bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the accuracy of 68Ga‐PSMA PET/CT compared with MRI in the initial diagnosis of prostate malignancy: A cohort analysis of 114 consecutive patients
Authors: Paterson Felix , Nottage Michelle , Kitchener Michael , Jarvis Matthew , Reid Jessica , Oakden‐Rayner Luke
Published: July 2021

Introduction

Prostate cancer diagnosis is shifting towards a minimally invasive approach, maintaining accuracy and efficacy while reducing morbidity. We aimed to assess if PSMA–Ga68 PET/CT can accurately grade and localise prostatic malignancy using objective methods, compared with pathology and MRI.

Methods

Retrospective analysis on 114 consecutive patients undergoing staging PSMA PET/CT scans over 12 months was carried out. The SUVmax and site of highest PSMA activity within the prostate gland were recorded. Pathology/biopsy review assessed maximum Gleason score (and location). MRI analysis assessed the highest PIRADS score and location. The grade, location and size of malignant tissue on biopsy, and PSA, were correlated with the SUVmax and the PIRADS score.

Results

SUVmax was significantly elevated in cases with PSA ≥10 (P = 0.003) and Gleason score ≥8 (P = 0.0002). SUVmax demonstrated equivalent sensitivity to MRI‐PIRADS in predicting Gleason ≥8 disease, with higher specificity when tested under a high‐specificity regime (SUVmax ≥10, PIRADS = 5, P = 0.002). Furthermore, the region of highest SUVmax was superior to MRI‐PIRADS for localising the highest grade tumour region, correctly identifying 71% of highest grade regions compared to 54% with MRI (P = 0.015).

Conclusion

PSMA PET/CT is as effective as MRI in identifying high‐grade prostate malignancy. Our findings also support previous studies in showing a significant relationship between SUVmax and Gleason grade. These benefits, along with the known advantage in identifying distant metastases and the reduced cost, further support the argument that PSMA PET/CT should be offered as an initial investigation in the workup of prostate cancer.
RORC gene polymorphism is associated with acute kidney injury following cardiac surgery
Authors: Gholamipoor Zeynab , Rahimzadeh Mahsa , Montazerghaem Hossein , Naderi Nadereh
Published: July 2021

Background

Acute kidney injury (AKI) is a common complication of cardiopulmonary bypass (CPB), associated with increased mortality in surgical patients. It is well‐proven that Th17 and its hallmark cytokine, IL‐17, contribute to AKI development. Since the RAR‐related orphan receptor C (RORC) gene is a master regulator of the Th17 differentiation, we aimed to evaluate the association between its polymorphisms, CPB‐AKI and plasma IL‐17 levels among Iranian patients undergoing CPB.

Method

Totally, 138 patients undergoing CPB in Bandar Abbas, Iran, were enrolled. The allele and genotype frequencies of the selected SNPs were determined using PCR‐SSP. IL‐17 serum level was determined using an enzyme‐linked immunosorbent assay.

Results

Rs9017 GG genotype and G allele were associated with increased risk of CPB‐AKI (OR = 3, 95% CI = 1.4–6.6 and OR = 2.3, 95% CI = 1.3–3.9, respectively) while A allele was protective against the disease (OR = 0.4, 95% CI = 0.3–0.7, p = .02). There was not a statistically significant interaction between the three genotypes of rs9017 and AKI disease with IL‐17 serum level before (p = .9) and after (p = .6) the operation. The IL‐17 serum level before surgery was significantly higher in patients carrying GG genotype compared to GA genotype (p = .017).

Conclusion

Our results showed that the rs9017 GG genotype was associated with an increased level of IL‐17 and risk of CBP‐AKI in the Iranian population. Our current results suggest that the rs9017 GG genotype could be a probable predictor of AKI after cardiac surgery.
Enrollment with and without exception from informed consent in a pilot trial of tranexamic acid in children with hemorrhagic injuries
Authors: Linakis Seth W. , Kuppermann Nathan , Stanley Rachel M. , Hewes Hilary , Myers Sage , VanBuren John M. , Casper T. Charles , Bobinski Matthew , Ghetti Simona , Schalick Walton O. , Nishijima Daniel K. ,   TIC‐TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN)
Published: July 2021

Background

Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time‐sensitive, life‐threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries.

Methods

We conducted a four‐center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC.

Results

We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months.

Conclusions

In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.
Does receiving an eating disorder diagnosis increase the risk of a subsequent alcohol use disorder? A Danish nationwide register‐based cohort study
Authors: Mellentin Angelina Isabella , Skøt Lotte , Guala Maria Mercedes , Støving René Klinkby , Ascone Leonie , Stenager Elsebeth , Mejldal Anna
Published: July 2021

Background and aim

No large‐scale, longitudinal clinical study has examined whether patients with different types of eating disorders (ED) have an increased risk of a subsequent alcohol use disorder (AUD). This study aimed to assess the ongoing risk of receiving a diagnosis of AUD following a first‐time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED).

