bluuebunny/crossref_metadata_2025 huggingface dataset:
O242: Prolonged subnormothermic acellular machine perfusion of human kidneys
Authors: Akalay Sara , Kaczmarek Maja , Hosgood Sarah , Walker-Panse Léonie , MacMillan Serena , Nicholson Michael L
Published: March 2024

Introduction

Prolonged periods of ex vivo perfusion are required to effectively deliver regenerative therapies directly to a kidney before transplantation. This provides time to start repair processes and reduce the likelihood of early graft dysfunction. The aim of this study was to assess the capability of extending the preservation interval using subnormothermic acelllular machine perfusion (SNAP).

Methods

After a period of static cold storage, 12 human kidneys declined for transplantation were perfused with an oxygenated human serum albumin-based solution at 32°C for 6, 12 or 24h (n=4 per group). After preservation all kidneys were reperfused with a red blood cell-based solution at 37°C for 4h for assessment.

Results

Functional parameters remained stable during SNAP in all kidneys. However, the perfusate flow rate was significantly lower in the 24h group (24h 166±45, 12h 266±45, 6h 214±36 mL/min/100g; P=0.008). After reperfusion, levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL), insulin-like growth factor binding protein 7 (IGFBP7) and liver-type fatty acid-binding protein (L-FABP) were similar between groups (P>0.05). Levels of oxygen consumption were significantly lower in 24h kidneys compared to 12h (24h 1.45±0.86, 12h 4.3±1.78 mL/min/100g; P=0.0294). Histological evaluation showed a preserved renal morphology in all kidneys, except for the 24h group which showed a mild increase in tubular and endothelial damage.

Conclusion

This study demonstrated that human kidneys can be successfully preserved with SNAP for up to 12h. There was some evidence of additional ischaemic injury in the 24h SNAP kidneys which warrants further investigation.
O169: The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation
Authors: Malik Abdullah , Tingle Samuel , Chung Nicholas , Owen Ruth , Mahendran Balaji , Counter Claire , Sinha Sanjay , Pettigrew Gavin , Muthasamy Anand , Sutherland Andrew , Casey John , Drage Martin , van Dellan David , Callaghan Chris , Elker Doruk , Manas Derek , Wilson Colin , White Steven
Published: March 2024

Background

Agonal times can vary between organ donors after circulatory death (DCD) following withdrawal of treatment, which leads to variable warm ischaemic damage to pancreas grafts. Currently there is little evidence supporting procurement team standdown times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD transplantation.

Methods

Data were extracted from the UK transplant registry from 2014 to 2022. TTD was defined as withdrawal of life-sustaining treatment to donor asystole; asystolic time was the time from asystole to aortic perfusion. Predictors of graft loss were fitted into a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Statistical significance was set at P<0.05.

Results

375 DCD simultaneous kidney-pancreas transplant recipients were included. Median TTD was 13-minutes (IQR 10 to 16-minutes), median asystolic time was 13-minutes (IQR 11 to 15-minutes). Increasing TTD was not associated with poorer graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time was significantly associated with worse graft survival in the TTD model (aHR 2.51, 95%CI 1.16-5.43, P=0.020). RCS modelling confirmed there was no relationship between TTD and graft survival, however a non-linear relationship was demonstrated between asystolic time and graft survival.

Conclusion

We found no evidence that TTD impacts pancreas graft survival in DCD SPK transplantation, however increasing asystolic time was significant predictors of graft loss. Procurement teams should attempt to minimise asystolic time to reduce ischaemic injury to the pancreas graft.
O127: Global DELPHI Consensus Study on anticoagulation for splanchnic vein thrombosis in acute pancreatitis
Authors: Scott Michael , Ghazanfar Mudassar , Bekheit Mohammed , Ramsay George
Published: March 2024

Introduction

Splanchnic vein thrombosis (SpVT) occurs in 16.6%-22.6% of acute pancreatitis cases, influenced by pancreatitis severity and imaging techniques. Serious sequelae include hepatic and bowel failure, while management with anticoagulation remains controversial amidst perceived bleeding risks. This study's aim, driven by heterogeneity in literature, utilized DELPHI methodology to discern expert consensus on SpVT treatment, advocating for standardized research approaches.

Methods

Using purposive, non-probability sampling and DELPHI methodology, n=173 global experts in SpVT-related acute pancreatitis were engaged from international networks. From April 2022-2023, a three-round Delphi process was implemented to completion. n=26 statements were posed, spanning diagnosis, prognosis, management, and outcomes, with feedback via a 4-point Likert scale. By Round 3, n=54/173 participants remained.

