bluuebunny/crossref_metadata_2025 huggingface dataset:
PET in bladder cancer imaging
Authors: Muin Dina , Laukhtina Ekaterina , Hacker Marcus , Shariat Shahrokh F.
Published: March 2023

Purpose of review

The aim of this study was to summarize the available evidence on different PET imaging modalities for the staging of patients diagnosed with bladder cancer (BCa). We further discuss the use of PET/computed tomography (CT) and PET/MRI with different radiopharmaceuticals to characterize tumour biology for treatment guidance.

Recent findings

Available evidence supports the benefits of PET/CT in BCa staging due to its higher accuracy in the detection of nodal metastases compared with CT alone. The use of PET/MRI is of major future interest due to the higher soft tissue contrast of MRI, which might enable the early detection of the tumour in the bladder. For the time being, the sensitivity of PET/MRI is still too low, when it comes to the diagnosis of early-stage BCa. This is mainly due to the renal excretion of the commonly used [18F]FDG PET tracer, wherefore small lesions in the wall of the bladder can be missed. Novel studies using PET radiopharmaceuticals to target immune checkpoints or other immune cell targets (immunoPET) demonstrated high uptake in tumour lesions with high PD-L1 expression. The use of immunoPET could therefore help identify BCa patients who exhibit PD-L1 positive tumours for systemic immune-therapy.

PET/CT and PET/MRI seem to be promising imaging tools in BCa staging, especially for the detection of lymph node and distant metastases, as they are more accurate than conventional CT. Future clinical trials with novel radiopharmaceuticals and machine-learning driven PET-technologies bear the potential to help in the early detection, staging, monitoring and precision-medicine approach. Specifically, immunoPET is of high future interest, as it could help develop the concept of precision-medicine in the age of immunotherapy.
Thoracic Aortic Aneurysm and Dissection
Authors: Krywanczyk Alison , Rodriguez E. Rene , Tan Carmela D. , Gilson Thomas
Published: March 2023

Aortic dissection and rupture (collectively termed “sudden aortic death”) are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.

Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.

This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.
Prognosis Prediction of Lung Adenocarcinoma Patients Based on Molecular Subgroups of DNA Methylation
Authors: Rao Xiao , Xue Jianbo , Du Yinggan , Zhou Zhiyou , Lu Yunping
Published: March 2023

Lung adenocarcinoma (LUAD) is a malignant tumor with high mortality. At present, the clinicopathologic feature is the main breakthrough to assess the prognosis of LUAD patients. However, in most cases, the results are less than satisfactory. Cox regression analysis was conducted in this study to obtain methylation sites with significant prognostic relevance based on mRNA expression, DNA methylation data, and clinical data of LUAD from The Cancer Genome Atlas Program database. LUAD patients were grouped into 4 subtypes according to different methylation levels using K-means consensus cluster analysis. By survival analysis, patients were grouped into high-methylation and low-methylation groups. Later, 895 differentially expressed genes (DEGs) were obtained. Eight optimal methylation signature genes associated with prognosis were screened by Cox regression analysis, and a risk assessment model was constructed based on these genes. Samples were then classified into high-risk and low-risk groups depending on the risk assessment model, and prognostic, predictive ability was assessed using survival and receiver operating characteristic (ROC) curves. The results showed that this risk model had a great efficacy in predicting the prognosis of patients, and it was, therefore, able to be an independent prognostic factor. At last, the enrichment analysis demonstrated that the signaling pathways, including cell cycle, homologous recombination, P53 signaling pathway, DNA replication, pentose phosphate pathway, and glycolysis gluconeogenesis were remarkably activated in the high-risk group. In general, we construct an 8-gene model based on DNA methylation molecular subtypes by a series of bioinformatics methods, which can provide new insights for predicting the prognosis of patients with LUAD.
Improving Daily Patient Goal-Setting and Team Communication: The Liber8 Glass Door Project*
Authors: Jones Ian G. R. , Friedman Shayne , Vu Michael , Awladthani Saif , Watts Cathy , Simpson Andrea , Al-Farsi Ahmed A. , Gupta Ronish , Cupido Cynthia , Choong Karen
Published: March 2023

OBJECTIVES:

To develop and implement a tool to improve daily patient goal setting, team collaboration and communication.

DESIGN:

Quality improvement implementation project.

SETTING:

Tertiary-level PICU.

PATIENTS:

Inpatient children less than 18 years old requiring ICU level care.

INTERVENTION:

A “Glass Door” daily goals communication tool located in the door front of each patient room.

