bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescribing Practices for Agitation Medication in Obese Patients Admitted to the Emergency Department
Authors: Kang Connie , Williams Andrew , Butala Niyati 
Published: September 2023

Introduction:
Weight is a factor that influences the dosages of many medications, although no clinical studies have evaluated this factor in the use of agitation medications in the obese population. The objectives of this study were to assess the need for weight considerations in dosing antipsychotics and benzodiazepines for patients with agitation and to assess prescribing patterns in agitated patients.

Methods:
This retrospective cohort study compared outcomes between obese and nonobese adult patients who received at least one parenteral administration of an antipsychotic or benzodiazepine for agitation in the emergency department. The primary outcomes were total antipsychotic and benzodiazepine doses within 24 hours (in chlorpromazine equivalents and lorazepam equivalents, respectively). Key secondary outcomes included antipsychotic and benzodiazepine doses used for first administration, incidence of repeat emergency medication administration within 24 hours, time to next administration, and number of repeat administrations within 24 hours.

Results:
The study examined 115 patient encounters in each cohort of patients in the study. The baseline characteristics of the 2 study cohorts were similar. Both groups had similar mean 24-hour antipsychotic usage [272.7 chlorpromazine equivalents (nonobese cohort), 313.5 chlorpromazine equivalents (obese cohort); P=0.157] and mean 24-hour benzodiazepine usage [0.9 lorazepam equivalents (both cohorts); P=0.750]. Differences between the study cohorts on all of the secondary outcomes were also not statistically significant (P>0.05).

Discussion:
This study did not find the use of higher dosages of agitation medication in the obese compared with the nonobese population. Future prospective trials, with possible emphasis on individual medications, specific etiologies of agitation, or morbid obesity, are required to confirm this finding or to elucidate potential differences in optimal medication dosages for the obese population.
Acute respiratory distress syndrome, acute kidney injury, and mortality after trauma are associated with increased circulation of syndecan-1, soluble thrombomodulin, and receptor for advanced glycation end products
Authors: Dixon Alexandra , Kenny James E. , Buzzard Lydia , Holcomb John , Bulger Eileen , Wade Charles , Fabian Timothy , Schreiber Martin ,   the PROPPR Study Group
Published: September 2023

Abstract

Background
Disruption of the vascular endothelium and endothelial glycocalyx (EG) has been described after severe trauma. Plasma has been suggested to restore microvascular integrity by preservation and repair of the EG. We sought to evaluate whether plasma administered in a 1:1:1 ratio was associated with less endothelial marker circulation than a 1:1:2 ratio.

Methods
This is a secondary analysis of the PROPPR trial which investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Syndecan-1, soluble thrombomodulin (sTM), and receptor for advanced glycation end products (RAGE) were quantified for each treatment group on admission and at 2, 4, 6, 12, 24, 48, and 72 hours. Patients were excluded if they did not survive longer than 3 hours or had data from fewer than two time points.

Results
308 patients in the 1:1:1 group and 291 in the 1:1:2 group were analyzed. There were no statistically significant differences in syndecan-1, sTM, or RAGE between treatment groups at any time point (p > 0.05). Patients who developed acute respiratory distress syndrome, acute kidney injury, and death had significantly elevated biomarker expression at most time points when compared to patients who did not develop these sequelae (p < 0.05).

Conclusions
Administration of FFP in a 1:1:1 ratio does not consistently affect circulation of endothelial biomarkers following significant trauma when compared to a 1:1:2 ratio. The development of post-traumatic ARDS, AKI, and death was associated with increased endothelial biomarker circulation.

Level of Evidence
Secondary analysis of Level I evidence
Balanced resuscitation with whole blood versus component therapy in critically injured preadolescent children: Getting there faster with fewer exposures
Authors: McLoughlin Robert J. , Josephson Cassandra D. , Neff Lucas P. , Chandler Nicole M. , Gonzalez Raquel , Russell Robert T. , Snyder Christopher W. 
Published: September 2023

PURPOSE
Balanced blood product resuscitation with red blood cells, plasma, and platelets can be achieved using whole blood (WB) or component therapy (CT). However, balanced resuscitation of younger children with severe traumatic hemorrhage may be complicated by delays in delivering all blood components and concerns regarding multiple product exposures. We hypothesized that WB achieves balanced resuscitation faster than CT, with fewer product exposures and improved clinical outcomes.

