bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrofulguration‐assisted dermabrasion is comparable to manual dermabrasion in patients undergoing autologous non‐cultured epidermal cell suspension for treatment of stable vitiligo: A randomized controlled trial
Authors: Dev Anubha , Vinay Keshavamurthy , Kumaran Muthu Sendhil , Bishnoi Anuradha , Srivastava Niharika , Dogra Sunil , Parsad Davinder
Published: June 2021

Background

Recipient site preparation is a crucial step in non‐cultured epidermal cell suspension (NCES) as it facilitates proper uptake of the grafted melanocytes.

Objectives

To compare the repigmentation rate of recipient sites prepared with manual dermabrasion (MD) versus electrofulguration‐assisted dermabrasion (EF) in patients undergoing NCES for treatment of stable vitiligo.

Methods

This was a prospective randomized study including 26 patients of stable vitiligo (VIDA 0 or −1), each having two patches of size greater than 3 × 3 cm located symmetrically or at the same site or a single patch of 6 × 6 cm or larger. After randomization of patches in the given patient, MD and EF were performed on recipient areas followed by NCES. The patients were followed up at 4 weekly intervals up to 24 weeks and assessed for extent of repigmentation and adverse effects if any.

Results

Greater than 75% repigmentation was observed in 69.3% of the patches prepared by MD as compared to 73.1% patches prepared by EF at the end of 24 weeks (p = 0.791). The mean improvement in target VASI was 64.0% in the MD group as compared to 68.8% in the EF group (p = 0.21). Patches prepared by EF achieved successful repigmentation earlier as compared to patches prepared by MD (9.4 weeks vs 11.4 weeks, p = 0.12).

Conclusion

Both MD and EF have comparable outcomes with respect to all parameters.
Efficacy and safety of topical administration of tacrolimus in oral lichen planus: An updated systematic review and meta‐analysis of randomized controlled trials
Authors: Su Zhangci , Hu Jiaqi , Cheng Bin , Tao Xiaoan
Published: June 2021

Background

Symptomatic oral lichen planus is a common chronic T‐cell‐mediated disorder characterized by pain and inflammation. The meta‐analysis aimed to compare and evaluate the effects and safety of tacrolimus for treating patients with symptomatic oral lichen planus.

Methods

A comprehensive literature review was performed, including PubMed, the Cochrane Library, Embase, and Web of Science published up to and including December 2020. ClinicalTrials.gov was searched for ongoing trials. There were no restrictions on language or date of publication. Using the Cochrane Collaboration tool, we assessed the risk of bias for randomized controlled trials and estimated the proportion of between‐trial heterogeneity.

Results

A total of 9 RCTs evaluating the effects of tacrolimus were included in this study. The results revealed no significant difference in clinical resolution and relapse between tacrolimus and corticosteroids. However, tacrolimus may be more likely to cause mild adverse effects. In particular, clinical resolution was not significantly different between tacrolimus and clobetasol propionate, and between tacrolimus and triamcinolone acetonide, while tacrolimus was more likely to cause adverse effects than triamcinolone acetonide and clobetasol propionate. Moreover, there was no significant difference in pain resolution between tacrolimus and clobetasol. Furthermore, adverse effects were not significantly different between tacrolimus and pimecrolimus.

Conclusions

This systematic review and meta‐analysis of 9 clinical trials supported the short‐term application of tacrolimus as an effective regimen in OLP patients resistant to other topical and systemic therapies. Furthermore, the adverse effects of tacrolimus were minor and transient and did not affect tacrolimus’ continued application.
Treatment of advanced‐stage canine nasal carcinomas with toceranib phosphate: 23 cases (2015–2020)
Authors: Merino‐Gutierrez V. , Borrego J. F. , Puig J. , Hernández A. , Clemente‐Vicario F.
Published: June 2021

Objective

To determine the median survival time (MST) of dogs with nasal carcinoma treated with toceranib phosphate.

Material and methods

The databases of four Spanish referral hospitals were retrospectively searched for dogs with a diagnosis of nasal tumours presented between January 2015 and October 2020. Dogs treated with radiotherapy or other chemotherapies prior toceranib were excluded.

Results

Twenty‐three dogs with a confirmed nasal carcinoma treated with toceranib phosphate and with a CT scan for initial staging according to Adams Modified Staging System were included. Nine dogs had a stage III nasal carcinoma whereas 14 dogs had a stage IV nasal carcinoma. No dog had stages I and II nasal carcinoma. The median overall survival time was 139 days. The difference between the MST between dogs with stages III and IV was not statistically significant [P = 0.6, 140 days for stage III (range 46–401)vs120 days for stage IV (range 23–600)]. Overall, dogs with epistaxis achieved a longer median survival (166 days) than dogs without epistaxis (83 days). Toceranib phosphate was generally well tolerated. Most dogs had an initial clinical benefit followed by progressive disease.

