bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Diagnosis of Necrotizing Enterocolitis in Neonates Using an Electronic Nose
Authors: Prabhakar Mira , Markel Troy 
Published: December 2021

Background: Necrotizing enterocolitis (NEC) is a devastating clinical problem that often necessitates resection of necrotic intestine, leaving infants with a suboptimal length of intestine to absorb nutrition. There are no adequate tests or biomarkers to predict NEC onset. We hypothesized that assessment of biological samples with a novel electronic nose can be used with machine learning algorithms to detect aberrancies in stool and urine volatile organic compounds to predict NEC risk.
Methods: 18 infants of gestational age ≤34 weeks in the Riley Hospital NICU were enrolled in the study and underwent stool (38 control, 3 NEC) and urine (42 control, 5 NEC) sample collection. Stool was collected by the bedside nurse via the infant’s diaper or ostomy bag. Urine was collected using a bag around the infant’s perineum or via foley catheter if already present. Stool samples and 250uL urine samples were aliquoted into Eppendorf tubes and covered with Parafilm. Samples were heated to 40°C, 30 minutes for stool, and 10 minutes for urine. Sample headspace was analyzed using the Cyranose 320 electronic nose, creating a “smellprint” comprised of readings from 32 unique sensors. Individual sensors were compared using Mann-Whitney U test. P<0.05 was significant.
Results: There was no significant difference in urine or stool signals among the 32 sensors between NEC and control groups.
Potential Impact: While no significant difference was found, this study is greatly limited by the number of patients enrolled, with only 2 of the 18 being diagnosed with NEC. Past retrospective studies with this device have found differences between NEC and non-NEC stool. The future goals of this study are to continue enrolling patients to have a more robust data set. Using machine learning, we aim to create a model to predict NEC before its clinical manifestation so that beneficial treatment can be initiated earlier.

Acknowledgment: This project was funded, in part, with support from the NIH NHLBI Short-Term Training Program in Biomedical Sciences Grant funded, in part by T35HL110854 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Analysis of Lipid-Associated Gene Expression in Mouse Endotoxin Model
Authors: Price Charles , Hato Takashi 
Published: December 2021

Background/Objective:
Sepsis-induced kidney injury is a major clinical problem and is an independent risk factor for mortality. We and others have reported that renal tissue metabolism is profoundly altered in the septic milieu. However, whether such metabolic shift is an adaptive response or pathologic process remains unclear. For instance, decreased lipid metabolism in the renal peroxisomes could limit the genesis of deleterious reactive oxygens species whereas the lack of lipid usage in peroxisomes could contribute to energy depletion. Accordingly, here we examined gene expression changes involved in lipid metabolism using mouse models of endotoxemia. Specifically, we compared gene expression changes between injurious high-dose endotoxemia and protective low-dose endotoxin preconditioning models with the goal of identifying favorable reprogramming in lipid metabolism.

Methods:
To induce protective preconditioning, mice were subjected to low-dose endotoxin followed 24 hours later by high-dose endotoxin. Non-preconditioned mice were subjected to a single high-dose endotoxin. Renal tissues were processed and single-cell RNA-sequencing was performed. Tissue metabolomic data was also obtained.

Results:
We found that renal lipid metabolism is deranged in the non-preconditioned endotoxemia model. Plin2, a marker for lipid accumulation, was significantly upregulated in the proximal tubules of non-preconditioned animals. In contrast, Plin2 expression was preserved in the preconditioned animals, suggesting that altered Plin2 expression is a maladaptive response. Similarly, Pdzk1 and Lrp2, genes involved in HDL/LDL receptor expression, were concurrently downregulated in the injurious model, whereas their expression levels were preserved in the protective model. The stable expression of these two genes may be important for maintaining metabolic capacity and anti-inflammatory effects observed in the preconditioned state. These findings were further supported by our tissue metabolomics analysis.

