bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery
Authors: Raphael Jacob , Feng Xiaoke , Shotwell Matthew S. , Mazzeffi Michael A. , Bollen Bruce A. , Shah Ashish S. , Kertai Miklos D.
Published: December 2022

Objective:

We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery.

Background:

Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking.

Methods:

A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes.

Results:

Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22–1.32), 1.21 (1.16–1.26), 1.93 (1.85–2.00), 1.82 (1.75–1.89)], deep venous thrombosis [ORs: 1.39 (1.33–1.46), 1.38 (1.32–1.44), 2.18 (2.09–2.28), 1.82 (1.74–1.91], operative mortality [ORs: 1.11 (1.08–1.14), 1.16 (1.13–1.19), 1.29 (1.26–1.32), 1.47 (1.43–1.50)], readmission within 30 days [ORs: 1.05 (1.04–1.06), 1.16 (1.13–1.19), 1.29 (1.26–1.32), 1.47 (1.43–1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19–0.27), 0.34 (0.30–0.39), 0.69 (0.64–0.74), 0.77 (0.72–0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91–1.06), 0.75 (0.68–0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09–1.29), 1.35 (1.25–1.48)].

Conclusions:

Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.
Impact of the Percentage of Overlapping Surgery on Patient Outcomes
Authors: Pitts Charles C. , Ponce Brent A. , Arguello Alexandra M. , Willis Joseph G. , McGwin Gerald , Vatsia Sohrab , Parks Chris T. , Wills Brad W.
Published: December 2022

Objectives:

The primary objective of this study was to analyze the relationship of percentage of surgical overlap with patient outcomes to determine if a detrimental level of overlap exists.

Background:

Overlapping surgery is defined as 1 attending physician supervising 2 or more operative cases simultaneously, without the critical portions of the cases occurring concurrently. To date, no study has examined the relationship of percent overlap, or the percentage of 1 case that is spent overlapping with another, to outcomes, efficiency, safety, and complications.

Methods:

This study is a retrospective cohort study conducted at a large tertiary referral center. The primary outcomes of interest included operative duration, in-hospital mortality, 30-day readmission, and patient safety indicators (PSIs). The Cochran-Armitage test for trend was used to evaluate the outcomes of interest. P values of ≤0.05 were considered statistically significant.

Results:

A total of 87,426 cases were included in this study. There were 62,332 cases without overlap (Group 0), 10,514 cases with 1% to 25% overlap (Group 1), 5303 cases with 26% to 50% overlap (Group 2), 4296 cases with 51% to 75% overlap (Group 3), and 4981 cases with >75% overlap (Group 4). In-hospital mortality decreased as overlap increased (P
trend<0.0001). Operative time increased with increasing overlap (P
trend<0.0001) while readmission rates showed no statistical significance between groups (P
trend=0.5078). Rates of PSIs were lower for Groups 1, 2, and 3 (1.69%, 2.01%, and 2.08%) when compared to Group 0 (2.24%). Group 4 had the highest rate of PSIs at 2.35% (P=0.0086).

Conclusion:

Overlapping surgery was shown to have reduced in-hospital mortality and similar PSI and readmission rates when compared to nonoverlapping cases. Operative time was shown to increase in overlapping surgeries when compared to nonoverlapping surgeries. The results from this study indicate that the percentage of surgical overlap does not detrimentally affect most patient outcomes, especially with overlap of <75%.
Optimal Timing of Perioperative Chemical Thromboprophylaxis in Elective Major Abdominal Surgery
Authors: Klonis Christopher , Ashraf Hamza , Cabalag Carlos S. , Wong Darren J. , Stevens Sean G. , Liu David S.
Published: December 2022

Objective:

To investigate the effect of the timing of chemoprophylaxis on venous thromboembolisms (VTEs) and bleeding rates in patients undergoing major abdominal surgery.

Background:

Postoperative bleeding and VTE incur significant morbidity, mortality, and health care costs. Chemoprophylaxis is used routinely to prevent VTEs but increases bleeding risk. The perioperative timing of chemoprophylaxis initiation may influence both VTE and bleeding risks. The optimal window for commencing chemoprophylaxis in the perioperative period is unclear.

Methods:

MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched using PRISMA guidelines. Randomized trials and cohort studies published between January 1, 2000 to May 10, 2022, which reported on chemoprophylaxis timing as well as the incidence of VTE and bleeding after elective abdominal surgery were meta-analyzed.

Results:

From 6175 studies, 14 (24,922 patients) were meta-analyzed. Bariatric (4 studies), antireflux (1 study), hepato-pancreatic-biliary (5 studies), colorectal (1 study), ventral hernia (1 study), and major intra-abdominal surgeries (2 studies) were included. Chemoprophylaxis was initiated before skin closure in 10,403 patients, and postoperatively in 14,519 patients. Both symptomatic [risk ratios (RR), 0.81; 95% CI, 0.45-1.43; P=0.460] and overall (RR, 0.74; 95% CI, 0.45-1.24; P=0.250) VTE rates were comparable between study groups. Compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (RR, 1.56; 95% CI, 1.13-2.15; P=0.007), major bleeding (RR, 1.63; 95% CI, 1.16-2.28; P=0.005), blood transfusion (RR, 1.48; 95% CI, 1.24-1.76; P<0.001), and reintervention (RR, 1.94; 95% CI, 1.19-3.18; P=0.008).