Significance

This is the first study to report the MST in dogs with stages III and IV nasal carcinoma treated with toceranib phosphate. This retrospective study showed that toceranib phosphate decreases the clinical signs associated with nasal carcinomas.
Translocations maintain genetic diversity and increase connectivity in sea otters, Enhydra lutris
Authors: Larson Shawn , Gagne Roderick B. , Bodkin Jim , Murray Michael J. , Ralls Katherine , Bowen Lizabeth , Leblois Raphael , Piry Sylvain , Penedo Maria Cecilia , Tinker M. Tim , Ernest Holly B.
Published: June 2021

Sea otters, Enhydra lutris, were once abundant along the nearshore areas of the North Pacific. The international maritime fur trade that ended in 1911 left 13 small remnant populations with low genetic diversity. Subsequent translocations into previously occupied habitat resulted in several reintroduced populations along the coast of North America. We sampled sea otters between 2008 and 2011 throughout much of their current range and used 19 nuclear microsatellite markers to evaluate genetic diversity, population structure, and connectivity between remnant and reintroduced populations. Average genetic diversity within populations was similar: observed heterozygosity 0.55 and 0.53, expected heterozygosity 0.56 and 0.52, unbiased expected heterozygosity 0.57 and 0.52, for reintroduced and remnant populations, respectively. Sea otter population structure was greatest between the Northern and Southern sea otters with further structuring in Northern sea otters into Western, Central, and Southeast populations (including the reintroduced populations). Migrant analyses suggest the successful reintroductions and growth of remnant groups have enhanced connectivity and gene flow between populations throughout many of the sampled Northern populations. We recommend that future management actions for the Southern sea otter focus on future reintroductions to fill the gap between the California and Washington populations ultimately restoring gene flow to the isolated California population.
COVID‐19‐associated mucormycosis: An updated systematic review of literature
Authors: Pal Rimesh , Singh Birgurman , Bhadada Sanjay Kumar , Banerjee Mainak , Bhogal Ranjitpal Singh , Hage Neemu , Kumar Ashok
Published: June 2021

In its wake, the COVID‐19 pandemic has ushered in a surge in the number of cases of mucormycosis. Most cases are temporally linked to COVID‐19; hence, the entity is described as COVID‐19‐associated mucormycosis (CAM). The present systematic review was undertaken to provide an up‐to‐date summary of the hitherto available literature on CAM. PubMed, Scopus and Google Scholar databases were systematically searched using appropriate keywords till 14 May 2021, to identify case reports/case series pertaining to mucormycosis in patients with COVID‐19. Relevant data extracted included demographic characteristics, comorbidity profile, clinical category of mucormycosis, glucocorticoid use, treatment offered and patient outcome. We identified 30 case reports/case series, pooling data retrieved from 99 patients with CAM. Most cases were reported from India (72%). The majority of the patients was male (78%) and had diabetes mellitus (85%). A prior history of COVID‐19 was present in 37% patients with mucormycosis developing after an initial recovery. The median time interval between COVID‐19 diagnosis and the first evidence of mucormycosis infection or CAM diagnosis was 15 days. Glucocorticoid use was reported in 85% of cases. Rhino‐orbital mucormycosis was most common (42%), followed by rhino‐orbito‐cerebral mucormycosis (24%). Pulmonary mucormycosis was observed in 10 patients (10%). The mortality rate was 34%; the use of adjunct surgery, which was undertaken in 81% of patients, was associated with better clinical outcomes (p < .001). In conclusion, CAM is an emerging problem necessitating increased vigilance in COVID‐19 patients, even those who have recovered. CAM portends a poor prognosis and warrants early diagnosis and treatment.
The Ernest Gellner Nationalism Lecture: Nationalism and the crises of global modernity
Authors: Duara Prasenjit
Published: June 2021

Whether or not there is a direct causal relationship, nationalism is at the heart of all the crises in the modern world and becomes entangled in its effects. As the fundamental source of authority for all modes of governance in the world, we are beholden to its capacity to resolve these cascading crises. I argue that the nation form is the ‘epistemic engine’ driving the globally circulatory and doxic Enlightenment ideal of the conquest of nature and perpetual growth that sustains the runaway technosphere. The cascading crises that we have already witnessed in this century—financial, economic, epidemic and climatological—are rooted significantly in this technosphere. At the same time, we will have to find our way through and out of these forms to secure a sustainable planet. I explore the interstitial spaces and counter‐flows of social movements that are seeking to develop a post‐Enlightenment and a planetary, rather than a global, cosmology.
Source‐to‐sink response to high‐amplitude lake level rise driven by orbital‐scale climate change: An example from the Pleistocene Lake Malawi (Nyasa) Rift, East Africa
Authors: Tan Mingxuan , Scholz Christopher A.
Published: June 2021