Conclusion/Impact:
Our data indicate that aberrant lipid metabolism is a prominent feature of endotoxin-induced kidney injury. The use of protective preconditioning served as a platform to identify several candidate genes that could be studied further for the development of biomarkers and precise intervention.
Are age-related biomarkers of dementia risk accelerated by low educational attainment?
Authors: Schaefer Katherine A. , Unverzagt Frederick W. , Xu Huiping , Clark Daniel O. 
Published: December 2021

Background: Low education significantly elevates dementia risk but it is not clear whether this is through chronic systemic inflammation, early-onset dementia pathology, or other factors. This project compares biomarkers of inflammation and dementia pathology in a young-old and older cohort. Due to significantly lower education in the young-old cohort, we hypothesized evidence of similar or higher biomarker levels in the young-old cohort compared to the older cohort.
Methods: Blood samples were used to measure pro-inflammatory cytokines (C-reactive protein (CRP), tumor necrosis factor (TNF interleukin (IL)-6, and IL-1 anti-inflammatory cytokines (IL-10 and IL-1RA), and the brain biomarkers phosphorylated tau (p-tau) and neurofilament light (NfL). Inflammatory markers were measured at the Considine Lab at the Indiana University School of Medicine using ELISA assays while p-tau and NfL were measured with Simoa assays at the Quanterix lab in Massachusetts. We used the natural logarithm of all biomarker variables to address skewed data. Linear regression was used to investigate race- and gender-adjusted differences in the biomarkers.
Results: The young-old cohort (N=42) has a mean age of 62.4, 69.1% are female, and 78.6% are non-Hispanic black (NHB), while the older cohort (N=60) has a mean age of 80.3, 60% are female, and 20% are NHB. Median education in the young-old cohort is 12 vs 16 in the older cohort. Adjusted models showed higher mean CRP (p=0.004) and lower mean IL-10 (p<0.001) in the young-old cohort. TNF- (p <0.001), IL-6 (p=0.021), and IL-1(p=0.017), P-tau (p=0.003), and NfL (p<0.001) were all higher in the older cohort.
Conclusion: We found partial support of our hypothesis in that the younger, low education cohort had higher mean CRP and lower mean IL-10 (anti-inflammatory). However, brain biomarkers were higher in the older cohort. More research will be needed to determine if and how low education elevates ADRD risk through systemic inflammation.
A 12-Month Retrospective Comparison of the Efficacy and Complications of Device-Based and Non-Device-Based MIGS Procedures
Authors: Amjad Rabiah , Cantor Louis 
Published: December 2021

Background: Minimally Invasive Glaucoma Surgery (MIGS) encompasses a group of procedures designed to reduce trauma to the target tissue and reduce the incidence of complications. MIGS procedures can be divided into two overall categories: device-based procedures and non-device-based procedures. The purpose of this study is to compare the efficacy and complications of device-based and non-device-based MIGS procedures in eyes combined with phacoemulsification.
Methods: 55 eyes from 36 patients with combined MIGS (iStent, GATT, ABIC, BANG, and KDB) and phacoemulsification were included. The glaucoma diagnoses included primary open angle glaucoma (POAG), secondary open angle glaucoma (SOAG), and combined-mechanism glaucoma (CMG). The efficacy of the device-based and non-device-based procedures was determined by the mean postoperative IOP and glaucoma medication reduction. Early complications included adverse events and IOP spikes. Late complications included additional surgeries.
Results: At 12 months post-operatively, non-device-based eyes had a greater statistically significant reduction in IOP (3.6 ± 1.3 mmHg) when compared to device-based eyes (.07 ± 1.3 mmHg). There was not a statistically significant difference regarding glaucoma medication burden change between the non-device-based eyes (.58 ± .20, 29.7% reduction) and the device-based eyes (.76 ± .19, 31.7% reduction) (p = .52). The occurrence of hyphema was not statistically significantly greater in device-based eyes compared to non-device-based eyes with the sample sizes in this study. The difference between IOP spikes in the two groups was not statistically significant.
Conclusion: Non-device-based MIGS procedures reduced the 12-month post-operative IOP more than the device-based MIGS procedures. There was not a statistically significant difference regarding glaucoma medication burden change between the study groups. Post-operative complications occurred at a similar frequency between the two groups.
Clinical Impact and Implications: The results of this study can help surgeons choose the appropriate MIGS procedure for their patients depending on the efficacy and safety profile.
Do Hispanic Patients Who Require a Medical Interpreter Understand the Severity of Their Glaucoma Diagnosis?
Authors: Bertot Sophia , Cantor Louis 
Published: December 2021

