bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of naive indolent lymphoma using whole-body diffusion-weighted imaging and T2-weighted MRI: results of a prospective study in 30 patients
Authors: Hong Gil-Sun , Chae Eun Jin , Ryu Jin-Sook , Chae Sun Young , Lee Hyo Sang , Yoon Dok Hyun , Suh Cheolwon
Published: January 2021

Background

We prospectively evaluated the diagnostic utility of whole-body diffusion-weighted imaging with background body signal suppression and T2-weighted short-tau inversion recovery MRI (WB-DWIBS/STIR) for the pretherapeutic staging of indolent lymphoma in 30 patients.

Methods

This prospective study included 30 treatment-naive patients with indolent lymphomas who underwent WB-DWIBS/STIR and conventional imaging workup plus biopsy. The pretherapeutic staging agreement, sensitivity, and specificity of WB-DWIBS/STIR were investigated with reference to the multimodality and multidisciplinary consensus review for nodal and extranodal lesions excluding bone marrow.

Results

In the pretherapeutic staging, WB-DWIBS/STIR showed very good agreement (κ = 0.96; confidence interval [CI], 0.88–1.00), high sensitivity (93.4–95.1%), and high specificity (99.0–99.4%) for the whole-body regions. These results were similar to those of 18F-FDG-PET/CT, except for the sensitivity for extranodal lesions. For extranodal lesions, WB-DWIBS/STIR showed higher sensitivity compared to 18F-FDG-PET/CT for the whole-body regions (94.9–96.8% vs. 79.6–86.3%, P = 0.058).

Conclusion

WB-DWIBS/STIR is an effective modality for the pretherapeutic staging of indolent lymphoma, and it has benefits when evaluating extranodal lesions, compared with 18F-FDG-PET/CT.
Design and implementation of a maxi-sized mobile robot (Karo) for rescue missions
Authors: Habibian Soheil , Dadvar Mehdi , Peykari Behzad , Hosseini Alireza , Salehzadeh M. Hossein , Hosseini Alireza H. M. , Najafi Farshid
Published: January 2021

Rescue robots are expected to carry out reconnaissance and dexterity operations in unknown environments comprising unstructured obstacles. Although a wide variety of designs and implementations have been presented within the field of rescue robotics, embedding all mobility, dexterity, and reconnaissance capabilities in a single robot remains a challenging problem. This paper explains the design and implementation of Karo, a mobile robot that exhibits a high degree of mobility at the side of maintaining required dexterity and exploration capabilities for urban search and rescue (USAR) missions. We first elicit the system requirements of a standard rescue robot from the frameworks of Rescue Robot League (RRL) of RoboCup and then, propose the conceptual design of Karo by drafting a locomotion and manipulation system. Considering that, this work presents comprehensive design processes along with detail mechanical design of the robot’s platform and its 7-DOF manipulator. Further, we present the design and implementation of the command and control system by discussing the robot’s power system, sensors, and hardware systems. In conjunction with this, we elucidate the way that Karo’s software system and human–robot interface are implemented and employed. Furthermore, we undertake extensive evaluations of Karo’s field performance to investigate whether the principal objective of this work has been satisfied. We demonstrate that Karo has effectively accomplished assigned standardized rescue operations by evaluating all aspects of its capabilities in both RRL’s test suites and training suites of a fire department. Finally, the comprehensiveness of Karo’s capabilities has been verified by drawing quantitative comparisons between Karo’s performance and other leading robots participating in RRL.
Comparison of feasibility, time consumption and costs of three virtual planning systems for surgical correction of midfacial deficiency
Authors: Willinger Katrin , Guevara-Rojas Godoberto , Cede Julia , Schicho Kurt , Stamm Tanja , Klug Clemens
Published: January 2021

Background

Today virtual surgical planning (VSP) is a standard method in maxillofacial corrective surgery and is the key to reach satisfactory esthetic outcomes. The purpose of this study was to evaluate usability of three established virtual surgical planning software applications by comparing feasibility, time consumption, and costs in a standardized workflow for a modified intraoral quadrangular Le Fort II osteotomy (IQLFIIO).

Results

A cross-sectional study was performed based on retrospective and re-planned data of patients with midfacial deficiency treated by modified IQLFIIO, using three software applications: IPS Case Designer ®, Dolphin Imaging ®, and ProPlan CMF ®. Feasibility: All evaluated steps of the VSP procedure could be successfully performed in all three evaluated applications. In all software packages, it was possible to design the surgical splints with CAD/CAM technology. Working time: The mean value of time needed was IPS Case Designer ®, 36.5 min; Dolphin Imaging ®, 33.6 min; ProPlan CMF ®, 45.5 min. We found statistical significant difference between ProPlan CMF ® and Dolphin Imaging ® (p value, 0.02). Costs: Asset costs for acquiring the software, license fee, license possibilities, paying for support services, and service contracts were evaluated and are found in similar ranges.

