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Background & Aims: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in 2017., Method: All patients with ACLF-3 (n = 73), as well as their transplanted matched controls with ACLF-2 (n = 145), 1 (n = 119) and no ACLF (n = 292), who participated in the Princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survival rates, causes of death and their predictive factors., Results: Median follow-up of patients with ACLF-3 was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patient survival rates were 72.6% vs. 69.7% vs. 76.4% vs. 77.0%, respectively (p = 0.31). Ten-year patient survival for ACLF-3 was 56.8% and was not different to other groups (p = 0.37). Leading causes of death in patients with ACLF-3 were infections (33.3%) and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and CLIF-C ACLF score were independently associated with 10-year patient survival. Long-term graft survival rates were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years., Conclusion: 5- and 10-year patient and graft survival rates were not different in patients with ACLF-3 compared to matched controls. 5-year patient survival is higher than the 50%-70% threshold defining the utility of a liver graft. Efforts should focus on candidate selection based on comorbidities, as well as the prevention of infection and cardiovascular events., Impact and Implications: While short-term outcomes following liver transplantation in the most severely ill patients with cirrhosis (acute-on-chronic liver failure grade 3 [ACLF-3]) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favourable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in patients with ACLF-3 compared to matched patients with ACLF-2, ACLF-1, and no-ACLF. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidity evaluation, such as the age-adjusted Charlson comorbidity index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding whether to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and tightly managing cardiovascular risk over time., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support., Objective: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale., Design: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France., Results: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% ( n  = 3) and 22% ( n  = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively., Conclusions: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.

Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes., (© 2024. The Author(s).)

Purpose: This study evaluated the usefulness of SUV analysis of 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy including SUV analysis of the cardiac blood pool normalized by blood volume as a predictor of short-term survival in severe liver failure., Patients and Methods: We enrolled 24 patients with severe liver failure who underwent 99mTc-GSA scintigraphy and were admitted to the intensive care unit. Patients were divided into survival and non-survival groups at 7, 14, and 28 days from the performance of 99mTc-GSA scintigraphy. From SPECT images we calculated SUVs of the cardiac blood pool, performing normalization for body weight, lean body weight, Japanese lean body weight, and blood volume and we calculated SUVs of the liver, normalizing by body weight, lean body weight, and Japanese lean body weight. We also calculated the uptake ratio of the heart at 15 min to that at 3 min (HH15) and the uptake ratio of the liver at 15 min to the liver plus the heart at 15 min (LHL15) from planar images of 99mTc-GSA scintigraphy., Results: There were significant differences between the 7 day survival and non-survival groups for all SUVs of the heart and the liver and HH15, for 14 day survival groups in SUVs of the heart normalized by Japanese lean body weight and blood volume, and no significant differences between 28 day survival groups for any SUVs, HH15, or LHL15. Although the difference was not significant, SUV analysis of the heart normalized by blood volume showed the highest value for the area under the receiver-operating-characteristics curve for both 7 day and 14 day survival., Conclusion: SUV analysis of 99mTc-GSA including SUV analysis of cardiac blood pool normalized by blood volume is of value for prediction of short-term survival in cases with severe liver failure., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background and Aims: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cirrhosis has been increasing these last decades. There are no data regarding the prevalence of MASLD-related cirrhosis in intensive care unit (ICU)., Methods: Prospective single-centre study in a cohort of patients hospitalized in the ICU of Hepatology La Pitié-Salpêtrière Hospital between January 2019 and September 2021. We analysed three groups of patients: MASLD-cirrhosis (alcohol ≤210 g for men and 140 g weekly for women), ALD (alcohol-related liver disease, alcohol>140 g weekly for women or >210 g for men)-cirrhosis alone and MetALD (metabolic and alcohol-related liver disease)-cirrhosis. Endpoints were 1-year transplant-free survival (TFS), further acute decompensation (AD) and re-admission., Results: A total of 410 patients were hospitalized, and 315 analysed: 39 in MASLD, 160 in ALD and 116 in MetALD groups. The global prevalence was 10% for MASLD, 41% ALD and 29.7% for MetALD. Patients in the MASLD group were significantly older (65 vs. 57 and 59 years, p < 0.001), and had lower Child-Pugh (8 vs. 11 vs. 10, p < 0.001) and MELD score (17 vs. 22 vs. 21, p < 0.001). The 1-year TFS was not different between groups (53% vs. 54% vs. 54%, p = 0.96). Cardiovascular mortality was <5% in all groups. The 1-year probability of developing hepatic encephalopathy was significantly higher in the MASLD group (73% vs. 27% and 21%, p < 0.001). There was no difference regarding the development of other complications between groups., Conclusion: MASLD or MetALD was responsible for 1/3 of the causes of cirrhosis in the ICU. MASLD-related cirrhosis is as severe as ALD-related cirrhosis. Liver transplantation should be rapidly discussed., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: There is considerable debate over the indication of liver transplantation (LT) for critically ill patients with cirrhosis, in part due to their potentially poor post-LT prognosis. We analyzed the epidemiology and outcome of LT for critically ill patients with cirrhosis over 4 time periods of 4 years., Methods: We included adult patients who underwent liver transplant alone between 2005 and 2020 using the United Network for Organ Sharing registry database. We defined critically ill patients with cirrhosis as being in the intensive care unit with 1 or more of the following characteristics at the time of LT: (i) grade III/IV hepatic encephalopathy, (ii) mechanical ventilation, (iii) dialysis, and (iv) vasopressors., Results: A total of 85,594 LT recipients were included, 5,827 (6.8%) of whom were classified as being critically ill with cirrhosis at the time of LT. The number and percentage of critically ill LT recipients with cirrhosis increased over the study period: 819 (4.3%) in 2005-2008 vs 2,067 (7.9%) in 2017-2020, P < 0.001. There was a 17% absolute increase in 1-year survival after LT: 72.5% in 2005-2008 vs 89.5% in 2017-2020, P < 0.001. The 1-year post-LT survival gap between critically ill and noncritically ill patients with cirrhosis narrowed over the study period: 16.7 percentage points in 2005-2008 vs 4.6 percentage points in 2017-2020. The year of LT was independently associated with lower 1-year post-LT mortality (hazard ratio 0.92, 95% confidence interval 0.91-0.93, P < 0.001)., Discussion: The absolute number and relative percentage of LT recipients who were critically ill increased over time, as did 1-year post-LT survival. Meanwhile, the gap in survival between this group of patients and noncritically ill patients with cirrhosis decreased but persisted. Cautious access to selected LT candidates who are critically ill may be warranted, provided the gap in survival with noncritically ill patients remains as small as possible., (Copyright © 2024 by The American College of Gastroenterology.)