Results

The mean acute pancreatitis caseload per expert per year was 68.0, 72.6 and 73.0 across successive DELPHI rounds. Regarding SpVT anatomical location, there was strong consensus favouring anticoagulation for portal vein (90.7%) and SMV thrombosis (92.6%), but no consensus to treat splenic vein thrombosis (48.2%). 83.7% advocated anticoagulation for complete thrombus occlusion and 70.9% for partial occlusion. Expert views on anticoagulation duration were dichotomous, with 40.7% endorsing 3 or 6 months. In DELPHI Round 3, 74.1% rejected radiological resolution as a definitive treatment endpoint.

Conclusion

Grading of recommendations for SpVT treatment is precluded by heterogeneity in the evidence base. This inaugural DELPHI study underscores the salient considerations for future research. Overwhelming consensus stratified treatment for SpVT localization and degree of thrombus occlusion. 94.5% of experts agree on the feasibility of RCT to investigate treatment of SpVT.
P115: Autologous Fat Grafting as a Treatment for Head and Neck Radiation-Induced Fibrosis: A Systematic Review of Patient Outcomes
Authors: Langridge Benjamin , Jasionowska Sara , Turner Benedict , Awad Laura , Frommer Marvin , Bollen Edward , Kalavrezos Nicholas , Thompson Anna , Sinha Deepti , Butler Peter
Published: March 2024

Background

Radiation-induced fibrosis (RIF) is a chronic, progressive complication of radiotherapy in head and neck cancer with no effective treatment. It has significant impact on quality of life, including pain, poor cosmesis and head and neck contracture. Autologous fat grafting (AFG) is an emerging treatment for RIF. We systematically review the evidence for AFG as a treatment for Head and Neck RIF.

Methods

A systematic search strategy was designed a priori to established PRISMA guidelines. MEDLINE, Embase, Cochrane Library, and clinical trial registries were searched from inception. Eligibility criteria included any study investigating AFG as an intervention for RIF following head and neck cancer.

Results

Fourteen studies met the inclusion criteria, all of which reported physician-assessed aesthetic improvement. No study reported objective measurements of skin biomechanics. Functional outcomes were assessed in eight studies, using the UW-QOL V4, FOIS, VAS and penetration-aspiration scale. Psychological and quality of life outcomes were assessed in four studies via the UW-QOL V4, POS head/neck, SWOL-QOL, DAS24, SF-36 and VAS. Complication rates were low.

Conclusions

Clinical studies demonstrate that AFG may be an effective treatment for RIF in head and neck cancer patients. Outcome measures used varied between studies; development of a core outcomes set including PROMs and objective biomechanical measures of fibrosis would improve the quality of future research and a candidate list of outcomes is proposed.
P136: Artificial Intelligence (AI) and its role in the diagnosis of surgical disease: panacea or potentially dangerous?
Authors: Hammett Felix , Brown Ayla , Patel Rutti , Saha Arin
Published: March 2024

Background

AI algorithms are used in many healthcare settings, though concerns about underlying bias and accuracy exist. This study assessed accuracy of AI in investigation and diagnosis of acute surgical patients, when compared with clinicians’ performance.

Methods

Consecutive patients who attended a surgical SDEC unit over a two-week period in October 2023 were identified. The documented clerking history was inputted into ChatGPT (v3.5) and the algorithm was asked to give the most likely diagnosis and a list of recommended investigations. Clinical records were compared to the AI recommendations. Primary outcome measures were the investigative and diagnostic accuracy of the AI.

Results

88 patients were identified. The most common presenting complaints were abdominal pain (57 patients, 64.8%), abdominal swelling (10 patients, 11.4%) or abscess (8 patients, 9.1%). AI correctly diagnosed 32 patients (36%). AI accuracy was greatest for patients with an abscess (6 patients, 75%), and less accurate for abdominal masses (4 patients, 40%) and abdominal pain (12 patients, 21%). AI recommended fewer investigations that doctors (6 versus 7 tests, median). AI recommended fewer blood tests (3 versus 5 tests, median) yet was more likely to recommend cross-sectional imaging and microbiological investigations.

Conclusions

At present, ChatGPT lacks sufficient diagnostic and investigative maturity to confidently replace a formal surgical clerking and misdiagnosed almost 80% of patients with abdominal pain as well as under-investigating most acute general surgical patients. Development of a bespoke machine-learning algorithm may improve accuracy and enhance the role of AI in triage and initial investigation.
P238: The use of artificial intelligence in 3D imaging modalities and diabetic foot disease – a systematic review
Authors: Ahmad Manal , Tan Matthew , Bergman Henry , Shalhoub Joseph , Davies Alun
Published: March 2024

Introduction

Diabetic foot disease (DFD) is serious complication of diabetes with a multifactorial aetiology and carries a significant risk. The prevalence of DFD continues to grow globally. Artificial intelligence has been proposed in aiding early detection and risk stratification for ulceration and other major complications including sepsis, minor or major lower limb amputation and death.