Design

Retrospective cohort study.

Setting

Danish nationwide registries, January 1994 to December 2018.

Participants

A total of 20 759 ED patients and 83 036 controls were followed from the date of first ED diagnosis (index date) until the date of first AUD diagnosis, death, emigration, or the end of the study. Controls were selected in a 1:4 ratio and matched on month and year of birth, gender and ethnicity.

Measurements

We obtained data on ED (AN, BN, USED; exposure) and AUD (abuse/dependence; outcome) diagnoses as well as sociodemographics and other psychiatric diagnoses. Time to AUD was generated from the index date. Risk of AUD after the index date was assessed among those without a prior AUD diagnosis while adjusting for sociodemographics and prior psychiatric diagnoses.

Findings

Compared with controls, an increased relative risk of AUD after the index date was observed in AN patients throughout the study lasting 15 + years (adjusted hazard ratios [HRs] ranging from 2.49 [99% CI = 1.46, 4.25] to 6.83 [2.84, 16.41]), in BN patients during the first year of follow‐up and from 2 years onward (2.72 [1.66, 4.44] to 17.44 [6.01, 50.63]), and in USED patients during the first year and 2–15 years of follow‐up (2.52 [1.54, 4.14] to 14.17 [5.86, 34.27]). In all three groups, estimates were highest during the first year, particularly among BN patients.

Conclusions

Patients with anorexia nervosa, bulimia nervosa, or unspecified eating disorders appear to have an increased ongoing risk of receiving a diagnosis of alcohol use disorder following their first eating disorder diagnosis compared with controls.
Effects of natural forest and tree plantations on leaf‐litter frog assemblages in Southern Brazil
Authors: Cicheleiro Juciela , Santos‐Pereira Manuela , Luza André Luís , Huning Douglas da Silva , Zanella Noeli
Published: July 2021

Anuran amphibians are extremely sensitive to changes in the environment and are severely threatened with extinction by human activities. The conversion of natural habitats to tree plantations is expanding in southern Brazil, emphasising the need for both scientists and society to understand the potential effects of this practice on animal communities. Here, we evaluated whether the richness, composition and abundance of leaf‐litter frogs change among natural forests, plantations of the native Araucaria angustifolia and plantations of an introduced pine Pinus spp. We obtained data on the composition of the leaf‐litter frog assemblages by sampling natural forest and tree plantations in the Passo Fundo National Forest, southern Brazil. We sampled leaf‐litter frogs using pitfall trap arrays from March 2017 to February 2018. We used generalised linear mixed models to estimate the effect of habitat type on leaf‐litter frogs while considering variation induced by season effect and spatial autocorrelation. We recorded 311 individual leaf‐litter frogs belonging to nine species and five families. We did not find differences in species richness and composition, total abundance and abundance of the most frequent species Physalaemus cuvieri, P. carrizorum and Rhinella icterica among Pinus plantations, Araucaria angustifolia plantations and natural forests. These results indicate that tree plantations and natural forests can be equally suitable to leaf‐litter frogs. Such suitability is promoted by the light levels of management exerted on these plantations, the old age of the plantations and the heterogeneous mosaic of habitat types maintained within this National Forest. Our study shows that some management decisions can preserve habitat quality to wildlife in modified landscapes.
Climate‐based ensemble modelling to evaluate the global distribution ofAnoplophora glabripennis(Motschulsky)
Authors: Byeon Dae‐hyeon , Kim Se‐Hyun , Jung Jae‐Min , Jung Sunghoon , Kim Kwang‐Ho , Lee Wang‐Hee
Published: July 2021

Anoplophora glabripennis(Motschulsky) (Coleoptera: Cerambycidae) is a forest pest that damages a wide range of trees in areas where it has recently been introduced, demanding a proactive evaluation of its possible future distribution.

This study aimed to project the potential distribution ofA. glabripennisusing species distribution modelling and constructed an ensemble map for evaluating global risk areas.

We used CLIMEX and MaxEnt to evaluate the potential distribution ofA. glabripennisas a function of current and future climates.

The results showed that the models predicted a high probability ofA. glabripennisdistribution where this species is currently found, and the suitable climate was shifted northward due to climate change.

The projected area differed between the models because of different modelling algorithm and climate change scenario; thus, an ensemble map projecting the consensus areas from two models was constructed to identify the risk areas that corresponded to the eastern United States, Europe, and native countries, Korea and China, and nearby Japan.

