bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrocytic Changes in Mitochondrial Oxidative Phosphorylation Protein Levels in Parkinson's Disease
Authors: Chen Chun , Mossman Emily , Malko Philippa , McDonald David , Blain Alasdair P. , Bone Laura , Erskine Daniel , Filby Andrew , Vincent Amy E. , Hudson Gavin , Reeve Amy K.
Published: November 2021

Background

Mitochondrial dysfunction within neurons, particularly those of the substantia nigra, has been well characterized in Parkinson's disease and is considered to be related to the pathogenesis of this disorder. Dysfunction within this important organelle has been suggested to impair neuronal communication and survival; however, the reliance of astrocytes on mitochondria and the impact of their dysfunction on this essential cell type are less well characterized.

Objective

This study aimed to uncover whether astrocytes harbor oxidative phosphorylation (OXPHOS) deficiencies in Parkinson's disease and whether these deficiencies are more likely to occur in astrocytes closely associated with neurons or those more distant from them.

Methods

Postmortem human brain sections from patients with Parkinson's disease were subjected to imaging mass cytometry for individual astrocyte analysis of key OXPHOS proteins across all five complexes.

Results

We show the variability in the astrocytic expression of mitochondrial proteins between individuals. In addition, we found that there is evidence of deficiencies in respiratory chain subunit expression within these important glia and changes, particularly in mitochondrial mass, associated with Parkinson's disease and that are not simply a consequence of advancing age.

Conclusion

Our data show that astrocytes, like neurons, are susceptible to mitochondrial defects and that these could have an impact on their reactivity and ability to support neurons in Parkinson's disease.
Patient posture correction and alignment using mixed reality visualization and the HoloLens 2
Authors: Johnson Perry B. , Jackson Amanda , Saki Mohammad , Feldman Emily , Bradley Julie
Published: November 2021

Purpose

The purpose of this study was to develop and preliminarily test a radiotherapy system for patient posture correction and alignment using mixed reality (MixR) visualization. The write‐up of this work also provides an opportunity to introduce the concepts and technology of MixR for a medical physics audience who may be unfamiliar with the topic.

Methods

A MixR application was developed for on optical‐see‐through head‐mounted display (HoloLens 2) allowing a user to simultaneously and directly view a patient and a reference hologram derived from their simulation CT scan. The hologram provides a visual reference for the exact posture needed during treatment and is initialized in relation to the origin of a radiotherapy device using marker‐based tracking. The system further provides marker‐less tracking that allows the user tofreely navigate the room as they view and align the patient from various angles. The system was preliminarily tested using both a rigid (pelvis) and nonrigid (female mannequin) anthropomorphic phantom. Each phantom was aligned via hologram and accuracy quantified using CBCT and CT.

Results

A fully realized system was developed. Rigid registration accuracy was on the order of 3.0 ± 1.5 mm based on the performance of three users repeating alignment five times each. The lateral direction showed the most variability among users and was associated with the largest off‐sets (approximately 2.0 mm). For nonrigid alignment, the MixR setup outperformed a setup based on three‐point alignment and setup photos, the latter of which showed a difference in arm position of 2 cm and a torso roll of 6–7°.

Conclusions

MixR visualization is a rapidly emerging domain that has the potential to significantly impact the field of medicine. The current application is an illustration of this and highlights the advantages of MixR for patient setup in radiation oncology. The key feature of the system is the way in which it transforms nonrigid registration into rigid registration by providing an efficient, portable, and cost‐effective mechanism for reproducing patient posture without the use of ionizing radiation. Preliminary estimates of registration accuracy indicate clinical viability and form the foundation for further development and clinical testing.
A strategy to reduce the sensitivity of inhomogeneous magnetization transfer (ihMT) imaging to radiofrequency transmit field variations at 3 T
Authors: Soustelle Lucas , Troalen Thomas , Hertanu Andreea , Mchinda Samira , Ranjeva Jean‐Philippe , Guye Maxime , Varma Gopal , Alsop David C. , Duhamel Guillaume , Girard Olivier M.
Published: November 2021

Purpose

To minimize the sensitivity of inhomogeneous magnetization transfer gradient‐echo (ihMT‐GRE) imaging to radiofrequency (RF) transmit field () inhomogeneities at 3 T.

Methods

The ihMT‐GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global drop. The resulting relative variations (δihMTR) were evaluated voxelwise as a function of the local distribution. The reproducibility of the protocol providing minimal bias was assessed in a test‐retest experiment.

Results

In line with simulations, ihMT‐GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the inhomogeneity effects in the human WM. Under the optimal conditions of 350‐ms TR and 3‐µT root mean square (RMS) saturation power, 73% of all WM voxels presented δihMTR below 10%. Reproducibility analysis yielded a close‐to‐zero systematic bias (ΔihMTR = −0.081%) and a high correlation (ρ² = 0.977) between test and retest experiments.