Sedimentary systems respond to environmental forcings in dissimilar ways over different timescales. The Lake Malawi (Nyasa) Rift is an ideal natural laboratory for evaluating the overall functioning of lacustrine source‐to‐sink systems on orbital or younger scales. These closed sedimentary systems exhibited high spatiotemporal climate variability, and their responses to two late Pleistocene lake‐level stillstands are evaluated. The coarse‐grained deposits documented a dramatic transgression from 350 to 200 m below present lake‐level (BPLL) developed during an important climate transition in tropical Africa. Based on an integrated analysis of a digital elevation model and high‐resolution single/multi‐channel seismic profiles, catchment geomorphology has been linked with sediment delivery in the sink area. The coarse‐grained deposition of each source‐to‐sink system is quantified through a sediment mass calculation. A modified empirically‐derived ‘BQART’ predictor with a bedload equation to assess the sediment discharge is employed based on a Monte Carlo simulation, considering temperature lapse rate and topographic effects. The river discharges are estimated by specific empirical relationships that associate catchment area to various climate systems, developed using a global modern river database. The results show that the total sediment discharge increases from 7.53 to 9.50 Mt year−1; likewise, the preserved coarse‐grained deposits also record a significant increase in deposition rate from 350 to 200 m BPLL stage, indicating that the short length‐scale source‐to‐sink systems are sensitive to the high‐amplitude lake transgression developed from the climate shift. The volume of upstream buffered deposits may decrease within the progressively wetter climate, while the buffering degree was substantially influenced by the pre‐existing landforms. Moreover, the substantial deep‐water mud dispersal is not well‐developed, despite the relatively higher lake‐level and slightly wetter climate. This quantitative source‐to‐sink analysis with the modified sediment predictor yields preliminary constraints for system functioning in response to high‐amplitude climate change in a closed sedimentary system.
Medical students’ experiences of health inequalities and inclusion health education
Authors: Dixon Hannah , Povall Anna , Ledger Alison , Ashwell Gemma
Published: June 2021

Background

Inclusion health groups experience a significantly larger burden of morbidity and mortality than the general public. Despite this, undergraduate medical education is often limited in its approach to inclusion health curricula, leaving students disengaged and lacking understanding.

Methods

We conducted two research studies to explore medical students’ experiences of inclusion health education. All participants were studying medicine at the University of Leeds at the time of data collection. We gathered experiences of both compulsory and elective inclusion health education via semi‐structured interviews. Interview responses were audio‐recorded, transcribed and analysed thematically.

Findings

We identified several key findings across the two studies.

Firstly, medical students felt unprepared to work with inclusion health groups.

Further to this, medical students have a preference for interactive teaching and learning in inclusion health education.

Finally, encountering inclusion health groups by chance (on placement) or choice (optional initiatives) present different opportunities.

Discussion and Conclusion

Our research suggests that simply being exposed to inclusion health groups through lectures and on placement is not considered sufficient by medical students, and in fact can lead to the perpetuation of misinformation and stigma.

Participants perceived that optional initiatives or ‘choice encounters’ had profoundly positive impacts on attitudes and interest, particularly when there were opportunities to learn directly from individuals with lived experience of exclusion. We suggest that a flipped classroom approach to inclusion health education along with integrated experiential learning would provide medical students with comprehensive and patient‐focused learning opportunities.
Spatial key performance indicators on the statewide ambulance service coverage of multiple regional classifications
Authors: Lee EunSu , McDonald Melanie , Montgomery William , O’Neill Erin
Published: June 2021

The total population covered by the current ambulance service under threshold response time and policy is one of the major concerns for policymakers and ambulance service designers. This study investigates the statewide service coverage based on regional types of urban, rural, and frontier to address emergency medical service (EMS) disparity. A statewide ambulance coverage case study is conducted for the state of North Dakota. This study revisited the spatial key performance indicators (SKPIs) of EMS and proposed innovative spatial modeling for statewide EMS coverage in view of service users, providers, and public health designers. Statewide ground ambulance service coverages were mapped to three types of indicators, including: (a) geographical backup coverages; (b) predicted response and travel time distance at census block level; and (c) the ratio of population being covered by the threshold response time coverage at the county level using GIS. The study demonstrated that the service shortage and multiple service areas are clearly explained using the suggested SKPIs, and the underserved areas are drilled down into expected response and travel time for each census block and the population‐covered ratio for each county for further investigation.
Contrast enhanced computed tomography assessment of superficial inguinal lymph node metastasis in canine mammary gland tumors
Authors: Soultani Christina , Patsikas Michail N. , Mayer Monique , Kazakos Georgios M. , Theodoridis Theodoros D. , Vignoli Massimo , Ilia Tatiani Soultana M. , Karagiannopoulou Maria , Ilia Georgia M. , Tragoulia Ioanna , Angelou Vasileia N. , Chatzimisios Kyriakos , Tselepidis Stavros , Papadopoulou Paraskevi L. , Papazoglou Lysimachos G.
Published: June 2021

Mammary gland neoplasms are predominant in dogs. However, sentinel lymph node (SLN) status assessment criteria have not been established for these cases. In this retrospective, secondary analysis, diagnostic case control study, CT images of 65 superficial inguinal SLNs were obtained before and 1, 3, 5, and 10 min after intravenous administration of contrast agent (iopamidol 370 mgI/mL). The presence and degree of postcontrast enhancement were assessed, by means of the median absolute density value and the maximum absolute density value at any time point in the center and in the periphery of each SLN measured in Hounsfield units (HU), before and after contrast agent administration. These values were compared with histopathological findings postsurgical excision. Receiver operating characteristic analysis was conducted. The absolute density values ranged widely at each time point and within each group of nodes (negative, positive, control group). At all time points, the median density value in the center and in the periphery was significantly higher in metastatic than in non‐metastatic SLNs (P ≤ .014). Among the parameters tested, the median absolute density value measured in the periphery of the SLN 3 min after injection showed the highest sensitivity, specificity, and accuracy (AUC) (87.5%, 82.1%, and 92.1% respectively), with a cutoff value of 50.9 HU. The maximum absolute density value at any time point in the center and periphery of the SLNs was also significantly higher in metastatic SLNs compared to non‐metastatic (P ≤ .001). With a cutoff value of 59.5 HU, the maximum absolute density value in the periphery of the SLN displayed high sensitivity and specificity (87.5% and 89.3%, respectively). The results of this study support the hypothesis that contrast enhanced CT imaging may aid in the assessment of SLN metastasis in dogs with mammary gland neoplasms.
Bending Frequency of a Rotating Cantilever Beam
Authors: Schilhansl M. J.
Published: June 2021

