bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated delineation of head and neck organs at risk using synthetic MRI‐aided mask scoring regional convolutional neural network
Authors: Dai Xianjin , Lei Yang , Wang Tonghe , Zhou Jun , Roper Justin , McDonald Mark , Beitler Jonathan J. , Curran Walter J. , Liu Tian , Yang Xiaofeng
Published: August 2021

Purpose

Auto‐segmentation algorithms offer a potential solution to eliminate the labor‐intensive, time‐consuming, and observer‐dependent manual delineation of organs‐at‐risk (OARs) in radiotherapy treatment planning. This study aimed to develop a deep learning‐based automated OAR delineation method to tackle the current challenges remaining in achieving reliable expert performance with the state‐of‐the‐art auto‐delineation algorithms.

Methods

The accuracy of OAR delineation is expected to be improved by utilizing the complementary contrasts provided by computed tomography (CT) (bony‐structure contrast) and magnetic resonance imaging (MRI) (soft‐tissue contrast). Given CT images, synthetic MR images were firstly generated by a pre‐trained cycle‐consistent generative adversarial network. The features of CT and synthetic MRI were then extracted and combined for the final delineation of organs using mask scoring regional convolutional neural network. Both in‐house and public datasets containing CT scans from head‐and‐neck (HN) cancer patients were adopted to quantitatively evaluate the performance of the proposed method against current state‐of‐the‐art algorithms in metrics including Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), mean surface distance (MSD), and residual mean square distance (RMS).

Results

Across all of 18 OARs in our in‐house dataset, the proposed method achieved an average DSC, HD95, MSD, and RMS of 0.77 (0.58–0.90), 2.90 mm (1.32–7.63 mm), 0.89 mm (0.42–1.85 mm), and 1.44 mm (0.71–3.15 mm), respectively, outperforming the current state‐of‐the‐art algorithms by 6%, 16%, 25%, and 36%, respectively. On public datasets, for all nine OARs, an average DSC of 0.86 (0.73–0.97) were achieved, 6% better than the competing methods.

Conclusion

We demonstrated the feasibility of a synthetic MRI‐aided deep learning framework for automated delineation of OARs in HN radiotherapy treatment planning. The proposed method could be adopted into routine HN cancer radiotherapy treatment planning to rapidly contour OARs with high accuracy.
Managing occupational doses with smartphones in interventional radiology
Authors: Sánchez Roberto M. , Fernández Daniel , Vañó Eliseo , Fernández José M.
Published: August 2021

Purpose

This study presents a prototype smartphone application for occupational dosimetry in interventional practices based on electronic personal dosimeters to assist in dose monitoring.

Methods

The prototype receives and records information from the occupational dose report containing the cumulative dose of electronic personal dosimeters worn over the apron at chest level and electronic area dosimeters located on C‐arms (reference dosimeters), for each fluoroscopy‐guided procedure. Using their smartphones, personnel involved in interventional practices can review and compare their occupational records with an investigation level, the dose limits, and their department colleagues (anonymously). The ratio between Hp(10) measured by the personal and the reference dosimeters at the C‐arm is presented as an indicator of consistent use of suspended operator shield. Some general results extracted from the first months of use are presented.

Results

The reference dosimeter located at the C‐arm (without lead protection and acting as an ambient dosimeter) recorded in one of the laboratories 217 mSv during 308 procedures over 5 months, showing an indication of the radiation risk present in an interventional laboratory. The ratio between the personal cumulative dose and the dose at a reference C‐arm dosimeter ranged from 0.2% to 1.67% (a factor of 8.5) for different interventionalists. These differences suggest different protection habits among interventional operators, as well as a target for dose reduction.

Conclusions

With this system, professionals have easy access to their occupational dosimetry records (including information on the workload) in the setting of their interventional departments, to thereby actively engage in the protection process.
Patient satisfaction and savings, and clinical outcomes of televisits in female pelvic medicine and reconstructive surgery at an urban academic center
Authors: Shin Christina , Allen Ariel Z. , Zhu Denzel , Tellechea Laura , Watts Kara L. , Abraham Nitya E.
Published: August 2021

Aim

To evaluate patient satisfaction and savings, and compare visit outcomes based on chief complaint (CC) of women presenting for a televisit to a female pelvic medicine and reconstructive surgery (FPMRS) clinic at an urban academic center.

Methods

A cross‐sectional study of women completing a televisit with an FPMRS specialist at our institution from June 19, 2020 to July 17, 2020 was conducted. A telephone questionnaire was administered to patients to assess satisfaction and savings (travel costs/time avoided). Electronic medical records were reviewed to collect patient demographics and comorbidities, CC, and televisit outcomes (e.g., face‐to‐face (F2F) exam scheduled, orders placed). Logistic regression was used to analyze predictors of satisfaction and need for F2F follow‐up.