Conclusion

Concentrating RF saturation energy in ihMT‐GRE sequences mitigates the sensitivity of the ihMTR to variations and allows for clinical‐ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra‐high field applications.
The impact of action observation and motor imagery on the aesthetic preference of Chinese calligraphy
Authors: He Mingcheng , He Xianyou , Zheng Zixin , Deng Jiamin , Wu Chenjing
Published: November 2021

The creation of artwork requires motor activity. However, few empirical studies have directly explored the relationship between the experience of an artist's action and aesthetic experience. This study aimed to examine the effect of observing and imagery of the artist's action on the participants’ aesthetic preferences. In Experiment 1 and 2, we took hard‐pen and brush‐pen Chinese calligraphy images as the stimulus, respectively, to explore the influence of action observation on the aesthetic preference by manipulating the artists’ actions. The results of both Experiment 1 and 2 show that when participants observed the artists’ actions, they tended to report a higher preference for calligraphy images compared with the control condition. In Experiments 3 and 4, we used instructions to manipulate the motor imagery tasks and investigated the effect of imaging the artist's action on the participants’ aesthetic preferences. The results showed that both kinesthetic imagery and visual imagery increased the participants’ preference. In general, our study shows that both action observation and motor imagery contribute to participants’ aesthetic preferences. The results are discussed in terms of how artists’ actions possibly influence the aesthetic preference of Chinese calligraphy.
The effect of graph standardization on intervention evaluation of practitioner‐created graphs
Authors: Lewis Heather H. J. , Radley Keith C , Dart Evan H.
Published: November 2021

Single‐case design (SCD) is frequently utilized in applied contexts, such as schools or clinics, due to its utility in evaluating individual intervention effects of students. Data collected in SCD are often displayed in a linear graph, which can vary drastically in their construction leading to inconsistencies in rater interpretation. This has led to a need for a standardized format for linear graphs for practitioners and researchers to follow when constructing graphs. The purpose of this study was both to evaluate how well practitioner‐created graphs adhered to Standard Assembly (SA) guidelines and to investigate visual analytic differences in graphs generated by practitioners and the same data replotted in adherence to SA guidelines. Practitioner graphs were collected from fourteen practicing school psychologists and evaluated against SA guidelines. Graphs were found to have vast differences in graph characteristics. Twenty‐seven participants, faculty members with experience in SCD, were asked to evaluate 32 graphs—16 of which were practitioner created and the other 16 being the same data sets regraphed according to SA standards. Participants were asked to rate the interpretability of each graph and evaluate the magnitude of the intervention effect. Results indicate that there were no significant differences between the practitioner‐created graphs and SA graphs in intervention effect estimates, but the SA graphs were rated as significantly more interpretable.
Three‐dimensional gynaecological ultrasound part two: A pictorial essay
Authors: Deslandes Alison , Croft Anthea , Panuccio Catrina
Published: November 2021

Three‐dimensional ultrasound (3DUS) is becoming a standard part of obstetric and gynaecological ultrasound examinations. With most high‐end ultrasound systems now incorporating three‐dimensional functionality, the technology can be used to enhance and/or confirm a diagnosis in many gynaecological pathologies. Part one of this two‐part series covered the technical aspects of performing three‐dimensional gynaecological ultrasound. This paper, part two, presents a pictorial essay of 3DUS in gynaecological imaging serving to educate sonographers and other ultrasound users on the typical appearance of some common, and not so common ultrasound findings.
Service life of reinforced concrete structures made with blended cements and exposed in urban environment
Authors: Lollini Federica , Redaelli Elena
Published: November 2021

Carbonation‐induced corrosion is one of the main causes of degradation of reinforced concrete (RC) structures exposed outdoor in urban environment. To prevent steel corrosion, a durability design, that considers both the initiation and the propagation time, is of fundamental importance. At this aim, the resistance to carbonation of concrete and the steel corrosion rate in the exposure environment need to be known. This paper reports the carbonation coefficient and the corrosion rate of 7‐day cured RC specimens made with different binders and exposed outdoor in Milan in unsheltered conditions. Corrosion rates in laboratory conditions with different temperatures and relative humidities are also reported. Experimental data were used to evaluate the service life in unsheltered condition. RC specimens made with Portland cement exhibited the lowest carbonation coefficient and corrosion rate, while specimens with 30% limestone and with 70% ground granulated blast furnace slag the highest.
Retracted: Prediction of the elastic modulus of recycled aggregate concrete applying hybrid artificial intelligence and machine learning algorithms
Authors: Zhang Qian , Afzal Mansour
Published: November 2021

