Graph neural networks-enhanced relation prediction for ecotoxicology (GRAPE).

Exposure to toxic chemicals threatens species and ecosystems. This study introduces a novel approach using Graph Neural Networks (GNNs) to integrate aquatic toxicity data, providing an alternative to complement traditional in vivo ecotoxicity testing. This study pioneers the application of GNN in ecotoxicology by formulating the problem as a relation prediction task. GRAPE's key innovation lies in simultaneously modelling 444 aquatic species and 2826 chemicals within a graph, leveraging relations from existing datasets where informative species and chemical features are augmented to make informed predictions. Extensive evaluations demonstrate the superiority of GRAPE over Logistic Regression (LR) and Multi-Layer Perceptron (MLP) models, achieving remarkable improvements of up to a 30% increase in recall values. GRAPE consistently outperforms LR and MLP in predicting novel chemicals and new species. In particular, GRAPE showcases substantial enhancements in recall values, with improvements of ≥ 100% for novel chemicals and up to 13% for new species. Specifically, GRAPE correctly predicts the effects of novel chemicals (104 out of 126) and effects on new species (7 out of 8). Moreover, the study highlights the effectiveness of the proposed chemical features and induced network topology through GNN for accurately predicting metallic (74 out of 86) and organic (612 out of 674) chemicals, showcasing the broad applicability and robustness of the GRAPE model in ecotoxicological investigations. The code/data are provided at https://github.com/csiro-robotics/GRAPE.

Prokaryotic microbial ecology as an ecosurveillance tool for eukaryotic pathogen colonisation: Meiothermus and Naegleria fowleri.

Naegleria fowleri has been detected in drinking water distribution systems (DWDS) in Australia, Pakistan and the United States and is the causative agent of the highly fatal disease primary amoebic meningoencephalitis. Previous small scale field studies have shown that Meiothermus may be a potential biomarker for N. fowleri. However, correlations between predictive biomarkers in small sample sizes often breakdown when applied to larger more representative datasets. This study represents one of the largest and most rigorous temporal investigations of Naegleria fowleri colonisation in an operational DWDS in the world and measured the association of Meiothermus and N. fowleri over a significantly larger space and time in the DWDS. A total of 232 samples were collected from five sites over three-years (2016-2018), which contained 29 positive N. fowleri samples. Two specific operational taxonomic units assigned to M. chliarophilus and M. hypogaeus, were significantly associated with N. fowleri presence. Furthermore, inoculation experiments demonstrated that Meiothermus was required to support N. fowleri growth in field-collected biofilms. This validates Meiothermus as prospective biological tool to aid in the identification and surveillance of N. fowleri colonisable sites.

Green horizons: how plant synthetic biology can enable space exploration and drive on Earth sustainability.

As humanity looks towards expanding activity from low Earth orbit to the Moon and beyond, resource use efficiency and self-sustainability will be critical to ensuring success in the long term. Furthermore, solutions developed for the stringent requirements of space will be equally valuable in meeting sustainability goals here on Earth. Advances in synthetic biology allow us to harness the complex metabolism of life to produce the materials we need in situ. Translating those lessons learned from microbial systems to more carbon-efficient photosynthetic organisms is an area of growing interest. Plants can be engineered to sustainably meet a range of needs, from fuels to materials and medicines.

Realized impact of COVID-19 related disruptions on the National Bowel Cancer Screening Program.

