bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique TLR9 Activation by Helicobacter pylori Depends on the cag T4SS, But Not on VirD2 Relaxases or VirD4 Coupling Proteins
Authors: Tegtmeyer Nicole , Linz Bodo , Yamaoka Yoshio , Backert Steffen
Published: March 2022

The genomes of the gastric bacterial pathogen Helicobacter pylori harbor multiple type-IV secretion systems (T4SSs). Here we analyzed components of three T4SSs, the cytotoxin-associated genes (cag) T4SS, TFS3 and TFS4. The cag T4SS delivers the effector protein CagA and the LPS-metabolite ADP-heptose into gastric epithelial cells, which plays a pivotal role in chronic infection and development of gastric disease. In addition, the cag T4SS was reported to facilitate conjugative transport of chromosomal bacterial DNA into the host cell cytoplasm, where injected DNA activates intracellular toll-like receptor 9 (TLR9) and triggers anti-inflammatory signaling. Canonical DNA-delivering T4SSs in a variety of bacteria are composed of 11 VirB proteins (VirB1-11) which assemble and engage VirD2 relaxase and VirD4 coupling proteins that mediate DNA processing and guiding of the covalently bound DNA through the T4SS channel. Nevertheless, the role of the latter components in H. pylori is unclear. Here, we utilized isogenic knockout mutants of various virB (virB9 and virB10, corresponding to cagX and cagY), virD2 (rlx1 and rlx2), virD4 (cag5, traG1/2) and xerD recombinase genes in H. pylori laboratory strain P12 and studied their role in TLR9 activation by reporter assays. While inactivation of the structural cag T4SS genes cagX and cagY abolished TLR9 activation, the deletion of rlx1, rlx2, cag5, traG or xerD genes had no effect. The latter mutants activated TLR9 similar to wild-type bacteria, suggesting the presence of a unique non-canonical T4SS-dependent mechanism of TLR9 stimulation by H. pylori that is not mediated by VirD2, VirD4 and XerD proteins. These findings were confirmed by the analysis of TLR9 activation by H. pylori strains of worldwide origin that possess different sets of T4SS genes. The exact mechanism of TLR9 activation should be explored in future studies.
Reproducibility and diagnostic accuracy of pocket-sized ultrasound devices in ruling out compensated cirrhosis of mixed etiology
Authors: Costantino Andrea , Piagnani Alessandra , Nandi Nicoletta , Sciola Valentina , Maggioni Marco , Donato Francesca , Vecchi Maurizio , Lampertico Pietro , Casazza Giovanni , Fraquelli Mirella
Published: March 2022

Objective

Fibrosis is the key prognostic factor in chronic liver disease patients. Liver surface nodularity (LSN) is the ultrasonographic sign with the highest accuracy to detect advanced liver fibrosis. The use of pocket-sized ultrasound devices (PUDs) has been assessed in several clinical settings but never as regards chronic liver disease (CLD) severity. Our study aimed at evaluating the feasibility, reproducibility, and diagnostic accuracy of PUD in LSN identification.

Methods

We enrolled all the consecutive adults referred for percutaneous liver biopsy. Two independent operators evaluated LSN by PUD; one sonographer used standard ultrasound (US). Transient elastography (TE) and liver biopsy were performed on all the patients. PUD reproducibility was evaluated by Cohen’s k statistic. PUD, standard US, and TE results were compared with histology staging.

Results

A total of 104 consecutive patients (aged 54 ± 14 years) with mixed-etiology CLD were studied. Assessment by PUD was feasible in all the patients and showed very good inter-observer agreement with Cohen’s k = 0.87 (95% CI 0.72–0.95). The diagnostic accuracy estimates for PUD in diagnosing compensated cirrhosis (F = 4) were 87.5% sensitivity, 76.8% specificity, positive likelihood ratio (LR) 3.78, and negative likelihood ratio (LR-) 0.16, while those for standard US and TE (> 12.5 kPa) were, respectively, 87.5% sensitivity, 72.6% specificity, LR+ 3.2, and LR- 0.17, and 87.5% sensitivity, 90.5% specificity, LR + 9.2, and LR- 0.13.

Conclusions

PUD reproducibility in assessing LSN was excellent even with operators of different experience. PUD performed very well in excluding advanced CLD. PUD can be used as a first-line tool for screening patients to undergo more invasive techniques, thus shortening the time for clinical decision-making.

Key Points

• PUD is highly reproducible in assessing the sign of liver surface nodularity.

• PUD showed high diagnostic accuracy in excluding the presence of advanced chronic liver disease.

• PUD can be used as a first-line tool for screening patients with CLD who should undergo more invasive techniques.
Developing an understanding of artificial intelligence lung nodule risk prediction using insights from the Brock model
Authors: Chetan Madhurima R. , Dowson Nicholas , Price Noah Waterfield , Ather Sarim , Nicolson Angus , Gleeson Fergus V.
Published: March 2022

Objectives

To determine if predictions of the Lung Cancer Prediction convolutional neural network (LCP-CNN) artificial intelligence (AI) model are analogous to the Brock model.

