bluuebunny/crossref_metadata_2025 huggingface dataset:
Sirolimus in renal transplant recipients with malignancies in Germany
Authors: Naik Marcel G , Arns Wolfgang , Budde Klemens , Diekmann Fritz , Eitner Frank , Gwinner Wilfried , Heyne Nils , Jürgensen Jan Steffen , Morath Christian , Riester Udo , Heller Katharina M , Fischereder Michael
Published: December 2020

Background

Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited.

Methods

We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity.

Results

Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen’s disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with patients without a history of cancer. After conversion to SRL, cancer incidence rates (IRs) of all tumours were lower compared with rates before conversion. Cancer IRs after conversion were higher in patients with malignancy before conversion compared with those without. Patient survival was worse in patients with solid cancers compared with patients with skin cancers or without malignancies. Biopsy-proven acute rejections in the first year after conversion were less frequent in patients with malignancy compared with those without. Graft survival and renal function in all cancer types were better than in patients converted to SRL without cancers.

Conclusions

Conversion to SRL in patients with a history of cancer is safe regarding renal function and graft survival, while patient survival is largely dependent on tumour entity.
Five reasons COVID-19 is less severe in younger age-groups
Authors: Turke Paul W
Published: December 2020

The severity of COVID-19 is age-related, with the advantage going to younger age-groups. Five reasons are presented. The first two are well-known, are being actively researched by the broader medical community, and therefore are discussed only briefly here. The third, fourth and fifth reasons derive from evolutionary life history theory, and potentially fill gaps in current understanding of why and how young and old age-groups respond differently to infection with SARS-CoV-2. Age of onset of generalized somatic aging and the timing of its progression are identified as important causes of these disparities, as are specific antagonistic pleiotropic tradeoffs in immune system function. Lay Summary: Covid-19 is less severe in younger age-groups than it is in older age-groups. Five advantages of youth are identified and explained in light of evolutionary life history theory, with a focus on the pattern of aging and specific tradeoffs between early and late immune system function.
Height and well-being during the transition from plan to market
Authors: Adserà Alícia , Dalla Pozza Francesca , Guriev Sergei , Kleine-Rueschkamp Lukas , Nikolova Elena
Published: December 2020

Kleine-Rueschkamp, and Elena Nikolova?>Using newly available data, we re-evaluate the impact of transition from plan to market in former communist countries on objective and subjective well-being. We find clear evidence of the high social cost of early transition reforms: cohorts born around the start of transition are about 1 cm shorter than their older or younger peers. We provide suggestive evidence on the importance on mechanisms that partially explain these results: the decline of GDP per capita and the deterioration of healthcare systems. On the bright side, we find that cohorts that experienced transition in their infancy are now better educated and more satisfied with their lives than their counterparts. Taken together, our results imply that the transition process has been a traumatic experience, but that its negative impact has largely been overcome.
Device closure for patent foramen ovale in patients with cryptogenic stroke: which patients should get it?
Authors: Parrini Iris , Cecchi Enrico , Forno Davide , Lyon Alexander R , Asteggiano Riccardo
Published: December 2020

Patent foramen ovale (PFO) and cryptogenic stroke (CS) both have a high prevalence. The optimal treatment to reduce stroke recurrence after CS remains controversial. Results from clinical trials, meta-analyses, and position papers, support percutaneous PFO device closure and medical therapy compared to medical therapy alone. However, the procedure may be associated with cardiac complications including an increased incidence of new atrial fibrillation. The benefit/risk balance should be determined on a case-by-case basis with the greatest benefit of PFO closure in patients with atrial septal aneurysm and PFO with large shunts. Future studies should address unsolved questions such as the choice of medical therapy in patients not undergoing closure, the duration of antiplatelet therapy, and the role of PFO closure in patients over 60 years old.
Prevention of stroke in patients with chronic coronary syndromes or peripheral arterial disease
Authors: Parker William A E , Gorog Diana A , Geisler Tobias , Vilahur Gemma , Sibbing Dirk , Rocca Bianca , Storey Robert F
Published: December 2020

Stroke is a common and devastating condition caused by atherothrombosis, thromboembolism, or haemorrhage. Patients with chronic coronary syndromes (CCS) or peripheral artery disease (PAD) are at increased risk of stroke because of shared pathophysiological mechanisms and risk-factor profiles. A range of pharmacological and non-pharmacological strategies can help to reduce stroke risk in these groups. Antithrombotic therapy reduces the risk of major adverse cardiovascular events, including ischaemic stroke, but increases the incidence of haemorrhagic stroke. Nevertheless, the net clinical benefits mean antithrombotic therapy is recommended in those with CCS or symptomatic PAD. Whilst single antiplatelet therapy is recommended as chronic treatment, dual antiplatelet therapy should be considered for those with CCS with prior myocardial infarction at high ischaemic but low bleeding risk. Similarly, dual antithrombotic therapy with aspirin and very-low-dose rivaroxaban is an alternative in CCS, as well as in symptomatic PAD. Full-dose anticoagulation should always be considered in those with CCS/PAD and atrial fibrillation. Unless ischaemic risk is particularly high, antiplatelet therapy should not generally be added to full-dose anticoagulation. Optimization of blood pressure, low-density lipoprotein levels, glycaemic control, and lifestyle characteristics may also reduce stroke risk. Overall, a multifaceted approach is essential to best prevent stroke in patients with CCS/PAD.
Safety, effectiveness, and quality of life following pulmonary vein isolation with a multi-electrode radiofrequency balloon catheter in paroxysmal atrial fibrillation: 1-year outcomes from SHINE
Authors: Schilling Richard , Dhillon Gurpreet Singh , Tondo Claudio , Riva Stefania , Grimaldi Massimo , Quadrini Federico , Neuzil Petr , Chierchia Gian-Battista , de Asmundis Carlo , Abdelaal Ahmed , Vanderlinden Liesbeth , Tan Tiffany , Ding Wern Yew , Gupta Dhiraj , Reddy Vivek Y
Published: December 2020