Background and Hypothesis: Glaucoma is a group of progressive optic neuropathies characterized by a degeneration of retinal ganglion cells with characteristic changes in the visual field. The Los Angeles Latino Eye Study (LALES) is the largest and most recent study to determine the prevalence of open-angle glaucoma in Hispanics; reported at nearly 5%. Between 2010 – 2019, Hispanic patients accounted for more than half of the United States population growth, reaching a record of 60.6 million Hispanics living in the United States. With an influx of Hispanic’s migrating to the United States, there is an increased need for medical interpreters to assist medical professionals in encounters with Hispanic patients. The success of a medical encounter relies on a multitude of factors, but when a medical interpreter is involved, the stakes are even higher. We hypothesize that Hispanic speaking patients will have lower rates of understanding their glaucoma diagnosis and severity, in comparison to English speaking patients due to gaps in translation provided by medical interpreters.
Project Methods: Native Spanish and native English-speaking patients from the Eskenazi Health Eye Clinic were recruited via phone, reminding them of their upcoming eye appointment and their eligibility to participate in the study. Interested patients were provided with information regarding the study and consent materials at the start of the medical encounter. Participants who consented were administered the survey at the end of their medical encounter, in their preferred language, in person, at the clinic.
Results: This is an ongoing prospective study.
Potential Impact: This study will determine if medical interpreters successfully relay all the necessary information regarding a Hispanic patient’s glaucoma diagnosis. This study could also provide a partial explanation as to why there is a high no show rate and high medication noncompliance rate within the Eskenazi Health Eye Clinic Hispanic population.
PGC1α protects against cisplatin-induced skeletal muscle dysfunction
Authors: Chatterjee Rohit , Huot Joshua , Pin Fabrizio , Bonetto Andrea 
Published: December 2021

Background and Hypothesis: We and others have shown that chemotherapy promotes skeletal muscle wasting and weakness (i.e., cachexia) by disrupting mitochondrial homeostasis and causing oxidative stress. Peroxisome proliferative-activated receptor gamma coactivator 1-alpha (PGC1α) is a pivotal regulator of mitochondrial biogenesis and is involved in reducing oxidative damage in skeletal muscle. Hence, in the present study we investigated whether overexpression of skeletal muscle PGC1α (mPGC1α) was sufficient to preserve skeletal muscle mass and function in young and old mice treated with cisplatin.
Experimental Design or Project Methods: Young (2-month; n = 5) and old (18-month; n = 5-8) male wild type (WT) or mPGC1α transgenic mice were treated with cisplatin (2.5mg/kg), while age-matched WT mice received vehicle for 2 weeks. Animals were assessed for muscle force and motor unit number estimation (MUNE). Skeletal muscles were weighed and processed for molecular analyses, including assessment of mitochondrial protein content.
Results: Young WT mice exposed to cisplatin showed evidence of cachexia, as indicated by reduced gastrocnemius size (-16%), plantarflexion force (-8%) and MUNE (-56%), whereas mPGC1α mice were only partially protected. Interestingly, despite exacerbated cachexia in aged WT mice treated with chemotherapy, as demonstrated by markedly decreased gastrocnemius size (-22%), plantarflexion force (-18%) and MUNE (-80%) compared to untreated WT, muscle mass, strength and innervation were fully preserved in age-matched mPGC1α mice. Follow-up molecular analyses revealed that WT animals exposed to chemotherapy present loss of muscle mitochondrial proteins PGC1α, OPA1 and CytochromeC, whereas their levels in mPGC1α mice were robustly increased.
Conclusion and Potential Impact: Altogether, our data suggest that PGC1α plays a pivotal role in preserving skeletal muscle mass and function, usually impaired by anticancer treatments. These findings enforce developing mitochondria-targeting therapeutics to combat the negative consequences that chemotherapy has on skeletal muscle.
Non-Invasive Myocardial Infarction Ischemic Area Estimation Through Four-Dimensional Ultrasound
Authors: Clark Sydney Q. , Earl Conner C. , Gruber Joseph M. , Annamalai Karthik S. , Schepers Luke E. , Goergen Craig J. 
Published: December 2021

