bluuebunny/crossref_metadata_2025 huggingface dataset:
An artificial intelligence accelerated virtual screening platform for drug discovery
Authors: Zhou Guangfeng , Rusnac Domnita-Valeria , Park Hahnbeom , Canzani Daniele , Nguyen Hai Minh , Stewart Lance , Bush Matthew F. , Nguyen Phuong Tran , Wulff Heike , Yarov-Yarovoy Vladimir , Zheng Ning , DiMaio Frank
Published: March 2024

Structure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding pose and binding affinity predicted by computational docking. Here we developed a highly accurate structure-based virtual screen method, RosettaVS, for predicting docking poses and binding affinities. Our approach outperforms other state-of-the-art methods on a wide range of benchmarks, partially due to our ability to model receptor flexibility. We incorporate this into a new open-source artificial intelligence accelerated virtual screening platform for drug discovery. Using this platform, we screened multi-billion compound libraries against two unrelated targets, a novel ubiquitin ligase target KLHDC2 and the human voltage-gated sodium channel NaV1.7. On both targets, we discover hits, including seven novel hits (14% hit rate) to KLHDC2 and four novel hits (44% hit rate) to NaV1.7 with single digit micromolar binding affinities. Screening in both cases was completed in less than seven days. Finally, a high resolution X-ray crystallographic structure validates the predicted docking pose for the KLHDC2 ligand complex, demonstrating the effectiveness of our method in lead discovery.
Three Modes of Viral Adaption by the Heart
Authors: Griffiths Cameron D. , Shah Millie , Shao William , Borgman Cheryl A. , Janes Kevin A.
Published: March 2024

Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly one thousand human hearts profiled by RNA sequencing. Among virus-positive cases (∼20%), we identified three robust adaptions in the host transcriptome related to inflammatory NFκB signaling and post-transcriptional regulation by the p38–MK2 pathway. The adaptions are not determined by the infecting virus, and they recur in infections of human or animal hearts and cultured cardiomyocytes. Adaptions switch states when NFκB or p38–MK2 are perturbed in cells engineered for chronic infection by the cardio-pathogenic virus, coxsackievirus B3. Stratifying viral responses into reversible adaptions adds a targetable systems-level simplification for infections of the heart and perhaps other organs.
Repurposing Clinical MRI Archives for Multiple Sclerosis Research with a Flexible, Single-Modality Approach: New Insights from Old Scans
Authors: Goebl Philipp , Wingrove Jed , Abdelmannan Omar , Vega Barbara Brito , Stutters Jonathan , Graca Ramos Silvia Da , Kenway Owain , Rosoor Thomas , Wassmer Evangeline , Chataway Jeremy , Arnold Douglas , Collins Louis , Hemmingway Cheryl , Narayanan Sridar , Chard Declan , Iglesias Juan Eugenio , Barkhof Frederik , Hacohen Yael , Thompson Alan , Alexander Daniel , Ciccarelli Olga , Eshaghi Arman
Published: March 2024

In multiple sclerosis (MS), magnetic resonance imaging (MRI) biomarkers are critical for research in diagnosis, prognosis and assessing treatment efficacy. Traditionally, extracting relevant biomarkers of disease activity and neurodegeneration requires multimodal MRI protocols, limiting the use of the already existing vast amount of incomplete or single-modality MRI data which are acquired in clinical settings. We developed MindGlide, a deep learning model that extracts volums of brain regions and lesion from a single MRI modality, simplifying analysis and enabling the use of heterogeneous clinical archives. We trained MindGlide on a dataset of 4,247 brain MRI scans from 2,934 MS patients across 592 MRI scanners and validated it on 14,952 brain MRI scans from 1001 patients from three unseen external validation cohorts including 161 adolescent patients. Using dice scores, we demonstrated that MindGlide accurately estimated white matter lesion, cortical, and deep grey matter volumes. These volumes correlated with disability (Expanded Disability Status Scale, absolute correlation coefficients 0.1-0.2, p<0.05), and MindGlide outperformed an established tool in this regard. MindGlide robustly detected treatment effects across clinical trials, including disease activity and neurodegeneration (as shown by lesion accrual and brain tissue loss, respectively), even when analysing MRI modalities not traditionally used for such detailed measurements. Our results indicate the potential to indirectly reduce scan time and drug development costs in clinical trials while directly transforming the utility of retrospective analysis of real-world data acquired in clinical settings. As a consequence, scan time will be reduced and, in turn, the cost of trials.
THE USE OF BOTULINUM TOXIN FOR SPASTICITY IN PEOPLE AFFECTED BY SPINAL CORD INJURY: A SCOPING REVIEW PROTOCOL
Authors: Alessandro Zadra , Daniel Feller , Irene Maini , Michele Zarbo , Jacopo Bonavita
Published: March 2024

Introduction

Up to 80% of individuals affected by Spinal Cord Injury (SCI) develops spasticity, both in the acute and chronic phases. Botulinum NeuroToxin (BoNT) injections have been proven to be an effective intervention to treat focal spasticity in Stroke, Cerebral Palsy and Multiple Sclerosis. However, to the best of our knowledge, only one systematic review published in 2015 evaluated the efficacy of BoNT in treating spasticity in patients affected by SCI.