Conclusion

All three tested software applications are usable for virtual planning of an IQLFIIO and splint production by CAD/CAM technology. Successful movement of bone segments and overlaying soft tissues proved feasibility. Time consumption and costs were found in similar ranges.
Renovascular hypertension in children
Authors: Patel Premal Amrishkumar , Cahill Anne Marie
Published: January 2021

Paediatric hypertension, defined as systolic blood pressure > 95th percentile for age, sex and height is often incidentally diagnosed. Renovascular hypertension (RVH) is responsible for 5–25% of hypertension in children. Renal artery stenosis and middle aortic syndrome can both can be associated with various conditions such as fibromuscular dysplasia, Williams syndrome & Neurofibromatosis type 1. This paper discusses the approaches to diagnosis and interventional management and outcomes of renovascular hypertension in children. Angiography is considered the gold standard in establishing the diagnosis of renovascular disease in children. Angioplasty is beneficial in the majority of patients and generally repeated angioplasty is considered more appropriate than stenting. Surgical options should first be considered before placing a stent unless there is an emergent requirement. Given the established safety and success of endovascular intervention, at most institutions it remains the preferred treatment option.
A technique for intra-procedural blood velocity quantitation using time-resolved 2D digital subtraction angiography
Authors: Hoffman Carson , Periyasamy Sarvesh , Longhurst Colin , Medero Rafael , Roldan-Alzate Alejandro , Speidel Michael A. , Laeseke Paul F.
Published: January 2021

Background

2D digital subtraction angiography (DSA) is utilized qualitatively to assess blood velocity changes that occur during arterial interventions. Quantitative angiographic metrics, such as blood velocity, could be used to standardize endpoints during angiographic interventions.

Purpose

To assess the accuracy and precision of a quantitative 2D DSA (qDSA) technique and to determine its feasibility for in vivo measurements of blood velocity.

Materials and methods

A quantitative DSA technique was developed to calculate intra-procedural blood velocity. In vitro validation was performed by comparing velocities from the qDSA method and an ultrasonic flow probe in a bifurcation phantom. Parameters of interest included baseline flow rate, contrast injection rate, projection angle, and magnification. In vivo qDSA analysis was completed in five different branches of the abdominal aorta in two 50 kg swine and compared to 4D Flow MRI. Linear regression, Bland-Altman, Pearson’s correlation coefficient and chi squared tests were used to assess the accuracy and precision of the technique.

Results

In vitro validation showed strong correlation between qDSA and flow probe velocities over a range of contrast injection and baseline flow rates (slope = 1.012, 95% CI [0.989,1.035], Pearson’s r = 0.996, p < .0001). The application of projection angle and magnification corrections decreased variance to less than 5% the average baseline velocity (p = 0.999 and p = 0.956, respectively). In vivo validation showed strong correlation with a small bias between qDSA and 4D Flow MRI velocities for all five abdominopelvic arterial vessels of interest (slope = 1.01, Pearson’s r = 0.880, p = <.01, Bias = 0.117 cm/s).

Conclusion

The proposed method allows for accurate and precise calculation of blood velocities, in near real-time, from time resolved 2D DSAs.
Melting heat transfer assessment on magnetic nanofluid flow past a porous stretching cylinder
Authors: Singh Khilap , Pandey Alok Kumar , Kumar Manoj
Published: January 2021

The assessment of melting heat transfer and non-uniform heat source on magnetic Cu–H2O nanofluid flow through a porous cylinder was studied. The transformed differential equations describing the motion of Cu–H2O fluid together with pertinent boundary conditions were handled numerically with the assistance of Keller box method. The ranges of volume fraction of copper particles were taken as 0–25%. The impacts of various governing parameters on the physical measures such as Nusselt number, surface drag force, temperature and velocity were analyzed by representing through graphs and tables. It was noted that the flow was influenced accordingly with the governing parameters. The outcomes showed that the rate of heat exchange improved with elevated Reynolds number, space and temperature-dependent internal heat source and melting parameters. The comparison of our data in relation to those of previous works has been shown.
Evidence-based surgical technique for medial unicompartmental knee arthroplasty
Authors: Kim Tae Kyun , Mittal Anurag , Meshram Prashant , Kim Woo Hyun , Choi Sang Min
Published: January 2021

Unicompartmental knee arthroplasty (UKA) is a successful treatment modality in selected patients having advanced, single-compartment osteoarthritis of the knee. The bone and ligament preservation leading to shorter recovery periods, better functional outcomes, lower perioperative complication rates, and easier revision, if needed, are proposed as some of the advantages of UKA over total knee arthroplasty (TKA). Despite several advantages, UKA is reported to have higher failure rates as compared to TKA. The prosthesis failure of UKA is directly correlated to intraoperative technique-related factors like malpositioning of components and the inability to replicate the target-limb alignment as per preoperative planning. An evidence-based surgical technique for UKA may help surgeons to avoid the intraoperative technique-related errors. The purpose of this paper is to describe a stepwise surgical technique for the fixed-bearing medial UKA.
Applying human-centered design to maximize acceptability, feasibility, and usability of mobile technology supervision in Kenya: a mixed methods pilot study protocol
Authors: Triplett Noah S. , Munson Sean , Mbwayo Anne , Mutavi Teresia , Weiner Bryan J. , Collins Pamela , Amanya Cyrilla , Dorsey Shannon
Published: January 2021