Conclusions:

Our findings advocate for initiating chemoprophylaxis postoperatively in elective abdominal surgery to minimize bleeding risk without compromising VTE protection.
Just What the Doctor Ordered
Authors: Baimas-George Maria R. , Ross Samuel W. , Yang Hongmei , Matthews Brent D. , Nimeri Abdelrahman , Reinke Caroline E.
Published: December 2022

Objective:

To define the impact of missed ordering of venous thromboembolism (VTE) chemoprophylaxis in high-risk general surgery populations.

Background:

The primary cause of preventable death in surgical patients is VTE. Although guidelines and validated risk calculators assist in dosing recommendations, there remains considerable variability in ordering and adherence to recommended dosing.

Methods:

All adult inpatients who underwent a general surgery procedure between 2016 and 2019 and were entered into Atrium Health National Surgical Quality Improvement Program registry were identified. Patients at high risk for VTE (2010 Caprini score ≥5) and without bleeding history and/or acute renal failure were included. Primary outcome was 30-day postoperative VTE. Electronic medical record identified compliance with “perfect” VTE chemoprophylaxis orders (pVTE): no missed orders and no inadequate dose ordering. Multivariable analysis examined association between pVTE and 30-day VTE events.

Results:

A total of 19,578 patients were identified of which 4252 were high-risk inpatients. Hospital compliance of pVTE was present in 32.4%. pVTE was associated with shorter postoperative length of stay and lower perioperative red blood cell transfusions. There was 50% reduced odds of 30-day VTE event with pVTE (odds ratio: 0.50; 95% CI, 0.30−0.80) and 55% reduction in VTE event/mortality (odds ratio: 0.45; 95% CI, 0.31–0.63). After controlling for relevant covariates, pVTE remained significantly associated with decreased odds of VTE event and VTE event/mortality.

Conclusions:

pVTE ordering in high-risk general surgery patients was associated with 42% reduction in odds of postoperative 30-day VTE. Comprehending factors contributing to missed or suboptimal ordering and development of quality improvement strategies to reduce them are critical to improving outcomes.
Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial
Authors: Maemoto Ryo , Noda Hiroshi , Ichida Kosuke , Miyakura Yasuyuki , Kakizawa Nao , Machida Erika , Aizawa Hidetoshi , Kato Takaharu , Iseki Masahiro , Fukui Taro , Muto Yuta , Fukai Shota , Tsujinaka Shingo , Hatsuzawa Yuuri , Watanabe Fumiaki , Nagamori Masakazu , Takahashi Jun , Kimura Yasuaki , Maeda Shimpei , Takayama Noriya , Sakio Ryotaro , Takahashi Rei , Takenami Tsutomu , Matsuzawa Natsumi , Mieno Makiko , Rikiyama Toshiki
Published: December 2022

Objective:

This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI).

Background:

IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low.

Methods:

This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set.

Results:

Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P=0.154).

Conclusion:

The current recommendation of IOWI with aqueous PVP-I should be reconsidered.
Antidepressant drug prescription and incidence of COVID-19: a retrospective cohort study
Authors: Glebov Oleg O. , Mueller Christoph , Stewart Robert , Aarsland Dag , Perera Gayan
Published: December 2022

While antidepressant drugs (ADs) have shown some efficacy in treatment of COVID-19, their preventative potential remains unexplored. To investigate association between AD and COVID-19 incidence in the community, we analysed data from community-living, non-hospitalized adults admitted to inpatient care of the South London&’Maudsley (SLaM) NHS Foundation Trust during the 1st wave of COVID-19 pandemic in the UK. Prescription of ADs within the period of 1 to 3 months before admission was associated with an approximately 40% decrease in positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was specifically observed for ADs of the Selective Serotonin Reuptake Inhibitor (SSRI) class. These results suggest that ADs, specifically SSRIs, may help prevent COVID-19 infection in the community. Definitive determination of AD preventative potential warrants prospective studies in the wider general population.

Key points

Question

Is there an association between prescription of antidepressants and incidence of COVID-19 in the general population?

Findings

In this retrospective cohort study of mental health outpatients with a recent (1-3 months) antidepressant prescription, there was a statistically significant 40% decrease in positive COVID-19 tests. This association was specifically observed for the most commonly prescribed antidepressant class, Selective Serotonin Reuptake Inhibitors, and remained when adjusted for socioeconomic parameters and physical health.

