bluuebunny/crossref_metadata_2025 huggingface dataset:
Correcting for the effect of ambient pressure fluctuations on measured output from a linear accelerator with a sealed monitor chamber
Authors: Takagi Masafumi , Narita Yuichiro , Chai Hongbo , Kimura Tomomi , Soda Kenji , Kattou Keiichi
Published: January 2023

Objective. Ambient pressure fluctuations deform the walls of a sealed monitor chamber in a linear accelerator (LINAC) and affect the output. This study retrospectively quantified the output variations accompanying ambient pressure fluctuations in a LINAC equipped with a sealed monitor chamber and introduced a novel approach of calculating the adjusted output free from the effect of ambient pressure fluctuations. Approach. The output data for the 6 MV and 10 MV X-rays measured between March 2014 and September 2015 were analysed. This period was further divided into four sub-periods according to the output calibrations. Output behaviours were modelled using multiple regression analysis with ambient pressure and the time elapsed since the last calibration as explanatory variables. The output variations accompanying ambient pressure fluctuations were calculated using regression parameters and were subtracted from the measured outputs to obtain the adjusted outputs. Main results. The partial regression coefficients for ambient pressure varied from −2.3 × 10−4 to −1.8 × 10−4 cGy/MU/hPa for 6 MV and from −1.9 × 10−4 to −1.2 × 10−4 cGy/MU/hPa for 10 MV X-rays. These partial regression coefficient values were comparable among the four sub-periods and the two x-ray energies, respectively. These findings suggest that the degree of the output variations accompanying ambient pressure fluctuations is independent of x-ray energies and is determined by the internal structure of the chamber and the pressure differential between the inside and outside of the chamber. The adjusted outputs showed a better fit with the time trend line than the measured outputs. Significance. This study demonstrates a novel procedure for obtaining the adjusted outputs and allows precise observation of the output behaviours of a LINAC equipped with a sealed monitor chamber. Combined observation of the measured and adjusted output facilitates the detection of output anomalies, thus contributing to quality control (QC) of LINACs.
Roadmap for optical tweezers
Authors: Volpe Giovanni , Maragò Onofrio M , Rubinsztein-Dunlop Halina , Pesce Giuseppe , Stilgoe Alexander B , Volpe Giorgio , Tkachenko Georgiy , Truong Viet Giang , Chormaic Síle Nic , Kalantarifard Fatemeh , Elahi Parviz , Käll Mikael , Callegari Agnese , Marqués Manuel I , Neves Antonio A R , Moreira Wendel L , Fontes Adriana , Cesar Carlos L , Saija Rosalba , Saidi Abir , Beck Paul , Eismann Jörg S , Banzer Peter , Fernandes Thales F D , Pedaci Francesco , Bowen Warwick P , Vaippully Rahul , Lokesh Muruga , Roy Basudev , Thalhammer-Thurner Gregor , Ritsch-Marte Monika , García Laura Pérez , Arzola Alejandro V , Castillo Isaac Pérez , Argun Aykut , Muenker Till M , Vos Bart E , Betz Timo , Cristiani Ilaria , Minzioni Paolo , Reece Peter J , Wang Fan , McGloin David , Ndukaife Justus C , Quidant Romain , Roberts Reece P , Laplane Cyril , Volz Thomas , Gordon Reuven , Hanstorp Dag , Marmolejo Javier Tello , Bruce Graham D , Dholakia Kishan , Li Tongcang , Brzobohatý Oto , Simpson Stephen H , Zemánek Pavel , Ritort Felix , Roichman Yael , Bobkova Valeriia , Wittkowski Raphael , Denz Cornelia , Kumar G V Pavan , Foti Antonino , Donato Maria Grazia , Gucciardi Pietro G , Gardini Lucia , Bianchi Giulio , Kashchuk Anatolii V , Capitanio Marco , Paterson Lynn , Jones Philip H , Berg-Sørensen Kirstine , Barooji Younes F , Oddershede Lene B , Pouladian Pegah , Preece Daryl , Adiels Caroline Beck , De Luca Anna Chiara , Magazzù Alessandro , Bronte Ciriza David , Iatì Maria Antonia , Swartzlander Grover A
Published: January 2023

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects, ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in the life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nano-particle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration.
Soft robotics for physical simulators, artificial organs and implantable assistive devices
Authors: Zrinscak Debora , Lorenzon Lucrezia , Maselli Martina , Cianchetti Matteo
Published: January 2023

In recent years, soft robotics technologies enabled the development of a new generation of biomedical devices. The combination of elastomeric materials with tunable properties and muscle-like motions paved the way toward more realistic phantoms and innovative soft active implants as artificial organs or assistive mechanisms. This review collects the most relevant studies in the field, giving some insights about their distribution in the past 10 years, their level of development and opening a discussion about the most commonly employed materials and actuating technologies. The reported results show some promising trends, highlighting that the soft robotics approach can help replicate specific material characteristics in the case of static or passive organs but also reproduce peculiar natural motion patterns for the realization of dynamic phantoms or implants. At the same time, some important challenges still need to be addressed. However, by joining forces with other research fields and disciplines, it will be possible to get one step closer to the development of complex, active, self-sensing and deformable structures able to replicate as closely as possible the typical properties and functionalities of our natural body organs.
Accurately modeling biased random walks on weighted networks usingnode2vec+
Authors: Liu Renming , Hirn Matthew , Krishnan Arjun
Published: January 2023