Aims

To evaluate the safety and effectiveness of a compliant multi-electrode radiofrequency balloon catheter (RFB) used with a multi-electrode diagnostic catheter for pulmonary vein isolation (PVI).

Methods and results

This prospective, multicentre, single-arm study was conducted at six European sites and enrolled patients with symptomatic paroxysmal atrial fibrillation. The primary effectiveness endpoint was entrance block in treated pulmonary veins (PVs) after adenosine/isoproterenol challenge. The primary safety endpoint was the occurrence of primary adverse events (PAEs) within 7 days. Cerebral magnetic resonance imaging and neurological assessments were performed pre- and post-ablation in a subset of patients. Atrial arrhythmia recurrence was assessed over 12 months via transtelephonic and Holter monitoring. Quality of life was assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. Of 85 patients undergoing ablation per study protocol, PV entrance block was achieved in all (one PV required touch-up with a focal catheter). Acute reconnection of ≥1 PVs after adenosine/isoproterenol challenge was observed in 9.3% (30/324) of PVs ablated. Post-ablation, silent cerebral lesions were detected in 9.7% (3/31) of patients assessed, all of which was resolved at 1-month follow-up. One patient experienced a PAE (retroperitoneal bleed). Freedom from documented symptomatic and all arrhythmia was 72.2% and 65.8% at 12 months. Four patients (4.7%) underwent repeat ablation. Significant improvements in all AFEQT subscale scores were seen at 6 and 12 months.

Conclusion

PVI with the novel RFB demonstrated favourable safety and effectiveness, with low repeat ablation rate and clinically meaningful improvement in quality of life.

ClinicalTrials.gov Registration Number

NCT03437733.
DrivAER: Identification of driving transcriptional programs in single-cell RNA sequencing data
Authors: Simon Lukas M , Yan Fangfang , Zhao Zhongming
Published: December 2020

Background

Single-cell RNA sequencing (scRNA-seq) unfolds complex transcriptomic datasets into detailed cellular maps. Despite recent success, there is a pressing need for specialized methods tailored towards the functional interpretation of these cellular maps.

Findings

Here, we present DrivAER, a machine learning approach for the identification of driving transcriptional programs using autoencoder-based relevance scores. DrivAER scores annotated gene sets on the basis of their relevance to user-specified outcomes such as pseudotemporal ordering or disease status. DrivAER iteratively evaluates the information content of each gene set with respect to the outcome variable using autoencoders. We benchmark our method using extensive simulation analysis as well as comparison to existing methods for functional interpretation of scRNA-seq data. Furthermore, we demonstrate that DrivAER extracts key pathways and transcription factors that regulate complex biological processes from scRNA-seq data.

Conclusions

By quantifying the relevance of annotated gene sets with respect to specified outcome variables, DrivAER greatly enhances our ability to understand the underlying molecular mechanisms.
Time-dependent and spatiotemporal statistical analysis of intraplate anomalous seismicity: Sarria-Triacastela-Becerreá (NW Iberian Peninsula, Spain)
Authors: Crespo-Martín Cristina , Martín-González Fidel , Yazdi Pouye , Hainzl Sebastian , Rincón Marta
Published: December 2020