From the perspective of ensemble modelling for evaluating species distributions with reduced uncertainties, this study will enhance the model reliability for defining areas at risk ofA. glabripennisoccurrence.
Improving the resolution of canine genome‐wide association studies using genotype imputation: A study of two breeds
Authors: Jenkins Christopher A. ,   Dog Biomedical Variant Database Consortium, Schofield Ellen C. , Mellersh Cathryn S. , De Risio Luisa , Ricketts Sally L
Published: July 2021

Genotype imputation using a reference panel that combines high‐density array data and publicly available whole genome sequence consortium variant data is potentially a cost‐effective method to increase the density of extant lower‐density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed‐specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R
2 = 0.94) and the highest for the Italian Spinone dataset (mean R
2 = 0.97). This study’s findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed‐specific array data and multi‐breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed‐specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.
You Are Going to Get Us Killed: Fugitive Archival Practice and the Carceral State
Authors: Sojoyner Damien M.
Published: July 2021

The carceral state has been the dominant voice of state governance in the United States over the past forty years. This article takes the archive as a key site of struggle to understand the power dynamics at play with the development of and fight against the carceral state. Utilizing the intervention of the fugitive archival practice, the article analyzes the multifaceted ways in which Black residents and communal institutions of Los Angeles, California, develop strategies and techniques located within past struggles against what I call the carceral state archive. The carceral state archive consists of both the recording mechanisms of state power and the institutions and structures that buttress that power. Built upon a multilayered methodological approach, the framing of the argument includes ethnographic and archival analysis of communal institutions such as the Southern California Library, communal organizations such as the Coalition Against Police Abuse, and the community members who all form the making of the fugitive archival practice. [carceral studies, race, urban anthropology, archives]
Ergonomics in the anaesthetic workplace
Authors: Bailey C. R. , Radhakrishna S. , Asanati K. , Dill N. , Hodgson K. , McKeown C. , Pawa A. , Plaat F. , Wilkes A.
Published: July 2021

Ergonomics in relation to anaesthesia is the scientific study of the interaction between anaesthetists and their workspace environment in order to promote safety, performance and well‐being. The foundation for avoiding pain or discomfort at work is to adopt and maintain a good posture, whether sitting or standing. Anaesthetists should aim to keep their posture as natural and neutral as possible. The successful practice of anaesthesia relies on optimisation of ergonomics and lack of attention to detail in this area is associated with impaired performance. The anaesthetic team should wear comfortable clothing, including appropriately‐sized personal protective equipment where necessary. Temperature, humidity and light should be adequate at all times. The team should comply with infection prevention and control guidelines and monitoring as recommended by the Association of Anaesthetists. Any equipment or machinery that is mobile should be positioned where it is easy to view or reach without having to change the body or head position significantly when interacting with it. Patients who are supine should, whenever possible, be raised upwards to limit the need to lean towards them. Any item required during a procedure should be positioned on trays or trolleys that are close to the dominant hand. Pregnancy affects the requirements for standing, manually handling, applying force when operating equipment or moving machines and the period over which the individual might have to work without a break. Employers have a duty to make reasonable adjustments to accommodate disability in the workplace. Any member of staff with a physical impairment needs to be accommodated and this includes making provision for a wheelchair user who needs to enter the operating theatre and perform their work.
Outsourcing robotic‐assisted operations to private hospitals: cost analysis of a retrospective cohort
Authors: Young Edward , Vissapragada Ravi , Bulamu Norma B. , Raju Devinder Philip , McDonald Christopher Richard
Published: July 2021

Background

The Lyell McEwin Hospital entered into a public–private collaborative agreement in 2019 in order to access Da Vinci® Xi Surgical Systems (Intuitive Surgical, Sunnyvale, CA, USA) in private hospitals. This study aimed to examine the costs associated with usage of robot surgical systems under the agreement, and the potential for acquisition in the public hospital.

Methods

Retrospective data on robotic‐assisted and equivalent operations performed between 1 May 2019 and 30 April 2020 were collected and formed subsequent model inputs. Cost data were from hospital records and the local Da Vinci® Xi distributor. Clinical workflow of operations was simulated with a decision‐analytic model, with output being costs incurred. The model's base case scenario assumed 5% of cases were robotically assisted.

Results

A total of 35 robotic‐assisted, 101 laparoscopic and 34 open operations were performed. Patients were predominantly male and overweight with multiple comorbidities. Length of stay and duration of operation were associated with increased costs (p < 0.001,r20.72). In the base case scenario, there was a cost of AU$26 424 per patient, with an open conversion rate of 11%. Increasing robotic‐assisted case percentage resulted in reduced cost, open conversion rates and length of stay. Extrapolation of cost model data indicated if 50% were robotic‐assisted cases, then the initial capital investment (assumed at AU$4 000 000) could be recovered in 10 years.