Objective

We formulated the following research question: “What is known from the existing literature about the use of BoNT for treating spasticity in patients affected by SCI?”.

Material and methods

We will include studies focusing on using BoNT to treat spasticity in patients with SCI due to any cause. We will search the following databases: MEDLINE (via PubMed), Embase, CENTRAL, Scopus, and PEDro. In addition, grey literature and the reference lists of all relevant studies will be searched. Two authors will independently perform the study selection and data extraction phases. Results from the scoping review will be summarized descriptively through tables and diagrams.
Physics and physiology determine strategies of bacterial investment in flagellar motility
Authors: Lisevich Irina , Colin Remy , Yang Hao Yuan , Ni Bin , Sourjik Victor
Published: March 2024

Regulatory strategies that allow microorganisms to balance their investment of limited resources in different physiological functions remain poorly understood, particularly for numerous cellular functions that are not directly required for growth. Here, we investigate the allocation of resources to flagellar swimming, the most prominent and costly behavior in bacteria that is not directly required for growth. We show that the dependence of motile behavior on gene expression in Escherichia coli is determined by the hydrodynamics of propulsion, which limits the ability of bacteria to increase their swimming by synthesizing more than a critical number of flagellar filaments. Together with the fitness cost of flagellar biosynthesis, this defines the physiologically relevant range of investment in motility. Gene expression in all E. coli isolates tested falls within this range, with many strains maximizing motility under nutrient-rich conditions, particularly when grown on a porous medium. The hydrodynamics of swimming may further explain the bet-hedging behavior observed at low levels of motility gene expression.
Scaffolded cooperative problem-based approach in entrepreneurship education for vocational preservice teacher
Authors: Widiastuti Indah , Budiyanto Cucuk Wawan , Towip Towip , Estriyanto Yuyun , Hassan Syed Ahmad Helmi Syed , Pratami Devi
Published: March 2024

Purpose

This study aims to comprehend vocational preservice teachers' recalled experiences with the Cooperative Problem-based Learning (CPBL) pedagogical approach in an entrepreneurship course and to reveal how these experiences will impact their future teaching practice. The course under study intends to improve preservice teachers' entrepreneurial attitudes while equipping them with the skills necessary to create a comparable teaching strategy at school after graduation.

Design/methodology/approach

This study used the semi-structured interview data to triangulate the qualitative data collected from the students' reflection journals. The data were thematically analyzed whereas the codes with comparable elements were combined, resulting in themes that describe the relevance of scaffolding used with each component of the MUSIC motivational model.

Findings

The results revealed that the student teachers who took part in the research stated in their comments how the scaffolds used in the CPBL sessions impacted their learning. Additionally, they could articulate the experiences that strengthened their perceptions regarding entrepreneurs and entrepreneurship education.

Practical implications

By implementing scaffolded CPBL in entrepreneurship course during the teacher preparation program, the preservice teachers would be able to put a similar approach into the practice of their future teaching profession in guiding students to accomplish instructional outcomes.

Originality/value

This study highlights the importance of providing more innovative practices for entrepreneurship education across teacher preparation curricula to help develop the skills necessary for entering the future profession. The findings also emphasize the value of scaffolding in PBL, including expert, peer and activity design scaffolding. It also completes the body of research indicating that PBL-based entrepreneur education instruction can help students develop their entrepreneurial skills and attitudes while also providing a great chance to improve their teaching abilities.
Digital twins for smart building at the facility management stage: a systematic review of enablers, applications and challenges
Authors: Ghansah Frank Ato
Published: March 2024

Purpose

Despite the opportunities of digital twins (DTs) for smart buildings, limited research has been conducted regarding the facility management stage, and this is explained by the high complexity of accurately representing and modelling the physics behind the DTs process. This study thus organises and consolidates the fragmented literature on DTs implementation for smart buildings at the facility management stage by exploring the enablers, applications and challenges and examining the interrelationships amongst them.

Design/methodology/approach

A systematic literature review approach is adopted to analyse and synthesise the existing literature relating to the subject topic.

Findings

The study revealed six main categories of enablers of DTs for smart building at the facility management stage, namely perception technologies, network technologies, storage technologies, application technologies, knowledge-building and design processes. Three substantial categories of DTs application for smart buildings were revealed at the facility management stage: efficient operation and service monitoring, efficient building energy management and effective smart building maintenance. Subsequently, the top four major challenges were identified as being “lack of a systematic and comprehensive reference model”, “real-time data integration”, “the complexity and uncertainty nature of real-time data” and “real-time data visualisation”. An integrative framework is finally proposed by examining the interactive relationship amongst the enablers, the applications and the challenges.