BACKGROUND: Colorectal cancer is the second most common cause of cancer mortality in Australia (1). The National Bowel Cancer Screening Program (NBCSP) aims to reduce mortality through early detection with a biennial faecal occult blood test for Australians aged 50-74 years (2). Modelling predicted COVID-19 would reduce participation and delay colonoscopies despite the NBCSP continuing during the pandemic (3). This study analyses the realized impact of COVID-19 related disruptions on the NBCSP and the effect on mortality. METHODS: NBCSP participation, time to colonoscopy and annualized mortality were compared before and during COVID-19. The effect on mortality was determined using a validated microsimulation model (4, 5). RESULTS: From 1 January 2018 to 31 December 2019, 2 497 317 people participated in the NBCSP and 168 390 received a colonoscopy, compared to 2 490 265 and 162 573 from 1 January 2020 to 31 December 2021. Relative participation decreased 6 % and the proportion of colonoscopies performed within the recommended 120 days increased 14.5%. A disproportionally greater impact was observed outside major cities and in lower socioeconomic areas. An estimated 98-111 additional colorectal cancer deaths resulted from 3 % fewer colonoscopies performed during the pandemic. CONCLUSION: This study presents the most comprehensive analysis of the realized impact of COVID-19 on the NBCSP. Catch-up screening would be best targeted at Australians from rural and lower socioeconomic areas where participation remains low. Streamlined referral pathways and additional colonoscopy provisioning is required as less than two thirds of screen positive patients receive a colonoscopy within the recommended 120 days.

p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients.

The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells' behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.

IgA vasculitis nephritis-outcomes in adult-onset disease.

OBJECTIVES: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes. METHODS: We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. RESULTS: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. CONCLUSIONS: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.

Mortality Rate Among Patients with Alcohol Use Disorder with Two or More Readmissions to the Hospital.

Background: Alcohol use disorder is associated with high morbidity and mortality rates, leading to a significant burden worldwide. Increased hazardous alcohol consumption has been reported during the COVID-19 pandemic raising concerns for greater impact of this already prevalent serious medical condition. Methods: We conducted chart reviews and described demographic and clinical data for patients with two or more hospital readmissions from June 2020 to July 2021 and followed survival status through June 2022. Results: We found a high mortality rate of 10.3%. Most patients had psychiatric conditions listed in the chart (n = 70, 80%). Only 34% (n = 24) of living patients and 6% (n = 1) of deceased patients were under psychiatric care. Rates of the utilization of medications for alcohol use disorder were low (n = 23, 26%). Interpretation: We found high mortality rates in patients with two or more hospital readmissions with low rates of utilization of medications for alcohol use disorder and psychiatric care, thus identifying areas of potential improvement.

Impact of obesity on patients undergoing surgery for rectal cancer in Australia and New Zealand.

PURPOSE: Patients with obesity undergoing rectal cancer surgery may have an increased risk of developing complications, though evidence is inconclusive. The aim of this study was to determine the direct impact of obesity on postoperative outcomes using data from a large clinical registry. METHOD: The Binational Colorectal Cancer Audit registry was used to identify patients who underwent rectal cancer surgery in Australia and New Zealand from 2007-2021. Primary outcomes were inpatient surgical and medical complications. Logistic regression models were developed to describe the association between body-mass index (BMI) and outcomes. RESULTS: Among 3,708 patients (median age 66 years [IQR 56.75-75], 65.0% male), 2.0% had a BMI < 18.5 kg/m2, 35.4% had a BMI of 18.5-24.9 kg/m2, 37.6% had a BMI of 25.0-29.9 kg/m2, 16.7% had a BMI of 30.0-34.9 kg/m2, and 8.2% had a BMI ≥ 35.0 kg/m2. Surgical complications occurred in 27.7% of patients with a BMI of 18.5-24.9 kg/m2, 26.6% of patients with a BMI of 25.0-29.9 kg/m2 (OR 0.91, 95% CI 0.76-1.10), 28.5% with a BMI of 30.0-34.9 kg/m2 (OR 0.96, 95% CI 0.76-1.21), and 33.2% with a BMI ≥ 35.0 kg/m2 (OR 1.27, 95% CI 0.94-1.71). Modelling BMI as a continuous variable confirmed a J-shaped relationship. The association between BMI and medical complications was more linear. CONCLUSION: Risk of postoperative complications is increased in patients with obesity undergoing rectal cancer surgery.