The Sarria-Triacastela-Becerreá seismicity is located in an intraplate region considered seismically stable, but in 1995 started an unprecedented earthquake activity in the area. Since then an anomalous long-term continuous seismicity remains until now in the same location. Despite the long-term seismicity and the large magnitudes for the region standards (5.1 Mw), the origin and mechanisms of this seismicity remains unclear. The isolation of background from the main shock–aftershock contribution by means of the application of the Epidemic Type Aftershock Sequences (ETAS) model, the spatial depiction and the resemblance to near seismic regions allow us to identify several seismicity behaviours. From 1995 to 1998/99, the seismicity in this location mainly consists of intensive and deeper earthquake sequences linked to the 1995 and 1997 main shocks. Our results suggest that the main shocks triggered aftershocks and additionally initiated or facilitated aseismic processes. A likely scenario is that the main shocks broke a sealed source at depth allowing a subsequent intrusion of high-pressurized fluids from depth. The resemblance of this period with Zamora seismic characteristics proposes that Triacastela seismicity was also initiated by tectonic activity. From 1998/99 to 2018, a change in seismicity is observed, the background contribution took control and swarm-type activity is predominant. While the earthquake rate decreases, the relative background contribution goes up. Actually, after 2013 the clusters almost disappear and background contribution achieves 55 per cent of the total activity. The spatial migration to the southeast and the upward trend to shallower depth support fluid migration as possible driving mechanism responsible for the transient seismicity in this period. The swarm-type activity in Triacastela in later periods and the resemblance of b-values with Ponte Caldelas and Ventaniella seismicity suggest that the seismicity in Triacastela is related to fluid migration and the reactivation of fractured areas. We propose that the mechanism of this anomalous and long-term seismicity in Triacastela is the mix of different mechanisms, starting with the tectonic seismicity, generated during the 1995 and 1997 seismic sequences, which initiated a fluid upward migration through fractured crustal fault patches, observed after 1998–1999, and responsible for the seismicity during the following 20 yr.
Understanding disparities in person-centred maternity care: the potential role of provider implicit and explicit bias
Authors: Afulani Patience A , Ogolla Beryl A , Oboke Edwina N , Ongeri Linnet , Weiss Sandra J , Lyndon Audrey , Mendes Wendy Berry
Published: December 2020

Studies in low-resource settings have highlighted disparities in person-centred maternity care (PCMC)—respectful and responsive care during childbirth—based on women’s socioeconomic status (SES) and other characteristics. Yet few studies have explored factors that may underlie these disparities. In this study, we examined implicit and explicit SES bias in providers’ perceptions of women’s expectations and behaviours, as well as providers’ general views regarding factors influencing differential treatment of women. We conducted a convergent mixed-methods study with 101 maternity providers in western Kenya. Implicit SES bias was measured using an adaptation of the Implicit Association Test (IAT) and explicit SES bias assessed using situationally specific vignettes. Qualitative data provided additional details on the factors contributing to disparities. Results provide evidence for the presence of both implicit and explicit bias related to SES that might influence PCMC. Differential treatment was linked to women’s appearance, providers’ perceptions of women’s attitudes, assumptions about who is more likely to understand or be cooperative, women’s ability to advocate for themselves or hold providers accountable, ability to pay for services in a timely manner, as well as situational factors related to stress and burnout. These factors interact in complex ways to produce PCMC disparities, and providing better care to certain groups does not necessarily indicate preference for those groups or a desire to provide better care to them. The findings imply the need for multilevel approaches to addressing disparities in maternity care. This should include provider training on PCMC and their biases, advocacy for women of low SES, accountability mechanisms, and structural and policy changes within health care settings.
RPGR isoform imbalance causes ciliary defects due to exon ORF15 mutations in X-linked retinitis pigmentosa (XLRP)
Authors: Moreno-Leon Laura , West Emma L , O’Hara-Wright Michelle , Li Linjing , Nair Rohini , He Jie , Anand Manisha , Sahu Bhubanananda , Chavali Venkat Ramana Murthy , Smith Alexander J , Ali Robin R , Jacobson Samuel G , Cideciyan Artur V , Khanna Hemant
Published: December 2020

Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause severe retinal ciliopathy, X-linked retinitis pigmentosa. Although two major alternatively spliced isoforms, RPGRex1-19 and RPGRORF15, are expressed, the relative importance of these isoforms in disease pathogenesis is unclear. Here, we analyzed fibroblast samples from eight patients and found that all of them form longer cilia than normal controls, albeit to different degrees. Although all mutant RPGRORF15 messenger RNAs (mRNAs) are unstable, their steady-state levels were similar or higher than those in the control cells, suggesting there may be increased transcription. Three of the fibroblasts that had higher levels of mutant RPGRORF15 mRNA also exhibited significantly higher levels of RPGRex1-19 mRNA. Four samples with unaltered RPGRex1-19 levels carried mutations in RPGRORF15 that resulted in this isoform being relatively less stable. Thus, in all cases, the RPGRex1-19/RPGRORF15 isoform ratio was increased, and this was highly correlative to the cilia extension defect. Moreover, overexpression of RPGRex1-19 (mimicking the increase in RPGRex1-19 to RPGRORF15 isoform ratio) or RPGRORF15 (mimicking reduction of the ratio) resulted in significantly longer or shorter cilia, respectively. Notably, the cilia length defect appears to be attributable to both the loss of the wild-type RPGRORF15 protein and to the higher levels of the RPGRex1-19 isoform, indicating that the observed defect is due to the altered isoform ratios. These results suggest that maintaining the optimal RPGRex1-9 to RPGRORF15 ratio is critical for cilia growth and that designing strategies that focus on the best ways to restore the RPGRex1-19/RPGRORF15 ratio may lead to better therapeutic outcomes.
Urine Concentration Does Not Affect Biochemical Testing for Non-adherence
Authors: Burns A D , Alghamadi R , Iqbal A , Davies T , Lane D , Patel P , Gupta P
Published: December 2020

