bluuebunny/crossref_metadata_2025 huggingface dataset:
Bringing tax avoiders to light: moral framing and shaming in a public goods experiment
Authors: Tsikas Stefanos A.
Published: March 2021

With a linear public goods game played in six different variants, this article studies two channels that might moderate social dilemmas and increase cooperation without using pecuniary incentives: moral framing and shaming. We find that cooperation is increased when noncontributing to a public good is framed as morally debatable and socially harmful tax avoidance, while the mere description of a tax context has no effect. However, without social sanctions in place, cooperation quickly deteriorates due to social contagion. We find ‘shaming’ free-riders by disclosing their misdemeanor to act as a strong social sanction, irrespective of the context in which it is applied. Moralizing tax avoidance significantly reinforces shaming, compared with a simple tax context.
Factors Associated with Quality of Life in Adults with Persistent Post-Concussion Symptoms
Authors: Popov Nadejda , Mercier Leah J. , King Regan , Fung Tak , Debert Chantel T.
Published: March 2021

Objective:

To assess demographic, clinical, and injury characteristics associated with health-related quality of life (HRQOL) in adults with persistent post-concussion symptoms (PPCS).

Methods:

Adults with PPCS presenting to a specialized brain injury clinic completed demographic, injury, and clinical outcome questionnaires at the initial clinic assessment. Clinical outcome measures were collected including the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and the Fatigue Severity Scale (FSS). HRQOL was measured using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. Stepwise hierarchical multiple regression analysis adjusting for age, sex, and months since injury was used to determine associations between quality of life and clinical outcome measures.

Results:

Overall, 125 participants were included. The PHQ-9, FSS, and GAD-7 were significant predictors of QOLIBRI scores (R2= 0.481, p < .001), indicating that participants with higher levels of depressive symptoms, fatigue, and anxiety reported poorer HRQOL. The PHQ-9 score was the strongest predictor, accounting for 42.0% of the variance in QOLIBRI scores. No demographic or injury characteristics significantly predicted QOLIBRI scores. There was a high prevalence of depressive symptoms with 72.8% of participants having PHQ-9 scores ≥ 10.

Conclusion:

Among patients with PPCS, mental health and fatigue are important contributors to HRQOL. As there is a high burden of mood disorders and fatigue in this population, targeted treatments for these concerns may impact the quality of life.
Stroke in Male-to-Female Transgenders: A Systematic Review and Meta-Analysis
Authors: Ignacio Katrina Hannah D. , Diestro Jose Danilo B. , Espiritu Adrian I. , Pineda-Franks Maria Carissa
Published: March 2021

Background:

The effect of hormonal therapy has been extensively studied in women. However, similar data on male-to-female (MTF) transgenders, another important population that receives hormonal therapy is lacking. Existing studies in MTF transgenders are skewed toward mental health and health-harming behaviors while few have focused on chronic health conditions. Our study aims to review the existing data on stroke in MTF transgenders and perform a quantitative analysis on the frequency of this condition in this special population.

Methods:

PubMed, Cochrane, Scopus, Embase, ClinicalTrials.gov, and Web of Science were systematically searched for studies that reported data on the occurrence of cerebrovascular diseases in MTF transgenders. We reported the hormonal regimens, clinical characteristics, and outcomes of stroke in MTF transgenders. A meta-analysis of proportions was performed by the random-effects model to compute for the frequency of cerebrovascular events in MTF transgenders.

Results:

Fourteen studies were included in the qualitative analysis while five studies were included in the quantitative analysis. A total of 109 MTF transgenders (Mean 14; range 1–53) suffered a cerebrovascular event. Random-effect modeling analysis showed an overall estimated frequency of 2% for cerebrovascular events in transgenders with a moderate degree of heterogeneity (I2 = 62%).

Conclusion:

Hormonal therapy in MTF transgenders may confer cardiovascular risks in this population. However, more population-based studies that include clinical characteristics and outcomes of chronic health diseases in MTF transgenders are warranted. Such studies may be crucial in directing future guidelines on the health care and management of MTF transgenders.
Is It Time to Consider Implementation of Telemedicine in Current Oral Health Care Services?
Authors: Ilhan Betul , Bayrakdar Ibrahim Sevki , Baydar Oguzhan , Guneri Pelin
Published: March 2021