Background

Although research continues to support task-shifting as an effective model of delivering evidence-based practices (EBPs), little scholarship has focused how to scale up and sustain task-shifting in low- and middle-income countries, including how to sustainably supervise lay counselors. Ongoing supervision is critical to ensure EBPs are delivered with fidelity; however, the resources and expertise required to provide ongoing supervision may limit the potential to scale up and sustain task shifting. Opportunities may exist to leverage mobile technology to replace or supplement in-person supervision in low-resource contexts, but contextual variables, such as network connectivity and lay counselor preferences surrounding mobile technology, must be examined and considered when designing and implementing mobile technology supervision.

Methods

This study builds from an existing randomized trial in Kenya, wherein teachers and community health volunteers have been trained to provide trauma-focused cognitive behavioral therapy as lay counselors. The study will use an iterative and mixed methods approach, with qualitative interviews and a Human-Centered Design (HCD) workshop informing a non-randomized pilot trial. Semi-structured interviews will be conducted with lay counselors and supervisors to understand how mobile technology is currently being used for supervision and determine the barriers and facilitators to mobile technology supervision. Data from these interviews will inform an HCD workshop, where lay counselors and supervisors “re-design” supervision to most effectively leverage mobile technology. Workshop participants will also participate in focus groups to gather perceptions on the use of HCD techniques. The final outcome of the workshop will be a set of refined workflows, which will be tested in a mixed method, nonrandomized pilot with newly trained lay counselors and existing supervisors. The pilot trial will evaluate the acceptability, feasibility, and usability of mobile technology supervision through self-report questionnaires as well as perceptions of effectiveness through qualitative interviews with a subset of lay counselors and all supervisors.

Discussion

This study will provide a launching point for future research on supervision and methods to engage stakeholders to design and tailor interventions and implementation supports to fit low-resourced contexts.

Trial registration

The parent trial from which this study builds was registered on ClinicalTrials.gov on August 9, 2017 (NCT03243396).
Exploring implementation processes in general practice in a feedback intervention aiming to reduce potentially inappropriate prescribing: a qualitative study among general practitioners
Authors: Høj Kirsten , Mygind Anna , Bro Flemming
Published: January 2021

Background

Potentially inappropriate prescribing (PIP) has been linked with adverse health outcomes and increased healthcare costs. Feedback interventions targeting PIP have shown promising results. However, translation from research to everyday practice remains a challenge. With the Normalisation Process Theory (NPT) as overarching framework, we aimed to explore the implementation processes performed by general practices in a real-life, quality improvement intervention using feedback on practice-level prescribing.

Methods

All 376 general practices in the Central Denmark Region received a prescribing feedback intervention targeting selected types of PIP. Six months later, they received an evaluation questionnaire, to which 45% responded. Among 102 practices reporting to have made changes in response to the intervention, we conducted individual, semi-structured interviews with ten GPs. Maximum variation was sought in terms of baseline prescribing status, implementation activities, practice type and geographical location. The interviews were analysed thematically using NPT.

Results

The implementation processes in general practice reflected the four NPT constructs. Key motivators for implementation included the GPs’ professional values and interests, but pragmatic considerations were also of importance (coherence). A collective versus an individual approach to the engagement and planning of the implementation process (cognitive participation) was observed. Similarly, a distinction was evident between practice-level actions involving the entire practice team as opposed to individual-level actions performed by the individual GP (collective action). Several challenges to the implementation processes were identified, including patient influences and competing priorities at multiple levels (reflexive monitoring). Additionally, internal evaluation and normalisation of new practices occurred in varying degrees.

Conclusion

NPT provided a useful framework for understanding implementation processes in general practice. Our results emphasise that clear professional aims and feasible content of interventions are key for GP motivation. This may be ensured through cooperation with GPs’ professional organisation, which may strengthen intervention legitimacy and uptake. Two main implementation strategies were identified: practice-level and GP-level strategies. Intervention developers need to recognise both strategies to deliver intervention content and implementation support that promote sustainable improvements in prescribing practice. Competing demands and patient influences remain important challenges that need to be addressed in future studies to further facilitate the reduction of PIPs.
Determination of enantiomer impurity in Bortezomib lyo injection formulation by using normal-phase liquid chromatography
Authors: Najana Sanni Babu , Bollikolla Hari Babu
Published: January 2021

Background

A highly stereo-specific liquid chromatographic technique was built up and authenticated to quantify the (1S,2R-enantiomer) impurity in Bortezomib lyo injection formulation. The separation was achieved on Chiral Pak ID-3 (3 μm, 4.6 × 250 mm) column (“amylose-based 3-chlorophenylcarbamate” chiral stationary phase) through a movable segment consisting of n-heptane, 2-propanol, ethyl alcohol, and TFA (82:15:3:0.1, v/v/v/v) at a flow rate of 0.6 mL/min. Column temperature preserved 25 °C, injection level 20 μL, sample cooler temperature ambient, and detection wavelength 270 nm.

