of all dental preventive services according to demographic characteristics, viz. age, ethnicity, location (rural or urban), primary language spoken, and insurance status. There were 30.39 times higher odds of utilizing preventive dental services in a rural zip code compared to an urban zip code. Individuals with multicultural ethnicities (OR= 0.91, 95% CI: 0.54, 1.53) were less likely to utilize preventive dental services than the "Other" category, although the value was not significant (p = 0.72). Also, the younger age group (less than 17 years) was more likely to utilize preventive dental services than the older age group (p < 0.001).
Conclusions: Inequities in the utilization of preventive dental services were identified among the underserved population of Indiana, according to demographic characteristics
Unveiling and Installation of Riley Hospital for Children Historical Marker
No full textPhotos and information from media stories about the unveiling of a new Indiana state historical marker from the Indiana Historical Bureau commemorating Riley Hospital for Children's century of care. The historical marker was unveiled by Dr. Richard Schreiner (retired Chairman, Department of Pediatrics and Chairman, Riley Hospital Historic Preservation Committee)and Riley Children’s Health President, David Biggerstaff in the hospital's Lilly Auditorium during a Town Hall meeting of hospital leadership on November 6, 2025. The installation of the Riley Hospital for Children historical marker on the hospital grounds took place on November 11, 2025. Photos provided courtesy of Riley Children's Health.
The text, which appears below the marker headline, is engraved on both sides and reads as follows: "Prominent friends of children’s poet James Whitcomb Riley agreed to open a hospital to honor him after his death in 1916. The Riley Memorial Association, formed in 1921, worked with Indiana University, the State of Indiana, and private donors to construct the hospital. Riley Hospital for Children opened in 1924 and treated nearly 40,000 children in its first decade. The hospital quickly became a national leader in pediatric diagnoses, treatment, and surgery, with advancements in heart surgery, cochlear implants, and neonatal care. Partnering with the IU School of Medicine, Riley physicians have conducted innovative research in specialized areas such as cancer and diabetes, driving breakthroughs in children’s health care.