Recycled aggregates (RAGs) usage in concrete is surging, inspired by environmental and economic concerns. Regarding predicting various models designed the values of modulus of elasticity (MOE) of concrete with natural aggregates and, in conclusion, they would probably be unreliable when used to concrete with RAG. In the present study, two new gray wolf multi‐layer perceptron neural networks (GWMLP) and gray wolf support vector regression (GWSVR) algorithms were proposed to predict RAG concrete's elastic modulus. About 400 records were gathered from published articles to develop these models. The results show that among the GWMLP models with different hidden layers, GWM3L with three hidden layers could get the highest score (TRS) at 39. Simultaneously, in the testing phase, the GWSVR was the first‐rank model because of the lower RMSE (0.6381), MAE (0.1541), and a larger (0.9707) compared with GWMLP models. Therefore, it can result that the GWSVR model could predict the elastic modulus of RAG concrete precisely even better than GWM3L, which is well over the accuracy of the developed models.
Torsional behavior of glass textile‐reinforced concrete beams with minimum transverse reinforcements: Experimental study
Authors: Le Dang Dung , Tran Cao Thanh Ngoc , Nguyen Huy Cuong , Nguyen Xuan Huy
Published: November 2021

Torsional tests for four concrete beams reinforced with glass fiber reinforced polymer (GFRP) bars as torsional longitudinal reinforcements and glass textile grids as torsional transverse reinforcements are conducted to study the possibility in using noncorrosive and cold‐bendable glass textile grids as minimum torsional transverse reinforcements. These beams are compared with three control beams reinforced with GFRP torsional transverse reinforcements. Two investigated variables in this experimental study are the number of layers of textile grids and the orientation of torsional transverse reinforcements. Grade 40 fine‐grained concrete is used for all tested beams. A standard pure torsional test is used to study the torsional behaviors of these beams. The experimental behaviors of the tested beams are compared in terms of recorded torque‐twist curves; strain gauge readings in transverse, longitudinal reinforcements, and concrete at critical positions; observed cracking patterns and failure modes. The experimental results are compared with the recommendations for minimum torsional transverse reinforcements in the existing design codes and guidelines such as the ACI 318‐19, EC2, ACI 440.1R‐15, and CSA S806. The comparison indicates that the existing guidelines are unsafe in estimating the minimum transverse torsional reinforcements for glass textile‐reinforced concrete beams.
Co-creating Sustainable Urban Mobility Solutions for Guests and Citizens: The Experience in the Elba Island
Authors: Sessa Carlo
Published: November 2021

This chapter illustrates a co-creation approach engaging stakeholders and citizens to develop a shared agenda of sustainable transport solutions, responding to travel needs which are qualitatively and quantitatively different for residents and tourists. The chapter is articulated in three sections. The first section illustrates the co-creation approach and the topics addressed in all six DESTINATIONS demonstration sites where this approach has been used to a greater or lesser extent. The second section describes more extensively the application of the co-creation approach in the Elba island case, illustrating the process and its main outcomes, including the definition of a strategic agenda of goals and actions included in a draft Sustainable Mobility Plan for the whole Elba island, and a hypothesis of new bus services operating in the high season co-created with the engagement of managers from the regional Public Transport Authority (Osservatorio della Mobilità—Provincia di Livorno) and from the Transport Operator (CTT-Nord). The third section discusses some lessons that can be drawn from the successes and failures of the co-creation approach in the Elba case. The application has demonstrated the feasibility and suitability of the co-creation process to effectively engage stakeholders and groups of visionary citizens (the “change agents”) in the formulation of sustainable mobility plans and agendas. On the other hand, follow-up was lacking—no formal procedures to implement decisions based on the shared agenda were initiated—and the concluding section of the chapter discusses some reasons for this failure, and possible remedies for better anchoring the co-creation approach in future policymaking
Shared Mobility Services in Malta: User Needs and Perceptions
Authors: Maas Suzanne , Attard Maria
Published: November 2021

Malta is a small island state home to nearly half a million inhabitants. It is a major tourist destination in the Mediterranean, with visitor numbers totalling 2.6 million in 2018. There are 799 vehicles for every thousand inhabitants and the modal split shows a 74.6% reliance on the car. Ownership and use of private cars are at an all-time high in Malta. This dependence on the car has increased congestion and given rise to parking issues in many localities, taken-up limited space in the urban area, increased air and noise pollution, and created accessibility problems for pedestrians and cyclists. Shared mobility services (bicycle, car, scooter sharing) have been introduced in Malta very recently. Malta is one of the case study sites in the CIVITAS DESTINATIONS project, which focused on sustainable mobility in tourist destinations. As part of the project, a survey was conducted to understand the awareness and acceptance of these shared mobility services by Maltese residents (n = 1,100). Insights from this survey used to understand user needs and perceptions in light of such mobility innovations and what might encourage people to start using them as an alternative to private car use.
Introduction
Authors: Lovell Heather
Published: November 2021

This chapter introducesUnderstanding Energy Innovation, a book that is about the process of digital innovation within the electricity sector, with a focus on the social and political. This chapter covers who the book is for, its aims and themes, summarises key theories of energy innovation, and defines smart grids. Smart grids involve the incorporation of new digital and information and communication technologies into utility infrastructures, and they are used as a case study throughout the book to explore energy innovation. The chapter concludes with a brief history of smart grids.
Networks
Authors: Lovell Heather
Published: November 2021