Results

One hundred eighty‐seven of 290 (64.5%) women called completed the survey, of whom 168 (89.8%) were satisfied with their televisit. Eighty‐eight (48.1%) saved at least an hour and 54 (28.9%) saved more than $25 on transportation. There were no significant associations between patient characteristics, CC, or televisit outcomes and satisfaction. Ninety‐nine (52.9%) televisits resulted in F2F follow‐up, with CC of prolapse (odds ratio [OR] = 4.2 (1.7–10.3); p = 0.002), new patient (OR = 2.2 (1.2–4.2); p = 0.01), and Hispanic ethnicity (OR = 3.9 (1.2–13.6); p=.03) as significant predictors.

Conclusion

Most patients were satisfied with FPMRS televisits at our urban academic center. Televisits resulted in patient travel time and cost savings. Women presenting with prolapse and for new patient visits would likely benefit from initial F2F visits instead of televisits. Televisits are an important mode of health care and in some cases can replace F2F visits.
Insulin delivery devices 100 years on
Authors: Sharp Patrick , Ives Emma
Published: August 2021

The extraction of insulin from the pancreas and its subsequent use in the treatment of diabetes presented a new set of problems. Of these, insulin delivery is perhaps so obvious that it does not get the attention it deserves. Syringes dedicated to the delivery of insulin made minor progress for the first 60 years but the development of the pen injector from the 1980s onward has been fertile ground for innovation. Near field connectivity in various forms continues to push the boundaries. In the background, there is slow progress on development of non‐injectable delivery modalities. Copyright © 2021 John Wiley & Sons.
Type 1 diabetes: dietary modification over 100 years since insulin
Authors: Dyson Pamela
Published: August 2021

Diet has been central for the management of type 1 diabetes for over three thousand years, and the discovery of insulin in 1921 was associated with the introduction of formal dietary education. Carbohydrate was soon identified as the macronutrient responsible for postprandial glucose excursions and over the past one hundred years, dietary interventions have alternated between severe carbohydrate restriction and so‐called free diets. The very low carbohydrate diets of the 1920s gave way to the free diets of the 1930s, and carbohydrate restriction was then reintroduced in the 1940s to the 1960s. In the 1970s, carbohydrate intake was increased with an emphasis on dietary fibre and low fat, healthy eating was recommended in the 1980s. The past few decades have reflected the growing evidence following the DCCT and DAFNE trials and dietary interventions are now individualised and emphasise carbohydrate counting and insulin adjustment and quality of life. Copyright © 2021 John Wiley & Sons.
What do people with diabetes really think about remote consultations?
Authors: Kilvert Anne , Fox Charles , Calladine Lee
Published: August 2021

In 2017 the diabetes service in Newham reported a positive response to a trial of virtual clinics but their own NHS trust (Barts Health) struggled to expand the number of virtual services offered. When COVID struck in March 2020, the NHS immediately obtained a licence to a secure platform for video consultations; many appointments took place by phone and the number of face‐to‐face clinics declined dramatically.

Whether people with diabetes prefer face‐to‐face, telephone or video consultations depends on whom you ask. We summarise the findings of two published online surveys and report the results of our own paper survey, distributed through the Diabetes Research & Wellness Foundation monthly newsletter, Diabetes Wellness News. Respondents to the online surveys were positive about the benefits of virtual consultations, although there were concerns about confidentiality, safeguarding and identification of emotional issues. In contrast, the paper survey (n=301) found that 91% of respondents preferred a face‐to‐face consultation. Although 36% of respondents had access to video technology, only 7.2% had been offered a video consultation (24% with type 1 diabetes and 3.8% with type 2) and 87% of remote consultations had been by phone. While two‐thirds of respondents were at least fairly satisfied with their remote consultations, most people preferred to return to face to face when possible, the most common reason being that communication was easier.

In conclusion, remote consultations will remain an important option in the future, but individual preferences must be taken into account; a combination of remote and face to face may be the most effective approach. Copyright © 2021 John Wiley & Sons.
Critical Initiation Threshold of Covered Finite Thickness Explosive under Impact of Shaped Charge Jet
Authors: Chen Si‐min , Jia Xin , Xia Ming , Huang Zheng‐xiang , Wang Jian‐hui , Xiao Qiang‐qiang , Tang De‐rong
Published: August 2021

The compression depth of explosives is obtained on the basis of Lee penetration equation and the upper bound method to analyze the critical initiation threshold of finite thickness explosives. According to the pop curve, a theoretical model that reflects the relationship between critical initiation threshold and explosive thickness is established. Numerical simulation was carried out to simulate the initiation process and initiation threshold of explosives with different cover plate thicknesses. At the same time, we combine with the experimental data, to compare with the theoretical results. The calculations are in good agreement with data. Results show that the height of the bulge on the back of the cover plate and the compression depth of the explosive gradually increase with the thickness of the cover plate. When the cover plate reaches a certain thickness, there is no significant change on the final height of the bulge and the compression depth of the explosive. The decrease in explosive thickness increases the critical initiation threshold value, and the logarithm of the critical initiation threshold of the finite thickness explosive is approximately linearly related to the logarithm of the explosive thickness minus the compression depth. Therefore, this study can provide a reference for the initiation and simple calculation of the critical threshold of finite thickness explosives.
Multivariate Gaussian RBF‐net for smooth function estimation and variable selection
Authors: Roy Arkaprava
Published: August 2021