Conclusion

Our model highlights potential advantages of performing greater numbers of robotic‐assisted operations in a collaborative environment. Cost‐effective analysis with prospective data could evaluate if these results are translatable and potentially support acquisition of robotic systems in the public sector.
Optical coherence tomography angiography in the multimodal assessment of the retinal posterior pole in autosomal dominant optic atrophy
Authors: Cesareo Massimo , Giannini Clarissa , Di Marino Matteo , Aloe Gianluca , Martucci Alessio , Aiello Francesco , Cusumano Andrea , Mancino Raffaele , Ricci Federico , Sorge Roberto Pietro , Nucci Carlo
Published: July 2021

Purpose

To assess retinal vascular involvement in patients with autosomal dominant optic atrophy (ADOA) genetically confirmed by the presence of the OPA1 (Optic Atrophy 1) gene mutation using a multimodal protocol of investigation of retinal posterior pole.

Methods

In this cross‐sectional, case–control, observational study, both eyes of 13 patients with a genetic diagnosis of ADOA were compared with both eyes of 13 healthy controls (HCs). All subjects underwent full ophthalmological examination, spectral domain‐optical coherence tomography (SD‐OCT), fundus perimetry (FP) and OCT angiography (OCTA).

Results

Vessel density (VD) of the superficial and deep macular vascular plexi and of the radial peripapillary capillary plexus were significantly decreased (p ≤ 0.001) in ADOA patients compared with HCs. The area under the receiver operating characteristics analysis also revealed high values of sensitivity and specificity of OCTA parameters in distinguish between patients and HCs. A strong correlation (Pearson Coefficient, r = 0.91) emerged between OCTA VD of the superficial retinal plexus and the average Ganglion Cell Layer (GCL) thickness as measured by SD‐OCT; a slightly lower correlation (Pearson Coefficient, r = 0.89) was also found between VD of the deep plexus and the average GCL thickness of the same eyes in patients with ADOA. The correlation among values of differential light sensitivity (DLS) measured by FP with VD and GCL thickness parameters was also investigated. The correlation analysis among DLS and the VD parameters showed from low‐to‐moderate correlation (ranging from r = 0.29 for the deep fovea VD to r = 0.59 for the deep whole image VD). The correlation coefficient between the mean DLS and the average thickness of GCL was more significant (Pearson Coefficient, r = 0.75). A significant correlation emerged also between the VD and the visual acuity, in terms of LogMAR BCVA (best‐corrected visual acuity), especially for the VD of the deep capillary plexus (Pearson Coefficient for the Deep whole Image VD and LogMAR BCVA r = −0.75; for the Deep parafovea VD and LogMAR BCVA r = −0.78).

Conclusion

Retinal microvascular assessment by OCTA angiography can provide relevant clinical information on retinal involvement in ADOA patients. In patients with genetically confirmed OPA1‐related ADOA, there is a decrease in retinal vessel density associated with GCL thinning and DLS reduction.
Explicability of artificial intelligence in radiology: Is a fifth bioethical principle conceptually necessary?
Authors: Ursin Frank , Timmermann Cristian , Steger Florian
Published: July 2021

Recent years have witnessed intensive efforts to specify which requirements ethical artificial intelligence (AI) must meet. General guidelines for ethical AI consider a varying number of principles important. A frequent novel element in these guidelines, that we have bundled together under the term explicability, aims to reduce the black‐box character of machine learning algorithms. The centrality of this element invites reflection on the conceptual relation between explicability and the four bioethical principles. This is important because the application of general ethical frameworks to clinical decision‐making entails conceptual questions: Is explicability a free‐standing principle? Is it already covered by the well‐established four bioethical principles? Or is it an independent value that needs to be recognized as such in medical practice? We discuss these questions in a conceptual‐ethical analysis, which builds upon the findings of an empirical document analysis. On the example of the medical specialty of radiology, we analyze the position of radiological associations on the ethical use of medical AI. We address three questions: Are there references to explicability or a similar concept? What are the reasons for such inclusion? Which ethical concepts are referred to?
Fear of childbirth, nonurgent obstetric interventions, and newborn outcomes: A randomized controlled trial comparing mindfulness‐based childbirth and parenting with enhanced care as usual
Authors: Veringa‐Skiba Irena K. , de Bruin Esther I. , van Steensel Francisca J. A. , Bögels Susan M.
Published: July 2021

Objective

To investigate whether mindfulness‐based childbirth and parenting (MBCP) or enhanced care as usual (ECAU) for expectant couples decreases fear of childbirth (FOC) and nonurgent obstetric interventions during labor and improves newborn outcomes.

Design

Randomized controlled trial.

Setting

Midwifery settings, the Netherlands, April 2014‐July 2017.

Population

Pregnant women with high FOC (n = 141) and partners.

Methods

Allocation to MBCP or ECAU. Hierarchical multilevel and intention‐to‐treat (ITT) and per‐protocol (PP) analyses.

Main outcome measures

Primary: pre‐/postintervention FOC, labor anxiety disorder, labor pain (catastrophizing and acceptance), and preferences for nonurgent obstetric interventions. Secondary: rates of epidural analgesia (EA), self‐requested cesarean birth (sCB), unmedicated childbirth, and 1‐ and 5‐minute newborn's Apgar scores.