Background: The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients., Aim: Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care., Methods: We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care., Results: Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource., Conclusions: Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Liver transplantation (LT) is the gold standard for end-stage liver disease, yet postoperative complications challenge patients and physicians. Indocyanine green (ICG) clearance, a quantitative dynamic test of liver function, is a rapid, reproducible, and reliable test of liver function. This study aimed to systematically review and summarize current literature analyzing the association between ICG tests and post-LT outcomes., Methods: This systematic review was conducted according to PRISMA guidelines. MEDLINE and Cochrane Library, as main databases, and other sources were searched until August 2022 to identify articles reporting the prognostic value of postoperative ICG tests associated with outcomes of adult LT recipients.Risk of bias of included articles was assessed using Quality In Prognosis Studies tool. Methodological quality varied from low to high across risk of bias domains., Results: Six studies conducted between 1994 and 2018 in Europe, America, and Asia were included. The study population ranged from 50 to 332 participants. ICG clearance on the first postoperative day was associated with early allograft dysfunction, graft loss, 1-month and 3-month patient survival probability, prolonged ICU, and hospital stay. The dichotomized ICG plasma disappearance rate (PDR) provided a strong association with medium-term and long-term outcomes: PDR less than 10%/min with 1-month mortality or re-transplantation (odds ratio: 7.89, 95% CI 3.59-17.34, P <0.001) and PDR less than 16.0%/min with 3-month patient survival probability (hazard ratio: 13.90, 95% CI 4.67-41.35, P <0.01). The preoperative model for end-stage liver disease and body mass index were independent prognostic factors for early allograft dysfunction, early complications, and prolonged ICU stay; post-LT prothrombin time and INR were independently associated with graft loss and bilirubin with a prolonged hospital stay., Conclusion: This review shows that ICG clearance tests are associated with graft function recovery, suggesting that a potential prognostic role of ICG test, as an aid in predicting the post-LT course, could be considered., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: We aimed to retrospectively investigate an outbreak of linezolidresistant Staphylococcus epidermidis (LRSE), at Tours University Hospital between 2017 and 2021. Methods: Twenty of the 34 LRSE isolates were included in the study. Antimicrobial susceptibility testing was performed using the disk diffusion method and MICs of last-resort antibiotics were determined using broth microdilution or Etest®. Seventeen of the 20 resistant strains were sent to the French National Reference Centre for Staphylococci to determine the mechanism of resistance to linezolid. The clonal relationship between LRSE strains was assessed by PFGE and the sequence type determined by MLST. We retrospectively evaluated a new typing tool, IR-Biotyper®, and compared its results to PFGE to evaluate its relevance for S. epidermidis typing. Medical records were reviewed, and antibiotic consumption was determined. Search for a cross transmission was performed. Results: All LRSE strains showed high levels of resistance to linezolid (MICs = 256 mg/L) and were multi-drug resistant. Linezolid resistance was associated with the 23S rRNA G2576T mutation and none of the 17 strains analyzed carried the cfr gene. Ninety-five percent of the 20 LRSE studied strains were genetically related and belonged to sequence-type ST2. The dendrogram obtained from IR-Biotyper® showed 87% congruence with the PFGE analysis. Prior to isolation of the LRSE strain, 70% of patients received linezolid. No patients stayed successively in the same room. Conclusion: Linezolid exposure may promote the survival and spread of LRSE strains. At Tours University Hospital, acquisition of the resistant clone may also have been triggered by hand-to-hand transmission by healthcare workers. In addition, IR-Biotyper® is a promising typing tool for the study of clonal outbreaks due to its low cost and short turnaround time, although further studies are needed to assess the optimal analytical parameters for routine use. [ABSTRACT FROM AUTHOR]

