bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining the educational impact of virtual patients on trauma team training during a multinational, large-scale civil military simulation exercise
Authors: Sonesson Linda , Boffard Kenneth D. , Örtenwall Per , Vekzsler Péter 
Published: May 2023

BACKGROUND
With asymmetrical conflicts ongoing, many countries have an increasing number of major trauma events but limited capacity to cope with these events. Training for such events comprises primarily of simulations requiring significant resources and that are time-consuming and expensive. Virtual patients are defined as computer-based programs presenting authentic cases support training in trauma management.

HYPOTHESIS
Assisted learning technologies augment simulated trauma team training and can improve trauma team competencies. The aim was to investigate if virtual patients increased competencies in decision making required and to identify deficiencies in care for the management of trauma patients during a multinational civil military trauma exercise.

METHODS
A prospective educational intervention study with mixed methods, measuring the effects of a novel virtual patient model on trauma teams, was performed. The population consisted of surgeons, anesthesiologists, emergency department physicians, nurses, and paramedics (n = 30) and constituted six trauma teams from eight countries; three trauma teams formed the participating group, and three were allocated as control group. The participating group was exposed to virtual patients before, during, and after the live simulation exercise. Data sources were derived from individual preassessments and postassessments, evaluations made by experts in trauma, and video recordings of performance during the live simulation exercise and analyzed by the thematic analysis method.

RESULTS
Using virtual patients contributed to improved individual knowledge about the management of major trauma patients and improved teamwork. Virtual patients as support for reasoning in decision making were directly correlated to level of previous knowledge and experience. Two of the three participating trauma teams showed lower levels of existing knowledge and competence in managing major trauma patients and therefore made more efficient use of the virtual patients.

CONCLUSION
Results demonstrated advantages using virtual patients during a major civil military trauma live simulation exercise and appear to be supportive especially for teams who are not as experienced.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Long term stability of patients undergoing endovascular parent artery occlusion of their intracranial artery
Authors: Koizumi Satoshi , Shojima Masaaki , Ota Takahiro , Dofuku Shogo , Miyawaki Satoru , Kiyofuji Satoshi , Maeda Keiichiro , Ochi Takashi , Ito Akihiro , Hidaka Yukihiro , Oya Soichi , Saito Akira , Yoshikawa Gakushi , Yanai Kei , Inoue Tomohiro , Tsunoda Sho , Hoya Katsumi , Saito Nobuhito 
Published: May 2023

AbstractBackgroundAlthough endovascular parent artery occlusion (PAO) of the intracranial artery is a well-established treatment option, the long-term stability of cerebral blood flow remains a concern. This study aimed to evaluate the long-term clinical and radiological outcomes of patients who underwent PAO.MethodsThe patients who underwent endovascular PAO of their internal carotid or vertebral artery (VA) between April 2011 and March 2022 were included in this observational study. Information about patient characteristics, details of the endovascular treatment, and clinical and radiological follow-up were collected.ResultsThe study included a total of 104 cases (average age 52.9±12.6 years old, male 73 (70.2%) cases, 95 (91.3%) VA PAO cases) from eight centers. Most cases were performed in an emergency condition, such as ruptured vertebral artery dissecting aneurysm (73 cases [70.2%]). PAO was successful in all cases. Early stroke (within 30 days) occurred in 33 (31.7%) cases (31 cases in VA PAO and two cases in internal carotid PAO) with ischemic stroke (29 cases) comprising the largest group. Clinical follow-up over 12 months was available in 78 cases. During an average follow-up period of 49.5 ± 24.3 months, one case in VA PAO experienced a stroke without functional deterioration. Imaging follow-up was performed in 73 cases. Recanalization of the occluded VA was observed in two cases. The remaining image change was contralateral VA stenosis after VA PAO. The incidence of clinical and radiological events was 0.95 and 1.1% per patient-year, respectively.ConclusionsOnce the patients surpass the acute phase after PAO, their mid-to-long term course was stable. The risk of late stroke or de novo aneurysm formation was lower than expected in the literature, and the direct comparison to novel reconstructiv techniques is warranted in future studies.Registrationhttps://www.umin.ac.jp/ctr/index.html, trial ID: UMIN000045160
A near-complete genome sequence of einkorn wheat provides insight into the evolution of wheat A subgenomes
Authors: Wang Xiangfeng , Li Hongna , Shen Tao , Wang Xinrui , Yi Shu , Meng Tan , Sun Jie , Wang Xiaoliang , Qu Xiaojian , Chen Shisheng , Guo Li 
Published: May 2023

