Guided versus non-guided chin repositioning: a retrospective study on accuracy.

Genioplasty is a widely used surgical approach to address chin deformities by performing an osteotomy on the inferior border of the mandible to allow for comprehensive repositioning of the chin. This study aimed to compare the accuracy of freehand chin repositioning with a guided technique that employed specialised surgical guides. For this retrospective study, data from 30 adult patients who underwent orthognathic surgery to correct dentofacial deformities were analysed. All patients underwent virtual planning before surgery, with half of them treated using freehand chin repositioning and the other half using the guided technique. The surgical outcomes were measured and compared with the virtual plan to assess the positional and rotational accuracy of the techniques. In terms of translational assessment, noteworthy values that exceeded clinically acceptable limits were observed only in sagittal movement in the freehand group (0.97 mm, interquartile range (IQR) 0.73-2.29 mm). Regarding rotational accuracy, both groups exhibited an IQR that surpassed acceptable limits for pitch (3.26°, IQR 2.06-5.20 for the guided group and 2.57°, IQR 1.63-4.24° for the freehand group). The Mann-Whitney test indicated no statistical differences between the groups in any translational or rotational assessment. In conclusion, although there was no statistical difference, the guided technique proved effective in achieving clinically acceptable accuracy in all positions and almost all rotations, displaying superior results in sagittal positioning compared with the freehand technique. To fully harness the advantages of guides and to guarantee accuracy in all rotations, we recommend further research involving guides made of more rigid materials, and customised implants.

A Splenic Abscess in a Trauma Setting: A Case Report and Comprehensive Literature Review.

A splenic abscess is rare after trauma, and it has been reported with high mortality rates. Treatment options include antibiotics, percutaneous pigtail drain, or surgical intervention; however, there are no specific guidelines for the treatment of splenic abscesses in trauma settings. We report a 69-year-old male who came in with a splenic abscess after angioembolisation for a splenic laceration after having a right hemicolectomy. Our case presents new information and current recommendations for the management of splenic abscesses based on a comprehensive literature review.

ezBIDS: Guided standardization of neuroimaging data interoperable with major data archives and platforms.

Data standardization promotes a common framework through which researchers can utilize others' data and is one of the leading methods neuroimaging researchers use to share and replicate findings. As of today, standardizing datasets requires technical expertise such as coding and knowledge of file formats. We present ezBIDS, a tool for converting neuroimaging data and associated metadata to the Brain Imaging Data Structure (BIDS) standard. ezBIDS contains four major features: (1) No installation or programming requirements. (2) Handling of both imaging and task events data and metadata. (3) Semi-automated inference and guidance for adherence to BIDS. (4) Multiple data management options: download BIDS data to local system, or transfer to OpenNeuro.org or to brainlife.io. In sum, ezBIDS requires neither coding proficiency nor knowledge of BIDS, and is the first BIDS tool to offer guided standardization, support for task events conversion, and interoperability with OpenNeuro.org and brainlife.io.

Bortezomib in relapsed/refractory immune thrombotic thrombocytopenic purpura: A single-centre retrospective cohort and systematic literature review.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune-modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27-53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow-up.

SMARTERscreen protocol: a three-arm cluster randomised controlled trial of patient SMS messaging in general practice to increase participation in the Australian National Bowel Cancer Screening Program.