Motivation

Accurately representing biological networks in a low-dimensional space, also known as network embedding, is a critical step in network-based machine learning and is carried out widely using node2vec, an unsupervised method based on biased random walks. However, while many networks, including functional gene interaction networks, are dense, weighted graphs, node2vec is fundamentally limited in its ability to use edge weights during the biased random walk generation process, thus under-using all the information in the network.

Results

Here, we present node2vec+, a natural extension of node2vec that accounts for edge weights when calculating walk biases and reduces to node2vec in the cases of unweighted graphs or unbiased walks. Using two synthetic datasets, we empirically show that node2vec+ is more robust to additive noise than node2vec in weighted graphs. Then, using genome-scale functional gene networks to solve a wide range of gene function and disease prediction tasks, we demonstrate the superior performance of node2vec+ over node2vec in the case of weighted graphs. Notably, due to the limited amount of training data in the gene classification tasks, graph neural networks such as GCN and GraphSAGE are outperformed by both node2vec and node2vec+.

Availability and implementation

The data and code are available on GitHub at https://github.com/krishnanlab/node2vecplus_benchmarks. All additional data underlying this article are available on Zenodo at https://doi.org/10.5281/zenodo.7007164.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical significance of the rivaroxaban–dronedarone interaction: insights from physiologically based pharmacokinetic modelling
Authors: Hügl Burkhard , Horlitz Marc , Fischer Kerstin , Kreutz Reinhold
Published: January 2023

Patients with atrial fibrillation may require rhythm control therapy in addition to anticoagulation therapy for the prevention of stroke. Since 2012, the European Society of Cardiology and European Heart Rhythm Association guidelines have recommended non-vitamin K antagonist oral anticoagulants, including rivaroxaban, for the prevention of stroke in patients with atrial fibrillation. During the same period, these guidelines have also recommended dronedarone or amiodarone as second-line rhythm control agents in certain patients with atrial fibrillation and no contraindications. Amiodarone and dronedarone both strongly inhibit P-glycoprotein, while dronedarone is a moderate and amiodarone a weak inhibitor of cytochrome P450 3A4 (CYP3A4). Based on these data and evidence from physiologically based pharmacokinetic modelling, amiodarone and dronedarone are expected to have similar effects on rivaroxaban exposure resulting from P-glycoprotein and CYP3A4 inhibition. However, the rivaroxaban label recommends against the concomitant use of dronedarone, but not amiodarone, citing a lack of evidence on the concomitant use of rivaroxaban and dronedarone as the reason for the different recommendations. In this report, we discuss evidence from clinical studies and physiologically based pharmacokinetic modelling on the potential for increased rivaroxaban exposure resulting from drug–drug interaction between rivaroxaban and dronedarone or amiodarone. The current evidence supports the same clinical status and concomitant use of either amiodarone or dronedarone with rivaroxaban, which could be considered in future recommendations.
Queer Hostages for Hanoi
Authors: Duberman Martin
Published: January 2023

This memoir of peace activism in the United States in the early 1970s, as the Vietnam war was drawing to a close, focuses on the difficulties of sustaining an effective anti-war campaign. It describes several key protests: sit-ins outside the Senate chamber in Washington, after one of which the writer was briefly jailed; the attempt to secure the Nobel Peace Prize for all those Americans who refused to fight in Vietnam; and in particular a keenly debated and eventually unsuccessful initiative, led by sexual dissidents, to enlist prominent Americans to travel to Hanoi to deter American bombing of the North Vietnamese capital. Based on his own experiences and recollections, Martin Duberman discusses the overlap between the peace movement, the emerging gay and feminist movements, and the sporadic attempts to ally with the Black liberation movement. He speculates, as well, about the overall effectiveness of the anti-war movement in helping to bring the disastrous conflict in Vietnam – which claimed more than two-million lives – to a close.
On Figaro’s Alleged Minuet and Some Challenges and Opportunities of Topic Theory
Authors: Sánchez-Kisielewska Olga
Published: January 2023

Wye Allanbrook (1983) famously observed a humorous allusion to the minuet style in the aria “Se vuol ballare” from Le Nozze di Figaro. This article provides a close reading of the opening measures of Figaro’s cavatina, investigating how this music may or may not have elicited associations with minuet music for Mozart’s intended audience. A close comparison of the musical features of “Se vuol ballare”—including phrase structure, hypermeter, and rhythm—with those of danceable minuets of the time will show that Mozart’s tune is anything but a prototypical member of the category. Instead of (or in addition to) a minuet, historical listeners might have perceived an allusion to another familiar dance: the contredanse. Such an association would have triggered different ideas about social class and afforded an alternative ironic reading of the passage. By challenging a widely accepted interpretation, this case study addresses the broader issue of how to identify topics (as a cognitive process of categorization) and explores avenues for practicing topical analysis in increasingly transparent and historically sensitive ways.
Challenges implementing recent recommendations of daily formula supplementation for allergy prevention and practical real-world options
Authors: Ridley Denise , Abrams Elissa M , Wong Peter , Chan Edmond S
Published: January 2023