Real-world annualized relapse rates from contemporary multiple sclerosis clinics in the UK: a retrospective multicentre cohort study.

BACKGROUND: Annualized relapse rate (ARR) is used as an outcome measure in multiple sclerosis (MS) clinical trials. Previous studies demonstrated that ARR has reduced in placebo groups between 1990 and 2012. This study aimed to estimate real-world ARRs from contemporary MS clinics in the UK, in order to improve the feasibility estimations for clinical trials and facilitate MS service planning. METHODS: A multicentre observational, retrospective study of patients with MS from 5 tertiary neuroscience centres in the UK. We included all adult patients with a diagnosis of MS that had a relapse between 01/04/2020 and 30/06/2020. RESULTS: One hundred thirteen out of 8783 patients had a relapse during the 3-month study period. Seventy-nine percent of the patients with a relapse were female, the mean age was 39 years, and the median disease duration was 4.5 years; 36% of the patients that had a relapse were on disease-modifying treatment. The ARR from all study sites was estimated at 0.05. The ARR for relapsing remitting MS (RRMS) was estimated at 0.08, while the ARR for secondary progressive MS (SPMS) was 0.01. CONCLUSIONS: We report a lower ARR compared to previously reported rates in MS.

JBrowse 2: a modular genome browser with views of synteny and structural variation.

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. It retains core features of JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. It allows users to share sessions, open multiple genomes, and navigate between views. It can be embedded in a web page, used as a standalone application, or run from Jupyter notebooks or R sessions. These improvements are enabled by a ground-up redesign using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers.

MRI of Benign Prostatic Hyperplasia: Important Pre- and Posttherapeutic Considerations.

New minimally invasive techniques that reduce morbidity while improving lower urinary tract symptoms (LUTS) due to benign prostatic hypertrophy (BPH) have become attractive alternatives for patients, in comparison to traditional techniques such as transurethral resection of the prostate (TURP) and simple prostatectomy. Pre- and postprocedural MRI is not routinely performed for LUTS due to BPH treatments. However, because of the combination of rapidly evolving treatments available for LUTS due to BPH and increasing demand for prebiopsy prostate MRI for detection of clinically significant prostate cancer (PCa), an understanding of procedural techniques and expected changes are important for accurate interpretation of prostate MRI performed after treatment of BPH. The authors discuss the imaging evaluation of LUTS due to BPH and emerging predictors of treatment success. The posttreatment appearance and underlying anatomic changes in the prostate after medical, surgical, and minimally invasive treatments including TURP, simple prostatectomy, laser enucleations and ablations, prostatic urethral lift, water vapor thermal therapy, and prostate artery embolization are detailed. Most procedures reduce prostate volume, notably in the periurethral prostatic tissue. Ablations create areas of necrosis and can distort the normal zonal anatomy between the transition zone and the peripheral zone, and prostate artery embolization creates infarcts in the transition zone. Mechanical prostatic urethral lift devices open the anterior channel at the bladder base but create susceptibility artifacts that can obscure and prevent detection of a lesion in the transition zone. Also discussed are the detection of clinically significant prostate cancer in the postprocedural prostate and imaging of BPH procedure complications such as urethral strictures, abscesses, and hematuria. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Purysko in this issue.

Haloperidol vs. placebo for the treatment of delirium in ICU patients: a pre-planned, secondary Bayesian analysis of the AID-ICU trial.