Practical implications

The findings could guide facility managers/engineers to fairly understand the enablers, applications and challenges when DTs are being implemented to improve smart building performance and achieve user satisfaction at the facility management stage.

Originality/value

This study contributes to the knowledge body on DTs by extending the scope of the existing studies to identify the enablers and applications of DTs for smart buildings at the facility management stage and the specific challenges.
Intrinsic and extrinsic drivers of organic matter processing along phosphorus and salinity gradients in coastal wetlands
Authors: Anderson Kenneth J. , Kominoski John S. , Sah Jay P.
Published: March 2024

Climate change is accelerating sea‐level rise and saltwater intrusion in coastal regions world‐wide and interacting with large‐scale changes in species composition in coastal wetlands. Quantifying macrophyte litter breakdown along freshwater‐to‐marine coastal gradients is needed to predict how carbon stores will respond to shifts in both macrophyte communities and water chemistry under changing environmental conditions.

To test the interactive drivers of changing species identity and water chemistry, we performed a reciprocal transplant of four macrophyte litter species in seven sites along freshwater‐to‐marine gradients in the Florida Coastal Everglades. We measured surface water chemistry (dissolved organic carbon, total nitrogen and total phosphorus), litter chemistry (% nitrogen, % phosphorus, change in N:P molar ratio, % cellulose and % lignin as proxies for recalcitrance) and litter breakdown rates (k/degree‐day).

Direct effects of salinity and surface water nutrients were the strongest drivers of k, but unexpectedly, litter chemistry did not correlate with litter k. However, salinity strongly correlated with changes in litter chemistry, whereby litter incubated in brackish and marine wetlands was more labile and gained more phosphorus compared with litter in freshwater marshes. Our results suggest that litter k in coastal wetlands is explained by species‐specific interactions among water and litter chemistries. Water nutrient availability was an important predictor of breakdown rates across species, but breakdown rates were only explained by the carbon recalcitrance of litter in the species with the slowest breakdown (Cladium jamaicense), indicating the importance of carbon structure, and species identity on breakdown rates.

Synthesis. In oligotrophic ecosystems, nutrients are often the primary driver of organic matter breakdown. However, we found that variation in macrophyte breakdown rates in oligotrophic coastal wetlands was also explained by salinity and associated seawater chemistry, emphasising the need to understand how saltwater intrusion will alter organic matter processing in wetlands. Our results suggest that marine subsidies associated with sea‐level rise have the potential to accelerate leaf litter breakdown. The increase in breakdown rates could either be buffered or increase further as sea‐level rise also shifts macrophyte community composition to more or less recalcitrant species.
Small‐scale dispersal and gene flow of the agricultural pest two‐spotted spider mite in apple orchards: Implication from landscape ecological and population genetic analyses
Authors: Komagata Yasuyuki , Oe Takaho , Sekine Takayuki , Kimura Yuta , Hirota Shun K. , Taguchi Hiroya , Suyama Yoshihisa
Published: March 2024

The two‐spotted spider mite, Tetranychus urticae Koch (Acarina, Tetranychidae), is a notorious agricultural pest known for its high dispersal ability. Understanding the dispersal patterns of T. urticae is crucial for studying its population dynamics and assessing the risk of gene dispersal related to acaricide resistance. We investigated the impact of surrounding landscapes on T. urticae occurrence and detected gene flow between nearby apple orchards. Land use data within 0.2–2 km radius buffers of the orchards were extracted and summarized using principal component analysis. The effects of landscape composition on the occurrence of T. urticae in apple orchards were analyzed using a hierarchical Bayesian model that considers spatial autocorrelation. In addition, we conducted a population genetic analysis on samples collected from five orchards. The results indicate that the best model was one at a 200‐m scale, revealing a positive correlation between forest area ratio and T. urticae occurrence. The population genetic analysis demonstrated distinct genetic structures within T. urticae populations across different orchards. However, we estimated gene flow among some orchards that were geographically close. These findings suggest that T. urticae may migrate from surrounding landscapes, particularly forests, and nearby orchards to apple orchards. These findings have substantial implications for developing control units based on the gene flow range of the two‐spotted spider mite, as well as for assessing the risk of infestation in each orchard.
Pollination ecology of Ranzania japonica (Berberidaceae), a perennial plant of a monotypic genus endemic to deep‐snow regions in Japan
Authors: Okawa Masahiro , Sakata Yuzu
Published: March 2024