The Canadian Paediatric Society’s Position statement ‘Dietary exposures and allergy prevention in high-risk infants’ December 2021 provides recommendations for regular ingestion of cow’s milk protein (CMP) once introduced in early infancy. These recommendations are based on evidence from randomized controlled trials (RCTs) where researchers supported participants in adhering to diet recommendations. Real-life dilemmas that relate to dietary adherence including cost, food wastage, and practicality are not addressed and are the crux of where ­evidence-based recommendations fail. This commentary highlights the difficulties in carrying out the proposed recommendation for regular ingestion of CMP in practice and offers three practical real-world options instead.
A generative adversarial model of intrusive imagery in the human brain
Authors: Cushing Cody A , Dawes Alexei J , Hofmann Stefan G , Lau Hakwan , LeDoux Joseph E , Taschereau-Dumouchel Vincent
Published: January 2023

The mechanisms underlying the subjective experiences of mental disorders remain poorly understood. This is partly due to long-standing over-emphasis on behavioral and physiological symptoms and a de-emphasis of the patient’s subjective experiences when searching for treatments. Here, we provide a new perspective on the subjective experience of mental disorders based on findings in neuroscience and artificial intelligence (AI). Specifically, we propose the subjective experience that occurs in visual imagination depends on mechanisms similar to generative adversarial networks that have recently been developed in AI. The basic idea is that a generator network fabricates a prediction of the world, and a discriminator network determines whether it is likely real or not. Given that similar adversarial interactions occur in the two major visual pathways of perception in people, we explored whether we could leverage this AI-inspired approach to better understand the intrusive imagery experiences of patients suffering from mental illnesses such as post-traumatic stress disorder (PTSD) and acute stress disorder. In our model, a nonconscious visual pathway generates predictions of the environment that influence the parallel but interacting conscious pathway. We propose that in some patients, an imbalance in these adversarial interactions leads to an overrepresentation of disturbing content relative to current reality, and results in debilitating flashbacks. By situating the subjective experience of intrusive visual imagery in the adversarial interaction of these visual pathways, we propose testable hypotheses on novel mechanisms and clinical applications for controlling and possibly preventing symptoms resulting from intrusive imagery.
Experimental measurements and CFD modelling of hydroxyapatite scaffolds in perfusion bioreactors for bone regeneration
Authors: d’Adamo Alessandro , Salerno Elisabetta , Corda Giuseppe , Ongaro Claudio , Zardin Barbara , Ruffini Andrea , Orlandi Giulia , Bertacchini Jessika , Angeli Diego
Published: January 2023

In the field of bone tissue engineering, particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to in vivo ones, e.g. by artificially producing mechanical stresses promoting a biological response (mechanotransduction). Of particular relevance in this context are the effects generated by the flow shear stress, which governs the nutrients delivery rate to the growing cells and which can be controlled in perfusion reactors. However, the introduction of 3D scaffolds complicates the direct measurement of the generated shear stress on the adhered cells inside the matrix, thus jeopardizing the potential of using multi-dimensional matrices. In this study, an anisotropic hydroxyapatite-based set of scaffolds is considered as a 3D biomimetic support for bone cells deposition and growth. Measurements of sample-specific flow resistance are carried out using a perfusion system, accompanied by a visual characterization of the material structure. From the obtained results, a subset of three samples is reproduced using 3D-Computational Fluid Dynamics (CFD) techniques and the models are validated by virtually replicating the flow resistance measurement. Once a good agreement is found, the analysis of flow-induced shear stress on the inner B-HA structure is carried out based on simulation results. Finally, a statistical analysis leads to a simplified expression to correlate the flow resistance with the entity and extensions of wall shear stress inside the scaffold. The study applies CFD to overcome the limitations of experiments, allowing for an advancement in multi-dimensional cell cultures by elucidating the flow conditions in 3D reactors.
Muscle injury induces an increase in total and non-rapid eye movement sleep time
Authors: Vanneau T , Quiquempoix M , Erkel M C , Drogou C , Trignol A , Sauvet F , Léger D , Gomez-Merino D , Chennaoui M
Published: January 2023

Study Objectives

This study describes macro- and micro-sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms.

Methods

We recorded the electroencephalogram (EEG)/electromyogram (EMG) of 24 Wistar rats before and after induction of tibialis anterior muscle injury (n = 8 per group: control, control + buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), insulin-like growth factor-1 (IGF-1), and brain and muscle ARNT-like 1 (BMAL1) in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at day +2 after injury from non-EEG/EMG implanted rats.