Methods

In total, 10,485 lung nodules in 4660 participants from the National Lung Screening Trial (NLST) were analysed. Both manual and automated nodule measurements were inputted into the Brock model, and this was compared to LCP-CNN. The performance of an experimental AI model was tested after ablating imaging features in a manner analogous to removing predictors from the Brock model. First, the nodule was ablated leaving lung parenchyma only. Second, a sphere of the same size as the nodule was implanted in the parenchyma. Third, internal texture of both nodule and parenchyma was ablated.

Results

Automated axial diameter (AUC 0.883) and automated equivalent spherical diameter (AUC 0.896) significantly improved the accuracy of Brock when compared to manual measurement (AUC 0.873), although not to the level of the LCP-CNN (AUC 0.936). Ablating nodule and parenchyma texture (AUC 0.915) led to a small drop in AI predictive accuracy, as did implanting a sphere of the same size as the nodule (AUC 0.889). Ablating the nodule leaving parenchyma only led to a large drop in AI performance (AUC 0.717).

Conclusions

Feature ablation is a feasible technique for understanding AI model predictions. Nodule size and morphology play the largest role in AI prediction, with nodule internal texture and background parenchyma playing a limited role. This is broadly analogous to the relative importance of morphological factors over clinical factors within the Brock model.

Key Points

• Brock lung cancer risk prediction accuracy was significantly improved using automated axial or equivalent spherical measurements of lung nodule diameter, when compared to manual measurements.

• Predictive accuracy was further improved by using the Lung Cancer Prediction convolutional neural network, an artificial intelligence-based model which obviates the requirement for nodule measurement.

• Nodule size and morphology are important factors in artificial intelligence lung cancer risk prediction, with nodule texture and background parenchyma contributing a small, but measurable, role.
A common-sense approach to the problem of the itinerary stadion
Authors: Tupikova Irina
Published: March 2022

Estimating the length of the Greek stadion remains controversial. This paper highlights the pitfalls of a purely metrological approach to this problem and proposes a formal differentiation between metrologically defined ancient measuring units and other measures used to estimate long distances. The common-sense approach to the problem is strengthened by some cross-over documentary evidence for usage of the so-calleditinerarystadion in antiquity. We discuss the possibility of using statistical analysis methods to estimate the length of the stadion by comparing ancient routes with the actual distances. Simple numerical examples explain the limits of this approach, caused by the low number of data and by their mixed character. A special case of distances which can be calculated with the help of coordinates given in Ptolemy’sGeographyis discussed, and has been shown to lead unavoidably to ambiguous solutions.
Post mortem computed tomography meets radiomics: a case series on fractal analysis of post mortem changes in the brain
Authors: De-Giorgio Fabio , Ciasca Gabriele , Fecondo Gennaro , Mazzini Alberto , Di Santo Riccardo , De Spirito Marco , Pascali Vincenzo L.
Published: March 2022

Estimating the post-mortem interval is a fundamental, albeit challenging task in forensic sciences. To this aim, forensic practitioners need to assess post-mortem changes through a plethora of different methods, most of which are inherently qualitative, thus providing broad time intervals rather than precise determinations. This challenging problem is further complicated by the influence of environmental factors, which modify the temporal dynamics of post-mortem changes, sometimes in a rather unpredictable fashion. In this context, the search for quantitative and objective descriptors of post-mortem changes is highly demanded. In this study, we used computed tomography (CT) to assess the post-mortem anatomical modifications occurring in the time interval 0–4 days after death in the brain of four corpses. Our results show that fractal analysis of CT brain slices provides a set of quantitative descriptors able to map post-mortem changes over time throughout the whole brain. Although incapable of producing a direct estimation of the PMI, these descriptors could be used in combination with other more established methods to improve the accuracy and reliability of PMI determination.
Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers
Authors: Ukkola Iiris , Nummela Pirjo , Kero Mia , Tammio Hanna , Tuominen Jenni , Kairisto Veli , Kallajoki Markku , Haglund Caj , Peltomäki Päivi , Kytölä Soili , Ristimäki Ari
Published: March 2022

Gene fusions can act as oncogenic drivers and offer targets for cancer therapy. Since fusions are rare in colorectal cancer (CRC), their universal screening seems impractical. Our aim was to investigate gene fusions in 62 CRC cases with deficient MLH1 (dMLH1) and BRAFV600E wild-type (wt) status from a consecutive real-life series of 2079 CRCs. First, gene fusions were analysed using a novel FusionPlex Lung v2 RNA–based next-generation sequencing (NGS) panel, and these results were compared to a novel Idylla GeneFusion assay and pan-TRK immunohistochemistry (IHC). NGS detected seven (7/62, 11%) NTRK1 fusions (TPM3::NTRK1, PLEKHA6::NTRK1 and LMNA::NTRK1, each in two cases, and IRF2BP2::NTRK1 in one case). In addition, two ALK, four RET and seven BRAF fusions were identified. Idylla detected seven NTRK1 expression imbalances, in line with the NGS results (overall agreement 100%). Furthermore, Idylla detected the two NGS–identified ALK rearrangements as one specific ALK fusion and one ALK expression imbalance, whilst only two of the four RET fusions were discovered. However, Idylla detected several expression imbalances of ALK (n = 7) and RET (n = 1) that were found to be fusion negative with the NGS. Pan-TRK IHC showed clearly detectable, fusion partner-dependent staining patterns in the seven NTRK1 fusion cases. Overall agreement for pan-TRK antibody clone EPR17341 was 98% and for A7H6R 100% when compared to the NGS. Of the 62 CRCs, 43 were MLH1 promoter hypermethylated (MLH1ph) and 39 were RASwt. All fusion cases were both MLH1ph and RASwt. Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS.
Psychiatric training in perinatal mental health across Europe
Authors: Casanova Dias Marisa , Sönmez Güngör Ekin , Naughton Sean , Ryland Howard , Gargot Thomas , Pinto da Costa Mariana , Kanellopoulos Athanasios , Baessler Franziska , De Picker Livia
Published: March 2022