Plants that bloom in early spring often face constraints on reproduction, which are influenced by low temperatures and unpredictable weather conditions that affect pollinator activity. We aimed to elucidate the pollination ecology and the mating system of Ranzania japonica (Berberidaceae), a perennial plant of a monotypic genus endemic to deep‐snow regions in Japan. We documented the flowering phenology and visiting insects in the field, and conducted pollination experiments by using artificial treatments. R. japonica was suggested to be self‐incompatible but not pollen‐limited. Fruit set varied between years, and florivory seemed to have a negative influence on fruit set. Insects from various taxa were observed to visit the flowers of R. japonica, with Eusphalerum sp. (rove beetle) being the most abundant, followed by Bombylius major and hymenopteran species. The stamen movement in response to insect visits was observed. The results of the observation and the pollination treatments suggested that small‐ and medium‐sized Hymenoptera were the main pollinators and rove beetles may also contribute to pollination in R. japonica. Because early spring weather can be unsuitable for activity of bees, rove beetles may act as supplementary pollinators of R. japonica. The role of the supplementary pollinators may be an overlooked but important aspect for understanding the pollination biology of early‐spring blooming plants.
The New Transition Politics of Net Zero
Authors: Bloomfield Jon , Steward Fred
Published: March 2024

The net zero transition requires concurrent and rapid decarbonisation in five major consumption‐production systems—transport, housing, industry, food and power. These systems differ in their public visibility and institutional makeup, as well as in their technologies. Transition politics needs dexterity to facilitate transformation of these multiple systems. Yet, there remain big contrasts in the rate of change of different systems. These are shown by the variation in the fulfilment of the 2020 system targets which were set in the 2009 UK Low Carbon Transition Plan. Comparison of the transition pathways of renewable electricity production and home insulation indicates that current UK net zero transition politics is poorly suited to the transformation of household energy use. A more proactive state and wider public participation are needed for a more effective place‐based approach. Environmental activism and populist backlash have focused attention on everyday transformative change. A new type of transition politics which engages with multiple systems is needed to rise to this urgent climate challenge.
The effects of the Veterans Health Administration's Referral Coordination Initiative on referral patterns and waiting times for specialty care
Authors: Asfaw Daniel A. , Price Megan E. , Carvalho Kristina M. , Pizer Steven D. , Garrido Melissa M.
Published: March 2024

Objective

To investigate whether the Veterans Health Administration's (VA) 2019 Referral Coordination Initiative (RCI) was associated with changes in the proportion of VA specialty referrals completed by community‐based care (CC) providers and mean appointment waiting times for VA and CC providers.

Data Sources/Study Settings

Monthly facility level VA data for 3,097,366 specialty care referrals for eight high‐volume specialties (cardiology, dermatology, gastroenterology, neurology, ophthalmology, orthopedics, physical therapy, and podiatry) from October 1, 2019 to May 30, 2022.

Study Design

We employed a staggered difference‐in‐differences approach to evaluate RCI's effects on referral patterns and wait times. Our unit of analysis was facility‐month. We dichotomized facilities into high and low RCI use based on the proportion of total referrals for a specialty. We stratified our analysis by specialty and the staffing model that high RCI users adopted: centralized, decentralized, and hybrid.

Data Collection/Extraction Methods

Administrative data on referrals and waiting times were extracted from the VA's corporate data warehouse. Data on staffing models were provided by the VA's Office of Integrated Veteran Care.

Principal Findings

We did not reject the null hypotheses that high RCI use do not change CC referral rates or waiting times in any of the care settings for most specialties. For example, high RCI use for physical therapy—the highest volume specialty studied—was associated with −0.054 (95% confidence interval [CI]: −0.114 to 0.006) and 2.0 days (95% CI: −4.8 to 8.8) change in CC referral rate and waiting time at CC providers, respectively, among centralized staffing model adopters.

Conclusions

In the initial years of the RCI program, RCI does not have a measurable effect on waiting times or CC referral rates. Our findings do not support concerns that RCI might be impeding Veterans' access to CC providers. Future evaluations should examine whether RCI facilitates Veterans' ability to receive care in their preferred setting.
Decomposing household income differences between farmers and non‐farmers: Empirical evidence from Norway
Authors: Mittenzwei Klaus , Berglann Helge , Hoveid Øyvind , Matthews Alan , Storm Hugo
Published: March 2024

Income comparisons between farm and non‐farm households play a crucial role in many aspects of farm policy. Using household income data from tax returns of all Norwegian taxpayers in the period 2006–2015 we study these income differences. We find that the unconditional mean income is higher for farm households, but with important differences depending on the comparison group considered. We also find that the income difference is reduced when we control for differences in the personal characteristics of the different non‐farm comparison sub‐groups. This finding implies that income comparison using unconditional means, as frequently done in agricultural policy making, is potentially misleading. We also show that the income effect of personal characteristics is not the same for different comparison sub‐groups, as has been assumed in previous studies of income disparities. Differences in personal characteristics, and the income effect of those characteristics, therefore need to be accounted for if income comparisons between farmers and non‐farmers are to inform farm support policies.
Epigenetic clocks, sex markers and age‐class diagnostics in three harvested large mammals
Authors: Czajka Natalie , Northrup Joseph M. , Jones Meaghan J. , Shafer Aaron B. A.
Published: March 2024