Telemedicine offers an excellent opportunity to provide continuing health care for those in need during local/global pandemics and disasters. It provides a safe and effective communication tool between health professionals and can be used as “forward triage” to manage medical/dental emergencies and to minimize the contact between the patients and clinicians during the coronavirus disease (COVID-19) pandemic. Patients with noncommunicable diseases, like cancer, diabetes, cardiovascular, or chronic respiratory diseases, may present with critical health problems due to less access to health care systems during global disasters; opportunities for screening oral mucosa might be significantly disrupted, leading to delayed diagnosis of malignant/potentially malignant lesions. Telemedicine and oral health care associated mobile applications should be implemented to provide equal access to care, to eliminate unnecessary visits to health centers, and to improve practical coordination between professionals and health facilities.
The Perception of the Legitimacy of Citizens’ Assemblies in Deeply Divided Places? Evidence of Public and Elite Opinion from Consociational Northern Ireland
Authors: Garry John , Pow James , Coakley John , Farrell David , O'Leary Brendan , Tilley James
Published: March 2021

How much public and elite support is there for the use of a citizens’ assembly – a random selection of citizens brought together to consider a policy issue – to tackle major, deadlock-inducing disagreements in deeply divided places with consociational political institutions? We focus on Northern Ireland and use evidence from a cross-sectional attitude survey, a survey-based experiment and elite interviews. We find that the general public support decision-making by a citizens’ assembly, even when the decision reached is one they personally disagree with. However, support is lower among those with strong ideological views. We also find that elected politicians oppose delegating decision-making power to an ‘undemocratic’ citizens’ assembly, but are more supportive of recommendation-making power. These findings highlight the potential for post-conflict consociations to be amended, with the consent of the parties, to include citizens’ assemblies that make recommendations but not binding policy.
Ice thickness estimates of Lemon Creek Glacier, Alaska, from active-source seismic imaging
Authors: Veitch Stephen A. , Karplus Marianne , Kaip Galen , Gonzalez Lucia F. , Amundson Jason M. , Bartholomaus Timothy C.
Published: March 2021

Lemon Creek Glacier, a temperate valley glacier in the Juneau Icefield of Southeast Alaska, is the site of long running (>60 years) glaciological studies. However, the most recent published estimates of its thickness and subglacial topography come from two ~50 years old sources that are not in agreement and do not account for the effects of years of negative mass balance. We collected a 1-km long active-source seismic line on the upper section of the glacier parallel and near to the centerline of the glacier, roughly straddling the equilibrium-line altitude. We used these data to perform joint reflection-refraction velocity modeling and reflection imaging of the glacier bed. We find that this upper section of Lemon Creek Glacier is as much as 150 m (~65%) thicker than previously suggested with a large overdeepening in an area previously believed to have a uniform thickness. Our results lead us to reinterpret the impact of basal motion on ice flow and have a significant impact on expectations of subglacial hydrology. We suggest that further efforts to develop a whole-glacier model of subglacial topography are necessary to support studies that require accurate models of ice thickness and subglacial topography.
Common Medicine for the Common Man: Picturing the “Striped Layman” in Early Vernacular Print
Authors: Taape Tillmann
Published: March 2021

The disruptive figure of the “striped layman” appeared in printed texts and images around the year 1500 in the southern German lands. This essay shows how it came to represent a new kind of reader of vernacular medical publications. Exploring the illustrated books of the Strasbourg surgeon-apothecary Hieronymus Brunschwig, their local context of humanist discourse, and the visual practice of their publisher, Johann Grüninger, I argue that their oft-neglected woodcuts of people in striped clothes constitute powerful visual commentary of Brunschwig's (and others’) mission to impart medical agency and expertise to the “common man” at the eve of the Reformation.
An Infinity of Relics: Erasmus and the Copious Rhetoric of John Calvin'sTraité des reliques
Authors: Weinreich Spencer J.
Published: March 2021

John Calvin's “Traité des reliques” (1543) inventories early modern Europe's fraudulent relics. Yet, theologically speaking, authenticity is irrelevant: all relics are idols to the evangelical Protestant, while for Catholics prayer's intention, not its conduit, was paramount. This article locates a solution in Calvin's humanist formation: chiefly, his debt to Desiderius Erasmus—not to Erasmus's satirical or devotional works, but to his rhetorical theory ofcopia. The “Traité” amasses acopia, an abundance, of fakes, burying the cult of relics in its own contradictions. Fusing rhetoric and proof, this mass juxtaposition subjects sacred presence to noncontradiction, patrolling vital confessional borders in Reformation theology.
A policy of day-case sinonasal surgery is safe, well tolerated and cost-effective
Authors: Duignan M , Lao C , Lawrenson R , Wood A J
Published: March 2021

Objective

Practices vary regarding the timing of discharge after sinonasal surgery. This study aimed to examine the cost-effectiveness of same-day discharge compared to next-day discharge after sinonasal surgery.