Hypertension is one of the most important modifiable risk factor causing cardiovascular disease. Unfortunately, non-adherence to antihypertensive medications is frequently observed in hypertensive patients and can lead to an increase in morbidity and mortality. Until recently, there was no robust clinical method to objectively diagnose non-adherence. Recently, the detection of medications in urine or blood by mass spectrometry techniques such as liquid chromatography-tandem mass spectrometry (LC–MS-MS) has been accepted as the diagnostic method of choice for the detection of non-adherence. Despite this, it is unclear whether the concentration of urine can affect the detection of medications in urine. Therefore, this study aimed to assess the effect of urine concentration on detection of antihypertensive medications by LC–MS-MS in which urine creatinine is used as an independent marker of urine concentration. Biochemical adherence results for 22 different medications (1,709 prescriptions) in 463 different subjects were converted to an adherence score. The adherence score was defined as the ratio of the total number of subjects in which the drug was detected to the total number of subjects to whom the drug was prescribed. The adherence scores for each medication were correlated with urine creatinine concentration for each medication. Non-adherence was observed in 47.1% of samples with a mean urine creatinine concentration of these samples of 9.4 ± 7.1 mmol/L. There was no significant difference between the urine creatinine concentrations in the detected vs non-detected groups for each of the 22 medications. Furthermore, there are no differences in adherence scores across the urine creatinine concentration. This is the first study to demonstrate that urine creatinine concentration does not affect the results of the adherence screening by LC–MS-MS.
Transitioning to Practice: Getting up to Speed in Efficiency and Accuracy
Authors: Patel Miral M , Kapoor Megha M , Whitman Gary J
Published: December 2020

The transition from trainee to breast radiologist is challenging. The many new responsibilities that breast radiologists acquire while establishing themselves as clinicians may increase stress and anxiety. Taking inventory of existing knowledge and skills and addressing deficits toward the end of one’s training can be beneficial. New breast radiologists should expect to be slower and gain proficiency in the first several years out of training. Having realistic expectations for oneself with respect to screening mammography interpretation and following up on the subsequent diagnostic imaging workup of screening callback examinations can increase competence and confidence. Familiarity with the available literature to guide management in the diagnostic setting can increase efficiency. Planning ahead for localizations and biopsies also allows for efficiency while alleviating anxiety. Ultimately, adapting to a new work environment using a collaborative approach with primary healthcare providers, pathologists, and surgeons while remembering to have mentors within and beyond the field of radiology allows for a more successful transition.
How Does Public Disclosure of Performance Information Affect Politicians’ Attitudes towards Effort Allocation? Evidence from a Survey Experiment
Authors: Desmidt Sebastian , Meyfroodt Kenn
Published: December 2020

Does relative performance information (PI) still impact politicians’ attitudes when the potential for external blame or credit is limited? And, if not, is the active disclosure of PI about government activities with a low propensity for media attention an effective strategy for increasing the effect of PI? Despite the tendency to progressively disclose PI, empirical evidence on the effectiveness of publicly disclosing PI is almost non-existent. Hence, a survey embedded experiment was developed, building on self-determination theory and blame-avoidance theory, to assess how the provision of PI with a low propensity to attract media attention affects politicians’ attitudes towards resource allocation and whether this effect is altered by the public disclosure of PI. Data from 795 Belgian (Flemish) local councilors indicates that PI with a low propensity for media attention does impact politicians’ attitudes towards effort allocation but that public disclosure of PI mitigates the effect size in the case of negative-valence PI. Thus, the results draw attention to the unintended—and potentially dysfunctional—effects of the disclosure of PI.
Automated approach for segmenting gross tumor volumes for lung cancer stereotactic body radiation therapy using CT-based dense V-networks
Authors: Cui Yunhao , Arimura Hidetaka , Nakano Risa , Yoshitake Tadamasa , Shioyama Yoshiyuki , Yabuuchi Hidetake
Published: December 2020

The aim of this study was to develop an automated segmentation approach for small gross tumor volumes (GTVs) in 3D planning computed tomography (CT) images using dense V-networks (DVNs) that offer more advantages in segmenting smaller structures than conventional V-networks. Regions of interest (ROI) with dimensions of 50 × 50 × 6–72 pixels in the planning CT images were cropped based on the GTV centroids when applying stereotactic body radiotherapy (SBRT) to patients. Segmentation accuracy of GTV contours for 192 lung cancer patients [with the following tumor types: 118 solid, 53 part-solid types and 21 pure ground-glass opacity (pure GGO)], who underwent SBRT, were evaluated based on a 10-fold cross-validation test using Dice’s similarity coefficient (DSC) and Hausdorff distance (HD). For each case, 11 segmented GTVs consisting of three single outputs, four logical AND outputs, and four logical OR outputs from combinations of two or three outputs from DVNs were obtained by three runs with different initial weights. The AND output (combination of three outputs) achieved the highest values of average 3D-DSC (0.832 ± 0.074) and HD (4.57 ± 2.44 mm). The average 3D DSCs from the AND output for solid, part-solid and pure GGO types were 0.838 ± 0.074, 0.822 ± 0.078 and 0.819 ± 0.059, respectively. This study suggests that the proposed approach could be useful in segmenting GTVs for planning lung cancer SBRT.
Disseminated cutaneous leishmaniasis in a Thai foreign worker in Israel
Authors: Dalal Adam , Barzilai Aviv , Baum Sharon , Schwartz Eli
Published: December 2020