MEASUREMENTS AND MAIN RESULTS:

We used Pronovost’s 4 E’s model to implement the Glass Door. Primary outcomes were uptake of goal setting, healthcare team discussion rate around goals, rounding efficiency, acceptability and sustainability of the Glass Door. The total implementation duration from engagement to evaluation of sustainability was 24 months. Goal setting increased significantly from 22.9% to 90.7% (p < 0.01) patient-days using the Glass Door compared to a paper-based daily goals checklist (DGC). One-year post implementation, the uptake was sustained at 93.1% (p = 0.04). Rounding time decreased from a median of 11.7 minutes (95% CI, 10.9–12.4 min) to 7.5 minutes (95% CI, 6.9–7.9 min) per patient post-implementation (p < 0.01). Goal discussions on ward rounds increased overall from 40.1% to 58.5% (p < 0.01). Ninety-one percent of team members perceive that the Glass Door improves communication for patient care, and 80% preferred the Glass Door to the DGC for communicating patient goals with other team members. Sixty-six percent of family members found the Glass Door helpful in understanding the daily plan and 83% found it helpful in ensuring thorough discussion among the PICU team.

CONCLUSIONS:

The Glass Door is a highly visible tool that can improve patient goal setting and collaborative team discussion with good uptake and acceptability among healthcare team members and patient families.
Early Changes in Arterial Partial Pressure of Carbon Dioxide and Blood Pressure After Starting Extracorporeal Membrane Oxygenation in Children: Extracorporeal Life Support Organization Database Study of Neurologic Complications*
Authors: Shah Neel , Li Xilong , Shanmugham Prashanth , Fan Eddy , Thiagarajan Ravi R. , Venkataraman Ramgopal , Raman Lakshmi
Published: March 2023

Objective:

Neurologic complications in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) are common and lead to morbidity and mortality; however, few modifiable factors are known.

Design:

Retrospective study of the Extracorporeal Life Support Organization registry (2010–2019).

Setting:

Multicenter international database

Patients:

Pediatric patients receiving ECMO (2010–2019) for all indications and any mode of support.

Interventions:

None.

Measurements and Main Results:

We investigated if early relative change in Paco
2 or mean arterial blood pressure (MAP) soon after starting ECMO was associated with neurologic complications. The primary outcome of neurologic complications was defined as a report of seizures, central nervous system infarction or hemorrhage, or brain death. All-cause mortality (including brain death) was used as a secondary outcome.

Out of 7,270 patients, 15.6% had neurologic complications. Neurologic complications increased when the relative Paco
2 decreased by greater than 50% (18.4%) or 30–50% (16.5%) versus those who had a minimal change (13.9%, p < 0.01 and p = 0.046). When the relative MAP increased greater than 50%, the rate of neurologic complications was 16.9% versus 13.1% those with minimal change (p = 0.007). In a multivariable model adjusting for confounders, a relative decrease in Paco
2 greater than 30% was independently associated with greater odds of neurologic complication (odds ratio [OR], 1.25; 95% CI, 1.07–1.46; p = 0.005). Within this group, with a relative decrease in Paco
2 greater than 30%, the effects of increased relative MAP increased neurologic complications (0.05% per BP Percentile; 95% CI, 0.001–0.11; p = 0.05).

Conclusions:

In pediatric patients, a large decrease in Paco
2 and increase in MAP following ECMO initiation are both associated with neurologic complications. Future research focusing on managing these issues carefully soon after ECMO deployment can potentially help to reduce neurologic complications.
Quantification of facial fat compartments variations according to gender, age and BMI: a 3-Dimensional morphometric analysis of the cheek
Authors: Estler Arne , Grözinger Gerd , Estler Eva , Hepp Tobias , Feng You-Shan , Daigeler Adrien , G. Jorge A. Cristina S. R. , Santos Stahl Adelana , Nikolaou Konstantin , Stahl Stéphane
Published: March 2023

Objective:

The contour of the cheek is the main determinant of facial attractivity. The aim of this study is to evaluate the relationship between age, gender and BMI and cheek fat volume in a large cohort to better understand and treat facial aging.

Materials and methods:

This study was performed by a retrospective review of the archives of the Department of Diagnostic and Interventional Radiology, University Hospital of Tübingen. Epidemiological data and medical history were assessed. The patients´ cheek superficial and deep fat compartment volumes were measured on magnetic resonance (MR) images. Statistical analyses were performed using the SPSS (Statistical Package for Social Sciences, version 27) and SAS statistical software package (Version 9.1; SAS Institute, Inc, Cary, NC).

Results:

87 patients with a mean age of 46.0 years (range: 18–81 years) were included. The superficial and deep fat compartment volumes of the cheek increase with BMI (p< 0.001 and p=0.005), but there was no significant relationship between age and volume. The ratio of superficial versus deep fat does not change with age. No significant difference of the superficial or deep fat compartments was found between men and women in a regression analysis (p=0.931 and p=0.057).

Conclusion:

Cheek fat volume measurements on MRI scans using reconstruction software suggest that the fat volume of the cheek increases with BMI but does not significantly change with age. Further studies will have to elucidate the role of age-related changes of bone structures or sagging of the fat compartments.