BACKGROUND: Australia persistently has one of the highest rates of colorectal cancer (CRC) in the world. Australia's National Bowel Cancer Screening Program (NBCSP) sends a biennial Faecal Immunochemical Test (FIT)-the 'NBCSP kit'-to everyone eligible for the programme between 50 and 74 years old; however, participation in the programme is low, especially in the 50- to 60-year-old age group. Our previous efficacy trial ('SMARTscreen') demonstrated an absolute increase in uptake of 16.5% (95% confidence interval = 2.02-30.9%) for people sent an SMS with motivational and instructional videos, from their general practice prior to receiving their NBCSP kit, compared to those receiving usual care. Building on the strengths of the SMARTscreen trial and addressing limitations, the 'SMARTERscreen' trial will test the effect on participation in the NBCSP of sending either an SMS only or an SMS with online video material to general practice patients due to receive their NBCSP compared to 'usual care'. METHODS: SMARTERscreen is a three-arm stratified cluster randomised controlled trial involving 63 general practices in two states in Australia. Eligible patients are patients who are aged 49-60 years and due to receive their NBCSP kit within the next 2 weeks during the intervention period. General practices will be equally randomised to three trial arms (21:21:21, estimated average 260 patients/practice). The two interventions include (i) an SMS with an encouraging message from their general practice or (ii) the same SMS with weblinks to additional motivational and instructional videos. The control arm will receive 'usual care'. Using the intention-to-treat approach, primary analysis will estimate the three pair-wise between-arm differences in the proportion of eligible patients who participate in the NBCSP within 6 months of when their kit is sent, utilising screening data from the Australian National Cancer Screening Register (NCSR). Patient intervention adherence to the interventions will also be evaluated. Findings will be incorporated into the Policy1-Bowel microsimulation model to estimate the long-term health benefits and cost-effectiveness of the interventions. DISCUSSION: SMARTERscreen will provide high-level evidence determining whether an SMS or an SMS with web-based material sent to general practice patients prior to receiving their NBCSP kit increases participation in bowel cancer screening. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000036617. Registered on 13 January 2023. Trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385119&isClinicalTrial=False.

Predicting the impact of sequence motifs on gene regulation using single-cell data.

The binding of transcription factors at proximal promoters and distal enhancers is central to gene regulation. Identifying regulatory motifs and quantifying their impact on expression remains challenging. Using a convolutional neural network trained on single-cell data, we infer putative regulatory motifs and cell type-specific importance. Our model, scover, explains 29% of the variance in gene expression in multiple mouse tissues. Applying scover to distal enhancers identified using scATAC-seq from the developing human brain, we identify cell type-specific motif activities in distal enhancers. Scover can identify regulatory motifs and their importance from single-cell data where all parameters and outputs are easily interpretable.

Unraveling allostery within the angiotensin II type 1 receptor for Gαq and ß-arrestin coupling.

G protein-coupled receptors engage both G proteins and ß-arrestins, and their coupling can be biased by ligands and mutations. Here, to resolve structural elements and mechanisms underlying effector coupling to the angiotensin II (AngII) type 1 receptor (AT1R), we combined alanine scanning mutagenesis of the entire sequence of the receptor with pharmacological profiling of Gαq and ß-arrestin engagement to mutant receptors and molecular dynamics simulations. We showed that Gαq coupling to AT1R involved a large number of residues spread across the receptor, whereas fewer structural regions of the receptor contributed to ß-arrestin coupling regulation. Residue stretches in transmembrane domain 4 conferred ß-arrestin bias and represented an important structural element in AT1R for functional selectivity. Furthermore, we identified allosteric small-molecule binding sites that were enclosed by communities of residues that produced biased signaling when mutated. Last, we showed that allosteric communication within AT1R emanating from the Gαq coupling site spread beyond the orthosteric AngII-binding site and across different regions of the receptor, including currently unresolved structural regions. Our findings reveal structural elements and mechanisms within AT1R that bias Gαq and ß-arrestin coupling and that could be harnessed to design biased receptors for research purposes and to develop allosteric modulators.

Studies on the Transcorrelated Method.

We investigate the possibility of using a transcorrelated (TC) Hamiltonian to describe electron correlation. A method to obtain TC wavefunctions was developed based on the mathematical framework of the bi-variational principle. This involves the construction of an effective TC Hamiltonian matrix, which can be solved in a self-consistent manner. This was optimized using a method we call second-order-moment minimization and demonstrate that it is possible to obtain highly accurate energies for some closed-shell atoms and helium-like ions. The effects of certain correlator terms on the description of electron-electron and electron-nuclear cusps were also examined graphically, and some TC wavefunctions were compared against near-exact Hylleraas wavefunctions.