Perinatal mental illness is associated with considerable maternal and infant morbidity and mortality. However, there are currently no specific guidelines on the standards and structure of postgraduate perinatal psychiatric training in Europe. We describe the characteristics of available and desired specialist perinatal psychiatry training from the perspective of European psychiatrists in training. An online survey was conducted among 34 national psychiatric trainee association representatives of the European Federation of Psychiatric Trainees (EFPT). Participants from the countries in which perinatal psychiatry training was available were invited to participate in in-depth follow-up interviews. Six countries out of 34 (18%) reported that specialist training in perinatal mental health was available (Finland, France, Germany, Ireland, Malta, and the UK). The nature of available training varied in duration, the supervision and assessment model employed, and the training scheme context. Of the 28 countries where specialist perinatal psychiatry training was unavailable, the majority of national representatives (22 countries, 76%) wanted specialist perinatal psychiatry training to be included in their national training curricula. There is a gap between the expected skills and the available training for psychiatrists to meet the mental healthcare needs of women in the perinatal period. Given the prevalence and impact of perinatal mental illness and the expressed desires of trainees themselves for specialist training, this finding should prompt urgent action.
Application of a novel cascade-routing and reinfiltration concept with a Voronoi unstructured grid in MODFLOW 6, for an assessment of surface-water/groundwater interactions in a hard-rock catchment (Sardon, Spain)
Authors: Daoud Mostafa Gomaa , Lubczynski Maciek W. , Vekerdy Zoltan , Francés Alain Pascal
Published: March 2022

Integrated hydrological modelling (IHM) can reliably characterize surface-water/groundwater interactions in complex hydrological systems such as hard-rock systems (HRS), located in water-limited environments (WLE). Such HRS-WLE conditions are represented by Sardon catchment (~80 km2) in Spain, where the MODFLOW 6 modelling environment was tested, applying the following improvements as compared to previous works in that catchment: a new conceptual model, driving forces redefined based on remote sensing data, an unstructured Voronoi grid, and, most importantly, a novel cascade-routing and reinfiltration (CRR) concept. In the standard MODFLOW 6, rejected infiltration and groundwater exfiltration have always been considered as sinks (evaporation). However, in reality, that water can not only evaporate but also reinfiltrate back to the subsurface or move as runoff towards drainage water bodies. The CRR improves surface–unsaturated-zone interactions and also surface-water/groundwater interactions. The standard and new capacities of MODFLOW 6 are presented in the transient model of the Sardon catchment, calibrated using 7 years of daily groundwater heads and streamflows. The results showed: the large spatio-temporal variability of the groundwater fluxes, the substantial role of groundwater exfiltration, the low catchment storage, the fast reaction of the water table and streams to rainfall, and the mosaic character of the net recharge. These characteristics are typical for HRS-WLEs with a shallow water table. MODFLOW 6 has many improvements compared to previous MODFLOW versions, so with the proposed CRR concept (still can be improved), the single-environment MODFLOW 6 has modelling capacity comparable with multienvironment IHMs, while being more flexible and more efficient.
Effects of Body Forces on Turbulent Kinetic Energy Transport in Premixed Flames
Authors: Varma Arun Ravi , Ahmed Umair , Chakraborty Nilanjan
Published: March 2022

The effects of buoyancy on turbulent premixed flames are expected to be strong due to the large changes in density between the unburned and fully burned gases. The present work utilises three-dimensional direct numerical simulations of statistically planar turbulent premixed flames under decaying turbulence to study the influence of buoyancy on the evolution of turbulent kinetic energy within the flame brush. Four sets of turbulence parameters have been studied, with four different values of Froude number for each set. It is found that for a given set of turbulence parameters, flame wrinkling increases with an increase in body force magnitude in the case of unstable stratification, which is also reflected in the increased values of turbulent burning velocity and flame surface area. An increase in body force magnitude in the case of stable stratification acts to reduce the extent of flame wrinkling. Turbulent kinetic energy and its dissipation rate are found to be affected by both the magnitude and direction of the body force. For low turbulence intensities considered here, turbulent kinetic energy increases from the leading edge of the flame brush before decaying eventually towards the product side of the flame brush. For high turbulence intensities, the turbulent kinetic energy is found to decay across the flame brush, and it is also found that the effect of body force on the evolution of turbulent kinetic energy is marginal in the case of high turbulence intensities. The effects of body force magnitude and direction on the statistical behaviours and closures of the various terms of the turbulent kinetic energy transport equation are analysed, and existing models have been modified to account for Froude number effects, where necessary.
Shake table tests of concrete anchors for non-structural components including innovative and alternative anchorage detailing
Authors: Ciurlanti Jonathan , Bianchi Simona , Pürgstaller Andreas , Gallo Patricio Quintana , Bergmeister Konrad , Pampanin Stefano
Published: March 2022