Level of Evidence:

II (Exploratory cohort study developing diagnostic criteria (with “gold” standard as reference) in a series of consecutive patients).
Deliberate Practice and Process Analysis in DIEP Flap Breast Reconstruction: An Immediate and Sustained Decrease in Morbidity and Operative Time
Authors: Haddock Nicholas T. , Tycher John T. , Teotia Sumeet S.
Published: March 2023

Background:

DIEP flaps are nuanced, multi-step complex procedures. Recent studies have hinted that operational flow can be a sensitive barometer for safety, efficiency and overall outcomes. We critically assess the utility of implementing deliberate practice and process mapping as a research tool in the context of morbidity and operative time.

Methods:

Co-surgeons at a university hospital implemented deliberate practice and performed two prospective process analysis studies evaluating critical steps in DIEP flap reconstruction. During the 9-month period (June 2018-February 2019), the flap harvest and microsurgery steps were assessed. During the 8-month period (January-August 2020), the analysis was expanded to encompass the entire operation. To evaluate the immediate and sustained impact of process analysis, 375 bilateral DIEP flap patients were divided into eight consecutive 9-month intervals completed before, during and after the two studies. Using risk-adjusted multivariate regressions morbidity and operative time was compared between groups.

Results:

Time intervals completed prior to the first study had comparable morbidity and operative time. During the first study, there is an immediate 83.8% (p<.001) decrease risk in morbidity. Operative time during the second study decreased by 2.19 hours (p<.001). Morbidity and operative time continue to decrease until the end of data collection (62.1% decrease risk in morbidity, p=.023 and 2.22 hours, p<.001).

Conclusions:

Deliberate practice and process analysis are powerful tools. Implementation of these tools can generate immediate and sustained decreases in morbidity and operative time for patients in procedures such as DIEP flap breast reconstruction.
The Impact of Lateral Relaxing Incision on Middle Ear Function in Cleft Palate Repair
Authors: Jeon Sungmi , Choe Goun , Oh Jayoung , Kim Suk Wha , Park Moo Kyun , Chung Jee Hyeok
Published: March 2023

Children with cleft palate are susceptible to otitis media with effusion. This study aimed to investigate the effect of lateral relaxing incision (RI) on middle ear function in cleft palate patients who underwent palatoplasty using double-opposing Z-plasty (DOZ). This is a retrospective study of patients who underwent bilateral ventilation tube insertion concurrently with DOZ, wherein RI was selectively performed on the right side of the palate (Rt-RI group) or not (No-RI group). The frequency of VTI, duration of the first ventilation tube retention, and hearing outcomes at the last follow-up were reviewed. Outcomes were compared using the χ2 test and t test. A total of 126 treated ears from 63 non-syndromic children (18 male, 45 female) with cleft palate were reviewed. The mean age at surgery was 15.8±6.17 months. There were no significant differences in the frequency of ventilation tube insertion between the right and left ears within the Rt-RI group or between the Rt-RI and no-RI groups in the right ear. Subgroup analysis for ventilation tube retention time, auditory brainstem response thresholds, and air-conduction pure tone averages showed no significant differences. In the DOZ, the use of RI had no significant effects on middle ear outcomes during 3 years of follow-up. Relaxing incision seems to be safe without concern for middle ear function in children with cleft palate.
A Novel Technique for Reduction and Fixation of Severe Extracapsular Condylar Fracture
Authors: Xu Huilin , Liu Daofeng , Wu Shiyan , Mao Runyi , Shi Jun , Zhang Wenbin
Published: March 2023

Introducing a novel surgical technique that uses 2 screws and 3 titanium plates to reduce and fix an extracapsular condylar fracture. This technique has been used on 18 sides of extracapsular condylar fracture over the last 3 years in the Department of Oral and Cranio-Maxillofacial Science of Shanghai Ninth People’s Hospital without severe complications in clinical practice. Applying this technique, the dislocated condylar segment can be reduced accurately and fixed efficiently.
Morphometry of the Bony Orbit and Periorbital Structures: Personal Perspectives From Decades of Related Research
Authors: Hwang Kun
Published: March 2023