Background/Objective: Following myocardial infarction, infarct size and cardiac function are significant predictors of long-term prognosis. Most echocardiography studies rely on two-dimensional analysis for estimation of left ventricular function and electrical activity analysis for estimation of infarct area. Other imaging modalities, such as cardiac magnetic resonance imaging, are limited by time, cost, availability, patient tolerance, and incompatible implantable devices. Using an experimental mouse model of myocardial infarction, we hypothesize that four-dimensional ultrasound offers a possible alternative for easy, quick, and reliable estimation of infarct size.
Methods: A cohort of 10 mice underwent four-dimensional cardiac imaging at baseline using a small animal high frequency ultrasound. A thoracotomy was subsequently performed, and a suture placed to ligate the left coronary artery approximately midway down the left ventricle. Sequential four-dimensional ultrasound was performed at six time points over 28 days, following which the mice were euthanized. The hearts were then removed and sent for embedding and sectioning into seven uniform segments stained using both H&E and Masson’ s Trichrome.
Results: Thus far, we have segmented the imaging and collected end diastolic volume, peak systolic volume, stroke volume, ejection fraction, transmural thickness, and circumferential strain. Additionally, four-dimensional models of the left ventricles have been rendered. Histological embedding, sectioning, and staining is still in progress, and therefore validation against the gold standard is still in process.
Conclusion and Impact: Treatment and monitoring of myocardial infarction patients is reliant upon accurate assessment of patient status and prognosis. This study provides initial evidence for the validity of four-dimensional ultrasound as a tool for estimation of myocardial infarction size, providing an alternative to current two-dimensional methods that are less accurate and a more accessible alternative to highly specialized and costly equipment. Improved and accessible imaging methods have the potential to enhance patient care, ultimately improving overall health outcomes.
The Influence of Medial Collateral Ligament and Lateral Collateral Ligament Pie Crusting in Primary Total Knee Arthroplasty on Patient Reported Outcomes
Authors: Cornwell Ethan , Deckard Evan R. , Sonn Kevin A. , Meneghini R. Michael 
Published: December 2021

Background and Hypothesis: Pie-crusting of the collateral ligaments can help achieve balanced gaps in total knee arthroplasty (TKA) in knees with varus or valgus deformity. However, the effect of this technique on patient-reported outcome measures (PROMs) is unknown. The purpose of this study was to compare PROMs following primary TKA for patients with and without medial collateral ligament (MCL) or lateral collateral ligament (LCL) pie-crusting.
Experimental Design or Project Methods: We retrospectively reviewed 1,305 primary TKAs. Intraoperative MCL or LCL pie-crusting was documented in all operative reports and recorded. Prospectively collected preoperative, 4-month postoperative, and minimum 1-year postoperative PROMs related to overall knee health, pain during functional activities, activity level, and overall satisfaction were compiled and compared between patients with and without MCL or LCL pie-crusting. Medians were evaluated with Kruskal-Wallis test adjusted for ties.
Results: The cohort was 67% female with mean age 66 years and BMI 34.0 kg/m2. MCL or LCL pie-crusting was performed in 13.0% of the cohort. There were no intraoperative or postoperative ruptures of the MCL or LCL. 6.3% of conforming bearing TKAs required a collateral ligament pie crusting versus 21.5% of standard bearing TKA (p<0.001). No significant differences were found in preoperative, 4-month, minimum 1-year, or change from preoperative baseline to minimum 1-year PROMs with and without pie-crusting of the collateral ligaments (p≥0.095). However, the LCL pie-crusting group had slightly better PROMs at minimum 1-year.
Conclusion and Potential Impact: These study results corroborate existing literature that pie-crusting of collateral ligaments is safe and effective to achieve a balanced TKA. Additionally, no significant outcome differences were found between groups with and without MCL or LCL pie-crusting. However, LCL pie-crusting for valgus knee correction had slightly better PROMs. Interestingly, conforming bearings may impart enhanced stability and mitigate the need for pie-crusting ligament releases in TKA.
Quality Improvement Initiative: Foley Catheters in Patients Undergoing Pectus Deformity Repair
Authors: Crabtree Jordan , Marke Troy 
Published: December 2021