AbstractEinkorn wheat (Triticum monococcum) is one of the oldest cereal crops to be domesticated by human beings, playing essential role in early agriculture development. Today, it is considered an important genomic resource for modern wheat improvement, especially for resistance against pests and diseases. However, the exploration and utilization of useful genes fromT. monococcumis limited due to the lack of a reference genome and annotation for this species. Here, we report a near-complete genome assembly forT. monococcumwith a total length of 5.11 Gb with a contig N50 of 131.2Mb and scaffold N50 of 728.66Mb, representing a genome assembly of highest quality for any wheat genome reported. Phylogenomic analysis confirmedT. monococcumis closely-related toT. urartu, the progenitor of wheat A subgenomes. A 4AL/5AL terminal translocation is present in the diploid speciesT. urartuandT. monococcum, taking place before wheat polyploidization.T. monococcumhas significantly expanded and unique gene families involved in DNA damage repair and heat stress tolerance, reflecting its adaptive evolution to cope with historical harsh climate in its natural habitat, South East Turkey. The genome sequence confirmed the introgression ofT. monococcumrust resistance genes at 5AmL into modern bread wheat varieties. This near-complete reference genome ofT. monococcumwill be an essential resource for wheat functional and evolutionary genomic studies and expedite the cloning of useful genes inT. monococcumfor future wheat improvement.
TBX2 driven switch from Androgen Receptor to Glucocorticoid Receptor signaling confers therapeutic resistance in Prostate Cancer
Authors: Dutta Sayanika , Patel Girijesh Kumar , Khedmatgozar Hamed , Latour Daniel , Tripathi Manisha , Nandana Srinivas 
Published: May 2023

AbstractRecent studies have highlighted that androgen receptor (AR) signaling can be bypassed via activation of the glucocorticoid receptor (GR), and that this bypass drives enzalutamide resistance in advanced prostate cancer (PCa). However, the molecular mechanism(s) that drive the switch from AR to GR signaling remain unknown. We have previously reported that TBX2, a developmental T-box transcription factor (TF), is over-expressed in castrate resistant prostate cancer (CRPC) and that TBX2 drives the CRPC phenotype via cell-intrinsic and exosome-mediated paracrine modes. Our current study demonstrates that TBX2, a TF with known repressor and activator functions, may be the molecular switch that represses AR on one hand while activating GR expression on the other to drive CRPC. Mechanistically, our studies revealed a two-tiered mechanism of AR repression by TBX2 wherein TBX2 directly binds to the promoters of AR and GATA2, an AR coregulator, thereby resulting in the repression of AR as well as GATA2. Conversely, our results demonstrate that TBX2 mediates increased expression of GR via directly binding to the GR promoter, and through TBX2-GR functional protein-protein interaction. Our results demonstrate that the TBX2 driven switch from AR to GR signaling results in enzalutamide resistance since GR inhibition in the context of TBX2 over-expression attenuates enzalutamide resistance. Further, we present evidence that SP2509 based allosteric inhibition of Lysine Specific Demethylase 1 (LSD1), a protein that interacts with TBX2 as part of the Co-repressor of RE1-Silencing Transcription Factor (COREST) complex, is able to disrupt TBX2-GR interaction. Taken together, our study has identified TBX2 as the molecular switch that drives AR to GR signaling and thereby confers enzalutamide resistance in CRPC. Furthermore, our study provides key insights into a potential therapeutic strategy of targeting the AR to GR switch wherein SP2509-based allosteric inhibition of TBX2-LSD1 could be harnessed to target the TBX2-GR interaction, thereby resulting in the inhibition of enzalutamide resistance in CRPC.
Nitrogen starvation causes lipid remodeling inRhodotorula toruloides
Authors: Mishra Shekhar , Deewan Anshu , Zhao Huimin , Rao Christopher V. 
Published: May 2023