Neural networks are routinely used for nonparametric regression modeling. The interest in these models is growing with ever‐increasing complexities in modern datasets. With modern technological advancements, the number of predictors frequently exceeds the sample size in many application areas. Thus, selecting important predictors from the huge pool is an extremely important task for judicious inference. This paper proposes a novel flexible class of single‐layer radial basis functions (RBF) networks. The proposed architecture can estimate smooth unknown regression functions and also perform variable selection. We primarily focus on Gaussian RBF‐net due to its attractive properties. The extensions to other choices of RBF are fairly straightforward. The proposed architecture is also shown to be effective in identifying relevant predictors in a low‐dimensional setting using the posterior samples without imposing any sparse estimation scheme. We develop an efficient Markov chain Monte Carlo algorithm to generate posterior samples of the parameters. We illustrate the proposed method's empirical efficacy through simulation experiments, both in high and low dimensional regression problems. The posterior contraction rate is established with respect to empiricaldistance assuming that the error variance is unknown, and the true function belongs to a Hölder ball. We illustrate our method in a Human Connectome Project dataset to predict vocabulary comprehension and to identify important edges of the structural connectome.
Flotation separation of dolomite from fluorapatite using NaF as an activator
Authors: Li Dewei , Nie Guanghua , Wang Zhiqiang , Li Jie , Li Jiaxin
Published: August 2021

For the reverse flotation of phosphate ore, a high amount of sulfuric acid is required. In this study, we used NaF as a flotation activator to separate dolomite and fluorapatite to reduce acid consumption in the flotation process. Both single and actual mineral flotations were conducted. The NaF addition significantly improved the floatability of dolomite and reduced the flotation system's acid consumption. We employed X‐ray photoelectron spectroscopy and Material Studio simulation to examine the effect of dolomite activator (NaF) on the surface of dolomite and fluoroapatite. The addition of NaF showed much less effect on fluoroapatite than dolomite, thereby increasing the difference in floatability between dolomite and fluoroapatite, which is beneficial to flotation.
Pleiotropy robust methods for multivariable Mendelian randomization
Authors: Grant Andrew J. , Burgess Stephen
Published: August 2021

Mendelian randomization is a powerful tool for inferring the presence, or otherwise, of causal effects from observational data. However, the nature of genetic variants is such that pleiotropy remains a barrier to valid causal effect estimation. There are many options in the literature for pleiotropy robust methods when studying the effects of a single risk factor on an outcome. However, there are few pleiotropy robust methods in the multivariable setting, that is, when there are multiple risk factors of interest. In this article we introduce three methods which build on common approaches in the univariable setting: MVMR‐Robust; MVMR‐Median; and MVMR‐Lasso. We discuss the properties of each of these methods and examine their performance in comparison to existing approaches in a simulation study. MVMR‐Robust is shown to outperform existing outlier robust approaches when there are low levels of pleiotropy. MVMR‐Lasso provides the best estimation in terms of mean squared error for moderate to high levels of pleiotropy, and can provide valid inference in a three sample setting. MVMR‐Median performs well in terms of estimation across all scenarios considered, and provides valid inference up to a moderate level of pleiotropy. We demonstrate the methods in an applied example looking at the effects of intelligence, education and household income on the risk of Alzheimer's disease.
p‐Type Carbon Dots for Effective Surface Optimization for Near‐Record‐Efficiency CsPbI2Br Solar Cells
Authors: Guo Xi , Zhao Biao , Xu Kunxiang , Yang Shaomin , Liu Zhike , Han Yu , Xu Jie , Xu Dongfang , Tan Zhanao , Liu Shengzhong (Frank)
Published: August 2021

Interface modification to minimize charge recombination and trapping for efficient charge transport is crucial for the performance of perovskite solar cells (PSCs). Herein, functionalized p‐type blue carbon dots (B‐CDs) are ventured as an interface passivation layer to enhance the efficiency and long‐term stability of all‐inorganic CsPbI2Br PSCs. It is found that first the blue carbon dots with abundant NH, CN, CO, and CO functional groups effectively passivate defects by reacting with I− and Pb2+ ions in the perovskite through hydrogen and coordinative bonds. Second, the p‐type B‐CDs modifiers form a P–N junction with the n‐type perovskite to provide efficient pathways for hole transfer and electron blocking. Third, the B‐CDs increase the hydrophobicity of the perovskite film to improve the stability of CsPbI2Br PSCs. With the above advantages, the CsPbI2Br PSC with B‐CDs modification shows an efficiency as high as 16.76%, one of the highest for its type. In addition, the modification renders significant improvement of air and light stability, with 95.33% of the initial PCE retained after storage in the ambient environment for 1000 h. This work demonstrates the great potential of B‐CDs application in perovskite‐based optoelectronic devices.
New risk stratification after colorectal polypectomy reduces burden of surveillance without increasing mortality
Authors: Waldmann Elisabeth , Kammerlander Andreas , Gessl Irina , Penz Daniela , Majcher Barbara , Hinterberger Anna , Trauner Michael , Ferlitsch Monika
Published: August 2021

Background

The 2020 postpolypectomy surveillance guideline update of European Society for Gastrointestinal Endoscopy defines a more restrictive group of individuals in need for surveillance 3 years after colonoscopy.

