51886 research outputs found
Sort by
Top five listicle assignment
No full textThis assignment was adapted from a sample syllabus by Dr. Charee Thompson posted on the NCA website in which she asked students to create a Top 5 list in the form of a 3-5 page paper. We adapted her original idea to the current assignment which asks students to create a Top 5 Listicle (i.e., a portmanteau of list + article) commonly used in media today that is usually a combination of text, statistics, graphics, charts, and other visual elements. We are thankful to Dr. Charee for the inspiration for this assignment and we hope the adaption we’ve described below is something that our fellow Communication scholars may find useful to integrate into their classes
Current Treatment Strategies and Supportive Care Practices in the Care of Children and Adolescents With Mature B‐Cell Non‐Hodgkin Lymphoma: A Survey of Children's Oncology Group Institutions
No full textTreatment strategies of mature B-cell non-Hodgkin lymphoma (B-NHL) have been investigated in cooperative group settings to balance toxicity and cure. A survey of institutions participating in the Children's Oncology Group (COG) was completed to assess current practice patterns for treatment strategies, supportive care, imaging, and potential interest in areas to de-escalate for lower risk patients. The survey results demonstrate heterogeneity in treatment regimens for lower risk patient populations but near uniformity in treatment regimens for higher risk patients. The supportive care provided and imaging utilized also varied amongst institutions that provide opportunities for further investigation into best practices
CauReL: Dynamic Counterfactual Learning for Precision Drug Repurposing in Alzheimer's Disease
No full textAlzheimer's disease has few effective therapies, and decades of amyloid- and tau-focused trials have delivered only modest benefit with substantial toxicity. Drug repurposing using real-world data offers a faster and lower-risk route to new treatments, yet current approaches typically average effects across populations, model disease onset and progression separately, and provide little insight into which patients are most likely to benefit. We present CauReL, a dynamic counterfactual representation learning framework that enables transparent, patient specific estimation of treatment effects from large-scale electronic health records for precision drug repurposing in AD. CauReL first learns balanced latent representations of treated and untreated patients using Integral Probability Metric regularization, then jointly predicts two clinically linked outcomes, incident AD and time from mild cognitive impairment (MCI) to AD, to generate paired counterfactual outcomes for every individual. A counterfactual explanation module quantifies how clinical features shape benefit at the patient level, and uplift trees transform complex heterogeneity into simple, rule-based subgroups suitable for trial enrichment and clinical decision support. Using independent cohorts from OneFlorida+ and All of Us, we screened outpatient prescriptions with at least 20 percent exposure among 28,605 individuals with mild cognitive impairment, of whom 4,990 progressed to Alzheimer's disease. CauReL substantially improved covariate balance and distributional overlap across drug cohorts and achieved strong predictive accuracy for both incidence (AUC greater than 0.90) and progression timing (C index 0.81 to 0.84; Spearman 0.80 to 0.86). Twenty drugs showed consistent protective associations, with four emerging as highly reproducible across both networks, the metabolic agents liraglutide and empagliflozin and the neuroactive agents entacapone and amantadine. These drugs were associated with meaningful absolute risk reductions and clinically significant delays in progression from mild cognitive impairment to Alzheimer's disease. Metabolic drugs produced the strongest benefits in individuals with diabetes, obesity, or cardiovascular disease, whereas neuroactive drugs provided broadly consistent protection across most subgroups. CauReL is available as an open source Python package with a companion web server for direct application to new cohorts or disease settings (https://caurel.site/). This work delivers a scalable and interpretable framework for prioritizing repurposable drugs and designing targeted clinical trials for the patients most likely to benefit
Genetic variants linked to cognitive longevity in SuperAgers
No full textBackground
“SuperAgers” are oldest‐old (ages 80+) adults with memory performance resembling adults in their 50s to mid‐60s. This study investigates the genetic drivers of SuperAging using a genome wide association study (GWAS).