Meaning

Antidepressant prescription was associated with lower incidence of COVID-19 in the community, warranting further investigation as prophylactics in prospective clinical studies.
Codon language embeddings provide strong signals for protein engineering
Authors: Outeiral Carlos , Deane Charlotte M.
Published: December 2022

Protein representations from deep language models have yielded state-of-the-art performance across many tasks in computational protein engineering. In recent years, progress has primarily focused on parameter count, with recent models’ capacities surpassing the size of the very datasets they were trained on. Here, we propose an alternative direction. We show that large language models trained on codons, instead of amino acid sequences, provide high-quality representations that outperform comparable state-of-the-art models across a variety of tasks. In some tasks, like species recognition, prediction of protein and transcript abundance, or melting point estimation, we show that a language model trained on codons outperforms every other published protein language model, including some that contain over 50 times more parameters. These results suggest that, in addition to commonly studied scale and model complexity, the information content of biological data provides an orthogonal direction to improve the power of machine learning in biology.
An improved habitat suitability index for the great crested newt
Authors: Seccombe Emily , Salguero-Gomez Roberto
Published: December 2022

Great crested newts (GCN) are a protected species whose conservation depends on the provision and protection of their breeding habitat. A habitat suitability index (HSI) developed in 2000 is extensively used in GCN conservation to assess breeding habitat quality. This two-decade old index is based on limited data and validation.

Here, we introduce a new HSI with an improved ability to reflect GCN presence/absence in UK ponds. This proposed HSI is easier, requires less data, and predicts GCN presence/absence better than the previous index.

To inform the new index, we used a dual approach to identify the relative importance of environmental criteria to predict GCN presence/absence. Firstly, we conducted a survey of 288 users of the GCN HSI to assess the perceived strengths and limitations of the existing index. Secondly, we analysed national datasets of GCN presence/absence and associated environmental data. Using these findings, we then tested various index modifications. The final modifications of the new HSI include: (i) using an arithmetic mean to combine variables, rather than a geometric mean, to reduce calculation errors and allow compensation between variables; (ii) excluding water quality and waterfowl impact as these lacked significant power to predict GCN presence/absence and were deemed inaccurate by HSI users; and (iii) changing the scoring relationship for pond area to better reflect current data and provide scores for ponds over 2000m2. Additionally, we present modified graphs to reduce errors in the calculation of pond density scores. We compared scores from the new and original HSIs using an independent dataset for validation, showing that the new HSI better reflects GCN present/absence (larger effect sizes and R-squared values) in comparison to the old HSI. Adopting this improved HSI will enable more effective conservation of the protected species via better-informed decision-making and monitoring.
Towards Cloud-Native, Machine Learning Based Detection of Crop Disease with Imaging Spectroscopy
Authors: Rubambiza Gloire , Galvan Fernando Romero , Pavlick Ryan , Weatherspoon Hakim , Gold Kaitlin M.
Published: December 2022

Developing actionable early detection and warning systems for agricultural stakeholders is crucial to reduce the annual $200B USD losses and environmental impacts associated with crop diseases. Agricultural stakeholders primarily rely on labor-intensive, expensive scouting and molecular testing to detect disease. Spectroscopic imagery (SI) can improve plant disease management by offering decision-makers accurate risk maps derived from Machine Learning (ML) models. However, training and deploying ML requires significant computation and storage capabilities. This challenge will become even greater as global scale data from the forthcoming Surface Biology & Geology (SBG) satellite becomes available. This work presents a cloud-hosted architecture to streamline plant disease detection with SI from NASA’s AVIRIS-NG platform, using grapevine leafroll associated virus complex 3 (GLRaV-3) as a model system. Here, we showcase a pipeline for processing SI to produce plant disease detection models and demonstrate that the underlying principles of a cloud-based disease detection system easily accommodate model improvements and shifting data modalities. Our goal is to make the insights derived from SI available to agricultural stakeholders via a platform designed with their needs and values in mind. The key outcome of this work is an innovative, responsive system foundation that can empower agricultural stakeholders to make data-driven plant disease management decisions, while serving as a framework for others pursuing use-inspired application development for agriculture to follow that ensures social impact and reproducibility while preserving stakeholder privacy.

Key Points

Cloud-based plant disease detection system, easily accommodates newly developed and/or improved models, as well as diverse data modalities.

Empower agricultural stakeholders to use hyperspectral data for decision support while preserving stakeholder data privacy.

Outline framework for researchers interested in designing geospatial/remote sensing applications for agricultural stakeholders to follow.
Development of a 3D Bioprinted Airway Smooth Muscle Model for Manipulating Structure and Measuring Contraction
Authors: Osagie Jeffery O , Syeda Sanjana S , Turner-Brannen Emily , Guimond Michelle , Parrenas Lumiere , Haroon Ahsen , Imasuen Philip , West Adrian R
Published: December 2022

The contractile function of airway smooth muscle (ASM) is inextricably linked to its mechanical properties and interaction with the surrounding mechanical environment. As tissue engineering approaches become more commonplace for studying lung biology, the inability to replicate realistic mechanical contexts for ASM will increasingly become a barrier to a fulsome understanding of lung health and disease. To address this knowledge gap, we describe the use of 3D bioprinting technology to generate a novel experimental model of ASM with a wide scope for modulating tissue mechanics.

