bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 on Mental Health of Oncology Health Care Workers and Interdisciplinary Collaboration: Results of Surveys in 2021 and 2022
Authors: Bienert Agnieszka , Meier Klaus , Kokisheva Antonina , Gama Brambila Rodrigo A. , Veraldi Marianna , de Lima Vilaca Marques Nuno Carlos Rosa , Kuzmanović Maja , Andreianu Dan Paul , Badibouidi Ferdinand , Vallespin Romina Morales 
Published: March 2023

Abstract

Introduction:
The 2019 coronavirus pandemic has caused serious health crises around the world such as psychological reactions of health workers. The way we work (stress, anxiety, and psychological problems) and the activities assigned to pharmacists, such as vaccination, have changed. So, we conducted a survey to investigate their psychophysical well-being and the influence of vaccination on the daily work of pharmacists.

Methods:
The survey (translated into 9 languages and distributed online) on mental health was sent to all ESOP members in March 2021 and February 2022 and on vaccination in December 2020, March 2021, and February 2022. The data were analyzed using Excel (Microsoft Office 2016, Microsoft, Redmond, WA) and basic descriptive statistics.

Results:
Over 800 colleagues from different health areas and 62 countries took part in the survey. As a result of poor mental health and increased workload as a consequence of the pandemic, it was observed in 30% (2021) and 15% (2022) of respondents, while increased cooperation among healthcare workers was observed in 65% of responders. In the vaccination survey, less than half of the professionals surveyed were directly involved in the vaccination process, conducted mainly in hospitals at first and then in other centers to increase coverage, such as “Community Pharmacy.” For the first time, there have been reports of pharmacists authorized to administer vaccines in some countries.

Conclusions:
With the spread of the virus, the increased workload has affected the mental health of health workers. Although a slight improvement from 2022 vs 2021 was observed, there is a need now to work on improving mental health of health care workers, to protect/care about them, and also to ensure that they will not leave the profession to ensure health care for patients with cancer and COVID-19 (and in general to all patients). Vaccination was an opportunity for the pharmacist to play a more active role that reinforces the value of pharmaceutical practice.
Development and Validation of a Mixed-Reality Simulator for Reducing Biopsy Core Deviation During Simulated Freehand Systematic Prostate Biopsy
Authors: Lampotang Samsun , Lizdas David E. , Johnson William T. , Mei Vincent , Wakim Jonathan , Lou XiangYang , DeStephens Anthony , Acar Yahya , Moy Louis , Ahmad Ardalanejaz , Brisbane Wayne , Stringer Thomas 
Published: March 2023

Introduction
We describe the development and validation of a mixed-reality prostate biopsy (PBx) simulator with built-in guidance aids and real-time 3-dimensional visualization.

Methods
We evaluated our simulator during one-on-one training sessions with urology residents and attendings from 2018 to 2022. Participants performed freehand, side-fire, double-sextant transrectal ultrasound-guided systematic prostate biopsy (sPBx). After a baseline assessment (first set of 12 biopsy cores), participants trained for 25 minutes with visualization and cognitive aids activated. Training was followed by an exit set of 12 biopsy cores without visualization or cognitive aids and afterward, subjective assessment by trainees of the simulator. Deviation is the shortest distance of the center of a core from its intended template location.

Results
Baseline deviations (mean ± SD) for residents (n = 24) and attendings (n = 4) were 13.4 ± 8.9 mm and 8.5 ± 3.6 mm (P < 0.001), respectively. Posttraining deviations were 8.7 ± 6.6 mm and 7.6 ± 3.7 mm (P = 0.271), respectively. Deviations between baseline and exit were decreased significantly for residents (P < 0.001) but not for attendings (P = 0.093). Overall feedback from participants was positive. Confidence in performing a PBx increased in novices after training (P = 0.011) and did not change among attendings (P = 0.180).

Conclusions
A new PBx simulator can quantify and improve accuracy during simulated freehand sPBx while providing visualization and graphical feedback. Improved simulated sPBx accuracy could lead to more even distribution of biopsy cores within the prostate when performed in clinical settings, possibly reducing the high risk of missing an existing lesion and thus decreasing the time to initiating treatment, if indicated.
Firearm legislation: The association between neighboring states and crude death rates
Authors: Chammas Majid , Pust Gerd Daniel , Meizoso Jonathan P. , Ramsay Ian A. , Ke Hengyi , Rattan Rishi , Namias Nicholas , Crandall Marie , Yeh D. Dante 
Published: March 2023

BACKGROUND
Few studies have examined the impact of interstate differences in firearm laws on state-level firearm mortality. We aim to study the association between neighboring states' firearm legislation and firearm-related crude death rate (CDR).