METHODS
Children younger than 12 years receiving balanced resuscitation within 4 hours of arrival were identified from the 2017 to 2019 Trauma Quality Improvement Program database. Time to balanced resuscitation was defined as the time of initiation of WB or all three components. Patient characteristics, resuscitation details, and outcomes were compared between WB and CT groups. Time to balanced resuscitation was compared using Kaplan-Meier analysis and Cox regression modeling to adjust for covariates. Additional multivariable regression models compared number of transfusion exposures, intensive care unit (ICU) length of stay, and mortality.

RESULTS
There were 390 patients (109 WB, 281 CT) with median age 7 years, 12% penetrating mechanism, 42% severe traumatic brain injury, and 49% in-hospital mortality. Time to balanced resuscitation was shorter for WB versus CT (median, 28 vs. 87 minutes; hazard ratio [HR], 2.93; 95% confidence interval [CI], 2.31–3.72; p < 0.0001). Whole blood patients received fewer transfusion exposures (mean, 3.2 vs. 3.9; adjusted incidence rate ratio, 0.82; 95% CI, 0.72–0.92; p = 0.001) and lower total product volumes (50 vs. 85 mL/kg; p = 0.01). Intensive care unit stays trended shorter for WB versus CT (median, 10 vs. 12 days; adjusted HR, 1.32; 95% CI, 0.93–1.86), while in-hospital mortality was similar (50% vs. 45%; adjusted odds ratio, 1.11; 95% CI, 0.65–1.88).

CONCLUSION
In critically injured preadolescent children receiving emergent transfusion, WB was associated with faster time to balanced resuscitation, fewer transfusion exposures, lower blood product volumes, and a trend toward shorter ICU stays than CT.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Emergency general surgery verification: Quality improvement and the case for optimal resources and process standards
Authors: Coleman Jamie J. , Davis Kimberly A. , Savage Stephanie A. , Staudenmayer Kristin , Coimbra Raul 
Published: September 2023

ABSTRACT
Patients with emergency general surgery (EGS) diagnoses comprise over 10% of all hospital admissions, resulting in a projected number of 4.2 million admissions for 2023. Approximately 25% will require emergency surgical intervention, half will sustain a postoperative complication, and 15% will have a readmission within the first 30 days of surgery. In the face of this growing public health burden and to better meet the needs of these acutely ill patients, it was recognized that a formal quality improvement program, including standardization of data collection and the development of systems of care specifically for EGS have been lacking. Establishing standardized processes for quality improvement, including a national databank, and maintaining adherence to these processes as ensured by a robust verification process has improved outcomes research and patient care in the field of trauma, another time-sensitive specialty. In response to this perceived deficit, the “Optimal Resources for Emergency General Surgery” was developed. An extension of the current National Surgical Quality Improvement Program platform, specifically for operative and non-operative EGS cases, was developed and implemented. A robust set of standards were outlined to verify EGS programs/services. Defining the elements of an effective EGS program and developing hospital and practice standards consolidated EGS as an integral component of Acute Care Surgery. The verification program addresses a societal need and allows hospitals to better organize EGS care delivery and benchmark their results nationally.
Assessing variation inCitrus limon‘Assam lemon’: morphological, seed availability pattern, and biochemical diversity across different districts of Assam
Authors: Akhtar Suraiya , Ahmed Raja , Begum Khaleda , Das Ankur , Saikia Sarat , Banu Sofia 
Published: September 2023

AbstractThe Assam lemon is a highly valuedCitruscultivar known for its unique aroma, flavor, and seedless fruit characteristic. This study aimed to investigate for the first time the morphological, seeding pattern, and biochemical, variations within 133 populations of Assam lemon cultivar growing across 22 districts of Assam, India, and including control population, with the objective to offer comprehensive understanding that could facilitate the improvement of breeding programs and further improvement of this important cultivar. Using the dendrogram-based UPGMA algorithm, morphological and seeding pattern data were analyzed at both district and population levels. The resulting dendrograms revealed two major clusters, where all the populations of Upper Assam districts were in the same cluster with the original stock (control population). However, populations from Tinsukia and Dhemaji districts displayed more close similarities with the control population in comparison to other populations of Upper Assam districts. Another interesting observation was regarding flowering patterns, while some populations displayed both bisexual and unisexual flowers with less concentration of unisexual flowers, others had bisexual and unisexual flowers of almost equal concentration. Unisexual flowers contained only the male reproductive organs with 40 anthers, while bisexual flowers had 36 anthers. Seeding patterns were examined across the districts, and it was found that populations from Tinsukia, Dhemaji, Lakhimpur, Dibrugarh, Jorhat, and the control population exhibited seedless characteristic while populations from other selected districts displayed a combination of seedless and seeded traits. Interestingly, Golaghat district appears as the linking district and showed availability of both seeded and seedless Assam lemon fruit, connecting the regions of Upper, Central, Lower and North Assam and Barak valley. Biochemical analysis showed significant variations across districts, however, the populations from Dhemaji, Tinsukia, Lakhimpur, Dibrugarh, and Jorhat districts displayed similarity with the control population. The study also investigated variability in soil nutrient content revealing substantial variation among the populations studied, potentially influencing observed morphological variations. This comprehensive investigation provides valuable insights into the morphological, seeding pattern, and biochemical diversity within the Assam lemon cultivar. These findings can be instrumental in breeding programs to enhance thisCitruscultivar, particularly in producing high-quality seedless fruits to meet consumer demands.
G-PLIP: Knowledge graph neural network for structure-free protein-ligand bioactivity prediction
Authors: Crouzet Simon J. , Lieberherr Anja Maria , Atz Kenneth , Nilsson Tobias , Sach-Peltason Lisa , Müller Alex T. , Dal Peraro Matteo , Zhang Jitao David 
Published: September 2023