AbstractThe oleaginous yeastRhodotorula toruloidesis a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited byR. toruloidesunder nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers. Here, we present a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Through an integrative lens of transcriptomic and lipidomic analysis, we identify thatR. toruloidesundergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals.HighlightsThe oleaginous yeastR. toruloidesdisplays enhanced lipid accumulation during nitrogen starvation.A multi-omic investigation of the lipid accumulation phenotype was carried out.Lipid remodeling was observed during the accumulation phase, wherein carbon was transferred from phospholipids to storage lipids.Multi-omic analysis suggested that selective regulation within lipid biosynthesis controls for the specific increase of storage lipids.
High-resolution spatial multi-omics reveals cell-type specific nuclear compartments
Authors: Takei Yodai , Yang Yujing , White Jonathan , Yun Jina , Prasad Meera , Ombelets Lincoln J , Schindler Simone , Cai Long 
Published: May 2023

AbstractThe mammalian nucleus is compartmentalized by diverse subnuclear structures. These subnuclear structures, marked by nuclear bodies and histone modifications, are often cell-type specific and affect gene regulation and 3D genome organization1–3. Understanding nuclear organization requires identifying the molecular constituents of subnuclear structures and mapping their associations with specific genomic loci in individual cells, within complex tissues. Here, we introduce two-layer DNA seqFISH+, which allows simultaneous mapping of 100,049 genomic loci, together with nascent transcriptome for 17,856 genes and a diverse set of immunofluorescently labeled subnuclear structures all in single cells in cell lines and adult mouse cerebellum. Using these multi-omics datasets, we showed that repressive chromatin compartments are more variable by cell type than active compartments. We also discovered a single exception to this rule: an RNA polymerase II (RNAPII)-enriched compartment was associated with long, cell-type specific genes (> 200kb), in a manner distinct from nuclear speckles. Further, our analysis revealed that cell-type specific facultative and constitutive heterochromatin compartments marked by H3K27me3 and H4K20me3 are enriched at specific genes and gene clusters, respectively, and shape radial chromosomal positioning and inter-chromosomal interactions in neurons and glial cells. Together, our results provide a single-cell high-resolution multi-omics view of subnuclear compartments, associated genomic loci, and their impacts on gene regulation, directly within complex tissues.
Persistent humoral immunity in children and adolescents throughout the COVID-19 pandemic (June 2020 to July 2022): a prospective school-based cohort study (Ciao Corona) in Switzerland
Authors: Raineri Alessia , Radtke Thomas , Rueegg Sonja , Haile Sarah R. , Menges Dominik , Ballouz Tala , Ulyte Agne , Fehr Jan , Cornejo Daniel L. , Pantaleo Giuseppe , Pellaton Céline , Fenwick Craig , Puhan Milo A. , Kriemler Susi 
Published: May 2023

AbstractObjectivesTo assess the longitudinal development of humoral immunity in children and adolescents during the COVID-19 pandemic, with a particular focus on how anti-spike IgG antibodies and neutralising response changed during the first Omicron peak (December 2021 to May 2022).DesignProspective school-based study during the COVID-19 pandemic (June 2020 to July 2022) including five testing rounds with corresponding cross-sectional cohorts and a longitudinal cohort who participated in at least four rounds.Setting55 randomly selected schools in the Canton of Zurich, Switzerland.ParticipantsBetween 1875 to 2500 children and adolescents per testing round and 751 in the longitudinal cohort.Main outcome measuresDevelopment of SARS-CoV-2 seroprevalence, anti-spike IgG antibodies and neutralising antibody response over time, persistence of antibodies and variation of antibody levels in individuals only infected, vaccinated or with hybrid immunity during the early Omicron period.ResultsBy July 2022 96.9% (95% credible interval [CrI] 95.2 to 98.1%) of children and adolescents had anti-spike IgG antibodies against SARS-CoV-2. The substantial increase in seroprevalence during the first peak of the Omicron wave was largely driven by primary infections in mostly unvaccinated children under the age of 12 (28.4% [95% CrI 24.2 to 33.2%] in December 2021, to 95.7% [95% CrI 93.4 to 97.4%] in July 2022). This stands in contrast to adolescents aged 12 years and older (69.4% [95% CrI 64.0 to 75.4%] in December 2021 to 98.4% [95% CrI 97.3 to 99.2%] in July 2022), who were eligible for vaccination since June 2021. Children and adolescents with hybrid immunity or immunity from vaccination had high anti-spike IgG titres (median Mean Fluorescence Intensity (MFI) ratio of 136.2 [Inter Quartile Range [IQR]: 121.9 to 154.3] and 127.6 [IQR: 114.1 to 151.0]) and strong neutralising responses (e.g., anti-Omicron 98.9% [95% Confidence Interval [CI] 96.0 to 99.7%] and 81.6% [95% CI 74.9 to 86.9%]). Meanwhile, infected but unvaccinated children and adolescents had substantially lower anti-spike IgG titres (median MFI ratio of 54.8 [IQR: 22.8 to 89.8]) and neutralising responses (e.g., anti-Omicron 64.9% [95% CI 59.8 to 69.7%]).ConclusionThese findings show that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity and boosted anti-spike IgG titres and neutralising capacity in children and adolescents. This was particularly driven by unvaccinated children (<12 years), who became seropositive due to the highly infectious Omicron variant. Nevertheless, during the entire study period parents of only one adolescent reported hospital stay of less than 24 hours related to a possible acute infection.
Neuromodulation for peripheral arterial disease of lower extremities: A 10-year analysis
Authors: Kretzschmar Michael , Okaro Udoka , Schwarz Marcus , Reining Marco , Lesser Thomas 
Published: May 2023