The stiffening effect of the centrifugal forces on the first-mode bending frequency of a rotating cantilever beam of uniform cross section is investigated by means of the method of successive approximations. It depends upon the angle made by the minor axis of inertia with the direction of the circumferential velocity.
The Pressure for Indenting Material Resting on a Rough Foundation
Authors: Johnson W. , Woo D. M.
Published: June 2021

To indent a material on a rough foundation under conditions of plane strain, a slip-line-field solution is proposed and a general expression obtained for the necessary pressure. For extreme values of friction, calculated values are given.
The Bursting Pressure of Cylindrical and Spherical Vessels
Authors: Svensson N. L.
Published: June 2021

The relationship between pressure and change of dimensions for cylindrical and spherical vessels subjected to internal pressure is considered for a material having a stress-strain curve of the form σ = σ0ϵn. The equations obtained are analyzed further to obtain expressions for the bursting pressure for these vessels. From these results simplified expressions are obtained for the calculation of the bursting pressure for any vessel. Comparison with one set of experimental results shows excellent agreement.
Stress Distribution Around a Circular Inclusion in a Semi-Infinite Elastic Plate
Authors: Saleme E. M.
Published: June 2021

This paper contains an exact two-dimensional solution in series form for the stresses and displacements around a circular inclusion perfectly bonded to a semi-infinite elastic plate. At infinity the plate is assumed to be in a state of uniform tension parallel to the straight boundary. It should be emphasized, however, that the method of solution presented may be applied to other types of loading. Numerical results are given for the variation along the axis of symmetry of the normal stress which is parallel to the straight boundary, for a given geometry, and various ratios of the elastic moduli of the plate and the inclusion. Finally, the known solutions corresponding to an infinite plate with a circular inclusion and to a semi-infinite plate with a circular hole are obtained as limiting cases.
Comments on the Cutting of Metal Plates With High Explosive Charges
Authors: Drummond W. E.
Published: June 2021

The problem of the cutting of metal plates with high explosive charges is analyzed by treating the metal hydrodynamically. The hydrodynamic problem is solved in the linearized approximation and it is assumed that the metal splits wherever the pressure becomes sufficiently negative. It is shown that such negative pressures occur where two rarefaction waves meet and the predicted location of these splits is in qualitative agreement with experiment.
An Experimental Study of Initial and Subsequent Yield Surfaces in Plasticity
Authors: Naghdi P. M. , Essenburg F. , Koff W.
Published: June 2021

Experimental results for twenty-five tubular specimens of a 24S-T-4 aluminum alloy, subjected to combined torsion-tension-reversed torsion, are reported in a study of the initial and two subsequent yield surfaces covering the first and the fourth quadrant of the axial stress-shear stress plane. Results are also given for two additional specimens subjected to tension followed by torsion, in order to compare the values of the initial shear modulus at the initiation of twist with the elastic shear modulus.
Further Studies of Stress Distribution in Rotating Disks and Cylinders Under Elevated-Temperature Creep Conditions
Authors: Wahl A. M.
Published: June 2021

The analysis previously given for stress in rotating disks having central holes and under steady-state creep conditions is extended to cases where the radial and tangential stresses are equal over all or a portion of the disk, both constant and variable-thickness cases being considered. In addition, the solid rotating disk and the long rotating solid cylinder are treated, peak stresses above the elastic values being found under certain conditions. Charts are presented for determining ratios σtm/σtav between peak stress and average stress, for various diameter ratios, disk contours, and values of n in the power-function stress-creep rate relation. These indicate somewhat lower ratios of peak to average stress for the variable-thickness disks. Based on the theoretical results, curves of stress distribution are also worked out for several typical cases.
The Synthesis of a Four-Bar Mechanism for Prescribed Extreme Values of the Angular Velocity of the Driven Link
Authors: Hirschhorn J.
Published: June 2021

The “component method” of synthesis of four-bar mechanisms was discussed in detail in a previous publication. The present paper shows the application of this method to the synthesis of four-bar linkages with prescribed extremes of the angular velocity of the driven or output link.
Large Deflection of Stiffened Plates
Authors: Soper W. G.
Published: June 2021

The problem of nonlinear deflection of orthogonally stiffened plates subjected to static lateral load is treated using the concept of equivalent orthotropic plates. Equations are derived which are the appropriate generalizations of von Karman’s equations for isotropic plates. Rectangular plates are considered in detail, and an approximate solution is obtained through trigonometric series. The solution allows for rotational constraint along the plate boundary. All cases from simple support to complete fixity of boundary can therefore be treated.
Pitch and Curvature Corrections for Helical Springs
Authors: Ancker C. J. , Goodier J. N.
Published: June 2021