In recent years, the growing need for reducing non-structural damage after earthquakes has stimulated a dedicated effort to develop innovative types of fasteners for anchoring non-structural components (NSCs) to reinforced concrete (RC) host-structures. To contribute to such need, and building on previous research, this paper presents the results of a series of uni-directional shake-table tests of simulated NSCs anchored to concrete via: (1) expansion, and (2) chemical anchors; post-installed into: (a) uncracked, and (b) cracked concrete. Considering different construction details, the experimental investigation focused on traditional anchorage systems, alternative solutions comprising mortar filling into the gap clearance, and a low-damage system relying on supplemental damping devices, capable of reducing the acceleration of the NSCs as well as the force of the anchorage during seismic shakings. The experimental tests provided significant evidence on the beneficial effects of a dissipative anchorage protecting both the non-structural component and the anchorage itself, even during strong earthquakes. Moreover, when construction details allow to close the fixture clearance with a mortar filling, this stiffer solution provide an additional reduction of NSCs seismic accelerations and forces. Therefore, suggestions for further improvements of the adopted low-damage solution are also proposed.
Factors influencing persistence of a threatened amphibian in restored wetlands despite severe population decline during climate change driven weather extremes
Authors: Beranek Chad T. , Sanders Samantha , Clulow John , Mahony Michael
Published: March 2022

Biodiversity is in global decline during the Anthropocene. Declines have been caused by multiple factors, such as habitat removal, invasive species, and disease, which are often targets for conservation management. However, conservation interventions are under threat from climate change induced weather extremes. Weather extremes are becoming more frequent and devastating and an example of this was the 2019/2020 Australian drought and mega-fires. We provide a case study the impacts of these extreme weather events had on a population of the threatened frog Litoria aurea that occurs in a constructed habitat which was designed to reduce the impact of introduced fish and chytrid-induced disease. We aimed to determine what factors influenced persistence so that the design of wetlands can be further optimised to future-proof threatened amphibians. We achieved this with 4 years (2016–2020) of intensive capture–recapture surveys during austral spring and summer across nine wetlands (n = 94 repeat surveys). As hypothesized, drought caused a sharp reduction in population size, but persistence was achieved. The most parsimonious predictor of survival was an interaction between maximum air temperature and rainfall, indicating that weather extremes likely caused the decline. Survival was positively correlated with wetland vegetation coverage, positing this is an important feature to target to enhance resilience in wetland restoration programs. Additionally, the benefits obtained from measures to reduce chytrid prevalence were not compromised during drought, as there was a positive correlation between salinity and survival. We emphasize that many species may not be able to persist under worse extreme weather scenarios. Despite the potential for habitat augmentation to buffer effects of extreme weather, global action on climate change is needed to reduce extinction risk.
When is Environmentalism Good for the Environment?
Authors: Marini Marco A. , Tarola Ornella , Thisse Jacques-François
Published: March 2022

We study how the supply of environmentalism, which is defined by psychic benefits (costs) associated with the purchase of high-environmental (low-environmental) qualities, affects the way firms choose their prices and products and the ensuing consequences for the global level of pollution. Contrary to general belief, a high supply of environmentalism does not necessarily give rise to a better environmental outcome because it endows the green firms with more market power which they use to charge higher prices. Nonetheless, environmentalism can be used to effectively complement more traditional policy instruments such as a minimum environmental standard.
Coping with local peoples' livelihood dependence on the transboundary Dinder–Alatish National Parks in Sudan and Ethiopia from the Sudanese Perspective
Authors: Geleto Mati Amano , Kapp Gerald , Sanjak Elamin
Published: March 2022

The local peoples’ dependence on Dinder National Park, Sudan, for their livelihoods and economic and conservation implications of the livelihood activities were analyzed. Our study attempted to answer major questions about the main livelihood strategies, their economic and conservation implications as well as the perceptions of local people and park administration on the use and management of the park and cooperation for TBPA management. A mixed research method was employed in this study in data collection Households’ livelihood strategies are ranked according to their share in households’ total income. Accordingly, 92% of respondents ranked agriculture as a primary source of livelihood in the rank 1 category, and 33% of respondents ranked livestock rearing as the primary source in the rank 2 category important source of livelihood. The ranking of second and third options varied across both households and villages. Households collect forest products to supplement their livelihoods and the collection of other environmental goods is irregular and difficult to quantify. Further human activities in the area are compiled from different publication and annual reports. Agricultural expansion into the park and livestock trespassing are the major threats to Dinder and neighboring Alatish National Park. A cooperative transboundary response will be helpful to cope with these challenges.
Abusive comments in student evaluations of courses and teaching: the attacks women and marginalised academics endure
Authors: Heffernan Troy
Published: March 2022

