bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile health follow-up screening to risk stratify patients in need of further care in a low resource setting: Results from a prospective multisite implementation study
Authors: Christie S. Ariane , Mbianyor Mbiarikai , Oke Rasheedat , Dissak-Delon Fanny , Yakue Florentine , Essomba Frank , Mbuh Golda , Yost Mark , Dicker Rochelle , Chichom-Mefire Alain , Juillard Catherine 
Published: October 2023

BACKGROUND
Routine in-person follow-up for injured patients after hospital discharge is unfeasible in low- and middle-income countries where trauma morbidity and mortality are the highest. Mobile technology screening may facilitate early detection of complications and timely treatment. In this prospective, multisite implementation study, we cross-validate the performance of a cellphone screening tool developed to risk stratify trauma patients in need of further care after discharge in Cameroon.

METHODS
Between June 2019 and August 2022, research assistants contacted trauma patients by cellphone 2 weeks after discharge to administer a 14-question follow-up survey. All surveyed patients were asked to return for a physical examination. Physicians blinded to survey results categorized patients as low or moderate or high risk (HR) for poor outcomes without further care. Logistic regression tested associations between each survey question and physician examination. Predictive survey questions generated a preliminary model with high sensitivity for identifying patients in need of further care.

RESULTS
Of 1,712 successfully contacted patient households, 96% (1643) participated in telephone triage compared with 33% (560) who returned for physician examination. Physicians designated 39% (220) as being HR. On multiple logistic regression, 8 of 13 candidate triage questions were independently associated with HR. Positive survey response on the resultant eight question screen yielded 89.2% sensitivity for HR with a 10.8% false negative rate. Weighted for variable importance based on triage risk scores, 39% of triaged patients screened as low risk, 39% as moderate risk, and 22% as high risk for HR. Likelihood of HR was significantly greater for patients screening as high (odds ratio, 5.9) or moderate risk (odds ratio, 1.9; both p < 0.01).

CONCLUSION
Cellphone triage provides sensitive risk stratification of patients in need of further care after hospital discharge in Cameroon. Given low in-person return rates, limited resources should highly prioritize efforts to repatriate patients screening as high risk for poor outcomes.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Effects of prior injury on long term patient reported outcomes after trauma
Authors: Beyer Carl A. , Hatchimonji Justin S. , Candido Katelyn , Chreiman Kristen , Martin Niels , Cannon Jeremy W. , Reilly Patrick M. , Kaufman Elinore J. , Seamon Mark J. 
Published: October 2023

BACKGROUND
Trauma is an episodic, chronic disease with substantial, long-term physical, psychological, emotional, and social impacts. However, the effect of recurrent trauma on these long-term outcomes remains unknown. We hypothesized that trauma patients with a history of prior traumatic injury (PTI) would have poorer outcomes 6 months (6mo) after injury compared with patients without PTI.

METHODS
Adult trauma patients admitted at an urban, academic, Level I trauma center were screened for inclusion (October 2020 to November 2021). Enrolled patients were administered the PROMIS-29 instrument, the primary care post-traumatic stress disorder screen, and standardized questions about prior trauma hospitalization, substance use, employment, and living situation at baseline and 6mo after injury. Assessment data was merged with clinical registry data, and outcomes were compared with respect to PTI.

RESULTS
Of 3,794 eligible patients, 456 completed baseline assessments and 92 completed 6mo surveys. Between those with or without PTI, there were no differences at 6mo after injury in the proportion of patients reporting poor function in social participation, anxiety, depression, fatigue, pain interference, or sleep disturbance. Prior traumatic injury patients reported poor physical function less often than patients without PTI (10 [27.0%] vs. 33 [60.0%], p = 0.002). After controlling for age, gender, race, injury mechanism, and Injury Severity Score, PTI correlated with a fourfold decrease in poor physical function risk (adjusted odds ratio, 0.243; 95% confidence interval, 0.081–0.733; p = 0.012) in the multivariable logistic regression model.

