bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine storm associated with severe COVID‐19 infections: The potential mitigating role of omega‐3 fatty acid triglycerides in the ICU
Authors: Driscoll David F. , Bistrian Bruce R. 
Published: June 2023

AbstractCytokine storm during severe COVID‐19 infection increases the risk of mortality in critically ill patients in the intensive care unit. Multiple therapeutic proposals include, for example, anti‐inflammatory and immunosuppressive agents, selective inhibitors of key pro‐inflammatory receptors, and key enzymes necessary for viral replication. Unfortunately, safe and effective therapy remains an elusive goal. An alternative anti‐inflammatory approach vis á vis omega‐3 fatty acids, which yields less pro‐inflammatory mediators by altering eicosanoid metabolism, has been proposed. Although theoretically promising, enteral tube delivery or oral capsules containing specific doses of omega‐3 fatty acids take precious time (7 days to 6 weeks) to be incorporated in plasma cell membranes to be most effective, making this route of administration in the acute care setting an unfeasible therapeutic approach. Parenteral administration of precise doses of omega‐3 fatty acid triglycerides in an injectable emulsion can greatly accelerate the incorporation and potential therapeutic effects (within hours), but at present, there is no commercially available product designed for this purpose. We describe a potential formulation that may address this deficiency, while recognizing that the high incidence of hyperlipidemia that occurs during severe COVID‐19 infection must be recognized as a complicating factor, and, therefore, caution is advised.
Pediatric Lateral Humeral Condyle Fractures: Reliability of a Modified Jakob Classification System and its Impact on Treatment Planning With or Without Arthrography
Authors: Miller Joseph S. , Weishuhn Luke , Goodrich Eric , Patel Jay , McCarthy James J. , Mehlman Charles T. 
Published: June 2023

Background:
Various lateral humeral condyle fracture (LHCF) classification systems have been in use since the 1950s, but limited research exists on their reliability. The most widely utilized, yet un-validated system is that of Jakob and colleagues. The purpose of the current study was to analyze the reliability of a modified Jakob classification system and its value in guiding treatment either with or without arthrography.

Methods:
Interrater and intrarater reliability studies were performed using radiographs and arthrograms from 32 LHCFs. Radiographs were presented to 3 pediatric orthopaedic surgeons and 6 pediatric orthopaedic surgery residents who were asked to classify the fractures according to a modified Jakob classification system, enunciate their treatment plan, and whether they would utilize arthrography. Classification was repeated within 2 weeks to assess intrarater reliability. The treatment plan using radiographs only and radiographs with arthrography were compared at both rating points.

Results:
The modified Jakob system had excellent interrater reliability using only radiographs with a kappa value of 0.82 and an overall agreement of 86%. The average kappa for intrarater reliability using only radiographs was 0.88 with a range of 0.79 to 1.00 and an average overall agreement of 91% with a range of 84% to 100%. Interrater and intrarater reliability was poorer using both radiographs and arthrography. On average, arthrography changed the treatment plan in 8% of cases.

Conclusions:
The modified Jakob classification system proved to be a reliable classification system for LHCFs, independent of arthrography, given the excellent free-marginal multirater kappa values.

Level of Evidence:
Level III—diagnostic.
Cast or Nail? Using a Preference-Based Tool for Shared Decision-Making in Pediatric Femoral Shaft Fracture Treatment
Authors: Catanzano Anthony A. , Hutyra Carolyn , Risoli Thomas J. , Green Cynthia L. , Mather R. Chad , Alman Benjamin 
Published: June 2023

Background:
Femoral shaft fractures are common injuries in children 2 to 7 years of age, with treatments ranging from casting to flexible intramedullary nails (FIN). Each treatment has unique attributes and outcomes are overall similar. Given equivalent outcomes, we hypothesized that a shared decision-making process, using adaptive conjoint analysis (ACA), can be used to assess individual family situations to determine ultimate treatment choice.