The author introduces his personal perspectives on the bony orbit, nerves, arteries, and ligaments relating to orbital re- construction surgery. A supraorbital fissure was 40.0 ± 2.5 mm from the supraorbital notch. Posterior ethmoidal foramen was 31.7 ± 3.0 mm from the anterior lacrimal crest. The infraorbital fissure, where the infraorbital groove started, was 26.4 ± 2.6 mm from the infraorbital foramen. The supraorbital fissure was 34.3 ± 2.7 mm from the frontozygomatic suture. The medial palpebral ligament consisted of 2 layers. The superficial layer of the palpebral ligament (SMPL) was from the anterior lacrimal crest to the upper and lower tarsal plates. The deep layer of the palpebral ligament (DMPL) lay from the anterior lacrimal crest to the posterior lacrimal crest, covering the lacrimal sac. Horner muscle was at the posterior lacrimal crest just lateral to the attachment of the DLPL and ran laterally to the tarsal plate deep to the SLPL. Three components of the lateral canthal area are: (1) lateral palpebral raphe, (2) superficial lateral palpebral ligament (SLPL), and (3) deep lateral palpebral ligament (DLPL). The lateral ends of superior and inferior orbicularis oculi muscles interlaced at the lateral commissure and formed the lateral palpebral raphe. The superficial lateral palpebral ligament extended from the lateral ends of the tarsal plate to the periosteum of the lateral orbital rim. The lateral palpebral ligament extended from the lateral ends of the tarsal plate deep to the origin of SLPL to the Whitnall tu- bercle on the zygomatic bone. The palpebral branch of the in- fraorbital artery emerged from the infraorbital foramen and ran superior and lateral to the orbital septum. After passing through the orbital septum, distributed to the orbital fat.
Tricuspid Regurgitation After Heart Transplantation: The Cause or the Result of Graft Dysfunction?
Authors: Bart Nicole K. , Hungerford Sara L. , Namasivayam Mayooran , Granger Emily , Conellan Mark , Kotlyar Eugene , Muthiah Kavitha , Jabbour Andrew , Hayward Christopher , Jansz Paul C. , Keogh Anne M. , Macdonald Peter S.
Published: March 2023

Background.

Tricuspid regurgitation (TR) is common following heart transplantation and has been shown to adversely influence patient outcomes. The aim of this study was to identify causes of progression to moderate–severe TR in the first 2 y after transplantation.

Methods.

This was a retrospective, single-center study of all patients who underwent heart transplantation over a 6-y period. Transthoracic echocardiogram (TTE) was performed at month 0, between 6 and 12 mo, and 1–2 y postoperatively to determine the presence and severity of TR.

Results.

A total of 163 patients were included, of whom 142 underwent TTE before first endomyocardial biopsy. At month 0, 127 (78%) patients had nil–mild TR before first biopsy, whereas 36 (22%) had moderate–severe TR. In patients with nil–mild TR, 9 (7%) progressed to moderate–severe TR by 6 mo and 1 underwent tricuspid valve (TV) surgery. Of patients with moderate–severe TR before first biopsy, by 2 y, 3 had undergone TV surgery. The use of postoperative extracorporeal membrane oxygenation (ECMO) in the latter group was significant (78%; P < 0.05) as was rejection profile (P = 0.02). Patients with late progressive moderate–severe TR had a significantly higher 2-y mortality than those who had moderate–severe TR immediately.

Conclusions.

Overall, our study has shown that in the 2 main groups of interest (early moderate–severe TR and progression from nil–mild to moderate–severe TR), TR is more likely to be the result of significant underling graft dysfunction rather than the cause of it.
Effects of Exercise on Testosterone and Implications of Drug Abuse: A Review
Authors: Perreault Brendan , Hammond Nikki , Thanos Panayotis K.
Published: March 2023

Objective

Research points to exercise having a positive effect in fighting relapse and use of drugs of abuse. Through conducting this research, differences have been observed in the effects of exercise on drug abuse between sexes. Many of the studies found that exercise tends to cause a more profound effect in blocking drug relapse or reinstatement in males when compared with females.

Methods

Our hypothesis is that these differences in response to drugs of abuse after an exercise regimen could in part be attributed to variations in testosterone levels between males and females.

Results

Testosterone has been shown to have a modulatory impact on the dopaminergic activity in the brain, causing an effect on the brain's response to drugs of abuse. Exercise has demonstrated a causal effect on increasing testosterone levels in males, whereas drugs of abuse decrease testosterone levels in males.

Conclusions

Thus, exercise raising testosterone levels in males helps to decrease the dopaminergic response in the brain to drugs of abuse causing attenuation to drugs. To find sex-specific exercise treatments for drugs of abuse, it is important to continue researching exercise's efficacy against drugs of abuse.
Multiple Sleep Latency Test/Maintenance of Wakefulness Test and Central Hypersomnias: Evolving Diagnostic and Therapeutic Approaches
Authors: Sampat Ajay C. , Avidan Alon Y.
Published: March 2023

Central disorders of hypersomnolence include a spectrum of conditions, such as narcolepsy, idiopathic hypersomnia, and Kleine–Levin syndrome, in which excessive daytime sleepiness is the primary feature. Subjective testing with tools, such as sleep logs and sleepiness scales, are often helpful in the evaluation of these disorders but do not necessarily correlate well with objective testing, such as polysomnography and multiple sleep latency test and maintenance of wakefulness test. The most recent International Classification of Sleep Disorders-Third Edition has incorporated biomarkers, such as cerebrospinal fluid hypocretin level, into the diagnostic criteria and have restructured the classification of conditions based on our evolved understanding of their underlying pathophysiologic mechanisms. Therapeutic approaches largely consist of behavioral therapy, with a focus on optimizing sleep hygiene, optimizing opportunity for sleep, and strategic napping, along with judicious use of analeptic and anticataleptic agents when necessary. Emerging therapy has revolved around hypocretin-replacement therapy, immunotherapy, and nonhypocretin agents, with the goal of better targeting the underlying pathophysiology of these disorders rather than addressing symptoms. The most novel treatments have targeted the histaminergic system (pitolisant), dopamine reuptake transmission (solriamfetol), and gamma-aminobutyric acid modulation (flumazenil and clarithromycin) to promote wakefulness. Continued research is required for a more solid understanding of the biology of these conditions to develop a more robust armamentarium of therapeutic options.
A Concise Review of Polysomnography and Obstructive Sleep Apnea for the Neurophysiologist
Authors: Soltis Marjorie E. , Spector Andrew R.
Published: March 2023