CONCLUSION
Compared with patients suffering their first injury, trauma patients with PTI have better self-reported physical function after a subsequent injury and otherwise equivalent outcomes across a range of HRQoL domains at 6mo. There remains substantial room for improvement to mitigate the long-term challenges faced by trauma patients and to facilitate their societal reintegration, regardless of the number of times they are injured.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Finding the bleeding edge: 24-hour mortality by unit of blood product transfused in combat casualties from 2002–2020
Authors: Gurney Jennifer M. , Staudt Amanda M. , Holcomb John B. , Martin Matthew , Spinella Phil , Corley Jason B. , Rohrer Andrew J. , Trevino Jennifer D. , del Junco Deborah J. , Cap Andrew , Schreiber Martin 
Published: October 2023

BACKGROUND
Transfusion studies in civilian trauma patients have tried to identify a general futility threshold. We hypothesized that in combat settings there is no general threshold where blood product transfusion becomes unbeneficial to survival in hemorrhaging patients. We sought to assess the relationship between the number of units of blood products transfused and 24-hour mortality in combat casualties.

METHODS
A retrospective analysis of the Department of Defense Trauma Registry supplemented with data from the Armed Forces Medical Examiner. Combat casualties who received at least one unit of blood product at US military medical treatment facilities (MTFs) in combat settings (2002–2020) were included. The main intervention was the total units of any blood product transfused, which was measured from the point of injury until 24 hours after admission from the first deployed MTF. The primary outcome was discharge status (alive, dead) at 24 hours from time of injury.

RESULTS
Of 11,746 patients included, the median age was 24 years, and most patients were male (94.2%) with penetrating injury (84.7%). The median injury severity score was 17 and 783 (6.7%) patients died by 24 hours. Median units of blood products transfused was 8. Most blood products transfused were red blood cells (50.2%), followed by plasma (41.1%), platelets (5.5%), and whole blood (3.2%). Among the 10 patients who received the most units of blood product (164 units to 290 units), 7 survived to 24 hours. The maximum amount of total blood products transfused to a patient who survived was 276 units. Of the 58 patients who received over 100 units of blood product, 20.7% died by 24 hours.

CONCLUSION
While civilian trauma studies suggest the possibility of futility with ultra-massive transfusion, we report that the majority (79.3%) of combat casualties who received transfusions greater than 100 units survived to 24 hours. These results do not support a threshold for futility of blood product transfusion. Further analysis as to predictors for mortality will help in situations of blood product and resource constraints.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Assessment of ethynylestradiol-3-sulfate on coagulation, metabolism, and survival in pigs with traumatic hemorrhage
Authors: Martini Wenjun Z. , Xia Hui , Le Tuan D. , Cap Andrew P. 
Published: October 2023

BACKGROUND
The beneficial effects of estrogens on survival from hemorrhage have been suggested in some preclinical models. This study investigated the effects of ethynylestradiol-3-sulfate (EE-3-S) on coagulation, metabolism and survival in pigs following traumatic hemorrhage.

METHODS
Twenty-six pigs were randomized into: normal saline group (NS, n = 10), EE-3-S group (EE-3, n = 11) groups, and no resuscitation group (NR, n = 5). Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and a 10-minute shock period. Afterward, pigs were resuscitated with a small volume of either NS alone (4 mL/kg) or EE-3-S with NS (1 mL/kg at concentration of 1 mg/mL, plus NS solution of 3 mL/kg). Pigs in NR group were not resuscitated with any fluid. All pigs were then monitored for 6 hours or until death, with hemodynamics and survival times recorded. Blood samples were taken during the study for measurements of oxygen metabolism (oxygen delivery, extraction, and consumption) and coagulation function (using Rotem with Extem reagents).