We present JWST/NIRSpec prism spectroscopy of MACS0647−JD, a triply lensed z ∼ 11 candidate discovered in Hubble Space Telescope imaging and spatially resolved by JWST imaging into two components, A and B. Spectroscopy of component A yields a spectroscopic redshift z = 10.17 based on seven detected emission lines: C iii ] λ λ 1907, 1909, [O ii ] λ 3727, [Ne iii ] λ 3869, [Ne iii ] λ 3968, H δ λ 4101, H γ λ 4340, and [O iii ] λ 4363. These are the second-most distant detections of these emission lines to date, in a galaxy observed just 460 million years after the Big Bang. Based on observed and extrapolated line flux ratios we derive a gas-phase metallicity 12 + log(O/H) ∼ 7.5–8.0, or Z ∼ (0.06–0.2) Z ⊙, ionization parameter log (U) = −1.9 ± 0.2, and an ionizing photon production efficiency log (ξ ion) = 25.2 ± 0.2 erg−1 Hz. The spectrum has a softened Ly α break, evidence for a strong Ly α damping wing. The Ly α damping wing also suppresses the F150W photometry, explaining the slightly overestimated photometric redshift z = 10.6 ± 0.3. MACS0647−JD has a stellar mass log(M / M ⊙) = 8.1 ± 0.3, including ∼6 × 107 M ⊙ in component A, most of which formed recently (within ∼20 Myr) with a star formation rate ∼ 2 ± 1 M ⊙ yr−1, all within an effective radius 70 ± 24 pc. Spectroscopy of a fainter companion galaxy C separated by a distance of ∼ 3 kpc reveals a Lyman break consistent with z ∼ 10.17. MACS0647−JD is likely the most distant galaxy merger known. [ABSTRACT FROM AUTHOR]

Human SULT2B1gene is responsible for expressing SULT2B1a and SULT2B1b enzymes, which are phase II metabolizing enzymes known as pregnenolone and cholesterol sulfotransferase (SULT), respectively. They are expressed in several tissues and contribute to steroids and hydroxysteroids homeostasis. Genetic variation of the SULT2B1 is reported to be associated with various pathological conditions, including autosomal recessive ichthyosis, cardiovascular disease, and different types of cancers. Understanding the pathological impact of SULT2B1 genetic polymorphisms in the human body is crucial to incorporating these findings in evaluating clinical conditions or improving therapeutic efficacy. Therefore, this paper summarized the most relevant reported studies concerning SULT2B1 expression, tissue distribution, substrates, and reported genetic polymorphisms and their mechanisms in enzyme activity and pathological conditions. [ABSTRACT FROM AUTHOR]

Observations of gravitational waves from binary black hole (BBH) mergers have measured the redshift evolution of the BBH merger rate. The number density of galaxies in the Universe evolves differently with redshift based on their physical properties, such as their stellar masses and star formation rates. In this work we show that the measured population-level redshift distribution of BBHs sheds light on the properties of their probable host galaxies. We first assume that the hosts of BBHs can be described by a mixture model of galaxies weighted by stellar mass or star formation rate, and find that we can place upper limits on the fraction of mergers coming from a stellar-mass-weighted sample of galaxies. We then constrain the parameters of a physically motivated power-law delay-time distribution using GWTC-3 data, and self-consistently track galaxies in the UniverseMachine simulations with this delay-time model to infer the probable host galaxies of BBHs over a range of redshifts. We find that the inferred host galaxy distribution at redshift z = 0.21 has a median star formation rate ∼ 0.9 M ⊙ yr−1 and a median stellar mass of ∼1.9 × 1010 M ⊙. We also provide distributions for the mean stellar age, halo mass, halo radius, peculiar velocity, and large-scale bias associated with the host galaxies, as well as their absolute magnitudes in the B and Ks bands. Our results can be used to design optimal electromagnetic follow-up strategies for BBHs, and also to aid the measurement of cosmological parameters using the statistical dark-siren method. [ABSTRACT FROM AUTHOR]