Using a stiffness modifiable alginate-collagen-fibrinogen bioink, we demonstrate that modulating the stiffness of free-floating ASM ‘bare rings’ is unfeasible; bioink conditions favorable for muscle formation produce structures that rapidly collapse. However, the creation of novel ‘sandwich’ and ‘spiderweb’ designs that encapsulate the ASM bundle within stiff acellular load bearing frames successfully created variable elastic loads opposing tissue collapse and contraction. Sandwich and spiderweb constructs demonstrated realistic actin filament organisation, generated significant baseline tone, and responded appropriately to acetylcholine, potassium chloride and cytochalasin D. Importantly, the two designs feasibly simulate different mechanical contexts within the lung. Specifically, the sandwich was relatively compliant and subject to plastic deformation under high contractile loads, whereas the stiffer spiderweb was more robust and only deformed minimally after repeated maximal contractions.

Thus, our model represents a new paradigm for studying ASM contractile function in a realistic mechanical context. Moreover, it holds significant capacity to study the effects of ECM composition, multiple cell types and fibrosis on lung health and disease.

GRANTS

Natural Sciences and Engineering Research Council, Discovery Grant (Adrian West)

Research Manitoba, New Investigator Operating Grant (Adrian West)

Children’s Hospital Research Institute of Manitoba, Operating Grant (Adrian West)

Canadian Foundation for Innovation, John R. Evans Leaders Fund (Adrian West)

University of Manitoba, Manitoba Graduate Scholarship (Jeffery Osagie)

Research Manitoba, Master’s Studentship Award (Jeffery Osagie)

Research Manitoba, Master’s Studentship Award (Sanjana Syeda)

Children’s Hospital Research Institute of Manitoba, Summer Studentship (Michelle Guimond)

University of Manitoba, Jack Prior Memorial Undergraduate Student Research Award (Lumiere Parrenas)

University of Manitoba, Undergraduate Research Award (Ahsen Haroon)

University of Manitoba, UMSU Undergraduate Research Award (Philip Imasuen)

The grant bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Assessing multiple evidence streams to decide on confidence for identification of post-translational modifications, within and across data sets
Authors: Camacho Oscar M , Ramsbottom Kerry A , Collins Andrew , Jones Andrew R
Published: December 2022

Phosphorylation is a post-translational modification of great interest to researchers due to its relevance in many biological processes. LC-MS/MS techniques have enabled high-throughput data acquisition with studies claiming identification and localisation of thousands of phosphosites. The identification and localisation of phosphosites emerge from different analytical pipelines and scoring algorithms, with uncertainty embedded throughout the pipeline. For many pipelines and algorithms, arbitrary thresholding is used, but little is known about the actual global false localisation rate in these studies. Recently, it has been suggested using decoy amino acids to estimate global false localisation rates of phosphosites, amongst the peptide-spectrum matches reported. We here describe a simple pipeline aiming to maximize the information extracted from these studies by objectively collapsing from peptide-spectrum match to peptidoform-site level, as well as combining findings from multiple studies while maintaining track of false localisation rates. We show that the approach is more effective than current processes that use a simpler mechanism for handling phosphosite identification redundancy within and across studies. In our case study using 8 rice phophoproteomics data sets, 6,368 unique sites were identified confidently identified using our decoy approach compared to 4,687 using traditional thresholding in which false localisation rates are unknown.
Okapi-EM – a napari plugin for processing and analysing cryogenic serial FIB/SEM images
Authors: Perdigão Luís M. A. , Ho Elaine M. L. , Cheng Zhiyuan C. , Yee Neville B.-y. , Glen Thomas , Wu Liang , Grange Michael , Dumoux Maud , Basham Mark , Darrow Michele C.
Published: December 2022

An emergent volume electron microscopy (vEM) technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualisation and analysis of the data is possible. SEM images are affected by noise, drift, and charging effects, that can make precise 3D reconstruction of biological features difficult. This paper presents Okapi-EM, an open-source Napari plugin(1)developed to process and analyse cryogenic serial FIB/SEM images. Okapi-EM enables automated image registration of slices, evaluation of image quality metrics specific to FIB-SEM imaging, and mitigation of charging artefacts. Implementation of Okapi-EM within the Napari framework ensures that the tools are both user- and developer-friendly, through provision of a graphical user interface and access to Python programming. Napari also hosts a variety of other image processing plugins so Okapi-EM tools can be integrated into and combined with other workflows. Okapi-EM can be downloaded freely athttps://github.com/rosalindfranklininstitute/okapi-em, or installed from Python package index (PyPI).