RESULTS
All baseline measurements were similar among the three groups. In the NS group, femur fracture and hemorrhage immediately reduced mean arterial pressure (MAP, 74 ± 3 mm Hg to 44 ± 4 mm Hg) and increased heart rate (97 ± 5 bpm to 218 ± 14 bpm, both p < 0.05). Similar changes in MAP and heart rate were observed in the EE-3 and NR groups. There were no differences observed in changes of Rotem® measurements or oxygen metabolism among the groups during the study. At 6 hours, four pigs in NS, four pigs in EE-3-S, and two pigs in the NR group survived to the end of the study. The mean survival times were similar among the NS (212 ± 43 minutes), EE-3 (212 ± 39 minutes), and NR (223 ± 63 minutes) groups (p = 0.9845).

CONCLUSION
Following severe traumatic hemorrhage, hypotensive resuscitation with EE-3-S did not impact coagulation, metabolism, or survival in pigs.
Striatin plays a major role in angiotensin II-induced cardiomyocyte and cardiac hypertrophy in micein vivo
Authors: Cull JJ , Cooper STE , Alharbi HO , Chothani SP , Rackham OJL , Meijles DN , Dash PR , Kerkelä Risto , Ruparelia N , Sugden PH , Clerk A 
Published: October 2023

AbstractThe three striatins (STRN, STRN3, STRN4) form the core ofSTRiatin-InteractingPhosphatase andKinase (STRIPAK) complexes. These place protein phosphatase 2A (PP2A) in proximity to protein kinases thereby restraining kinase activity and regulating key cellular processes. Our aim was to establish if striatins play a significant role in cardiac remodelling associated with cardiac hypertrophy and heart failure. All striatins were expressed in control human hearts, with upregulation of STRN and STRN3 in failing hearts. We used mice with global heterozygote gene deletion to assess the roles of STRN and STRN3 in cardiac remodelling induced by angiotensin II (AngII; 7 days). Using echocardiography, we detected no differences in baseline cardiac function or dimensions in STRN+/-or STRN3+/-male mice (8 weeks) compared with wild-type littermates. Heterozygous gene deletion did not affect cardiac function in mice treated with AngII, but the increase in left ventricle mass induced by AngII was inhibited in STRN+/-(but not STRN3+/-) mice. Histological staining indicated that cardiomyocyte hypertrophy was inhibited. To assess the role of STRN in cardiomyocytes, we converted the STRN knockout line for inducible cardiomyocyte-specific gene deletion. There was no effect of cardiomyocyte STRN knockout on cardiac function or dimensions, but the increase in left ventricle mass induced by AngII was inhibited. This resulted from inhibition of cardiomyocyte hypertrophy and cardiac fibrosis. The data indicate that cardiomyocyte striatin is required for early remodelling of the heart by AngII and identify the striatin-based STRIPAK system as a signalling paradigm in the development of pathological cardiac hypertrophy.Clinical perspectivesBackground.Striatins form the core ofSTRiatin-InteractingPhosphataseAndKinase (STRIPAK) complexes that regulate crucial cellular processes such as those associated with heart failure.Summary.The three striatins are expressed in human hearts, with upregulation of STRN and STRN3 in failing hearts, whilst studies in mice indicate that STRN is required in cardiomyocytes for early remodelling of the hypertensive heart.Potential significance of results to human health and disease.STRN-based STRIPAKs represent a novel signalling paradigm in the development of pathological cardiac hypertrophy, and modulating this system may provide therapeutic options for managing the cardiac effects of hypertensive heart disease.
Explicit Scale Simulation for analysis of RNA-sequencing with ALDEx2
Authors: Gloor Gregory B. , Nixon Michelle Pistner , Silverman Justin D. 
Published: October 2023