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival. [ABSTRACT FROM AUTHOR]

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. [ABSTRACT FROM AUTHOR]

The granulation of red supergiants (RSGs) in the Magellanic Clouds is systematically investigated by combining the latest RSG samples and light curves from the Optical Gravitational Lensing Experiment and the All-Sky Automated Survey for Supernovae. The present RSG samples are first examined for foreground stars and possible misidentified sources, and the light curves are sequentially checked to remove the outliers by white noise and photometric quality. The Gaussian process (GP) regression is used to model the granulation, and the Markov Chain Monte Carlo is applied to derive the granulation amplitude σ and the period of the undamped oscillator ρ, as well as the damping timescale τ. The dimensionless quality factor Q is then calculated through Q = π τ / ρ. RSGs around Q = 1 / 2 are considered to have significant granulation signals and are used for further analysis. Combining granulation parameters with stellar parameters, robust scaling relations for the timescale ρ are established, while the scaling relations for amplitude σ are represented by a piecewise function, possibly related to the tendency of amplitudes in faint RSGs to converge toward a certain value. Comparing results between the Small Magellanic Cloud and the Large Magellanic Cloud confirms that amplitudes and timescales become larger with metallicity. In examining the scaling relations between the two galaxies, it is found that ρ is nearly independent of metallicity, whereas σ is more significantly affected by metallicity. The GP method is compared with the periodogram fitting of the granulations, and the advantages of either are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Intertidal habitat preferences and spatiotemporal variation in the abundance of juvenile Chinese mitten crab Eriocheir sinensis in Yangtze Estuary are reported. Methods: The size and abundance of this crab are reported for mud flat, gravel, root belt, and marsh habitats in this estuary's lower, middle, and upper reaches from June 2021 (spring) to February 2022 (winter) using quadrat method. Results: Juvenile E. sinensis of carapace length (CL) 5.5 ± 2.1 mm (mean ± standard deviation) were collected; no juveniles were found in February 2022. Crab abundance in root belt and gravel habitats usually exceeded that of marsh habitat; no juveniles were found in mud flat habitat. The greatest abundances and smallest individuals were found when megalopa recruited in early spring (June); juvenile abundance decreased sharply afterwards, and crabs were absent from the intertidal during winter. Size and relative growth rate of juvenile crabs were greater in root belt and gravel habitat than in marsh habitat from June to August. Recruitment primarily drove changes in crab abundance and size during June and July, and temperature best correlated with changes in the winter. Many stage I juveniles (CL < 3.1 mm) occurred in the lower estuarine reaches, while stage III and IV juveniles (CL 3.9-6.5 mm) primarily occurred in the middle and upper estuarine reaches. Discussion: Although intertidal wetland habitat in Yangtze Estuary is severely degraded and reduced in area, it remains important for recruitment and maintenance of mitten crab populations. An understanding of the habitat requirements of this species will benefit management of this crab resource and the prioritized restoration of intertidal habitat. [ABSTRACT FROM AUTHOR]

Engaged communication between mother and a child in their early developmental stages is one of the predictors of children's development of higher-order thinking skills. For deaf children, this engaged communication between mother and child hinges on the home language environment (HLE) being fully accessible to the child. This research uses agogical phenomenology in exploring the lived experiences of participants' HLE where sign language is used, with particular focus on the opportunities for extended discourse. Data were collected via semistructured interviews with the deaf children and their parents and observations in the HLEs of five signing families with at least one deaf child in the southwestern United States. The aim of this study was to document and provide insights into how language use in deaf children's HLE can impact their knowledge development; these insights uncovered the essence of reciprocal and contingent family interactions as a central aspect of the deaf child's HLE. It is hoped that the qualitative phenomenological findings will frame subsequent quantitative investigations of the variability in language access to home language components. [ABSTRACT FROM AUTHOR]

Acute liver failure is a life-threatening organ dysfunction with systemic organ involvement and is associated with significant mortality and morbidity unless specific management is undertaken. This meta-analysis aimed to assess the effects of intravenous N-acetylcysteine (NAC) on mortality and the length of hospital stay in patients with non-acetaminophen acute liver failure. Two hundred sixty-six studies from four databases were screened, and four randomized control trials were included in the final analysis. Our results could not demonstrate increased overall survival (OR 0.70, 95% CI [0.34, 1.44], p = 0.33) or transplant-free survival (OR 0.90, 95% CI [0.25, 3.28], p = 0.87) in patients treated with intravenous NAC. We observed an increased overall survival in adult patients treated with NAC (OR 0.59, 95% CI [0.35, 0.99], p = 0.05) compared to pediatric patients, but whether this is attributed to the age group or higher intravenous dose administered remains unclear. We did not observe a decreased length of stay in NAC-treated patients (OR −5.70, 95% CI [−12.44, 1.05], p = 0.10). In conclusion, our meta-analysis could not demonstrate any significant benefits on overall and transplant-free patient survival in non-acetaminophen ALF. Future research should also focus on specific etiologies of ALF that may benefit most from the use of NAC. [ABSTRACT FROM AUTHOR]