Aim

The aim of this cohort study was to validate the new guideline recommendation.

Methods

Based on a national quality assurance program, we compared the 2020 risk group definition with the previous 2013 recommendations for their strength of association with (1) colorectal cancer death, and (2) all‐cause death.

Results

A total of 265,608 screening colonoscopies were included in the study. Mean age was 61.1 years (SD ±9.0), and 50.6% were women. During a mean follow‐up of 59.3 months (SD ±35.0), 170 CRC deaths and 7723 deaths of any cause were identified. 62.4% of colonoscopies were negative and 4.9% were assigned to surveillance after 3 years according to the 2020 guidelines versus 10.4% following the 2013 guidelines, which corresponds to a relative reduction in colonoscopies by 47%. The strength of association with CRC mortality was markedly higher with the 2020 surveillance group as compared to the 2013 guidelines (HR 2.56, 95% CI 1.62–4.03 vs. HR 1.73, 95% CI 1.13–2.62), while the magnitude of association with CRC mortality for low risk individuals was lower (HR 1.17, 95% CI 0.83–1.63 vs. 1.25, 95% CI 0.88–1.76).

Conclusions

Adherence to the updated guidelines reduces the burden of surveillance colonoscopies by 47% while preserving the efficacy of surveillance in preventing CRC mortality.
People in Contact with Criminal Justice Systems Participating in Service Redesign: Vulnerable Citizens or Democratic Partners?
Authors: Parker Jonathan , Heaslip Vanessa , Ashencaen Crabtree Sara , Johnsen Berit , Hean Sarah
Published: August 2021

This chapter presents a conceptual consideration of the centrality of ‘voice’ in the Criminal Justice System (CJS), particularly in respect of service development. The hidden perspectives of those who are ‘subject to’, working with or working in the CJS represent important aspects to consider when seeking to change, develop or evaluate services. After emphasising the turn to including the voices of those often excluded from participation we explore aspects of the contested concept of ‘vulnerability’ as a label often applied to those working with CJS. We widen this to consider the vulnerabilities by association that professional take on as popular discourses permeate perceptions of CJS cultures. Subsequently, we examine some of the ways in which the inclusion of hidden and potentially vulnerable voices of those citizens involved with CJS can assist the transformative development of services by irritating the normative perspectives. We advocate an approach based around critical ethnography as a means of sitting with and walking besides people intimately involved in CJS.
Mirrors of Prison Life—From Compartmentalised Practice Towards Boundary Crossing Expertise
Authors: Nielsen Søren Walther , Kajamaa Anu
Published: August 2021

In this chapter, our aim is to broaden the understanding of the compartmentalisation of practices within and between different service providers in the prison setting and to emphasise the need to cross professional boundaries between these services treating the same inmates. For this, we will provide a multidimensional “mirror” into prison life by bringing forth the different voices of the professional groups involved in the provision of mental health and prison services. A key finding is that the tensions emerging during the activities between the service providers are historically accumulated and caused by the inflexible division of labour and the lack of interagency expertise. New models to enable the crossing of the organizationel boundaries between parties are thus needed.
Non-negativity of BMN two-point functions with three string modes
Authors: Du Bao-ning , Huang Min-xin
Published: August 2021

Abstract

Recently, we proposed a novel entry of the pp-wave holographic dictionary, which equated the Berenstein-Maldacena-Nastase (BMN) two-point functions in free $$ \mathcal{N} $$
N
= 4 super-Yang-Mills theory with the norm squares of the quantum unitary transition amplitudes between the corresponding tensionless strings in the infinite curvature limit, for the cases with no more than three string modes in different transverse directions. A seemingly highly non-trivial conjectural consequence, particularly in the case of three string modes, is the non-negativity of the BMN two-point functions at any higher genus for any mode numbers. In this paper, we further perform the detailed calculations of the BMN two-point functions with three string modes at genus two, and explicitly verify that they are always non-negative through mostly extensive numerical tests.
Orthosymplectic implosions
Authors: Bourget Antoine , Dancer Andrew , Grimminger Julius F. , Hanany Amihay , Kirwan Frances , Zhong Zhenghao
Published: August 2021

Abstract

We propose quivers for Coulomb branch constructions of universal implosions for orthogonal and symplectic groups, extending the work on special unitary groups in [1]. The quivers are unitary-orthosymplectic as opposed to the purely unitary quivers in the A-type case. Where possible we check our proposals using Hilbert series techniques.
Ergodic equilibration of Rényi entropies and replica wormholes
Authors: Sasieta Martin
Published: August 2021

Abstract

We study the behavior of Rényi entropies for pure states from standard assumptions about chaos in the high-energy spectrum of the Hamiltonian of a many-body quantum system. We compute the exact long-time averages of Rényi entropies and show that the quantum noise around these values is exponentially suppressed in the microcanonical entropy. For delocalized states over the microcanonical band, the long-time average approximately reproduces the equilibration proposal of H. Liu and S. Vardhan, with extra structure arising at the order of non-planar permutations. We analyze the equilibrium approximation for AdS/CFT systems describing black holes in equilibrium in a box. We extend our analysis to the situation of an evaporating black hole, and comment on the possible gravitational description of the new terms in our approximation.
Hemiarthroplasty of the hip using the direct anterior approach
Authors: Nogler Michael , Randelli Filippo , Macheras George A. , Thaler Martin
Published: August 2021

Objective

Minimally invasive approach in total hip arthroplasty for the treatment of femoral neck fractures with a hemiarthroplasty.

