bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices
Authors: Bhuva Anish N , Moralee Russell , Brunker Tamara , Lascelles Karen , Cash Lizette , Patel Kush P , Lowe Martin , Sekhri Neha , Alpendurada Francisco , Pennell Dudley J , Schilling Richard , Lambiase Pier D , Chow Anthony , Moon James C , Litt Harold , Baksi A John , Manisty Charlotte H
Published: May 2021

Aims

Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified ‘non-MR conditional’ due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.

Methods and results

Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1–8.3).

Conclusions

There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.
Mild Parkinsonian Signs, Energy Decline, and Striatal Volume in Community-Dwelling Older Adults
Authors: Tian Qu , Ehrenkranz Rebecca , Rosso Andrea L , Glynn Nancy W , Chahine Lana M , Hengenius James , Zhu Xiaonan , Rosano Caterina
Published: May 2021

Background

Mild parkinsonian signs (MPS), highly prevalent in older adults, predict disability. It is unknown whether energy decline, a predictor of mobility disability, is also associated with MPS. We hypothesized that those with MPS had greater decline in self-reported energy level (SEL) than those without MPS, and that SEL decline and MPS share neural substrates.

Method

Using data from the Health, Aging and Body Composition Study, we analyzed 293 Parkinson’s disease-free participants (83 ± 3 years old, 39% Black, 58% women) with neuroimaging data, MPS evaluation by Unified Parkinson Disease Rating Scale in 2006–2008, and ≥3 measures of SEL since 1999–2000. Individual SEL slopes were computed via linear mixed models. Associations of SEL slopes with MPS were tested using logistic regression models. Associations of SEL slope with volume of striatum, sensorimotor, and cognitive regions were examined using linear regression models adjusted for normalized total gray matter volume. Models were adjusted for baseline SEL, mobility, demographics, and comorbidities.

Results

Compared to those without MPS (n = 165), those with MPS (n = 128) had 37% greater SEL decline in the prior 8 years (p = .001). Greater SEL decline was associated with smaller right striatal volume (adjusted standardized β = 0.126, p = .029). SEL decline was not associated with volumes in other regions. The association of SEL decline with MPS remained similar after adjustment for right striatal volume (adjusted odds ratio = 2.03, 95% CI: 1.16–3.54).

Conclusion

SEL decline may be faster in those with MPS. Striatal atrophy may be important for declining energy but does not explain the association with MPS.
Sex Difference in the Case Fatality of Older Myocardial Infarction Patients
Authors: Kytö Ville , Nuotio Maria , Rautava Päivi
Published: May 2021

Background

The female sex is associated with poorer outcomes after myocardial infarction (MI), although current evidence in older patients is limited and mixed. We sought to evaluate sex-based differences in outcome after MI in older patients.

Method

Consecutive older (≥70 years) all-comer patients with out-of-hospital MI admitted to 20 hospitals in Finland between 2005 and 2014 were studied using national registries (n = 40 654, mean age 80 years, 50% women). The outcome of interest was death within 1 year after MI. Differences between sexes (age, baseline features, medication, comorbidities, revascularization, and treating hospital) were balanced by inverse probability weighting.

Results

Adjusted all-cause case fatality was lower in women than in men at 30 days (16.0% vs 19.0%, respectively) and at 1 year (27.7% vs 32.4%, respectively) after MI (hazard ratio: 0.83; confidence interval [CI]: 0.80–0.86; p < .0001). Excess 1-year case fatality after MI compared to the corresponding general population was 22.1% (CI: 21.4%–22.8%) in women and 24.1% (CI: 23.4%–24.9%) in men. Women had a lower adjusted hazard of death after MI in subgroups of patients aged 70–79 years and ≥80 years, patients with and without ST elevation MI, revascularized and non-revascularized patients, patients with and without atrial fibrillation, and patients with and without diabetes. The sex difference in case fatality remained similar during the study period.

Conclusions

Older women were found to have a lower hazard of death after an out-of-hospital MI when compared to older men with similar features and treatments. This finding was consistent in several subgroups.
Loyalties Beyond Life: An Essay on the Film Coco From a Transgenerational Perspective
Authors: Schuler Emily , Dias Cristina M d S B
Published: May 2021

The animated film Coco tells the story of the web of relationships of a multigenerational family that faces its history, myths, and loyalties. Miguel, the film’s protagonist, is confronted with his family history when he expresses his dream of being a musician, and he goes through an adventure of finding himself in the midst of his family’s loyalties to the past and its history with music, spanning several generations. The aim of this article is to analyze the film from a transgenerational approach, conversing with systemic theory as well, taking into consideration questions about the characters of the Rivera multigenerational family, the dynamics of their relationships, and the invisible loyalties that present themselves in the movie. Thus, the film was analysed as a case study, using also as instrument simplified genogram. The film reveals the loyalties that are passed on from generation to generation, derived from a myth and a family secret, unveiled in the plot, which will explain inter- and transgenerational relationships in the film’s family. The role of the great-grandmother stands out as a hidden protagonist in the movie.
Improved full waveform moment tensor inversion of Cratonic intraplate earthquakes in southwest Australia
Authors: Lin Xiangdong , Yuan Huaiyu , Dentith Michael C , Murdie Ruth , Gessner Klaus , Nayak Avinash
Published: May 2021