Results

Muscle injury induces a significant increase in TST at 48 and 72 h post-injury, specific to non-rapid eye movement (NREM) sleep. These increases occur during the dark period and are associated with the higher stability of sleep over 24 h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1β, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time.

Conclusion

Muscle injury induces an increase in total sleep time at 48- and 72-h post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 h.
Adapting adaptive design methods to accelerate adoption of a digital asthma management intervention
Authors: Bender Bruce G , Cvietusa Peter J , Goodrich Glenn K , King Diane K , Shoup Jo Ann
Published: January 2023

Investigators conducting translational research in real-world settings may experience changes that create challenges to the successful completion of the trial as well as post-trial adoption and implementation. Adaptive designs support translational research by systematically adapting content and methods to meet the needs of target populations, settings and contexts. This manuscript describes an adaptive implementation research model that provides strategies for changing content, delivery processes, and research methods to correct course when anticipated and unanticipated circumstances occur during a pragmatic trial. The Breathewell Program included two large pragmatic trials of the effectiveness of a digital communication technology intervention to improve symptom management and medication adherence in asthma care. The first trial targeted parents of children with asthma; the second targeted adults with asthma. Adaptations were made iteratively to adjust to dynamic conditions within the healthcare setting, informed by prospectively collected stakeholder input, and were categorized retrospectively by the authors as proactive or reactive. Study outcomes demonstrated improved treatment adherence and clinical efficiency. Kaiser Permanente Colorado, the setting for both studies, adopted the speech recognition intervention into routine care, however, both interventions required numerous adaptations, including changes to target population, intervention content, and internal workflows. Proactive and reactive adaptations assured that both trials were successfully completed. Adaptive research designs will continue to provide an important pathway to move healthcare delivery research into practice while conducting ongoing effectiveness evaluation.
First Report of Mosaic Disease of Crape Myrtle Caused by Watermelon Mosaic Virus in Jiangsu Province in China
Authors: Hang Chen , Huang Cheng-Rui , Zhu Feng
Published: January 2023

The crape myrtle ( Lagerstroemia indica) is a deciduous shrub that has become a popular landscape tree on public and private properties. However, crape myrtle is constantly subjected to multiple pathogen attacks, which severely affect the yield and quality and cause economic losses. In June 2019, foliar virus-like symptoms of chlorosis and mosaic were observed on crape myrtle in Yangzhou city, Jiangsu Province, East China. Leaf samples were collected from symptomatic plants. All samples were assayed by western blotting using a polyclonal antiserum to cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) and a double-antibody sandwich-ELISA assay for watermelon mosaic virus (WMV). The results revealed that all samples reacted positively with the WMV but negatively with CMV and TMV. RT-PCR was employed to confirm the obtained serological results. An amplicon of 288 bp was obtained from all the samples. Nucleotide BLAST analysis revealed that the sequence had 98.25 to 100% nucleotide identity to eight WMV isolate sequences available in GenBank. A pathogenicity assay was conducted using virus-free Nicotiana benthamiana seedlings inoculated with sap extracted from symptomatic crape myrtle leaves. Systemic infection of WMV was also confirmed in N. benthamiana by RT-PCR. On the basis of the data from serological and molecular analyses, the virus was identified as WMV. To our knowledge, this is the first report of WMV on crape myrtle in Jiangsu Province in China.
Integration of Sclerotinia sclerotiorum-Targeted Biofungicides Coniothyrium minitans and Bacillus amyloliquefaciens into Season-Long Soybean Pest Management Practices in Indiana
Authors: Conrad Audrey M. , Johnson William G. , Cruz C. D. , Telenko Darcy E. P.
Published: January 2023

Two biofungicides, Coniothyrium minitans and Bacillus amyloliquefaciens, are commercially available and have been shown to limit or suppress Sclerotinia sclerotiorum in soybean. S. sclerotiorum is a soilborne pathogen of soybean that can cause significant yield losses under cool and wet environmental conditions. Integrated soybean pest management practices can include the application of herbicides, fungicides, and insecticides at various times during the growing season to minimize yield losses. However, limited information is available regarding how these biofungicides can be successfully incorporated into a soybean-integrated pest management program. To assess the sensitivity of C. minitans and B. amyloliquefaciens biological activity on S. sclerotiorum to pesticides commonly used in soybean-production systems, a poison plate assay and soil plate and growth chamber experiments were conducted. In the poison plate assay, C. minitans was most sensitive to the preemergence herbicide flumioxazin and the synthetic fungicides boscalid and fluazinam, whereas B. amyloliquefaciens was sensitive only to the synthetic fungicide fluazinam. In the soil plate assay, the mycoparasitic activity of C. minitans on S. sclerotiorum was sensitive to flumioxazin, metribuzin, glyphosate, picoxystrobin, and boscalid. In the controlled environment experiments, none of the pesticides tested decreased the efficacy of B. amyloliquefaciens.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Mucinous appendiceal adenocarcinoma invading the bladder: not always an easy diagnosis. A case report
Authors: Eugenia Lavorini , Giovanni Alemanno , Andrea Mari , Maria Rosaria Raspollini , Gianni Vittori , Mara Bacchiani , Gherardo Maltinti , Daniele Lavacchi , Lorenzo Antonuzzo , Andrea Minervini , Paolo Prosperi
Published: January 2023