Indications

Femoral neck fractures of patients without hip osteoarthritis where the acetabulum is still intact.

Contraindications

Lesions and infections of the skin in the approach area; hip osteoarthritis; surgeon’s lack of experience with the technique.

Surgical technique

The direct anterior approach (DAA) uses the Smith–Peterson interval between the tensor fasciae latae (TFL) and the rectus and sartorius muscle. After coagulation of the ascending branches of the femoral circumflex vessels, the capsule is opened. The remaining parts of the femoral neck are removed and osteotomized if necessary. The femoral head is removed with a cork screw. Then the shaft is supported by 2 sharp retractors at the greater trochanter from cranial, and the leg is externally rotated, hyperextended, and adducted. A TFL release can be performed which we also recommend. The femoral canal is opened step by step and extended with rasps which are introduced with the double curved broach handle. Cement and the final implant are introduced and after the trial reduction also the final head. The hip is reduced, the capsule adapted and the wound closed.

Postoperative management

For this approach, there are no approach specific recommendations. Postoperative treatment depends on whether the approach was extended with muscle releases and on the type of reconstruction performed. If the approach was limited to the minimally invasive direct anterior portal, quicker rehabilitation can be expected due to the reduced muscle damage. We prefer mobilization with full weight bearing as tolerated on the next day.
Medial meniscal ramp lesions in ACL-injured elite athletes are strongly associated with medial collateral ligament injuries and medial tibial bone bruising on MRI
Authors: Willinger Lukas , Balendra Ganesh , Pai Vishal , Lee Justin , Mitchell Adam , Jones Mary , Williams Andy
Published: August 2021

Purpose

Medial menisco-capsular separations (ramp lesions) are typically found in association with anterior cruciate ligament (ACL) deficiency. They are frequently missed preoperatively due to low MRI sensitivity. The purpose of this article was to describe demographic and anatomical risk factors for ramp lesions, and to identify concomitant lesions and define their characteristics to improve diagnosis of ramp lesions on MRI.

Methods

Patients who underwent anterior cruciate ligament (ACL) reconstruction between September 2015 and April 2019 were included in this study. The presence/absence of ramp lesions was recorded in preoperative MRIs and at surgery. Patients’ characteristics and clinical findings, concomitant injuries on MRI and the posterior tibial slope were evaluated.

Results

One hundred patients (80 male, 20 female) with a mean age of 22.3 ± 4.9 years met the inclusion criteria. The incidence of ramp lesions diagnosed at surgery was 16%. Ramp lesions were strongly associated with injuries to the deep MCL (dMCL, p < 0.01), the superficial medial collateral ligament (sMCL, p < 0.01), and a small medial–lateral tibial slope asymmetry (p < 0.05). There was also good correlation between ramp lesions and bone oedema in the posterior medial tibia plateau (MTP, p < 0.05) and medial femoral condyle (MFC, p < 0.05). A dMCL injury, a smaller differential medial–lateral tibial slope than usual, and the identification of a ramp lesion on MRI increases the likelihood of finding a ramp lesion at surgery. MRI sensitivity was 62.5% and the specificity was 84.5%.

Conclusion

The presence on MRI of sMCL and/or dMCL lesions, bone oedema in the posterior MTP and MFC, and a smaller differential medial–lateral tibial slope than usual are highly associated with ramp lesions visible on MRI. Additionally, a dMCL injury, a flatter lateral tibial slope than usual, and the identification of a ramp lesion on MRI increases the likelihood of finding a ramp lesion at surgery. Knowledge of the risk factors and secondary injury signs associated with ramp lesions facilitate the diagnosis of a ramp lesion preoperatively and should raise surgeons’ suspicion of this important lesion.

Level of evidence

Diagnostic study, Level III.
Homogenous overexpression of the extracellular matrix protein Netrin-1 in a hollow fiber bioreactor
Authors: Moya-Torres Aniel , Gupta Monika , Heide Fabian , Krahn Natalie , Legare Scott , Nikodemus Denise , Imhof Thomas , Meier Markus , Koch Manuel , Stetefeld Jörg
Published: August 2021

The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems.