Aims

To systematically review the literature available on the use of artificial intelligence in three-dimensional imaging modalities in diabetic foot disease.

Method

A literature review was conducted in accordance with PRISMA guidelines. Embase and Medline (via the Ovid interface), CINAHL (via Ebsco Host), Web of Science and Scopus databases were searched. The grey literature was also reviewed on ClinicalTrials.gov and the NIHR journals library. The medical subject headings terms “Diabetes” AND “Diabetic foot disease” AND “Artificial intelligence” and various permutations of three-dimensional imaging modalities including “Computed Tomography”, “Magnetic Resonance Imaging” and “Positron Emission Tomography” were employed in the primary search string. Articles were independently screened by two reviewers.

Results

4,865 studies were identified. 102 duplicates were removed. 4,721 were excluded in the abstract screening. 42 articles underwent full text review. Existing use centers around binary use of CT based imaging in predicting risk.

Conclusion

The use of deep learning models is still being explored and evaluated. Current methodologies focus on wound imaging classification, plantar thermography and plantar pressures. Specialised models which evaluate 3D imaging have potential for generation of supra-human insights into extraction of novel metadata features and prediction utilising integration of multidimensional patient characteristics.
P165: Thoracic Endovascular Aortic Repair in Traumatic Blunt Thoracic Aortic Injury: A Systematic Review & Meta-analysis
Authors: Jubouri Matti , Surkhi Abdelaziz , D’Oria Mario , Bailey Damian , Williams Ian , Bashir Mohamad
Published: March 2024

Background

Blunt thoracic aortic injury (BTAI) represents one of the most devastating scenarios of vascular trauma. Different management strategies are available with varying clinical outcomes, however, thoracic endovascular aortic repair (TEVAR) has become the first-line option for most BTAI patients, mainly owing to its minimally invasive nature yielding improved immediate results. This meta-analysis aims to investigate mortality and long-term survival as well as reintervention following TEVAR in BTAI.

Methods

In a systematic review, a comprehensive literature search was conducted on multiple electronic databases using strict search terms. Twenty-five studies met the set inclusion/exclusion criteria. Proportional meta-analysis of extracted data was conducted using the R-studio and STATA software.

Results

The final analysis included 1367 BTAI patients with who underwent TEVAR. Using the SVS grading system, 2.4% of the population had Grade 1 injuries, 12.8% Grade 2, 60.2% Grade, 22.6% Grade 4, and 1.7% unspecific. All-cause mortality did not exceed 20% in all studies except one outlier with a 37% mortality rate. Using the random-effects model, the pooled estimate of overall mortality was 6.95% (95%CI 5.35-8.55%; I2 = 70.6%). This was 91.2% (95%CI, 88.6-93.2; I2= 30.2%) at 6 months, 89.8% (95%CI, 86.7-92.3; I2 = 53.6%) at 1-year, 88.9% (95%CI, 85.2-91.8; I2= 62.3%) at 2 years, and 87.6% (95%CI, 83.3-90.9; I2 = 69.6%) at 5 years. Moreover, the pooled estimate of reintervention was 0.19% (95%CI, 0.1-0.49%; I2 = 81.7%).

Conclusion

Despite the high morbidity and mortality associated with BTAI, TEVAR has proven to be a safe and effective management strategy.
May Measurement Month 2021: an analysis of blood pressure screening results from a suburban community in the Democratic Republic of the Congo
Authors: Buila Nathan B , Tshiswaka Tresor M , Lubenga Yves N , Katamba Fortunat K , Bayauli Pascal M , Ngoyi Georges N , Bantu Jean-Marc B , Beaney Thomas , Kerr Gabriele , Poulter Neil R , M’Buyamba-Kabangu Jean-René
Published: March 2024