Methods

A retrospective single-surgeon audit of sinonasal surgery over a 12-month period was performed. Demographic and clinical details, including distance travelled home, timing of discharge, hospital re-presentation, and complications, were collected and compared between the same-day discharge and next-day discharge groups. A cost-effectiveness analysis was performed.

Results

A total of 181 patients were identified; 117 underwent day-case surgery, of which 6 re-presented to the emergency department. Sixty-four patients stayed overnight after surgery, and six of those patients re-presented to the emergency department. The per patient cost was $3262 for day-case sinonasal surgery and $5050 for those admitted overnight after surgery (p < 0.001).

Conclusion

Routine same-day discharge after sinonasal surgery is achievable, safe and cost-effective.
Efficacy of attention bias modification training for depressed adults: a randomized clinical trial
Authors: Hsu Kean J. , Shumake Jason , Caffey Kayla , Risom Semeon , Labrada Jocelyn , Smits Jasper A. J. , Schnyer David M. , Beevers Christopher G.
Published: March 2021

Background

This study examined the efficacy of attention bias modification training (ABMT) for the treatment of depression.

Methods

In this randomized clinical trial, 145 adults (77% female, 62% white) with at least moderate depression severity [i.e. self-reported Quick Inventory of Depressive Symptomatology (QIDS-SR) ⩾13] and a negative attention bias were randomized to active ABMT, sham ABMT, or assessments only. The training consisted of two in-clinic and three (brief) at-home ABMT sessions per week for 4 weeks (2224 training trials total). The pre-registered primary outcome was change in QIDS-SR. Secondary outcomes were the 17-item Hamilton Depression Rating Scale (HRSD) and anhedonic depression and anxious arousal from the Mood and Anxiety Symptom Questionnaire (MASQ). Primary and secondary outcomes were administered at baseline and four weekly assessments during ABMT.

Results

Intent-to-treat analyses indicated that, relative to assessment-only, active ABMT significantly reduced QIDS-SR and HRSD scores by an additional 0.62 ± 0.23 (p = 0.008, d = −0.57) and 0.74 ± 0.31 (p = 0.021, d = −0.49) points per week. Similar results were observed for active v. sham ABMT: a greater symptom reduction of 0.44 ± 0.24 QIDS-SR (p = 0.067, d = −0.41) and 0.69 ± 0.32 HRSD (p = 0.033, d = −0.42) points per week. Sham ABMT did not significantly differ from the assessment-only condition. No significant differences were observed for the MASQ scales.

Conclusion

Depressed individuals with at least modest negative attentional bias benefitted from active ABMT.
Tweeting Beyond Tahrir
Authors: Siegel Alexandra A. , Nagler Jonathan , Bonneau Richard , Tucker Joshua A.
Published: March 2021

abstract

Do online social networks affect political tolerance in the highly polarized climate of postcoup Egypt? Taking advantage of the real-time networked structure of Twitter data, the authors find that not only is greater network diversity associated with lower levels of intolerance, but also that longer exposure to a diverse network is linked to less expression of intolerance over time. The authors find that this relationship persists in both elite and non-elite diverse networks. Exploring the mechanisms by which network diversity might affect tolerance, the authors offer suggestive evidence that social norms in online networks may shape individuals’ propensity to publicly express intolerant attitudes. The findings contribute to the political tolerance literature and enrich the ongoing debate over the relationship between online echo chambers and political attitudes and behavior by providing new insights from a repressive authoritarian context.
Experiences of loneliness among older people living alone. A qualitative study in Quebec (Canada)
Authors: Charpentier Michèle , Kirouac Laurie
Published: March 2021

In this article, we analyse experiences of loneliness among older people living alone. Current knowledge suggests that loneliness is a significant social issue that can compromise health and wellbeing, and that seniors living alone are at a higher risk of loneliness. Based on a qualitative methodological approach and semi-structured interviews conducted with 43 people aged 65 or over living alone in Montreal (Quebec, Canada), this study sought to understand how they perceive, reflect on and react to loneliness. The results show that these seniors perceive loneliness as a dynamic, and rarely static, experience, which has a very different significance, depending on whether it is chosen or circumstantially imposed. The experience of loneliness recounted by the seniors we met is characterised by its heterogeneity, and involves, to varying degrees, their relationship to themselves (solitude), to others (family (and friends) lonelinessandloneliness in love) and/or to the world (existential lonelinessandaloneness). Lastly, our analyses highlight how social factors, such as age, gender, marital status, social network and socio-economic conditions, shape the experience of loneliness among seniors. These factors also influence the strategies that seniors develop to prevent or alleviate loneliness, strategies that yield very mixed results.
‘Spending all this time stressing and worrying and calculating’: marginal food security and student life at a Diverse Urban University
Authors: Gamba Ryan J , Schmeltz Michael T , Ortiz Nancy , Engelman Alina , Lam Juleen , Ampil Adianez , Pritchard Maria M , Santillan Joshua Kier Adrian , Rivera Esteban S , Wood Lana Mariko , Ingram Darice , Cheyne Kate , Taylor Sarah
Published: March 2021