Social scientists study many different types of networks, from policy networks to sociotechnical networks, in order to better understand processes of change. These diverse networks have a number of characteristics in common, including interconnectedness, flows, and fragility. Exploring these characteristics in relation to smart grids helps us to better understand the social nature of energy sector innovation. In this chapter, I use these themes and concepts to assess three examples: international smart grid policy networks; a local community network on Bruny Island, Australia; and a fragile network, the digital metering programme in the State of Victoria, Australia.
Nostalgia
Authors: Lovell Heather
Published: November 2021

Nostalgia is a longing for the past and the way we remember how things used to be done, including a wish for things to stay the same. Nostalgia is a central part of understanding societal responses to change because every new technology and way of doing something is, in effect, competing with nostalgia. In this chapter, I examine how nostalgia can hamper efforts at energy innovation, particularly in terms of how it blinds us to change already under way, and how memories of certain innovations can in subtle ways encourage or hinder innovation. I explore three diverse case studies about nostalgia: memories of pioneering international smart grid experiments, scarce data about off-grid households, and big infrastructure energy solutions.
Trauma patients with SARS-CoV-2 in German ICUs during the 2nd wave of the COVID-19 pandemic
Authors: Hamsen Uwe , Waydhas Christian , Bayer Jörg , Wutzler Sebastian , Horst Klemens , Hildebrand Frank ,   Trauma Section of the German Interdisciplinary Association of Critical Care, Emergency Medicine (DIVI)
Published: November 2021

Purpose

In January and February 2021, about 4000 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) positive patients were treated daily in German intensive care units (ICUs). The number of SARS-CoV-2-positive ICU patients with trauma, however, is not known and neither whether the trauma itself or COVID-19 causes the critical illness.

Methods

A total of 173 German ICUs, representing 3068 ICU beds, participated in a survey developed by the Trauma Section of the German Interdisciplinary Association of Intensive Care Medicine (DIVI).

Results

Participating ICUs reported an overall 1-day prevalence of 20 and an overall 7-day prevalence of 35 SARS-CoV-2-positive trauma patients in the ICU. Critical illness was triggered by trauma alone in 50% of cases and by the combination of trauma and COVID-19 in 49% of cases; 70% of patients were older than 65 years and suffered from a single injury, predominantly proximal femur fractures. The distribution of patients was comparable regarding the level of care of the trauma centre (local, regional, and supra-regional).

Conclusion

The proportion of trauma patients of all SARS-CoV-2-positive critically ill patients is small (~ 1%) but relevant. There is no concentration of these patients at Level 1 trauma centres. However, the traumatic insult is the most relevant cause for ICU treatment in most of these patients. Regarding a new wave of the pandemic, adequate trauma dedicated resources and perioperative structures and expertise have to be provided for COVID-19 trauma patients.
Hit-and-run: a Swedish nationwide cohort study of serious transport accidents and convictions due to traffic offenses in obsessive–compulsive disorder
Authors: Mataix-Cols David , Fernández de la Cruz Lorena , Brander Gustaf , Andersson Erik , D’Onofrio Brian M. , Rück Christian , Larsson Henrik , Lichtenstein Paul , Sidorchuk Anna
Published: November 2021

Purpose

Individuals with obsessive–compulsive disorder (OCD) often report driving-related obsessions, such as fears of causing accidents, but the risk of transport accidents in OCD is unknown. We investigated whether individuals with OCD have an increased risk of serious transport accidents and convictions due to traffic offenses and explored the role of psychiatric comorbidities.

Methods

We included all individuals ≥ 18 years living in Sweden between 1997 and 2013 (N = 5,760,734). A total of 23,126 individuals had a diagnosis of OCD in the National Patient Register. We also identified 16,607 families with full siblings discordant for OCD. Cox proportional hazards regression models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of three outcomes in individuals with OCD, compared to unexposed individuals and their unexposed full siblings: injuries or deaths due to transport accidents, injuries or deaths due to motor vehicle accidents, and convictions related to traffic offenses. Psychiatric comorbidities were systematically adjusted for.

Results

Women, but not men, with OCD had a marginally increased risk of serious transport accidents (adjusted HR = 1.20 [95% CI 1.13–1.28]) and motor vehicle accidents (adjusted HR = 1.20 [95% CI 1.09–1.31]), compared to unaffected individuals. Neither women nor men with OCD had a significantly increased risk of convictions. The sibling comparisons showed no significant associations. When psychiatric comorbidities were adjusted for, several observed associations became non-significant or inversed (HRs and 95% CIs below one).