EvoAug: improving generalization and interpretability of genomic deep neural networks with evolution-inspired data augmentations.

Deep neural networks (DNNs) hold promise for functional genomics prediction, but their generalization capability may be limited by the amount of available data. To address this, we propose EvoAug, a suite of evolution-inspired augmentations that enhance the training of genomic DNNs by increasing genetic variation. Random transformation of DNA sequences can potentially alter their function in unknown ways, so we employ a fine-tuning procedure using the original non-transformed data to preserve functional integrity. Our results demonstrate that EvoAug substantially improves the generalization and interpretability of established DNNs across prominent regulatory genomics prediction tasks, offering a robust solution for genomic DNNs.

The Influence of Cannabinoids on Drosophila Behaviors, Longevity, and Traumatic Injury Responses of the Adult Nervous System.

Introduction: The legalization of cannabis products has increased their usage in the United States. Among the ∼500 active compounds, this is especially true for cannabidiol (CBD)-based products, which are being used to treat a range of ailments. Research is ongoing regarding the safety, therapeutic potential, and molecular mechanism of cannabinoids. Drosophila (fruit flies) are widely used to model a range of factors that impact neural aging, stress responses, and longevity. Materials and Methods: Adult wild-type Drosophila melanogaster cohorts (w1118/+) were treated with different Δ9-tetrahydrocannabinol (THC) and CBD dosages and examined for neural protective properties using established neural aging and trauma models. The therapeutic potential of each compound was assessed using circadian and locomotor behavioral assays and longevity profiles. Changes to NF-κB pathway activation were assessed by measuring expression levels of downstream targets using quantitative real-time polymerase chain reaction analysis of neural cDNAs. Results: Flies exposed to different CBD or THC dosages showed minimal effects to sleep and circadian-based behaviors or the age-dependent decline in locomotion. The 2-week CBD (3 µM) treatment did significantly enhance longevity. Flies exposed to different CBD and THC dosages were also examined under stress conditions, using the Drosophila mild traumatic brain injury (mTBI) model (10×). Pretreatment with either compound did not alter baseline expression of key inflammatory markers (NF-κB targets), but did reduce neural mRNA profiles at a key 4-h time point following mTBI exposure. Locomotor responses were also significantly improved 1 and 2 weeks following mTBI. After mTBI (10×) exposure, the 48-h mortality rate improved for CBD (3 µM)-treated flies, as were global average longevity profiles for other CBD doses tested. While not significant, THC (0.1 µM)-treated flies show a net positive impact on acute mortality and longevity profiles following mTBI (10×) exposure. Conclusions: This study shows that the CBD and THC dosages examined had at most a modest impact on basal neural function, while demonstrating that CBD treatments had significant neural protective properties for flies following exposure to traumatic injury.

Potential of the omnidirectional walking platform with virtual reality as a rehabilitation tool.

Introduction: The combination of virtual reality (VR) with an omnidirectional walking platform (ODWP) may have potential in rehabilitation settings. However, its use, acceptance, safety, and effectiveness are unclear. This preliminary study aims to understand the feasibility, safety, and user experience (including investigating the onset of cybersickness) while walking on the ODWP with fully immersive VR. Methods: Participants engaged with eight immersive VR walking scenarios. The scenarios were created using 360-degree videos and were programmed to run with the ODWP. Safety modifications for the ODWP were made, with the addition of parallel bars. Quantitative feedback on the perceived safety and acceptance of using VR with an ODWP for rehabilitation was collected. Cybersickness was evaluated using the Simulation Symptoms Questionnaire (SSQ). Results: Thirty-five participants (n = 8 physiotherapists, n = 27 healthy adults) were recruited for this study. The mean perceived safety score was 78.9/100 and acceptance was 64.5/100. Seventy-one percent of participants experienced mild to moderate symptoms of cybersickness as reported on the SSQ. The SSQ scores were not correlated to participant age or simulation exposure time. Conclusion: VR while using ODWP has the potential for rehabilitation, however, more consideration is needed to address acceptance and cybersickness.