Hypertension remains the most powerful contributor to the global morbidity and mortality. May Measurement Month (MMM), a worldwide screening campaign initiated by the International Society of Hypertension (ISH), is organized annually to increase awareness of high blood pressure (BP). We screened 20 913 adult (≥18 years) residents of suburb hamlets of Mbujimayi (mean age 35.1 ± 15.1 years; Black ethnicity: 98.8%; women: 29.6%; diabetes: 1.6%; alcohol drinkers: 16.8% and smokers: 6.7%, previous myocardial infarction: 1.4%; stroke: 0.8%; taking aspirin: 3.2%; taking statins: 1.9%). Three sitting BP readings were taken, and hypertension was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Half of the participants had never had their BP checked, whilst 4.2% of respondents had participated in the MMM19 campaign. 0.9% and 1.7% reported COVID-19 vaccination and positive test, respectively. After multiple imputation of missing BP readings, 14.0% of respondents had hypertension of which 35.8% were aware, 28.0% were on antihypertensive medication and 14.1% had controlled BP. Of those on antihypertensive medication, 40.4% were on monotherapy, 37.2% adhered to taking their medication regularly, and 50.4% had controlled BP (<140/90 mmHg). In regression analyses adjusted for age, sex, and antihypertensive treatment, smoking was associated with lower systolic BP, having more years of education was associated with higher systolic and diastolic BP, and physical activity was associated with lower systolic and diastolic BP. This campaign contributes somewhat to reducing the ‘black hole’ on the prevalence of hypertension in DRC pending systematic countrywide BP screening.
May Measurement Month 2021: an analysis of blood pressure screening results from the UK and Republic of Ireland
Authors: Lee Shaun C , Warrington Daniel , Beaney Thomas , Cockcroft John R , Pugh Christopher J A , Williams Abbie , Olding Tyler , Dolan Eamon , O’Brien Eoin , Hynes Lisa , Rabbitt Madeline , Cunnane Paul , Schutte Aletta E , Poulter Neil R , McDonnell Barry J
Published: March 2024

We participated in the UK and Republic of Ireland May Measurement Month 2021 (MMM21) campaign to raise awareness about blood pressure (BP) measurement and the dangers posed by elevated BP and hypertension. In addition, the campaign aimed to collect and report levels of BP awareness and control in the community setting. The MMM21 campaign set up opportunistic community screening sites at hospitals, general practice (GP) surgeries, community pharmacies, gyms, and various other public places. The campaign screened 1322 participants (mean age 46 years, 55% women) and found that 522 (39.5%) had hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or on antihypertensive medication) at the time of testing. Of the 522 participants identified with hypertension, only 47.2% were aware of their condition. Of those on antihypertensive medication, only 45.7% had controlled BP (systolic BP < 140 mmHg and diastolic BP < 90 mmHg), and of all hypertensives, only 19.0% were controlled. Our UK and Ireland data continue to shed further light on low levels of awareness and control of hypertension in the UK and Ireland community setting. This evidence supports a critical need to further highlight the importance of identifying and taking action against raised BP.
May Measurement Month 2021: an analysis of blood pressure screening results from Venezuela
Authors: Hernández-Hernández Rafael , Guzmán-Franulic Mónica L , Rawik-Dagher Yuly , Beaney Thomas , Poulter Neil R , Duin-Balza Amanda , Armas-Hernández María J , Silva Egle , Morr Igor , Octavio-Seijas José Andrés , Toopchiani Sima , Armas-Padilla María C
Published: March 2024

Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90 mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.
Limitations and drawbacks of DQE estimation methods applied to electron detectors
Authors: Marcelot Olivier , Marcelot Cécile , Rolando Sébastien
Published: March 2024

The detective quantum efficiency (DQE) is generally accepted as the main figure of merit for the comparison between electron detectors, and most of the time given as a unique number at the Nyquist frequency while it is known to vary with electron dose. It is usually estimated, thanks to a method improved by McMullan in 2009. The purpose of this work is to analyze and to criticize this DQE extraction method on the basis of measurement and model results, and to give recommendations for fair comparison between detectors, wondering if the DQE is the right figure of merit for electron detectors.
Microequity: some thoughts for an emerging research agenda
Authors: Meki Muhammad , Quinn Simon
Published: March 2024

This paper summarizes recent research in performance-based microfinance, and outlines future directions for research. We use the term ‘microequity’ to refer to any small-enterprise financing contract in which the repayment owed in each instalment depends positively upon the variable performance of the enterprise. We summarize research from financial economics and development economics to highlight the importance of implicit insurance in microequity contracts, and present a theoretical framework to illustrate the potential of microequity in supporting capital investment and incentivizing asset use. We conclude by highlighting directions for future research in this emerging field of microfinance.
Bone metastases among newly diagnosed cancer patients: a population-based study
Authors: Chen Feng , He Bo , Wang Yang
Published: March 2024

Purpose

(i) To analyze age-adjusted incidence rates of synchronous bone metastases diagnosed alongside primary malignancy from 2010 to 2018 in the US population, (ii) determine the incidence proportions (IPs) and characteristics of synchronous bone metastases among newly diagnosed cancer patients in the USA especially pediatric cases, and (iii) assess the implications of synchronous bone metastases on cancer patient’s survival, and identify the survival risk factors for these cancer patients.

Methods

Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program (2010–2018), we calculated age-adjusted IPs and annual percentage change (APC), and employed logistic regression and Cox regression models for our analysis.