Sleep as an electrical phenomenon in the brain was first recorded in 1875. Over the next 100 years, recordings of sleep evolved into modern-day polysomnography, which includes not only electroencephalography but also combinations of electro-oculography, electromyography, nasal pressure transducers, oronasal airflow monitors, thermistors, respiratory inductance plethysmography, and oximetry. The most common usage of polysomnography is to identify obstructive sleep apnea (OSA). Research has demonstrated that subjects with OSA have distinctive patterns detected by EEG. The evidence indicates that increased slow activity is seen in both sleep and wake for subjects with OSA and that these changes are reversible with treatment. This article reviews normal sleep, changes in sleep that result from OSA, and the effect that treatment of OSA via continuous positive airway pressure therapy has on normalizing the EEG. A review of alternative OSA treatment options is included, although their effects on EEG in OSA patients have not been studied.
Face2face: advancing the science of social interaction
Authors: Hamilton Antonia F de C. , Holler Judith
Published: March 2023

Face-to-face interaction is core to human sociality and its evolution, and provides the environment in which most of human communication occurs. Research into the full complexities that define face-to-face interaction requires a multi-disciplinary, multi-level approach, illuminating from different perspectives how we and other species interact. This special issue showcases a wide range of approaches, bringing together detailed studies of naturalistic social-interactional behaviour with larger scale analyses for generalization, and investigations of socially contextualized cognitive and neural processes that underpin the behaviour we observe. We suggest that this integrative approach will allow us to propel forwards the science of face-to-face interaction by leading us to new paradigms and novel, more ecologically grounded and comprehensive insights into how we interact with one another and with artificial agents, how differences in psychological profiles might affect interaction, and how the capacity to socially interact develops and has evolved in the human and other species. This theme issue makes a first step into this direction, with the aim to break down disciplinary boundaries and emphasizing the value of illuminating the many facets of face-to-face interaction.

This article is part of a discussion meeting issue ‘Face2face: advancing the science of social interaction’.
Long gaps between turns are awkward for strangers but not for friends
Authors: Templeton Emma M. , Chang Luke J. , Reynolds Elizabeth A. , Cone LeBeaumont Marie D. , Wheatley Thalia
Published: March 2023

When people feel connected they tend to respond quickly in conversation, creating short gaps between turns. But are long gaps always a sign that things have gone awry? We analysed the frequency and impact of long gaps (greater than 2 s) in conversations between strangers and between friends. As predicted, long gaps signalled disconnection between strangers. However, long gaps between
friends
marked moments of
increased
connection and friends tended to have more of them. These differences in connection were also perceived by independent raters: only the long gaps between strangers were rated as awkward, and increasingly so the longer they lasted. Finally, we show that, compared to strangers, long gaps between friends include more genuine laughter and are less likely to precede a topic change. This suggests that the gaps of friends may not function as ‘gaps’ at all, but instead allow space for enjoyment and mutual reflection. Together, these findings suggest that the turn-taking dynamics of friends are meaningfully different from those of strangers and may be less bound by social conventions. More broadly, this work illustrates that samples of convenience—pairs of strangers being the modal paradigm for interaction research—may not capture the social dynamics of more familiar relationships.

This article is part of a discussion meeting issue ‘Face2face: advancing the science of social interaction’.
Intertwining the social and the cognitive loops: socially enactive cognition for human-compatible interactive systems
Authors: Kahl Sebastian , Kopp Stefan
Published: March 2023

It is increasingly important for technical systems to be able to interact flexibly, robustly and fluently with humans in real-world scenarios. However, while current AI systems excel at narrow task competencies, they lack crucial interaction abilities for the adaptive and co-constructed social interactions that humans engage in. We argue that a possible avenue to tackle the corresponding computational modelling challenges is to embrace interactive theories of social understanding in humans. We propose the notion of socially enactive cognitive systems that do not rely solely on abstract and (quasi-)complete internal models for separate social perception, reasoning and action. By contrast, socially enactive cognitive agents are supposed to enable a close interlinking of the enactive socio-cognitive processing loops within each agent, and the social-communicative loop between them. We discuss theoretical foundations of this view, identify principles and requirements for according computational approaches, and highlight three examples of our own research that showcase the interaction abilities achievable in this way.