Leave No Trace? Ecological and anthropogenic determinants of antibiotic resistant bacteria in a recreational alpine environment.

Antibiotic resistant bacteria (ARB) have been detected in remote environments, but the degree to which their presence is due to anthropogenic contamination remains unclear. Here, anthropogenic and ecological determinants of ARB were characterized in remote and highly visited areas of Rocky Mountain National Park in the United States. Soil and water samples were collected from 29 sites once a month for three months and measured for bacteria resistant to seven antibiotics with flow cytometry. A novel index of the likelihood of human presence (HPI) was generated for estimating human impact on ARB abundance. The HPI accounted for 44% of variation in ARB abundance in water samples (p < 0.0001) and 51% of variation in soil samples (p < 0.00001). Human presence index was illustrated as a reliable predictor of ARB abundance despite a tendency to underpredict at higher levels of human impact. Ecological determinants such as temperature, elevation, slope, and aspect were also found to be significantly associated with ARB abundance. These findings suggest that human presence drives the abundance of ARB in Rocky Mountain National Park, but ecological variables play a significant role in their presence and dispersal.

Behavioral trajectories of aging prairie voles (Microtus ochrogaster): Adapting behavior to social context wanes with advanced age.

Several studies using mice have examined the effects of aging on cognitive tasks, as well as sensory and motor functions. However, few studies have examined the influence of aging on social behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous and biparental rodent that live in small family groups and are now among the most popular rodent models for studies examining social behavior. Although the social behavioral trajectories of early-life development in prairie voles have been well-studied, how social behavior may change throughout adulthood remains unknown. Here we examined behavior in virgin male and female prairie voles in four different age groups: postnatal day (PND) 60-80, 140-160, 220-240, and 300-320. All animals underwent testing in a novel object task, a dominance test, a resident-intruder test, and several iterations of social approach and social interaction tests with varying types of social stimuli (i.e., novel same-sex conspecific, novel opposite-sex conspecific, familiar same-sex sibling/cagemate, small group of novel same-sex conspecifics). We found that age influenced neophobia and dominance, but not social approach behavior. Further, we found that young adult, but not older adult, prairie voles adapt prosocial and aggressive behavior relative to social context, and that selective aggression occurs in relation to age even in the absence of a pair bond. Our results suggest that prairie voles calibrate social phenotype in a context-dependent manner in young adulthood and stop adjusting behavior to social context in advanced age, demonstrating that social behavior is plastic not only throughout early development, but also well into adulthood. Together, this study provides insight into age-related changes in social behavior in prairie voles and shows that prairie voles may be a viable model for studying the cognitive and physiological benefits of social relationships and social engagement in advanced age.

Prognostic value of cardiac magnetic resonance derived global longitudinal strain analysis in patients with ischaemic and non-ischaemic dilated cardiomyopathy: a systematic review and meta-analysis.

Cardiac magnetic resonance (CMR) derived left ventricular global longitudinal strain (LV-GLS) for evaluating dilated cardiomyopathy patients has been addressed in studies with contradictory results. We therefore performed the first systematic review evaluating evidence on the prognostic value of CMR derived LV-GLS for ischaemic (IDCM) and non-ischaemic dilated cardiomyopathy (NDCM) patients. Systematic review (PROSPERO CRD42020171582) identified studies up to January 2021 that measured LV-GLS for predicting major adverse cardiac events among dilated cardiomyopathy patients. Studies were identified from MEDLINE, Embase and PubMed by two independent reviewers. 2099 studies were screened. Three prospective and three retrospective observational studies comprising of 1758 patients (29% IDCM patients; 71% NDCM patients) with a weighted mean follow up of 3 years (SD = 1 year) were identified. All six studies included mortality in the primary composite outcome. LV-GLS was associated with increase primary composite outcome among mild to moderately impaired left ventricular ejection fraction (LVEF) IDCM and NDCM patients (> 30%) in univariable and multivariable analysis. Association was lost among severely impaired LVEF patients (< 30%). From sensitivity analysis, LV-GLS showed significant association with death among NDCM patients (HR 1.27; 95% CI 1.10-1.46; p = 0.001; I2 = 59%) but insignificant for heart transplant outcome (HR 1.23; 95% CI 0.46-3.33; p = 0.68, I2 = 44%). LV-GLS threshold for effectively stratifying patients is - 12.5% to - 13.5%. LVEF in IDCM and NDCM became an insignificant prognostic marker in multivariable analysis. CMR LV-GLS shows promise as an independent predictor of mortality in IDCM and NDCM patients. However, in patients with LVEF < 30% LV-GLS may have less prognostic value.Prospero Registration: CRD42020171582.

Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance.

Bladder cancer is one of the top ten most common cancers and top ten causes of cancer death globally. 5-year survival rates have decreased in Australia from 66% to 55% in the past three decades. The current gold standard for diagnosis is cystoscopy. However, cystoscopies are an invasive and health-resource intensive procedure which has sub-optimal sensitivity for flat lesions such as CIS (carcinoma in situ) and low specificity for differentiating inflammation from cancer - hence requiring biopsies under anesthesia. Frequent and life-long surveillance cystoscopy is required for most patients since there are high rates of progression and local recurrence in high-risk non-muscle invasive cancer (NMIBC) as well as poor outcomes associated with delayed detection of muscle-invasive bladder cancer (MIBC). There is an unmet need for a non-invasive test to provide better discrimination and risk-stratification of bladder cancer which could aid clinicians by improving patient selection for cystoscopy; enhanced risk stratification methods may guide the frequency of surveillance cystoscopies and inform treatment choices. Exosomes, which are nano-sized extracellular vesicles containing genetic material and proteins, have been shown to have functional roles in the development and progression of bladder cancer. Exosomes have also been demonstrated to be a robust source of potential biomarkers for bladder cancer diagnosis and prognosis and may also have roles as therapeutic agents. In this review, we summarize the latest evidence of biological roles of exosomes in bladder cancer and highlight their clinical significance in bladder cancer diagnosis, surveillance and treatment.

Immature Platelet Fraction as a Biomarker for Disease Severity in Pediatric Respiratory Coronavirus Disease 2019.

In this retrospective single-institution cohort study of 113 hospitalized pediatric patients with respiratory coronavirus disease 2019, those admitted to the intensive care unit or requiring mechanical ventilation had significantly higher immature platelet fractions than those who did not require intensive care unit-level care or ventilation. Immature platelet fraction may be an accessible biomarker for disease severity in pediatric respiratory coronavirus disease 2019.

Multivalent Aptamer Approach: Designs, Strategies, and Applications.

Aptamers are short and single-stranded DNA or RNA molecules with highly programmable structures that give them the ability to interact specifically with a large variety of targets, including proteins, cells, and small molecules. Multivalent aptamers refer to molecular constructs that combine two or more identical or different types of aptamers. Multivalency increases the avidity of aptamers, a particularly advantageous feature that allows for significantly increased binding affinities in comparison with aptamer monomers. Another advantage of multivalency is increased aptamer stabilities that confer improved performances under physiological conditions for various applications in clinical settings. The current study aims to review the most recent developments in multivalent aptamer research. The review will first discuss structures of multivalent aptamers. This is followed by detailed discussions on design strategies of multivalent aptamer approaches. Finally, recent developments of the multivalent aptamer approach in biosensing and biomedical applications are highlighted.

WSES guidelines on blunt and penetrating bowel injury: diagnosis, investigations, and treatment.

The aim of this paper was to review the recent literature to create recommendations for the day-to-day diagnosis and surgical management of small bowel and colon injuries. Where knowledge gaps were identified, expert consensus was pursued during the 8th International Congress of the World Society of Emergency Surgery Annual (September 2021, Edinburgh). This process also aimed to guide future research.