Decompensated liver disease is complicated by multi‐organ failure and poor prognosis. The prognosis of patients with liver failure often dictates clinical management. Current prognostic models have focused on biomarkers considered as individual isolated units. Network physiology assesses the interactions among multiple physiological systems in health and disease irrespective of anatomical connectivity and defines the influence or dependence of one organ system on another. Indeed, recent applications of network mapping methods to patient data have shown improved prediction of response to therapy or prognosis in cirrhosis. Initially, different physical markers have been used to assess physiological coupling in cirrhosis including heart rate variability, heart rate turbulence, and skin temperature variability measures. Further, the parenclitic network analysis was recently applied showing that organ systems connectivity is impaired in patients with decompensated cirrhosis and can predict mortality in cirrhosis independent of current prognostic models while also providing valuable insights into the associated pathological pathways. Moreover, network mapping also predicts response to intravenous albumin in patients hospitalized with decompensated cirrhosis. Thus, this review highlights the importance of evaluating decompensated cirrhosis through the network physiologic prism. It emphasizes the limitations of current prognostic models and the values of network physiologic techniques in cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora–bile acids–liver axis in BAP‐ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP‐ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP‐ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP‐ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP‐ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP‐ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP‐ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP‐ALI mice and suggest that YCHD treatment may confer protection against BAP‐ALI via the gut microflora–bile acids–liver axis. [ABSTRACT FROM AUTHOR]

The vast majority of cultural heritage objects consist of materials that can be subjected to biodeterioration. Currently, there is significant number of publications showing which materials are capable of destroying certain organisms, and what conservation and restoration procedures are required. However, there is neither a clear classification of these diverse events nor their visual representation. In our review, for the first time, an attempt is made to compare the type of biodeterioration, based on the destruction of a particular material, with a specific color of the rainbow. In this regard, a cultural heritage objects made of a single material are designated as one color icon; and those made of composite materials are designated as pictogram consisting of several icons of corresponding colors. For example, a stone sculpture, in accordance with the rainbow code, is assigned a gray color, which was introduced to visualize stone materials. The drum corresponds to a pictogram consisting of violet (corresponds to leather) and brown (corresponds to wood). A work of easel painting on canvas corresponds to a pictogram consisting of a red color icon (corresponds to canvas) and a gold color icon (corresponds to painting materials). We used cold color shades to denote basic inorganic materials, and cold color shades to denote organic materials. The proposed rainbow code for biodetermination is an open platform that can be expanded by adding new colors for new materials introduced, and allows to translate potentially any cultural heritage object into a pictogram with colors that correspond to the materials used in its manufacture. Such a graphical interpretation can help both systematize the storage conditions of museum exhibits and facilitate understanding of the processes of biodeterioration of composite materials. [ABSTRACT FROM AUTHOR]

Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VLs) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VLs have been repeatedly studied in both normal and difficult airways. The superiority of VLs then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) was noticed two decades ago. Since then, sporadic clinical experiences of use have appeared in the literature. In this review article, we presented our vast use experiences of the styletubation (more than 55,000 patients since 2016). We found this technique to be swift (the time to intubate from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satisfaction and fast learning curve for the novice trainees) in both normal and difficult airway scenarios. We, therefore, propose that the styletubation technique can be feasibly applied as universal routine use for tracheal intubation. [ABSTRACT FROM AUTHOR]

Objective To evaluate the value of bronchoalveolar lavage fluid Aspergillus-specific fluorescent PCR assay combined with galactomannan (GM) assay in the diagnosis of patients with non-neutropenic invasive pulmonary aspergillosis (IPA). Methods From March 2022 to December 2023, 113 hospitalized patients with clinically suspected IPA were selected from the Zibo First Hospital of Zibo City, Shandong Province. Bronchoalveolar lavage fluid samples from each patient were simultaneously subjected to potassium hydroxide microscopy, fungal culture, GM assay, and Aspergillus-specific fluorescence PCR assay. According to the diagnostic criteria of IPA, patients were divided into clinically diagnosed IPA and non-IPA groups. The values of these four methods for the diagnosis of IPA were compared. Results According to the diagnostic criteria for IPA, 37 out of the 113 suspected patients were clinically diagnosed as IPA. The proportion of diabetic patients was significantly higher in the IPA group compared to the non-IPA group (χ² =7.494, P=0.006); similarly, the proportion of patients using glucocorticoids was significantly higher in the IPA group (χ² =6.981, P=0.008). Patients in the IPA group more frequently showed cavitation within consolidation areas on imaging, which was statistically significant (χ2 =15.603, P<0.001). There were significant differences in the sensitivity of the four fungal detection methods in the diagnosis of IPA (χ2 =45.803, P<0.001), with Aspergillus-specific PCR assay showing the highest sensitivity at 94.59%. Specificity also varied significantly across the four methods (χ² =31.511, P<0.001), with the highest specificity being seen in potassium hydroxide microscopy and fungal culture at 100.00%. There were significant differences in the clinical coincidence rate of the four methods in the diagnosis of IPA (χ² = 11.768, P=0.008), with Aspergillus-specific fluorescence PCR assay having the highest coincidence rate at 90.27%. The AUC of the ROC curve of Aspergillus-specific fluorescent PCR assay combined with the GM assay was 0.976 7, higher than 0.913 8 by Aspergillus-specific fluorescent PCR assay merely. Conclusions The combination of Aspergillus-specific fluorescent PCR assay and GM assay using bronchoalveolar lavage fluid could significantly improve the accuracy of IPA diagnosis in patients without neutropenia. [ABSTRACT FROM AUTHOR]