METHODS
The CDC Web-based Injury Statistics Query and Reporting System was queried for adult all-intent (accidental, suicide, and homicide) firearm-related CDR among the 50 states from 2012 to 2020. States were divided into five cohorts based on the Giffords Law Center Annual Gun Law Scorecard, and two groups were constructed: Strict (A, B, C) and Lenient (D, F). We examined the effect of (1) a single incongruent neighbor, defined as “Different” if the state is bordered by ≥1 state with a grade score difference >1, and (2) the average grade of all neighboring states, defined as “Different” if the average of all neighboring states resulted in a grade score difference >1.

RESULTS
Strict states with similar average neighbors had significantly lower CDR compared with Strict states with different average neighbors (2.98 [1.91–5.06] vs. 3.87 [2.37–5.94], p = 0.02), while Lenient states with similar average neighbors had significantly higher CDR compared with Lenient states with different average neighbors (6.02 [4.56–8.11] vs. 4.7 [3.95–5.35], p = 0.002). Lenient states surrounded by all similar Lenient states had the highest CDR, which was significantly higher than Lenient states with ≥1 different neighbor (6.52 [5.09–8.96] vs. 5.19 [3.85–6.61], p < 0.001). However, Strict states with ≥1 different neighbor did not have higher CDR compared with Strict states surrounded by all similar Strict states (3.39 [2.17–5.35] vs. 3.14 [1.91–5.38], p = 0.5).

CONCLUSION
We report a lopsided neighboring effect whereby Lenient states may benefit from at least one Strict neighbor, while Strict states may be adversely affected only when surrounded by mostly Lenient neighbors. These findings may assist policymakers regarding the efficacy of their own state's legislation in the context of incongruent neighboring states.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Optimal Prehospital Crystalloid Resuscitation Volume in Trauma Patients at Risk for Hemorrhagic Shock
Authors: Deeb Andrew-Paul , Lu Liling , Guyette Frank X , Peitzman Andrew B , Daley Brian J , Miller Richard S , Harbrecht Brian G , Phelan Herb A , Sperry Jason L , Brown Joshua B 
Published: March 2023

Background:
Prehospital resuscitation guidelines vary widely and blood products, although likely superior, are not available for most patients in the prehospital setting. Our objective was to determine the prehospital crystalloid volume associated with the lowest mortality among patients in hemorrhagic shock.

Study Design:
This is a secondary analysis of the Prehospital Air Medical Plasma trial. Injured patients from the scene with hypotension and tachycardia or severe hypotension were included. Segmented regression and generalized additive models (GAM) were used to evaluate non-linear effects of prehospital crystalloid volume on 24-hour mortality. Logistic regression evaluated the association between risk-adjusted mortality and prehospital crystalloid volume ranges to identify optimal target volumes. Inverse propensity weighting was performed to account for patient heterogeneity.

Results:
There were 405 patients included. Segmented regression suggested the nadir of 24-hour mortality lay within 377-1419mL of prehospital crystalloid. GAM suggested the nadir of 24-hour mortality lay within 242-1333mL of prehospital crystalloid. A clinically operationalized range of 250-1250mL was selected based on these findings. Odds of 24-hour mortality were higher for patients receiving <250mL (aOR 2.46; 95%CI 1.31—4.83, p=0.007) and >1250mL (aOR 2.57; 95%CI 1.24—5.45, p=0.012) compared to 250-1250mL. Propensity weighted regression similarly demonstrated odds of 24-hour mortality were higher for patients receiving <250mL (aOR 2.62; 95%CI 1.34—5.12, p=0.005) and >1250mL (aOR 2.93; 95%CI 1.36—6.29, p=0.006) compared to 250-1250mL.