Objective:

Food security status is a continuum ranging from high to very low food security. While marginal food security falls next to high food security on the spectrum, new quantitative research indicates marginal food security status is associated with negative health outcomes and poor academic performance among college students. Qualitative research focusing on college students experiencing marginal food security has not been conducted. The current study aims to qualitatively explore experiences of college students with marginal food security and to identify themes to better understand and provide context regarding how marginal food security impacts students.

Design:

Students were recruited for semi-structured interviews with questions designed to study the challenges associated with students’ food situations. All interviews were recorded and transcribed with themes identified via an inductive approach.

Setting:

A large public university on the US west coast.

Participants:

Thirty college students.

Results:

Key themes that emerged: purchasing cheap unhealthy foods, insufficient time to prepare and eat meals on a regular basis, stress and anxiety around the inability to eat healthy food and future health issues, self-perception of health when eating poorly along with physical symptoms and low academic motivation by not fully participating in their courses due to few healthy food options or missing meals.

Conclusion:

Marginal food security can potentially diminish students’ health and their capacity to learn and succeed in their coursework. The results emphasise that students experiencing marginal food security should not be grouped with students experiencing high food security.
Pellagra in South Africa from 1897 to 2019: a scoping review
Authors: Viljoen Margaretha , Bipath Priyesh , Tosh Cheryl
Published: March 2021

Objective:

Pellagra is a nutritional deficiency disease associated with niacin (vitamin B3) deficiency. The history of pellagra is well documented for Europe and the USA, but less is known about the prevalence in sub-Saharan African countries. This study documents the history of pellagra in South Africa, as diagnosed based on dermatological symptoms.

Design:

Scoping review of information from scientific databases, library archives, other archives and record services and from Statistics South Africa.

Setting:

South Africa, 1897–2019.

Participants:

South African.

Results:

Pellagra was first officially recorded in South Africa in 1906, but there are earlier indications of the disease. The prevalence of pellagra peaked after it was all but eradicated in the USA and Europe. Pellagra was never as prevalent in South Africa as in Europe, the USA and Egypt, where special hospitals for pellagrins were established. However, studies on urinary excretion of metabolites conducted in 1960s and 1970s suggested a high prevalence of subclinical (sub-pellagra) niacin deficiency, especially in previously disadvantaged Black populations. As in Europe and the USA, pellagra was associated with poverty and an overdependence on maize as staple food. Malnutrition was the main cause of the disease, but alcohol abuse might have been a contributing factor. In South Africa, reports of pellagra had declined by the late 1980s/early 1990s and hardly any cases were reported by the year 2000.

Conclusions:

Although pellagra, diagnosed based on dermatological symptoms, appears to be largely eradicated in South Africa, it does not rule out the potential for subclinical niacin deficiency.
Prevalence of depressive symptoms among Chinese university students amid the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Luo Wei , Zhong Bao-Liang , Chiu Helen Fung-Kum
Published: March 2021

Aims

Chinese university students are at high risk for depressive symptoms and the ongoing coronavirus disease 2019 (COVID-19) pandemic may have exacerbated the mental health of university students. However, existing studies on depressive symptoms in Chinese university students during the COVID-19 pandemic reported a wide range of prevalence estimates, making mental health planning for this population difficult. The objective of this study was to conduct a systematic review and meta-analysis of surveys that assessed the prevalence of depressive symptoms in Chinese university students amid the COVID-19 pandemic.

Methods

Major Chinese (CNKI, Wanfang, VIP) and English (PubMed, Embase, PsycInfo) databases and preprint platforms were searched to identify cross-sectional studies containing data on the prevalence of depressive symptoms in Chinese university students during the pandemic. Two authors independently retrieved the literature, evaluated the eligibility of potential studies, assessed the risk of bias (RoB) of included studies, and extracted data. RoB was assessed with the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.