Conclusion

The risks of serious transport accidents and driving-related criminal convictions in OCD are negligible and heavily influenced by psychiatric comorbidity.
Organophosphorus pesticides exhibit compound specific effects in rat precision-cut lung slices (PCLS): mechanisms involved in airway response, cytotoxicity, inflammatory activation and antioxidative defense
Authors: Tigges Jonas , Worek Franz , Thiermann Horst , Wille Timo
Published: November 2021

Organophosphorus compound pesticides (OP) are widely used in pest control and might be misused for terrorist attacks. Although acetylcholinesterase (AChE) inhibition is the predominant toxic mechanism, OP may induce pneumonia and formation of lung edema after poisoning and during clinical treatment as life-threatening complication. To investigate the underlying mechanisms, rat precision-cut lung slices (PCLS) were exposed to the OP parathion, malathion and their biotransformation products paraoxon and malaoxon (100–2000 µmol/L). Airway response, metabolic activity, release of LDH, cytokine expression and oxidative stress response were analyzed. A concentration-dependent inhibition of airway relaxation was observed after exposure with the oxon but not with the thion-OP. In contrast, cytotoxic effects were observed for both forms in higher concentrations. Increased cytokine expression was observed after exposure to parathion and paraoxon (IL-6, GM-CSF, MIP-1α) and IL-6 expression was dependent on NFκB activation. Intracellular GSH levels were significantly reduced by all four tested OP but an increase in GSSG and HO-1 expression was predominantly observed after malaoxon exposure. Pretreatment with the antioxidant N-acetylcysteine reduced malaoxon but not paraoxon-induced cytotoxicity. PCLS as a 3D lung model system revealed OP-induced effects depending on the particular OP. The experimental data of this study contribute to a better understanding of OP toxicity on cellular targets and may be a possible explanation for the variety of clinical outcomes induced by different OP.
Deep learning–based denoising of low-dose SPECT myocardial perfusion images: quantitative assessment and clinical performance
Authors: Aghakhan Olia Narges , Kamali-Asl Alireza , Hariri Tabrizi Sanaz , Geramifar Parham , Sheikhzadeh Peyman , Farzanefar Saeed , Arabi Hossein , Zaidi Habib
Published: November 2021

Purpose

This work was set out to investigate the feasibility of dose reduction in SPECT myocardial perfusion imaging (MPI) without sacrificing diagnostic accuracy. A deep learning approach was proposed to synthesize full-dose images from the corresponding low-dose images at different dose reduction levels in the projection space.

Methods

Clinical SPECT-MPI images of 345 patients acquired on a dedicated cardiac SPECT camera in list-mode format were retrospectively employed to predict standard-dose from low-dose images at half-, quarter-, and one-eighth-dose levels. To simulate realistic low-dose projections, 50%, 25%, and 12.5% of the events were randomly selected from the list-mode data through applying binomial subsampling. A generative adversarial network was implemented to predict non-gated standard-dose SPECT images in the projection space at the different dose reduction levels. Well-established metrics, including peak signal-to-noise ratio (PSNR), root mean square error (RMSE), and structural similarity index metrics (SSIM) in addition to Pearson correlation coefficient analysis and clinical parameters derived from Cedars-Sinai software were used to quantitatively assess the predicted standard-dose images. For clinical evaluation, the quality of the predicted standard-dose images was evaluated by a nuclear medicine specialist using a seven-point (− 3 to + 3) grading scheme.

Results

The highest PSNR (42.49 ± 2.37) and SSIM (0.99 ± 0.01) and the lowest RMSE (1.99 ± 0.63) were achieved at a half-dose level. Pearson correlation coefficients were 0.997 ± 0.001, 0.994 ± 0.003, and 0.987 ± 0.004 for the predicted standard-dose images at half-, quarter-, and one-eighth-dose levels, respectively. Using the standard-dose images as reference, the Bland–Altman plots sketched for the Cedars-Sinai selected parameters exhibited remarkably less bias and variance in the predicted standard-dose images compared with the low-dose images at all reduced dose levels. Overall, considering the clinical assessment performed by a nuclear medicine specialist, 100%, 80%, and 11% of the predicted standard-dose images were clinically acceptable at half-, quarter-, and one-eighth-dose levels, respectively.

Conclusion

The noise was effectively suppressed by the proposed network, and the predicted standard-dose images were comparable to reference standard-dose images at half- and quarter-dose levels. However, recovery of the underlying signals/information in low-dose images beyond a quarter of the standard dose would not be feasible (due to very poor signal-to-noise ratio) which will adversely affect the clinical interpretation of the resulting images.
MoG+: a database of genomic variations across three mouse subspecies for biomedical research
Authors: Takada Toyoyuki , Fukuta Kentaro , Usuda Daiki , Kushida Tatsuya , Kondo Shinji , Kawamoto Shoko , Yoshiki Atsushi , Obata Yuichi , Fujiyama Asao , Toyoda Atsushi , Noguchi Hideki , Shiroishi Toshihiko , Masuya Hiroshi
Published: November 2021

Laboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.
Does caffeine consumption affect laparoscopic skills in a motion tracking analysis? A prospective, randomized, blinded crossover trial
Authors: von Bechtolsheim Felix , Oehme Florian , Maruschke Michael , Schmidt Sofia , Schneider Alfred , Weitz Jürgen , Distler Marius , Bodenstedt Sebastian , Funke Isabel , Speidel Stefanie , Mees Soeren Torge
Published: November 2021

Background

Coffee can increase vigilance and performance, especially during sleep deprivation. The hypothetical downside of caffeine in the surgical field is the potential interaction with the ergonomics of movement and the central nervous system. The objective of this trial was to investigate the influence of caffeine on laparoscopic performance.