This paper examines the volume and type of anonymous comments academics receive in student evaluations of courses and teaching (SETs) at the 16,000 higher education institutions that collect this data at the end of each teaching period. Existing research has increasingly pointed to the negative issues of student surveys, but very little research has focused on the volume, type, and impact of anonymous student comments on academics. This paper analyses the survey results of 674 academics to inform higher education leaders and the sector more widely of the amount and type of abusive comments academics are receiving. The work also demonstrates that the highest volume, most derogatory, and most threatening abuse is directed towards women academics and those academics from marginalised groups. The paper finds that previous estimates of the rate and severity of abusive comments that academics receive, and the impact to academics’ wellbeing, mental health, and career progression, have underestimated what is taking place. The paper argues that many universities are failing to protect their staff from this abuse, and the prejudice nature of SET results, which will continue to have a negative impact on the career progression of marginalised academics - a major flaw in a sector that prides itself on diversity and inclusion.
Insights from bauhaus innovation for education and workplaces in a post-pandemic world
Authors: White-Hancock Lorraine
Published: March 2022

This paper examines Bauhaus School (1919–1933) innovation and relevance today. The School is a landmark in the history of design as a discipline and the development of design education. The School was also a workplace, commercialising Bauhaus-designed products. While drawing global interest in its innovations, the School faced resistance in Germany because it challenged conventions. This problem raises the questions: How did the School-workplace generate innovations amid the calamity of post-war Germany, and what is the significance of the Bauhaus for post-pandemic education and workplaces one hundred years on? The concept of ‘transgression’ is used to understand innovation at the Bauhaus School-workplace. Haraway discusses transgressive practices that disrupt established knowledges, moving ways of thinking and doing in new directions. Analysis of workplace learning research reveals that three interfacing dimensions make up innovation: (1) workplace environments, (2) the culture-order that facilitates innovation, and (3) learning in practice in authentic settings. This qualitative case study reports on how Bauhaus innovation emerged at the intersection of these key dimensions. There are surprising commonalities between the Bauhaus approach to innovation in challenging times and contemporary thinking about supporting innovation which are relevant to education, particularly STEAM (Science, Technology, Engineering, Arts and Mathematics) education, and workplaces in a world affected by the COVID 19 pandemic. Thus, encouraging people who challenge boundaries, rules or ‘the way things are’ can support innovation. This paper addresses a gap in workplace learning research on interrelated dimensions of innovation which the Bauhaus recognized. The study also offers an innovative approach to the examination of innovation across time and space whereas most contemporary studies of innovation focus on the present. Further, conceptualizing innovation as transgression offers a new way of thinking about innovation in design and in the workplace.
Spectrofluorimetric Approach for Quantification of Cyclizine in the Presence of its Toxic Impurities in Human Plasma; in silico Study and ADMET Calculations
Authors: Fares Michel Y. , Abdelwahab Nada S. , El-Sayed Ghada M. , Hegazy Maha A. , Abdelrahman Maha M.
Published: March 2022

Cyclizine (CYZ); an antiemetic compound; is widely misused for its euphoric or hallucinatory effects, either by oral or intravenous routes. The concomitant abuse of CYZ among addicted adolescents contributes to neuromuscular disorders that are life-threatening. Consequently, with the company of 1-Methylpiperazine (MPZ) and diphenylmethanol (DPM, Benzhydrol) as pharmacopoeia-reported CYZ impurities, a novel spectrofluorimetric assay for the detection of CYZ, has been established either in human plasma samples or in its parenteral formulation. The native fluorescence of CYZ has been investigated under various conditions. Different parameters affecting relative fluorescence intensity of CYZ including diluting solvent, surfactant, plasma protein solvent, and pH were studied and optimized. The linearity obtained between the fluorescence intensity at emission wavelength 350 nm after excitation at 244 nm and the corresponding CYZ concentrations was in the range 10–1000 ng/mL for measurement of CYZ either in pure form or in human plasma samples, with a appropriate correlation coefficient (r = 0.9999) and 3.10 ng/mL as the limit of detection and 9.41 ng/mL as the limit of quantitation. The suggested procedure was created and validated in accordance with ICH guidelines for quantification of CYZ either in its pure form or its dosage form, and FDA guidelines for the assay of CYZ in human plasma. Finally, in silico study and ADMET predictions were conducted for the studied drug impurities to estimate their pharmacokinetic behaviors. The results showed that both CYZ impurities have higher cellular permeability and maximum tolerated doses, DPM has higher BBB and CNS permeability than MPZ, while MPZ exceeds DPM in total clearance and volume of distribution.