Appendiceal neoplasms account for less than 1% of intestinal cancers and their clinical manifestation is typically, nonspecific and ambiguous. Appendiceal tumor infiltrating the urinary tract is extremely rare and few cases are mentioned in literature. A 72-year-old woman presented gross hematuria and right colic pain. No prior urologic disease was reported. Cystoscopic examination showed a large lesion on the right side of posterior bladder wall, with multiple ulcerated areas and microscopical examination of the specimen revealed a mucinous adenocarcinoma infiltrating urinary bladder. Contrast-enhanced computed tomography (CT) scan identified focal thickening of bladder dome 21 × 7 cm with a possible origin from the appendix and with an unclear relationship with the uterus and the right fallopian tube. These findings were discussed with the local gastrointestinal multidisciplinary team, where a decision to perform upfront surgery was made. Explorative laparotomy confirmed a tumor of the appendix invading the urinary bladder. We performed an en-bloc resection including right colon, 40 cm of terminal ileum with a partial cystectomy removing the infiltrated area of the right bladder wall, and an omentectomy. Reconstruction was made first with a full-thickness suture of the bladder, then with an ileo-colon stapled anastomosis. The postoperative course was uneventful and the CT scan at 9 months from surgery did not show any recurrence. Right hemicolectomy is considered the gold standard for all lesions with invasion beyond the mucosa, and, appendicectomy alone seems to be the ideal treatment for in situ and localized cases.
Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective
Authors: Huang Hui , Chen Ruxuan , Shao Chi , Xu Zuojun , Wolters Paul J.
Published: January 2023

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians’ perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.
Alternative Approaches to Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention, How Do They Compare?: A Systematic Review and Meta-Analysis
Authors: EL-Andari Ryaan , Bozso Sabin J. , Fialka Nicholas M. , Kang Jimmy J. H. , Hassanabad Ali Fatehi , Nagendran Jeevan
Published: January 2023

Coronary artery disease (CAD) is a leading cause of mortality worldwide. Severe symptomatic CAD is treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Alternative CABG (ACABG) approaches including thoracotomy, off-pump, total endoscopic, and robotic-assisted CABG are increasing in prevalence to address the increased early risk of CABG. This systematic review and meta-analysis aims to review the contemporary literature comparing outcomes after ACABG and PCI. Pubmed, Medline, and Embase were systematically searched by 2 authors for articles comparing the outcomes after ACABG and PCI. A total of 1154 articles were screened, and 11 were included in this review. The RevMan 5.4 software was used to perform a meta-analysis of the pooled data. Individual studies found rates of long-term survival, major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and repeat revascularization either favored ACABG or did not differ significantly. Pooled estimates of the compiled data identified rates of MACCE, MI, and repeat revascularization favored ACABG. The results of this review demonstrated the favorable rates of long-term mortality, MACCE, MI, and repeat revascularization for ACABG in addition to similar short-term mortality and stroke when compared with PCI. Advancement of both CABG and PCI continues to improve patient outcomes. With the increasing prevalence of ACABG, similar studies will need to be undertaken with further direct comparisons between ACABG and PCI. Finally, hybrid revascularization should continue to be explored for its combined benefits of long-term outcomes, short-term safety, and ability to achieve complete revascularization.
Bone loss and kidney stone risk in weightlessness
Authors: Buckey Jay C. , Thamer Semran , Lan Mimi
Published: January 2023

Purpose of review

Weightlessness increases both bone loss and kidney stone formation risk. The large interior volume of the International Space Station (ISS) has allowed for a mix of exercise devices to help maintain the skeleton. But space exploration is changing. Long stays on the ISS will be replaced by journeys in smaller spacecraft both to and around the Moon. Small private space stations are under development. This will limit the ability to do exercise countermeasures, which can increase both bone loss and kidney stone risk. This review examines this risk and how it can be minimized in this new era of spaceflight.

Recent findings

Simple, low-mass, low-power ways to track bone loss and kidney stone risk in space are being researched. Tracking urinary calcium concentration in the first morning void and targeting additional countermeasures (e.g. bisphosphonates) to those who run consistently high levels is one promising approach.

New exploration spacecraft would not have the room and capability to replicate the current 2 h, daily exercise countermeasure programme on the ISS. A monitoring approach, perhaps using urinary calcium as a marker, is needed to find those at greatest risk. This would allow countermeasures to be targeted individually and used efficiently.
Sortilin and hypertension
Authors: Avvisato Roberta , Jankauskas Stanislovas S. , Varzideh Fahimeh , Kansakar Urna , Mone Pasquale , Santulli Gaetano
Published: January 2023

Purpose of review

The current review aims to present the latest scientific updates on the role of Sortilin in the pathophysiology of hypertension.