The development of epigenetic clocks, or the DNA methylation‐based inference of age, is an emerging tool for ageing in free ranging populations. In this study, we developed epigenetic clocks for three species of large mammals that are the focus of extensive management throughout their range in North America: white‐tailed deer, black bear and mountain goat. We quantified differential DNA methylation patterns at over 30,000 cytosine‐guanine sites (CpGs) from tissue samples of all three species (black bear n = 49; white‐tailed deer n = 47; mountain goat n = 45). We used a penalized regression model (elastic net) to build explanatory (black bear r = .95; white‐tailed deer r = .99; mountain goat r = .97) and robust (black bear Median Absolute Error or MAE = 1.33; white‐tailed deer MAE = 0.29; mountain goat MAE = 0.61) models of age or clocks. We also characterized individual CpG sites within each species that demonstrated clear differences in methylation levels between age classes and sex, which can be used to develop a suite of accessible diagnostic markers. This tool has the potential to contribute to wildlife monitoring by providing easily obtainable representations of age structure in managed populations.
Familial Reputation, Bias and Impartial Arbitrators “on the Field”*
Authors: Lenten Liam J. A. , Barake Adrian J. , Stewart Mark F.
Published: March 2024

Those with intra‐organisational familial links often advance more quickly due to nepotism. We harness a large database from a natural setting relating to a specific paternal mechanism in professional sport; with our results suggesting that when external arbitrators are utilised as a tool to ensure fairness of assessments, there is effectively no evidence of performance evaluation bias in favour of subjects with the internal benefit of family reputation. This suggests that impartial assessors may be an appropriate method of safeguarding against nepotism within organisations. However, there is still some weak evidence that the influence of the agent's family name can itself still make a difference.
Circ‐POSTN promotes the progression and reduces radiosensitivity in esophageal cancer by regulating the miR‐876‐5p/FYN axis
Authors: Chu Alan , Sun Chen , Liu Zongwen , Liu Shijia , Li Mengxi , Song Rui , Gan Lanlan , Wang Yongtai , Fan Ruitai
Published: March 2024

Background

Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ‐POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated.

Methods

The expression of circ‐POSTN, microRNA‐876‐5p (miR‐876‐5p), and proto‐oncogene tyrosine‐protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT‐qPCR). Cell proliferation was assessed by MTT, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual‐luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR‐876‐5p and circ‐POSTN or FYN. The role of circ‐POSTN in vivo was explored by establishing mice xenograft model.

Results

Circ‐POSTN was overexpressed in EC tissues and cells. Knockdown of circ‐POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR‐876‐5p was a direct target of circ‐POSTN, and its knockdown reversed the role of sh‐circ‐POSTN in EC cells. FYN was a direct target of miR‐876‐5p, and FYN elevation weakened the effects of miR‐876‐5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ‐POSTN acted as a miR‐876‐5p sponge to regulate FYN expression. Circ‐POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo.

Conclusion

Circ‐POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR‐876‐5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.
Which PDE5 inhibitor is the most effective in the treatment of erectile dysfunction in men with spinal cord injury? A systematic review and network meta‐analysis
Authors: Tienforti Daniele , Felzani Giorgio , Di Pasquale Alfonso Boris , Barbonetti Arcangelo
Published: March 2024

Background

Phosphodiesterase 5 inhibitors (PDE5i) are the first‐line drugs for erectile dysfunction (ED) but differences among available molecules should drive therapy personalization. Choosing one PDE5i over another is a challenge in men with spinal cord injury (SCI), as the evidence of efficacy for each molecule is derived from few studies and comparative “head‐to‐head” trials are lacking.

Objective

To assess the efficacy of the different PDE5i for SCI‐related ED with a network meta‐analysis (NMA) approach.

Materials and methods

Databases from PubMed, Web of Science, Scopus, and Cochrane Library were checked for randomized controlled trials (RCTs) comparing any PDE5i to each other or placebo in men with traumatic SCI lasting ≥6 months. Data were incorporated in a random‐effect NMA, where treatments’ efficacy was ranked using the surface under the cumulative ranking curve (SUCRA).

Results

The 10 RCTs included provided information about 1,492 men with ED due to traumatic SCI. Intervention arms included sildenafil, tadalafil, and/or vardenafil. Overall, at the pairwise meta‐analysis, PDE5i were four times more effective than placebo in improving erectile function (risk ratio: 4.13, 95% CI: 2.76, 6.19). The comparative analysis from NMA revealed that tadalafil was associated with the highest SUCRA value (81%), followed by vardenafil (68%) and sildenafil (49%).