AbstractProtein-ligand interaction (PLI) shapes efficacy and safety profiles of small molecule drugs. Existing methods rely on either structural information or resource-intensive computation to predict PLI, making us wonder whether it is possible to perform structure-free PLI prediction with low computational cost. Here we show that a light-weight graph neural network (GNN), trained with quantitative PLIs of a small number of proteins and ligands, is able to predict the strength of unseen PLIs. The model has no direct access to structural information of protein-ligand complexes. Instead, the predictive power is provided by encoding the entire chemical and proteomic space in a single heterogeneous graph, encapsulating primary protein sequence, gene expression, protein-protein interaction network, and structural similarities between ligands. The novel model performs competitively with or better than structure-aware models. Our observations suggest that existing PLI-prediction methods may be further improved by using representation learning techniques that embed biological and chemical knowledge.
Diet-induced plasticity of life-history traits and gene expression in outbredDrosophila melanogasterpopulation
Authors: Mudunuri Akhila , Chandrakanth M , Khan Soumen , Sura Chand , Kumar Nishant , Tung Sudipta 
Published: September 2023

AbstractFood is fundamental for the survival of organisms, governing growth, maintenance, and reproduction through the provision of essential macronutrients. However, access to food with optimum macronutrient composition, which will maximize the evolutionary fitness of an organism, is not always guaranteed. This leads to dietary mismatches with potential impacts on organismal performance. To understand the consequences of such dietary mismatches, we examined the effects of isocaloric diets varying in macronutrient composition on eight key organismal traits spanning across the lifespan of a large outbredDrosophila melanogasterpopulation (n ∼ 2500). Our findings reveal that carbohydrate-reduced isocaloric diets correlates to accelerated pre-adult development and boosts reproductive output without impacting pre-adult viability and body size. Conversely, an elevated dietary carbohydrate content correlated to reduced lifespan in flies, evidenced by accelerated functional senescence including compromised locomotor activity and deteriorating gut integrity. Furthermore, transcriptomic analysis indicated a substantial difference in gene regulatory landscapes between flies subject to high carbohydrate vs high protein diet, with elevated protein levels indicating transcriptomes primed for reduced synthesis of fatty acids. Taken together, our study helps advance our understanding of the effect of macronutrient composition on life history traits and their interrelations, offering critical insights into potential adaptive strategies that organisms might adopt against the continual dietary imbalances prevalent in the rapidly evolving environment.
Scalable bio-platform to recover critical metals from complex waste sources
Authors: Good Nathan M. , Kang-Yun Christina S. , Su Morgan Z. , Zytnick Alexa M. , Vu Huong N. , Grace Joseph M. , Nguyen Hoang H. , Park Dan M. , Skovran Elizabeth , Fan Maohong , Martinez-Gomez N. Cecilia 
Published: September 2023

ABSTRACTChemical methods for extraction and refinement of technologically critical rare earth elements (REEs) are energy intensive, hazardous, and environmentally destructive. Current bio-based extraction systems rely on extremophilic organisms and generate many of the same detrimental effects as chemical methodologies. The mesophilic methylotrophic bacteriumMethylobacterium extorquensAM1 was previously shown to grow using electronic waste by naturally acquiring REEs to power methanol metabolism. Here we show that growth using electronic waste as a sole REE source is scalable up to 10 L with consistent metal yields, without the use of harsh acids or high temperatures. Addition of organic acids increases REE leaching in a nonspecific manner. REE-specific bioleaching can be engineered through the overproduction of REE-binding ligands (called lanthanophores) and pyrroloquinoline quinone. REE bioaccumulation increases with leachate concentration and is highly specific. REEs are stored intracellularly in polyphosphate granules, and genetic engineering to eliminate exopolyphosphatase activity increases metal accumulation, confirming the link between phosphate metabolism and biological REE use. Finally, we report the innate ability ofM. extorquensto grow using other complex REE sources including pulverized smart phones, demonstrating the flexibility and potential for use as a recovery platform for these critical metals.
Membrane Lipid Nanodomains Modulate HCN Pacemaker Channels in Nociceptor DRG Neurons
Authors: Handlin Lucas J. , Macchi Natalie L. , Dumaire Nicolas L.A. , Salih Lyuba , Lessie Erin N. , McCommis Kyle S. , Moutal Aubin , Dai Gucan 
Published: September 2023