Conclusion:
Prehospital crystalloid volumes between 250-1250mL are associated with lower mortality compared to lower or higher volumes. Further work to validate these finding may provide practical volume targets for prehospital crystalloid resuscitation.
Health Circuit: a practice-proven adaptive case management approach for innovative healthcare services
Authors: Herranz Carmen , Martín Laura , Dana Fernando , Sisó-Almirall Antoni , Roca Josep , Cano Isaac 
Published: March 2023

AbstractDigital health tools may facilitate care continuum. However, enhancement of digital aid is imperative to prevent information gaps or redundancies, as well as to facilitate support of flexible care plans. The study presents Health Circuit, a digital health tool with an adaptive case management approach and analyses its healthcare impact, as well as its usability (SUS) and acceptability (NPS) by healthcare professionals and patients. In 2018-19, an initial prototype of Health Circuit was tested in a cluster randomized clinical pilot (n=100) in patients with high risk for hospitalization (Study I). In 2021, a pilot version of Health Circuit was evaluated in 104 high risk patients undergoing prehabilitation before major surgery (Study II). In study I, Health Circuit resulted in reduction of emergency room visits [4 (13%) vs 7 (44%)] and enhanced patients’ empowerment (p<0.0001) and showed good acceptability/usability scores (NPS 31 and SUS 54/100). In Study II, NPS scored 40 and SUS 85/100. The acceptance rate was also high (mean score of 8.4/10). Health Circuit showed potential for healthcare value generation, good both acceptability and usability despite being a prototype system, prompting the need for testing a completed system in real-world scenarios.
Sterile faecal filtrate transplantation alters phage-microbe dynamics in individuals with metabolic syndrome: a double blind, randomised, placebo-controlled clinical trial assessing efficacy and safety
Authors: Wortelboer Koen , de Jonge Patrick A. , Scheithauer Torsten P.M. , Attaye Ilias , Marleen Kemper E. , Nieuwdorp Max , Herrema Hilde 
Published: March 2023

ABSTRACTObjectiveBacteriophages (phages) are viruses of bacteria and have been shown to shape microbial communities. Previous studies have shown that altering the microbiota through faecal microbiota transplantation (FMT) can improve insulin resistance in individuals with metabolic syndrome (MetSyn). Interestingly, similar effects were observed in diet-induced obese mice after a faecal virome transplantation (FVT), raising the question whether phages of a healthy donor can improve glucose metabolism in individuals with MetSyn as well.DesignWe performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with MetSyn were randomised to receive a sterile faecal filtrate transplantation (FFT) from a lean healthy donor or a placebo. From baseline up to 28 days, we assessed safety, effects on glucose metabolism, and longitudinal changes within the bacteriome and phageome.ResultsThe FFT was well-tolerated and safe and glucose variability (time between 3.9-10 mmol/L glucose) improved in the week following the FFT. Glucose excursions during oral glucose tolerance tests were comparable in both the FFT and placebo group after 28 days. The phage virion composition was significantly altered two days after FFT as compared to placebo. Moreover, we found that FFT induced more virulent phage-microbe interactions within the first two days after administration, while these interactions appeared more temperate in the placebo group.ConclusionWe provide evidence that gut phages from a healthy donor can be safely administered to transiently alter the gut microbiota of recipients, thereby providing a critical basis for follow-up studies.Trial registration numberDutch Trial Registry: NL8289
Prediction of a major adverse coronary event in Women through CORSWO
Authors: Romero-Farina Guillermo , Aguadé-Bruix Santiago , Ferreira-González Ignacio 
Published: March 2023