Graphic Abstract
Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection
Authors: Barroso-Arévalo Sandra , Sánchez-Morales Lidia , Barasona Jose A. , Rivera Belén , Sánchez Rocío , Risalde María A. , Agulló-Ros Irene , Sánchez-Vizcaíno José M.
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic disease denominated as Coronavirus Disease 2019 (COVID-19). Several studies suggest that the original source of this virus was a spillover from an animal reservoir and its subsequent adaptation to humans. Of all the different animals affected, cats are one of the most susceptible species. Moreover, several cases of natural infection in domestic and stray cats have been reported in the last few months. Although experimental infection assays have demonstrated that cats are successfully infected and can transmit the virus to other cats by aerosol, the conditions used for these experiments have not been specified in terms of ventilation. We have, therefore, evaluated the susceptibility of cats using routes of infection similar to those expected under natural conditions (exposure to a sneeze, cough, or contaminated environment) by aerosol and oral infection. We have also evaluated the transmission capacity among infected and naïve cats using different air exchange levels. Despite being infected using natural routes and shed virus for a long period, the cats did not transmit the virus to contact cats when air renovation features were employed. The infected animals also developed gross and histological lesions in several organs. These outcomes confirm that cats are at risk of infection when exposed to infected people, but do not transmit the virus to other cats with high rates of air renovation.
Repeat and Near Repeat Burglary Victimization in Taiwan
Authors: Kuo Tien-Li , Sidebottom Aiden , Wortley Richard , Tsai Tyan-muh
Published: March 2022

Extensive evidence shows that repeat victimization is common and widespread, but studies on the prevalence of repeat victimization in Asia are limited. This study examines the extent and patterns of repeat and near-repeat burglary victimization in Taiwan using both 2015 Taiwan Area Victimization Survey data and police recorded burglary data. Results indicated that: (1) burglaries against the same household in Taiwan are highly concentrated (with the top 10% most burgled households making up around 30% of reported victimizations), more so than is often found in many Western countries; (2) the risk of (repeat) burglary is not consistently spread over space and time, particularly within the 100-m range of an initial burglary incident; and (3) the levels of near repeat burglaries identified in this study are notably lower than was observed in prior studies both in China and in many western countries. The findings highlight the value of developing prevention strategies specifically targeting repeat burglary victimization.
Clinic, Home, and Kiosk Blood Pressure Measurements for Diagnosing Hypertension: a Randomized Diagnostic Study
Authors: Green Beverly B , Anderson Melissa L , Cook Andrea J , Ehrlich Kelly , Hall Yoshio N , Hsu Clarissa , Joseph Dwayne , Klasnja Predrag , Margolis Karen L , McClure Jennifer B , Munson Sean A , Thompson Mathew J
Published: March 2022

Background

The US Preventive Services Task Force recommends blood pressure (BP) measurements using 24-h ambulatory monitoring (ABPM) or home BP monitoring before making a new hypertension diagnosis.

Objective

Compare clinic-, home-, and kiosk-based BP measurement to ABPM for diagnosing hypertension.

Design, Setting, and Participants

Diagnostic study in 12 Washington State primary care centers, with participants aged 18–85 years without diagnosed hypertension or prescribed antihypertensive medications, with elevated BP in clinic.

Interventions

Randomization into one of three diagnostic regimens: (1) clinic (usual care follow-up BPs); (2) home (duplicate BPs twice daily for 5 days); or (3) kiosk (triplicate BPs on 3 days). All participants completed ABPM at 3 weeks.

Main Measures

Primary outcome was difference between ABPM daytime and clinic, home, and kiosk mean systolic BP. Differences in diastolic BP, sensitivity, and specificity were secondary outcomes.

Key Results

Five hundred ten participants (mean age 58.7 years, 80.2% white) with 434 (85.1%) included in primary analyses. Compared to daytime ABPM, adjusted mean differences in systolic BP were clinic (−4.7mmHg [95% confidence interval −7.3, −2.2]; P<.001); home (−0.1mmHg [−1.6, 1.5];P=.92); and kiosk (9.5mmHg [7.5, 11.6];P<.001). Differences for diastolic BP were clinic (−7.2mmHg [−8.8, −5.5]; P<.001); home (−0.4mmHg [−1.4, 0.7];P=.52); and kiosk (5.0mmHg [3.8, 6.2]; P<.001). Sensitivities for clinic, home, and kiosk compared to ABPM were 31.1% (95% confidence interval, 22.9, 40.6), 82.2% (73.8, 88.4), and 96.0% (90.0, 98.5), and specificities 79.5% (64.0, 89.4), 53.3% (38.9, 67.2), and 28.2% (16.4, 44.1), respectively.

Limitations

Single health care organization and limited race/ethnicity representation.

Conclusions

Compared to ABPM, mean BP was significantly lower for clinic, significantly higher for kiosk, and without significant differences for home. Clinic BP measurements had low sensitivity for detecting hypertension. Findings support utility of home BP monitoring for making a new diagnosis of hypertension.