Methods:
An interactive survey incorporating an ACA exercise to elicit the preferences of individuals was created. Amazon Mechanical Turk was used to recruit survey respondents simulating the at-risk population. Basic demographic information and family characteristics were collected. Sawtooth Software was utilized to generate relative importance values of five treatment attributes and determine subjects’ ultimate treatment choice. Student’s t-test or Wilcoxon rank sum test was used to compare relative importance between groups.

Results:
The final analysis included 186 subjects with 147 (79%) choosing casting as their ultimate treatment choice, while 39 (21%) chose FIN. Need for second surgery had the highest overall average relative importance (42.0), followed by a chance of serious complications (24.6), time away from school (12.9), effort required by caregivers (11.0), and return to activities (9.6). Most respondents (85%) indicated the generated relative importance of attributes aligned “very well or well” with their preferences. For those who chose casting instead of FIN, the need for secondary surgery (43.9 vs. 34.8, P<0.001) and the chance of serious complications (25.9 vs. 19.6, P<0.001) were the most important factors. In addition, returning to activities, the burden to caregivers, and time away from school were all significantly more important to those choosing surgery versus casting (12.6 vs. 8.7 P<0.001, 12.6 vs. 9.8 P=0.014, 16.6 vs. 11.7 P<0.001, respectively).

Conclusions:
Our decision-making tool accurately identified subjects’ treatment preferences and appropriately aligned them with a treatment decision. Given the increased emphasis on shared decision-making in health care, this tool may have the potential to improve shared decision-making and family understanding, leading to improved satisfaction rates and overall outcomes.

Level of Evidence:
Level—III.
Assessing Factors Influencing Commitment to a Disparities Reduction Intervention: Social Justice Attitudes and Organizational Mission
Authors: Marsteller Jill A. , Hsu Yea-Jen , Weeks Kristina , Oduwole Modupe , Boonyasai Romsai T. , Avornu Gideon D. , Dietz Katherine B. , Zhou Zehui , Brown Deven , Hines Anika , Chung Suna , Lubomski Lisa , Carson Kathryn A. , Ibe Chidinma , Cooper Lisa A. ,   for the RICH LIFE Project Investigators
Published: June 2023

ABSTRACT
This mixed-methods study aims to understand what the perceptions of leaders and healthcare professionals are regarding causes of disparities, cultural competence, and motivation before launching a disparity reduction project in hypertension care, contrasting perceptions in Federally Qualified Health Centers (FQHCs), and in a non-FQHC system. We interviewed leaders of six participating primary care systems and surveyed providers and staff. FQHC respondents reported more positive cultural competence attitudes and behavior, higher motivation to implement the project, and less concern about barriers to caring for disadvantaged patients than those in the non-FQHC practices; however, egalitarian beliefs were similar among all. Qualitative analysis suggested that the organizational missions of the FQHCs reflect their critical role in serving vulnerable populations. All system leaders were aware of the challenges of provider care to underserved groups, but comprehensive initiatives to address social determinants of health and improve cultural competence were still needed in both system types. The study provides insights into the perceptions and motivations of primary care organizational leaders and providers who are interested in improving chronic care. It also offers an example for care disparity programs to understand commitment and values of the participants for tailoring interventions and setting baseline for progress.
Can the Buffalo Concussion Treadmill Test Be Used as a Prognostic Indicator for Patients With Sport-Related Mild Traumatic Brain Injury?
Authors: Kumar Amitesh , Kara Stephen , van der Werf Bert , Fulcher Mark 
Published: June 2023

Objective:
To establish whether time to exercise cessation using the Buffalo Concussion Treadmill Test (BCTT) protocol can be used as a prognostic indicator of recovery after sport-related mild traumatic brain injury (SR-mTBI).

Design:
Retrospective analysis of prospectively collected data.

Setting:
Specialist Concussion Clinic.

Participants:
Three hundred and twenty one patients presenting between 2017 and 2019 who underwent BCTT for SR-mTBI.

Interventions:
Participants who remained symptomatic at a 2-week follow-up appointment after SR-mTBI underwent BCTT to develop a progressive subsymptom threshold exercise program with fortnightly follow-up until clinical recovery.