We report a case of disseminated cutaneous leishmaniasis (CL) acquired in Israel. This very unusual presentation of CL was caused by Leishmania major in an immunocompetent foreign worker from Thailand. CL is an emerging skin infection in travellers and immigrants with a varied, and possibly misleading, clinical presentation.
Against ‘ideological neutrality’: on the limits of liberal and neoliberal economic and social human rights
Authors: Manfredi Zachary
Published: December 2020

This article intervenes in contemporary debates about the future of economic and social human rights. It analyses neoliberal and mainstream liberal theories and argues that both approaches substantially limit understanding of these rights. The article concludes by discussing some of the challenges facing an alternative, socialist conception of economic and social rights.
Cloud cover and aurora contamination at dome A in 2017 from KLCAM
Authors: Yang Xu , Shang Zhaohui , Hu Keliang , Hu Yi , Ma Bin , Wang Yongjiang , Cao Zihuang , Ashley Michael C B , Wang Wei
Published: December 2020

Dome A in Antarctica has many characteristics that make it an excellent site for astronomical observations, from the optical to the terahertz. Quantitative site testing is still needed to confirm the site’s properties. In this paper, we present a statistical analysis of cloud cover and aurora contamination from the Kunlun Cloud and Aurora Monitor (KLCAM). KLCAM is an automatic unattended all-sky camera aiming for long-term monitoring of the usable observing time and optical sky background at Dome A. It was installed at Dome A in January 2017, worked through the austral winter, and collected over 47 000 images over 490 d. A semi-quantitative visual data analysis of cloud cover and auroral contamination was carried out by five individuals. The analysis shows that the night sky was free of clouds for 83 per cent of the time, which ranks Dome A highly in a comparison with other observatory sites. Although aurorae were detected somewhere on an image for nearly 45 per cent of the time, the chance of a point on the sky being affected by an aurora is small. The strongest auroral emission lines can be filtered out with customized filters.
Detection of giant pulses in PSR J1047−6709
Authors: Sun S N , Yan W M , Wang N
Published: December 2020

We report the emission variations in PSR J1047−6709 observed at 1369 MHz using the Parkes 64-m radio telescope. This pulsar shows two distinct emission states: a weak state and a bright emission state. We detected giant pulses (GPs) in the bright state for the first time. We found 75 GPs with pulse width ranging from 0.6 to 2.6 ms. The energy of GPs follows a power-law distribution with the index α = −3.26 ± 0.22. The peak flux density of the brightest GP is 19 Jy which is 110 times stronger than the mean pulse profile. The polarization properties of the average profile of GPs are similar to that of the pulses with energy less than 10 times average pulse energy in the bright state. This indicates that the emission mechanism is basically the same for them. Our results provide a new insight into the origin of the GPs in pulsars.
Slow magnetoacoustic waves in gravitationally stratified two-fluid plasmas in strongly ionized limit
Authors: Alharbi A , Ballai I , Fedun V , Verth G
Published: December 2020

The plasma dynamics at frequencies comparable with collisional frequency between various species has to be described in multifluid framework, where collisional interaction between particles is an important ingredient. In our study, we will assume that charged particles are strongly coupled, meaning that they form a single fluid that interacts with neutrals, therefore we will employ a two-fluid model. Here, we aim to investigate the evolutionary equation of slow sausage waves propagating in a gravitationally stratified flux tube in the two-fluid solar atmosphere in a strongly ionized limit using an initial value analysis. Due to the collisional interaction between massive particles (ions and neutrals), the governing equations are coupled. Solutions are sought in the strongly ionized limit and the density ratio between neutrals and charged particles is a small parameter. This limit is relevant to the upper part of the chromosphere. Our results show that slow sausage waves associated with charged particles propagate such that their possible frequency is affected by a cut-off due to the gravitational stratification. In contrast, for neutral acoustic waves the cut-off value applies on their wavelength and only small wavelength waves are able to propagate. Slow modes associated with neutrals are driven by the collisional coupling with ions.
Serendipitous discovery of a dusty disc around WDJ181417.84−735459.83
Authors: González Egea E , Raddi R , Koester D , Rogers L K , Marocco F , Cooper W J , Beamin J C , Burningham B , Day−Jones A , Forbrich J , Pinfield D J
Published: December 2020