Background and Hypothesis: Pectus excavatum and carinatum are sternal deformities that often require surgeries with significant postoperative pain that can limit a patient’s ability to void. An indwelling urinary catheter is placed for the operation, but is often removed on the first postoperative day due to concerns of infection, which begs the necessity of these catheters in the first place. In this study, we hypothesized that there would be no increased risk of urinary retention or urinary tract infection irrespective of whether urinary catheters were utilized.
Experimental Design: A pre/post quality improvement study was undertaken of patients undergoing pectus excavatum/carinatum repair between June 1, 2015 and May 31, 2022. The pre intervention group spanned from June 1, 2015 to May 31, 2021, where Foley catheters were placed intraoperatively and removed the first postoperative day. Pediatric surgery and anesthesia groups changed practice effective June 1, 2021 and decided to no longer utilize urinary catheters in pectus repairs. Pre-intervention patients were acquired through the surgery billing database. Post-intervention patients were acquired prospectively. Rates of urinary retention (any event requiring mechanical intervention for voiding) and urinary tract infections (UTI, >100,000 CFU bacteria/mL urine) were compiled into REDCap. Data are expressed as percent of the total cohort.
Results: Of 179 patients undergoing pectus repair (162 Excavatum, 17 Carinatum), 12 patients (6.7%) in the pre-intervention group experienced urinary retention. Of these, 9 received in/out catheterization, 1 had a Foley catheter replaced, and 2 underwent in/out catheterization and had a Foley replaced. There were no urinary tract infections recorded among the pre-intervention group.
Conclusion and Potential Impacts: Urinary retention and UTI are rare in patients who have an indwelling urinary catheter. Data acquired over the next year from the post-intervention group will help determine the true necessity for these catheters in the perioperative pectus population.
Development of Automated Angiogram Labeling via AI Active Learning Pipeline
Authors: Kersey Kolten , Gonzalez Andrew 
Published: December 2021

Background and Objective: As technology is integrated further into medicine, more specialties are discovering new uses for it in their clinical practice. However, the tasks that we want technology to complete are often removed from developer’s intended tasks. A field of research is growing that integrates medicine with current AI technology to bridge the gap and utilize already existing technology for medical uses. We desire to use an active learning pipeline (a form of machine learning) to automate the labeling of blood vessels on angiograms and potentially develop the ability to detect occlusions. By using machine learning, it would essentially allow the machine to teach itself with human guidance.

Methods: A machine learning pipeline is in development for automation of the process. To create a baseline for the machine to start learning, the first set of angiograms are being labeled by hand using the program 3D Slicer. For the first pass, we have been quickly labeling the blood vessels by changing the color sensitivity threshold to highlight the darker blood vessels juxtaposed next to lighter tissue. For the second pass, we have erased any erroneous highlighting that was picked up in the first pass such as tools, tissue, contrast outside the injection site, and sutures. For the third pass, we have labeled and segmented the arteries into specific vessels such as femoral, common iliac, internal iliac, etc. This will then be entered into the machine for automated learning.

Results: We are in the process of labeling the initial image set.

Potential Impact: By creating a lab for angiogram automation, it will allow physicians to efficiently search images for specific arteries and save valuable time usually spent searching images. This would also allow for automated labeling of occlusions that a physician could then look at to verify.