Results

In total, 1177 records were retrieved, and 84 studies involving 1 292 811 Chinese university students during the pandemic were included. None of the included studies were rated as completely low RoB. Statistically significant heterogeneity in the prevalence estimates of included studies was detected (I2 = 99.9%, p < 0.001). The pooled prevalence of depressive symptoms was 26.0% (95%CI: 23.3–28.9%), which was significantly higher in female than in male students (30.8% v. 28.6%, p < 0.001), in postgraduates than in undergraduates (29.3% v. 22.9%, p < 0.001), in students living inside than in those living outside the COVID-19 epicentre (27.5% v. 22.3%, P < 0.001), in students from universities at the epicentre than in those from universities outside the epicentre (26.2% v. 23.1%, p < 0.001), in students who had close contact with COVID-19 than in those who did not (46.0% v. 25.0%, p < 0.001), and in students who had acquaintances or relatives infected with COVID-19 (39.7% v. 24.0%, p < 0.001) than in those who did not. Five sources of heterogeneity were identified from the subgroup analysis: survey period, % of males among the survey sample, scale of depressive symptoms, cutoff score of the scale and level of RoB.

Conclusions

Over one-fourth of Chinese university students experienced depressive symptoms during the COVID-19 pandemic. Mental health services for this population should include periodic evaluation of depressive symptoms, expanded social support and psychiatric assessment and treatment when necessary. It is also necessary to design depression prevention programmes that target higher-risk cohorts of university students.
Bayesian Seismic Refraction Inversion for Critical Zone Science and Near‐Surface Applications
Authors: Huang Mong‐Han , Hudson‐Rasmussen Berit , Burdick Scott , Lekic Vedran , Nelson Mariel D. , Fauria Kristen E. , Schmerr Nicholas
Published: March 2021

The critical zone (CZ) is the region of the Earth’s surface that extends from the bottom of the weathered bedrock to the tree canopy and is important because of its ability to store water and support ecosystems. A growing number of studies use active source shallow seismic refraction to explore and define the size and structure of the CZ across landscapes. However, measurement uncertainty and model resolution at depth are generally not evaluated, which makes the identification and interpretation of CZ features inconclusive. To reliably resolve seismic velocity with depth, we implement a Transdimensional Hierarchical Bayesian (THB) framework with reversible‐jump Markov Chain Monte Carlo to generate samples from the posterior distribution of velocity structures. We also perform 2D synthetic tests to explore how well THB traveltime inversion can resolve different subsurface velocity structures. We find that THB recovers both sharp changes in velocity as well as gradual velocity increases with depth. Furthermore, we explore the velocity structure in a series of ridge‐valley systems in northern California. The posterior velocity model shows an increasing thickness of low velocity material from channels to ridgetops along a transect parallel to bedding strike, implying a deeper weathering zone below ridgetops and hillslopes than below channels. The THB method enhances the ability to reliably image CZ structure, and the model uncertainty estimates it yields provides an objective way to interpret deep CZ structure. The method can be applied across other near‐surface studies, especially in the presence of significant surface topography.
The Atlantic Jet Response to Stratospheric Events: A Regime Perspective
Authors: Goss Michael , Lindgren Erik A. , Sheshadri Aditi , Diffenbaugh Noah S.
Published: March 2021

The tropospheric response to Sudden Stratospheric Warmings (SSWs) is associated with an equatorward shift in the midlatitude jet and associated storm tracks, while Strong Polar Vortex (SPV) events elicit a contrasting response. Recent analyses of the North Atlantic jet using probability density functions of a jet latitude index have identified three preferred jet latitudes, raising the question of whether the tropospheric response to SSWs and SPVs results from a change in relative frequencies of these preferred jet regimes rather than a systematic jet shift. We explore this question using atmospheric reanalysis data from 1979 to 2018 (26 SSWs and 33 SPVs), and a 202‐years integration of the Whole Atmosphere Community Climate Model (92 SSWs and 68 SPVs). Following SSWs, the northern jet regime becomes less common and the central and southern regimes become more common. These changes occur almost immediately following “split” vortex events, but are more delayed following “displacement” events. In contrast, the northern regime becomes more frequent and the southern regime less frequent following SPV events. Following SSWs, composites of 500‐hPa geopotential heights, surface air temperatures, and precipitation most closely resemble composites of the southern jet regime, and are generally opposite in sign to the composites of the northern jet regime. These comparisons are reversed following SPVs. Thus, one possible interpretation is that the two southernmost regimes appear to be favored following SSWs, while the southernmost regime becomes less common following SPVs.
Flying Saucers Could One Day Probe the Mesosphere
Authors: Benningfield Damond
Published: March 2021

Researchers have created thin, levitating disks that could be used to study the mesosphere, a layer of Earth’s atmosphere that’s difficult to reach with conventional flyers.
Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study
Authors: Cardwell Chris R. , O’Sullivan Joe M. , Jain Suneil , Hicks Blánaid M. , Devine Paul A. , McMenamin Úna C.
Published: March 2021

Background

Hormone therapy is widely used in prostate cancer. However, studies have raised concerns that hormone therapy, particularly the use of gonadotropin-releasing hormone agonists, could increase the risk of acute kidney injury.