Results

3 300 736 cancer patients were identified. The age-adjusted incidence rates of synchronous bone metastases increased from 2010 (18.04/100 000) to 2018 (20.89/100 000; APC: 2.3, 95% confidence interval [CI], 1.4–3.1), but decreased in lung cancer (average APC: –1.0, 95% CI, −1.8 to −0.3). The highest IPs were observed in pediatric neuroblastoma (43.2%; 95% CI, 39.8%–46.7%) and adult small cell carcinoma (23.1%; 95% CI, 22.7%–23.4%). Multivariate logistic analyses revealed that primary tumor characteristics were correlated with higher bone metastases risk. Survival analyses also showed varied prognostic outcomes based on metastasis sites and demographics among cancer patients. Landmark analyses further indicated among long-term cancer survivors (≥3 and ≥5 years), patients with de novo bone metastases had the poorest survival rates compared with those with other synchronous metastases (P < 0.001).

Conclusion

This study provides a population-based estimation of the incidence and prognosis for synchronous bone metastases. Our findings highlight the need for early identification of high-risk groups and multidisciplinary approaches to improve prognosis of cancer patients with de novo bone metastases.
Where are they and how do they perform? Measuring long-term career outcomes of public health doctoral recipients
Authors: Wang Bo , Wang Cheng , Hanks Andrew S
Published: March 2024

Background

Doctoral recipients of public health play pivotal roles in the support and leadership of the public health industry and academic research. We conducted this study to assess and track the long-term career outcomes of public health PhDs (PHPhD).

Methods

We linked data from the Survey of Doctorate Recipients to the Survey of Earned Doctorates and tracked the long-term career outcomes and job placements of PHPhD from 2001 to 2017. Logistic regression and ordinary least squares regression models were used to model career outcomes and behavioral characteristics.

Results

PHPhD specializing in biometrics and biostatistics had the highest annual income. In all, 59.5% of PHPhD chose academia to likely continue research activities. However, 11.1% of PHPhD shifted job sectors from academia to industry or government 10 years postgraduation. Persistent disparities across racial and gender groups were observed in job outcomes such as salary, working hours and job satisfaction.

Conclusions

These results provide instructive insights PHPhD can use for long-term career planning. Public health program administrators, employers and stakeholders may use the results to address labor outcome disparities in race and gender.
Electroencephalogram rhythmic and arrhythmic spectral components and functional connectivity at resting state may predict the development of synucleinopathies in idiopathic rapid eye movement sleep behavior disorder
Authors: Hernandez Jimmy , Lina Jean-Marc , Dubé Jonathan , Lafrenière Alexandre , Gagnon Jean-François , Montplaisir Jacques-Yves , Postuma Ronald B , Carrier Julie
Published: March 2024

Study Objectives

Idiopathic/isolated rapid eye movement-sleep behavior disorder (iRBD) often precedes the onset of synucleinopathies. Here, we investigated whether baseline resting-state EEG advanced spectral power and functional connectivity differed between iRBD patients who converted towards a synucleinopathy at follow-up and those who did not.

Methods

Eighty-one participants with iRBD (66.89 ± 6.91 years) underwent a baseline resting-state EEG recording, a neuropsychological assessment, and a neurological examination. We estimated EEG power spectral density using standard analyses and derived spectral estimates of rhythmic and arrhythmic components. Global and pairwise EEG functional connectivity analyses were computed using the weighted phase-lag index (wPLI). Pixel-based permutation tests were used to compare groups.

Results

After a mean follow-up of 5.01 ± 2.76 years, 34 patients were diagnosed with a synucleinopathy (67.81 ± 7.34 years) and 47 remained disease-free (65.53 ± 7.09 years). Among patients who converted, 22 were diagnosed with Parkinson’s disease and 12 with dementia with Lewy bodies. As compared to patients who did not convert, patients who converted exhibited at baseline higher relative theta standard power, steeper slopes of the arrhythmic component and higher theta rhythmic power mostly in occipital regions. Furthermore, patients who converted showed higher beta global wPLI but lower alpha wPLI between left temporal and occipital regions.