This article is part of a discussion meeting issue ‘Face2face: advancing the science of social interaction’.
Self-Configuring Capsule Networks for Brain Image Segmentation
Authors: Avesta Arman , Hossain Sajid , Aboian Mariam , Krumholz Harlan M. , Aneja Sanjay
Published: March 2023

When an auto-segmentation model needs to be applied to a new segmentation task, multiple decisions should be made about the pre-processing steps and training hyperparameters. These decisions are cumbersome and require a high level of expertise. To remedy this problem, I developed self-configuring CapsNets (scCapsNets) that can scan the training data as well as the computational resources that are available, and then self-configure most of their design options. In this study, we developed a self-configuring capsule network that can configure its design options with minimal user input. We showed that our self-configuring capsule netwrok can segment brain tumor components, namely edema and enhancing core of brain tumors, with high accuracy. Out model outperforms UNet-based models in the absence of data augmentation, is faster to train, and is computationally more efficient compared to UNet-based models.
Leisure time sedentary behaviour and risks of breast, colorectal, and prostate cancer: A Mendelian randomization analysis
Authors: Papadimitriou Nikos , Kazmi Nabila , Dimou Niki , Tsilidis Konstantinos K , Martin Richard M , Lewis Sarah J , Lynch Brigid M , Hoffmeister Michael , Kweon Sun-Seog , Li Li , Milne Roger L , Sakoda Lori C , Schoen Robert E , Phipps Amanda I , Figueiredo Jane C , Peters Ulrike , Dixon-Suen Suzanne C. , Gunter Marc J , Murphy Neil
Published: March 2023

Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. We examined potential causal associations between self-reported leisure television watching and computer use and risks of breast, colorectal, and prostate cancer using a two-sample Mendelian randomization framework. Genetic variants were identified from a recent genome-wide association study (GWAS). Cancer data were obtained from cancer GWAS consortia. Additional sensitivity analyses were applied to examine the robustness of the results. A 1-standard deviation increment in hours of television watching increased risk of breast (OR: 1.15, 95% confidence interval [CI]: 1.05,1.26) and colorectal cancer (OR: 1.32, 95%CI: 1.16,1.49) with little evidence of an association for prostate cancer risk. In multivariable models adjusted for years of education, the effect estimates for television watching were attenuated (breast cancer, OR: 1.08, 95%CI: 0.92,1.27; colorectal cancer, OR: 1.08, 95%CI: 0.90,1.31). Post-hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed by sex (colorectal cancer), anatomical subsites, and cancer subtypes. There was little evidence of associations between computer use and cancer risk. We found evidence of positive associations between hours of television watching and risks of breast and colorectal cancer. However, these findings should be interpreted cautiously given the complex role of education. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development.

Novelty and impact

Evidence from observational studies that examined associations between sedentary behaviours and common cancers is mixed and causality is uncertain. In our Mendelian randomization analyses, higher levels of leisure television watching were found to increase the risks of breast and colorectal cancer, suggesting that the that the promotion of lowering sedentary behaviour time could be an effective strategy in the primary prevention of these commonly diagnosed cancers.

Article category

Cancer Epidemiology
Virological evidence of the impact of non-pharmaceutical interventions against COVID-19 in a resource-limited setting
Authors: Moreira-Soto Andres , Bruno Alfredo , de Mora Doménica , Paez Michelle , Garces Jimmy , Wulf Ben , Sander Anna-Lena , Olmedo Maritza , Basantes Mantilla Maria José , Gonzalez Manuel , Nárvaez Alberto Orlando , Salgado Silvia , Zevallos Juan Carlos , Drexler Jan Felix
Published: March 2023

Ecuador was an early COVID-19 hotspot with substantial COVID-19-mortality. In developed countries, low socioeconomic status is associated with COVID-19 infection and low compliance with non-pharmaceutical interventions (NPIs). However, if NPI were successful in resource-limited settings with high human mobility and informal labour is still unclear. We performed a retrospective observational molecular and serological study of Ecuador’s reference laboratory. We tested 1,950 respiratory samples from COVID-19 surveillance for SARS-CoV-2 and 12 respiratory viruses using RT-PCR, characterized 642 SARS-CoV-2 genomes, and examined SARS-CoV-2 seroprevalence in 1,967 samples from patients with fever in Ecuador’s reference laboratory during 2020-2021. Molecular and serological data were compared to NPI stringency in Bayesian, maximum-likelihood and modelling frameworks.