The tension and torsion helical springs of round cross section have been analyzed by a “thin-slice” method [1]. The effects of both curvature and pitch are included. The results of this analysis are given and discussed in this paper. Stresses, deflections, curvature changes, diametral contractions, and coupling effects are included.
A Simple Approach to an Approximate Two-Dimensional Cascade Theory
Authors: Schilhansl Max J.
Published: June 2021

The following simple approach to an approximate theory of incompressible two-dimensional flow past cascades, Fig. 1, is based on the so-called singularity method, in which the blade sections are replaced by sheets of vortexes, sources and sinks, and the flow induced by these singularities is calculated. The condition that the flow must be tangential to the blade surface, sometimes termed as the tangency condition, leads to a relation between the geometrical shape of the blade sections (camber and thickness), the cascade parameters (solidity and stagger angle), and the singularity distributions along the mean camber lines. As soon as these distributions are known, the pressure distribution and the lift may be determined. The calculation of the velocities at the blades is the most laborious portion of the whole problem. It has been carried out by various authors [1–4], with different mathematical methods. In this paper, a short, simple method of calculating the velocities induced by the singularities will be described. This approach has already been applied by others [5, 6], in less elaborate form.
An Improvement of the Holzer Method
Authors: Mahalingam S.
Published: June 2021

This paper presents a method of obtaining the next trial frequency from the results given by the previous Holzer table. The basis of the method is the effect of a small (fictitious) change in moment of inertia on the natural frequency of the torsional system. Although basically different, the method leads to a result which is very close to that given by Crandall and Strang. The relative merits of the two methods depend on whether the trial frequency is above or below the exact one and on whether or not the next approximation will overshoot the exact value.
Theoretical explanation of uneven frequency response of time-domain acoustic contrast control method
Authors: Hu Meiling , Lu Jing
Published: June 2021

Acoustic contrast control (ACC) is one of the most commonly utilized sound zone control methods, which maximizes the ratio of the average squared sound pressure in two control zones. The time-domain formulation of ACC (TACC) is usually preferred since it can optimize the whole bandwidth in a single step and the resulting control filter is guaranteed to be causal. Many researchers have noted that TACC suffers from uneven frequency response. However, a convincing theoretical explanation of this problem is yet to be investigated. In this letter, an asymptotically equivalent frequency-domain form of TACC is constructed, based on which it can be proven that TACC has the tendency of extracting the specific frequency component with the highest contrast. Simulation results validate the efficacy of this theoretical analysis.
Polyphonic training set synthesis improves self-supervised urban sound classification
Authors: Gontier Félix , Lostanlen Vincent , Lagrange Mathieu , Fortin Nicolas , Lavandier Catherine , Petiot Jean-François
Published: June 2021

Machine listening systems for environmental acoustic monitoring face a shortage of expert annotations to be used as training data. To circumvent this issue, the emerging paradigm of self-supervised learning proposes to pre-train audio classifiers on a task whose ground truth is trivially available. Alternatively, training set synthesis consists in annotating a small corpus of acoustic events of interest, which are then automatically mixed at random to form a larger corpus of polyphonic scenes. Prior studies have considered these two paradigms in isolation but rarely ever in conjunction. Furthermore, the impact of data curation in training set synthesis remains unclear. To fill this gap in research, this article proposes a two-stage approach. In the self-supervised stage, we formulate a pretext task (Audio2Vec skip-gram inpainting) on unlabeled spectrograms from an acoustic sensor network. Then, in the supervised stage, we formulate a downstream task of multilabel urban sound classification on synthetic scenes. We find that training set synthesis benefits overall performance more than self-supervised learning. Interestingly, the geographical origin of the acoustic events in training set synthesis appears to have a decisive impact.
Spatiotemporally confined red light-controlled gene delivery at single-cell resolution using adeno-associated viral vectors
Authors: Hörner Maximilian , Jerez-Longres Carolina , Hudek Anna , Hook Sebastian , Yousefi O. Sascha , Schamel Wolfgang W. A. , Hörner Cindy , Zurbriggen Matias D. , Ye Haifeng , Wagner Hanna J. , Weber Wilfried
Published: June 2021

Engineered red light-responsive OptoAAV system allows spatiotemporally controlled gene transfer at single-cell resolution.
Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4
Authors: Hoeksema Marten A. , Shen Zeyang , Holtman Inge R. , Zheng An , Spann Nathan J. , Cobo Isidoro , Gymrek Melissa , Glass Christopher K.
Published: June 2021

Genetic variants in transcription factor motifs result in divergent IL-4 responses in macrophages from inbred strains of mice.
Following spatial Aβ aggregation dynamics in evolving Alzheimer’s disease pathology by imaging stable isotope labeling kinetics
Authors: Michno Wojciech , Stringer Katie M. , Enzlein Thomas , Passarelli Melissa K. , Escrig Stephane , Vitanova Karina , Wood Jack , Blennow Kaj , Zetterberg Henrik , Meibom Anders , Hopf Carsten , Edwards Frances A. , Hanrieder Jörg
Published: June 2021