Recent findings

The main focus of this systematic overview is on the functional contribution of Sortilin to the pathogenesis of hypertension. Sortilin is a glycoprotein mostly known for its actions as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Emerging evidence indicates that Sortilin is associated with pathological conditions, including inflammation, arteriosclerosis, dyslipidemia, insulin resistance, and vascular calcification. Most recently, Sortilin has been shown to finely control endothelial function and to drive hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress.

The latest findings linking Sortilin and hypertension that are herein discussed can inspire novel areas of research which could eventually lead to the discovery of new therapeutic strategies in cardiovascular medicine.
Comparing the Results of Latissimus Dorsi Versus Teres Major Transfer in Children With Obstetric Brachial Plexus Injury and Residual Shoulder Sequelae
Authors: Ibrahim Marwa Raafat , Abdelmaksoud Islam Mohamed , Ahmad Mohammad Hasan , Semaya Ahmed Elsayed
Published: January 2023

Background

Obstetric brachial plexus injury (OBPI) remains a fairly common problem in newborns despite the improved obstetric care. Children who do not show complete recovery often present with residual shoulder deformity of limited external rotation and abduction. Secondary interventions in the form of tendon transfer and soft tissue release are aimed at correcting the implicated muscular imbalance to restore shoulder function.

Aim

The aim of this work was to compare the results of latissimus dorsi versus teres major tendon transfer in patients with OBPI with limited shoulder external rotation.

Patients and Methods

This study included 40 patients admitted to El Hadara University Hospital with OBPI and limited shoulder abduction and external rotation aged between 1.5 and 4 years. Half of the patients had a latissimus dorsi transfer, and the other half, a teres major one. Children with limited preoperative passive external rotation in both groups required a subscapularis slide. Patients were evaluated preoperatively, at 6 months, and 12 months postoperatively using the Gilbert scale.

Results

Teres major tendon transfer showed better results in restoring limited shoulder abduction and external rotation than latissimus dorsi transfer. Limited shoulder internal rotation was the main complication occurring postoperatively. Loss of the last degree of internal rotation occurred in most patients who had subscapularis slide. Most patients regained functional midline abilities with physiotherapy and required no further interventions.

Conclusions

Isolated teres major transfer has shown better results in improving the range of external rotation and abduction compared with isolated latissimus dorsi tendon transfer. Age of the patients did not affect the overall final improvement in shoulder range of motion. Limited internal rotation is the main complication postoperatively, which was prevalent in patients who required a subscapularis slide but was not statistically significant.
Collaboration Scripts or Checklists to Engage Novice Observers in Immersive Simulation?
Authors: Tremblay Marie-Laurence , Lafleur Alexandre , Dieckmann Peter , Rethans Jan-Joost , Dolmans Diana
Published: January 2023

Introduction

In simulation, students often observe their peers perform a task. It is still unclear how different types of instructional guidance can turn the observational phase into an active learning experience for novices. This mixed-method study aims to understand similarities and differences between use of collaboration scripts and checklists by observers in terms of cognitive load and perception of learning.

Methods

Second-year pharmacy students (N = 162) were randomly assigned to 1 of 4 conditions when observing a simulation: collaboration scripts (heuristic to analyze in dyads while observing), checklists, both, or no guidance. We measured observers' intrinsic and extraneous cognitive load and self-perceived learning and conducted focus group interviews.

Results

Intrinsic cognitive load was significantly lower for checklists (M = 3.6/10) than for scripts (M = 4.7/10) or scripts and checklists combined (M = 4.7/10). Extraneous cognitive load was significantly lower for checklists (M = 1.5/10) than for scripts combined with checklists (M = 2.6/10) or no guidance (M = 1.8/10). There was no statistical difference between conditions for self-perceived learning. Coding of focus group interviews revealed 6 themes on observers' perception of learning under different conditions of instructional guidance. Students explained that collaboration scripts felt more complex, whereas checklists were perceived as a simple fact-checking exercise. Observing the simulation, regardless of guidance, was a meaningful learning experience.

Conclusions

With or without guidance, observers are actively engaged with the simulation, but their effort differed depending on instructions. When choosing between checklists or collaboration scripts, educators should be guided by the type of simulation task.
Structural Determinants of Redox Conduction Favor Robustness over Tunability in Microbial Cytochrome Nanowires
Authors: Guberman-Pfeffer Matthew J.
Published: January 2023