In contrast to global observations in stable continental crust, the present-day orientation of the maximum horizontal stress in Western Australia is at a high angle to plate motion, suggesting that in addition to large-scale plate driving forces, local factors also play an important role in stress repartitioning. As a reliable stress indicator, full waveform moment tensor solutions are calculated for earthquakes that occurred between 2010 and 2018 in the southern Yilgarn Craton and the adjacent Albany-Fraser Orogen in southwestern Australia. Due to regional velocity heterogeneities in the crust, we produced two geographically distinct shear wave velocity models by combining published crustal velocity models with new ambient noise tomography results. We applied a full waveform inversion technique to 15 local earthquakes and obtained 10 robust results. Three of these events occurred near Lake Muir in the extreme south of the study area within the Albany-Fraser Orogen. The focal mechanism of the 16th September 2018 Lake Muir event is thrust; two ML≥ 4.0 aftershocks are normal and strike-slip. Our results are consistent with field observations, fault orientations inferred from aeromagnetic data and surface displacements mapped by Interferometric Synthetic Aperture Radar which are all consistent with reactivation of existing faults. The other seven solutions are in the southeastern Yilgarn Craton. These solutions show that the faulting mechanisms are predominantly thrust and strike-slip. This kinematic framework is consistent with previous studies that linked active seismicity in the Yilgarn Craton to the reactivation of the NNW–SSE oriented Neoarchean structures by an approximately E–W oriented regional stress field. Our results suggest that the kind of faulting that occurs in southwest Australia is critically dependent on the local geological structure. Thrust faulting is the dominant rupture mechanism, with some strike-slip faulting occurring on favourably oriented structures.
Disruptions in maternal and child health service utilization during COVID-19: analysis from eight sub-Saharan African countries
Authors: Shapira Gil , Ahmed Tashrik , Drouard Salomé Henriette Paulette , Amor Fernandez Pablo , Kandpal Eeshani , Nzelu Charles , Wesseh Chea Sanford , Mohamud Nur Ali , Smart Francis , Mwansambo Charles , Baye Martina L , Diabate Mamatou , Yuma Sylvain , Ogunlayi Munirat , Rusatira Rwema Jean De Dieu , Hashemi Tawab , Vergeer Petra , Friedman Jed
Published: May 2021

The coronavirus-19 pandemic and its secondary effects threaten the continuity of essential health services delivery, which may lead to worsened population health and a protracted public health crisis. We quantify such disruptions, focusing on maternal and child health, in eight sub-Saharan countries. Service volumes are extracted from administrative systems for 63 954 facilities in eight countries: Cameroon, Democratic Republic of Congo, Liberia, Malawi, Mali, Nigeria, Sierra Leone and Somalia. Using an interrupted time series design and an ordinary least squares regression model with facility-level fixed effects, we analyze data from January 2018 to February 2020 to predict what service utilization levels would have been in March–July 2020 in the absence of the pandemic, accounting for both secular trends and seasonality. Estimates of disruption are derived by comparing the predicted and observed service utilization levels during the pandemic period. All countries experienced service disruptions for at least 1 month, but the magnitude and duration of the disruptions vary. Outpatient consultations and child vaccinations were the most commonly affected services and fell by the largest margins. We estimate a cumulative shortfall of 5 149 491 outpatient consultations and 328 961 third-dose pentavalent vaccinations during the 5 months in these eight countries. Decreases in maternal health service utilization are less generalized, although significant declines in institutional deliveries, antenatal care and postnatal care were detected in some countries. There is a need to better understand the factors determining the magnitude and duration of such disruptions in order to design interventions that would respond to the shortfall in care. Service delivery modifications need to be both highly contextualized and integrated as a core component of future epidemic response and planning.
Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells
Authors: Barndt Robert B , Lee Mon-Juan , Huang Nanxi , Lu Dajun D , Lee See-Chi , Du Po-Wen , Chang Chun-Chia , Tsai Ping-Feng B , Huang Yu-Siou K , Chang Hao-Ming , Wang Jehng-Kang , Lai Chih-Hsin , Johnson Michael D , Lin Chen-Yong
Published: May 2021

Mutations of SPINT2, the gene encoding the integral membrane, Kunitz-type serine inhibitor HAI-2, primarily affect the intestine, while sparing many other HAI-2-expressing tissues, causing sodium loss in patients with syndromic congenital sodium diarrhea. The membrane-bound serine protease prostasin was previously identified as a HAI-2 target protease in intestinal tissues but not in the skin. In both tissues, the highly related inhibitor HAI-1 is, however, the default inhibitor for prostasin and the type 2 transmembrane serine protease matriptase. This cell-type selective functional linkage may contribute to the organ-selective damage associated with SPINT 2 mutations. To this end, the impact of HAI-2 deletion on matriptase and prostasin proteolysis was, here, compared using Caco-2 human colorectal adenocarcinoma cells and HaCaT human keratinocytes. Greatly enhanced prostasin proteolytic activity with a prolonged half-life and significant depletion of HAI-1 monomer were observed with HAI-2 loss in Caco-2 cells but not HaCaT cells. The constitutive, high level prostasin zymogen activation observed in Caco-2 cells, but not in HaCaT cells, also contributes to the excessive prostasin proteolytic activity caused by HAI-2 loss. HAI-2 deletion also caused increased matriptase zymogen activation, likely as an indirect result of increased prostasin proteolysis. This increase in activated matriptase, however, only had a negligible role in depletion of HAI-1 monomer. Our study suggests that the constitutive, high level of prostasin zymogen activation and the cell-type selective functional relationship between HAI-2 and prostasin renders Caco-2 cells more susceptible than HaCaT cells to the loss of HAI-2, causing a severe imbalance favoring prostasin proteolysis.
Authentic Research in the Classroom Increases Appreciation for Plants in Undergraduate Biology Students
Authors: Hiatt Anna C , Hove Alisa A , Ward Jennifer Rhode , Ventura Liane , Neufeld Howard S , Boyd Amy E , Clarke H David , Horton Jonathan L , Murrell Zack E
Published: May 2021