Spectroscopic observations of white dwarfs reveal that many of them are polluted by exoplanetary material, whose bulk composition can be uniquely probed this way. We present a spectroscopic and photometric analysis of the DA white dwarf WDJ181417.84−735459.83, an object originally identified to have a strong infrared (IR) excess in the 2MASS and WISE catalogues that we confirmed to be intrinsic to the white dwarf, and likely corresponding to the emission of a dusty disc around the star. The finding of Ca, Fe, and Mg absorption lines in two X-SHOOTER spectra of the white dwarf, taken 8 years apart, is further evidence of accretion from a dusty disc. We do not report variability in the absorption lines between these two spectra. Fitting a blackbody model to the IR excess gives a temperature of 910 ± 50 K. We have estimated a total accretion flux from the spectroscopic metal lines of $|\dot{\rm M}| = 1.784 \times 10^{9}\,$g s−1.
Relevance of angiogenesis in autoimmune testis inflammation
Authors: Gualdoni Gisela Soledad , Jacobo Patricia Verónica , Sobarzo Cristian Marcelo , Pérez Cecilia Valeria , Durand Luis Alberto Haro , Theas María Susana , Lustig Livia , Guazzone Vanesa Anabella
Published: December 2020

Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significantly increased percentage of testicular endothelial cells and interstitial testicular blood vessels, indicating an ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis, can stimulate endothelial cell proliferation, chemotaxis and vascular permeability. The aim of this study was to explore the role of VEGFA in the pathogenesis of testicular inflammation. Our results found VEGFA expression in Leydig cells, endothelial cells and macrophages in testis of rats with autoimmune orchitis. VEGFA level was significantly higher in testicular fluid and serum of rats at the end of the immunization period, preceding testicular damage. VEGF receptor (VEGFR) 1 is expressed mainly in testicular endothelial cells, whereas VEGFR2 was detected in germ cells and vascular smooth muscle cells. Both receptors were expressed in testicular interstitial cells. VEGFR2 increased after the immunization period in the testicular interstitium and VEGFR1 was downregulated in EAO testis. In-vivo-specific VEGFA inhibition by Bevacizumab prevented the increase in blood vessel number and reduced EAO incidence and severity. Our results unveil relevance of VEGFA-VEGFR axis during orchitis development, suggesting that VEGFA might be an early marker of testicular inflammation and Bevacizumab a therapeutic tool for treatment of testicular inflammation associated with subfertility and infertility.
SUMOylation mediates CtIP’s functions in DNA end resection and replication fork protection
Authors: Locke Andrew J , Hossain Lazina , McCrostie Glynnis , Ronato Daryl A , Fitieh Amira , Rafique Tanzeem Ahmed , Mashayekhi Fatemeh , Motamedi Mobina , Masson Jean-Yves , Ismail Ismail Hassan
Published: December 2020

Double-strand breaks and stalled replication forks are a significant threat to genomic stability that can lead to chromosomal rearrangements or cell death. The protein CtIP promotes DNA end resection, an early step in homologous recombination repair, and has been found to protect perturbed forks from excessive nucleolytic degradation. However, it remains unknown how CtIP’s function in fork protection is regulated. Here, we show that CtIP recruitment to sites of DNA damage and replication stress is impaired upon global inhibition of SUMOylation. We demonstrate that CtIP is a target for modification by SUMO-2 and that this occurs constitutively during S phase. The modification is dependent on the activities of cyclin-dependent kinases and the PI-3-kinase-related kinase ATR on CtIP’s carboxyl-terminal region, an interaction with the replication factor PCNA, and the E3 SUMO ligase PIAS4. We also identify residue K578 as a key residue that contributes to CtIP SUMOylation. Functionally, a CtIP mutant where K578 is substituted with a non-SUMOylatable arginine residue is defective in promoting DNA end resection, homologous recombination, and in protecting stalled replication forks from excessive nucleolytic degradation. Our results shed further light on the tightly coordinated regulation of CtIP by SUMOylation in the maintenance of genome stability.
Partition of tRNAGly isoacceptors between protein and cell-wall peptidoglycan synthesis in Staphylococcus aureus
Authors: Rietmeyer Lauriane , Fix-Boulier Nicolas , Le Fournis Chloé , Iannazzo Laura , Kitoun Camelia , Patin Delphine , Mengin-Lecreulx Dominique , Ethève-Quelquejeu Mélanie , Arthur Michel , Fonvielle Matthieu
Published: December 2020

The sequence of tRNAs is submitted to evolutionary constraints imposed by their multiple interactions with aminoacyl-tRNA synthetases, translation elongation factor Tu in complex with GTP (EF-Tu•GTP), and the ribosome, each being essential for accurate and effective decoding of messenger RNAs. In Staphylococcus aureus, an additional constraint is imposed by the participation of tRNAGly isoacceptors in the addition of a pentaglycine side chain to cell-wall peptidoglycan precursors by transferases FmhB, FemA and FemB. Three tRNAGly isoacceptors poorly interacting with EF-Tu•GTP and the ribosome were previously identified. Here, we show that these ‘non-proteogenic’ tRNAs are preferentially recognized by FmhB based on kinetic analyses and on synthesis of stable aminoacyl-tRNA analogues acting as inhibitors. Synthesis of chimeric tRNAs and of helices mimicking the tRNA acceptor arms revealed that this discrimination involves identity determinants exclusively present in the D and T stems and loops of non-proteogenic tRNAs, which belong to an evolutionary lineage only present in the staphylococci. EF-Tu•GTP competitively inhibited FmhB by sequestration of ‘proteogenic’ aminoacyl-tRNAs in vitro. Together, these results indicate that competition for the Gly-tRNAGly pool is restricted by both limited recognition of non-proteogenic tRNAs by EF-Tu•GTP and limited recognition of proteogenic tRNAs by FmhB.
Modern Sexism in Modern Times Public Opinion in the #Metoo Era
Authors: Archer Allison M N , Kam Cindy D
Published: December 2020