Results

The retention time of (1S,2R-enantiomer) impurity and Bortezomib was determined 10.57 and 17.98 min, respectively. The resolution between (1S,2R-enantiomer) impurity and Bortezomib was found to be 4.2. The acceptance limit of the (1S,2R-enantiomer) impurity is 0.5%. The established method was authenticated as per ICH guidelines in respect of precision, accuracy, sensitivity, linearity, specificity, ruggedness, and robustness. The minimum quantity of the sample required for detection (LOD) was observed at 0.282 μg per mL and similarly the quantifying sample (LOQ) was observed to be 0.896 μg per mL.

Conclusion

The proposed normal phase-HPLC method that can quantify (1S,2R-enantiomer) impurity in Bortezomib lyo injection formulation at trace level concentration has been urbanized and authenticated as per ICH guidelines. The effectiveness of the technique was ensured by the specificity, exactitude, linearity, and accuracy. Hence, the method well suit for their intended purposes and can be successfully useful for regular analysis in laboratories and is suitable for the quality control.
Source deghosting of coarsely sampled common-receiver data using a convolutional neural network
Authors: Vrolijk Jan-Willem , Blacquière Gerrit
Published: January 2021

It is well known that source deghosting can best be applied to common-receiver gathers, whereas receiver deghosting can best be applied to common-shot records. The source-ghost wavefield observed in the common-shot domain contains the imprint of the subsurface, which complicates source deghosting in the common-shot domain, in particular when the subsurface is complex. Unfortunately, the alternative, that is, the common-receiver domain, is often coarsely sampled, which complicates source deghosting in this domain as well. To solve the latter issue, we have trained a convolutional neural network to apply source deghosting in this domain. We subsample all shot records with and without the receiver-ghost wavefield to obtain the training data. Due to reciprocity, these training data are a representative data set for source deghosting in the coarse common-receiver domain. We validate the machine-learning approach on simulated data and on field data. The machine-learning approach gives a significant uplift to the simulated data compared to conventional source deghosting. The field-data results confirm that the proposed machine-learning approach can remove the source-ghost wavefield from the coarsely sampled common-receiver gathers.
Seismoelectric surface-wave analysis for characterization of formation properties, using dispersive relative spectral amplitudes
Authors: Grobbe Niels , de Ridder Sjoerd A. L.
Published: January 2021

We have studied seismoelectric (SE) surface-wave signals and found that they can be used to infer changes in the SE coupling properties at depth. SE surface-wave signals have much higher amplitudes than SE body-wave signals. We measured the seismic and the electrical potential or electromagnetic (EM) field along the surface of the earth. We used dispersive relative spectral amplitudes (DRSAs) that measure the frequency-dependent relative strength of electrical signals versus seismic signals associated with SE surface-wave signals. We find that DRSAs have sensitivity to contrasts in the electrokinetic coupling coefficient and other relevant petrophysical properties at depth. Our discovery can mitigate the major limitation that plagues body-wave-based SE methods: the relative weakness of the converted EM signals from seismic body waves. We envision applications to characterize subsurface rock, fluid, and fluid-flow properties (e.g., porosity, permeability, and dynamic fluid viscosity, salinity) in the near surface, for aquifers, and shallow geothermal reservoirs.
System-level barriers to personal recovery in mental health: qualitative analysis of co-productive narrative dialogues between users and professionals
Authors: Nakanishi Miharu , Kurokawa George , Niimura Junko , Nishida Atsushi , Shepherd Geoff , Yamasaki Syudo
Published: January 2021

Background

No co-productive narrative synthesis of system-level facilitators and barriers to personal recovery in mental illness has been undertaken.

Aims

To clarify system-level facilitators and barriers to personal recovery of people with mental illness.

Method

Qualitative study guided by thematic analysis. Data were collected through one focus group, which involved seven service users and three professionals. This group had 11 meetings, each lasting 2 h at a local research institute, between July 2016 to January 2018.

Results

The analysis yielded three themes: barriers inhibiting positive interaction within personal relationship networks, roots of barriers from mental health systems and the social cultural context, and possible solutions to address the roots. Barriers were acknowledged as those related to sense of safety, locus of control within oneself and reunion with self. The roots of barriers were recognised within mental health services, including system without trauma sensitivity, lack of advocacy support and limited access to psychosocial approaches. Roots from social cultural context were also found. There were no narratives relating to facilitators. A possible solution was to address the roots from systems. Social cultural change was called for that makes personalised goals most valued, with an inclusive design that overcomes stigma, to achieve an open and accepting community.