Results

MBCP was significantly superior to ECAU in decreasing FOC, catastrophizing of labor pain, preference for nonurgent obstetric interventions, and increasing acceptance of labor pain. MBCP participants were 36% less likely to undergo EA (RR 0.64, 95% CI [0.43‐0.96]), 51% less likely to undergo sCB (RR 0.49, 95% CI [0.36‐0.67]), and twice as likely to have unmedicated childbirth relative to ECAU (RR 2.00, 95% CI [1.23‐3.20]). Newborn's 1‐minute Apgar scores were higher in MBCP (DM −0.39, 95% CI [−0.74 to −0.03]). After correction for multiple testing, results remained significant in ITT and PP analyses, except EA in ITT analyses and 1‐minute Apgar.

Conclusions

MBCP for pregnant couples reduces mothers’ fear of childbirth, nonurgent obstetric interventions during childbirth and may improve childbirth outcomes. MBCP adapted for pregnant women with high FOC and their partners appears an acceptable and effective intervention for midwifery care.
Efficacy information influences intention to take COVID‐19 vaccine
Authors: Davis Colin J. , Golding Matt , McKay Ryan
Published: July 2021

Objectives

A successful response to the COVID‐19 pandemic requires achieving high levels of vaccine uptake. We tested whether directly contrasting the high efficacy of COVID‐19 vaccines with the lower efficacy of the annual flu vaccine would increase intentions to take a COVID‐19 vaccine.

Design

A pre‐registered online study of 481 participants compared four information conditions: (1) no information; (2) COVID‐19 Vaccine Information Only; and COVID‐19 Vaccine Information combined with flu vaccine information suggesting either (3) 60% efficacy or (4) 40% efficacy; we measured COVID‐19 and flu vaccine intentions along with several other vaccine‐related variables.

Methods

The Prolific platform was used to recruit 481 UK participants (64% female; aged between 18 and 85 years) who had been pre‐screened to have intermediate levels of vaccine hesitancy. After reading a short text (~200 words) about COVID‐19 vaccines, participants were asked about their vaccination intentions.

Results

Providing information about the safety and efficacy of the new COVID‐19 vaccines resulted in vaccination intentions that were, on average, 0.39 standard deviations (SDs) higher than those in the no information condition; providing the same COVID vaccine efficacy information in the context of information about flu vaccine efficacy resulted in a further significant increase in vaccination intentions that were 0.68 SD higher than those in the no information condition. This positive contrast effect for the COVID‐19 vaccine was not associated with reduced flu vaccine intentions.

Conclusions

Vaccination intentions can be strengthened through a simple messaging intervention that utilizes context effects to increase perceived response efficacy.
Macrophage migration inhibitory factor exerts pro‐proliferative and anti‐apoptotic effects via CD74 in murine hepatocellular carcinoma
Authors: Wirtz Theresa H. , Saal Alena , Bergmann Irina , Fischer Petra , Heinrichs Daniel , Brandt Elisa F. , Koenen Maria T. , Djudjaj Sonja , Schneider Kai M. , Boor Peter , Bucala Richard , Weiskirchen Ralf , Bernhagen Jürgen , Trautwein Christian , Berres Marie‐Luise
Published: July 2021

Background and Purpose

Macrophage migration inhibitory factor (MIF) is an inflammatory and chemokine‐like protein expressed in different inflammatory diseases as well as solid tumours. CD74—as the cognate MIF receptor—was identified as an important target of MIF. We here analysed the role of MIF and CD74 in the progression of hepatocellular carcinoma (HCC) in vitro and in vivo.

Experimental Approach

Multilocular HCC was induced using the diethylnitrosamine/carbon tetrachloride (DEN/CCl4) model in hepatocyte‐specific Mif knockout (Mif Δhep), Cd74‐deficient, and control mice. Tumour burden was compared between the genotypes. MIF, CD74 and Ki67 expression were investigated in tumour and surrounding tissue. In vitro, the effects of the MIF/CD74 axis on the proliferative and apoptotic behaviour of hepatoma cells and respective signalling pathways were assessed after treatment with MIF and anti‐CD74 antibodies.

Key Results

DEN/CCl4 treatment of Mif Δhep mice resulted in reduced tumour burden and diminished proliferation capacity within tumour tissue. In vitro, MIF stimulated proliferation of Hepa 1–6 and HepG2 cells, inhibited therapy‐induced cell death and induced ERK activation. The investigated effects could be reversed using a neutralizing anti‐CD74 antibody, and Cd74−/− mice developed fewer tumours associated with decreased proliferation rates.