Synopsis

Engaging students in authentic research increases student knowledge, develops STEM skills, such as data analysis and scientific communication, and builds community. Creating authentic research opportunities in plant biology might be particularly crucial in addressing plant awareness disparity (PAD) (formerly known as plant blindness), producing graduates with botanical literacy, and preparing students for plant-focused careers. Our consortium created four CUREs (course-based undergraduate research experiences) focused on dual themes of plant biology and global change, designed to be utilized by early and late-career undergraduates across a variety of educational settings. We implemented these CURES for four semesters, in a total of 15 courses, at four institutions. Pre- and post-course assessments used the Affective Elements of Science Learning Questionnaire and parts of a “plant blindness” instrument to quantify changes in scientific self-efficacy, science values, scientific identity, and plant awareness or knowledge. The qualitative assessment also queried self-efficacy, science values, and scientific identity. Data revealed significant and positive shifts in awareness of and interest in plants across institutions. However, quantitative gains in self-efficacy and scientific identity were only found at two of four institutions tested. This project demonstrates that implementing plant CUREs can produce affective and cognitive gains across institutional types and course levels. Focusing on real-world research questions that capture students’ imaginations and connect to their sense of place could create plant awareness while anchoring students in scientific identities. While simple interventions can alleviate PAD, implementing multiple CUREs per course, or focusing more on final CURE products, could promote larger and more consistent gains in student affect across institutions.
Bene“fit” Assessment in Pollination Coevolution: Mechanistic Perspectives on Hummingbird Bill–Flower Matching
Authors: Rico-Guevara Alejandro , Hurme Kristiina J , Elting Rosalee , Russell Avery L
Published: May 2021

One of the reasons why flowering plants became the most diverse group of land plants is their association with animals to reproduce. The earliest examples of this mutualism involved insects foraging for food from plants and, in the process, pollinating them. Vertebrates are latecomers to these mutualisms, but birds, in particular, present a wide variety of nectar-feeding clades that have adapted to solve similar challenges. Such challenges include surviving on small caloric rewards widely scattered across the landscape, matching their foraging strategy to nectar replenishment rate, and efficiently collecting this liquid food from well-protected chambers deep inside flowers. One particular set of convergent traits among plants and their bird pollinators has been especially well studied: the match between the shape and size of bird bills and ornithophilous flowers. Focusing on a highly specialized group, hummingbirds, we examine the expected benefits from bill–flower matching, with a strong focus on the benefits to the hummingbird and how to quantify them. Explanations for the coevolution of bill–flower matching include (1) that the evolution of traits by bird-pollinated plants, such as long and thin corollas, prevents less efficient pollinators (e.g., insects) from accessing the nectar and (2) that increased matching, as a result of reciprocal adaptation, benefits both the bird (nectar extraction efficiency) and the plant (pollen transfer). In addition to nectar-feeding, we discuss how interference and exploitative competition also play a significant role in the evolution and maintenance of trait matching. We present hummingbird–plant interactions as a model system to understand how trait matching evolves and how pollinator behavior can modify expectations based solely on morphological matching, and discuss the implications of this behavioral modulation for the maintenance of specialization. While this perspective piece directly concerns hummingbird–plant interactions, the implications are much broader. Functional trait matching is likely common in coevolutionary interactions (e.g., in predator–prey interactions), yet the physical mechanisms underlying trait matching are understudied and rarely quantified. We summarize existing methods and present novel approaches that can be used to quantify key benefits to interacting partners in a variety of ecological systems.
C*-blocks and crossed products for classical p-adic groups
Authors: Afgoustidis Alexandre , Aubert Anne-Marie
Published: May 2021

Let $G$ be a real or $p$-adic reductive group. We consider the tempered dual of $G$, and its connected components. For real groups, Wassermann proved in 1987, by noncommutative-geometric methods, that each connected component has a simple geometric structure which encodes the reducibility of induced representations. For $p$-adic groups, each connected component of the tempered dual comes with a compact torus equipped with a finite group action, and we prove that a version of Wassermann’s theorem holds true under a certain geometric assumption on the structure of stabilizers for that action. We then focus on the case where $G$ is a quasi-split symplectic, orthogonal or unitary group, and explicitly determine the connected components for which the geometric assumption is satisfied.
Short-term forecasting of the COVID-19 outbreak in India
Authors: Mangla Sherry , Pathak Ashok Kumar , Arshad Mohd , Haque Ubydul
Published: May 2021