Methods

Men newly diagnosed with non-metastatic prostate cancer, from 2012 to 2017, were identified from the Scottish Cancer Registry. A matched comparison cohort of prostate cancer-free men was also identified. Hormone therapy use was determined from the Prescribing Information System in Scotland. The primary outcome was hospitalisations with acute kidney injury taken from Scottish hospital records (SMR01) up to June 2019. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for acute kidney injury by hormone therapy use.

Results

The prostate cancer cohort contained 10,751 patients followed for 41,997 person years, during which there were 618 hospitalisations with acute kidney injury. Prostate cancer patients had higher rates of acute kidney injury compared with cancer-free controls (adjusted HR = 1.47 95% CI 1.29, 1.69). However, prostate cancer patients currently using hormone therapy (adjusted HR = 1.14 95% CI 0.92, 1.41), including gonadotropin-releasing hormone (GnRH) agonists (adjusted HR = 1.13 95% CI 0.90, 1.40), did not appear to have a marked increase in acute kidney injury compared with prostate cancer patients not using hormone therapy after adjusting for potential confounders.

Conclusions

In our cohort, there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.
MIRLET7BHG promotes hepatocellular carcinoma progression by activating hepatic stellate cells through exosomal SMO to trigger Hedgehog pathway
Authors: Xia Yunhong , Zhen Lu , Li Hongxia , Wang Shuomin , Chen Sun , Wang Chongchong , Yang Xiaoyu
Published: March 2021

Hepatocellular carcinoma (HCC), commonly caused by liver fibrosis, is a global challenge with high morbidity. Activation of hepatic stellate cells (HSCs) contributes to hepatic fibrosis. Exosomes are small vesicles that play a significant role in cell-to-cell communication. Smoothened (SMO) is the key signal transducer for Hedgehog pathway. This study was designed to study the function and underlying mechanism of SMO in HSC activation. Functional assays including 5-Ethynyl-2´-deoxyuridine, colony formation, wound healing, transwell, and sphere formation assays disclosed the function of SMO. Western blot analysis of exosome biomarkers, immunofluorescence staining assay, electron microscope, and flow cytometry revealed the existence of exosomes. Bioinformatics analyses and mechanistic assays uncovered the interplays between RNAs. Nude mice xenograft model was established to evaluate HCC tumor growth. We uncovered that SMO was an oncogene in HCC cells and was low-expressed in quiescent HSCs. Then, SMO was upregulated in HSCs cultured with HCC cells-conditioned medium. Next, it was revealed that HCC cells-derived exosomes activated HSCs by transmitting SMO to HSCs. Subsequently, we recognized that microRNA let-7b host gene (MIRLET7BHG) served as the competing endogenous RNA against miR-330-5p to upregulate SMO. In turn, SMO induced hedgehog pathway to promote GLI family zinc finger 1 (Gli1), leading to transcriptional activation of MIRLET7BHG in activated HSCs. In summary, this study demonstrated that Gli1-induced MIRLET7BHG facilitated HCC by activating HSCs through exosomal SMO to stimulate hedgehog pathway, providing a new road for HCC treatment.
Development of short and long-range magnetic order in the double perovskite based frustrated triangular lattice antiferromagnet Ba$$_{2}$$MnTeO$$_{6}$$
Authors: Khatua J. , Arh T. , Mishra Shashi B. , Luetkens H. , Zorko A. , Sana B. , Rao M. S. Ramachandra , Nanda B. R. K. , Khuntia P.
Published: March 2021

Frustrated magnets based on oxide double perovskites offer a viable ground wherein competing magnetic interactions, macroscopic ground state degeneracy and complex interplay between emergent degrees of freedom can lead to correlated quantum phenomena with exotic excitations highly relevant for potential technological applications. By local-probe muon spin relaxation ($$\mu$$
μ
SR) and complementary thermodynamic measurements accompanied by first-principles calculations, we here demonstrate novel electronic structure and magnetic phases of Ba$$_{2}$$

2

MnTeO$$_{6}$$

6

, where Mn$$^{2+}$$

2
+

ions with S = 5/2 spins constitute a perfect triangular lattice. Magnetization results evidence the presence of strong antiferromagnetic interactions between Mn$$^{2+}$$

2
+

spins and a phase transition at $$T_{N}$$

T
N

= 20 K. Below $$T_{N}$$

T
N

, the specific heat data show antiferromagnetic magnon excitations with a gap of 1.4 K, which is due to magnetic anisotropy. $$\mu$$
μ
SR reveals the presence of static internal fields in the ordered state and short-range spin correlations high above $$T_{N}$$