ABSTRACTBACKGROUNDIn women, risk stratification for a major adverse coronary event (MACE) is complex, and moreover women have often been underrepresented in cardiovascular studies. This study aims to establish aCOronaryRiskScore inWOmen (CORSWO) to predict MACE.METHODSFrom a cohort of 25,943 consecutive patients referred for clinical gSPECT-MPI (gated single-photon emission computed tomography myocardial perfusion imaging), 2,226 women (aged 66.7±11.6 years) were included. During the follow-up (mean 4±2.7 years) post gSPECT-MPI, MACE (unstable-angina requiring hospitalization, non-fetal myocardial infarction, coronary revascularization, cardiac death) was assessed. The patients were divided into training (n=1460) and validation (n=766) groups. To obtain the predictor model, LASSO-regression analysis with 10-fold cross-validation was used.RESULTSIn training group, 148 women had MACE (0.026/patient/year). The best model (ROC area:0.8, Brier score:0.0777) to stratify women included: age >69 years (OR:1.6); diabetes mellitus (OR:2); angina-history (OR:1.6); nitrate (OR:1.5); left bundle branch block (OR:1.2); pharmacological test (OR:1.6); ST-segment-depression (≥1mm) (OR:2); stress angina (OR:1.3); myocardial ischemia >5% (OR:2.6); perfusion defect at rest >9% (OR:2.4); perfusion defect at stress >6% (OR:1.7); end-systolic volume index >15 ml (OR:1.6); and left ventricular ejection fraction <50% (OR:1.2). This model was validated (validation group) with a strong prediction (ROC area:0.8, Brier score:0.0747). The CORSWO obtained from these variables allows the stratification of women into five risk levels: very low (score:0,HR:1), low (score:1-2,HR:1.5), moderate (score:3-6,HR:2.7), high (score:7-10,HR:6.9) and very high (score:≥11,HR:21.7).CONCLUSIONSIn a clinical practice setting we can obtain an excellent coronary risk stratification in women, however at the expense of multiple variables.CLINICAL PERSPECTIVEWhat Is New?The coronary risk stratification of women depends on of the multiple clinical, exercise and imaging variables.This new risk score allows the risk to be calculated for individual women in a simple way with a mean of a 4-year follow-up.What Are the Clinical Implications?CORSWO is an effective tool to stratify the risk for major adverse coronary event in 5 risk levels, very low, low, moderate, high and very high risk with a good accuracy.
Measuring extracellular human brain pH and amino acid metabolism with hyperpolarized [1-13C]pyruvate
Authors: Khan Alixander S , McLean Mary A , Kaggie Joshua D , Horvat-Menih Ines , Matys Tomasz , Schulte Rolf F , Locke Matthew J , Grimmer Ashley , Wodtke Pascal , Latimer Elizabeth , Frary Amy , Graves Martin J , Gallagher Ferdia A 
Published: March 2023

AbstractHyperpolarized carbon-13 MRI has shown promise for non-invasive assessment of the cerebral metabolism of [1-13C]pyruvate in both healthy volunteers and in patients. Exchange of pyruvate to lactate catalyzed by lactate dehydrogenase (LDH), and pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH), are the most widely studied reactionsin vivo. Here we show the potential of the technique to probe other metabolic reactions in the human brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high flip angle pulses were used to detect cerebral13C-labelled carbon dioxide (13CO2), in addition to the13C-bicarbonate (H13CO2-) subsequently formed by carbonic anhydrase. Brain pH weighted towards the extracellular compartment was calculated from the ratio of H13CO3-to13CO2in seven volunteers using the Henderson-Hasselbalch equation, demonstrating an average pH ± S.D. of 7.40 ± 0.02, with inter-observer reproducibility of 0.04. In addition, hyperpolarized [1-13C]aspartate was also detected in four of nine volunteers demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC), and subsequent transamination by aspartate aminotransferase (AST), with this flux being approximately 6% of that through PDH. Hyperpolarized [1-13C]alanine signal was also detected within the head but this was localized to muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized carbon-13 MRI to assess cerebral and extracerebral [1-13C]pyruvate metabolism in addition to LDH and PDH activity. Non-invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance.
Proteogenomic integration reveals CXCL10 as a potentially downstream causal mediator for IL-6 signaling on atherosclerosis
Authors: Prapiadou Savvina , Živković Luka , Thorand Barbara , George Marc J. , van der Laan Sander W. , Malik Rainer , Herder Christian , Koenig Wolfgang , Ueland Thor , Kleveland Ola , Aukrust Pal , Gullestad Lars , Bernhagen Jürgen , Pasterkamp Gerard , Peters Annette , Hingorani Aroon D. , Rosand Jonathan , Dichgans Martin , Anderson Christopher D. , Georgakis Marios K. 
Published: March 2023