Issues of sexual assault, sexual harassment, and gendered power imbalances have risen to prominence in the wake of the 2016 US presidential election and the rise of the #MeToo movement. This paper uses original panel and cross-sectional data to assess the degree to which levels of sexism have changed in response to current events, and finds very little change in levels of sexism from 2004 to 2018. The results also suggest that modern sexism significantly correlates with views undercutting the pervasiveness of sexual misconduct, purporting that #MeToo has gone too far, and opposing mandatory workplace harassment training, among other beliefs. Overall, the evidence suggests that modern sexism is firmly entrenched in the public mind and readily connected to public opinion in the wake of #MeToo.
Graviton loop contribution to Higgs potential in gauge–Higgs unification
Authors: Nishikawa Yasunari
Published: December 2020

We study the two-loop finiteness of an effective potential for a Higgs boson that is the fifth component of a gauge field in a $U(1)$ gauge theory coupled to quantum gravity on the five-dimensional space-time $M^4\times S^1$. There are two types of diagrams including quantum gravitational corrections. We find that only one type of diagram contributes to the effective potential for the Higgs boson, and its magnitude is finite.
Connecting active and passive $\mathcal{PT}$-symmetric Floquet modulation models
Authors: Harter Andrew K , Joglekar Yogesh N
Published: December 2020

Open systems with gain, loss, or both, described by non-Hermitian Hamiltonians, have been a research frontier for the past decade. In particular, such Hamiltonians which possess parity-time ($\mathcal{PT}$) symmetry feature dynamically stable regimes of unbroken symmetry with completely real eigenspectra that are rendered into complex conjugate pairs as the strength of the non-Hermiticity increases. By subjecting a $\mathcal{PT}$-symmetric system to a periodic (Floquet) driving, the regime of dynamical stability can be dramatically affected, leading to a frequency-dependent threshold for the $\mathcal{PT}$-symmetry breaking transition. We present a simple model of a time-dependent $\mathcal{PT}$-symmetric Hamiltonian which smoothly connects the static case, a $\mathcal{PT}$-symmetric Floquet case, and a neutral-$\mathcal{PT}$-symmetric case. We analytically and numerically analyze the $\mathcal{PT}$ phase diagrams in each case, and show that slivers of $\mathcal{PT}$-broken ($\mathcal{PT}$-symmetric) phase extend deep into the nominally low (high) non-Hermiticity region.
Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis: a longitudinal Swedish study
Authors: Do Lan , Granåsen Gabriel , Hellman Urban , Lejon Kristina , Geijer Mats , Baraliakos Xenofon , Witte Torsten , Forsblad-d’Elia Helena
Published: December 2020

Objectives

Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes.

Methods

IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden.

Results

A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4) years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9–17.9) U/ml] compared with controls [10.9 (7.2–14.6) U/ml, P = 0.003]. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P = 0.002). Multivariable logistic regression analyses revealed ≥1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P = 0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed.

Conclusion

Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.
Towards a Medical Utopia: Medicine, Politics and Citizenship in Post-Unified Italy (1861–1910)
Authors: Turbil Cristiano
Published: December 2020

In post-unified Italy, public health became a central concern for both politicians and medical doctors. The aim of this article is to look at the social and political roles played by hygiene in the post-unified Italian popular context, with a particular focus on the work of the scientist, politician and populariser Paolo Mantegazza (1831–1910). Mantegazza’s work offers an overview of how hygiene was popularised for the first generation of Italians using a variety of methods, including political and public talks, books and periodical articles but first and foremost, science fiction. The latter offers a possibility of exploring how medicine was considered a tool for a better future—a sort of political manifesto designed to both educate and galvanise Italians about the importance of health first for themselves but also the prosperity of the nation as a whole.
Secured transactions and patterns of legal change: the contribution of comparative law
Authors: Fiorentini Francesca
Published: December 2020

The article analyses the many actors and initiatives that, in the last decades, have pursued the goal of worldwide harmonization of secured transaction laws, scrutinizing the achievements and the limits of these experiments. In light of such results, the article also outlines the methodological contribution that comparative law can offer to legal change in the sector of secured transactions law, by way of confronting positive law models with meta-legal elements such as culture, society, economy, law-making processes, and geopolitics.
A Subscapular Approach to the Dissection of the Human Brachial Plexus
Authors: Hager Shaun , Backus Timothy , Futterman Bennett , Solounias Nikos , Mihlbachler Matthew C
Published: December 2020

Cadaver‐based human anatomy courses traditionally dissect the brachial plexus (BP) through the axilla. This approach fails to expose the proximal and posterior parts of the BP. In contrast, non‐human BP dissections use a subscapular approach that exposes the entire BP, from roots to branches. Using four human cadavers, we developed a subscapular approach modeled after a surgical method where the BP is accessed posteriorly. Medical students then used the posterior approach along with the traditional axillary approach during an anatomy class involving 42 cadavers. In all cases, students were able to expose the entire BP from roots to distal branches with minimal additional damage to surrounding structures. Students frequently exposed the origins of more proximal BP branches (e.g. long thoracic and suprascapular nerves) and mid‐proximal branches (e.g. subscapular nerves) not normally exposed during the axillary approach. The addition of the posterior approach did not increase the amount of classroom time needed to complete the dissection of the arm and shoulder. Inclusion of the posterior approach to BP dissection will provide anatomy students an improved opportunity to understand the anatomy of the BP.