As the outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading in different parts of India, a reliable forecast for the cumulative confirmed cases and the number of deaths can be helpful for policymakers in making the decisions for utilizing available resources in the country. Recently, various mathematical models have been used to predict the outbreak of COVID-19 worldwide and also in India. In this article we use exponential, logistic, Gompertz growth and autoregressive integrated moving average (ARIMA) models to predict the spread of COVID-19 in India after the announcement of various unlock phases. The mean absolute percentage error and root mean square error comparative measures were used to check the goodness-of-fit of the growth models and Akaike information criterion for ARIMA model selection. Using COVID-19 pandemic data up to 20 December 2020 from India and its five most affected states (Maharashtra, Karnataka, Andhra Pradesh, Tamil Nadu and Kerala), we report 15-days-ahead forecasts for cumulative confirmed cases and the number of deaths. Based on available data, we found that the ARIMA model is the best-fitting model for COVID-19 cases in India and its most affected states.
Assessing hospital electronic health record vendor performance across publicly reported quality measures
Authors: Holmgren A Jay , Kuznetsova Masha , Classen David , Bates David W
Published: May 2021

Objective

Little is known regarding variation among electronic health record (EHR) vendors in quality performance. This issue is compounded by selection effects in which high-quality hospitals coalesce to a subset of market leading vendors. We measured hospital performance, stratified by EHR vendor, across 4 quality metrics.

Materials and Methods

We used data on 1272 hospitals in 2018 across 4 quality measures: Leapfrog Computerized Provider Order Entry/EHR Evaluation, Centers for Medicare and Medicaid Services Hospital Compare Star Ratings, Hospital-Acquired Condition (HAC) score, and Hospital Readmission Reduction Program (HRRP) ratio. We examined score distributions and used multivariable regression to evaluate the association between vendor and score, recovering partial R2 to assess the proportion of quality variation explained by vendor.

Results

We found significant variation across and within EHR vendors. The largest vendor, vendor A, had the highest mean score on the Leapfrog Computerized Provider Order Entry/EHR Evaluation and HRRP ratio, vendor G had the highest Hospital Compare score, and vendor F had the highest HAC score. In adjusted models, no vendor was significantly associated with higher performance on more than 2 measures. EHR vendor explained between 1.2% (HAC) and 7.6 (HRRP) of the variation in quality performance.

Discussion

No EHR vendor was associated with higher quality across all measures, and the 2 largest vendors were not associated with the highest scores. Only a small fraction of quality variation was explained by EHR vendor choice.

Conclusions

Top performance on quality measures can be achieved with any EHR vendor; much of quality performance is driven by the hospital and how it uses the EHR.
Community Responses to a Changing Security Landscape at the Colombia–Venezuela Border: The Case of La Guajira
Authors: Masullo Juan , Zulver Julia , Idler Annette
Published: May 2021

The Colombian–Venezuelan borderlands are facing a ‘double crisis’: at the same time as armed groups reconfigure following the demobilization of the Revolutionary Armed Forces of Colombia (FARC), Colombia is concurrently receiving millions of refugees, migrants, and Colombian returnees from neighbouring Venezuela. While much international coverage of the crisis has focused on Cúcuta, the major border crossing in the department of Norte de Santander, the crossing via the Guajira Peninsula is the second most frequented official land crossing into Colombia. In 2020, La Guajira was home to more than 166,000 refugees and migrants, the third highest concentration in the country. This happened at the same time as new and old armed groups were using violent measures to control strategic territory in the region. This practice note takes stock of the risks that affect security conditions as perceived and experienced by communities in La Guajira, and outlines the self-protection strategies that some communities employ to respond to the changing security conditions. It demonstrates the need for enhancing efforts for integration (for example, documentation) and response mechanisms that are shared between Colombia and other countries in the region in order to mitigate risks for Venezuelans in border regions of Colombia. The information reported here comes from a targeted civil society workshop held in Riohacha—the capital city of La Guajira—and a field visit made in April 2019 under the research programme ‘From Conflict Actors to Architects of Peace—CONPEACE’.
Stereotactic body radiation therapy for Japanese patients with localized prostate cancer: 2-year results and predictive factors for acute genitourinary toxicities
Authors: Ito Makoto , Yoshioka Yasuo , Takase Yuuki , Suzuki Junji , Matsunaga Takuma , Takahashi Hironori , Takeuchi Arisa , Adachi Sou , Abe Souichirou , Oshima Yukihiko , Ohtakara Kazuhiro , Suzuki Kojiro , Okuda Takahito
Published: May 2021

Objective

We aimed to report the 2-year results of stereotactic body radiation therapy for prostate cancer and identify the clinical and dosimetric factors that predict acute genitourinary toxicities.

Methods

We retrospectively reviewed the medical records of patients with non-metastatic prostate cancer treated at Toyota Memorial Hospital between 2017 and 2020. The patients were treated with stereotactic body radiation therapy with a total dose of 36.25 Gy in five fractions on consecutive weekdays. While low-risk patients received radiotherapy alone, intermediate- to high-risk patients also received androgen deprivation therapy.