ABSTRACTBackgroundGenetic and experimental studies support a causal involvement of interleukin-6 (IL-6) signaling in atheroprogression. While trials targeting IL-6 signaling are underway, any benefits must be balanced against an impaired host immune response. Dissecting the mechanisms that mediate the effects of IL-6 signaling on atherosclerosis could offer insights about novel drug targets with more specific effects.MethodsLeveraging data from 522,681 individuals, we constructed a genetic instrument of 26 variants in the gene encoding the IL-6 receptor (IL-6R) that proxied for pharmacological IL-6R inhibition. Using Mendelian randomization (MR), we assessed its effects on 3,281 plasma proteins quantified with an aptamer-based assay in the INTERVAL cohort (n=3,301). Using mediation MR, we explored proteomic mediators of the effects of genetically proxied IL-6 signaling on coronary artery disease (CAD), large artery atherosclerotic stroke (LAAS), and peripheral artery disease (PAD). For significant mediators, we tested associations of their circulating levels with incident cardiovascular events in a population-based study (n=1,704) and explored the histological, transcriptomic, and cellular phenotypes correlated with their expression levels in samples from human atherosclerotic lesions.ResultsWe found significant effects of genetically proxied IL-6 signaling on 70 circulating proteins involved in cytokine production/regulation and immune cell recruitment/differentiation, which correlated with the proteomic effects of pharmacological IL-6R inhibition in a clinical trial. Among the 70 significant proteins, genetically proxied circulating levels of CXCL10 were associated with risk of CAD, LAAS, and PAD with up to 67% of the effects of genetically downregulated IL-6 signaling on these endpoints mediated by decreases in CXCL10. Higher midlife circulating CXCL10 levels were associated with a larger number of cardiovascular events over 20 years, whereas higherCXCL10expression in human atherosclerotic lesions correlated with a larger lipid core and a transcriptomic profile reflecting immune cell infiltration, adaptive immune system activation, and cytokine signaling.ConclusionsIntegrating multiomics data, we found a proteomic signature of IL-6 signaling activation and mediators of its effects on cardiovascular disease. Our analyses suggest the interferon-γ-inducible chemokine CXCL10 to be a potentially causal mediator for atherosclerosis in three vascular compartments and as such could serve as a promising drug target for atheroprotection.
exFINDER: identify external communication signals using single-cell transcriptomics data
Authors: He Changhan , Zhou Peijie , Nie Qing 
Published: March 2023

ABSTRACTCells make decisions through their communication with other cells and receiving signals from their environment. Using single-cell transcriptomics, computational tools have been developed to infer cell-cell communication through ligands and receptors. However, the existing methods only deal with signals sent by the measured cells in the data, the received signals from the external system are missing in the inference. Here, we present exFINDER, a method that identifies such external signals received by the cells in the single-cell transcriptomics datasets by utilizing the prior knowledge of signaling pathways. In particular, exFINDER can uncover external signals that activate the given target genes, infer the external signal-target signaling network (exSigNet), and perform quantitative analysis on exSigNets. The applications of exFINDER to scRNA-seq datasets from different species demonstrate the accuracy and robustness of identifying external signals, revealing critical transition-related signaling activities, inferring critical external signals and targets, clustering signal-target paths, and evaluating relevant biological events. Overall, exFINDER can be applied to scRNA-seq data to reveal the external signal-associated activities and maybe novel cells that send such signals.
Deep Boosted Molecular Dynamics (DBMD): Accelerating molecular simulations with Gaussian boost potentials generated using probabilistic Bayesian deep neural network
Authors: Do Hung N. , Miao Yinglong 
Published: March 2023

AbstractWe have developed a new Deep Boosted Molecular Dynamics (DBMD) method. Probabilistic Bayesian neural network models were implemented to construct boost potentials that exhibit Gaussian distribution with minimized anharmonicity, thereby allowing for accurate energetic reweighting and enhanced sampling of molecular simulations. DBMD was demonstrated on model systems of alanine dipeptide and the fast-folding protein and RNA structures. For alanine dipeptide, 30ns DMBD simulations captured up to 83-125 times more backbone dihedral transitions than 1µs conventional molecular dynamics (cMD) simulations and were able to accurately reproduce the original free energy profiles. Moreover, DBMD sampled multiple folding and unfolding events within 300ns simulations of the chignolin model protein and identified low-energy conformational states comparable to previous simulation findings. Finally, DBMD captured a general folding pathway of three hairpin RNAs with the GCAA, GAAA, and UUCG tetraloops. Based on Deep Learning neural network, DBMD provides a powerful and generally applicable approach to boosting biomolecular simulations. DBMD is available with open source in OpenMM athttps://github.com/MiaoLab20/DBMD/.