Method
Harmonized, longitudinal memory, executive function, and language scores for participants with European ancestry were obtained from the ADSP Phenotype Harmonization Consortium. In addition to exceptional memory, SuperAgers (N = 1,171) must have language and executive function domain scores within normal limits and remain cognitively normal across visits if longitudinal datapoints were available. We compared SuperAgers to Alzheimer's disease (AD) cases (N = 5,372) and controls (N = 4,012) in age‐defined subgroups (middle‐aged=ages 50‐64, old=ages 65‐79, oldest‐old=age 80+). We performed a logistic regression based GWAS comparing SuperAgers and their counterparts, adjusting for age, sex, education, and the first five principal components for population substructure.
Result
Comparing SuperAgers with middle‐aged cases (ages 50‐64, Figure 1), multiple variants in the confirmed AD loci APOE and BIN1 regions were associated with genome‐wide significance (GWS; indexes p = 1.12×10‐41 and p = 5.48×10‐9, respectively). Additionally, we observed GWS association on chromosome 4 loci (rs79973832, index p = 2.95×10‐8, Figure 2), which centers on a ring finger protein gene, RNF150. This family of genes are involved in the ubiquitin‐proteasome system and regulate antiviral immune responses. While several members of the RNF gene family have been liked to AD and cognitive performance, there is currently no established association between RNF150 and AD. Analyses comparing SuperAgers to old and oldest‐old cases (ages 65‐79 and 80+, respectively) found GWS only in the APOE region (indexes p = 1.90×" role="presentation" style="‐webkit‐user‐drag: none; ‐webkit‐tap‐highlight‐color: transparent; margin: 0px; padding: 0px; user‐select: text; display: inline‐table; font‐style: normal; font‐weight: normal; line‐height: normal; font‐size: 16px; font‐size‐adjust: none; text‐indent: 0px; text‐align: center; text‐transform: none; letter‐spacing: normal; word‐spacing: normal; overflow‐wrap: normal; white‐space: pre !important; float: none; direction: ltr; max‐width: none; max‐height: none; min‐width: 0px; min‐height: 0px; border: 0px; position: relative;" tabindex="0">×10‐80 and p = 2.53×10‐13, respectively). No controls had GWS associations, with the strongest associations inconsistent among age group comparisons.
Conclusion
Our extreme‐phenotype GWAS comparing SuperAgers to middle‐aged cases identified both the established APOE and BIN1 genes and the novel loci rs79973832 for AD. Both Old Cases and Oldest‐old Cases reached GWS only in the APOE region. With additional harmonization efforts, larger sample sizes will allow for better comprehension of the genetic architecture of SuperAging. Future work will extend to rare variant analyses of SuperAging using Whole Genome Sequencing (WGS)
Symptomatic pulmonary cement embolism following PMMA vertebroplasty: Clinical presentation and management
No full textBackground: Vertebroplasty, a minimally invasive technique frequently used for spine stabilization and vertebral compression fractures, uses polymethylmethacrylate (PMMA) bone cement. Although usually benign, pulmonary cement embolism (PCE) is an uncommon but potentially dangerous consequence that arises when bone cement enters the pulmonary circulation through the vertebral venous system. Although the majority of PCE cases are underdiagnosed and asymptomatic, the incidence varies between 2.1 % and 26 % of vertebroplasty surgeries. To prevent incorrect diagnoses and needless treatments, early detection is essential.
Case presentation: We present the case of a 71-year-old woman with a history of type 2 diabetes mellitus and hypertension. She underwent laminectomy at the L3/4 and L4/5 levels in addition to PMMA cement-augmented intrapedicular fixation because of her severe spinal stenosis, hypertrophic facet joints, and instability. Three days following surgery, the patient had severe respiratory symptoms, including tachypnea, tachycardia, hypoxemia, and dyspnea. Additional oxygen was required due to oxygen desaturation. Non-contrast chest CT confirmed the presence of multiple bilateral high-density branching opacities in the pulmonary arteries that were compatible with PMMA emboli.