Conclusions

The analysis yielded system-level barriers specific to each recovery process. Roots of barriers that need transformation to facilitate personal recovery were identified within mental health services. Social interventions should be further explored to translate the suggested social cultural changes into action.
COVID-19 pandemic-related anxiety, distress and burnout: prevalence and associated factors in healthcare workers of North-West Italy
Authors: Naldi Andrea , Vallelonga Fabrizio , Di Liberto Alessandra , Cavallo Roberto , Agnesone Monica , Gonella Marco , Sauta Maria Domenica , Lochner Piergiorgio , Tondo Giacomo , Bragazzi Nicola Luigi , Botto Rossana , Leombruni Paolo
Published: January 2021

Background

The COVID-19 pandemic caused drastic changes in healthcare and severe social restrictions. Healthcare workers (HCWs) are on the front line against the virus and have been highly exposed to pandemic-related stressors, but there are limited data on their psychological involvement for a large sample in Italy.

Aims

To investigate the prevalence of anxiety, distress and burnout in HCWs of North-West Italy during the COVID-19 pandemic, and to detect potential psychosocial factors associated with their emotional response.

Method

This cross-sectional, survey-based study enrolled 797 HCWs. Participants completed the Impact of Event Scale – Revised, the State-Trait Anxiety Inventory – Form Y and the Maslach Burnout Inventory; demographic, family and work characteristics were also collected. Global psychological outcome, differences among professions and independent factors associated with worst psychological outcome were assessed.

Results

Almost a third of the sample had severe state anxiety and distress, high emotional exhaustion and depersonalisation, and low personal accomplishment. Distress was higher in women and nurses, whereas depersonalisation was higher in men. Family division, increased workload, job changes and frequent contact with COVID-19 were associated with worst psychological outcome. Trait anxiety was associated with significantly higher risk for developing state anxiety, distress and burnout.

Conclusions

An elevated psychological burden related to the COVID-19 pandemic was observed in HCWs of North-West Italy. The identification of family and work characteristics and a psychological pre-existing condition as factors associated with worst psychological outcome may help provide a tailored, preventive, organisational and psychological approach in counteracting the psychological effects of future pandemics.
Risk of mortality and complications in patients with schizophrenia and diabetes mellitus: population-based cohort study
Authors: Chan Joe Kwun Nam , Wong Corine Sau Man , Or Philip Chi Fai , Chen Eric Yu Hai , Chang Wing Chung
Published: January 2021

Background

Schizophrenia patients have markedly elevated prevalence of diabetes compared with the general population. However, risk of mortality and diabetes-related complications among schizophrenia patients with co-occurring diabetes is understudied.

Aims

We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes.

Method

This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68 682 patients with incident diabetes only between 2001 and 2016 in Hong Kong using a medical record database of public healthcare services. Association between schizophrenia and all-cause mortality was examined with a Cox proportional hazards model. Effect of schizophrenia on first-year complication occurrence following diabetes diagnosis and post-complication mortality rates were evaluated.

Results

Schizophrenia was associated with increased all-cause mortality (adjusted hazards ratio [aHR] 1.11, 95% CI 1.05–1.18), particularly among men and older age groups. Schizophrenia patients with diabetes had higher metabolic complication rate (aHR 1.99, 95% CI 1.63–2.42), lower microvascular complication rate (aHR 0.75, 95% CI 0.65–0.86) and comparable macrovascular complication rate (aHR 0.93, 95% CI 0.85–1.03), relative to patients with diabetes only. Among patients with diabetes complications, schizophrenia was associated with elevated all-cause mortality after macrovascular (aHR 1.19, 95% CI 1.04–1.37) and microvascular (aHR 1.33, 95% CI 1.08–1.64) complications. Gender-stratified analyses revealed that a significant effect of schizophrenia on heightened post-complication mortality was observed in men only.

Conclusions

Schizophrenia patients with co-occurring diabetes are at increased risk of excess mortality, including post-complication mortality. Further research identifying effective interventions is warranted to optimise diabetes-related outcomes in this vulnerable population.
Incidence of neurodegenerative and cerebrovascular diseases associated with antihypertensive drug classes
Authors: Harrison Paul J. , Colbourne Lucy , Luciano Sierra
Published: January 2021