Impact statement

Cryogenic serial pFIB/SEM is an emerging microscopy technique that is used to visualise 3D structures of biological features at mesoscale resolutions(2). This technique requires common post processing of data such as alignment and charge mitigation to enable robust segmentation and analysis. In addition, approaches are needed to quantify data quality to enable an assessment of features and tune data acquisition parameters to enable optimal image acquisition. This article presents Okapi-EM, a combination of software tools designed to facilitate these important initial steps in assessing and processing images from these experiments. These tools have been assembled as a plugin for a popular 3D biological image visualiser called Napari, making their usage user-friendly and readily accessible.
Surface tension drives neuronal sorting in magnetically engineered brain-like tissue
Authors: Perez Jose E. , Jan Audric , Villard Catherine , Wilhelm Claire
Published: December 2022

Engineered 3D brain-like models have advanced the understanding of neurological mechanisms and disease, yet their mechanical signature, while fundamental for brain function, remains understudied. The surface tension for instance controls brain development and is a marker of cell-cell interactions. Here, we engineered 3D magnetic brain-like tissue spheroids composed of intermixed primary glial and neuronal cells at different ratios. Remarkably, the two cell types self-assemble into a functional tissue, with the sorting of the neuronal cells towards the periphery of the spheroids, whereas the glial cells constitute the core. The magnetic fingerprint of the spheroids then allows their deformation when placed under a magnetic field gradient, at a force equivalent to a 70 g increased gravity at the spheroid level. The tissue surface tension and elasticity can be directly inferred from the resulting deformation, revealing a transitional dependence on the glia/neuron ratio, with the surface tension of neuronal tissue being much lower. This provides the underlying mechanical explanation for the exclusion of the neurons towards the outer spheroid region, and depicts the glia/neuron organization as a surface tension-driven sophisticated mechanism that should in turn influence brain development and homeostasis.
Drinkable, liquidin situ-forming and tough hydrogels for gastrointestinal therapeutics
Authors: Liu Gary W. , Pickett Matthew J. , Kuosmanen Johannes L. P. , Ishida Keiko , Madani Wiam A. M. , White Georgia N. , Jenkins Joshua , Feig Vivian R. , Jimenez Miguel , Lopes Aaron , Morimoto Joshua , Fitzgerald Nina , Cheah Jaime H. , Soule Christian K. , Fabian Niora , Hayward Alison , Langer Robert S. , Traverso Giovanni
Published: December 2022

Tablets and capsules are a cornerstone of medicine, but these solid dosage forms can be challenging to swallow for geriatric and pediatric patients. While liquid formulations are easier to ingest, these formulations lack the capacity to localize therapeutics and excipients nor act as controlled release devices. To bridge the advantages of solid and liquid dosage forms, here we describe drug formulations based on liquidin situ-forming and tough (LIFT) hydrogels. Drug-loaded LIFT hydrogels are formed directly in the stomach through the sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by the ingestion of a drug-containing polymer solution of alginate and 4-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels are mechanically tough and able to robustly form in the presence of complex gastric fluid andin vivoin rat and porcine stomachs. LIFT hydrogels are retained within the porcine stomach for up to 24 h, biocompatible, and safely cleared. These hydrogels deliver a total dose comparable to unencapsulated drug but with delayed and lower maximum drug plasma concentrations, providing a method for controlled release that may mitigate drug toxicity. Co-encapsulation of lactase as a model biologic drug and calcium carbonate mitigated gastric-mediated deactivation of encapsulated enzyme in rat and porcine models. We also demonstrate the potential of these hydrogels to encapsulate and protect a model therapeutic bacterium,E. coliNissle 1917, against acid. LIFT hydrogels present a biocompatible means of tough, double-network hydrogel formationin situin the gastric cavity, and may expand medication access for patients with difficulty swallowing.
A new simulation framework to evaluate the suitability of eDNA for marine and aquatic Environmental Impact Assessments
Authors: Coston-Guarini J. , Hinz S. , Mirimin L. , Guarini J.-M.
Published: December 2022

This study evaluates how eDNA information could be used within Environmental Impact Assessment (EIA). We developed an original model to simulate the conditions for which an eDNA signal detects, or does not detect, an impact on a targeted (receptor) species in a given project area. The simulation has four consecutive steps. First, a deterministic model simulated the dynamics of the receptor population and their eDNA fragment concentrations in the environment. Second, random distributions of receptor organisms and eDNA fragment quantities at steady-state were simulated within the project area. Then Simple Random Samplings were performed for both the receptor and eDNA. Third, post-sampling processes (eDNA extraction, amplification, analysis) were simulated to estimate the detection probability of the species from sample plan characteristics (size of sampling unit, number of samples collected). Fourth, we simulated an impact by modifying the growth, mortality and mobility (null, passive and active) parameters of the receptor species, then determined if an impact was detected. Detection probability curves were estimated for a range of sample volumes fitted with a Weibull cumulative distribution function. An F-like statistic compared detection curves before and after impact. Twelve scenarios were simulated. A statistically significant impact was detected with eDNA when receptor species growth rate was halved, but only in cases of null or passive mobility. When the receptor experienced both reduced growth and increased mortality rates, an impact was detected in all three mobility cases (null, passive and active). Our results suggest that an impact could be detected using eDNA if both the population dynamics of the receptor and the dynamics of DNA shed into the environment are known. These results indicate that caution should be exercised with eDNA data for EIA, but the proposed framework provides a valuable starting point to improve interpretation of indirect observation methods such as eDNA.
Mapping current and future thermal limits to suitability for malaria transmission by the invasive mosquitoAnopheles stephensi
Authors: Ryan Sadie J. , Lippi Catherine A. , Villena Oswaldo C. , Singh Aspen , Murdock Courtney C. , Johnson Leah R.
Published: December 2022