Conclusion: This example emphasizes how difficult it can be to diagnose symptomatic PCE after spinal instrumentation and how crucial it is to keep a high level of suspicion when patients arrive with unexplained respiratory symptoms after vertebroplasty. The preferred diagnostic method remains non-contrast chest CT, and the majority of symptomatic individuals can be conservatively treated with extra oxygen and anticoagulation when necessary
A Novel Design of a Portable Birdcage via Meander Line Antenna (MLA) to Lower Beta Amyloid (Aβ) in Alzheimer’s Disease
No full textLate Onset Alzheimer's Disease (LOAD) is the most common cause of dementia, characterized by the deposition of plaques primarily of neurotoxic amyloid-[Formula: see text] ([Formula: see text]) peptide and tau protein. Our objective is to develop a noninvasive therapy to decrease the toxic A[Formula: see text] levels, using repeated electromagnetic field stimulation (REMFS) in the brain of Alzheimer's disease patients. We previously examined the effects of REMFS on [Formula: see text] levels in primary human brain (PHB) cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro (DIV7) treated with 64 MHz with a SAR of 0.6 W/Kg, one hour daily for 14 days (DIV 21) had significantly reduced (p =0.001) levels of secreted [Formula: see text]-42 and [Formula: see text]-40 peptide without evidence of toxicity. The EMF frequency and power, and SAR levels used in our work is utilized in MRI's, thus suggesting REMFS can be further developed in clinical settings to lower ([Formula: see text]) levels and improve the memory in AD patients. These findings and numerous studies in rodent AD models prompted us to design a portable RF device, appropriate for human use, that will deliver a homogeneous RF power deposition with a SAR value of 0.4-0.9 W/kg to all human brain memory areas, lower ([Formula: see text]) levels, and potentially improve memory in human AD patients.The research took place at the Indiana University School of Medicine (IUSM) and Purdue University Indianapolis. The first phase was done in PHB cultures at the IUSM. Through this phase, we found that a 64 MHz frequency and an RF power deposition with a SAR of 0.4-0.6 W/kg reduced the (A[Formula: see text]) levels potentially impacting Alzheimer's disease. The second phase of the project was conducted at Purdue University, we used ANSYS HFSS (High Frequency Simulation System) to design the devices that produced an appropriate penetration depth, polarization, and power deposition with a SAR of 0.4-0.9 W/kg to all memory brain areas of several numerical models. In Phase II-B will validate the device in a physical phantom. Phase III will require the FDA approval and application in clinical trials.The research parameters were translated into a designed product that fits comfortably in human head and fed from an external RF source that generates an RF power deposition with a SAR of 0.4-0.9 W/kg to a realistic numerical brain. The engineering design is flexible by varying the leg capacitors of the Meander Line Antenna (MLA) devices. Thermal outcomes of the results guarantee less than 0.5 C temperature increase within one-hour time of exposure, which can be used in clinical trials for AD patients. Design parameters include dimension of the coil, the MLA structure, conducting material, and capacitance values with the produced EM fields. The flexible design was achieved by varying the additive capacitance between conductors, and via a hybrid approach integrating a birdcage with sixteen MLA. A coil antenna size within 16 cm radius and 13 cm length was achieved. A capacitance between 6.9 nF and 9.2 nF were observed when copper materials with 16 conductors were used to achieve the research parameters in focus.The medical project proposed here has three phases: The initial phase of determining the research parameters for reducing A[Formula: see text] levels in human brain cultures and animal studies was completed at the IUSM. The translational engineering design of the REMS device and the numerical head and Antenna devices was successfully completed and presented in this paper by Purdue University and IUSM. Future phases will require manufacture and experimental validation of the REMS device with FDA approval for human application. Clinical impact: Our biological studies in human brain cultures showed that an RF power with a SAR of 0.4-0.9 W/kg at 64 MHz, lowered A[Formula: see text] levels, which potentially will prevent the death of the brain neurons and improve memory in AD. The fact that we found a safe RF power deposition with a SAR value associated with the proposed biological effects in human neurons and that 64 MHz provides a penetration depth of 13.5 cm that reaches all memory areas in a human brain makes the design and manufacture of this device of high clinical impact in the study of these exposures on the treatment of Alzheimer's and other protein associate diseases. Also, 64 MHz and RF power deposition with similar SAR levels are administer routinely in routine MRI for more than 4 decades makes it a safe framework for these novel therapeutic strategy.Clinical and