Antihypertensive drugs (AHTs) are associated with lowered risks of neurodegenerative diseases and stroke. However, the relative risks associated with different AHT classes are unclear. Using an electronic health record network with 34 million eligible patients, we compared rates of these disorders over a 2-year period, in propensity score-matched cohorts of people taking calcium channel blockers (CCBs) compared with those taking other AHT classes. CCBs were associated with a higher incidence of all disorders compared with renin-angiotensin system agents, and a higher incidence of dementia and cerebrovascular disease compared with diuretics. CCBs were associated with a lower incidence of movement disorders and cerebrovascular disease compared with beta-blockers. The data show that AHT classes confer differential risks of neurodegenerative and cerebrovascular diagnoses.
Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing’s Syndrome Treatment
Authors: Creemers Sara G , Feelders Richard A , de Jong Frank H , Franssen Gaston J H , de Rijke Yolanda B , van Koetsveld Peter M , Hofland Leo J
Published: January 2021

Introduction

Racemic ketoconazole (RK) is a steroidogenesis inhibitor used for treatment of Cushing’s syndrome. Levoketoconazole (COR-003), the pure 2S,4R enantiomer, is potentially more potent and safe compared to RK. We compared in vitro effects of levoketoconazole and RK on adrenocortical and pituitary adenoma cells.

Materials and methods

HAC15 cells and 15 primary human neoplastic adrenocortical cultures (+/− ACTH), and murine (AtT20) and human corticotroph adenoma cultures were incubated with levoketoconazole or RK (0.01-10 µM). Cortisol and ACTH were measured using a chemiluminescence immunoassay system, and steroid profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

In HAC15, levoketoconazole inhibited cortisol at lower concentrations (IC50: 0.300 µM) compared to RK (0.611 µM; P < 0.0001). IC50 values of levoketoconazole for basal cortisol production in primary adrenocortical cultures varied over a 24-fold range (0.00578-0.140 µM), with 2 patients having a higher sensitivity for levoketoconazole vs RK (2.1- and 3.7-fold). LC-MS/MS analysis in selected cases revealed more potent inhibition of cortisol and other steroid profile components by levoketoconazole vs RK. In AtT20, levoketoconazole inhibited cell growth and ACTH secretion (10 µM: −54% and −38%, respectively), and levoketoconazole inhibited cell number in 1 of 2 primary human corticotroph pituitary adenoma cultures (−44%, P < 0.001).

Conclusion

Levoketoconazole potently inhibits cortisol production in adrenocortical cells, with a variable degree of suppression between specimens. Levoketoconazole inhibits adrenal steroid production more potently compared to RK and might also inhibit ACTH secretion and growth of pituitary adenoma cells. Together with previously reported potential advantages, this indicates that levoketoconazole is a promising novel pharmacotherapy for Cushing’s syndrome.
Turgor-dependent and coronin-mediated F-actin dynamics drive septin disc-to-ring remodeling in the blast fungus Magnaporthe oryzae
Authors: Dulal Nawaraj , Rogers Audra Mae , Proko Rinalda , Bieger Baronger Dowell , Liyanage Rohana , Krishnamurthi Venkata Rao , Wang Yong , Egan Martin John
Published: January 2021

The fungus Magnaporthe oryzae uses a specialized pressure-generating infection cell called an appressorium to break into rice leaves and initiate disease. Appressorium functionality is dependent on the formation of a cortical septin ring during its morphogenesis, but precisely how this structure assembles is unclear. Here, we show that F-actin rings are recruited to the circumference of incipient septin disc-like structures in a pressure-dependent manner, and that this is necessary for their contraction and remodeling into rings. We demonstrate that the structural integrity of these incipient septin discs requires both an intact F-actin and microtubule cytoskeleton and provide fundamental new insight into their functional organization within the appressorium. Lastly, using proximity-dependent labeling, we identify the actin modulator coronin as a septin-proximal protein and show that F-actin-mediated septin disc-to-ring remodeling is perturbed in the genetic absence of coronin. Taken together, our findings provide new insight into the dynamic remodeling of infection-specific higher-order septin structures in a globally significant fungal plant pathogen.
Ferroptosis induces membrane blebbing in placental trophoblasts
Authors: Kajiwara Kazuhiro , Beharier Ofer , Chng Choon-Peng , Goff Julie P. , Ouyang Yingshi , St Croix Claudette M. , Huang Changjin , Kagan Valerian E. , Hsia K. Jimmy , Sadovsky Yoel
Published: January 2021

Ferroptosis is a regulated, non-apoptotic form of cell death, characterized by hydroxy-peroxidation of discrete phospholipid hydroperoxides, particularly hydroperoxyl (Hp) forms of arachidonoyl- and adrenoyl-phosphatidylethanolamine, with a downstream cascade of oxidative damage to membrane lipids, proteins and DNA, culminating in cell death. We recently showed that human trophoblasts are particularly sensitive to ferroptosis caused by depletion or inhibition of glutathione peroxidase 4 (GPX4) or the lipase PLA2G6. Here, we show that trophoblastic ferroptosis is accompanied by a dramatic change in the trophoblast plasma membrane, with macro-blebbing and vesiculation. Immunofluorescence revealed that ferroptotic cell-derived blebs stained positive for F-actin, but negative for cytoplasmic organelle markers. Transfer of conditioned medium that contained detached macrovesicles or co-culture of wild-type target cells with blebbing cells did not stimulate ferroptosis in target cells. Molecular modeling showed that the presence of Hp-phosphatidylethanolamine in the cell membrane promoted its cell ability to be stretched. Together, our data establish that membrane macro-blebbing is characteristic of trophoblast ferroptosis and can serve as a useful marker of this process. Whether or not these blebs are physiologically functional remains to be established.