Background

Anopheles stephensiis a malaria-transmitting mosquito that has recently expanded from its primary range in Asia and the Middle East, to locations in Africa. This species is a competent vector of bothP. falciparum(PF) andP. vivax(PV) malaria. Perhaps most alarming, the characteristics ofAn. stephensi, such as container breeding and anthropophily, make it particularly adept at exploiting built environments in areas with no prior history of malaria risk.

Methods

In this paper we created global maps of thermal transmission suitability and people at risk (PAR) for malaria transmission byAn. stephensi, under current and future climate. Temperature-dependent transmission suitability thresholds derived from recently published species-specific thermal curves were used to threshold gridded, monthly mean temperatures under current and future climatic conditions. These temperature driven transmission models were coupled with gridded population data for 2020 and 2050, under climate-matched scenarios for future outcomes, to compare with baseline predictions for 2020 populations.

Results

Using the Global Burden of Disease regions approach, we found that heterogenous regional increases and decreases in risk did not mask the overall pattern of massive increases of PAR for malaria transmission suitability withAn. stephensipresence. General patterns of poleward expansion for thermal suitability were seen for both PF and PV transmission potential.

Conclusions

Understanding the potential suitability forAn. stephensitransmission in a changing climate provides a key tool for planning, given an ongoing invasion and expansion of the vector. Anticipating the potential impact of onward expansion to transmission suitable areas, and the size of population at risk under future climate scenarios, andwherethey occur, can serve as a large-scale call for attention, planning, and monitoring.
Accurate cell type deconvolution in spatial transcriptomics using a batch effect-free strategy
Authors: Wang Linhua , Wu Ling , Liu Chaozhong , Wang Wanli , Zhang Xiang H.-F. , Liu Zhandong
Published: December 2022

Sequencing-based spatial transcriptomics (ST) techniques have been groundbreaking in dissecting cell-cell communications within tissues by profiling positional gene expression. However, the most widely used ST technique, Visium Spatial Gene Expression by 10x Genomics (Visium), does not provide single-cell resolution, making it difficult to profile cell type-level information. Many reference-based deconvolution methods have been developed to increase its resolution, but the platform and batch effects between the reference and ST data compromise their accuracy. Here, we propose a new approach,Region-based cellSorting (ReSort), that generates a pseudo-internal-reference to reduce these platform effects. By simulating ST datasets under various scenarios, we demonstrate that ReSort significantly improves the accuracy of six state-of-the-art reference-based deconvolution methods. Moreover, applying ReSort to a mouse breast cancer tumor bearing both epithelial and mesenchymal clones identifies the spatial differences of immune cells between the clones, providing important insights for understanding the relationship between epithelial-mesenchymal transition and immune infiltration in breast cancer.
Highly contiguous genome assembly and population sequencing reveal three distinct populations and signatures of insecticide resistance ofTuta absolutain Latin America
Authors: Lewald Kyle M. , Tabuloc Christine A. , Godfrey Kristine E. , Arnó Judit , Perini Clérison R. , Guedes Jerson C. , Chiu Joanna C.
Published: December 2022

Tuta absolutais one of the largest threats to tomato agriculture worldwide. Native to South America, it has rapidly spread throughout Europe, Africa, and Asia over the past two decades. To understand howT. absolutahas been so successful and to improve containment strategies, high quality genomic resources and an understanding of population history is critical. Here, we describe a highly contiguous annotated genome assembly, as well as a genome-wide population analysis of samples collected across Latin America. The new genome assembly has an L50 of 17 with only 132 contigs. Based on hundreds of thousands of SNPs, we detect three major population clusters in Latin America with some evidence of admixture along the Andes Mountain range. Based on coalescent simulations, we find these clusters diverged from each other tens of thousands of generations ago prior to domestication of tomatoes. We further identify several genomic loci under selection related to insecticide resistance, immunity, and metabolism. This data will further future research toward genetic control strategies and inform future containment policies.
Effect of pregnancy and hypertension on kidney function in female rats: Modeling and functional implications
Authors: Stadt Melissa M. , West Crystal A. , Layton Anita T.
Published: December 2022