Translational Impact Statement: The basic science work presented previously is both mechanistic and translational, and would advance the field of neuroscience as well as AD. This prompted us to joint efforts between the Indiana University School of Medicine and the electrical and computer engineering at Purdue University to design and develop a suitable EMF device for human treatments. Recently, our engineering team designed a birdcage antenna that generate a homogeneous RF power deposition with the same SAR values of our biological experiments in a realistic numerical human brain. Here, the engineering research has been extended to investigate the design of a portable flexible birdcage antenna that will enable adjustments to fit physical patient's characteristics, such as geometry, head size, and tissue dimensions. This new device is expected to improve SAR uniformity and may reduce the likelihood of untreated regions in the brains of patients during treatments. Also, here we determined that the maximum temperature rise of these exposures was less than 0.5°C, which is a safe level per regulatory agencies. This study considers a portable device system that will achieve the research parameters and patient satisfaction regarding reliability and comfort
Factors associated with increased burnout in genetic counseling students
No full textGenetic counseling students face numerous stressors during their graduate program, which can lead to negative outcomes such as burnout. Burnout can negatively impact students' ability to perform well, maintain stamina, and feel competent throughout their training. The Maslach Burnout Inventory (MBI) is a validated survey that assesses three domains that together define burnout: exhaustion, cynicism, and low self-efficacy. One hundred eighty genetic counseling students from the classes of 2024 and 2025 within the United States and Canada completed a cross-sectional, quantitative survey which included the MBI validated for students, a list of 19 situations tailored to students in genetic counseling training programs that may cause stress, and three open-ended questions asking what activities helped reduce stress, including resources provided by the program and resources students would like to be provided. Genetic counseling students endorsed an average of nine situations that caused them "some" or "a lot" of stress. Results revealed that 12% of current students met criteria for having burnout (defined as high exhaustion, high cynicism, and low self-efficacy); an additional 20% met criteria for two of the three burnout subscales. The most consistent predictors of burnout were the numbers of situations causing a student stress and being in the latter part of training. Thematic analyses revealed that personal activities, social activities, and mental health services helped reduce stress, while support in relation to academics was a desired resource. This study reveals that burnout is experienced by genetic counseling students and is associated with factors such as having a high number of situations causing a student stress or being more than halfway through the graduate program. These results provide insight into areas and methods for genetic counseling graduate programs to attenuate burnout in their students
Quantitative evaluation of low-frequency oscillations using real-time phase-contrast MRI during drowsiness
No full textBackground: Low-frequency oscillations (LFOs) in the brain are increasingly recognized for their role in driving brain clearance during sleep and drowsiness. However, human studies have largely relied on qualitative assessment. Quantitative assessments of LFO-driven flow dynamics remain limited, and findings across animal and human studies are mixed. Some report that ventricular CSF inflow is dominated by LFO activity, whereas others suggest that cardiac pulsations are the primary driver of CSF motion along its circulation pathways. In this study, we employed real-time phase-contrast (RT-PC) MRI to quantitatively measure blood and cerebrospinal fluid (CSF) flow rates at the cervical level. Our goal was to assess contributions of LFOs across vascular and CSF compartments and to examine their changes between wakefulness and drowsiness.
Methods: RT-PC MRI was acquired at the cervical (C2/C3) level in thirty-eight healthy participants to measure arterial, venous, and CSF flow rates. Each participant underwent two RT-PC sessions: one with eyes open and another with eyes closed, following a 30-minute in-scanner eyes-closed rest period. Frequency-domain analysis quantified power within LFO, respiratory, and cardiac bands across artery, vein, net arteriovenous flow (A + V), and CSF signals. Time domain analysis was used to calculate arterial-to-venous delays (A-V delay) for each pulsation type.
Results: Cardiac pulsations dominated the flow rate oscillations, accounting for 95.2%, 85.1%, 81.2%, and 94.2% of the total power in artery, vein, A + V, and CSF, respectively. LFO contributions were lower, accounting for 3.2%, 4.9%, 3.5%, and 0.8%. After 30 min of rest, LFO power increased significantly and consistently in all compartments (p 0.1).