Metabolic isotope labeling and imaging mass spectrometry delineate early events of precipitating Aβ plaque pathology.
Longitudinal high-resolution imaging through a flexible intravital imaging window
Authors: Jacquemin Guillaume , Benavente-Diaz Maria , Djaber Samir , Bore Aurélien , Dangles-Marie Virginie , Surdez Didier , Tajbakhsh Shahragim , Fre Silvia , Lloyd-Lewis Bethan
Published: June 2021

A fully flexible imaging window acting as an implantable transparent “second skin” upgrades in vivo imaging.
Evaluation of Self-Collected Midturbinate Nasal Swabs and Saliva for Detection of SARS-CoV-2 RNA
Authors: Boerger Aimee C. , Buckwalter Seanne , Fernholz Emily C. , Jannetto Paul J. , Binnicker Matthew J. , Reed Katelyn , Walchak Robert , Woodliff Ethan , Johnson Michael , Pritt Bobbi S.
Published: June 2021

Rapid and accurate diagnostic testing is essential to bring the ongoing COVID-19 pandemic to an end. As the demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to increase amid supply shortages, many laboratories have investigated the use of sources other than nasopharyngeal (NP) swabs.
Capsid Proteins Are Necessary for Replication of a Parvovirus
Authors: Labadie Thomas , Garcia Deborah , Mutuel Doriane , Ogliastro Mylène , Cambray Guillaume
Published: June 2021

Densoviruses could be used as biological control agents to manage insect pests. Such applications require an in-depth biological understanding and associated molecular tools.
Pneumocystis Mating-Type Locus and Sexual Cycle during Infection
Authors: Hauser Philippe M.
Published: June 2021

Pneumocystis
species colonize mammalian lungs and cause deadly pneumonia if the immune system of the host weakens. Each species presents a specificity for a single mammalian host species.
Pneumocystis jirovecii
infects humans and provokes pneumonia, which is among the most frequent invasive fungal infections.
Identification and Removal of Potential Contaminants in 16S rRNA Gene Sequence Data Sets from Low-Microbial-Biomass Samples: an Example from Mosquito Tissues
Authors: Díaz Sebastián , Escobar Juan S. , Avila Frank W.
Published: June 2021

The study of tissue-associated microbiota from mosquitoes (primarily from the gut) has grown significantly in the last several years. Mosquito tissue samples represent a challenge for researchers given their low microbial biomass and similar taxonomic composition commonly found in the laboratory environment and in molecular reagents.
Structural Basis and Function of the N Terminus of SARS-CoV-2 Nonstructural Protein 1
Authors: Zhao Kaitao , Ke Zunhui , Hu Hongbing , Liu Yahui , Li Aixin , Hua Rong , Guo Fangteng , Xiao Junfeng , Zhang Yu , Duan Ling , Yan Xin-Fu , Gao Yong-Gui , Liu Bing , Xia Yuchen , Li Yan
Published: June 2021

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive.
Supplemental Material: The Origin and Tectonic Significance of the Basin and Range–Rio Grande Rift Boundary in Southern New Mexico, USA
Authors: Ricketts Jason W. , al. et
Published: June 2021

Full description of zircon (U-Th)/He modeling, inputs, and assumptions.
P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials
Authors: Valgimigli Marco , Gragnano Felice , Branca Mattia , Franzone Anna , Baber Usman , Jang Yangsoo , Kimura Takeshi , Hahn Joo-Yong , Zhao Qiang , Windecker Stephan , Gibson Charles M , Kim Byeong-Keuk , Watanabe Hirotoshi , Song Young Bin , Zhu Yunpeng , Vranckx Pascal , Mehta Shamir , Hong Sung-Jin , Ando Kenji , Gwon Hyeon-Cheol , Serruys Patrick W , Dangas George D , McFadden Eùgene P , Angiolillo Dominick J , Heg Dik , Jüni Peter , Mehran Roxana
Published: June 2021

Objective

To assess the risks and benefits of P2Y
12
inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients’ characteristics.

Design

Individual patient level meta-analysis of randomised controlled trials.

Data sources

Searches were conducted in Ovid Medline, Embase, and three websites (
www.tctmd.com
,
www.escardio.org
,
www.acc.org/cardiosourceplus
) from inception to 16 July 2020. The primary authors provided individual participant data.

Eligibility criteria

Randomised controlled trials comparing effects of oral P2Y
12
monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation.

Main outcome measures

The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding.

Results

The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y
12
inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ
2
=0.00) and in 303 (2.94%) with P2Y
12
inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ
2
=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y
12
inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y
12
inhibitor monotherapy than with DAPT (97 (0.89%)
v
197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ
2
=0.03), which was consistent across subgroups, except for type of P2Y
12
inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y
12
inhibitor rather than clopidogrel was part of the DAPT regimen.

Conclusions

P2Y
12
inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT.

Registration

PROSPERO CRD42020176853.
Identification of candidate gene variants of monogenic diabetes using targeted panel sequencing in early onset diabetes patients
Authors: Lee Dong-Hwa , Kwak Soo-Heon , Park Hee Sue , Ku Eu Jeong , Jeon Hyun Jeong , Oh Tae Keun
Published: June 2021

Introduction

Monogenic diabetes is attributed to genetic variations in a single gene. Maturity-onset diabetes of the young (MODY) is the most common phenotype associated with monogenic diabetes, but is frequently misdiagnosed as either type 1 or type 2 diabetes. Increasing our basic understanding of genetic variations in MODY may help to improve the accuracy of providing the correct diagnosis and personalize subsequent treatment regimens in different racial populations. For this reason, this study was designed to identify nucleotide variants in early onset diabetes patients with clinically suspected MODY in a Korean population.

Research design and methods

Among 2908 Korean patients diagnosed with diabetes, we selected 40 patients who were diagnosed before 30 years old and were clinically suspected of MODY. Genetic testing was performed using a targeted gene sequencing panel that included 30 known monogenic diabetes genes. The pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG-AMP) guidelines.

Results

A total of six rare missense variants (p.Ala544Thr in HNF1A, p.Val601Ile and p.His103Tyr in ABCC8, p.Pro33Ala in PDX1, p.Gly18Glu in INS, and p.Arg164Gln in PAX4) in five distinct MODY genes were identified in five patients. In addition, a variant was identified in mitochondrial DNA at 3243A>G in one patient. The identified variants were either absent or detected at a rare frequency in the 1000 Genomes Project. These variants were classified as uncertain significance using the ACMG-AMP guidelines.

Conclusion

Using a targeted gene sequencing panel, we identified seven variants in either MODY genes or mitochondrial DNA using a Korean patient population with early onset diabetes who were clinically suspected of MODY. This genetic approach provides the ability to compare distinct populations of racial and ethnic groups to determine whether specific gene is involved in their diagnosis of MODY.
Degenerative cervical spine changes among early career fighter pilots: a 5-year follow-up
Authors: Keskimölö Tuomas , Pernu J , Karppinen J , Niinimäki J , Oura P , Leino T , Honkanen T
Published: June 2021

Introduction

Degenerative changes of the cervical spine often cause disability and flight duty limitations among Finnish Air Force (FINAF) fighter pilots. We aimed to study the effect of +Gz exposure on degenerative changes in the cervical spine by comparing cervical MRIs of FINAF fighter pilots and controls.

Methods

At baseline, the volunteer study population consisted of 56 20-year-old FINAF male fighter pilots (exposure group) and 56 21-year-old Army and Navy cadets (control group). Both groups underwent MRI of the cervical spine at the baseline and after 5 years. Degenerative changes evaluated using MRI included intervertebral disc (IVD) degeneration (Pfirrmann classification), disc herniations, uncovertebral arthrosis, Schmorl’s nodes, Modic changes, spinal canal stenosis, kyphosis and scoliosis.

Results

The degree of IVD degeneration in the whole cervical spine increased significantly in both populations with no between-group differences. The prevalence of disc herniations also tended to increase in both populations with no difference in the incidence over the follow-up. However, pilots proved to have more disc herniations at the baseline and at the follow-up. There were virtually no between-group differences in other assessed degenerative changes.

Discussion

We found that IVD degeneration and the prevalence of disc herniations increased at a similar rate for fighter pilots and non-flying military students when all cervical levels were summed up. The lack of difference may be explained by the relatively low cumulative +Gz exposure during the first 5 years of a pilots’ career.
Intensity of statin therapy and muscle symptoms: a network meta-analysis of 153 000 patients
Authors: Davis John W , Weller Susan C
Published: June 2021

Objective

To estimate relative risk (RR) of statin-associated musculoskeletal symptoms by statin therapy intensity.

Setting

Network meta-analysis assessing multicentre randomised controlled trials (RCTs) across several countries.

Participants

PubMed, Web of Science, Cochrane database and ClinicalTrials.gov were searched through January 2021 for doubled-blinded RCTs testing the effect of statin therapy on lipids with at least 1000 participants and 2 years of intended treatment. Two coders assessed articles for final inclusion, quality and outcomes. Treatment intensity was categorised according to American Heart Association definitions.

Outcomes

Pairwise and network meta-analysis (NMA) estimated RR and risk difference with random effects modelling. Heterogeneity was evaluated with the I2statistic. Outcomes included muscle symptoms (any, myalgia and attrition due to muscle symptoms), rhabdomyolysis and elevated creatine kinase (CK) (>10 × upper limit of normal).

Results

Of 2919 RCTs, 24 (n=152 461) met inclusion criteria. NMA results indicated risk was significantly greater for high compared with moderate intensity statin therapy for any muscle problem (RR=1.04, 95% CI 1.00 to 1.07; I2=0%), myalgia (RR=1.04, 95% CI 1.00 to 1.08; I2=0%, number needed to harm (NNH)=173), attrition due to muscle problems (RR=1.37, 95% CI 1.09 to 1.73, I2=0%, NNH=218) and elevated CK (RR=4.69, 95% CI 2.50 to 8.80; I2=7%, NNH=527). Risk also was significantly higher for high intensity compared with placebo for any muscle problem (RR=1.05, 95% CI 1.01 to 1.09, I2=0%), myalgia (RR=1.13, 95% CI 1.05 to 1.23; I2=0%, NNH=182), attrition due to muscle problems (RR=1.55, 95% CI 1.15 to 2.08, I2=0%, NNH=187) and elevated CK (RR=5.37, 95% CI 2.48 to 11.61; I2=7%, NNH=589). Due to inconsistency of results across sensitivity analyses, estimates were inconclusive for rhabdomyolysis and CK. There were no significant differences in risk between moderate intensity therapy and placebo for all outcomes.

Conclusions

For approximately each 200 patients on high intensity statins, one additional patient may experience myalgia or discontinue therapy due to muscle problems compared with moderate intensity therapy.

Trial registration number

CRD42019112758.
Protocol for a randomised controlled trial on the feasibility and effects
of 10-hour time-restricted eating on cardiometabolic disease risk among
career firefighters doing 24-hour shift work: the Healthy Heroes
Study
Authors: Manoogian Emily N C , Zadourian Adena , Lo Hannah C , Gutierrez Nikko R , Shoghi Azarin , Rosander Ashley , Pazargadi Aryana , Wang Xinran , Fleischer Jason G , Golshan Shahrokh , Taub Pam R , Panda Satchidananda
Published: June 2021

Introduction

Career firefighters experience chronic circadian rhythm disruption,
increasing their risk of cardiometabolic disease. The recent discovery
that eating patterns regulate circadian rhythmicity in metabolic organs
has raised the hypothesis that maintaining a consistent daily cycle of
eating and fasting can support circadian rhythms and reduce disease
risks. Preclinical animal studies and preliminary clinical trials have
shown promising effects of time-restricted eating (TRE) to reduce
disease risk without compromising physical performance. However, there
is a lack of research on TRE in shift workers including firefighters.
This study aims to investigate the feasibility and efficacy of 10-hour
TRE on health parameters that contribute to cardiometabolic disease
risks among career firefighters who work on a 24-hour shift
schedule.

Methods and analyses

The Healthy Heroes Study is a randomised controlled parallel
open-label clinical trial with 150 firefighters over 1 year.
Firefighters are randomised with a 1:1 ratio to either the control or
intervention group. The control group receives Mediterranean diet
nutritional counselling (standard of care, ‘SOC’). The intervention
group receives the same SOC and a self-selected 10-hour TRE window.
After the 2-week baseline, participants enter a 3-month monitored
intervention, followed by a 9-month self-guided period with follow-up
assessments. The impact of TRE on blood glucose, body weight, body
composition, biomarkers (neuroendocrine, inflammatory and metabolic),
sleep and mood is evaluated. These assessments occur at baseline, at the
end of intervention and at 6, 9 and 12-month follow-ups. Temporal
calorie intake is monitored with the smartphone application
myCircadianClock throughout the study. Continuous glucose monitors,
wrist-worn actigraphy device and questionnaires are used to monitor
glucose levels, activity, sleep and light exposure.

Ethics and dissemination

The study was approved by the Institutional Review Boards of the
University of California San Diego and the Salk Institute for Biological
Studies. Results will be disseminated through peer-reviewed manuscripts,
reports and presentations.

Trial registration number

NCT03533023; Pre result.
Implementation of a diagnostic decision aid for people with memory complaints and their general practitioners: a protocol of a before and after pilot trial
Authors: Linden Iris , Wolfs Claire , Perry Marieke , Metsemakers Job , van der Weijden Trudy , de Vugt Marjolein , Verhey Frans R , Handels Ron , Olde Rikkert Marcel , Dirksen Carmen , Ponds Rudolf W H M
Published: June 2021

Introduction

Researchers, policy-makers and healthcare professionals often stress the importance of an early dementia diagnosis. Empirical evidence, however, is scarce leading to a lack of consensus on the necessity of diagnosing dementia early. We emphasise the need for a ‘timely’ diagnosis, that is, one that occurs at the right moment for a person with memory complaints and his/her significant other. As the optimal timing differs between individuals, the implementation of shared decision making (SDM), preferably by the general practitioner (GP), as the start of a diagnostic trajectory, could help to determine this timely moment. SDM, however, is rarely practised with respect to dementia diagnoses. Therefore, in the context of the Shared Decision-Making regarding Dementia Diagnosis project, a patient decision aid (PtDA) for ‘timely’ dementia diagnosis in general practice will be developed. This protocol will describe the planned before and after evaluation of its implementation.

Methods and analysis

In a mixed-methods pilot study, we will investigate decision-making processes and experiences regarding a diagnostic trajectory before and after the introduction of a PtDA for people with memory complaints, their significant others and their GPs. The ‘before group’ will receive diagnostics as usual from their GPs. The ‘after group’ will use the PtDA. We expect the PtDA to increase the level of SDM and to contribute to a timely and personalised diagnostic trajectory. Data will be collected using semistructured interviews, questionnaires and information retrieved from people with memory complaints’ medical records.

Ethics and dissemination

This study protocol was approved by the Medical Review Ethics Committee of the Maastricht University Medical Centre. The findings will be published in peer-reviewed international journals and presented at conferences. This study was funded by the public funded Dutch Research Institute for Care and Medical Sciences (ZonMw).

Trial registration number

NCT04531956.
Analytical stress–strain relation for soils
Authors: Krabbenhøft K. , Wang J.
Published: June 2021

A new stress–strain relation capable of reproducing the entire stress–strain range of typical soil tests is presented. The new relation involves a total of five parameters, four of which can be inferred directly from typical test data. The fifth parameter is a fitting parameter with a relatively narrow range. The capabilities of the new relation are demonstrated by the application to various clay and sand datasets.