Key points

• Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1

• Biolayer interferometry allows target protein quantitation in expression media

• High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality

Graphical abstract
FAP imaging in rare cancer entities—first clinical experience in a broad spectrum of malignancies
Authors: Dendl K. , Finck R. , Giesel F. L. , Kratochwil C. , Lindner T. , Mier W. , Cardinale J. , Kesch C. , Röhrich M. , Rathke H. , Gampp H. , Ristau J. , Adeberg S. , Jäger D. , Debus J. , Haberkorn U. , Koerber S. A.
Published: August 2021

Purpose

68 Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors.

Material and methods

Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a 68 Ga-FAPI-PET/CT scan. Fourteen women and 41 men (median age 60) were included within the following subgroups: cancer of unknown primary (n = 10), head and neck cancer (n = 13), gastrointestinal and biliary-pancreatic cancer (n = 17), urinary tract cancer (n = 4), neuroendocrine cancer (n = 4), and others (n = 7). Tracer uptake was quantified by standardized uptake values SUVmax and SUVmean and the tumor-to-background ratio (TBR) was determined (SUVmax tumor/SUVmean organ).

Results

In 20 out of 55 patients, the primary tumor was identified and 31 patients presented metastases (n = 88), characterized by a high mean SUVmax in primary (10.1) and metastatic lesions (7.6). The highest uptake was observed in liver metastases (n = 6) with a mean SUVmax of 9.8 and a high TBR of 8.7, closely followed by peritoneal carcinomatosis (n = 16) presenting a mean SUVmax of 9.8 and an excellent TBR of 29.6. In terms of the included subgroups, the highest uptake regarding mean SUVmax was determined in gastrointestinal and biliary-pancreatic cancer with 9.8 followed closely by urinary tract cancer with 9.5 and head and neck cancer (9.1).

Conclusion

Due to excellent tumor visualization and, thereby, sharp contrasts in terms of high TBRs in primary and metastatic lesions in different rare malignancies, 68 Ga-FAPI-PET/CT crystallizes as a powerful and valuable imaging tool, particularly with respect to epithelial carcinomas, and therefore an enhancement to standard diagnostics imaging methodologies. The realization of further and prospective studies is of large importance to confirm the potential of FAP imaging in oncology.
Central nervous system vasculopathy and Seckel syndrome: case illustration and systematic review
Authors: Khojah Osama , Alamoudi Saeed , Aldawsari Nouf , Babgi Mohammed , Lary Ahmed
Published: August 2021

Purpose

To systematically review reported cases of Seckel syndrome (SS) and point out cases associated with central nervous system (CNS) vasculopathy and provide a summary of their clinical presentation, management, and outcomes including our illustrative case.

Methods

We conducted a search on the MEDLINE, PubMed, Google Scholar, and Cochrane databases using the keywords “Seckel + syndrome.” We identified 127 related articles reporting 252 cases of SS apart from our case. Moreover, we searched for SS cases with CNS vasculopathies from the same databases. We identified 7 related articles reporting 7 cases of CNS vasculopathies in SS patients.

Results

The overall rate of CNS vasculopathy in SS patients is 3.16% (n = 8/253), where moyamoya disease (MMD) accounted for 1.97%. The mean age is 13.5 years (6–19 years), with equal gender distribution (M:F, 1:1). The most common presenting symptoms were headache and seizure followed by weakness or coma. Aneurysms were mostly located in the basilar artery, middle cerebral artery, and internal carotid artery, respectively. Regardless of the management approach, 50% of the cases sustained mild-moderate neurological deficit, 37.5% have died, and 12.5% sustained no deficit.

Conclusion

A high index of suspicion should be maintained in (SS) patients, and MMD should be part of the differential diagnosis. Prevalence of CNS vasculopathy in SS is 3.16% with a much higher prevalence of MMD compared to the general population. Screening for cerebral vasculopathy in SS is justifiable especially in centers that have good resources. Further data are still needed to identify the most appropriate management plan in these cases.
Variability and changes to the mean meridional circulation in isentropic coordinates
Authors: Lucas Christopher , Rudeva Irina , Nguyen Hanh , Boschat Ghyslaine , Hope Pandora
Published: August 2021

We examine the climatology, variability and change in the global mean meridional circulation (MMC) as measured in a dry isentropic coordinate system from 1979–2017 using the ERA-Interim reanalysis. The methodology presents a zonal-mean view of the MMC as a single thermally direct circulation cell in each hemisphere. The circulation is decomposed into 'steady' and 'transient' components which allows us to identify and quantify several MMC features, including the Intertropical Convergence Zone, the descending branches of the Hadley circulation and a 'transient updraft' associated with the extratropical storm track. Large changes were identified in the Southern Hemisphere (SH) in both the Hadley Cell and the extratropical storm track in the late-1990s. These changes intertwine with the Interdecadal Pacific Oscillation that changed from a warm to a cold phase around 2000. Less significant changes were observed in the Northern Hemisphere, although high rates of tropical expansion during boreal summer may have been exacerbated by volcanic eruptions in the 1980s and 1990s. Further to those changes, tropical expansion was observed in autumn, with little change in the extratropical storm track. While potential inhomogeneities in the reanalysis limit the certainty about the magnitude of the identified changes, multiple non-reanalysis-based datasets suggest that large changes did occur in the 1990s in the SH, supporting the presented analysis.
Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids
Authors: Romano Daniel R. , Hashino Eri , Nelson Rick F.
Published: August 2021