Throughout pregnancy, the kidneys undergo significant adaptations in morphology, hemodynamics, and transport to achieve the volume and electrolyte retention required to support a healthy pregnancy. Additionally, during pregnancies complicated by chronic hypertension, altered renal function from normal pregnancy occurs. The goal of this study is to analyze how inhibition of critical transporters affects gestational kidney function as well as how renal function is affected during chronic hypertension in pregnancy. To do this, we developed epithelial cell-based multi-nephron computational models of solute and water transport in the kidneys of a female rat in mid- and late pregnancy. We simulated the effects of key individual pregnancy-induced changes on renal Na+and K+transport: proximal tubule length, Na+/H+exchanger isoform 3 (NHE3) activity, epithelial Na+channel activity (ENaC), K+secretory channel expression, and H+-K+-ATPase activity. Additionally, we conducted simulations to predict the effects of inhibition and knockout of the ENaC and H+-K+-ATPase transporters on virgin and pregnant rat kidneys. Our simulation results predicted that the ENaC and H+-K+-ATPase transporters are essential for sufficient Na+and K+reabsorption during pregnancy. Last, we developed models to capture changes made during hypertension in female rats and considered what may occur when a rat with chronic hypertension becomes pregnant. Model simulations predicted that in hypertension for a pregnant rat there is a similar shift in Na+transport from the proximal tubules to the distal tubules as in a virgin rat.
Identification of EPHB4 variants in dilated cardiomyopathy patients
Authors: Luxán Guillermo , Muhly-Reinholz Marion , Glaser Simone F. , Trebing Johannes , Reich Christoph , Haas Jan , Sedaghat-Hamedani Farbod , Meder Benjamin , Dimmeler Stefanie
Published: December 2022

Cardiac homeostasis relies on the appropriate provision of nutrients to the working myocardium. EPHB4 is required for the maintenance of vascular integrity and correct fatty acid transport uptake in the heart via regulating the caveolar trafficking of the fatty acid receptor CD36. In the mouse, endothelial specific loss-of-function of the receptor EphB4, or its ligand ephrin-B2, induces Dilated Cardiomyopathy (DCM) like defects. Now, we have identified six newEPHB4variants with deleterious potential in a cohort of 573 DCM patients. Similar to the EphB4 mutant mice,EPHB4variants carrying patients show an altered expression pattern of CD36 and CAV1 in the heart. For the first time, our data identifies EPHB4 mutations in DCM patients. This observation supports the notion that the Eph-ephrin signalling pathway, and in particular the receptor EPHB4, plays a role in the development of DCM in human patients.
Patient Flow in Congested Intensive Care Unit /Step-down Unit system: Premature Step-down or not?
Authors: Kobara Yawo M. , Rodrigues Felipe F. , de Souza Camila P. E. , Stanford David A.
Published: December 2022

A Step-Down Unit (SDU) provides an intermediate Level of Care for patients from an Intensive Care Unit (ICU) as their condition becomes less acute. SDU congestion, as well as upstream patient arrivals, forces ICU administrators to incur costs, either in the form of overstays or premature step-downs. Basing on a proxy for patient acuity level called the ‘Nine Equivalents of Nursing Manpower Score (NEMS)’, patients were classified into two groups: high-acuity and low-acuity. Two patient flow policies were developed that select actions to optimize the system’s net health service benefit: one allowing for premature step-down actions, and the other allowing for patient rejection actions when the system is congested. The results show that the policy with patient rejection has a net health service benefit that significantly exceeds that of the policy with the premature step-down option. Based on these results, it can be concluded that premature step-down contributes to congestion downstream. Counter-intuitively, premature step-down should therefore be discouraged and patient rejection actions should be further explored as viable options for congested ICUs.
Estimating the Global Spread of Epidemic Human Monkeypox with Bayesian Directed Acyclic Graphic Model
Authors: Liao Ling-Chun , Hsu Chen-Yang , Lai Chao-Chih , Chen Tony Hsiu-Hsi
Published: December 2022

Objectives

A ‘Public Health Emergency of International Concern (PHEIC)’ monkeypox outbreak was declared by the World Health Organization on June 23, 2022. More than 16,000 monkeypox cases were reported in more than 75 countries across six regions as July 25.

Design

A modeling study.

Setting and Participants

Daily confirmed Monkeypox cases of the global, United States, Spain, Brazil, and United Kingdom were retrieved from the Global health team till September 23,2022. All conducted analyses are at the aggregate level.

without involvement of confidential information.

Primary and secondary outcome measures

The Bayesian SIR (Susceptible-Infected-Recovered) model with Directed Acyclic Graphic method was used to estimate the basic/effective reproductive number (R0/ Re) and to assess the epidemic spread of Monkeypox in the globe.

Results

The maximum estimated R0/ Rewas 1.16 (1.15-1.17), 1.20 (1.20-1.20), 1.34 (1.34-1.35), and 1.33 (1.33-1.33) in United States, Spain, Brazil, and United Kingdom, respectively. The values of R0/ Rewas toward to below 1 after August, 2022. The estimated infectious time before isolation ranged from 2.05 to 2.74 days.

Conclusions

The PHEIC of global spreading of human Monkeypox outside Africa has been contained so as to avoid a pandemic in the light of the reasoning-based epidemic model assessment.

Strengths and limitations of this study

We estimated the epidemiology parameters based on the Bayesian SIR model for the uncertainty transmission of monkeypox under assumptions of homogeneous random mixing population and surveillance systems were the same across countries.