Helical homopolymers of multiheme cytochromes catalyze biogeochemically significant electron transfers with a reported 103-fold variation in conductivity. Herein, classical molecular dynamics and hybrid quantum/classical molecular mechanics are used to elucidate the structural determinants of the redox potentials and conductivities of the tetra-, hexa-, and octaheme outer-membrane cytochromes E, S, and Z, respectively, fromGeobacter sulfurreducens. Second-sphere electrostatic interactions acting on minimally polarized heme centers are found to regulate redox potentials over a computed 0.5-V range. However, the energetics of redox conduction are largely robust to the structural diversity: Single-step electronic couplings (⟨Hmn⟩), reaction free energies, and reorganization energies (λmn) are always respectively <|0.026|, <|0.26|, and between 0.5 – 1.0 eV. With these conserved parameter ranges, redox conductivity differed by less than a factor of 10 among the ‘nanowires’ and is sufficient to meet the demands of cellular respiration if 102– 103‘nanowires’ are expressed. The ‘nanowires’ are proposed to be differentiated by the protein packaging to interface with a great variety of environments, and not by conductivity, because the rate-limiting electron transfers are elsewhere in the respiratory process. Conducting-probe atomic force microscopy measurements that find conductivities 103-106-fold more than cellular demands are suggested to report on functionality that is either not used or not accessible under physiological conditions. The experimentally measured difference in conductivity between Omc- S and Z is suggested to not be an intrinsic feature of the CryoEM-resolved structures.
Aurora B Kinase Dependent Phosphorylation of Keratin 8 is required for Cytokinesis in Mammalian Cells of Epithelial Origin
Authors: Harmanda Busra , Kaya Oyku , Waide Xenia , Qureshi Muhammed Haroon , Nesvizhskii Alexey , Mitchison Timothy J , Ozlu Nurhan
Published: January 2023

Keratins are the most diverse family of intermediate filaments and are expressed in most epithelial tissues and malignancies. They form highly stable polymers that need to be cut through during cytokinesis. Previous work suggested a role of phosphorylation, but keratin regulation during cell division is not understood in detail. Depletion of Keratin 8 in an epithelial cancer cell line (HeLa) caused chromosome segregation and cytokinesis defects. Aurora B kinase localization to midzones and cleavage furrows was reduced in Keratin 8 knockouts, suggesting that Keratin 8 helps scaffold Aurora B during cytokinesis. We mapped eleven Aurora B kinase sites in Keratin 8 that were associated with cell division. Keratin 8 S34 phosphorylation occurred specifically at the cleavage furrow and persisted at the midzone until the end of cytokinesis. Inhibition of Aurora B kinase or non-phosphorylatable Keratin 8 mutant prevented the disassembly of keratin bundles at the cleavage furrow, which blocked furrow ingression. Our data reveal a functional inter-dependency between Keratin 8 and Aurora B kinase in epithelial cells. Keratin 8 promotes the translocation of Aurora B to the midzone. Aurora B kinase then generates a local zone of Keratin phosphorylation which promotes keratin filament disassembly and allows the cleavage furrow to cut through the keratin network.
MEK1/2 inhibition decreases pro-inflammatory responses in macrophages from people with cystic fibrosis and mitigates severity of illness in experimental murine methicillin-resistantStaphylococcus aureusinfection
Authors: De Mithu , Hisert Katherine B. , Liles W. Conrad , Manicone Anne M. , Hemann Emily A. , Long Matthew E.
Published: January 2023

Chronic pulmonary bacterial infections and associated inflammation remain a cause of morbidity and mortality in people with cystic fibrosis (PwCF) despite new modulator therapies. Therapies targeting host factors that dampen detrimental inflammation without suppressing immune responses critical for controlling infections remain limited, while the acquisition of antibiotic resistance bacterial infections is an increasing global problem, and a significant challenge in CF. Pharmacological compounds targeting the mammalian MAPK proteins MEK1 and MEK2, referred to as MEK1/2 inhibitor compounds, have potential combined anti-microbial and anti-inflammatory effects. Here we examined the immunomodulatory properties of MEK1/2 inhibitor compounds PD0325901, trametinib, and CI-1040 on CF innate immune cells. Human CF macrophage and neutrophil phagocytic functions were assessed by quantifying phagocytosis of serum opsonized pHrodo redE. coli,Staphylococcus aureus, and zymosan bioparticles. MEK1/2 inhibitor compounds reduced CF macrophage pro-inflammatory cytokine production without impairing CF macrophage or neutrophil phagocytic abilities. Wild-type C57BL6/J andCftrtm1kth(F508del homozygous) mice were used to evaluate the in vivo therapeutic potential of PD0325901 compared to vehicle treatment in an intranasal methicillin-resistantStaphylococcus aureus(MRSA) infection with the community-acquired MRSA strain USA300. In both wild-type and CF mice, PD0325901 reduced infection related weight loss compared to vehicle treatment groups but did not impair clearance of bacteria in lung, liver, or spleen 1 day after infection. In summary, this study provides the first data evaluating the therapeutic potential of MEK1/2 inhibitor to modulate CF immune cells, and demonstrates that MEK1/2 inhibitors dampen pro-inflammatory responses without impairing host defense mechanisms mediating pathogen clearance.
Multiscale imaging and quantitative analysis of plasma membrane protein-cortical actin interplay
Authors: Dasgupta Aparajita , Ngo Huong-Tra , Tschoerner Deryl , Touret Nicolas , Rocha-Azevedo Bruno da , Jaqaman Khuloud
Published: January 2023