Conclusions

Analyses of resting-state EEG rhythmic and arrhythmic components and functional connectivity suggest an imbalanced excitatory-to-inhibitory activity within large-scale networks, which is associated with later development of a synucleinopathy in patients with iRBD.
CircTLK1: A novel regulator involved in VSMC phenotypic switching and the developmental process of atherosclerosis
Authors: Zhang Feng , Xiang Xuying , Wen Cheng , Guo Xiaoqing , Nie Lei , Chen Jiaojiao , Xia Yuanpeng , Hu Bo , Mao Ling
Published: March 2024

Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for atherosclerosis development. Circular RNA (circRNA) is a specific non‐coding RNA that is produced as a closed‐loop structure in mammals, and its specific expression pattern is closely related to its cell type and tissue. To clarify the roles of circTLK1 in VSMC phenotypic switching, we performed qRT‐PCR, immunoblotting, and immunostaining. qRT‐PCR revealed that circTLK1 was upregulated in both mouse models of atherosclerosis in vivo and PDGF (platelet‐derived growth factor)–BB‐induced VSMCs in vitro. Furthermore, the overexpression of circTLK1 promoted PDGF‐BB‐induced VSMC phenotypic switching. Conversely, experiments performed in vivo demonstrate that the knockdown of SMC‐specific circTLK1 led to a reduction in the development of atherosclerosis. The relationship between circTLK1 and miR‐513a‐3p and Krüppel‐like factor 4 (KLF4) was detected by RNA immunoprecipitation (RIP), luciferase reporter assay, RNA pull‐down, and RNA fluorescence in situ hybridization (RNA FISH). Mechanistically, circTLK1 acted as a sponge for miR‐513a‐3p, leading to the upregulation of KLF4, a key transcription factor for phenotypic switching. Targeting the circTLK1/miR‐513a‐3p/KLF4 axis may provide a potential therapeutic strategy for atherosclerosis.
Direct potable reuse and birth defects prevalence in Texas: An augmented synthetic control method analysis of data from a population-based birth defects registry
Authors: Schraw Jeremy M. , Rudolph Kara E. , Shumate Charles J. , Gribble Matthew O.
Published: March 2024

Background:

Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence.

Methods:

We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates.

Results:

There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged.

Conclusions:

We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.
ER stress promotes mitochondrial calcium overload and activates the ROS/NLRP3 axis to mediate fatty liver ischemic injury
Authors: Li Fei , Guan Zhu , Gao Yiyun , Bai Yan , Zhan Xinyu , Ji Xingyue , Xu Jian , Zhou Haoming , Rao Zhuqing
Published: March 2024

Background:

Fatty livers are widely accepted as marginal donors for liver transplantation but are more susceptible to liver ischemia and reperfusion (IR) injury. Increased macrophage-related inflammation plays an important role in the aggravation of fatty liver IR injury. Here, we investigate the precise mechanism by which endoplasmic reticulum (ER) stress activates macrophage NOD-like receptor thermal protein domain–associated protein 3 (NLRP3) signaling by regulating mitochondrial calcium overload in fatty liver IR.

Methods:

Control- and high-fat diet-fed mice were subjected to a partial liver IR model. The ER stress, mitochondrial calcium levels, and NLRP3 signaling pathway in macrophages were analyzed.

Results:

Liver steatosis exacerbated liver inflammation and IR injury and enhanced NLRP3 activation in macrophages. Myeloid NLRP3 deficiency attenuated intrahepatic inflammation and fatty liver injury following IR. Mechanistically, increased ER stress and mitochondrial calcium overload were observed in macrophages obtained from mouse fatty livers after IR. Suppression of ER stress by tauroursodeoxycholic acid effectively downregulated mitochondrial calcium accumulation and suppressed NLRP3 activation in macrophages, leading to decreased inflammatory IR injury in fatty livers. Moreover, Xestospongin-C–mediated inhibition of mitochondrial calcium influx decreased reactive oxygen species (ROS) expression in macrophages after IR. Scavenging of mitochondrial ROS by mito-TEMPO suppressed macrophage NLRP3 activation and IR injury in fatty livers, indicating that excessive mitochondrial ROS production was responsible for macrophage NLRP3 activation induced by mitochondrial calcium overload. Patients with fatty liver also exhibited upregulated activation of NLRP3 and the ER stress signaling pathway after IR.

Conclusions:

Our findings suggest that ER stress promotes mitochondrial calcium overload to activate ROS/NLRP3 signaling pathways within macrophages during IR-stimulated inflammatory responses associated with fatty livers.
Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis
Authors: Anouti Ahmad , Seif El Dahan Karim , Rich Nicole E. , Louissaint Jeremy , Lee William M. , Lieber Sarah R. , Arab Juan Pablo , Zhang Bill Y. , Patel Mausam J. , Thimphittaya Chanattha , Díaz Luis Antonio , Gregory Dyanna L. , Kozlitina Julia , VanWagner Lisa B. , King Andrea C. , Mitchell Mack C. , Singal Amit G. , Cotter Thomas G.
Published: March 2024

Background:

Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic disparities are evident within ALD; however, the precise nature of these disparities is poorly defined.