This article has an associated First Person interview with the first author of the paper.
GESTÃO DOS PRODUTOS COM BAIXO GIRO DE ESTOQUE EM UMA INDÚSTRIA DE MÉDIO PORTE DO SETOR ELÉTRICO
Authors: Cantele Marcos , Miri Daniel Hank , Reis Zaida Cristine dos , Machado Vanessa De Campos , Ganzer Paula Patrícia , Chais Cassiane , Matte Juliana , Olea Pelayo Munhoz
Published: January 2021

O objetivo deste artigo consiste em identificar as causas da obsolescência dos produtos em uma empresa de médio porte do setor elétrico, cujo processo de fabricação é caracterizado pelo Engineering-to-Order(ETO), propondo ações para sanar tal problemática. Para isso, procedeu-se à aplicação de entrevistas semiestruturadas e à coleta de documentos e relatórios da empresa em estudo. Foram identificados como causas solicitação de compra de materiais para projetos especiais, troca de itens de engenharia sem revisar o estoque, cadastro de produtos descentralizados, alteração do projeto com troca de material, compra de materiais por meio de kits e ausência de método que informe a existência de itens similares. Em face disso, asações propostas foram gerar pré-estrutura para compra conforme necessidades, realizar análise de estoques e compras para cadastro de novos produtos, limitar o número de usuários para cadastro de matéria-prima, enviar ao cliente materiais que sobraram em decorrência de alteração de projeto e utilizar os itens de forma avulsa.
AVALIAÇÃO DO ECOSSISTEMA DE INOVAÇÃO DE UMA UNIVERSIDADE NA REGIÃO SUL DO BRASIL
Authors: Bobsin Evandro Luis , Oliveira Jaqueline Da Silva , Casagrande Roberta Fischer , Alfonso Taís Oliveira da Silva , Silva Bibiana Porto da
Published: January 2021

O conhecimento gerado pelas universidades pode contribuir, de forma estratégica, para o desenvolvimento dos ecossistemas de inovação. As universidades são atores importantes nas articulações junto a governos, empresas e sociedade. Dada a importância desse papel, há um esforço da comunidade acadêmica em avaliar os ecossistemas de inovação em que as universidades estão presentes. Assim, o objetivo deste trabalho é analisar o ecossistema de inovação de uma universidade da região Sul do Brasil por meio de um modelo chamado de estrutura de capacidades dinâmicas. A universidade estudada foi analisada sob os eixos: pesquisa, educação e programas de suporte; estudantes e grupos de doutorado; incubadoras, aceleradoras e espaços de coworking; investidores, mentores e redes de alunos e treinamentos, competições, eventos e seminários. Concluiu-se que o ecossistema está no estágio de desenvolvimento conforme o modelo utilizado para análise e que, entre seus pontos fortes, estão as parcerias firmadas entre os atores do ecossistema.
Anti-c-myc cholesterol based lipoplexes as onco-nanotherapeutic agents in vitro
Authors: Habib Saffiya , Daniels Aliscia , Ariatti Mario , Singh Moganavelli
Published: January 2021

Background: Strategies aimed at inhibiting the expression of the c-myc oncogene could provide the basis for alternative cancer treatment. In this regard, silencing c-myc expression using small interfering RNA (siRNA) is an attractive option. However, the development of a clinically viable, siRNA-based, c-myc silencing system is largely dependent upon the design of an appropriate siRNA carrier that can be easily prepared. Nanostructures formed by the electrostatic association of siRNA and cationic lipid vesicles represent uncomplicated siRNA delivery systems.

Methods: This study has focused on cationic liposomes prepared with equimolar quantities of the cytofectin, N,N-dimethylaminopropylamido-succinylcholesteryl-formylhydrazide (MS09), and cholesterol (Chol) for the development of a simple, but effective anti- c-myc onco-nanotherapeutic agent. Liposomes formulated with dioleoylphosphatidylethanolamine (DOPE) in place of Chol as the co-lipid were included for comparative purposes.

Results: Liposomes successfully bound siRNA forming lipoplexes of less than 150 nm in size, which assumed bilamellar aggregrates. The liposome formulations were well tolerated in the human breast adenocarcinoma (MCF-7) and colon carcinoma (HT-29) cells, which overexpress c-myc. Lipoplexes directed against the c-myc transcript mediated a dramatic reduction in c-myc mRNA and protein levels. Moreover, oncogene knockdown and anti-cancer effects were superior to that of Lipofectamine™ 3000.