Results

We analysed a total of 104 patients, including 10, 60 and 34 low-, intermediate- and high-risk patients, respectively. The median follow-up duration was 2 years. We did not observe biochemical/clinical recurrence, distant metastasis or death from prostate cancer. One patient died of another cause. Grade 2 acute genitourinary toxicity was observed in 40 (38%) patients. Age (P = 0.021), genitourinary toxicity of grade ≥1 at baseline (P = 0.023) and bladder mean dose (P = 0.047) were significantly associated with the incidence of grade 2 acute genitourinary toxicity. The cut-off value of 65 years for age and 10.3 Gy for the bladder mean dose were considered the most appropriate. Grade 2 acute gastrointestinal toxicity was observed in five (5%) patients. None of the patients experienced grade ≥3 acute or late toxicity.

Conclusions

Stereotactic body radiation therapy is feasible for Japanese patients with prostate cancer, with acceptable acute toxicity. Age, genitourinary toxicity at baseline and bladder mean dose predict grade 2 acute genitourinary toxicity.
Self-sacrifice for the Common Good under Risk and Competition: An Experimental Examination of the Impact of Public Service Motivation in a Volunteer’s Dilemma Game
Authors: Heine Florian , van Witteloostuijn Arjen , Wang Tse-Min
Published: May 2021

Public service-motivated individuals have a greater concern for the delivery of public services and for the societal consequence of collective inaction, seeing themselves play a pivotal role in upholding public goods. Such self-efficacy and perceived importance of public service jointly motivate individuals to commit to sacrificing for the common good. Using an incentivized laboratory experiment with 126 undergraduate and graduate students at a university in the Netherlands, we explore the association between self-reported public service motivation (PSM) and voluntary self-sacrifice under different task characteristics and social contexts in a Volunteer’s Dilemma game. We find that risk-taking and intergroup competition negatively moderate the positive effect of PSM on volunteering. The risky situation may reduce an individual’s self-efficacy in making meaningful sacrifice, and intergroup competition may divert attention away from the concern for society at large to the outcome of the competition, compromising the positive effect of PSM on the likelihood to self-sacrifice for the common good.
Long noncoding RNA HOXA-AS2 accelerates cervical cancer by the miR-509-3p/BTN3A1 axis
Authors: Chen Ruxiang , He Ping
Published: May 2021

Objectives

Cervical cancer is an aggressive malignant tumour and causes high mortality in women. LncRNA HOXA-AS2 is a tumour promoter in many cancers. The current work was designed to elucidate the functions of HOXA-AS2 in cervical cancer and the underlying regulatory mechanism.

Methods

qRT-PCR was conducted to reveal RNA levels. A FISH assay was conducted for the identification of the subcellular location of HOXA-AS2. MTT, EdU, Transwell and tube formation were used for detection of cell growth, migration and angiogenesis, respectively. In-vivo studies were conducted to reveal the role of HOXA-AS2 on transplanted tumour growth in mice.

Key findings

The HOXA-AS2 level was found high in tissues and cells of cervical cancer. Silencing of HOXA-AS2 restrained cell proliferation, migration and invasion. Angiogenesis of HUVECs was restrained after silencing HOXA-AS2. Additionally, HOXA-AS2 upregulated the BTN3A1 by interaction with miR-509-3p. BTN3A1 overexpression rescues the inhibitory effect of silenced HOXA-AS2 on cell phenotypes in cervical cancer. Moreover, xenograft tumour growth in mice was suppressed by HOXA-AS2 depletion and was facilitated by BTN3A1 overexpression.

Conclusions

HOXA-AS2 accelerates cellular progression in cervical cancer by the miR-509-3p/BTN3A1 axis.
High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells
Authors: Permata Tiara Bunga Mayang , Sato Hiro , Gu Wenchao , Kakoti Sangeeta , Uchihara Yuki , Yoshimatsu Yukihiko , Sato Itaru , Kato Reona , Yamauchi Motohiro , Suzuki Keiji , Oike Takahiro , Tsushima Yoshito , Gondhowiardjo Soehartati , Ohno Tatsuya , Yasuhara Takaaki , Shibata Atsushi
Published: May 2021

Programmed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that induced by X-rays at the same physical and relative biological effectiveness (RBE) dose, and that the upregulation of PD-L1 induced by high LET carbon-ion irradiation was predominantly dependent on ataxia telangiectasia and Rad3-related (ATR) kinase activity. Moreover, we showed that the downstream signaling, e.g. STAT1 phosphorylation and IRF1 expression, was upregulated to a greater extent after high LET carbon-ion irradiation than X-rays, and that IRF1 upregulation was also ATR dependent. Finally, to visualize PD-L1 molecules on the cell surface in 3D, we applied immunofluorescence-based super-resolution imaging. The three-dimensional structured illumination microscopy (3D-SIM) analyses revealed substantial increases in the number of presented PD-L1 molecules on the cell surface after high LET carbon-ion irradiation compared with X-ray irradiation.
Putting collation of text witnesses on a formal basis
Authors: Dähne Janis , Pöckelmann Marcus , Ritter Jörg , Molitor Paul
Published: May 2021