Discussion and conclusion

Within the grading of comparison network, tadalafil appeared to be the best PDE5i in the treatment of SCI‐related ED. Further focused studies are warranted to confirm these findings and define optimal doses and duration of therapy.
General surgeon performed emergency craniotomies in regional Queensland hospitals: a 20‐year state‐wide study on patient outcomes
Authors: Kelly Madeleine Louise , Stuart Michael , Zouki Jason , Long Brittany , Sabat Nestor , Clark Claudia Rose , Donaldson Eric , Colbran Rachel Emily
Published: March 2024

Background

Traumatic brain injuries account for up to 50% of trauma related deaths and if surgical intervention is indicated, consensus suggests a maximum of 4 hours to surgical decompression. The occurrence and outcomes of craniotomies performed by non‐neurosurgeons in regional Queensland hospitals have never been reported previously in the literature.

Methods

A retrospective review was performed at all regional Queensland hospitals without an on‐site neurosurgical service from January 2001 to December 2022 to identify patients undergoing emergency craniotomy. Data recorded included basic demographics, history of anti‐coagulant use, mechanism of injury, type of haemorrhage, Glasgow Coma Score and Glasgow Outcome Scale (GOS) on discharge. Radiological parameters measured included midline shift and maximal coronal depth of haematoma. The primary aim of this study was to assess the clinical and radiological outcomes of patients who underwent a craniotomy performed by general surgeons.

Results

Over the past 20 years there have been 23 emergency decompressive procedures (one excluded) performed in regional Queensland. Preoperative imaging demonstrated 9 extradural haematomas and 13 subdural haematomas. Six of 17 transferred cases required reoperation after transfer to a neurosurgical centre. Survival was observed in 9 of 22 cases, with ‘good’ functional outcome (GOS ≥3) observed in 7 cases. In no cases were rurally performed burr holes effective.

Discussion

Qualitatively, a larger craniotomy may be associated with better clinical and radiological outcomes. Although rare occurrences, our results demonstrate that general surgeon performed craniotomies are frequently efficacious in producing radiological and/or clinical improvement and should be considered as a potentially lifesaving procedure.
National screening for colorectal cancer is associated with stage shift to earlier diagnosis
Authors: Sarofim Mina , Ashrafizadeh Amir , Gill Anthony J. , de Silva Keshani , Evans Justin , Clarke Stephen , Pavlakis Nick , Norton Ian , Engel Alexander
Published: March 2024

Background

Australia's National Bowel Cancer Screening Program consists of an immunohistochemical faecal occult blood test, targeting adults aged 50–74. Existing literature supports the principle of early detection of colorectal cancer (CRC) via national screening, but little is known about the association between colonoscopy or polypectomy rates and CRC stage over time. The aim of this study is to identify the longitudinal change to colonoscopy and polypectomy rates, and any stage shift associated with this screening program.

Methods

A retrospective data‐linkage study was performed using the Australian national health database (Medicare) to obtain colonoscopy and polypectomy rates between 1998 and 2017. A second prospective database of CRC resection specimens was analysed for this period. The cohort was divided based on time intervals related to the National Bowel Cancer Screening Program: pre‐commencement 1998–2006 (Period A), immediately post‐commencement 2007–2011 (Period B), and subsequent years 2012–2017 (Period C). Linear regression was used to test relation between annualized predictor and response variables.

Results

Annual colonoscopy rates doubled, and polypectomy rates tripled during the study (P < 0.001). Annual colonoscopy rate correlated to a lower T‐stage (P = 0.038) and lower N‐stage (P = 0.026), and there was a 7% increase in early CRC (stage I–II) in Period C (P < 0.001). Across the study period there was also a significant increase in right‐sided tumours, and concurrent MMR deficiency and BRAF mutation.

Conclusion

Polypectomy and colonoscopy rates increased after the introduction of the National Bowel Cancer screening program. There was a clinically significant shift to earlier CRC stage which manifested 5 years after its implementation.
Preoperative coil localization for spinal surgery is accurate, safe and effective: a single‐centre initial experience
Authors: Kam Jeremy K. T. , Castle‐Kirszbaum Mendel , Dhaliwal Tarundeep , Maingard Julian , Chandra Ronil , Quan Gerald , Gonzalvo Carlos Augusto , Goldschlager Tony
Published: March 2024

Objective and study design

This is a retrospective, descriptive study of consecutive patients undergoing novel preoperative pushable coil localization for spinal surgery, in order to evaluate its feasibility, safety and accuracy.

Methods

Consecutive patients who underwent pre‐operative coil marking for spinal surgery at our institution from May 2018 to July 2021 were included. Data were collected for coil placement, accuracy, complications and fluoroscopy usage. Patient demographic and relevant perioperative and procedural data were also collected.