AbstractIn high-throughput sequencing (HTS) studies, sample-to-sample variation in sequencing depth is driven by technical factors, and not by variation in the scale (e.g., total size, microbial load, or total mRNA expression) of the underlying biological systems. Typically a statistical normalization is used to remove unwanted technical variation in the data or the parameters of the model to enable analyses that are reliant on scale; e.g., differential abundance and differential expression analyses. We recently showed that all normalizations make implicit assumptions about the unmeasured system scale and that errors in these assumptions can dramatically increase false positive and false negative rates. We demonstrated that these errors can be mitigated by accounting for uncertainty about scale using ascale model, which we integrated into the ALDEx2 R package. This article provides new insights into those methods, focusing on the application to transcriptomic analysis. Here we provide transcriptomic case studies demonstrating how scale models, rather than traditional normalizations, can reduce false positive and false negative rates in practice while enhancing the transparency and reproducibility of analyses. We show that these scale models replace the need for dual cutoff approaches often used to address the disconnect between practical and statistical significance. We demonstrate the utility of that scale models built based on known housekeeping genes in complex metatranscriptomic datasets. Thus this work provides example and practical guidance on how to incorporate scale into transcriptomic analysis.
Regulating the proinflammatory response to implanted composite biomaterials comprising polylactide and hydroxyapatite by targeting immunometabolism
Authors: Maduka Chima V. , Makela Ashley V. , Ural Evran , Stivers Katlin B. , Kuhnert Maxwell M. , Tundo Anthony , Alhaj Mohammed , Apu Ehsanul Hoque , Ashammakhi Nureddin , Hankenson Kurt D. , Narayan Ramani , Elisseeff Jennifer H. , Contag Christopher H. 
Published: October 2023

AbstractComposite biomaterials comprising polylactide (PLA) and hydroxyapatite (HA) are applied in bone, cartilage and dental regenerative medicine, where HA confers osteoconductive properties. However, after surgical implantation, adverse immune responses to these composites can occur, which have been attributed to size and morphology of HA particles. Approaches to effectively modulate these adverse immune responses have not been described. PLA degradation products have been shown to alter immune cell metabolism, which drives the inflammatory response. Therefore, we aimed to modulate the inflammatory response to composite biomaterials by regulating glycolytic flux with small molecule inhibitors incorporated into composites comprised of amorphous PLA (aPLA) and HA (aPLA+HA). Inhibition at specific steps in glycolysis reduced proinflammatory (CD86+CD206-) and increased pro-regenerative (CD206+) immune cell populations around implanted aPLA+HA resulting in a pro-regenerative microenvironment. Notably, neutrophil and dendritic cell (DC) numbers along with proinflammatory monocyte and macrophage populations were decreased, and Arginase 1 expression among DCs was increased. Targeting immunometabolism to control the inflammatory response to biomaterial composites, and creating a pro-regenerative microenvironment, is a significant advance in tissue engineering where immunomodulation enhances osseointegration, and angiogenesis, which will lead to improved bone regeneration.
Bayesian inference for copy number intra-tumoral heterogeneity from single-cell RNA-sequencing data
Authors: Qiao PuXue , Kwok Chun Fung , Qian Guoqi , McCarthy Davis J 
Published: October 2023

AbstractHigh-resolution molecular characterization of intra-tumoral clonal structure defined by genomic and epigenomic alterations is crucial in understanding the natural history of tumors and advancing cancer treatment strategies. Copy number alterations (CNA) are of notable importance as both drivers and markers of clonal structure that can now be assayed at individual cell resolution. However, specific computational methods are needed for accurate inference of clonal profiles and cell states from sparse and noisy single-cell ’omics data. Here, we develop a new Bayesian model to utilize single-cell RNA sequencing (scRNA-seq) data for automatic analysis of intra-tumoral clonal structure with respect to CNAs, without reliance on prior knowledge. The model clusters cells into sub-tumoral clones while simultaneously identifying CNA events in each clone, jointly modelling input from gene expression and germline single-nucleotide polymorphisms. Unlike previous methods, our approach automatically infers the number of clones present in the tumor. In detailed simulation studies our model frequently achieves very high (>90%) cell clustering accuracy and high (>80%) CN state inference accuracy, even in settings of high variance and sparsity. Overall, our method compares strongly against existing software tools. Application to human metastatic melanoma tumor data demonstrates accurate clustering of tumor and non-tumor cells, and reveals clonal CNA profiles that highlight functional gene expression differences between clones from the same tumor. Our method is implemented in a publicly-available, open-source R package, Chloris.
Mobile DNA is replete with hotspots for the de novo emergence of gene regulation
Authors: Fuqua Timothy , Wagner Andreas 
Published: October 2023