Background: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. Objective: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. Methods: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. Results: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. Conclusion: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients. [ABSTRACT FROM AUTHOR]

Transplantology is a branch of medicine that is developing rapidly. Transplanted whole organs or segments of organs may be recovered from either living or deceased donors. New methods of preserving transplanted solid organs, including the kidney, liver, heart, lung, and pancreas, as well as tissues, such as the cornea and skin, are being developed. Preservation fluid, which is used to perfuse and store the donated organ or tissue, should reduce biological deterioration of organs and tissue, attenuate ischemia/reperfusion-induced cell/tissue injury, and protect against damage. Lowering the storage temperature of organs significantly reduces the risk of damage. Efforts are also made to shorten the time between collecting the organ or tissue from the donor and transplanting it in the recipient. However, during transplantation, the recipient may become infected, primarily with bacteria and fungi. Infections of organ recipients occur most often due to unhygienic organ collection, improper handling and transport, and inappropriate preservation conditions, especially contamination of preservation fluid. The literature on contamination of organ preservation fluid and infections in graft recipients is very diverse, both in terms of the isolated bacterial and fungal species and the number of incidents. A large percentage of contaminating microorganisms belong to the generally non-pathogenic skin microbiota, but there are also cases of multidrug-resistant bacteria. Besides, the transplanted organs themselves may pose a danger. They may contain latent microorganisms, mainly viruses and parasites, that could be activated in a patient who has been subjected to immunosuppression to reduce the risk of organ rejection. [ABSTRACT FROM AUTHOR]

Background: The study aims to analyze the epidemiology of preservation fluid (PF) contamination and investigate the impact of PF contamination and possible donor-derived infections(p-DDI) on early postoperative prognosis in kidney transplant (KT) recipients. Methods: A total of 256 PF samples were collected for microbiological evaluation from all KT recipients who received deceased donor donations in our hospital from June 2018 to August 2022. Data on the baseline and clinical characteristics of these PF corresponding to recipients and donors were extracted from the electronic medical record. It mainly included the early postoperative complications and prognosis of KT recipients. Results: From June 2018 to August 2022, 597 kidney transplants were performed in our center, with 260 recipients receiving kidney transplantation from donation after citizens' death. A total of 256 samples of PF were collected, of which 64.5% (165/256) were culture positive, and 24.6% (63/165) of the culture-positive PF were polymicrobial contamination. A total of 238 strains were isolated, of which coagulase-negative staphylococci (CoNS) had the highest proportion of 34.0% (81/238), followed by Klebsiella pneumoniae with 20.6% (49/238) and Escherichia coli with 8.8% (21/238). Recipients with culture-positive PF had a significantly higher incidence of postoperative infection (55.8% vs. 20.9%, P < 0.001) and DGF (38.2% vs. 24.2%, P = 0.023). In addition, the incidence of p-DDI was 12.9% (33/256). CRKP was the most common pathogen causing p-DDI. The recipients who developed p-DDI had a higher rate of graft loss (9.1% vs. 0.4%, P < 0.001), mortality (12.1% vs. 3.1%, P = 0.018), and longer postoperative hospital stay (30 days (19.5–73.5) vs. (22 days (18–32), P < 0.05) compared with recipients who did not develop p-DDI. Conclusions: Culture-positive PF is potentially significant for KT recipients, and p-DDI may increase the risk of poor prognosis for recipients. Prophylactic anti-infective treatment should be actively performed for highly virulent or multidrug-resistant (MDR) pathogens (especially Carbapenem-resistant Klebsiella pneumoniae, CRKP) in PF to avoid the occurrence of p-DDI. [ABSTRACT FROM AUTHOR]