Conclusion: Quantitative flow analysis demonstrated that LFOs contributed substantially less to blood and CSF flow oscillations than cardiac pulsations at the cervical level. However, LFO power increased significantly and consistently after rest in blood and CSF, supporting its role as a driver of fluid circulation during drowsiness. Notably, the detection of increased LFO power in arterial blood at the cervical level—upstream of cerebral flow—suggests a potential link to autonomic regulation of vascular tone.
Supplementary Information: The online version contains supplementary material available at 10.1186/s12987-025-00741-x
Validation of Video Administration of a Modified UDSv3 Cognitive Battery in Older Adults with and without Cognitive Impairment: The ‘VCog’ Study
No full textBackground:
Video‐interfacing is increasingly being used in research and healthcare. However, the validity of video‐based cognitive testing has not been adequately established. The ‘VCog’ Study is directly comparing video‐based cognitive assessments to in‐person assessments administered to a diverse cohort of older adults with normal cognition (CN), mild cognitive impairment (MCI), and dementia.
Method:
448 participants (age (M=75.7 (7.2)), race (23% non‐white), sex (52% female), and education (M=16.5 (2.5)) from 12 Alzheimer's Disease Research Centers (ADRCs) around the country completed, in randomized order, a video‐adapted version of the Uniform Data Set Version 3 (UDSv3) from their home 4‐8 weeks before or after their annual in‐person cognitive assessment. A subset of participants also completed the Rey Auditory Verbal Learning Test (RAVLT). Participants were previously classified by their ADRC as CN, MCI, or mild dementia. Participants used their own device (if it had A/V capabilities and Wi‐Fi) or they were provided a loaned device. All participants were oriented to video procedures before testing and were tested independently.
Result:
Pearson correlation coefficients were generally high and statistically significant (rs .73‐.86; ps .05).
Conclusion:
VCog is the first large, randomized, study of cognitively, ethnically and geographically diverse individuals to examine the validity of video‐administered UDSv3 cognitive battery relative to in‐person administration. Results show strong concordance between UDSv3 tests for individuals with and without cognitive impairment. Oral TMT‐A performed poorly due to being structurally different from written TMT‐A. Having a UDSv3 battery validated for video administration can help AD researchers reduce participant burden and increase accessibility to underserved populations
Impact of Rapid Blood Culture Identification on Antibiotic De-escalation at a Veterans Affairs Medical Center
No full textBackground: Timely de-escalation of antibiotics improves patient outcomes and reduces costs. The BioFire FilmArray Blood Culture Identification (BCID2) panel, a rapid diagnostic technology, enables enhanced antimicrobial stewardship. This study evaluated whether BCID2 use at Veteran Health Indiana (VHI) saved time and money to prescribe optimal antibiotics from blood culture draw pre- and postimplementation.
Methods: This pre-post quasi-experimental study evaluated patients with bacteremia at VHI between March 1, 2022, and October 1, 2023. Patient data were generated using electronic health records and microbiology laboratory data. A random sampling of eligible patients was included if they had a positive bacterial blood culture for which they received ≥ 1 antibiotic while hospitalized.
Results: Median difference in time to organism identification was 37.8 hours in the preintervention group vs 16.9 hours in the postintervention group (P < .001). Other differences in time were not statistically significant. Median difference in time to optimal antibiotics was 58.5 hours in the preintervention group vs 43.4 hours in the postintervention group (P = .11). Median difference in time on antibiotics was 45.2 hours in the preintervention group vs 46.6 hours in the postintervention group (P = .99). Median difference in time on appropriate antibiotics was 2.3 hours in the preintervention group vs 1.9 hours in the postintervention group (P = .79).
Conclusions: BCID2 use resulted in a decrease in median time to optimal antibiotics that was not statistically significant. Additional barriers to optimal antibiotic prescription should be addressed to maximize rapid blood culture identification technologies and enhance antimicrobial stewardship