This article presents an approach to the collation problem of text witnesses which is correct for all distance functions and is applicable to the alignment of any types of tokens, be it letters, words, sentences, or paragraphs. In contrast to the existing approaches, which all are heuristics in nature, we specify a formal model in the form of an integer linear program (ILP) that formally describes the optimization problem. For a special case that usually occurs in practice, we then transfer the ILP into an efficient algorithm that optimally solves the alignment problem. In the second part of the article, we apply our approach to the alignment of paragraphs of text witnesses—an alignment problem that has received little attention in the literature so far—and compare the results of our approach, which we have called TSaligner, with those of CollateX.
Uncertain times: the redshift–time relation from cosmology and stars
Authors: Boylan-Kolchin Michael , Weisz Daniel R
Published: May 2021

Planck data provide precise constraints on cosmological parameters when assuming the base ΛCDM model, including a 0.17 per cent measurement of the age of the Universe, $t_0=13.797 \pm 0.023\, {\rm Gyr}$. However, the persistence of the ‘Hubble tension’ calls the base ΛCDM model’s completeness into question and has spurred interest in models such as early dark energy (EDE) that modify the assumed expansion history of the Universe. We investigate the effect of EDE on the redshift–time relation z↔t and find that it differs from the base ΛCDM model by at least ${\approx } 4{{\ \rm per\ cent}}$ at all t and z. As long as EDE remains observationally viable, any inferred t ← z or z ← t quoted to a higher level of precision do not reflect the current status of our understanding of cosmology. This uncertainty has important astrophysical implications: the reionization epoch – 10 > z > 6 – corresponds to disjoint lookback time periods in the base ΛCDM and EDE models, and the EDE value of t0 = 13.25 ± 0.17 Gyr is in tension with published ages of some stars, star clusters, and ultrafaint dwarf galaxies. However, most published stellar ages do not include an uncertainty in accuracy (due to, e.g. uncertain distances and stellar physics) that is estimated to be $\sim 7\!-\!10{{\ \rm per\ cent}}$, potentially reconciling stellar ages with $t_{0,\rm EDE}$. We discuss how the big data era for stars is providing extremely precise ages ($\lt 1{{\ \rm per\ cent}}$) and how improved distances and treatment of stellar physics such as convection could result in ages accurate to $4\!-\!5{{\ \rm per\ cent}}$, comparable to the current accuracy of t↔z. Such precise and accurate stellar ages can provide detailed insight into the high-redshift Universe independent of a cosmological model.
A new look at old friends – I. Imaging classical radio galaxies with uGMRT and MeerKAT
Authors: Fanaroff Bernie , Lal Dharam V , Venturi Tiziana , Smirnov Oleg M , Bondi Marco , Thorat Kshitij , Bester Landman H , Józsa Gyula I G , Kleiner Dane , Loi Francesca , Makhathini Sphesihle , White Sarah V
Published: May 2021

We have undertaken a systematic study of FR I and FR II radio galaxies with the upgraded Giant Metrewave Radio Telescope (uGMRT) and MeerKAT. The main goal is to explore whether the unprecedented few μJy sensitivity reached in the range 550–1712 MHz at the resolution of ∼4–7 arcsec reveals new features in the radio emission which might need us to revise our current classification scheme for classical radio galaxies. In this paper, we present the results for the first set of four radio galaxies, i.e. 4C 12.02, 4C 12.03, CGCG 044–046, and CGCG 021–063. The sources have been selected from the 4C sample with well-defined criteria and have been imaged with the uGMRT in the range 550–850 MHz (band 4) and with the MeerKAT in the range 856–1712 MHz (L-band). Full resolution images are presented for all sources in the sample, together with MeerKAT in-band spectral images. Additionally, the uGMRT–MeerKAT spectral image and MeerKAT L-band polarization structure are provided for CGCG 044–046. Our images contain a wealth of morphological details, such as filamentary structure in the emission from the lobes, radio emission beyond the hotspots in three sources, and misalignments. We briefly discuss the overall properties of CGCG 044–046 in the light of the local environment as well, and show possible restarted activity in 4C 12.03 which needs to be confirmed. We conclude that at least for the sources presented here, the classical FR I/FR II morphological classification still holds with the current improved imaging capabilities, but the richness in details also suggests caution in the systematic morphological classification carried out with automatic procedures in surveys with poorer sensitivity and angular resolution.
An analysis of the time-frequency structure of several bursts from FRB 121102 detected with MeerKAT
Authors: Platts E , Caleb M , Stappers B W , Main R A , Weltman A , Shock J P , Kramer M , Bezuidenhout M C , Jankowski F , Morello V , Possenti A , Rajwade K M , Rhodes L , Wu J
Published: May 2021