Sensorineural hearing loss (SNHL) is a major cause of functional disability in both the developed and developing world. While hearing aids and cochlear implants provide significant benefit to many with SNHL, neither targets the cellular and molecular dysfunction that ultimately underlies SNHL. The successful development of more targeted approaches, such as growth factor, stem cell, and gene therapies, will require a yet deeper understanding of the underlying molecular mechanisms of human hearing and deafness. Unfortunately, the human inner ear cannot be biopsied without causing significant, irreversible damage to the hearing or balance organ. Thus, much of our current understanding of the cellular and molecular biology of human deafness, and of the human auditory system more broadly, has been inferred from observational and experimental studies in animal models, each of which has its own advantages and limitations. In 2013, researchers described a protocol for the generation of inner ear organoids from pluripotent stem cells (PSCs), which could serve as scalable, high-fidelity alternatives to animal models. Here, we discuss the advantages and limitations of conventional models of the human auditory system, describe the generation and characteristics of PSC-derived inner ear organoids, and discuss several strategies and recent attempts to model hereditary deafness in vitro. Finally, we suggest and discuss several focus areas for the further, intensive characterization of inner ear organoids and discuss the translational applications of these novel models of the human inner ear.
Constrained neural network training and its application to hyperelastic material modeling
Authors: Weber Patrick , Geiger Jeremy , Wagner Werner
Published: August 2021

Neural networks (NN) have been studied and used widely in the field of computational mechanics, especially to approximate material behavior. One of their disadvantages is the large amount of data needed for the training process. In this paper, a new approach to enhance NN training with physical knowledge using constraint optimization techniques is presented. Specific constraints for hyperelastic materials are introduced, which include energy conservation, normalization and material symmetries. We show, that the introduced enhancements lead to better learning behavior with respect to well known issues like a small number of training samples or noisy data. The NN is used as a material law within a finite element analysis and its convergence behavior is discussed with regard to the newly introduced training enhancements. The feasibility of NNs trained with physical constraints is shown for data based on real world experiments. We show, that the enhanced training outperforms state-of-the-art techniques with respect to stability and convergence behavior within FE simulations.
Influence of stress on physiological synchrony in a stressful versus non-stressful group setting
Authors: Denk Bernadette , Dimitroff Stephanie J. , Meier Maria , Benz Annika B. E. , Bentele Ulrike U. , Unternaehrer Eva , Popovic Nathalie F. , Gaissmaier Wolfgang , Pruessner Jens C.
Published: August 2021

Physiological synchrony (PS) is defined as the co-occurrence and interdependence of physiological activity between interaction partners. Previous research has uncovered numerous influences on the extent of PS, such as relationship type or individual characteristics. Here, we investigate the influence of acute stress on PS. We do so in a setting in which PS was not promoted, but contact between group members was explicitly minimized. We reanalyzed cortisol, alpha-amylase, and subjective stress data from 138 participants (mean age =$$23.48 \pm 3.99$$23.48±3.99, 47.1% female) who previously underwent the Trier Social Stress Test for groups (TSST-G) or a non-stressful control task together, collected as part of a larger project by Popovic et al. (Sci Rep 10: 7845, 2020). Using a stability and influence model, an established method to test for synchrony, we tested whether individuals’ cortisol and alpha-amylase concentrations could be predicted by group members’ levels. We found cortisol PS in participants who were in the same group, the extent of which was stronger in the non-stressful control condition. For alpha-amylase, participants were synchronized as well; furthermore, there was an interaction between previous stress levels and PS. This suggests that while synchrony of both stress markers can occur in group settings even with spurious interaction, stressor exposure might attenuate its extent. We argue that if PS occurs in a sample where interaction was minimal, the phenomenon might be more widespread than previously thought. Furthermore, stressor exposure might influence whether a situation allows for PS. We conclude that PS should be investigated within group settings with various degrees of social interaction to further expose mechanisms of and influence on PS.
Kompressionssyndrome der supraaortalen Gefäße
Authors: Bürger Th. , Bürger M. , Gebauer Th. , Stegemann E.
Published: August 2021

Vaskuläre Kompressionssyndrome betreffen meist die obere Thoraxapertur, häufig begleitet von einer nervalen Symptomatik, und werden zusammengefasst als Thoracic-outlet- (TOS) und, falls eine isolierte venöse Kompression im Vordergrund steht, als Thoracic-inlet-Syndrom (TIS) bezeichnet. Diagnostik und Therapie sind oft schwierig. Fehlende vaskuläre und neurogene Veränderungen indizieren als erstes meist eine konservative Therapie. Der embolische Verschluss der Armarterien bei jüngeren Patienten sowie eine erfolglose oder von Komplikationen gefolgte Embolektomie ohne offensichtliche andere Risikofaktoren sollten unbedingt an ein TOS denken lassen. TOS-Operationen sind technisch nicht einfach und sollten erfahrenen Fachabteilungen vorbehalten bleiben. Die richtige Patientenselektion ist mitentscheidend für ein erfolgreiches Ergebnis. Implantationen von Stents im Bereich des Schultergürtels sollten bei Kompressionssyndromen vermieden werden. Eine weitere Möglichkeit der supraaortalen Kompression ist durch eine A. lusoria möglich.
Perfusion imaging of neuroblastoma and nephroblastoma in a paediatric population using pseudo-continuous arterial spin-labelling magnetic resonance imaging
Authors: Harteveld Anita Adriaantje , Littooij Annemieke Simone , van Noesel Max Maria , van Stralen Marijn , Bos Clemens
Published: August 2021

Objectives

To examine the feasibility of performing ASL-MRI in paediatric patients with solid abdominal tumours.