ABSTRACTDNA mutations that create new gene expression are important raw materials for Darwinian evolution. One potential source of new gene regulation is mobile DNA, which can sometimes drive the expression of genes near its insertion site in a genome through outward-directed promoters. However, we do not know how frequent this ability is, nor how frequently mobile DNA may evolve such promotersde novo. Here we address these questions for the insertion sequence family IS3, the most abundant family of a simple form of prokaryotic mobile DNA. First, we estimate that at least 30% of IS3 sequences harbor outward-directed promoters. Second, we combine high-throughput mutagenesis with a massively parallel reporter assay to show that single point mutations suffice to create outward-directed promoters in all the IS3 sequences we studied. We found that in 5.6% of 18’607 mutant IS3 sequences, promoter activity emerged de novo. Promoters preferentially arise at emergence hotspots in each IS3 sequence. These hotspots overlap with promoter motifs that already exist or are newly created by mutation. One common route to promoter activity is gaining a -10 box downstream of an existing -35 box, which we call “Shiko Emergence.” Overall, we show that mobile DNA has a high latent potential to drive new gene expression. This makes mobile DNA ideal for domestication by its host organism. It also raises intriguing questions about how this potential has evolved.
Quality and sustainability of Ethiopia’s national surgical indicators
Authors: Cook Kayleigh R , Zeleke Zebenay B , Gebrehana Ephrem , Burssa Daniel , Yeshanew Bantalem , Michael Atkilt , Tediso Yoseph , Jaraczewski Taylor , Dodgion Chris , Beyene Andualem , Iverson Katherine R 
Published: October 2023

AbstractIn 2015, the Ethiopian Federal Ministry of Health (FMOH) developed the Saving Lives through Safe Surgery (SaLTS) initiative to improve national surgical care. Previous work led to development and implementation of 15 surgical key performance indicators (KPIs) to standardize surgical data practices. The objective of this project is to investigate current practices of KPI data collection and assess quality to improve data management and strengthen surgical systems.The first portion of the study documented the surgical data collection process including methods, instruments, and effectiveness at 10 hospitals across 2 regions in Ethiopia. Secondly, data for KPIs of focus [1. Surgical Volume, 2. Perioperative Mortality Rate (POMR), 3. Adverse Anesthetic Outcome (AAO), 4. Surgical Site Infection (SSI), and 5. Safe Surgery Checklist (SSC) Utilization] were compared between registries, KPI reporting forms, and the DHIS2 (district health information system) electronic database for a 6-month period (January - June 2022). Quality was assessed based on data completeness and consistency.The data collection process involved hospital staff recording data elements in registries, quality officers calculating KPIs, completing monthly KPI reporting forms, and submitting data into DHIS2 for the national and regional health bureaus. Data quality verifications revealed discrepancies in consistency at all hospitals, ranging from 1-3 indicators. For all hospitals, average monthly surgical volume was 57 cases, POMR was 0.38% (13/3399), inpatient SSI rate was 0.79% (27/3399), AAO rate was 0.15% (5/3399), and mean SSC utilization monthly was 93% (100% median). Half of the hospitals had incomplete data within the registries, ranging from 2-5 indicators. AAO, SSC, and SSI were commonly missing data in registries. Non-standardized KPI reporting forms contributed significantly to the findings.Facilitators to quality data collection included continued use of registries from previous interventions and use of a separate logbook to document specific KPIs. Delayed rollout of these indicators in each region contributed to issues in data quality. Barriers involved variable indicator recording from different personnel, data collection tools that generate false positives (i.e. completeness of SSC defined as paper form filled out prior to patient discharge) or missing data because of reporting time period (i.e. monthly SSI may miss infections outside of one month), inadequate data elements in registries, and lack of standardized monthly KPI reporting forms. As the FMOH introduces new indicators and changes, we recommend continuous and consistent quality checks and data capacity building, including the use of routinely generated health information for quality improvement projects at the department level.