We present a detailed study of the complex time-frequency structure of a sample of previously reported bursts of FRB 121102 detected with the MeerKAT telescope in September 2019. The wide contiguous bandwidth of these observations have revealed a complex bifurcating structure in some bursts at 1250 MHz. When de-dispersed to their structure-optimized dispersion measures (DMs), two of the bursts show a clear deviation from the cold plasma dispersion relationship below 1250 MHz. We find a differential DM of ${\sim }1{-}2~{\rm pc \, cm^{-3}}$ between the lower and higher frequency regions of each burst. We investigate the possibility of plasma lensing by Gaussian lenses of ∼10 au in the host galaxy, and demonstrate that they can qualitatively produce some of the observed burst morphologies. Other possible causes for the observed frequency dependence, such as Faraday delay, are also discussed. Unresolved sub-components in the bursts, however, may have led to an incorrect DM determination. We hence advise exercising caution when considering bursts in isolation. We analyse the presence of two apparent burst pairs. One of these pairs is a potential example of upward frequency drift. The possibility that burst pairs are echoes is also discussed. The average structure-optimized DM is found to be $563.5\pm 0.2 (\text{sys}) \pm 0.8 (\text{stat})\, {\rm pc \, cm^{-3}}$ – consistent with the values reported in 2018. We use two independent methods to determine the structure-optimized DM of the bursts: the DM_phase algorithm and autocorrelation functions. The latter – originally developed for pulsar analysis – is applied to fast radio bursts for the first time in this paper.
Discovery of a young low-mass brown dwarf transiting a fast-rotating F-type star by the Galactic Plane eXoplanet (GPX) survey
Authors: Benni P , Burdanov A Y , Krushinsky V V , Bonfanti A , Hébrard G , Almenara J M , Dalal S , Demangeon O D S , Tsantaki M , Pepper J , Stassun K G , Vanderburg A , Belinski A , Kashaev F , Barkaoui K , Kim T , Kang W , Antonyuk K , Dyachenko V V , Rastegaev D A , Beskakotov A , Mitrofanova A A , Pozuelos F J , Kuznetsov E D , Popov A , Kiefer F , Wilson P A , Ricker G , Vanderspek R , Latham D W , Seager S , Jenkins J M , Sokov E , Sokova I , Marchini A , Papini R , Salvaggio F , Banfi M , Baştürk Ö , Torun Ş , Yalçınkaya S , Ivanov K , Valyavin G , Jehin E , Gillon M , Pakštienė E , Hentunen V-P , Shadick S , Bretton M , Wünsche A , Garlitz J , Jongen Y , Molina D , Girardin E , Grau Horta F , Naves R , Benkhaldoun Z , Joner M D , Spencer M , Bieryla A , Stevens D J , Jensen E L N , Collins K A , Charbonneau D , Quintana E V , Mullally S E , Henze C E
Published: May 2021

We announce the discovery of GPX-1 b, a transiting brown dwarf with a mass of 19.7 ± 1.6 MJup and a radius of 1.47 ± 0.10 RJup, the first substellar object discovered by the Galactic Plane eXoplanet (GPX) survey. The brown dwarf transits a moderately bright (V = 12.3 mag) fast-rotating F-type star with a projected rotational velocity $v\sin {\, i_*}=40\pm 10$ km s−1. We use the isochrone placement algorithm to characterize the host star, which has effective temperature 7000 ± 200 K, mass 1.68 ± 0.10 $\mathrm{\it M}_\odot$, radius 1.56 ± 0.10 $\mathrm{\it R}_\odot$, and approximate age $0.27_{-0.15}^{+0.09}$ Gyr. GPX-1 b has an orbital period of ∼1.75 d and a transit depth of 0.90 ± 0.03  per cent. We describe the GPX transit detection observations, subsequent photometric and speckle-interferometric follow-up observations, and SOPHIE spectroscopic measurements, which allowed us to establish the presence of a substellar object around the host star. GPX-1 was observed at 30-min integrations by TESS in Sector 18, but the data are affected by blending with a 3.4 mag brighter star 42 arcsec away. GPX-1 b is one of about two dozen transiting brown dwarfs known to date, with a mass close to the theoretical brown dwarf/gas giant planet mass transition boundary. Since GPX-1 is a moderately bright and fast-rotating star, it can be followed-up by the means of the Doppler tomography.
An H α/X-ray orphan cloud as a signpost of intracluster medium clumping
Authors: Ge Chong , Luo Rongxin , Sun Ming , Yagi Masafumi , Jáchym Pavel , Boselli Alessandro , Fossati Matteo , Nulsen Paul E J , Sarazin Craig , Edge Tim , Gavazzi Giuseppe , Gaspari Massimo , Koda Jin , Komiyama Yutaka , Yoshida Michitoshi
Published: May 2021

Recent studies have highlighted the potential significance of intracluster medium (ICM) clumping and its important implications for cluster cosmology and baryon physics. Many of the ICM clumps can originate from infalling galaxies, as stripped interstellar medium (ISM) mixing into the hot ICM. However, a direct connection between ICM clumping and stripped ISM has not been unambiguously established before. Here, we present the discovery of the first and still the only known isolated cloud (or orphan cloud [OC]) detected in both X-rays and H α in the nearby cluster A1367. With an effective radius of 30 kpc, this cloud has an average X-ray temperature of 1.6 keV, a bolometric X-ray luminosity of ∼3.1 × 1041 erg s−1, and a hot gas mass of ∼1010 M⊙. From the Multi-Unit Spectroscopic Explorer (MUSE) data, the OC shows an interesting velocity gradient nearly along the east-west direction with a low level of velocity dispersion of ∼80 km s−1, which may suggest a low level of the ICM turbulence. The emission line diagnostics suggest little star formation in the main H α cloud and a low-ionization (nuclear) emission-line regions like spectrum, but the excitation mechanisms remain unclear. This example shows that stripped ISM, even long after the initial removal from the galaxy, can still induce ICM inhomogeneities. We suggest that the magnetic field can stabilize the OC by suppressing hydrodynamic instabilities and thermal conduction. This example also suggests that at least some ICM clumps are multiphase in nature and implies that the ICM clumps can also be traced in H α. Thus, future deep and wide-field H α surveys can be used to probe the ICM clumping and turbulence.
A search for pulsar companions around low-mass white dwarfs
Authors: Athanasiadis Tilemachos M , Berezina Marina , Antoniadis John , Champion David J , Cruces Marilyn , Spitler Laura , Kramer Michael
Published: May 2021