SARS-CoV-2 (Pearson correlation test; r=-0.74; p=0.01) and other respiratory viruses (r=-0.68; p=0.02) detection correlated negatively with NPI stringency. SARS-CoV-2 seroprevalence increased from <1% during February-March 2020 to 50% within 6 weeks and plateaued after NPI implementation. Decrease of effective reproduction number <1 and antibody reactivity over time suggested intense SARS-CoV-2 transmission during pandemic onset, subsequently limited by NPIs. Phylogeographic analyses revealed that travel restrictions were implemented late not preventing 100 near-parallel SARS-CoV-2 introductions, and implementation of NPIs modified SARS-CoV-2 geographic spread by restricting recreational activity. NPIs stringency correlated negatively with the number of circulating SARS-CoV-2 lineages (r=-0.69; p=0.02). Virological evidence supports NPIs restricting human movement as an effective public health tool to control the spread of respiratory pathogens in resource-limited settings, providing a template for emerging SARS-CoV-2 variants and future epidemics.
The Prevalence of Tuberculosis Infection Among Foreign-Born Canadians: A Modelling Study
Authors: Jordan Aria Ed , Nsengiyumva Ntwali Placide , Houben Rein M. G. J. , Dodd Peter J. , Dale Katie D. , Trauer James M. , Denholm Justin T. , Johnston James C. , Khan Faiz Ahmad , Campbell Jonathon R. , Schwartzman Kevin
Published: March 2023

Background

The prevalence of tuberculosis infection (TBI) is critical to designing tuberculosis (TB) prevention strategies, yet it is unknown in Canada. We estimated TBI prevalence among foreign-born Canadians.

Methods

Using a previously developed Gaussian process regression model, annual risk of infection trends abroad were constructed and used to estimate TBI prevalence by age and year of migration to Canada for persons from each of 168 countries. These stratified TBI prevalence estimates were combined with Canadian census data to estimate overall TBI prevalence among foreign-born residents during census years 2001, 2006, 2011, and 2016. We also estimated TBI prevalence according to age, WHO-estimated TB incidence in country of origin, and province/territory of residence. Finally, we estimated the prevalence of TBI acquired within the two preceding years.

Results

Estimated TBI prevalence among foreign-born Canadians overall was 25% (95% uncertainty interval [UI]: 20-35%), 24% (20-33%), 23% (19-30%), and 22% (19-28%) for census years 2001, 2006, 2011, and 2016, respectively. TBI prevalence increased with age at migration and TB incidence in the country of origin. In 2016, estimated TBI prevalence was lowest in Quebec (19%, 95% UI: 16-25) and highest in Alberta and British Columbia, at 24% each. Among all foreign-born Canadian residents with TBI in 2016, we estimated that only 1 in 440 were infected within the two preceding years.

Interpretation

Approximately 1 in 4 foreign-born Canadians has TBI; estimated prevalence has remained quite stable over the last two decades. However, a very small minority of people with TBI were infected within the last two years—the highest risk period for progression to TB disease. These data may inform future TBI screening policies.
Large Extracellular Vesicles Transfer Higher Levels of Prions and Infect Cell Culture Better than Small Extracellular Vesicles
Authors: Soukup Jakub , Moško Tibor , Kereïche Sami , Holada Karel
Published: March 2023

Prions are responsible for a number of lethal neurodegenerative and transmissible diseases in humans and animals. Extracellular vesicles, especially small exosomes, have been extensively studied in connection with various diseases. In contrast, larger microvesicles are often overlooked. In this work, we compared the ability of large extracellular vesicles (lEVs) and small extracellular vesicles (sEVs) to spread prions in cell culture. We utilized CAD5 cell culture model of prion infection and isolated lEVs by 20,000 × g force and sEVs by 110,000 × g force. The lEV fraction was enriched in β-1 integrin with a vesicle size starting at 100 nm. The fraction of sEVs was depleted of β-1 integrin with a mean size of 79 nm. Both fractions were enriched in prion protein, but the lEVs contained a higher prion-converting activity. In addition, lEV infection led to stronger prion signals in both cell cultures, as detected by cell and western blotting. These results were verified on N2a-PK1 cell culture. Our data suggest the importance of lEVs in the trafficking and spread of prions over extensively studied small EVs.
Long noncoding RNA AL109754.1 Regulates Myeloid Dendritic Cell Differentiation and Potentiates TLR signaling
Authors: Naqvi Raza Ali , Valverde Araceli , Naqvi Afsar
Published: March 2023

Dendritic cells (DCs) are key antigen presentation cells (APC) that bridge innate and adaptive immune functions to contain the pathogenic threats. Long noncoding RNAs (lncRNAs) are implicated in functional regulation of various biological processes including inflammation and immunity. However, the knowledge on myeloid DC expressed lncRNA repertoire and their regulatory functions is limited. In this study, we have reconnoitered the time-kinetics of lncRNA expression profiles during monocyte-to-DC differentiation and their roles in shaping DC functions. Our RNA-seq data identified thousands of differentially expressed lncRNAs associated with primary human monocyte-to-DC differentiationin vitro. We selected two lncRNAsviz., AL109754.1 and AC093278.2 that were enriched during DC differentiation. Knockdown of AL109754.1 but not AC093278 affects DCs differentiation as observed by marked reduction of surface markers CD1a, CD93 and CD209. These DCs also exhibit significant reduction in the expression of TLR 2, 4, 5, 7 and 9, suggesting that AL109754.1 expression is critical in maintaining TLR expression in DCs. Furthermore, reduced phosphorylation of NF-κB, IRF3 and IRF7 in AL109754.1 knockdown DCs treated with TLR agonists further substantiate their role in potentiating TLR signaling. Mechanistically, AL109754.1 knockdown DC showed significant downregulation of multiple NF-κB-induced genes and time-dependent inhibition of pro-inflammatory cytokine (IL-1β, IL-6, IL-8 and TNFα) secretion upon challenge with TLR 4, 5, or 7 agonists. Overall, this study characterized novel functions of AL109754.1 that regulates DC differentiation, and TLR-dependent innate immune activation.
Aging-related mechanical degradation of cortical bone is driven by microstrucural changes in addition to porosity
Authors: Marty André Gutiérrez
Published: March 2023