ABSTRACTCell membranes consist of heterogeneous lipid nanodomains that influence key cellular processes. Using FRET-based fluorescent assays and fluorescence lifetime imaging microscopy (FLIM), we found that the dimension of cholesterol-enriched ordered membrane domains (OMD) varies considerably, depending on specific cell types. Particularly, nociceptor dorsal root ganglion (DRG) neurons exhibit large OMDs. Disruption of OMDs potentiated action potential firing in nociceptor DRG neurons and facilitated the opening of native hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels. This increased neuronal firing is partially due to an increased open probability and altered gating kinetics of HCN channels. The gating effect on HCN channels was likely due to a direct modulation of their voltage sensors by OMDs. In animal models of neuropathic pain, we observed reduced OMD size and a loss of HCN channel localization within OMDs. Additionally, cholesterol supplementation inhibited HCN channels and reduced neuronal hyperexcitability in pain models. These findings suggest that disturbances in lipid nanodomains play a critical role in regulating HCN channels within nociceptor DRG neurons, influencing pain modulation.
Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity
Authors: Li Wei , Pucka Andrew Q , Debats Candice , Reyes Brandon , Syed Fahim , O’Brien Andrew R , Mehta Rakesh , Manchanda Naveen , Jacob Seethal A , Hardesty Brandon M , Greist Anne , Harte Steven E , Harris Richard E , Yu Qigui , Wang Ying 
Published: September 2023

AbstractThis study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients’ well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 37 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.
The selective D3-Receptor antagonist VK4-116 effectively treats behavioral inflexibility in rats caused by self-administration and withdrawal from cocaine
Authors: Panayi Marios C. , Shetty Shohan , Porod Micaela , Bahena Lisette , Xi Zheng-Xiong , Newman Amy Hauck , Schoenbaum Geoffrey 
Published: September 2023

AbstractChronic psychostimulant use can cause long lasting changes to neural and cognitive function that persist even after long periods of abstinence. As cocaine users transition from drug use to abstinence, a parallel transition from hyperactivity to hypoactivity has been found in orbitofrontal-striatal glucose metabolism, and striatal D2/D3 receptor activity. Targeting these changes pharmacologically, using highly selective dopamine D3 receptor (D3R) antagonists and partial agonists, has shown significant promise in reducing drug-taking, and attenuating relapse in animal models of cocaine and opioid use disorder. However, much less attention has been focused on treating inflexible and potentially maladaptive non-drug behaviors following chronic psychostimulant use. Here we tested the selective D3R antagonist VK4-116 as a treatment for the long-term behavioral inflexibility in abstinent male and female rats with a prior history of chronic cocaine use. Rats were first trained to self-administer cocaine (0.75 mg/kg/reinforcer) or a sucrose liquid (10%, .04 mL/reinforcer) for 2 weeks (FR1 schedule, max 60 reinforcers in 3 hrs/ day), followed by 4 weeks of abstinence. Cognitive and behavioral flexibilities were then assessed using a sensory preconditioning (SPC) learning paradigm. Rats were given an VK4-116 (15 mg/kg, i.p.) or vehicle 30 mins prior to each SPC training session, thus creating four drug-treatment groups: sucrose-vehicle, sucrose-VK4-116, cocaine-vehicle, cocaine-VK4-116. The control groups (sucrose-vehicle, sucrose-VK4-116) demonstrated significant evidence of flexible SPC behavior, whereas cocaine use (cocaine-vehicle) disrupted SPC behavior. Remarkably, the D3R antagonist VK4-116 mitigated this cocaine deficit in the cocaine-VK4-116 group, demonstrating flexible SPC to levels comparable to the control groups. These preclinical findings demonstrate that highly selective dopamine D3R antagonists, particularly VK4-116, show significant promise as a pharmacological treatment for the long-term negative behavioral consequences of cocaine use disorder.