Main Outcome Measures:
Clinical recovery was the primary outcome measure.

Results:
A total of 321 participants were eligible to participate in this study (mean age 22.94% and 46% female). The BCTT test duration was divided into 4-minute intervals and those who completed full 20 minutes. There was higher probability of clinical recovery in those who finished the entire 20-minute BCTT protocol compared with those who managed 17–<20 minutes (Hazard Ratio, HR 0.57), 13 to 16 minutes (HR 0.53), 9 to 12 minutes (HR 0.6), 5 to 8 minutes (HR 0.4), and 1 to 4 minutes (HR 0.7), respectively. Those seen earlier after injury (P = 0.009), male patients (P = 0.116), younger patients (P = 0.0003), and those with physiological or cervical dominant (P = 0.416) symptom clusters were more likely to achieve clinical recovery. Fifty percent of those who completed the full BCTT protocol achieved clinical recovery at day 19 post‐injury.

Conclusions:
The group completing full 20 minutes of BCTT achieved clinical recovery more quickly than those who did not complete full BCTT.
Dynamics of Serum CA19-9 in Patients Undergoing Pancreatic Cancer Resection
Authors: van Oosten A.F. , Groot V.P. , Dorland G. , Burkhart Richard A. , Wolfgang C.L. , van Santvoort H.C. , He J. , Molenaar I.Q , Daamen L.A. 
Published: June 2023

Background:
Carbohydrate antigen (CA) 19-9 is an established perioperative prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). However, it is unclear how CA19-9 monitoring should be used during postoperative surveillance to detect recurrence and to guide the initiation of recurrence-focused therapy.

Objective:
This study aimed to elucidate the value of CA19-9 as a diagnostic biomarker for disease recurrence in patients who underwent PDAC resection.

Methods:
Serum CA19-9 levels at diagnosis, after surgery, and during postoperative follow-up were analyzed in patients who underwent PDAC resection. All patients with at least two postoperative follow-up CA19-9 measurements prior to recurrence were included. Patients deemed to be non-secretors of CA19-9 were excluded. The relative increase in postoperative CA19-9 was calculated for each patient by dividing the maximum postoperative CA19-9 value by the first postoperative value. Receiver operating characteristic (ROC) analysis was performed to identify the optimal threshold for the relative increase in CA19-9 levels to identify recurrence in the training set using Youden’s index. The performance of this cutoff was validated in a test set by calculating the area under the curve (AUC) and was compared to the performance of the optimal cutoff for postoperative CA19-9 measurements as a continuous value. In addition, sensitivity, specificity, and predictive values were assessed.

Results:
In total, 271 patients were included, of whom 208 (77%) developed recurrence. ROC analysis demonstrated that a relative increase in postoperative serum CA19-9 of 2.6x was predictive of recurrence, with 58% sensitivity, 83% specificity, 95% positive predictive value, and 28% negative predictive value. The AUC for a 2.6x relative increase in CA19-9 level was 0.719 in the training set and 0.663 in the test set. The AUC of postoperative CA19-9 as a continuous value (optimal threshold, 52) was 0.671 in the training set. In the training set, the detection of a 2.6-fold increase in CA19-9 preceded the detection of recurrence by a mean difference of 7 months (P<0.001) and in the test set by 10 months (P<0.001).

Conclusion:
A relative increase in postoperative serum CA19-9 level of 2.6-fold is a stronger predictive marker for recurrence than a continuous CA19-9 cutoff. A relative CA19-9 increase can precede the detection of recurrence on imaging for up to 7–10 months. Therefore, CA19-9 dynamics can be used as a biomarker to guide the initiation of recurrence-focused treatment.
Predicting Outcomes Following Endovascular Abdominal Aortic Aneurysm Repair Using Machine Learning
Authors: Li Ben , Verma Raj , Beaton Derek , Tamim Hani , Hussain Mohamad A , Hoballah Jamal J , Lee Douglas S , Wijeysundera Duminda N , de Mestral Charles , Mamdani Muhammad , Al-Omran Mohammed 
Published: June 2023

Objective:
To develop machine learning (ML) models that predict outcomes following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA).