T
N

. It further unveils critical slowing-down of spin dynamics at $$T_{N}$$

T
N

and the persistence of spin dynamics even in the magnetically ordered state. Theoretical studies infer that Heisenberg interactions govern the inter- and intra-layer spin-frustration in this compound. Our results establish that the combined effect of a weak third-nearest-neighbour ferromagnetic inter-layer interaction (owing to double-exchange) and intra-layer interactions stabilizes a three-dimensional magnetic ordering in this frustrated magnet.
Co-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer
Authors: Slovak Ryan J. , Park Hong-Jai , Kamp William M. , Ludwig Johannes M. , Kang Insoo , Kim Hyun S.
Published: March 2021

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor dual checkpoint inhibition significantly affected the tumoral infiltration of lymphocytes. After treatment with dual inhibitors, infiltrating CD8+ T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p < 0.05) and LAG3 (446.2 vs. 694.4 and 707; p < 0.05) along with significantly more expression of TIM3 (12,611 vs. 2961 and 4259; p < 0.05) versus the control and anti-PD-1 groups. These results suggest that dual therapy with anti-CTLA-4 and anti-PD-1 antibodies significantly inhibits growth of microsatellite stable CRC by suppressing immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism and a target for future combination immunotherapies in CRC.
Predicting amyloid positivity in patients with mild cognitive impairment using a radiomics approach
Authors: Kim Jun Pyo , Kim Jonghoon , Jang Hyemin , Kim Jaeho , Kang Sung Hoon , Kim Ji Sun , Lee Jongmin , Na Duk L. , Kim Hee Jin , Seo Sang Won , Park Hyunjin
Published: March 2021

Predicting amyloid positivity in patients with mild cognitive impairment (MCI) is crucial. In the present study, we predicted amyloid positivity with structural MRI using a radiomics approach. From MR images (including T1, T2 FLAIR, and DTI sequences) of 440 MCI patients, we extracted radiomics features composed of histogram and texture features. These features were used alone or in combination with baseline non-imaging predictors such as age, sex, and ApoE genotype to predict amyloid positivity. We used a regularized regression method for feature selection and prediction. The performance of the baseline non-imaging model was at a fair level (AUC = 0.71). Among single MR-sequence models, T1 and T2 FLAIR radiomics models also showed fair performances (AUC for test = 0.71–0.74, AUC for validation = 0.68–0.70) in predicting amyloid positivity. When T1 and T2 FLAIR radiomics features were combined, the AUC for test was 0.75 and AUC for validation was 0.72 (pvs. baseline model < 0.001). The model performed best when baseline features were combined with a T1 and T2 FLAIR radiomics model (AUC for test = 0.79, AUC for validation = 0.76), which was significantly better than those of the baseline model (p < 0.001) and the T1 + T2 FLAIR radiomics model (p < 0.001). In conclusion, radiomics features showed predictive value for amyloid positivity. It can be used in combination with other predictive features and possibly improve the prediction performance.
Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)
Authors: Arévalo Jazmine , Lorente David , Trilla Enrique , Salcedo María Teresa , Morote Juan , Meseguer Anna
Published: March 2021

Clear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.
Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion
Authors: Verschoor Pola J. , Greig Fiona H. , Rochford Justin J. , Levate Giovanni , Delibegovic Mirela , Thompson Dawn , Leeson-Payne Alasdair , Dekeryte Ruta , Banks Ruth , Ramos Joe W. , Nixon Graeme F.
Published: March 2021

Excessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, phosphoprotein enriched in astrocytes (PEA)-15 has been linked to metabolic disease but its role in lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15−/− mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15−/− mice consistent with greater lipid storage capacity. Surprisingly, PEA-15−/− mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15−/− mice were crossed with the ApoE−/− mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.
Comparing survival outcomes for cervical cancer based on the 2014 and 2018 International Federation of Gynecology and Obstetrics staging systems
Authors: Shin Wonkyo , Ham Tae Young , Park Young Ran , Lim Myong Cheol , Won Young-Joo
Published: March 2021