Methods

Multi-delay ASL data sets were acquired in ten paediatric patients diagnosed with either a neuroblastoma (n = 4) or nephroblastoma (n = 6) during a diagnostic MRI examination at a single visit (n = 4 at initial staging, n = 2 neuroblastoma and n = 2 nephroblastoma patients; n = 6 during follow-up, n = 2 neuroblastoma and n = 4 nephroblastoma patients). Visual evaluation and region-of-interest (ROI) analyses were performed on the processed perfusion-weighted images to assess ASL perfusion signal dynamics in the whole tumour, contralateral kidney, and tumour sub-regions with/without contrast enhancement.

Results

The majority of the included abdominal tumours presented with relatively low perfusion-weighted signal (PWS), especially compared with the highly perfused kidneys. Within the tumours, regions with high PWS were observed which, at short PLD, are possibly related to labelled blood inside vessels and at long PLD, reflect labelled blood accumulating inside tumour tissue over time. Conversely, comparison of ASL perfusion-weighted image findings with T1w enhancement after contrast administration showed that regions lacking contrast enhancement also were void of PWS.

Discussion

This pilot study demonstrates the feasibility of utilizing ASL-MRI in paediatric patients with solid abdominal tumours and provides a basis for further research on non-invasive perfusion measurements in this study population.
Health insurance literacy assessment tools: a systematic literature review
Authors: Quiroga Gutiérrez Ana Cecilia
Published: August 2021

Aim

This systematic literature review aimed to find and summarize the content and conceptual dimensions assessed by quantitative tools measuring Health Insurance Literacy (HIL) and related constructs.

Methods

Using a Peer Review of Electronic Search Strategy (PRESS) and the PRISMA guideline, a systematic literature review of studies found in ERIC, Econlit, PubMed, PsycInfo, CINAHL, and Google Scholar was performed in April 2019. Measures for which psychometric properties were evaluated were classified based on the Paez et al. conceptual model for HIL and further assessed using COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) Risk of Bias checklist and criteria for good measurement properties.

Results

Out of 123 original tools, only 19 were tested for psychometric and measurement properties; 18 of these 19 measures were developed and used in the context of Medicare. Four of the found measures tested for psychometric properties evaluated all four domains of HIL according to Paez et al.’s conceptual model; the rest of the measures assessed three (3), two (8), or one domain (4) of HIL.

Conclusion

Most measurement tools for HIL and related constructs have been developed and used in the context of the USA health insurance system, primarily in Medicare, while there is a paucity of measurement tools for private health insurances and from other countries. Furthermore, there is a lack of conceptual consistency in the way HIL is measured. Standardization of HIL measurement is crucial to further understand the role and interactions of HIL in other insurance contexts.
AL-TUNE: A Family of Methods to Effectively Tune UAV Controllers in In-flight Conditions
Authors: Horla Dariusz , Giernacki Wojciech , Báča Tomas , Spurny Vojtech , Saska Martin
Published: August 2021

In the paper, a family of novel real-time tuning methods for an unmanned aerial vehicle (UAV) altitude controller in in-flight conditions. The methods allow the controller’s gains to be adapted only on the basis of measurements from a basic sensory equipment and by constructing the optimization cost function in an on-line fashion with virtually no impeding computational complexity; in the case of the altitude controller as in this paper for a hexacopter, altitude measurements were used only. The methods are not dependent on the measurement level, and present the approach in a generally applicable form to tuning arbitrary controllers with low number of parameters. Real-world experimental flights, preceded by simulation tests, have shown which method should behave best in a noisy environment when e.g. wind disturbances act on a UAV while it is in autonomous flight. As the methods can potentially be extended to other control loops or controller types, making this a versatile, rapid-tuning tool. It has been shown that a well-tuned controller using the proposed AL-TUNE scheme outperforms controllers that are tuned just to stabilize the system. AL-TUNE provides a new way of using UAVs in terms of adaptivity to changing their dynamic properties and can be deployed rapidly. This enables new applications and extends the usability of fully autonomous UAVs, unlike other tuning methods, which basically require the availability of a UAV model. The core difference with respect to other research from the field is that other authors either use a model of a UAV to optimize the gains analytically or use machine learning techniques, what increases time consumption, whereas the presented methods offer a rapid way to tune controllers, in a reliable way, with deterministic time requirements.