This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers loaded in uniaxial tension, which comprised osteons and interstitial tissue. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber “families.” Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created. Aging-related changes were modeled along three independent dimensions: (i) increased porosity, (ii) increased ratio of osteon fibers relative to interstitial fibers, and (iii) a change in fiber material properties.

The model captured decreases in modulus, yield stress, yield strain, ultimate stress, ultimate strain, and toughness with age of 14%, 11%, 8%, 6%, 20%, and 30%, respectively. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case.

Changes along all three dimensions were required for the model to capture aging-related decline in the strength, ductility, and toughness of cortical bone. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the microconstituent material properties of osteon and interstitial tissue, in order to further our understanding of aging-related changes in bone.
Screening tools used in primary health care settings to identify health behaviours in children (birth – 16 years); A systematic review of their effectiveness, feasibility and acceptability
Authors: Dutch Dimity , Bell Lucinda , Zarnowiecki Dorota , Johnson Brittany J , Denney-Wilson Elizabeth , Byrne Rebecca , Cheng Heilok , Rossiter Chris , Manson Alexandra , House Eve , Davidson Kamila , Golley Rebecca K
Published: March 2023

Background

Child health behaviour screening tools used in primary health care have potential as a transformative and effective strategy to support growth monitoring and the early identification of suboptimal behaviours to target strategies for intervention. This systematic review aimed to examine the effectiveness, acceptability and feasibility of child health behaviour screening tools used in primary health care settings.

Methods

A systematic review of studies published in English in five databases (CINAHL, Medline, Scopus, PsycINFO and Web of Science) prior to July 2022 was undertaken using a PROSPERO protocol and PRISMA guidelines. Eligible studies: 1) described screening tools for health behaviours (dietary, physical activity, sedentary or sleep-related behaviours) used in primary health care settings in children birth to 16 years of age; 2) reported their acceptability, feasibility or effectiveness on child or practitioner behaviour or 3) reported implementation of the screening tool. Study selection and data extraction were conducted in duplicate. Results were narratively synthesised.

Results

Of the 7145 papers identified, 22 studies reporting on 14 unique screening tools were included. Four screening tools measured diet, physical activity, sedentary and sleep behaviours domains, with most screening tools only measuring two or three behaviour domains. Ten studies reported screening tools were effective in changing practitioner self-reported behaviour, knowledge, self-efficacy and provision of health behaviour education. Administration of screening tools varied across studies including mode, timing and caregiver or practitioner completion. Implementation strategies described included practitioner training and integration into electronic medical records. Practitioners and caregivers identified numerous benefits and challenges to screening; however, child views were not captured.

Conclusions

Few screening tools exist to facilitate comprehensive screening of children’s health behaviours in primary health care. This review highlights the potential of health behaviour screening as an acceptable and feasible strategy to comprehensively assess and provide early intervention for children’s health behaviours in primary health care settings.

Potential conflicts of interest

All authors have no conflicts of interest to declare.
A critical role of a eubiotic microbiota in gating proper immunocompetence inArabidopsis
Authors: Paasch Bradley C. , Sohrabi Reza , Kremer James M. , Nomura Kinya , Cheng Yu Ti , Martz Jennifer , Kvitko Brian , Tiedje James M. , He Sheng Yang
Published: March 2023

Although many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system we found thatArabidopsisgrown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogenPseudomonas syringaepv.tomatoDC3000 and the fungal pathogenBotrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota, and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthyArabidopsisplants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.
“Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression”
Authors: Hasselluhn Marie C. , Decker-Farrell Amanda R. , Vlahos Lukas , Thomas Dafydd H. , Curiel-Garcia Alvaro , Maurer H. Carlo , Wasko Urszula N. , Tomassoni Lorenzo , Sastra Stephen A. , Palermo Carmine F. , Dalton Tanner C. , Ma Alice , Li Fangda , Tolosa Ezequiel J. , Hibshoosh Hanina , Fernandez-Zapico Martin E. , Muir Alexander , Califano Andrea , Olive Kenneth P.
Published: March 2023

The sparse vascularity of Pancreatic Ductal Adenocarcinoma (PDAC) presents a mystery: what prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell typesin vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues.