bluuebunny/crossref_metadata_2025 huggingface dataset:
Stage 1 Registered Report: Anomalous perception in a Ganzfeld condition - A meta-analysis of more than 40 years investigation
Authors: Tressoldi Patrizio E. , Storm Lance
Published: February 2021

This meta-analysis is an investigation into anomalous perception (i.e., conscious identification of information without any conventional sensorial means). The technique used for eliciting an effect is the ganzfeld condition (a form of sensory homogenization that eliminates distracting peripheral noise). The database consists of peer-reviewed studies published between January 1974 and June 2020 inclusive. The overall effect size will be estimated using a frequentist and a Bayesian random-effect model. Moderators analyses will be used to examine the influence of level of experience of participants, the type of task and the peer-review level. Publication bias will be estimated by using four different tests. Trend analysis will be conducted with a cumulative meta-analysis and a meta-regression model with Year of publication as covariate.
Effect of atorvastatin on subclinical atherosclerosis in virally-suppressed HIV-infected patients with CMV seropositivity: a randomized double-blind placebo-controlled trial
Authors: Yunihastuti Evy , Rusdi Lusiani , Syahrir Azizi Muhammad , Estiasari Riwanti , Jasirwan Chyntia Olivia Maurine , Wulandari Endah Ayu T. , Purnamasari Dyah , Shinta Noviar Mutiara , Aman Nasution Sally
Published: February 2021

Background: Persistent immune activation and inflammation in HIV-infection are linked to excess cardiovascular risk and other non-communicable diseases. Periodic asymptomatic CMV-reactivity in HIV infected patients over a lifetime may contribute to non-AIDS defining morbidity. Despite undetectable levels of HIV and CMV, these patients continue to have increased levels of biomarkers and immune activations. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels. It may also add beneficial effects against CMV infection.

Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1. This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. The study recruits 80 patients at HIV integrated care unit of Cipto Mangunkusumo hospital. All eligible subjects have CIMT evaluation as primary outcome, along with flow mediated vasodilatation (FMD), liver fibrosis and steatosis evaluation, fasting lipid, neurocognitive test, community periodontal index (CPI), and residual immune activation as secondary outcomes in 48 weeks.

Ethics and dissemination: This study has received an ethical approval from Health Research Ethics Commitee–Universitas Indonesia and Cipto Mangunkusumo Hospital. Before joining the study, all participants fill in an informed consent form. At the end of study analysis, the trial results will be published and disseminated in peer-reviewed journals.

Discussion: The main purpose of our study is to evaluate the effect of atorvastatin administration on CIMT changes in statin naïve virally suppressed HIV-infected patients with stable ART and CMV seropositivity

Registration: ClinicalTrials.gov ID NCT04101136; registered on 24 September 2019.
Increased expression of Polδ does not alter the canonical replication program in vivo
Authors: Zach Róbert , Carr Antony M.
Published: February 2021

Background: In vitro experiments utilising the reconstituted Saccharomyces cerevisiae eukaryotic replisome indicated that the efficiency of the leading strand replication is impaired by a moderate increase in Polδ concentration. It was hypothesised that the slower rate of the leading strand synthesis characteristic for reactions containing two-fold and four-fold increased concentration of Polδ represented a consequence of a relatively rare event, during which Polδ stochastically outcompeted Polε and, in an inefficient manner, temporarily facilitated extension of the leading strand. Inspired by this observation, we aimed to determine whether similarly increased Polδ levels influence replication dynamics in vivo using the fission yeast Schizosaccharomyces pombe as a model system.

Methods: To generate S. pombe strains over-expressing Polδ, we utilised Cre-Lox mediated cassette exchange and integrated one or three extra genomic copies of all four Polδ genes. To estimate expression of respective Polδ genes in Polδ-overexpressing mutants, we measured relative transcript levels of cdc1+, cdc6+ (or cdc6L591G), cdc27+ and cdm1+ by reverse transcription followed by quantitative PCR (RT-qPCR). To assess the impact of Polδ over-expression on cell physiology and replication dynamics, we used standard cell biology techniques and polymerase usage sequencing.

Results: We provide an evidence that two-fold and four-fold over-production of Polδ does not significantly alter growth rate, cellular morphology and S-phase duration. Polymerase usage sequencing analysis further indicates that increased Polδ expression does not change activities of Polδ, Polε and Polα at replication initiation sites and across replication termination zones. Additionally, we show that mutants over-expressing Polδ preserve WT-like distribution of replication origin efficiencies.

Conclusions: Our experiments do not disprove the existence of opportunistic polymerase switches; however, the data indicate that, if stochastic replacement of Polε for Polδ does occur in vivo, it represents a rare phenomenon that does not significantly influence canonical replication program.
Use of Mechanisms Marking Centers of Simplexes in Their 2-Dimensional Projections as Axonographs of Multidimensional Spaces
Authors: Abdurahmanov Sherzod
Published: February 2021

A brief historical excursion into the graphics of geometry of multidimensional spaces at the paper beginning clarifies the problem – the necessary to reduce the number of geometric actions performed when depicting multidimensional objects.

The problem solution is based on the properties of geometric figures called N- simplexes, whose number of vertices is equal to N + 1, where N expresses their dimensionality. The barycenter (centroid) of the N-simplex is located at the point that divides the straight-line segment connecting the centroid of the (N–1)-simplex contained in it with the opposite vertex by 1: N. This property is preserved in the parallel projection (axonometry) of the simplex on the drawing plane, that allows the solution of the problem of determining the centroid of the simplex in its axonometry to be assigned to a mechanism which is a special Assembly of pantographs (the author's invention) with similarity coefficients 1:1, 1:2, 1:3, 1:4,...1:N.

Next, it is established, that the spatial location of a point in N-dimensional space coincides with the centroid of the simplex, whose vertices are located on the point’s N-fold (barycentric) coordinates. In axonometry, the ends of both first pantograph’s links and the ends of only long links of the remaining ones are inserted into points indicating the projections of its barycentric coordinates and the mechanism node, which serves as a determinator, graphically marks the axonometric location of the point defined by its coordinates along the axes х1, х2, х3 … хN..

The translational movement of the support rods independently of each other can approximate or remote the barycentric coordinates of a point relative to the origin of coordinates, thereby assigning the corresponding axonometric places to the simplex barycenter, which changes its shape in accordance with its points’ occupied places in the coordinate axes. This is an axonograph of N-dimensional space, controlled by a numerical program. The last position indicates the possibility for using the equations of multidimensional spaces’ geometric objects given in the corresponding literature for automatic drawing when compiling such programs.
Descriptive Geometry Problems Visualization by Wolfram Mathematica
Authors: Ignat'ev S. , Folomkin A. , Muratbakeev E.
Published: February 2021

The possibilities of Wolfram Mathematica (WM), which is a package of symbolic mathematics, are endless. In this paper are investigated the possibilities of WM software product contextualization in the process of geometric-graphic teaching of students; is considered the experience for using a set of WM computational algorithms in teaching practice. The source codes and output data of our own WOLFRAM projects are offered, which are illustrative, in the form of interactive graphs, visualization of the solution for one of DG course’s basic problems on construction of points A, B, C and D, given by coordinates in space; construction a plane of general position passing through points A, B and C; determining positions of these points and the constructed plane in space; and also on determining the point D belonging to this plane. Have been presented examples of several of the existing WOLFRAM projects in the form of interactive graphs used in teaching. The study of applied issues and the ability to translate a professional problem into mathematical language, working in WM, provides a student with an opportunity to assimilate the necessary competencies.

Interactive visualization of solving DG problems, which can be carried out using WM, together with traditional problem solving, enriches the content of geometric education, introduces new opportunities in organization of the educational process, allows stimulate, maintain and increase students' interest in studying the discipline and further research in the area of DG. However, the ability to work in WM cannot replace the fundamental knowledge obtained by students of a technical high educational institute from the traditional course, but only complements the DG course by WM acquaintance.
Do Digital Platforms Reduce Moral Hazard? The Case of Uber and Taxis
Authors: Liu Meng , Brynjolfsson Erik , Dowlatabadi Jason
Published: February 2021

Digital platforms provide a variety of technology-enabled tools that enhance market transparency, such as real-time monitoring, ratings of buyers and sellers, and low-cost complaint channels. How do these innovations affect moral hazard and service quality? We investigate this problem by comparing driver routing choices and efficiency on a large digital platform, Uber, with traditional taxis. The identification is enabled by matching taxi and Uber trips at the origin-destination-time level so they are subject to the same underlying optimal route, by exploiting characteristics of the pricing schemes that differentially affect the incentives of taxi and Uber drivers in various circumstances, and by examining changes in behavior when drivers switch from taxis to Uber. We find that (1) taxi drivers route longer in distance than matched Uber drivers on metered airport routes by an average of 8%, with nonlocal passengers on airport routes experiencing even longer routing; (2) no such long routing is found for short trips in dense markets (e.g., within-Manhattan trips) or airport trips with a flat fare; and (3) long routing in general leads to longer travel time, instead of saving passengers time. These findings are consistent with digital platform designs reducing driver moral hazard, but not with competing explanations such as driver selection or differences in driver navigation technologies. We also find evidence of Uber drivers’ long routing on airport trips in times of surge pricing, suggesting that the tech-enabled market designs may not be binding in our setting.

This paper was accepted by Chris Forman, information systems.
Adaptation or Persistence? Emergence and Revision of Organization Designs in New Ventures
Authors: Alexy Oliver , Poetz Katharina , Puranam Phanish , Reitzig Markus
Published: February 2021

How organization designs evolve between adaptation to changing conditions and the pressures toward persistence of the designs adopted at founding remains an understudied phenomenon. To fill this lacuna, we conducted a longitudinal, multicase study of eight young ventures. We find that, in these ventures, specific organization design solutions changed frequently, triggered by various internal and external developments, although the changes were typically incremental and myopic. However, the more abstract principles of design, captured in the founders’ logics of organizing, were less amenable to change. This explains why observations of imprinting effects in logics of organizing may be consistent with observations of dynamic change to organization designs.
Drivers of health policy adoption: a political economy of HIV treatment policy
Authors: Kavanagh Matthew M. , Parish Kalind , Gupta Somya
Published: February 2021

Why do some countries rapidly adopt policies suggested by scientific consensus while others are slow to do so? Through a mixed methods study, we show that the institutional political economy of countries is a stronger and more robust predictor of health policy adoption than either disease burden or national wealth. Our findings challenge expectations in scholarship and among many international actors that policy divergence is best addressed through greater evidence and dissemination channels. Our study of HIV treatment policies shows that factors such as the formal structures of government and the degree of racial and ethnic stratification in society predict the speed with which new medical science is translated into policy, while level of democracy does not. This provides important new insights about the drivers of policy transfer and diffusion and suggests new paths for practical efforts to secure adoption of ‘evidence-based’ policies.
Digital platforms for the co-creation of public value
Authors: Meijer Albert , Boon Wouter
Published: February 2021

This article provides a theoretical understanding of the potential contribution of digital platforms to the co-creation of public value. On the basis of insights from different academic disciplines, a layered model is developed for the relations between technology, governance, users and societal outcomes. The theoretical model proposes that these layers can result in basic configurations – consistent combinations of the four elements – but also hybrid configurations. We identify three basic configurations: (1) a closed platform controlled by a private sector organisation, (2) an open platform controlled by a government organisation and (3) an open platform run by a civil society organisation. The configurations are illustrated with examples of digital platforms from all over the world. The configurational understanding of digital platforms for the co-creation of public value provides the basis for a systematic analysis of these rapidly growing practices in countries around the world.
Unlocking the ultrafast potential of gold nanowires for mode-locking in the mid-infrared region
Authors: Luo Hongyu , Li Siqing , Wu Xiaodong , Kang Zhe , Li Jianfeng , Qin Guanshi , Qin Weiping , Liu Yong
Published: February 2021

In this Letter, we present the mode-locking operation of a 2.87 µm

H
o

3
+

/

P
r

3
+

codoped fluoride fiber laser, helped by the ultrafast nonlinear optical absorption behavior of gold nanowires (GNWs). The mode locker is fabricated by depositing the GNW solution onto a silver mirror. It has a modulation depth of 14.2%, a saturation intensity of

26.2

M
W

/

c
m

2

, and a non-saturation loss of 29.9% at 2.87 µm. With an increased pump power, the laser operates in

Q

-switched mode-locking, fundamental mode-locking, and harmonic mode-locking (HML) states. This represents the first, to our knowledge, mid-infrared mode-locked laser using gold nanomaterials. Additionally, the HML is also the first observation in a laser in this band using material saturable absorbers, implying the capability of GNWs for high repetition rate generation.
Discrete probabilistic detection model for a Geiger-mode avalanche photodiode array with crosstalk
Authors: Qu Chengzhi , Zhang Yan , Yang Yang , Wang Shuang
Published: February 2021

A discrete-time probability model is proposed to predict the detection performance of the Geiger-mode avalanche photodiode array. This model is established by considering multiple influencing factors, and crosstalk is characterized in the form of a transition matrix during the modeling process. The verification experiment shows that the results are consistent with previous results for a crosstalk-free scenario. The performance analysis also indicates that the array detection performance decreases approximately linearly with the increase of crosstalk probability. When the crosstalk probability is 20%, compared with the scenario without considering crosstalk effects, the deviation of array detection probability reaches up to 27.05%.
Direct writing of optical waveguides in fused silica by the fundamental beam of an Yb:KGW femtosecond laser
Authors: Imai Ryo , Konishi Kuniaki , Yumoto Junji , Kuwata-Gonokami Makoto
Published: February 2021

We report the fabrication of an optical waveguide with a propagation loss below 1 dB/cm in fused silica using the fundamental beam of an Yb:KGW femtosecond laser. By selecting the pulse energy and pulse duration, we obtained a propagation loss comparable with that of a waveguide made using a Ti:Sapphire laser. We demonstrate that the nano-wrinkles and nano-pores, which dominate the losses, are not formed in the modified silica if the pulse energy is below 0.80 μJ and the pulses are shorter than 300 fs.
Sustained neural rhythms reveal endogenous oscillations supporting speech perception
Authors: van Bree Sander , Sohoglu Ediz , Davis Matthew H. , Zoefel Benedikt
Published: February 2021

Rhythmic sensory or electrical stimulation will produce rhythmic brain responses. These rhythmic responses are often interpreted as endogenous neural oscillations aligned (or “entrained”) to the stimulus rhythm. However, stimulus-aligned brain responses can also be explained as a sequence of evoked responses, which only appear regular due to the rhythmicity of the stimulus, without necessarily involving underlying neural oscillations. To distinguish evoked responses from true oscillatory activity, we tested whether rhythmic stimulation produces oscillatory responses which continue after the end of the stimulus. Such sustained effects provide evidence for true involvement of neural oscillations. In Experiment 1, we found that rhythmic intelligible, but not unintelligible speech produces oscillatory responses in magnetoencephalography (MEG) which outlast the stimulus at parietal sensors. In Experiment 2, we found that transcranial alternating current stimulation (tACS) leads to rhythmic fluctuations in speech perception outcomes after the end of electrical stimulation. We further report that the phase relation between electroencephalography (EEG) responses and rhythmic intelligible speech can predict the tACS phase that leads to most accurate speech perception. Together, we provide fundamental results for several lines of research—including neural entrainment and tACS—and reveal endogenous neural oscillations as a key underlying principle for speech perception.
Ancestral haplotype reconstruction in endogamous populations using identity-by-descent
Authors: Finke Kelly , Kourakos Michael , Brown Gabriela , Dang Huyen Trang , Tan Shi Jie Samuel , Simons Yuval B. , Ramdas Shweta , Schäffer Alejandro A. , Kember Rachel L. , Bućan Maja , Mathieson Sara
Published: February 2021

In this work we develop a novel algorithm for reconstructing the genomes of ancestral individuals, given genotype or sequence data from contemporary individuals and an extended pedigree of family relationships. A pedigree with complete genomes for every individual enables the study of allele frequency dynamics and haplotype diversity across generations, including deviations from neutrality such as transmission distortion. When studying heritable diseases, ancestral haplotypes can be used to augment genome-wide association studies and track disease inheritance patterns. The building blocks of our reconstruction algorithm are segments of Identity-By-Descent (IBD) shared between two or more genotyped individuals. The method alternates between identifying a source for each IBD segment and assembling IBD segments placed within each ancestral individual. Unlike previous approaches, our method is able to accommodate complex pedigree structures with hundreds of individuals genotyped at millions of SNPs.

We apply our method to an Old Order Amish pedigree from Lancaster, Pennsylvania, whose founders came to North America from Europe during the early 18th century. The pedigree includes 1338 individuals from the past 12 generations, 394 with genotype data. The motivation for reconstruction is to understand the genetic basis of diseases segregating in the family through tracking haplotype transmission over time. Using our algorithm thread, we are able to reconstruct an average of 224 ancestral individuals per chromosome. For these ancestral individuals, on average we reconstruct 79% of their haplotypes. We also identify a region on chromosome 16 that is difficult to reconstruct—we find that this region harbors a short Amish-specific copy number variation and the gene HYDIN. thread was developed for endogamous populations, but can be applied to any extensive pedigree with the recent generations genotyped. We anticipate that this type of practical ancestral reconstruction will become more common and necessary to understand rare and complex heritable diseases in extended families.
Balrog: A universal protein model for prokaryotic gene prediction
Authors: Sommer Markus J. , Salzberg Steven L.
Published: February 2021

Low-cost, high-throughput sequencing has led to an enormous increase in the number of sequenced microbial genomes, with well over 100,000 genomes in public archives today. Automatic genome annotation tools are integral to understanding these organisms, yet older gene finding methods must be retrained on each new genome. We have developed a universal model of prokaryotic genes by fitting a temporal convolutional network to amino-acid sequences from a large, diverse set of microbial genomes. We incorporated the new model into a gene finding system, Balrog (Bacterial Annotation by Learned Representation Of Genes), which does not require genome-specific training and which matches or outperforms other state-of-the-art gene finding tools. Balrog is freely available under the MIT license at https://github.com/salzberg-lab/Balrog.
Estimating the cumulative incidence of SARS-CoV-2 with imperfect serological tests: Exploiting cutoff-free approaches
Authors: Bouman Judith A. , Riou Julien , Bonhoeffer Sebastian , Regoes Roland R.
Published: February 2021

Large-scale serological testing in the population is essential to determine the true extent of the current SARS-CoV-2 pandemic. Serological tests measure antibody responses against pathogens and use predefined cutoff levels that dichotomize the quantitative test measures into sero-positives and negatives and use this as a proxy for past infection. With the imperfect assays that are currently available to test for past SARS-CoV-2 infection, the fraction of seropositive individuals in serosurveys is a biased estimator of the cumulative incidence and is usually corrected to account for the sensitivity and specificity. Here we use an inference method—referred to as mixture-model approach—for the estimation of the cumulative incidence that does not require to define cutoffs by integrating the quantitative test measures directly into the statistical inference procedure. We confirm that the mixture model outperforms the methods based on cutoffs, leading to less bias and error in estimates of the cumulative incidence. We illustrate how the mixture model can be used to optimize the design of serosurveys with imperfect serological tests. We also provide guidance on the number of control and case sera that are required to quantify the test’s ambiguity sufficiently to enable the reliable estimation of the cumulative incidence. Lastly, we show how this approach can be used to estimate the cumulative incidence of classes of infections with an unknown distribution of quantitative test measures. This is a very promising application of the mixture-model approach that could identify the elusive fraction of asymptomatic SARS-CoV-2 infections. An R-package implementing the inference methods used in this paper is provided. Our study advocates using serological tests without cutoffs, especially if they are used to determine parameters characterizing populations rather than individuals. This approach circumvents some of the shortcomings of cutoff-based methods at exactly the low cumulative incidence levels and test accuracies that we are currently facing in SARS-CoV-2 serosurveys.
Extracellular matrix density regulates the formation of tumour spheroids through cell migration
Authors: Gonçalves Inês G. , Garcia-Aznar Jose Manuel
Published: February 2021

In this work, we show how the mechanical properties of the cellular microenvironment modulate the growth of tumour spheroids. Based on the composition of the extracellular matrix, its stiffness and architecture can significantly vary, subsequently influencing cell movement and tumour growth. However, it is still unclear exactly how both of these processes are regulated by the matrix composition. Here, we present a centre-based computational model that describes how collagen density, which modulates the steric hindrance properties of the matrix, governs individual cell migration and, consequently, leads to the formation of multicellular clusters of varying size. The model was calibrated using previously published experimental data, replicating a set of experiments in which cells were seeded in collagen matrices of different collagen densities, hence producing distinct mechanical properties. At an initial stage, we tracked individual cell trajectories and speeds. Subsequently, the formation of multicellular clusters was also analysed by quantifying their size. Overall, the results showed that our model could accurately replicate what was previously seen experimentally. Specifically, we showed that cells seeded in matrices with low collagen density tended to migrate more. Accordingly, cells strayed away from their original cluster and thus promoted the formation of small structures. In contrast, we also showed that high collagen densities hindered cell migration and produced multicellular clusters with increased volume. In conclusion, this model not only establishes a relation between matrix density and individual cell migration but also showcases how migration, or its inhibition, modulates tumour growth.
Perceived barriers to Chagas disease screening among a diverse group of prenatal care providers
Authors: Mahoney West Helen , Milliren Carly E. , Vragovic Olivera , Köhler Julia R. , Yarrington Christina
Published: February 2021

Background

Chagas disease is a vector borne infection of poverty endemic to Latin America which affects an estimated 40,000 women of child-bearing age in the United States (US). In the US Chagas disease is concentrated among individuals who have lived in endemic areas. Prenatal diagnosis and treatment are needed to prevent congenital transmission. The objective of this study was to assess perceived barriers to Chagas disease screening among prenatal care providers in Obstetrics/Gynecology and Family Medicine Departments of a tertiary care safety-net hospital caring for a significant at-risk population.

Methodology/Principal findings

An anonymous survey was distributed to 178 Obstetrics/Gynecology and Family Medicine practitioners. Of the 66 respondents, 39% thought Chagas screening was very important, and 48% somewhat important as a public health initiative. One third judged screening patients during clinic visits as very important. Most respondents (64%) reported being familiar with Chagas disease. However, only 32% knew how to order a test and only 22% reported knowing what to do if a test was positive.

Conclusions/Significance

These findings will be incorporated into measures to facilitate full implementation of Chagas screening, and can inform initiatives at other centers who wish to address this deeply neglected infection among their patient families. Greater integration of information on Chagas disease screening and treatment in medical and nursing education curricula can contribute to addressing this disease with the focus that its potentially fatal sequelae merit.
A qualitative investigation of HIV treatment dispensing models and impacts on adherence among people living with HIV who use drugs
Authors: Fleming Taylor , Collins Alexandra B. , Bardwell Geoff , Fowler Al , Boyd Jade , Milloy M. J. , Small Will , McNeil Ryan
Published: February 2021

Antiretroviral therapy (ART) dispensing is strongly associated with treatment adherence. Among illicit drug-using populations, whom experience greater structural barriers to adherence, directly administered antiretroviral therapy (DAAT) is often regarded as a stronger predictor of optimal adherence over self-administered medications. In Vancouver, Canada, people living with HIV (PLHIV) who use drugs and live in low-income housing are a critical population for treatment support. This group is typically able to access two key DAAT models, daily delivery and daily pickup, in addition to ART self-administration. This ethno-epidemiological qualitative study explores how key dispensing models impact ART adherence among PLHIV who use drugs living in low-income housing, and how this is framed by structural vulnerability. Semi-structured interviews lasting 30–45 minutes were conducted between February and May 2018 with 31 PLHIV who use drugs recruited from an ongoing prospective cohort of PLHIV who use drugs. Interviews were audio-recorded, transcribed verbatim, and analyzed using QSR International’s NVivo 12 software. Interviews focused on housing, drug use, and HIV management. Models that constrained agency were found to have negative impacts on adherence and quality of life. Treatment interruptions were framed by structural vulnerabilities (e.g., housing vulnerability) that impacted ability to maintain adherence under certain dispensing models, and led participants to consider other models. Participants using DAAT models which accounted for their structural vulnerabilities (e.g., mobility issues, housing instability), credited these models for their treatment adherence, but also acknowledged factors that constrained agency, and the negative impacts this could have on both adherence, and quality of life. Being able to integrate ART into an established routine is key to supporting ART adherence. ART models that account for the structural vulnerability of PLHIV who use drugs and live in low-income housing are necessary and housing-based supports could be critical, but the impacts of such models on agency must be considered to ensure optimal adherence.
Polyphasic characterization of carbapenem-resistant Klebsiella pneumoniae clinical isolates suggests vertical transmission of the blaKPC-3 gene
Authors: Ferreira Catarina , Bikkarolla Santosh K. , Frykholm Karolin , Pohjanen Saga , Brito Margarida , Lameiras Catarina , Nunes Olga C. , Westerlund Fredrik , Manaia Célia M.
Published: February 2021

Carbapenem-resistant Klebsiella pneumoniae are a major global threat in healthcare facilities. The propagation of carbapenem resistance determinants can occur through vertical transmission, with genetic elements being transmitted by the host bacterium, or by horizontal transmission, with the same genetic elements being transferred among distinct bacterial hosts. This work aimed to track carbapenem resistance transmission by K. pneumoniae in a healthcare facility. The study involved a polyphasic approach based on conjugation assays, resistance phenotype and genotype analyses, whole genome sequencing, and plasmid characterization by pulsed field gel electrophoresis and optical DNA mapping. Out of 40 K. pneumoniae clinical isolates recovered over two years, five were carbapenem- and multidrug-resistant and belonged to multilocus sequence type ST147. These isolates harboured the carbapenemase encoding blaKPC-3 gene, integrated in conjugative plasmids of 140 kbp or 55 kbp, belonging to replicon types incFIA/incFIIK or incN/incFIIK, respectively. The two distinct plasmids encoding the blaKPC-3 gene were associated with distinct genetic lineages, as confirmed by optical DNA mapping and whole genome sequence analyses. These results suggested vertical (bacterial strain-based) transmission of the carbapenem-resistance genetic elements. Determination of the mode of transmission of antibiotic resistance in healthcare facilities, only possible based on polyphasic approaches as described here, is essential to control resistance propagation.
Psychophysiological responses to manual lifting of unknown loads
Authors: Khalaf Tamer M. , Ramadan Mohamed Z. , Ragab Adham E. , Alhaag Mohammed H. , AlSharabi Khalil A.
Published: February 2021

Background

The handling of unknown weights, which is common in daily routines either at work or during leisure time, is suspected to be highly associated with the incidence of low back pain (LBP).

Objectives

To investigate the effects of knowledge and magnitude of a load (to be lifted) on brain responses, autonomic nervous activity, and trapezius and erector spinae muscle activity.

Methods

A randomized, within-subjects experiment involving manual lifting was conducted, wherein 10 participants lifted three different weights (1.1, 5, and 15 kg) under two conditions: either having or not having prior knowledge of the weight to be lifted.

Results

The results revealed that the lifting of unknown weights caused increased average heart rate and percentage of maximum voluntary contraction (%MVC) but decreased average inter-beat interval, very-low-frequency power, low-frequency power, and low-frequency/high-frequency ratio. Regardless of the weight magnitude, lifting of unknown weights was associated with smaller theta activities in the power spectrum density (PSD) of the central region, smaller alpha activities in the PSD of the frontal region, and smaller beta activities in the PSDs of both the frontal and central regions. Moreover, smaller alpha and beta activities in the PSD of the parietal region were associated only with lifting of unknown lightweights.

Conclusions

Uncertainty regarding the weight to be lifted could be considered as a stress-adding variable that may increase the required physical demand to be sustained during manual lifting tasks. The findings of this study stress the importance of eliminating uncertainty associated with handling unknown weights, such as in the cases of handling patients and dispatching luggage. This can be achieved through preliminary self-sensing of the load to be lifted, or the cautious disclosure of the actual weight of manually lifted objects, for example, through clear labeling and/or a coding system.
Short-term changes in air humidity and water availability weakly constrain thermoregulation in a dry-skinned ectotherm
Authors: Le Galliard Jean-François , Rozen-Rechels David , Lecomte Anjélica , Demay Clémence , Dupoué Andréaz , Meylan Sandrine
Published: February 2021

Thermoregulation is critical for ectotherms as it allows them to maintain their body temperature close to an optimum for ecological performance. Thermoregulation includes a range of behaviors that aim at regulating body temperature within a range centered around the thermal preference. Thermal preference is typically measured in a thermal gradient in fully-hydrated and post-absorptive animals. Short-term effects of the hydric environment on thermal preferences in such set-ups have been rarely quantified in dry-skinned ectotherms, despite accumulating evidence that dehydration might trade-off with behavioral thermoregulation. Using experiments performed under controlled conditions in climatic chambers, we demonstrate that thermal preferences of a ground-dwelling, actively foraging lizard (Zootoca vivipara) are weakly decreased by a daily restriction in free-standing water availability (less than 0.5°C contrast). The influence of air humidity during the day on thermal preferences depends on time of the day and sex of the lizard, and is generally weaker than those of of free-standing water (less than 1°C contrast). This shows that short-term dehydration can influence, albeit weakly, thermal preferences under some circumstances in this species. Environmental humidity conditions are important methodological factors to consider in the analysis of thermal preferences.
The effect of lizards on the dispersal and germination of Capparis spinosa (Capparaceae)
Authors: Yang Yi , Lin Yingying , Shi Lei
Published: February 2021

Seed dispersal is a key component of the interactions between plants and animals. There is little research on the effects of lizard seed dispersal, which is more common on islands than elsewhere. In this study, the effects of the passage ofCapparis spinosaseeds throughTeratoscincus roborowskiilizard digestive tracts on the seed coats, water uptake rates and germination rates were investigated. In addition, the spatial patterns of fecal deposition by lizards in various microhabitats were assessed. Our results showed that the mean retention time (MRT) of mealworms was significantly longer than that ofC.spinosaseeds in both adult and juvenile lizards. The defecation rate ofC.spinosatended to be lower than that of mealworms, which might be beneficial for seed dispersal. It was determined that the longer MRT ofC.spinosaseeds enhanced the permeability of the seed coats, which promoted fast water uptake, broke seed dormancy and increased the seed germination rate. Furthermore, the seeds that passed through the digestive tracts of lizards were deposited in favorable germination microhabitats. By enhancing seed germination and depositing intact and viable seeds in safe potential recruitment sites, the lizardT.roborowskiiacts, at least qualitatively, as an effective disperser ofC.spinosa.
Histone H4 potentiates neutrophil inflammatory responses to influenza A virus: Down-modulation by H4 binding to C-reactive protein and Surfactant protein D
Authors: Hsieh I-Ni , White Mitchell , Hoeksema Marloes , Deluna Xavier , Hartshorn Kevan
Published: February 2021

Neutrophils participate in the early phase of the innate response to uncomplicated influenza A virus (IAV) infection but also are a major component in later stages of severe IAV or COVID 19 infection where neutrophil extracellular traps (NETs) and associated cell free histones are highly pro-inflammatory. It is likely that IAV interacts with histones during infection. We show that histone H4 binds to IAV and aggregates viral particles. In addition, histone H4 markedly potentiates IAV induced neutrophil respiratory burst responses. Prior studies have shown reactive oxidants to be detrimental during severe IAV infection. C reactive protein (CRP) and surfactant protein D (SP-D) rise during IAV infection. We now show that both of these innate immune proteins bind to histone H4 and significantly down regulate respiratory burst and other responses to histone H4. Isolated constructs composed only of the neck and carbohydrate recognition domain of SP-D also bind to histone H4 and partially limit neutrophil responses to it. These studies indicate that complexes formed of histones and IAV are a potent neutrophil activating stimulus. This finding could account for excess inflammation during IAV or other severe viral infections. The ability of CRP and SP-D to bind to histone H4 may be part of a protective response against excessive inflammation in vivo.
Evaluation of a real-time optoelectronic method in the diagnostics of CIN over four years of observations
Authors: Suchońska Barbara , Gajzlerska-Majewska Wanda , Wielgoś Mirosław
Published: February 2021

Cervical cancer is considered to be particularly amenable to prevention and highly treatable in its early stages. The real-time optoelectronic method of cervix examination seemed to be very promising in the detection of cervical squamous intraepithelial lesions and demonstrated relatively good efficacy. Although this method was introduced into clinics almost 10 years ago, it has not found its place in diagnostic schemes. At the moment, cytological smears and HPV detection with genotyping are still essential. TruScreen seems to be a slightly forgotten test. The aim of the study was to evaluate the efficacy and accuracy of TruScreen in detecting cervical pathology: CIN and cervical cancer confirmed with a histopathological diagnosis in comparison with other methods–cytology and colposcopy over four years of observations. The study was conducted on 130 women with abnormal Pap smear results. We can conclude that a real-time optoelectronic method like TruScreen can be useful as an effective initial cervical cancer screening in developing countries, possibly in combination with other methods. The combination of cytology and TruScreen examination may help clinicians to take decision about the next diagnostics steps (e.g. colposcopy) and contribute to better primary screening for cervical cancer.
Assessing civility at an academic health science center: Implications for employee satisfaction and well-being
Authors: Campbell Lisa A. , LaFreniere Jenna R. , Almekdash Mhd Hasan , Perlmutter David D. , Song Huaxin , Kelly Patricia J. , Keesari Rohali , Shannon Kay Leigh
Published: February 2021

Incivilities are pervasive among workers in healthcare institutions. Previously identified effects include deterioration of employee physical and mental health, absenteeism, burnout, and turnover, as well as reduced patient safety and quality of care. This study documented factors related to organizational civility at an academic health sciences center (AHSC) as the basis for future intervention work. We used a cross-sectional research design to conduct an online survey at four of five campuses of an AHSC. Using the Organizational Civility Scale (OCS), we assessed differences across gender, race (White and non-White) and job type (faculty or staff) in the eleven subscales (frequency of incivility, perceptions of organizational climate, existence of civility resources, importance of civility resources, feelings about current employment, employee satisfaction, sources of stress, coping strategies, overall levels of stress/coping ability, and overall civility rating). Significant gender differences were found in six of the eleven subscales: perception of organizational climate (p < .001), existence of civility resources (p = .001), importance of civility resources (p < .001), frequency of incivilities (p < .001), employee satisfaction (p = .002), and overall civility rating (p = .007). Significant differences between respondents by self-identified race were found only in one subscale: existence of civility resources (p = .048). Significant differences were found between faculty and staff in four subscales: perception of organizational climate (p = .001), importance of civility resources (p = .02), employee satisfaction (p = .01), and overall levels of stress (p = .03). Results suggest that gender and employment type differences exist in the perception of organizational climate at the academic health center, while significant racial differences only occurred in reference to reported existence of civility resources. Attention to these differences should be incorporated into the development of programs to address the problem.
Retrospective study of late radiation-induced damages after focal radiotherapy for childhood brain tumors
Authors: Cavatorta Claudia , Meroni Silvia , Montin Eros , Oprandi Maria C. , Pecori Emilia , Lecchi Mara , Diletto Barbara , Alessandro Ombretta , Peruzzo Denis , Biassoni Veronica , Schiavello Elisabetta , Bologna Marco , Massimino Maura , Poggi Geraldina , Mainardi Luca , Arrigoni Filippo , Spreafico Filippo , Verderio Paolo , Pignoli Emanuele , Gandola Lorenza
Published: February 2021

Purpose

To study a robust and reproducible procedure to investigate a relation between focal brain radiotherapy (RT) low doses, neurocognitive impairment and late White Matter and Gray Matter alterations, as shown by Diffusion Tensor Imaging (DTI), in children.

Methods and materials

Forty-five patients (23 males and 22 females, median age at RT 6.2 years, median age at evaluations 11.1 years) who had received focal RT for brain tumors were recruited for DTI exams and neurocognitive tests. Patients’ brains were parceled in 116 regions of interest (ROIs) using an available segmented atlas. After the development of an ad hoc, home-made, multimodal and highly deformable registration framework, we collected mean RT doses and DTI metrics values for each ROI. The pattern of association between cognitive scores or domains and dose or DTI values was assessed in each ROI through both considering and excluding ROIs with mean doses higher than 75% of the prescription. Subsequently, a preliminary threshold value of dose discriminating patients with and without neurocognitive impairment was selected for the most relevant associations.

Results

The workflow allowed us to identify 10 ROIs where RT dose and DTI metrics were significantly associated with cognitive tests results (p<0.05). In 5/10 ROIs, RT dose and cognitive tests were associated with p<0.01 and preliminary RT threshold dose values, implying a possible cognitive or neuropsychological damage, were calculated. The analysis of domains showed that the most involved one was the “school-related activities”.

Conclusion

This analysis, despite being conducted on a retrospective cohort of children, shows that the identification of critical brain structures and respective radiation dose thresholds is achievable by combining, with appropriate methodological tools, the large amount of data arising from different sources. This supported the design of a prospective study to gain stronger evidence.
Causal relationship between the timing of menarche and young adult body mass index with consideration to a trend of consistently decreasing age at menarche
Authors: Kim Hakyung , Choe Seung-Ah , Lee Soo Ji , Sung Joohon
Published: February 2021

Younger age at menarche (AAM) is associated with higher body mass index (BMI) for young women. Considering that continuous trends in decreasing AAM and increasing BMI are found in many countries, we attempted to assess whether the observed negative association between AAM and young adult BMI is causal. We included 4,093 women from the Korean Genome and Epidemiology Study (KoGES) and Healthy twin Study (HTS) with relevant epidemiologic data and genome-wide marker information. To mitigate the remarkable differences in AAM across generations, we converted the AAM to a generation-standardized AAM (gsAAM). To test causality, we applied the Mendelian randomization (MR) approach, using a genetic risk score (GRS) based on 14 AAM-associated single nucleotide polymorphisms (SNPs). We constructed MR models adjusting for education level and validated the results using the inverse-variance weighted (IVW), weighted median (WM), MR-pleiotropy residual sum and outliers test (MR-PRESSO), and MR-Egger regression methods. We found a null association using observed AAM and BMI level (conventional regression; -0.05 [95% CIs -0.10–0.00] per 1-year higher AAM). This null association was replicated when gsAAM was applied instead of AAM. Using the two-stage least squares (2SLS) approach employing a univariate GRS, the association was also negated for both AAM and gsAAM, regardless of model specifications. All the MR diagnostics suggested statistically insignificant associations, but weakly negative trends, without evidence of confounding from pleiotropy. We did not observe a causal association between AAM and young adult BMI whether we considered the birth cohort effect or not. Our study alone does not exclude the possibility of existing a weak negative association, considering the modest power of our study design.