SummaryIntroductionSpinal cord stimulation (SCS) or Dorsal root ganglion stimulation (DRG-S) can improve limb salvage, microcirculatory blood flow, and pain relief in patients with peripheral arterial disease (PAD) who are not candidates for revascularization or who have persistent ischemic-related pain after revascularization This retrospective analysis presents 10-year data on the effectiveness and safety outcomes of neuromodulation for PAD at a single center.ObjectiveThis study evaluated the survival and amputation outcome of subjects who received neuromodulation therapy for the management of PAD. Descriptive outcomes such as Walking distance (m), pain intensity (NRS), opioid consumption (MME [morphine milligram equivalents]/d), and self-rated health (EQ-VAS) were also analysed.MethodsThis study retrospectively reviews the health data of a single cohort of 51 patients who received an SCS or DRG-S from 2007 to 2022 in a single German center. Survival rate was determined using the Kaplan Meier (KM) curve and major amputation was determined as the amputation of a major limb above the ankle. Patients who received a toe amputation were excluded from the amputation analysis. Two patients were excluded (2 patients died at 3 and 5 months after implantation. Pain, quality of life, walking distance, and opioid usage were assessed before implantation (baseline), 1, 6, and 12 months after implantation, and then annually (during a follow-up visit). Implant-related complications were also documented.)Results51 patients (37 men [mean age 68.9± 10.2], 14 women [mean age (68.7 ± 14.6]) underwent SCS (n = 49) or DRG-S (n = 2) implantation due to persistent ischemic pain. The follow-up mean years ± SD is 4.04 ± 2.73 with a range of 1 – 10 years. Atherosclerosis (40.4%) and diabetic vascular disease (48.9%) were the most common pathologies with 48.9% of patients depending on nicotine. At baseline, patients were classified as Rutherford’s Category 3 (n = 23), Category 4 (n = 15), or Category 5 (n = 9). At 24M, 42/47 patients did not require a major amputation following the implant. All patients reported complete pain relief from pain at rest, and 93.3% reported no pain from walking. A total of 75% of patients were able to walk more than 200m and 87% of patients who used opioids at baseline were off this medication at 24 months. Overall, 93% of patients reported an improvement in their overall health assessment. These improved outcomes were sustained through years 3-10 for patients who have reported outcomes.ConclusionsOur single center data supports the efficacy of spinal neuromodulation for improvements in limb salvage, pain relief, mobility, and quality of life. Also, the data show that neuromodulative therapy has a long-term therapeutic effect in patients with chronic limb pain with Rutherford class 3, 4, and 5 peripheral arterial disease (both reconstructable and non-reconstructable).
A machine learning model for predicting out-of-hospital cardiac arrest incidence using meteorological, chronological, and geographical data from the United States
Authors: Nakashima Takahiro , Ogata Soshiro , Kiyoshige Eri , Al-Hamdan Mohammad Z , Wang Yifan , Noguchi Teruo , Shields Theresa A , Al-Araji Rabab , McNally Bryan , Nishimura Kunihiro , Neumar Robert W 
Published: May 2023