Conclusion and Implications

We identified a pro‐tumorigenic role of MIF during proliferation and therapy‐induced apoptosis of HCC cells. These effects were mediated via the MIF cognate receptor CD74. Thus, inhibition of the MIF/CD74 axis could represent a promising target with regard to new pharmacological therapies aimed at HCC.
Prediction model for malignant pulmonary nodules based on cfMeDIP‐seq and machine learning
Authors: Qi Jian , Hong Bo , Tao Rui , Sun Ruifang , Zhang Huanhu , Zhang Xiaopeng , Ji Jie , Wang Shujie , Liu Yanzhe , Deng Qingmei , Wang Hongzhi , Zhao Dahai , Nie Jinfu
Published: July 2021

Cell‐free methylated DNA immunoprecipitation and high‐throughput sequencing (cfMeDIP‐seq) is a new bisulfite‐free technique, which can detect the whole‐genome methylation of blood cell‐free DNA (cfDNA). Using this technique, we identified differentially methylated regions (DMR) of cfDNA between lung tumors and normal controls. Based on the top 300 DMR, we built a random forest prediction model, which was able to distinguish malignant lung tumors from normal controls with high sensitivity and specificity of 91.0% and 93.3% (AUROC curve of 0.963). In summary, we reported a non–invasive prediction model that had good ability to distinguish malignant pulmonary nodules.
A nationwide birth year‐by‐year analysis of effectiveness of HPV vaccine in Japan
Authors: Yagi Asami , Ueda Yutaka , Nakagawa Satoshi , Masuda Tatsuo , Miyatake Takashi , Ikeda Sayaka , Abe Hazuki , Hirai Kei , Sekine Masayuki , Miyagi Etsuko , Enomoto Takayuki , Nakayama Tomio , Kimura Tadashi
Published: July 2021

In Japan, the age‐adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20‐y‐old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as “the pre‐introduction generation”, was 1.42% (242/17 040). The incidence in the “vaccination generation” (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13‐16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year‐by‐year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre‐introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre‐introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre‐introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.
The engagement of children in out‐of‐home care with nursing and allied health professionals: A scoping review
Authors: Hickey Lyndal , Galvin Karyn , Parolini Arno , Nguyen Bao , Lokmic‐Tomkins Zerina , Toovey Rachel , Skeat Jemma , Wise Sarah
Published: July 2021

Background

Children living in out‐of‐home care (OOHC) have significant unmet health care needs and use more tertiary and specialist health care services compared with children from similar social and economic backgrounds. Allied health professionals and nurses have a central role in health care; however, very little is known about the engagement of children in OOHC with nursing and allied health professionals. This scoping review addresses this knowledge gap.

Methods

A scoping review methodology framework was used to search for relevant articles published between January 1970 and November 2019, identified using three databases: MEDLINE, CINAHL and ProQuest. Selection of studies was based on empirical research about the health of children in OOHC and their engagement with nursing or allied health services. A total of 37 relevant articles met the eligibility criteria for inclusion in this review.

Results

Findings could be summarized under five broad themes: (1) nursing and allied health professionals engaging with children in OOHC to support their health and development, (2) opportunities and challenges for nursing and allied health professionals to engage children in OOHC in healthcare, (3) identification and complexity of healthcare needs, (4) access to healthcare services and (5) coordination of healthcare.

Conclusions

Children in OOHC have multiple healthcare needs that require monitoring and treatment by allied health professionals and the health and development of these children is best supported through comprehensive health screening on entry into OOHC, and community‐based, multidisciplinary healthcare while children are living in OOHC. While nurses in hospitals and community settings were found to play a role in health assessment and care coordination targeted at children in OOHC, the literature was silent on the role of allied health professionals in this healthcare approach.
Distribution of comorbidities as primary diagnoses by obesity class among patients in a large US paediatric healthcare system
Authors: Nussbaum Brandon M. , Mathew Matthew Sunil , Atem Folefac , Barlow Sarah E. , Gupta Olga T. , Messiah Sarah E.
Published: July 2021

There is little documentation of the distribution of specific health conditions across obesity classes (I, II, III), especially for paediatric populations who are seen for routine care in large United States US healthcare systems. The aim of this study was to assess the odds of presenting ≥2 obesity‐related comorbidities as well as assess the overall distribution of these co‐morbidities in children by class I/II/III obesity status controlling for key sociodemographic characteristics. This retrospective (2015–2019) electronic health record review analysed 49 276 patients from the Children's Health System of Texas diagnosed with obesity‐related health conditions by obesity status (no obesity, class I, II, III). Crude and adjusted logistic regression models examined the association between obesity class and the likelihood of ≥2 comorbidities as primary diagnoses. Patients with class I obesity were 22% more likely (OR 1.22, 95% CI, 1.16, 1.27), patients with class II obesity were almost 50% more likely (OR 1.44, 95% CI, 1.35, 1.53) and those with class III obesity twice as likely (OR 2.04, 95% CI 1.91, 2.18) to be diagnosed with ≥2 comorbidities as primary diagnoses, compared with patients classified with no obesity. Children with obesity, particularly severe obesity, should be monitored closely by paediatricians for possible diagnoses of risk factors that could lead to adult chronic disease.
Level of inferior mesenteric artery ligation does not affect rectal cancer treatment outcomes despite better cancer‐specific survival after low ligation—randomized trial results
Authors: Kruszewski Wiesław Janusz , Szajewski Mariusz , Ciesielski Maciej , Buczek Tomasz , Kawecki Krzysztof , Walczak Jakub
Published: July 2021

Aim

In rectal cancer surgery, the problem about which of the mesenteric artery ligation variants (high or low) is more beneficial to the patient remains unsolved. Recent meta‐analyses suggest that the risk of surgical complications is similar for both ligation variants. The main objective was to compare the survival time in both groups with a minimum 48 months’ follow‐up. Secondary objectives were comparison of the number of harvested lymph nodes, the complication rate and other selected data related to the surgery.