Methods

Fifty laparoscopic novices participated in this prospective randomized, blinded crossover trial and were trained in a modified FLS curriculum until reaching a predefined proficiency. Subsequently, all participants performed four laparoscopic tasks twice, once after consumption of a placebo and once after a caffeinated (200 mg) beverage.

Comparative analysis was performed between the cohorts. Primary endpoint analysis included task time, task errors, OSATS score and a performance analysis with an instrument motion analysis (IMA) system.

Results

Fifty participants completed the study. Sixty-eight percent of participants drank coffee daily. The time to completion for each task was comparable between the caffeine and placebo cohorts for PEG transfer (119 s vs 121 s; p = 0.73), precise cutting (157 s vs 163 s; p = 0.74), gallbladder resection (190 s vs 173 s; p = 0.6) and surgical knot (171 s vs 189 s; p = 0.68). The instrument motion analysis showed no significant differences between the caffeine and placebo groups in any parameters: instrument volume, path length, idle, velocity, acceleration, and instrument out of view. Additionally, OSATS scores did not differ between groups, regardless of task. Major errors occurred similarly in both groups, except for one error criteria during the circle cutting task, which occurred significantly more often in the caffeine group (34% vs. 16%, p < 0.05).

Conclusion

The objective IMA and performance scores of laparoscopic skills revealed that caffeine consumption does not enhance or impair the overall laparoscopic performance of surgical novices. The occurrence of major errors is not conclusive but could be negatively influenced in part by caffeine intake.
Comparison of 180° anti-reflux mucosectomy versus 270° anti-reflux mucosectomy for treatment of refractory gastroesophageal reflux disease: a retrospective study
Authors: Yang Xinyi , Tan Jiacheng , Liu Yang , Feng Yadong , Shi Ruihua
Published: November 2021

Background

Anti-reflux mucosectomy (ARMS) is a novel endoscopic treatment for refractory gastroesophageal reflux disease (rGERD). Several studies have validated its safety and effectiveness, but postoperative dysphagia remains in concern. Since the influence of different resection ranges on efficacy and complications of ARMS has rarely been studied, this study aimed to compare outcomes of 180°ARMS and 270°ARMS in treatment of rGERD.

Methods

This study was conducted from August 2017 to September 2020. 39 eligible patients underwent either 180° ARMS or 270° ARMS and followed up at 6 months postoperation. Primary outcome measure was assessed by Gastroesophageal Reflux Disease Questionnaire (GERD-Q). Secondary outcomes included quality of life, PPI use, gastroesophageal flap valve grade, presence of reflux esophagitis, acid exposure time (AET), distal contractile integral (DCI), and integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) and complication rate. Per-protocol analysis was performed.

Results

Among 39 patients, 18 underwent 180° ARMS, while 21 underwent 270° ARMS. At postoperative 6 months follow-up period, primary outcome showed no significant difference between two groups (p = 0.34). Similarly, no significant difference was demonstrated between groups regarding most secondary outcomes except for fewer complaints of newly dysphagia in 180° ARMS group. No other serious complications were observed in both groups.

Conclusion

Although 180° ARMS and 270° ARMS could be equally effective for treatment of rGERD, 180° ARMS might be more recommended due to lower incidence of newly post-procedural dysphagia.
The effectiveness and safety of low-level laser therapy on breast cancer–related lymphedema: An overview and update of systematic reviews
Authors: Wang Yuping , Ge Yonggui , Xing Wenting , Liu Junping , Wu Jiqi , Lin Haijuan , Lu Yaqin
Published: November 2021