Conclusion: This anti- c-myc MS09:Chol lipoplex exemplifies a simple anticancer agent with enhanced c-myc gene silencing potential in vitro
Application of Value Clarification Technique (Vct) Models in Improving Learning Outcomes in Dangerous Goods Regulation
Authors: Setiawan Ariyono
Published: January 2021

Learning in school or in every educational institution has an important role as a media liaison between knowledge and students or students. There are many learning methods or models used in education. Of the many methods or modes, there is one of them is a clarification value technology (VCT) model. The teaching method is a knowledge of teaching methods used by a teacher or instructor. Another understanding is the presentation technique mastered by the teacher to teach or present learning materials to students in class both individually and in groups. the learning method by clarifying the value of the value clarification technique is teaching to shape students in finding and determining a value that is considered good in dealing with a problem through the process of analyzing existing values and embedded in students. Meanwhile, learning outcomes are abilities students have after they have a learning experience. The purpose of this study is to determine the level of learning outcomes of a particular institution. In this study the object of research from an educational institution that is competent in the field of flight is used. The institution is Surabaya Aviation Polytechnic. The subject of learning taken was Regulation of Dangerous Goods at Surabaya Aviation Polytechnic. In addition, this study was also conducted to determine differences in learning outcomes of cadets in the Lessons on Dangerous Goods Regulations in Surabaya Aviation using the Value Clarification Technique (VCT) method. This type of research is Classroom Action Research (CAR). The research carried out is included in the design of one group pretest and possttest research. the research design that contained pretest before being given treatment and posttest after being treated. This research was conducted at Surabaya Aviation Polytechnic. The data analysis technique used is the different test. Based on data management and analysis results, it can be concluded that the application of learning of Value Clarification Techniques can improve the learning outcomes of cadets. This is evidenced by the differences in learning outcomes of Cycle I and Cycle II significantly
The Development of Learning Media Using Interactive Jobsheets for Basic Subjects in Electricity and Electronics Using PSIM in Tamansiswa Vocational High School
Authors: Hidayat Nurul
Published: January 2021

This study aims to develop learning devices for the subjects of Elementary Electricity and Electronics in class X. As long as learning in class does not provide practical activities, it is necessary to develop learning devices equipped with practical activities as soon as possible.This study uses a 4-D model development model. This study consisted of 2 classes with 1 non-experimental class and 1 experimental class.The rating results show the percentage of 96% so that it can be concluded that the learning device meets eligibility. The results of sample t-test correlate results obtained are 39.480, the value of t table is 2.045. The rating results indicate the percentage of 88% so that it can be concluded that the learning tool helps students carry out learning activities and practicum. The results of t-test on 2 independent samples obtained 4.420, the value of t table is 2.045.
A natural fit
Authors: Gladwin Katharine
Published: January 2021

Dentists are inherently skilled to provide facial aesthetics – and dental nurses are well-placed to assist them. Katharine Gladwin shares her enthusiasm for these complementary cosmetic treatments
Giant Brillouin Amplification in Gases
Authors: Yang Fan , Gyger Flavien , Thévenaz Luc
Published: January 2021

The low-loss properties of hollow-core fibers all result from a much lower interaction between photons and dense fiber material. This dramatically reduces losses, but also significantly reduces the possibilities for direct optical amplification. This year, our team offered an efficient solution to this quandary.
Superwicking Black Metal Surface for Solar-Thermal Water Sanitation
Authors: Singh Subhash C. , ElKabbash Mohamed , Li Zilong , Li Xiaohan , Regmi Bhabesh , Madsen Matthew , Jalil Sohail A. , Zhan Zhibing , Zhang Jihua , Guo Chunlei
Published: January 2021

Wastewater recycling could be part of an environmentally feasible solution to an increasing global water crisis. In a recent work, we made a push toward that end, introducing a super-wicking, super-light-absorbing solar trackable panel for water sanitation.
Structural determination of Streptococcus pyogenes M1 protein interactions with human immunoglobulin G using integrative structural biology
Authors: Khakzad Hamed , Happonen Lotta , Karami Yasaman , Chowdhury Sounak , Bergdahl Gizem Ertürk , Nilges Michael , Tran Van Nhieu Guy , Malmström Johan , Malmström Lars
Published: January 2021

Streptococcus pyogenes(Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (FcγR) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify XLs between the constant region of the Fab-domain and certain regions of the M1 protein engaged in the Fab-mediated binding. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.
The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
Authors: Lee Bruce Y. , Bartsch Sarah M. , Ferguson Marie C. , Wedlock Patrick T. , O’Shea Kelly J. , Siegmund Sheryl S. , Cox Sarah N. , McKinnell James A.
Published: January 2021

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R0) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R0 2.0). With R0 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R0 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.