Methods:

We conducted a search of the PubMed/MEDLINE and EMBASE databases to identify studies published from inception through September 2023 that reported ALD incidence, prevalence, and mortality within the United States, stratified by race and ethnicity. We calculated pooled prevalence and incidence by race and ethnicity, including risk ratios and ORs for ALD pooled prevalence and alcohol-associated hepatitis/alcohol-associated cirrhosis pooled proportions, and OR for ALD mortality using the DerSimonian and Laird method for random-effect models.

Results:

We identified 25 relevant studies (16 for quantitative meta-analysis), comprising 76,867,544 patients. ALD prevalence was highest in Hispanic (4.5%), followed by White (3.1%) and Black (1.4%) individuals. Pooled risk ratios of ALD prevalence were 1.64 (95% CI: 1.12–2.39) for Hispanic and 0.59 (95% CI: 0.35–0.87) for Black compared to White individuals. Mortality among those with ALD did not significantly differ between White and Hispanic (OR: 1.54, 95% CI: 0.9–2.5; I
2=0%), Black (OR: 1.2, 95% CI: 0.8–1.6; I
2=0%), or Native American (OR: 2.41, 95% CI: 0.9–2.9) individuals, while there was a significant difference between White and Asian (OR: 0.1; 95% CI: 0.03–0.5) individuals. Most data were cross-sectional and assessed to be of poor or fair quality.

Conclusions:

Differences were observed in ALD epidemiology, including higher prevalence among Hispanic and lower prevalence among Black individuals, although there were smaller differences in ALD mortality. Differences in ALD prevalence and prognosis remain poorly defined based on existing data, highlighting a need for higher-quality epidemiological studies in this area.
False-Positive Rate for Suspected Drug-Related Deaths Following Full Autopsy
Authors: Hancock Addie , McLemore Jerri , Russell Greg
Published: March 2024

The sharp increase in drug-related deaths has tempted medical examiner/coroner offices to perform external examinations with comprehensive toxicology testing instead of performing a standard autopsy. Compounding the problem of an increasing workload has been the decrease in available forensic pathologists. Opting for external examinations on suspected drug-related fatalities, however, is antithetical to current best practices. The purpose of this study was to review case files, autopsy reports, and toxicologic results of all deaths that were autopsied at the authors' facility and decide whether significant disease processes or injuries that would supersede the results of toxicologic testing and external examination findings alone were being missed.
Uterine Leiomyosarcoma Associated With Perivascular Epithelioid Cell Tumor
Authors: Katsakhyan Levon , Shahi Maryam , Eugene Henrietta C. , Nonogaki Hiro , Gross John M. , Nucci Marisa R. , Vang Russell , Xing Deyin
Published: March 2024

Perivascular epithelioid cell tumor (PEComa) is a mesenchymal tumor thought to originate from perivascular epithelioid cells (PECs). The normal counterpart to PEC, however, has not been identified in any human organ, and the debate as to whether PEComa is related to smooth muscle tumors has persisted for many years. The current series characterizes 4 cases of uterine leiomyosarcoma (LMS) coexisting with PEComas. All cases exhibited an abrupt transition from the LMS to PEComa components. The LMS component displayed typical spindled morphology and fascicular growth pattern and was diffusely positive for desmin and smooth muscle myosin heavy chain, completely negative for HMB-45 and Melan A, and either negative or had focal/weak expression of cathepsin K and GPNMB. In contrast, the PEComa tumor cells in case 1 contained glycogen or lipid-distended cytoplasm with a foamy appearance (low grade), and in cases 2, 3, and 4, they displayed a similar morphology characterized by epithelioid cells with eosinophilic and granular cytoplasm and high-grade nuclear atypia. Different from the LMS component, the epithelioid PEComa cells in all cases were focally positive for HMB-45, and diffusely immunoreactive for cathepsin K and GPNMB. Melan A was focally positive in cases 1 and 3. Loss of fumarate hydratase expression (case 1) and RB1 expression (cases 2, 3, 4) was identified in both LMS and PEComa components, indicating that they are clonally related. In addition, both components showed an identicalTP53 p.R196*somatic mutation and complete loss of p53 and ATRX expression in case 2 and complete loss of p53 expression in case 3. We hypothesize that LMSs containing smooth muscle progenitor cells may give rise to divergent, lineage-specific PEComatous lesions through differentiation or dedifferentiation. While we do not dispute the recognition of PEComas as a distinct entity, we advocate the hypothesis that modified smooth muscle cells represent the origin of a subset of PEComas, and our case series provides evidence to suggest this theory.
Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma
Authors: Saka Manduwa , Fujimoto Masakazu , Mizoguchi Kai , Tsujimura Marina , Saeki Miho , Hirata Masahiro , Shibuya Shinsuke , Odani Kentaro , Sakurai Takaki , Yuba Yoshiaki , Moriyoshi Koki , Nakajima Naoki , Sumiyoshi Shinji , Kono Fumihiko , Ono Kazuo , Shirase Tomoyuki , Watanabe Chihiro , Yoshizawa Akihiko , Haga Hironori
Published: March 2024

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non–germinal center B cells were detected in only 2 samples (P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.
Preoperative 11C-Methionine PET-MRI in Pediatric Infratentorial Tumors
Authors: Beuriat Pierre-Aurélien , Flaus Anthime , Portefaix Aurélie , Szathmari Alexandru , Janier Marc , Hermier Marc , Lorthois-Ninou Sylvie , Scheiber Christian , Isal Sibel , Costes Nicolas , Merida Ines , Lancelot Sophie , Vasiljevic Alexandre , Leblond Pierre , Faure Conter Cécile , Saunier Clarisse , Kassai Behrouz , Vinchon Matthieu , Di Rocco Federico , Mottolese Carmine
Published: March 2024

Purpose

MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results.

Patients and Methods

Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADCmin) and contrast enhancement were compared with MET SUVmax. The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification.

Results

Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADCmin and SUVmax values (r = −0.39). Mean SUVmax was 3.8 (range, 3.3–4.2) in WHO grade 4 versus 2.5 (range, 1.7–3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values (r = 0.34). There was no correlation between SUVmax and contrast enhancement intensity (r = −0.15).

Conclusions

Preoperative 11C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.
Cross-talk and mutual shaping between the immune system and the microbiota during an oyster's life
Authors: Destoumieux-Garzón Delphine , Montagnani Caroline , Dantan Luc , Nicolas Noémie de San , Travers Marie-Agnès , Duperret Léo , Charrière Guillaume M. , Toulza Eve , Mitta Guillaume , Cosseau Céline , Escoubas Jean-Michel
Published: March 2024

The Pacific oyster
Crassostrea gigas
lives in microbe-rich marine coastal systems subjected to rapid environmental changes. It harbours a diversified and fluctuating microbiota that cohabits with immune cells expressing a diversified immune gene repertoire. In the early stages of oyster development, just after fertilization, the microbiota plays a key role in educating the immune system. Exposure to a rich microbial environment at the larval stage leads to an increase in immune competence throughout the life of the oyster, conferring a better protection against pathogenic infections at later juvenile/adult stages. This beneficial effect, which is intergenerational, is associated with epigenetic remodelling. At juvenile stages, the educated immune system participates in the control of the homeostasis. In particular, the microbiota is fine-tuned by oyster antimicrobial peptides acting through specific and synergistic effects. However, this balance is fragile, as illustrated by the Pacific Oyster Mortality Syndrome, a disease causing mass mortalities in oysters worldwide. In this disease, the weakening of oyster immune defences by OsHV-1 µVar virus induces a dysbiosis leading to fatal sepsis. This review illustrates the continuous interaction between the highly diversified oyster immune system and its dynamic microbiota throughout its life, and the importance of this cross-talk for oyster health.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
ATF4 orchestrates IL-1α-induced senescence in adult neural stem cells
Authors: Neumann Susanne , Thelin Eric P. , Sankavaram Sreenivasa Raghavan , Persson Sanna , Fonseca Leonor , Moruzzi Noah , Iacobaeus Ellen , Bergsland Maria , Popova Elena , Bader Michael , Svensson Mikael , Espinosa Alexander , Covacu Ruxandra , Brundin Lou
Published: March 2024

Adult neural stem cells (NSC) are a potential source for the regeneration of damaged tissue during neuropathological conditions, but much remains unexplored. In an attempt to study the influence of neuroinflammation on NSCs, we generated a transgenic reporter rat strain that expresses theDiscosoma sp. red (DsRed) fluorophore in NSCs and subjected it to traumatic brain injury (TBI). Transcriptomic analysis of NSCs isolated from TBI revealed an enrichment of stress response genes that pertained to endoplasmic reticulum (ER) stress and integrated stress response (ISR). Downstream analysis on NSC cultures pinpointed IL-1α as a trigger of ISR in these cells. At concentration levels similar to the ones measured post-TBI in rats, IL-1α induced the translation of activating transcription factor 4 (ATF4), an ISR master regulator. Further, ATF4 was necessary for the IL-1α -dependent induction of a senescent profile in NSCs, which included a metabolic shift towards glycolysis, induction of senescence-associated secretory phenotype, SASP, and cell cycle arrest. In summary, the ISR/ATF4 pathway seems to play a major role in NSC function during neuroinflammation and provides a therapeutic tool for protecting the NSC pool during these conditions.