The objective of our overview of systematic reviews was to critically analyze the evidence from existing systematic reviews investigating the effectiveness and safety of low-level laser therapy (LLLT) in patients with breast cancer–related lymphedema (BCRL). In addition, an updated and comprehensive systematic review was conducted, which aimed to provide updated evidence about this topic. PubMed, EMBASE, and Cochrane Library databases were systematically searched for systematic reviews and randomized controlled trials (RCTs) investigating the effectiveness and safety of LLLT in patients with BCRL. The methodological quality for each of included systematic reviews or RCTs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) tool or Cochrane risk of bias tool, respectively. The updated systematic review separately compared the effectiveness of LLLT to each of active or negative interventions. Data were pooled with random-effects models for each outcome per comparison. The evidence quality of outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) or GRADE-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) for quantitative studies and qualitative studies, respectively. Seven systematic reviews and ten RCTs met the eligibility criteria. Conflicting results regarding the effectiveness of LLLT were presented by the overview of systematic reviews. The AMSTAR 2 showed that the methodological quality of included systematic reviews was low or critically low quality due to one or more critical weaknesses. The GRADE and GRADE-CERQual showed that the evidence quality was low to very low for most outcomes. The updated systematic review showed that LLLT may offer additional benefits as compared to compression therapies (pneumatic compression or compression bandage), placebo laser, or no treatment for patients with BCRL. However, when compared to other types of active interventions, LLLT did not improve outcomes significantly. None of the treatment-related adverse event was reported. Many trials had a high or unclear risk of bias for two or more items, and our updated systematic review showed low quality of evidence per outcome using GRADE approach. Due to insufficient data and poor quality of evidence, there is uncertain to reach these conclusions that LLLT is superior to another active or negative intervention and is safe. More RCTs of high methodological quality, with large sample sizes and long-term follow-up, are needed to inform clinical guidelines and routine practice.
Real-world use of enzalutamide in men with nonmetastatic castration-resistant prostate cancer in Japan
Authors: Yokomizo Akira , Yonese Junji , Egawa Shin , Fukuhara Hiroshi , Uemura Hiroji , Nishimura Kazuo , Nagata Masayoshi , Saito Atsushi , Lee Takumi , Yamaguchi Susumu , Nonomura Norio
Published: November 2021

Background

The purpose of the study is to evaluate real-world effectiveness and safety of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in Japan.

Methods

This was a retrospective evaluation of medical records from men in Japan who started enzalutamide treatment from November 1, 2014, to March 31, 2018, and received androgen deprivation therapy throughout. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included PSA response rate, time to first use of new antineoplastic therapy, time to first use of cytotoxic chemotherapy, and enzalutamide treatment duration. An exploratory analysis of metastasis-free survival (MFS) was also performed. Adverse events (AEs) were analyzed to assess safety.

Results

Based on data from medical records of 205 men in Japan, median time to PSA progression was 27 months (95% confidence interval [CI] 19–not reached [NR]), with 82.5% and 52.0% of men achieving PSA response rates of ≥ 50% and ≥ 90%, respectively. Median time to first use of new antineoplastic therapy was 36 months (95% CI 27−NR) and median enzalutamide treatment duration was 13 months (interquartile range: 7–24). Median time to first use of cytotoxic chemotherapy was NR (95% CI 41−NR). Median MFS was 29 months (95% CI 23−35). In total, 51.7% of men experienced AEs, with malaise (18.5%), decreased appetite (10.7%), and nausea (4.9%) the most frequently reported.

Conclusions

This is the first study to demonstrate the real-world effectiveness and safety of enzalutamide in men with nmCRPC in Japan, further informing healthcare providers about available treatment options for this patient population.
Cost–utility analysis of risk-reducing strategies to prevent breast and ovarian cancer in BRCA-mutation carriers in Switzerland
Authors: Bommer Claudine , Lupatsch Judith , Bürki Nicole , Schwenkglenks Matthias
Published: November 2021

Objective

We aimed to identify the most cost-effective of all prophylactic measures available in Switzerland for women not yet affected by breast and ovarian cancer who tested positive for a BRCA1/2 mutation.

Methods

Prophylactic bilateral mastectomy (PBM), salpingo-oophorectomy (PBSO), combined PBM&PBSO and chemoprevention (CP) initiated at age 40 years were compared with intensified surveillance (IS). A Markov model with a life-long time horizon was developed from the perspective of the Swiss healthcare system using mainly literature-derived data to evaluate costs, quality-adjusted life years (QALYs) and survival. Costs and QALYs were discounted by 3% per year. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses.

Results

All prophylactic measures were found to be cost-saving with an increase in QALYs and life years (LYs) compared to IS. PBM&PBSO were found to be most cost-effective and dominated all other strategies in women with a BRCA1 or BRCA2 mutation. Lifetime costs averaged to 141,293 EUR and 14.5 QALYs per woman with a BRCA1 mutation under IS, versus 76,639 EUR and 19.2 QALYs for PBM&PBSO. Corresponding results for IS per woman with a BRCA2 mutation were 102,245 EUR and 15.5 QALYs, versus 60,770 EUR and 19.9 QALYs for PBM&PBSO. The results were found to be robust in sensitivity analysis; no change in the dominant strategy for either BRCA-mutation was observed.

Conclusion

All more invasive strategies were found to increase life expectancy and quality of life of women with a BRCA1 or BRCA2 mutation and were cost-saving for the Swiss healthcare system compared to IS.
Carbothermal reduction of mill scales formed on steel billets during continuous casting
Authors: Suarez S. M. Espinoza , Borja-Castro L. E. , Valerio-Cuadros M. I. , Domínguez A. Bustamante , Cabrera-Tinoco H. A. , Huaman E. , Valencia-Bedregal R. A. , Zhao Xiaoli , Zhang Youyun , Zhang Deliang , Barnes C. H. W. , Valladares L. De Los Santos
Published: November 2021