Results

A total of 34 patients were identified of which 32 (94%) had complete data and imaging at last clinical follow up, with a mean duration of 13.9 months. There were no incorrect level surgeries performed. There were no coil‐related complications found in our cohort.

Conclusions

Preoperative coil placement is an accurate, safe and well‐tolerated method for level localization in spinal surgeries.
Decibels in the operating theatre: a study of noise levels during surgical procedures
Authors: Au Joanne , Hamilton Sam , Webb Angela
Published: March 2024

Background

Exposure to excessive noise volumes is an occupational health and safety risk. Australian guidelines recommend a time weighted exposure maximum of 85 dB (dB) or a maximum peak noise level of up to 140 dB, as chronic and repeated high dB exposure can result in significant hearing impairment.

The aim of this study was to assess the volume of noise generated by common surgical instruments while utilizing the National Institute for Occupational Safety and Health (NIOSH) app.

Methods

Sound levels were measured using the NIOSH app. The NIOSH app was used to take equivalent continuous A‐weighted sound levels (LAeq) and the C‐weighted peak sound pressure (LCpeak) measurements for specific instruments while in use in theatre. A minimum of three readings per instrument were taken at immediate and working distances.

Results

LAeq measurements ranged from 62.9 to 89.3 dB. The Padgett Dermatome and Frazier Sucker exceeded recommended exposure limits with an averaged LAeq reading of 85.7 dB(A) and 85.1 dB(A) respectively. LCpeak readings ranged from 89.9 to 114.7 dB(C) with none of the instruments exceeding a peak sound level beyond the recommended level of 140 dB(C).

Conclusion

The cumulative effect of loud surgical instruments across prolonged or combined operations may result in theatre staff being exposed to hazardous noise levels, impacting the health and wellbeing of staff, staff performance and patient care. Utilization of a phone app can improve the awareness of noise pollution in theatres, thereby empowering staff to be proactive about their health and improvement of their work environment.
In vitro biomechanical properties of porcine perineal tissues to better understand human perineal tears during delivery
Authors: Lallemant Marine , Kadiakhe Tiguida , Chambert Jerôme , Lejeune Arnaud , Ramanah Rajeev , Mottet Nicolas , Jacquet Emmanuelle
Published: March 2024

Introduction

Data concerning the mechanical properties of the perineum during delivery are very limited. In vivo experiments raise ethical issues. The aim of the study was to describe some of the biomechanical properties of each perineal tissue layer collected from sows in order to better understand perineal tears during childbirth.

Material and methods

Samples of each perineal tissue layer were obtained from the skin, the vagina, the external anal sphincter (EAS), the internal anal sphincter (IAS), and the anal mucosa of fresh dead sows. They were tested in quasi‐static uniaxial tension using the testing machine Mach‐1®. Tests were performed at a displacement velocity of 0.1 mm·s−1. Stress–strain curves of each perineal tissue layer before the first damage for each sow were obtained and modeled using a hyperelastic Yeoh model described by three coefficients: C1, C2, and C3. Pearson correlation coefficients were calculated to measure the correlation between the C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture for each perineal tissue layer. Pearson correlation was computed between C1 and the number of microfailures before complete rupture for each tissue.

Results

Ten samples of each perineal tissue layer were analyzed. Mean values of C1 and corresponding standard deviations were 46 ± 15, 165 ± 60, 27 ± 10, 19 ± 13, 145 ± 28 kPa for the perineal skin, the vagina, the EAS, the IAS, and the anal mucosa, respectively. According to this same sample order, the first microfailure in the population of 10 sows appeared at an average of 54%, 27%, 70%, 131%, and 22% of strain. A correlation was found between C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture (r = 0.7, p = 0.02) or the number of microfailures before complete rupture only for the vagina (r = 0.7, p = 0.02).

Conclusions

In this population of fresh dead sow's perineum, the vagina and the anal mucosa were the stiffest tissues. The IAS and EAS were more extensible and less stiff. A significantly positive correlation was found between C1 and the duration between the first microfailure and the complete rupture of the vagina, and the duration between the first microfailure and the complete rupture of the vagina.
Effect of chlorhexidine, povidone‐iodine and betadine antiseptic eye drops on cultured human conjunctival goblet cell survival
Authors: Hadad Rubin , Hedengran Anne , Barnils Alex , Petrovski Goran , Cvenkel Barbara , Utheim Tor P. , Dartt Darlene A. , Heegaard Steffen , Kolko Miriam
Published: March 2024

Purpose

To compare the effect of the ocular antiseptic treatments 0.05% chlorhexidine, 5% povidone‐iodine (PI) and 5% betadine on cell viability and mucin secretion of primary cultured human goblet cells (GCs).

Method

GC viability was analysed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Expression of mucin was visualised by immunohistochemical MUC5AC staining.