Grant Funding Source: N/A
Secondary Syphilis With Elastophagocytosis: An Unusual Histologic Finding
Authors: Henebeng Esther , Karasko Erich , Robinson-Bostom Leslie , DiMarco Christopher
Published: December 2020

Elastophagocytosis is a characteristic finding of granulomatous and elastolytic disorders. It is defined by phagocytosed elastic fibers within histiocytes, multinucleated giant cells, or both. This finding has also been associated with certain medications, malignancies, inflammatory conditions, and infectious disorders. Although Drs Ragaz and Ackerman reported elastophagocytosis in a secondary syphilis lesion in a review of actinic granuloma in 1979, more recent publications have not recognized this finding. We present a case of elastophagocytosis within a lesion of secondary syphilis in a 65-year-old man. Biopsy from his left forearm demonstrated features of secondary syphilis including subtle vacuolar alteration with mild superficial and mid perivascular lymphoplasmacytic inflammation. There were interstitial giant cells with phagocytosed elastic fibers within the superficial dermis. Spirochete immunostain was positive with confirmatoryTreponema pallidumIgG antibody and RPR titer. In this report, we present a unique case of secondary syphilis.
Vertical Scrolling Axis of Corneal Endothelial Grafts for Descemet Membrane Endothelial Keratoplasty
Authors: Wacker Katrin , Fritz Marianne , Grewing Viviane , Maier Philip C. , Reinhard Thomas
Published: December 2020

Purpose:

Heterogeneity in scrolling behavior of Descemet membrane endothelial keratoplasty (DMEK) grafts complicates DMEK surgery. This prospective observational study assessed scrolling axes of DMEK grafts relative to the donor's eye.

Methods:

The eye bank randomly marked the rim of corneoscleral donor buttons during trephination and recorded the position relative to the donor's axis. Surgeons were masked to the absolute position of the eye bank marking and recorded the scrolling axis relative to the eye bank marking and DMEK upside-down orientation. The scrolling axis was categorized as vertical (0 to 30 degrees and 150 to 180 degrees), oblique (>30 to 60 degrees and 120 to <150 degrees), and horizontal (>60 to <120 degrees). Scrolling patterns of corneas from the same donor were assessed.

Results:

Scrolling patterns of 202 donor corneas from 149 donors were determined. The donor graft scrolled predominantly vertically to the donor's cornea [75%; 95% confidence interval (CI), 68%–80%]. Horizontal axes (11%) and oblique axes (14%) were less common. The median deviation in scrolling axes after unfolding the grafts was 0 degrees from the original scrolling axis (interquartile range, 0–15), indicating that scrolling axes were stable. Fellow eyes of 46 donors had 3.55 times higher odds of a nonvertical scrolling pattern if the first eye had a nonvertical scrolling pattern (95% CI, 1.37–9.20), suggesting that donor factors influencing both eyes could contribute to scrolling patterns.

Conclusions:

DMEK grafts have a natural and stable scrolling tendency at vertical axis of donor's cornea. Anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.
Epidemiology and Antimicrobial Susceptibility of Invasive Bacterial Infections in Children—A Population-Based Study From Norway
Authors: Thaulow Christian Magnus , Lindemann Paul Christoffer , Klingenberg Claus , Berild Dag , Salvesen Blix Hege , Myklebust Tor Åge , Harthug Stig
Published: December 2020

Objective:

To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0–18 years).

Methods:

Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults.

Results:

We included 1173 isolates from children and 44,561 isolates from adults. Staphylococcus aureus accounted for 220/477 (46.2%, 95% CI: 41.6–50.7) of all isolates in schoolchildren (6–18 years). Compared with Streptococcus pneumonia isolates from adults (N = 2674), we observed higher nonsusceptibility rates to penicillin in isolates from children (N = 151), 11.9% versus 5.8%, P < 0.01; also higher resistance rates to erythromycin (11.3% vs. 4.9%, P < 0.01), clindamycin (9.3% vs. 3.6%, P < 0.001), and trimethoprim/sulfamethoxazole (17.9% vs. 6.4%, P < 0.001). Compared with Escherichia coli isolates in adults (N = 9073), we found lower rates of ESBL in isolates from children (N = 212), 2.4% versus 6.4%, P < 0.05.

Conclusion:

The study indicates the importance of microbiologic surveillance strategies in children and highlights the need for pediatric AST data. The high rates of nonsusceptibility to commonly used antibiotics among S. pneumoniae in children and the high burden of invasive S. aureus infections in schoolchildren calls for modifications of Norwegian guidelines.