This approach can minimize biases between population, different surveillance systems across countries. Estimating results of R0 were limited but consistent between countries and similar to the simulation data by the deterministic SIR model.
Impact of patient habitus and acquisition protocol on iodine quantification in dual source photon-counting CT
Authors: Pua Rizza , Liu Leening P. , Dieckmeyer Michael , Shapira Nadav , Sahbaee Pooyan , Gang Grace J. , Litt Harold I. , Noël Peter B.
Published: December 2022

Objective

Evaluation of iodine quantification accuracy with varying iterative reconstruction level, patient habitus, and acquisition mode on a first-generation dual-source photon-counting computed tomography (PCCT) system.

Methods

A multi-energy CT phantom (20 cm diameter/small) was imaged with and without an extension ring (30 by 40 cm/large). It was equipped with various iodine inserts (0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 15.0 mg/ml) and scanned over a range of radiation dose levels (CTDIvol 0.5, 0.8, 1.2, 1.6, 2.0, 4.0, 6.0, 10.0, 15.0 mGy) using four different acquisition modes: single source 120 kVp (SS120), 140 kVp (SS140) and dual-source 120 kVp (DS120), 140 kVp (DS140). Iodine density maps were produced with different levels of iterative reconstruction (QIR 0, 2, 4). To assess the agreement between nominal and measured iodine concentrations, root mean square error (RMSE) and Bland-Altman plots were generated by grouping different radiation dose levels (ultra-low: < 1.5 mGy; low: 1.5 – 5 mGy; medium: 5 – 15 mGy) and iodine concentrations (low: < 5 mg/ml; high: 5 – 15 mg/ml).

Results

Overall, quantification of iodine concentrations was accurate and reliable even at ultra-low radiation dose levels. With low and high iodine concentrations, RMSE ranged from 0.25 to 0.37, 0.20 to 0.38, and 0.25 to 0.37 mg/ml for ultra-low, low, and medium radiation dose levels, respectively. Similarly, for the three acquisition modes (SS120, SS140, DS 120, DS140), RMSE was stable at 0.31, 0.28, 0.33 and 0.30 mg/ml, respectively. Considering all levels of radiation dose, acquisition mode, and iodine concentration, the accuracy of iodine quantification was higher for the phantom without extension ring (RMSE 0.21 mg/ml) and did not vary across different levels of iterative reconstruction.

Conclusions

The first-generation PCCT allows for accurate iodine quantification over a wide range of iodine concentrations and radiation dose levels. Even very small concentrations of iodine can be quantified accurately at different simulated patient sizes. Stable accuracy across iterative reconstruction levels may allow further radiation exposure reductions without affecting quantitative results.

Clinical photon-counting CT provides excellent iodine quantification performance for a wide range of parameters (patient habitus, acquisition parameters, and iterative reconstruction modes) due to its excellent ultra-low dose performance.

Key Results

First-generation PCCTs are capable of accurately quantifying iodine over a wide range of radiation dose levels and iodine concentrations.

Further radiation exposure reductions may be possible given stable accuracy across iterative reconstruction levels.

In the future, accurate and precise iodine quantification will allow for the development of spectral-based biomarkers.
CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to Navitoclax
Authors: Neault Mathieu , Lebert-Ghali Charles-Étienne , Fournier Marilaine , Capdevielle Caroline , Garfinkle Elizabeth A.R. , Obermayer Alyssa , Cotton Anitria , Boulay Karine , Sawchyn Christina , Nguyen Kamy H. , Assaf Béatrice , Mercier François E. , Delisle Jean-Sébastien , Drobetsky Elliot A. , Hulea Laura , Shaw Timothy I. , Zuber Johannes , Gruber Tanja A. , Melichar Heather J. , Mallette Frédérick A.
Published: December 2022

Pediatric acute megakaryoblastic leukemia (AMKL) is an aggressive, uncurable blood cancer associated with poor therapeutic response and high mortality. We developed CBFA2T3-GLIS2-driven mouse models of AMKL that recapitulate the phenotypic and transcriptional signatures of the human disease. We show that an activating Ras mutation, which occurs in human AMKL, increased the penetrance and decreased the latency of CBF2AT3-GLIS2-driven AMKL. CBFA2T3-GLIS2 and GLIS2 modulate similar transcriptional networks. We uncover the dominant oncogenic properties of GLIS2, which trigger AMKL in cooperation with oncogenic Ras. We find that both CBFA2T3-GLIS2 and GLIS2 alter the expression of numerous BH3-only proteins, causing AMKL cell sensitivity to the BCL-2 inhibitor navitoclax bothin vitroandin vivo, suggesting a novel therapeutic option for pediatric patients suffering from CBFA2T3-GLIS2-driven AMKL.

Key points

GLIS2 cooperates with activated Nras to promote the development of acute megakaryoblastic leukemia.

CBFA2T3-GLIS2 and GLIS2 alter the expression of BCL2 family members rendering AMKL cells sensitive to navitoclax.