Method

This was a randomized, single‐centre, unblinded clinical trial of adult patients (n = 130) with cT1‐3M0/ycT0‐3M0 rectal and rectosigmoid junction adenocarcinoma undergoing radical open surgery. The intervention level was inferior mesenteric artery ligation.

Results

The mean and median survival in the whole group was 45 months, while in the survivor group it was 83 and 82 months. The survival for 1–5 years, overall survival and disease‐free survival were similar in both groups. The cancer‐specific survival time was longer in the low inferior mesenteric artery ligation group (P = 0.005 for all and P = 0.02 for pTNM Stage III patients) There were no differences in the incidence of anastomotic leakage and overall morbidity. The median number of lymph nodes located at the root of the inferior mesenteric artery was 1; the mean was 1.7. They were not metastatic in any case. The median total number of harvested nodes was similar in both groups.

Conclusions

In radically treated adenocarcinoma of the rectum and the rectosigmoid junction, the level of inferior mesenteric artery ligation below the left colic artery branch provides similar treatment results to inferior mesenteric artery ligation just below its branching from the aorta in relation to overall and disease‐free survival, and the risk of complications. Low inferior mesenteric artery ligation results in better cancer‐specific survival. The risk of metastases at the mesenteric nodes is negligible.
Implicit learning in 3‐year‐olds with high and low likelihood of autism shows no evidence of precision weighting differences
Authors: Ward Emma K. , Buitelaar Jan K. , Hunnius Sabine
Published: July 2021

Predictive Processing accounts of autism claim that autistic individuals assign higher precision to their prediction errors than non‐autistic individuals, that is, autistic individuals update their predictions more readily when faced with unexpected sensory input. Since setting the level of precision is a fundamental part of perception and learning, we propose that such differences should be detectable in various domains at a very early age, before clinical symptoms have fully emerged. We therefore tested 3‐year‐old younger siblings of autistic children, with a high likelihood of later receiving an autism diagnosis themselves, and low‐likelihood children with an older sibling without autism. We used a novel implicit learning paradigm to examine the effect of sensory noise on the predictions participants built. In order to learn a sequence, our participants had to select which visual information to attend to and disregard low‐level prediction errors caused by the sensory noise, which the theory claims is more difficult for autistic individuals. Contrary to the proposed higher precision‐weighting of prediction errors in autism, the high‐likelihood children did not show signs of updating their predictions more readily when we added sensory noise compared to the low‐likelihood children, either in their reaction times or in the recurrence and determinism of their response locations. These results raise challenges for Predictive Processing theories of autism, specifically for the notion that prediction errors are inflexibly highly weighted by individuals with autism.
Metabolically healthy obesity and cardiovascular events: A nationwide cohort study
Authors: Fauchier Grégoire , Bisson Arnaud , Bodin Alexandre , Herbert Julien , Semaan Carl , Angoulvant Denis , Ducluzeau Pierre Henri , Lip Gregory Y. H. , Fauchier Laurent
Published: July 2021

Aim

To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population.

Materials and Methods

All patients discharged from French hospitals in 2013 with at least 5 years of follow‐up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE‐HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow‐up were adjusted on age, sex and smoking status at baseline.

Results

In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow‐up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE‐HF (multivariate‐adjusted HR 1.22, 95% confidence interval [CI]: 1.19‐1.24), new‐onset HF (HR 1.34, 95% CI 1.31‐1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30‐1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87‐0.98), ischaemic stroke (HR 0.93, 95% CI 0.88‐0.98) and cardiovascular death (HR 0.99, 95% CI 0.93‐1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12‐1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49‐0.99).