Summary Background Data:
EVAR carries non-negligible peri-operative risks; however, there are no widely used outcome prediction tools.

Methods:
The National Surgical Quality Improvement Program targeted database was used to identify patients who underwent EVAR for infrarenal AAA between 2011-2021. Input features included 36 pre-operative variables. The primary outcome was 30-day major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death). Data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 ML models were trained using pre-operative features. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. Subgroup analysis was performed to assess model performance based on age, sex, race, ethnicity, and prior AAA repair.

Results:
Overall, 16,282 patients were included. The primary outcome of 30-day MACE occurred in 390 (2.4%) patients. Our best performing prediction model was XGBoost, achieving an AUROC (95% CI) of 0.95 (0.94-0.96) compared to logistic regression [0.72 (0.70 – 0.74)]. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.06. Model performance remained robust on all subgroup analyses.

Conclusions:
Our newer ML models accurately predict 30-day outcomes following EVAR using pre-operative data and perform better than logistic regression. Our automated algorithms can guide risk mitigation strategies for patients being considered for EVAR.
Diagnosing Left Bundle Branch Block in 12-lead Electrocardiogram using Self-Attention Convolutional Neural Networks
Authors: Sadeghi Alireza , Rezaee Alireza , Hajati Farshid 
Published: June 2023

ABSTRACTThe left bundle branch block is a cardiac conduction disorder that affects the heart’s electrical system. It causes the left ventricle of the heart to contract later than the right ventricle, leading to an irregular heartbeat. The diagnosis of left bundle branch block is crucial in determining the most effective treatment for heart irregularities, including cardiac resynchronization therapy. Cardiac resynchronization therapy uses a pacemaker-like device to resynchronize the heart’s contractions and improve its function. However, diagnosing left bundle branch block accurately can be challenging using traditional diagnostic methods that rely on electrocardiograms. This study introduces Self-Attention Convolutional Neural Networks for the detection of left bundle branch block from 12-lead electrocardiograms data using SE-Residual blocks and a self-attention mechanism to highlight important input data features for more accurate diagnosis of left bundle branch block. The model is trained and validated on a database of 10,344 12-lead electrocardiogram samples using a 10-fold cross-validation approach. The results demonstrate an accuracy of 98.91% ± 0.1%, specificity of 99.28% ± 0.15%, precision of 73.09% ± 3.5%, recall or sensitivity of 82.83% ± 4.34%, F1 score of 77.5% ± 1.59%, and area under the receiver operating characteristics curve of 0.91 ± 0.02. The experimental results demonstrate that the proposed deep learning model achieves high accuracy, specificity, and F1 score. These findings suggest that the proposed model can serve as an effective diagnostic tool for identifying left bundle branch block with a high level of efficiency, improving the diagnostic process, and promoting early treatment in medical settings.
Identification of cross-reacting IgG hotspots to prevent immune evasion of SARS-CoV-2 variants
Authors: Harhala Marek , Gembara Katarzyna , Baniecki Krzysztof , Pikies Aleksandra , Nahorecki Artur , Jędruchniewicz Natalia , Kaźmierczak Zuzanna , Rybicka Izabela , Klimek Tomasz , Witkiewicz Wojciech , Barczyk Kamil , Kłak Marlena , Dąbrowska Krystyna 
Published: June 2023