We present near-infrared JHK photometry for the resolved stellar populations in 13 nearby galaxies: NGC 6822, IC 1613, NGC 3109, Sextans B, Sextans A, NGC 300, NGC 55, NGC 7793, NGC 247, NGC 5253, Cen A, NGC 1313, and M83, acquired from the 6.5 m Baade–Magellan telescope. We measure distances to each galaxy using the J-region asymptotic giant branch (JAGB) method, a new standard candle that leverages the constant luminosities of color-selected, carbon-rich AGB stars. While only single-epoch, random-phase photometry is necessary to derive JAGB distances, our photometry is time-averaged over multiple epochs, thereby decreasing the contribution of the JAGB stars' intrinsic variability to the measured dispersions in their observed luminosity functions. To cross-validate these distances, we also measure near-infrared tip of the red giant branch (TRGB) distances to these galaxies. The residuals obtained from subtracting the distance moduli from the two methods yield an rms scatter of σ JAGB−TRGB = ±0.07 mag. Therefore, all systematics in the JAGB method and TRGB method (e.g., crowding, differential reddening, star formation histories) must be contained within these ±0.07 mag bounds for this sample of galaxies because the JAGB and TRGB distance indicators are drawn from entirely distinct stellar populations and are thus affected by these systematics independently. Finally, the composite JAGB star luminosity function formed from this diverse sample of galaxies is well described by a Gaussian function with a modal value of M J = –6.20 ± 0.003 mag (stat), indicating that the underlying JAGB star luminosity function of a well-sampled full star formation history is highly symmetric and Gaussian based on over 6700 JAGB stars in the composite sample. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2's protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values < 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p < 0.0001), and a high proliferation index (p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a disease caused by the SARS-CoV-2 virus. Diagnosis and screening for COVID-19 are crucial in controlling the disease. RT-PCR is used for diagnosis. However, this test is high-risk, time-consuming, and expensive. There is a need for specific non-invasive biomarkers to detect COVID-19 rapidly. Volatile organic compounds (VOCs) produced by the human body can be used to depict metabolic conditions. A COVID-19 detection device is an electronic device designed to differentiate and detect odors. This study aims to assess the effectiveness of armpit sweat odor with a COVID-19 detection device to detect COVID-19. This study was an observational analytic study with a cross-sectional design conducted on COVID-19 and non-COVID-19 patients in the special isolation ward of Dr. Soetomo Hospital and the outpatient clinic of the Indonesian Navy Hospital during April 2021-December 2021. COVID-19 examination using armpit sweat odor with a COVID-19 detection device. The results of the COVID-19 detection device and RT-PCR were then compared using the McNemar test. The general characteristics of the 168 subjects (81 COVID-19 patients, 87 non-COVID-19 patients) showed that the most common gender was male with the most common comorbidities being hypertension and diabetes mellitus. The results of the diagnostic test showed sensitivity and specificity of 88.9% and 97.7%, respectively with accuracy of 93.45%. The McNemar test showed no significant difference with the RT-PCR results. The results of RT-PCR were not different from the results of armpit sweat odor using COVID-19 detection device. [ABSTRACT FROM AUTHOR]

Introduction: Canine olfaction is a potential means for detection of respiratory disease in beef cattle. In a prior study, two dogs were trained to discriminate between nasal swabs from healthy cattle and cattle that developed Bovine Respiratory Disease. Dogs had some ability to identify samples from BRD- affected cattle, but results were ambiguous. The purpose of this study was to evaluate more dogs using better-controlled training and testing procedures. Methods: Nasal and saliva swabs were collected from 96 cattle before and after administering a vaccine to induce an inflammatory immune response. Samples were stored at -80°C for up to 11 months before use, and samples from animals with an elevated body temperature at baseline were omitted. An automated olfactometer apparatus was constructed to improve blinding procedures and reduce opportunities for odor contamination. Four dogs were trained to distinguish between swabs from healthy and sickness-model cattle, including the two dogs from the previous study ("Runnels" and "Cheaps") and two inexperienced dogs ("Molokai" and "Amy"). During a seven-month training period, dogs were exposed to samples from 28 animals. Dogs were tested on 59 sets of unfamiliar samples. Results: Performance varied among dogs (2 = 10.48, p = 0.02). Molokai's performance was above chance (0.73 ± 0.06, p = 0.0006), while Amy (0.44 ± 0.06, p = 0.43), Cheaps (0.53 ± 0.07, p = 0.79), and Runnels (0.56 ± 0.06, p = 0.43) did not respond correctly at a rate different from chance. Accuracy did not differ between nasal swabs (0.63 ± 0.08) and saliva swabs (0.53 ± 0.08, 2 = 0.81, p = 0.37). Discussion: The results of this study indicate that canine olfaction may be an effective means of detecting illness in beef cattle. However, individual dogs' aptitude for this detection task varies. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to outline the use of population and disease registries for clinical trial pre-screening. Materials and methods: The search was conducted in the time period of January 2014 to December 2022 in three databases: MEDLINE, Embase, and Web of Science Core Collection. References were screened using the Rayyan software, firstly based on titles and abstracts only, and secondly through full text review. Quality of the included studies was assessed using the List of Included Studies and quality Assurance in Review tool, enabling inclusion of publications of only moderate to high quality. Results: The search originally identified 1430 citations, but only 24 studies were included, reporting the use of population and/or disease registries for trial pre-screening. Nine disease domains were represented, with 54% of studies using registries based in the USA, and 62.5% of the studies using national registries. Half of the studies reported usage for drug trials, and over 478,679 patients were identified through registries in this review. Main advantages of the pre-screening methodology were reduced financial burden and time reduction. Discussion and conclusion: The use of registries for trial pre-screening increases reproducibility of the pre-screening process across trials and sites, allowing for implementation and improvement of a quality assurance process. Pre-screening strategies seem under-reported, and we encourage more trials to use and describe their pre-screening processes, as there is a need for standardized methodological guidelines. [ABSTRACT FROM AUTHOR]