Conclusions

In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new‐onset HF and new‐onset AF. However, notable differences were observed in men and women in the sex‐stratified analysis.
Modelling state‐transition dynamics in resting‐state brain signals by the hidden Markov and Gaussian mixture models
Authors: Ezaki Takahiro , Himeno Yu , Watanabe Takamitsu , Masuda Naoki
Published: July 2021

Recent studies have proposed that one can summarize brain activity into dynamics among a relatively small number of hidden states and that such an approach is a promising tool for revealing brain function. Hidden Markov models (HMMs) are a prevalent approach to inferring such neural dynamics among discrete brain states. However, the impact of assuming Markovian structure in neural time series data has not been sufficiently examined. Here, to address this situation and examine the performance of the HMM, we compare the model with the Gaussian mixture model (GMM), which is with no temporal regularization and thus a statistically simpler model than the HMM, by applying both models to synthetic time series generated from empirical resting‐state functional magnetic resonance imaging (fMRI) data. We compared the GMM and HMM for various sampling frequencies, lengths of recording per participant, numbers of participants and numbers of independent component signals. We find that the HMM attains a better accuracy of estimating the hidden state than the GMM in a majority of cases. However, we also find that the accuracy of the GMM is comparable to that of the HMM under the condition that the sampling frequency is reasonably low (e.g., TR = 2.88 or 3.60 s) or the data are relatively short. These results suggest that the GMM can be a viable alternative to the HMM for investigating hidden‐state dynamics under this condition.
Hippocampal CA1 theta burst‐induced LTP from weaning to adulthood: Cellular and molecular mechanisms in young male rats revisited
Authors: Rodrigues Nádia Carolina , Silva‐Cruz Armando , Caulino‐Rocha Ana , Bento‐Oliveira Andreia , Alexandre Ribeiro Joaquim , Cunha‐Reis Diana
Published: July 2021

Long‐term potentiation (LTP) is a highly studied cellular process, yet determining the transduction and gamma aminobutyric acid (GABAergic) pathways that are the essential versus modulatory for LTP elicited by theta burst stimulation (TBS) in the hippocampal Cornu Ammonis 1 (CA1) area is still elusive, due to the use of different TBS intensities, patterns or different rodent/cellular models. We now characterised the developmental maturation and the transduction and GABAergic pathways required for mild TBS‐induced LTP in hippocampal CA1 area in male rats. LTP induced by TBS (5x4) (five bursts of four pulses delivered at 100 Hz) lasted for up to 3 h and was increasingly larger from weaning to adulthood. Stronger TBS patterns ‐ TBS (15x4) or three TBS (15x4) separated by 6 min induced nearly maximal LTP not being the best choice to study the value of LTP‐enhancing drugs. LTP induced by TBS (5x4) in young adults was fully dependent on N‐methyl D‐aspartate (NMDA) receptor and calmodulin‐dependent protein kinase II (CaMKII) activity but independent of protein kinase A (PKA) or protein kinase C (PKC) activity. Furthermore, it was partially dependent on GABAB receptor activation and was potentiated by GABAA receptor blockade and less by GAT‐1 transporter blockade. AMPA GluA1 phosphorylation on Ser831 (CaMKII target) but not GluA1 Ser845 (PKA target) was essential for LTP expression. The phosphorylation of the Kv4.2 channel was observed at Ser438 (CaMKII target) but not at Thr602 or Thr607 (ERK/MAPK pathway target). This suggests that cellular kinases like PKA, PKC, or kinases of the ERK/MAPK family although important modulators of TBS (5x4)‐induced LTP may not be essential for its expression in the CA1 area of the hippocampus.
Signal quality and power spectrum analysis of remote ultra long‐term subcutaneous EEG
Authors: Viana Pedro F. , Remvig Line S. , Duun‐Henriksen Jonas , Glasstetter Martin , Dümpelmann Matthias , Nurse Ewan S. , Martins Isabel P. , Schulze‐Bonhage Andreas , Freestone Dean R. , Brinkmann Benjamin H. , Kjaer Troels W. , Richardson Mark P.
Published: July 2021

Objective

Ultra long‐term subcutaneous electroencephalography (sqEEG) monitoring is a new modality with great potential for both health and disease, including epileptic seizure detection and forecasting. However, little is known about the long‐term quality and consistency of the sqEEG signal, which is the objective of this study.

Methods

The largest multicenter cohort of sqEEG was analyzed, including 14 patients with epilepsy and 12 healthy subjects, implanted with a sqEEG device (24/7 EEG™ SubQ), and recorded from 23 to 230 days (median 42 days), with a median data capture rate of 75% (17.9 hours/day). Median power spectral density plots of each subject were examined for physiological peaks, including at diurnal and nocturnal periods. Long‐term temporal trends in signal impedance and power spectral features were investigated with subject‐specific linear regression models and group‐level linear mixed‐effects models.

Results

sqEEG spectrograms showed an approximate 1/f power distribution. Diurnal peaks in the alpha range (8‐13Hz) and nocturnal peaks in the sigma range (12‐16Hz) were seen in the majority of subjects. Signal impedances remained low, and frequency band powers were highly stable throughout the recording periods.

Significance

The spectral characteristics of minimally invasive, ultra long‐term sqEEG are similar to scalp EEG, whereas the signal is highly stationary. Our findings reinforce the suitability of this system for chronic implantation on diverse clinical applications, from seizure detection and forecasting to brain‐computer interfaces.