AbstractThe major factor that shapes the global perspective for increase or diminution of successive pandemic waves of COVID-19 is the immunological protection. The SARS-CoV-2 virus constantly develops new variants, and capability of immune evasion is among the major factors that promote variant spreading in the human population. After two years of the pandemic and virus evolution, it is almost impossible to explain effects of all possible combinations different viral strains, a few types of vaccinations or new variants infecting an individual patient. Instead of variant-to-variant comparisons, identification of key protein regions linked to immune evasion could be efficient.Here we report an approach for experimental identification of SARS-CoV-2 protein regions that (i) have characteristics of cross-reacting IgG hot-spots, and (ii) are highly immunogenic. Cross-reacting IgG hot spots are regions of protein frequently recognized in many variants by cross-reacting antibodies. Immunogenic regions efficiently induce specific IgG production in SARS-CoV-2 infected patients. We determined four regions that demonstrate both significant immunogenicity and the activity of a cross-reacting IgG hot-spot in protein S, and two such regions in protein N. Their distribution within the proteins suggests that they may be useful in vaccine design and in serological diagnostics of COVID-19.
Limited effects of dehydration on object discrimination in the novel object recognition paradigm in young and middle-aged male and female rats
Authors: Santollo Jessica , Rainer Ivanka L. , Swanz Lillian , Steineker Madelyn H. , Holla Sahana 
Published: June 2023

AbstractDehydration is associated with impaired cognitive function in humans. Limited animal research also suggests that disruptions in fluid homeostasis impair performance in cognitive tasks. We previously demonstrated that extracellular dehydration impaired performance in the novel object recognition memory test in a sex and gonadal hormone specific manner. The experiments in this report were designed to further characterize the behavioral effects of dehydration on cognitive function in male and female rats. In Experiment 1, we tested whether dehydration during the training trial in the novel object recognition paradigm would impact performance, while euhydrated, in the test trial. Regardless of hydration status during training, all groups spent more time investigating the novel object during the test trial. In Experiment 2, we tested whether aging exacerbated dehydration-induced impairments on test trial performance. Although aged animals spent less time investigating the objects and had reduced activity levels, all groups spent more time investigating the novel object, compared to the original object, during the test trial. Aged animals also had reduced water intake after water deprivation and, unlike the young adult rats, there was no sex difference in water intake. Together these results, in combination with our previous findings, suggest that disruptions in fluid homeostasis have limited effects on performance in the novel object recognition test and may only impact performance after specific types of fluid manipulations.
Inhibition of auxin biosynthesis in early rice grains leads to extensive post-fertilisation grain abortion
Authors: Basunia Mafroz A. , Nonhebel Heather M. , Backhouse David , McMillan Mary 
Published: June 2023

AbstractIn spite of its abundant presence in rice grains, auxin functions during grain development are not understood well. Absence of grain-specific auxin biosynthesis mutants in rice further limits our understanding in this respect. Here, we report a chemical biology approach to inhibit auxin biosynthesis specifically in early rice grains as well as its subsequent effects on final grain yield. Exogenous application of two auxin biosynthesis inhibitors, namely L-kynurenine (L-Kyn) and 4-phenoxyphenylboronic acid (PPBo), to spikelets daily from three to ten days after pollination (DAP) significantly reduced grain levels of indole-3-acetic acid (IAA), the predominantin plantaauxin. The inhibitor-treated panicles showed extensive post-fertilisation seed abortion, leading to drastic reduction in total panicle weight at maturity. Locally synthesised auxin during early grain development may therefore play a crucial role in grain retention. This chemical biology approach can be an easy and cost-effective way to study auxin biosynthesis and signalling during grain development in rice and possibly other cereal crops.HighlightAuxin synthesised in early rice grains may play a crucial role in grain retention.
Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM2.5and Neuropathology Markers of Alzheimer’s Disease
Authors: Li Zhenjiang , Liang Donghai , Ebelt Stefanie , Gearing Marla , Kobor Michael S. , Konwar Chaini , Maclsaac Julie L. , Dever Kristy , Wingo Aliza , Levey Allan , Lah James J. , Wingo Thomas , Huels Anke 
Published: June 2023

AbstractINTRODUCTIONGrowing evidence indicates fine particulate matter (PM2.5) as risk factor for Alzheimer’s’ disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association.METHODSWe assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors’ residential traffic-related PM2.5exposure 1, 3 and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs.RESULTSPM2.5was significantly associated with differential DNAm at cg25433380 and cg10495669. Twenty-six CpG sites were identified as mediators of the association between PM2.5exposure and neuropathology markers, several located in genes related to neuroinflammation.DISCUSSIONOur findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM2.5and AD.