PURPOSE: The AID-ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID-ICU trial results. METHODS: We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors. The probabilities for any benefit/harm, clinically important benefit/harm, and no clinically important differences with haloperidol treatment according to pre-defined thresholds are presented for all outcomes. RESULTS: The mean difference for days alive and out of hospital to day 90 (primary outcome) was 2.9 days (95% credible interval (CrI) - 1.1 to 6.9) with probabilities of 92% for any benefit and 82% for clinically important benefit. The risk difference for mortality was - 6.8 percentage points (95% CrI - 12.8 to - 0.8) with probabilities of 99% for any benefit and 94% for clinically important benefit. The adjusted risk difference for serious adverse reactions was 0.3 percentage points (95% CrI - 1.3 to 1.9) with 98% probability of no clinically important difference. Results were consistent across sensitivity analyses using different priors, with more than 83% probability of benefit and less than 17% probability of harm with haloperidol treatment. CONCLUSIONS: We found high probabilities of benefits and low probabilities of harm with haloperidol treatment compared with placebo in acutely admitted, adult ICU patients with delirium for the primary and most secondary outcomes.

Neighborhood and Depressive Symptoms in Older Adults Living in Rural and Urban Regions in South Korea.

Neighborhoods have a significant impact on depressive symptoms in older adults. In response to the increasing depression of older adults in Korea, this study aims to identify the relationship between perceived and objective neighborhood characteristics in depressive symptoms and find differences between rural and urban areas. We used a National survey collected in 2020 of 10,097 Korean older adults aged 65 and older. We also utilized Korean administration data for identifying the objective neighborhood characteristics. Multilevel modeling results indicated that depressive symptoms decreased when older adults perceived their housing condition (b = -0.04, p < 0.001), their interaction with neighbors (b = -0.02, p < 0.001), and overall neighborhood environment (b = -0.02, p < 0.001) positively. Among the objective neighborhood characteristics, only nursing homes (b = 0.09, p < 0.05) were related to depressive symptoms of older adults living in urban areas. For older adults living in rural areas, the number of social workers (b = -0.03, p < 0.001), the number of senior centers (b = -0.45, p < 0.001), and nursing home (b = -3.30, p < 0.001) in the neighborhood were negatively associated with depressive symptoms. This study found that rural and urban areas have different neighborhood characteristics related to older adults' depressive symptoms in South Korea. This study encourages policymakers to consider neighborhood characteristics to improve the mental health of older adults.

Imaging of benign gallbladder and biliary pathologies in pregnancy.

The rising incidence combined with pregnancy-related physiological changes make gallbladder and biliary pathology high on the differential for pregnant patients presenting with right upper abdominal pain. Imaging plays a crucial role in determining surgical versus non-surgical management in pregnant patients with biliary or gallbladder pathology. Ultrasound (first-line) and magnetic resonance with magnetic resonance cholangiopancreatography (second-line) are the imaging techniques of choice in pregnant patients with suspected biliary pathology due to their lack of ionizing radiation. MRI/MRCP offers an excellent non-invasive imaging option, providing detailed anatomical detail without known harmful fetal side effects. This article reviews physiological changes in pregnancy that lead to gallstone and biliary pathology, key imaging findings on US and MRI/MRCP, and management pathways.

Radiologic findings of biliary complications post liver transplantation.

Liver transplantation is a potentially curative treatment for patients with acute liver failure, end-stage liver disease, and primary hepatic malignancy. Despite tremendous advancements in surgical techniques and immunosuppressive management, there remains a high rate of post-transplant complications, with one of the main complications being biliary complications. In addition to anastomotic leak and stricture, numerous additional biliary complications are encountered, including ischemic cholangiopathy due to the sole arterial supply of the bile ducts, recurrence of primary biliary disease, infections, biliary obstruction from stones, cast, or hemobilia, and less commonly cystic duct remnant mucocele, vanishing duct syndrome, duct discrepancy and kinking, post-transplant lymphoproliferative disorder, retained stent, and ampullary dysfunction. This article presents an overview of biliary anatomy and surgical techniques in liver transplantation, followed by a detailed review of post-transplant biliary complications with their corresponding imaging findings on multiple modalities with emphasis on magnetic resonance imaging and MR cholangiopancreatography.

Robotic-assisted versus laparoscopic rectal surgery in obese and morbidly obese patients: ACS-NSQIP analysis.