Trial Registration

ClinicalTrials.gov NCT03130257 https://clinicaltrials.gov/ct2/show/NCT03130257
Interplay Between Electronic States and Structural Stability in Cation-Deficient VCoSb, NbCoSb, and TaCoSb Half-Heuslers
Authors: Miranda Joaquin , Gruhn Thomas
Published: March 2022

The effects of the vacancy concentration at the cation site of three half-Heuslers, VCoSb, NbCoSb, and TaCoSb, were studied with a combination of two computational methods: density functional theory and Monte Carlo simulations, both linked by a cluster expansion method. Our density functional method allows us to follow a gap opening in the electronic density of states in NbCoSb and TaCoSb as a function of vacancy concentration, starting from a metallic state with the Fermi-level crossing the valence states in the pristine crystal, passing throughout a p-type doped behavior, down to a semiconducting state at 20% of vacancies. In the case of VCoSb, the transition starts from the half-metallic ferromagnetic state, where VCoSb remains half-metallic until it achieves a semiconductor state at V$$_{0.8}$$

0.8

CoSb composition, the transition leading to a magnetic–nonmagnetic crossover. Further increase of vacancies leads to non-polarized in-gap states in V$$_{0.75}$$

0.75

CoSb, and polarized in-gaps in Nb$$_{0.77}$$

0.77

CoSb, while Ta$$_{0.75}$$

0.75

CoSb recovers a metallic behavior but with an n-character. Based on our cluster expansion, we can assert that Ta$$_{0.8}$$

0.8

CoSb is slightly more stable than Nb$$_{0.8}$$

0.8

CoSb, while both are much more stable than V$$_{0.8}$$

0.8

CoSb. Temperature effects were studied through Monte Carlo simulations. The simulations show that, upon cooling, the ground states are hard to recover, and instead metastable states are formed. The vacancy arrangements were scrutinized with the help of suitable order parameters for the lattice vacancy occupation.
The clinicopathological characteristics, prognosis and immune microenvironment mapping in MSI-H/MMR-D endometrial carcinomas
Authors: Guo Yu-e , Liu Yin , Zhang Wei , Luo Heng , Shu Ping , Chen Guofang , Li Yuping
Published: March 2022

Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.
Biological constraints as norms in evolution
Authors: Tahar Mathilde
Published: March 2022

Biology seems to present local and transitory regularities rather than immutable laws. To account for these historically constituted regularities and to distinguish them from mathematical invariants, Montévil and Mossio (Journal of Theoretical Biology 372:179–191, 2015) have proposed to speak of constraints. In this article we analyse the causal power of these constraints in the evolution of biodiversity, i.e., their positivity, but also the modality of their action on the directions taken by evolution. We argue that to fully account for the causal power of these constraints on evolution, they must be thought of in terms of normativity. In this way, we want to highlight two characteristics of the evolutionary constraints. The first, already emphasised as reported by Gould (The structure of evolutionary theory, Harvard University Press, 2002), is that these constraints are both produced by and producing biological evolution and that this circular causation creates true novelties. The second is that this specific causality, which generates unpredictability in evolution, stems not only from the historicity of biological constraints, but also from their internalisation through the practices of living beings.
Arbeitsgestaltung bei Digitalisierung
Authors: Hacker Winfried
Published: March 2022

Der Arbeits- und Gesundheitsschutz bei vorwiegend informationsverarbeitenden, geistigen Erwerbstätigkeiten – zunehmend mit digitalen Arbeitsmitteln und künstlicher Intelligenz – erfordert das Verwirklichen der Merkmale menschenzentrierter Arbeitsgestaltung (DIN EN ISO 6385/2016).

Der Beitrag betrifft das menschzentrierte Gestalten des Arbeitsprozesses, nicht der Arbeitsmittel.

Das Erfüllen dieser Merkmale soll nicht nur physische und psychische Beeinträchtigungen der Arbeitenden verhindern, sondern auch ihre Kompetenzen erhalten und erweitern sowie das gesundheitliche Wohlbefinden und die Arbeitsleistung fördern.

Es werden übertragbare (generische) Vorschläge an die präventive, bedingungszentrierte und partizipative Gestaltung, insbesondere die Funktionsteilung zwischen Menschen und Technik und die Arbeitsorganisation/-teilung bei informationsverarbeitenden Tätigkeiten abgeleitet, die helfen, die Merkmale menschzentrierter Gestaltung zu erfüllen. Arbeitsschritte zur praktischen Verwirklichung sind skizziert.

Eine Schwierigkeit beim Anwenden der Vorschläge ist ihre allgemeingültige Form. Sie erfordert das Übertragen auf die vielfältigen informationsverarbeitenden Arbeitstätigkeiten. Eine Hilfe bei ihrer Übertragung sind bewährte duale, partizipative und iterative Strategien der Automatisierung.

Das Hauptanliegen ist zu verdeutlichen, dass und in welcher Hinsicht menschenzentrierte Arbeitsgestaltung auch bei vorwiegend informationsverarbeitenden, geistigen Erwerbstätigkeiten unerlässlich ist, und dass Digitalisierung diese präventive menschzentrierte Gestaltung nicht ersetzt, sondern voraussetzt.
Heavy Metal Removal from Aqueous Solutions Using Fly-Ash Derived Zeolite NaP1
Authors: Ankrah Archibald Frank , Tokay Begum , Snape Colin E.
Published: March 2022