The precise definition of the lower mass limit of red supergiant stars (RSGs) is an open question in astrophysics and does not attract much attention. Here, we assemble a spectroscopic evolved cool star sample with 6602 targets, including RSGs, asymptotic giant branch stars, and red giant branch stars, in the Large Magellanic Cloud based on Gaia DR3 and Sloan Digital Sky Survey IV/APOGEE-2. The reference spectrum of each stellar population is built according to the quantile range of relative intensity (1% ∼ 99%). Five different methods, e.g., χ 2, cosine similarity, machine learning (ML), equivalent width, and line ratio, are used in order to separate different stellar populations. ML and χ 2 provide the best and relatively consistent prediction of a certain population. The derived lower limit of the RSG population is able to reach the K s -band tip of the red giant branch (K s ≈12.0 mag), indicating a luminosity as low as about 103.5 L ⊙, which corresponds to a stellar radius of only about 100 R ⊙. Given the mass–luminosity relation of L / L ⊙ = f (M / M ⊙) 3 with f ≈ 15.5 ± 3 and taking into account the mass loss of faint RSGs up to now, the minimal initial mass of the RSG population would be about 6.1 ± 0.4 M ⊙, which is much lower than the traditional threshold of 8 M ⊙ for the massive stars. This is the first spectroscopic evidence, indicating that the lower mass limit of the RSG population is around 6 M ⊙. However, the destinies of such faint RSGs are still elusive and may have a large impact on stellar evolutionary and supernova models. [ABSTRACT FROM AUTHOR]

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options. [ABSTRACT FROM AUTHOR]

Radio galaxies in clusters of galaxies are a prominent reservoir of magnetic fields and of non-thermal particles, which become mixed with the intracluster medium. We review the observational and theoretical knowledge of the role of these crucial ingredients for the formation of diffuse radio emission in clusters (radio halos, relics, mini halos) and outline the open questions in this field. [ABSTRACT FROM AUTHOR]

The Arctic tundra has a relatively low biodiversity but species living there have unique adaptations and are exposed to unprecedented rates of climate warming. Monitoring changes in Arctic biodiversity and identifying the driving forces is thus a pressing issue. Bylot Island in the Canadian Arctic has one of the longest and most comprehensive monitoring programs of the tundra food web, spanning four decades. We provide a historical overview of ecological studies on Bylot Island, summarize their key scientific contributions, show their impacts, and present the ingredients for the success of the program and the main challenges encountered. Some major contributions include demonstrating the key role of predation in structuring the tundra food web, the importance of exchanges between ecosystems for the persistence of top predators and their cascading effects on trophic interactions, the apparent resistance of the vertebrate biota to climate warming, the need to consider multiple hypotheses to explain northward range expansion of species and the benefits of integrating scientific data and local knowledge into ecological monitoring. The program has produced >250 journal articles and >80 graduate student theses, which generated >7,700 citations in the scientific literature. A high proportion (65%) of the articles had more citations than comparable publications in their field. The longevity and success of the program can be attributed to several factors, including a researcher-driven (i.e. bottom-up) approach to design the monitoring; long-term commitment of a small number of dedicated researchers and the strong participation of graduate students; the adoption of a food web rather than a single species perspective; extensive presence in the field; the combination of several methodological approaches; and the use of multiple spatial scales adapted to research questions of interest. Challenges encountered include funding issues, transfer of expertise over time, limited spatial replication, statistical design and maintaining partnerships. Robust monitoring is essential to provide sound baseline to detect future changes, and lessons learned from our program could improve future monitoring schemes in the Arctic. Paradoxically, we believe that ecological monitoring on Bylot Island has been successful in large part because it was not originally designed as a monitoring program per se. [ABSTRACT FROM AUTHOR]