Laparoscopic rectal surgery within the confines of a narrow pelvis may be associated with a high rate of open conversion. In the obese and morbidly obese patient, the complexity of laparoscopic surgery increases substantially. Robotic technology is known to reduce the risk of conversion, but it is unclear if it can overcome the technical challenges associated with obesity. The ACS NSQIP database was used to identify obese patients who underwent elective laparoscopic or robotic-assisted rectal resection from 2015 to 2016. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m2. Morbid obesity was defined as a BMI greater than or equal to 35 kg/m2. The primary outcome was unplanned conversions to open. Other outcomes measures assessed included anastomotic leak, operative time, surgical site infections, length of hospital stay, readmissions and mortality. Statistical analyses were performed using SPSS 22.0 (IBM SPSS, USA). 1490 patients had robotic-assisted and 4967 patients had laparoscopic rectal resections between 2015 and 2016. Of those patients, 561 obese patients had robotic-assisted rectal resections and 1824 patients underwent laparoscopic rectal surgery. In the obese cohort, the rate of unplanned conversion to open in the robotic group was 14% compared to 24% in the laparoscopic group (P < 0.0001). Median operative time was significantly longer in the robotic group (248 min vs. 215 min, P < 0.0001). There was no difference in anastomotic leak or systemic sepsis between the laparoscopic and robotic rectal surgery groups. In morbidly obese patients (BMI ≥ 35 kg/m2), the rate of unplanned conversion to open in the robotic group was 19% compared to 26% in the laparoscopic group (P < 0.027). There was no difference in anastomotic leak, systemic sepsis or surgical site infection rates between robotic and laparoscopic rectal resection. Multivariate analysis showed that robotic-assisted surgery was associated with fewer unplanned conversions to open (OR 0.28, P < 0.0001). Robotic-assisted surgery is associated with a decreased risk of conversion to open in obese and morbidly obese patients when compared to conventional laparoscopic surgery. However, robotic surgery was associated with longer operative time and despite improvement in the rate of conversion to open, there was no difference in complications or length of stay. Our findings are limited by the retrospective non-randomised nature of the study, demographic differences between the two groups, and the likely difference in surgeon experience between the two groups. Large randomised controlled studies are needed to further explore the role of robotic rectal surgery in obese and morbidly obese patients.

Pelvic floor training improves faecal incontinence and obstructed defaecation despite the presence of rectal intussusception.

BACKGROUND: Rectal intussusception is often observed in patients with faecal incontinence and obstructed defaecation. The aim of this study is to assess if pelvic floor training improves faecal incontinence and obstructed defaecation in patients with rectal intussusception. METHODS: Case notes of all patients referred to Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018 for the management of faecal incontinence and obstructed defaecation and rectal intussusception were retrospectively reviewed using a prospectively maintained database. St Mark's faecal incontinence and Cleveland clinic constipation scores were obtained from patients before and after they underwent pelvic floor training. RESULTS: One hundred and thirty-one patients underwent pelvic floor training at Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018. Sixty-one patients had rectal intussusception (22 low-grade and 39 high-grade). Median St Marks score improved following pelvic floor training from 8 to 1 (P < 0.001). Median Cleveland Clinic constipation score improved from 8 to 5 (P < 0.001). In patients with low grade rectal intussusception, pelvic floor training improved median St Mark's score from 3 to 0 (P = 0.003), whereas Cleveland Clinic constipation score improved from 9 to 7 (P < 0.001). In patients with high-grade rectal intussusception, pelvic floor training improved median St Mark's score from 9 to 2 (P < 0.001), whereas median Cleveland Clinic constipation score improved from 8 to 4 (P < 0.001). CONCLUSION: Pelvic floor training without biofeedback therapy improves faecal incontinence and obstructed defaecation. Improvement in symptoms is unrelated to rectal intussusception observed on proctography or at examination under anaesthesia in these patients.