Fly-ash derived zeolites have recently -received great attention as cheaper adsorbents to remove heavy metals from water since they can be synthesized from a waste product. In this study, we evaluated the single- and multi-cation adsorption efficiencies of fly-ash derived NaP1 for the removal of zinc (Zn), copper (Cu) and lead (Pb). We also determined precipitation and leaching from NaP1 during the adsorption. Results showed that the uptake capacities for Zn (34 mg/g) and Pb (192 mg/g) were higher than other fly-ash derived NaP1 and adsorbents such as clinoptilolite and activated carbon. The Cu uptake was estimated ~ 14.6 mg/g. Pb2+  > Cu2+  > Zn2+ is the order for the metal cation selectivity of NaP1. Langmuir adsorption isotherm and pseudo-second order kinetic model fitted best for all elements. The metal uptake occurred in 15 min. Diffusion of hydrated metals through microporous channels is the rate-determining step.
Enhancement of structural and optical properties of transparent sodium zinc phosphate glass–ceramics nano composite
Authors: Farag M. A. , Ibrahim A. , Hassaan M. Y. , Ramadan R. M.
Published: March 2022

Transparent sodium phosphate glass–ceramics system according to the composition (55-x) P2O5.(30 + x)ZnO.15Na2O where x = 0, 2.5, 5, 7.5, and 10 was prepared with the melt quenching technique. Different techniques such as XRD and infrared spectroscopy (FTIR) were used to investigate the structure of the studied glass samples and glass–ceramics nano composite. XRD revealed the formation of crystalline phase. The crystalline phase of Na2Zn (P2O7) and Na2ZnP2O7.Zn2P2O7 has been detected which varies according to the ZnO concentration. The density increased whereas molar volume decreased as ZnO content was increased. Optical band gap values, direct and indirect, decreased with increasing ZnO content revealing that bridging oxygen linkage Zn–O-P present in the glass network. The band gaps were found to be ranging between 3.42 and 3.13 eV for indirect transition and ranging between 4.34 and 4.20 eV for direct transitions. It was concluded that the samples have a strong tendency to be crystallized with increasing ZnO content in the sample. This crystallization behavior with increasing the ZnO content affected the structure and optical properties of the prepared samples. In this work, a low cost, wide band gap transparent ceramic with wide range of transparency was prepared and investigated. Such glass–ceramic system is suitable for doping with rare-earth element and/or transition metals for laser and optical devices.
HMB – „heavy menstrual bleeding“
Authors: Theis Susanne , Stute Petra
Published: March 2022

Abnorme uterine Blutungen treten in der reproduktiven Phase einer Frau häufig auf. Tritt vom Volumen her eine besonders starke Blutung auf, wird diese als „heavy menstrual bleeding“ bezeichnet. Wichtig ist eine Unterscheidung zwischen akuter und chronischer abnormer uteriner Blutung, um die weiteren diagnostischen und therapeutischen Schritte entsprechend einleiten zu können. Akute Blutungen mit hämodynamischer Instabilität erfordern ein notfallmäßiges Handeln und werden meist operativ behandelt. Hämodynamisch stabile akute Blutungen sowie chronische Blutungen werden bevorzugt medikamentös behandelt.
Wearable gait analysis systems: ready to be used by medical practitioners in geriatric wards?
Authors: Ollenschläger Malte , Kluge Felix , Müller-Schulz Matthias , Püllen Rupert , Möller Claudia , Klucken Jochen , Eskofier Bjoern M.
Published: March 2022

Purpose

We assess feasibility of wearable gait analysis in geriatric wards by testing the effectiveness and acceptance of the system.

Methods

Gait parameters of 83 patients (83.34 ± 5.88 years, 58/25 female/male) were recorded at admission and/or discharge to/from two geriatric inpatient wards. Gait parameters were tested for statistically significant differences between admission and discharge. Walking distance measured by a wearable gait analysis system was correlated with distance assessed by physiotherapists. Examiners rated usability using the system usability scale. Patients reported acceptability on a five-point Likert-scale.

Results

The total distance measures highly correlate (r = 0.89). System Usability Scale is above the median threshold of 68, indicating good usability. Majority of patients does not have objections regarding the use of the system. Among other gait parameters, mean heel strike angle changes significantly between admission and discharge.

Conclusion

Wearable gait analysis system is objectively and subjectively usable in a clinical setting and accepted by patients. It offers a reasonably valid assessment of gait parameters and is a feasible way for instrumented gait analysis.
Semi-automated approach for generation of biological networks on drug-induced cholestasis, steatosis, hepatitis, and cirrhosis
Authors: Shin Hyun Kil , Florean Oana , Hardy Barry , Doktorova Tatyana , Kang Myung-Gyun
Published: March 2022

Drug-induced liver injury (DILI) is one of the leading reasons for discontinuation of a new drug development project. Diverse machine learning or deep learning models have been developed to predict DILI. However, these models have not provided an adequate understanding of the mechanisms leading to DILI. The development of safer drugs requires novel computational approaches that enable the prompt understanding of the mechanism of DILI. In this study, the mechanisms leading to the development of cholestasis, steatosis, hepatitis, and cirrhosis were explored using a semi-automated approach for data gathering and associations. Diverse data from ToxCast, Comparative Toxicogenomic Database (CTD), Reactome, and Open TG-GATEs on reference molecules leading to the development of the respective diseases were extracted. The data were used to create biological networks of the four diseases. As expected, the four networks had several common pathways, and a joint DILI network was assembled. Such biological networks could be used in drug discovery to identify possible molecules of concern as they provide a better understanding of the disease-specific key events. The events can be target-tested to provide indications for potential DILI effects.