Results

PI and betadine significantly reduced GC survival compared to the control (mean cell survival 23 ± 6% and 23 ± 7%, respectively, p < 0.05), whereas chlorhexidine did not significantly affect GC viability (mean cell survival: 78 ± 17%), as measured by the LDH assay. Similar results were obtained from the MTT assay, where PI and betadine caused a significant loss of GCs (mean cell survival: 26 ± 12% and 26 ± 13%, respectively, p < 0.05). Chlorhexidine did not significantly alter GC survival compared to the control (mean cell survival: 79 ± 8%). PI and betadine caused a dispersion of mucin secretion, which chlorhexidine did not.

Conclusion

The most used antiseptic treatments, PI and betadine, applied prior to ocular surgery are significantly more cytotoxic to conjunctival GCs than chlorhexidine treatment.
The selective deployment of AI in healthcare
Authors: Vandersluis Robert , Savulescu Julian
Published: March 2024

Machine‐learning algorithms have the potential to revolutionise diagnostic and prognostic tasks in health care, yet algorithmic performance levels can be materially worse for subgroups that have been underrepresented in algorithmic training data. Given this epistemic deficit, the inclusion of underrepresented groups in algorithmic processes can result in harm. Yet delaying the deployment of algorithmic systems until more equitable results can be achieved would avoidably and foreseeably lead to a significant number of unnecessary deaths in well‐represented populations. Faced with this dilemma between equity and utility, we draw on two case studies involving breast cancer and melanoma to argue for the selective deployment of diagnostic and prognostic tools for some well‐represented groups, even if this results in the temporary exclusion of underrepresented patients from algorithmic approaches. We argue that this approach is justifiable when the inclusion of underrepresented patients would cause them to be harmed. While the context of historic injustice poses a considerable challenge for the ethical acceptability of selective algorithmic deployment strategies, we argue that, at least for the case studies addressed in this article, the issue of historic injustice is better addressed through nonalgorithmic measures, including being transparent with patients about the nature of the current epistemic deficits, providing additional services to algorithmically excluded populations, and through urgent commitments to gather additional algorithmic training data from excluded populations, paving the way for universal algorithmic deployment that is accurate for all patient groups. These commitments should be supported by regulation and, where necessary, government funding to ensure that any delays for excluded groups are kept to the minimum. We offer an ethical algorithm for algorithms—showing when to ethically delay, expedite, or selectively deploy algorithmic systems in healthcare settings.
Exploring teachers' (future) digital assessment practices in higher education: Instrument and model development
Authors: Viberg Olga , Mutimukwe Chantal , Hrastinski Stefan , Cerratto‐Pargman Teresa , Lilliesköld Joakim
Published: March 2024

Digital technologies are increasingly used in assessment. On the one hand, this use offers opportunities for teachers to practice assessment more effectively, and on the other hand, it brings challenges to the design of pedagogically sound and responsible digital assessment. There is a lack of validated instruments and models that explain, assess and support teachers' critical pedagogical practice of digital assessment. This explorative work first develops and validates a survey instrument to examine teachers' digital assessment practices. Secondly, we build a model to investigate to what extent teachers' pedagogical digital assessment knowledge is a foundation for the future of digital assessment (ie, authentic, accessible, automated, continuous and responsible). A total of 219 university teachers at a large European university participated in the survey study. Factor exploratory analysis and structural equation modelling were used to validate the reliability and validity of items and internal causal relations of factors. The results show the survey is a valid and reliable instrument for assessing teachers' digital assessment practice in higher education. Teachers' pedagogical knowledge and pedagogical content knowledge of digital assessment is critical, while teachers' technological pedagogical knowledge seems to have a more limited impact on the future of digital assessment.

Practitioner notes

What is already known about this topic

Digital technologies are increasingly used in assessment in higher education.

Teachers are the key stakeholders in the assessment for learning.

There is a limited transformative nature of digital assessment practices.

What this paper adds

A validated instrument to assess teachers' pedagogical practice of digital assessment in higher education.

Teachers' pedagogical and pedagogical content knowledge of digital assessment is critical to the future of digital assessment.

Teachers' technological pedagogical knowledge of digital assessment has a more limited impact on the future of digital assessment.

Implications for practice and policy

Teachers need to be supported in developing pedagogical digital assessment practices in higher education.

Based on this study's outcomes, educators, institutions and policymakers can inform the design and implementation of effective and responsible digital assessment practices.

The design and implementation of responsible digital assessments will enhance the quality of higher education in the digital age.
The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells
Authors: Li Mengfan , Yang Junsheng , Xiao Rong , Liu Yunjie , Hu Jiaqi , Li Tingting , Wu Pengze , Zhang Meili , Huang Yue , Sun Yujie , Li Cheng
Published: March 2024

Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild‐type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi‐C, RNA‐seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter‐chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.