The spatiotemporal organization of cell surface receptors is important for cell signaling. Cortical actin (CA), the subset of the actin cytoskeleton subjacent to the plasma membrane (PM), plays a large role in cell surface receptor organization. This was however shown largely through actin perturbation experiments, which raise concerns of nonspecific effects and preclude quantification of actin architecture and dynamics under unperturbed conditions. These limitations make it challenging to predict how changes in CA properties can affect receptor organization. To derive direct relationships between the architecture and dynamics of CA and the spatiotemporal organization of PM proteins, including cell surface receptors, we developed a multiscale imaging and computational analysis framework based on the integration of single-molecule imaging (SMI) of PM proteins and fluorescent speckle microscopy (FSM) of CA (combined: SMI-FSM) in the same live cell. SMI-FSM revealed differential relationships between PM proteins and CA based on the PM proteins’ actin binding ability, diffusion type and local CA density. It also highlighted the complexity of cell wide actin perturbation, where we found that global changes in actin properties caused by perturbation were not necessarily reflected in the CA properties near PM proteins, and the changes in PM protein properties upon perturbation varied based on the local CA environment. Given the widespread use of SMI as a method to study the spatiotemporal organization of PM proteins and the versatility of SMI-FSM, we expect it to be widely applicable to enable future investigation of the influence of CA architecture and dynamics on different PM proteins, especially in the context of actin-dependent cellular processes, such as cell migration.

Significance

Plasma membrane protein organization, an important factor for shaping cellular behaviors, is influenced by cortical actin, the subset of the actin cytoskeleton near the plasma membrane. Yet it is challenging to directly and quantitatively probe this influence. Here, we developed an imaging and analysis approach that combines single-molecule imaging, fluorescent speckle microscopy and computational statistical analysis to characterize and correlate the spatiotemporal organization of plasma membrane proteins and cortical actin. Our approach revealed different relationships between different proteins and cortical actin, and highlighted the complexity of interpreting cell wide actin perturbation experiments. We expect this approach to be widely used to study the influence of cortical actin on different plasma membrane components, especially in actin-dependent processes.
Lack of Fzd6 in Ciliated Cells Suppresses Ferroptotic Pulmonary Alveolar Cell Death Induced by LPS and Coronavirus
Authors: Yuan Qianying , Luan Yi , Rajendran Barani Kumar , Compton Susan , Tang Wenwen , Wu Dianqing
Published: January 2023

Pulmonary inflammation compromises lung barrier function and underlies many lung diseases including acute lung injury and acute respiratory distress syndrome (ARDS). However, mechanisms by which lung cells respond to the damage caused by the inflammatory insults are not completely understood. Here we show that Fzd6-deficiency in Foxj1+ciliated cells reduces pulmonary permeability, lipid peroxidation, and alveolar cell death accompanied with an increase in alveolar number in lungs insulted by LPS or a mouse coronavirus. Single-cell RNA sequencing of lung cells indicates that the lack of Fzd6, which is expressed in Foxj1+cells, increases expression of the aldo-keto reductase Akr1b8 in Foxj1+cells. Intratracheal administration of the Akr1b8 protein phenocopies Fzd6-deficient lung phenotypes. In addition, ferroptosis inhibitors also phenocopy Fzd6-deficient lung phenotypes and exert no further effects in Fzd6-deficient lungs. These results reveal an important mechanism for protection of alveolar cells from ferroptotic death during pulmonary inflammation by Foxj1+ciliated cells via paracrine action of Akr1b8.
MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS
Authors: Pérez-Cabello Jesús A. , Silvera-Carrasco Lucía , Franco Jaime M. , Capilla-González Vivian , Armaos Alexandros , Gómez-Lima María , García-García Raquel , Yap Xin Wen , Leal-Lasarte M. Magdalena , Lall Deepti , Baloh Robert H. , Martínez Salvador , Miyata Yoshihiko , Tartaglia Gian G. , Sawarkar Ritwick , García-Dominguez Mario , Pozo David , Roodveldt Cintia
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease affecting motor neurons and characterized by microglia-mediated neurotoxic inflammation whose underlying mechanisms remain incompletely understood. In this work we reveal that MAPK/MAK/MRK overlapping kinase (MOK), with unknown physiological substrate, displays an immune function by controlling inflammatory and type-I IFN responses in microglia which are detrimental to primary motor neurons. Moreover, we uncover the epigenetic reader bromodomain-containing protein 4 (Brd4) as the first molecule regulated by MOK, by promoting Ser492-phospho-Brd4 levels. We further demonstrate that MOK regulates Brd4 functions by supporting its binding to cytokine gene promoters, therefore enabling innate immune responses. Remarkably, we show that MOK levels are increased in ALS spinal cord, particularly in microglial cells, and that administration of a chemical MOK-inhibitor to ALS model mice is able to modulate Ser492-phospho-Brd4 levels, suppress microglial activation and modify disease course, indicating a pathophysiological role of MOK kinase in ALS and neuroinflammation.