AbstractBackgroundDespite advances in pre- and post-resuscitation care, percentage of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) was extremely low. Development of an accurate system to predict the daily incidence of OHCA might provide a significant public health benefit. Here, we developed and validated a machine learning (ML) predictive model for daily OHCA incidence using high-resolution meteorological, chronological, and geographical data.MethodsWe analyzed a dataset from the United States that combined an OHCA nationwide registry, high-resolution meteorological data, chronological data, and geographical data. We developed a model to predict daily OHCA incidence with a training dataset for 2013–2017 using the eXtreme Gradient Boosting algorithm. A dataset for 2018–2019 was used to test the predictive model. The main outcome was the predictive accuracy for the number of daily OHCA events, based on root mean squared error (RMSE), mean absolute error (MAE), and mean absolute percentage error (MAPE). In general, a model with MAPE less than 10% is considered highly accurate.ResultsAmong the 446,830 OHCAs of non-traumatic cause where resuscitative efforts were initiated by a 911 responder, 264,916 in the training dataset and 181,914 in the testing dataset were included in the analysis. The ML model with combined meteorological, chronological, and geographical data had high predictive accuracy in relation to nationwide incidence rate per 100,000 at the nationwide level) in the training dataset (RMSE, 0.016; MAE, 0.013; and MAPE, 7.61%) and in the testing dataset (RMSE, 0.018; MAE, 0.014; and MAPE, 6.52%).ConclusionsA ML predictive model using comprehensive daily meteorological, chronological, and geographical data allows for highly precise estimates of OHCA incidence in the United States.Clinical PerspectiveWhat is new?A machine learning predictive model developed with a high-resolution meteorological dataset and chronological and geographical variables predicted the daily incidence of out-of-hospital cardiac arrest (OHCA) in the U.S. population with high precision. The predictive accuracy at the state level was greater in medium and high-temperature areas than in the low-temperature area.What are the clinical implications?This predictive model revealed complex associations between meteorological, chronological, and geographic variables in relation to predicting daily incidence of OHCA. It might be useful for public health strategies in temperate regions, for example, by providing a warning system for citizens and emergency medical services agencies on high-risk days.
Early recanalization among patients undergoing bridging therapy with tenecteplase or alteplase
Authors: Checkouri Thomas , Gerschenfeld Gaspard , Seners Pierre , Yger Marion , Hassen Wagih Ben , Chausson Nicolas , Olindo Stéphane , Caroff Jildaz , Marnat Gaultier , Clarençon Frédéric , Baron Jean-Claude , Turc Guillaume , Alamowitch Sonia 
Published: May 2023

ABSTRACTBackgroundIntravenous thrombolysis (IVT) with alteplase or tenecteplase prior to mechanical thrombectomy (MT) is the recommended treatment for large-vessel occlusion acute ischemic stroke (LVOS). There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before MT, and little data on their potential differences in terms of established ER predictors such as time elapsed between IVT and ER evaluation (IVT-to-ERevaltime), occlusion site and thrombus length.MethodsWe compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation LVOS patients from the PREDICT-RECANAL (alteplase) and TETRIS (tenecteplase) French multicenter registries. ER was defined as a modified thrombolysis in cerebral infarction score 2b-3 on first angiographic run or non–invasive vascular imaging (magnetic resonance or computed tomography angiography) in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (PSOW, leading to an exact balance in baseline characteristics between the treatment groups) and confirmed with adjusted logistic regression (sensitivity analysis).ResultsA total of 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95%CI 0.83–1.44];P=0.52). A differential effect of tenecteplasevsalteplase on the probability of ER according to thrombus length was observed (Pinteraction=0.003), with tenecteplase being associated with higher odds of ER in thrombi > 10 mm (odds ratio, 2.43 [95% CI 1.02-5.81];P=0.04). There was no differential effect of tenecteplasevsalteplase on the likelihood of ER according to the IVT-to-ERevaltime (Pinteraction=0.40) or occlusion site (Pinteraction=0.80).ConclusionBoth thrombolytics achieved ER in a fifth of LVOS patients, with potentially greater effect of tenecteplase in larger thrombi. There was no significant differential influence of IVT-to-ERevaltime or occlusion site on likelihood of ER.