We report on a search for pulsars at the positions of eight low-mass white dwarfs and one higher mass white dwarf with the 100-m Effelsberg Radio Telescope. These systems have orbital parameters suggesting that their unseen companions are either massive white dwarfs or neutron stars (NSs). Our observations were performed at 1.36 GHz, reaching sensitivities of 0.1–0.2 mJy. We searched our data accounting for the possible acceleration and jerk of the pulsar signals due to orbital motion, but found no significant pulsar signals. Considering our result jointly with 20 non-detections of similar systems with the Greenbank Radio Telescope, we infer fNS ≤ 0.10, for the fraction of NSs orbiting these white dwarfs. We discuss the sensitivity of this result to the underlying assumptions and conclude with a brief discussion on the prospects of targeted surveys for discovering millisecond pulsars.
Kinetics of heterochiral strand displacement from PNA–DNA heteroduplexes
Authors: Kundu Nandini , Young Brian E , Sczepanski Jonathan T
Published: May 2021

Dynamic DNA nanodevices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation remains challenging due to nuclease degradation and other cellular factors. Use of l-DNA, the nuclease resistant enantiomer of native d-DNA, provides a promising solution. On this basis, we recently developed a strand displacement methodology, referred to as ‘heterochiral’ strand displacement, that enables robust l-DNA nanodevices to be sequence-specifically interfaced with endogenous d-nucleic acids. However, the underlying reaction – strand displacement from PNA–DNA heteroduplexes – remains poorly characterized, limiting design capabilities. Herein, we characterize the kinetics of strand displacement from PNA–DNA heteroduplexes and show that reaction rates can be predictably tuned based on several common design parameters, including toehold length and mismatches. Moreover, we investigate the impact of nucleic acid stereochemistry on reaction kinetics and thermodynamics, revealing important insights into the biophysical mechanisms of heterochiral strand displacement. Importantly, we show that strand displacement from PNA–DNA heteroduplexes is compatible with RNA inputs, the most common nucleic acid target for intracellular applications. Overall, this work greatly improves the understanding of heterochiral strand displacement reactions and will be useful in the rational design and optimization of l-DNA nanodevices that operate at the interface with biology.
G-quadruplex binders as cytostatic modulators of innate immune genes in cancer cells
Authors: Miglietta Giulia , Russo Marco , Duardo Renée C , Capranico Giovanni
Published: May 2021

G-quadruplexes (G4s) are non-canonical nucleic acid structures involved in fundamental biological processes. As G4s are promising anticancer targets, in past decades the search for effective anticancer G4 binders aimed at the discovery of more cytotoxic ligands interfering with specific G4 structures at oncogenes or telomeres. Here, we have instead observed a significant activation of innate immune genes by two unrelated ligands at non-cytotoxic concentrations. The studied G4 binders (pyridostatin and PhenDC3) can induce an increase of micronuclei triggering the activation of the cytoplasmic STING (stimulator of interferon response cGAMP interactor 1) signaling pathway in human and murine cancer cells. Ligand activity can then lead to type I interferon production and innate immune gene activation. Moreover, specific gene expression patterns mediated by a G4 binder in cancer cells correlate with immunological hot features and better survival in human TCGA (The Cancer Genome Atlas) breast tumors. The findings open to the development of cytostatic G4 binders as effective immunomodulators for combination immunotherapies in unresponsive tumors.
High-performance polarization-sensitive photodetectors on two-dimensional β-InSe
Authors: Guo Zhinan , Cao Rui , Wang Huide , Zhang Xi , Meng Fanxu , Chen Xue , Gao Siyan , Sang David K , Nguyen Thi Huong , Duong Anh Tuan , Zhao Jinlai , Zeng Yu-Jia , Cho Sunglae , Zhao Bing , Tan Ping-Heng , Zhang Han , Fan Dianyuan
Published: May 2021

Two-dimensional (2D) indium selenide (InSe) has been widely studied for application in transistors and photodetectors, which benefit from its excellent optoelectronic properties. Among the three specific polytypes (γ-, ϵ- and β-phase) of InSe, only the crystal lattice of InSe in β-phase (β-InSe) belongs to a non-symmetry point group of $D_{6h}^4$, which indicates stronger anisotropic transport behavior and potential in the polarized photodetection of β-InSe-based optoelectronic devices. Therefore, we prepare the stable p-type 2D-layered β-InSe via temperature gradient method. The anisotropic Raman, transport and photoresponse properties of β-InSe have been experimentally and theoretically proven, showing that the β-InSe-based device has a ratio of 3.76 for the maximum to minimum dark current at two orthogonal orientations and a high photocurrent anisotropic ratio of 0.70 at 1 V bias voltage, respectively. The appealing anisotropic properties demonstrated in this work clearly identify β-InSe as a competitive candidate for filter-free polarization-sensitive photodetectors.