A billet is a bar made from crude steel which surface contains scales which are rich in iron oxides. This study presents the carbothermal reduction of the scales formed in steel billets. The process included the reaction of the iron oxides contents with carbon (in ratio 5:1) and annealing in a tubular furnace under argon atmosphere. The occurred reactions are discussed using thermodynamic calculations and thermal analysis which indicate a three-stage reduction process Fe3O4 ➔ FeO ➔ Fe3C ➔α-Fe with intermediate reactions at the interval temperature 960 and 1300 °C. The X-ray diffraction confirms the reduction to α-Fe with minor presence of unreacted C, magnetite and wustite. Mössbauer spectroscopy analysis was performed at room temperature where a typical sextet corresponding to the dominant α-Fe is shown as well as wustite, magnetite and cementite to a lesser extent. The magnetization measurements confirm the ferromagnetic state corresponding to the α-Fe.
Field evidence of UK wild bird exposure to fludioxonil and extrapolation to other pesticides used as seed treatments
Authors: de Montaigu Cannelle Tassin , Goulson Dave
Published: November 2021

We determine the exposure of wild birds to pesticides via consumption of fludioxonil-treated winter wheat seeds following autumn drilling. We recorded the density of seeds left on the soil surface, bird density, and consumption of pesticide-treated seed by birds using camera traps. We calculated the dose ingested by each bird species in a single feeding bout and if they ate treated seeds exclusively for 1 day. We extrapolated this for an additional 19 pesticides commonly used as seed treatments, assuming equal consumption rates. All three fields contained grains on the soil surface (mean 7.14 seeds/m2on sowing day). In total, 1,374 granivorous birds spanning 18 different species were observed in the fields, with 11 species filmed eating the seeds. Fludioxonil appears to pose a low risk to birds, with <1.14% of the LD50 potentially ingested by a bird for a daily maximum amount of seeds. Analysis of the further 19 pesticides commonly used as seed dressings suggests that the neonicotinoid insecticides imidacloprid, clothianidin, and thiamethoxam represent the highest risk for granivorous birds. For example, chaffinch (Fringilla coelebs) could consume 63% of LD50 of imidacloprid in a single feeding bout, and 370% in a day. Further investigation is clearly required to determine whether seeds treated with these other pesticides are consumed as readily as those treated with fludioxonil, as if so this is likely to cause significant harm.
Diabetes mellitus correlates with increased biological age as indicated by clinical biomarkers
Authors: Bahour Nadine , Cortez Briana , Pan Hui , Shah Hetal , Doria Alessandro , Aguayo-Mazzucato Cristina
Published: November 2021

Chronological age (CA) is determined by time of birth, whereas biological age (BA) is based on changes on a cellular level and strongly correlates with morbidity, mortality, and longevity. Type 2 diabetes (T2D) associates with increased morbidity and mortality; thus, we hypothesized that BA would be increased and calculated it from biomarkers collected at routine clinical visits. Deidentified data was obtained from three cohorts of patients (20–80 years old)—T2D, type 1 diabetes (T1D), and prediabetes—and compared to gender- and age-matched non-diabetics. Eight clinical biomarkers that correlated with CA in people without diabetes were used to calculate BA using the Klemera and Doubal method 1 (KDM1) and multiple linear regression (MLR). The phenotypic age (PhAge) formula was used with its predetermined biomarkers. BA of people with T2D was, on average, 12.02 years higher than people without diabetes (p < 0.0001), while BA in T1D was 16.32 years higher (p < 0.0001). Results were corroborated using MLR and PhAge. The biomarkers with the strongest correlation to increased BA in T2D using KDM were A1c (R2 = 0.23, p < 0.0001) and systolic blood pressure (R2 = 0.21, p < 0.0001). BMI had a positive correlation to BA in non-diabetes subjects but disappeared in those with diabetes. Mortality data using the ACCORD trial was used to validate our results and showed a significant correlation between higher BA and decreased survival. In conclusion, BA is increased in people with diabetes, irrespective of pathophysiology, and to a lesser extent in prediabetes.
Discrete-time inverse linear quadratic optimal control over finite time-horizon under noisy output measurements
Authors: Zhang Han , Li Yibei , Hu Xiaoming
Published: November 2021

In this paper, the problem of inverse quadratic optimal control over finite time-horizon for discrete-time linear systems is considered. Our goal is to recover the corresponding quadratic objective function using noisy observations. First, the identifiability of the model structure for the inverse optimal control problem is analyzed under relative degree assumption and we show the model structure is strictly globally identifiable. Next, we study the inverse optimal control problem whose initial state distribution and the observation noise distribution are unknown, yet the exact observations on the initial states are available. We formulate the problem as a risk minimization problem and approximate the problem using empirical average. It is further shown that the solution to the approximated problem is statistically consistent under the assumption of relative degrees. We then study the case where the exact observations on the initial states are not available, yet the observation noises are known to be white Gaussian distributed and the distribution of the initial state is also Gaussian (with unknown mean and covariance). EM-algorithm is used to estimate the parameters in the objective function. The effectiveness of our results are demonstrated by numerical examples.