The International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging system was modified in 2018, introducing new stage IB subdivisions and new lymph node status considerations in stage IIIC. We compared cervical cancer survival outcomes according to the 2014 and 2018 FIGO staging systems. We selected 10% of cervical cancer cases (2010–2015) from the Korean national cancer registry (2010–2015) through a systematic sampling method. We collected information using a collaborative stage data collection system and evaluated the results according to both staging systems. The log-rank test was used to analyze overall survival differences. No significant difference in survival was observed between 2018 subdivisions IB1/IB2/IB3 (P = 0.069), whereas a considerable difference was observed between these subdivisions according to histological subtypes. In the 2018 FIGO staging system, stage IIIC had better survival than stage IIIA/IIIB (P < 0.001). We observed considerable heterogeneity in 2018 stage IIIC related to the corresponding stages of the 2014 staging system (stages IA1–IIIB). The size of the primary cervical mass was related to survival (P < 0.001). In conclusion, using lymph node status to define stage IIIC captured a broad range of prognoses. The inclusion of primary tumor size considerations may improve the staging accuracy of advanced cervical cancer.
Associations of pathological diagnosis and genetic abnormalities in meningiomas with the embryological origins of the meninges
Authors: Okano Atsushi , Miyawaki Satoru , Hongo Hiroki , Dofuku Shogo , Teranishi Yu , Mitsui Jun , Tanaka Michihiro , Shin Masahiro , Nakatomi Hirofumi , Saito Nobuhito
Published: March 2021

Certain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10−10). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10–12). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10−2, Hazard Ratio 4.08, 95% Confidence Interval 1.28–13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.
Properties of assembly of superparamagnetic nanoparticles in viscous liquid
Authors: Usov N. A. , Rytov R. A. , Bautin V. A.
Published: March 2021

Detailed calculations of the specific absorption rate (SAR) of a dilute assembly of iron oxide nanoparticles with effective uniaxial anisotropy dispersed in a liquid are performed depending on the particle diameters, the alternating (ac) magnetic field amplitude H0 and the liquid viscosity. For small and moderate H0 values with respect to particle anisotropy field Hk the SAR of the assembly as a function of the particle diameter passes through a characteristic maximum and then reaches a plateau, whereas for sufficiently large amplitudes, H0 ~ Hk, the SAR increases monotonically as a function of diameter. The realization of viscous and magnetic oscillation modes for particle unit magnetization vector and director for moderate and sufficiently large H0 values, respectively, explains this behavior. It is found that the SAR of the assembly changes inversely with the viscosity only in a viscous mode, for nanoparticles of sufficiently large diameters. In the magnetic mode the SAR of the assembly is practically independent of the viscosity, since in this case the nanoparticle director only weakly oscillates around the ac magnetic field direction. The conditions for the validity of the linear response theory have been clarified by comparison with the numerical simulation data.
Vortex trapping recaptures energy in flying fruit flies
Authors: Lehmann Fritz-Olaf , Wang Hao , Engels Thomas
Published: March 2021

Flapping flight is one of the most costly forms of locomotion in animals. To limit energetic expenditures, flying insects thus developed multiple strategies. An effective mechanism to reduce flight power expenditures is the harvesting of kinetic energy from motion of the surrounding air. We here show an unusual mechanism of energy harvesting in an insect that recaptures the rotational energy of air vortices. The mechanism requires pronounced chordwise wing bending during which the wing surface momentary traps the vortex and transfers its kinetic energy to the wing within less than a millisecond. Numerical and robotic controls show that the decrease in vortex strength is minimal without the nearby wing surface. The measured energy recycling might slightly reduce the power requirements needed for body weight support in flight, lowering the flight costs in animals flying at elevated power demands. An increase in flight efficiency improves flight during aversive manoeuvring in response to predation and long-distance migration, and thus factors that determine the worldwide abundance and distribution of insect populations.
Using carpet plots to analyze transit times of low frequency oscillations in resting state fMRI
Authors: Fitzgerald Bradley , Yao Jinxia Fiona , Talavage Thomas M. , Hocke Lia M. , Frederick Blaise deB , Tong Yunjie
Published: March 2021

A “carpet plot” is a 2-dimensional plot (time vs. voxel) of scaled fMRI voxel intensity values. Low frequency oscillations (LFOs) can be successfully identified from BOLD fMRI and used to study characteristics of neuronal and physiological activity. Here, we evaluate the use of carpet plots paired with a developed slope-detection algorithm as a means to study LFOs in resting state fMRI (rs-fMRI) data with the help of dynamic susceptibility contrast (DSC) MRI data. Carpet plots were constructed by ordering voxels according to signal delay time for each voxel. The slope-detection algorithm was used to identify and calculate propagation times, or “transit times”, of tilted vertical edges across which a sudden signal change was observed. We aim to show that this metric has applications in understanding LFOs in fMRI data, possibly reflecting changes in blood flow speed during the scan, and for evaluating alternative blood-tracking contrast agents such as inhaled CO2. We demonstrate that the propagations of LFOs can be visualized and automatically identified in a carpet plot as tilted lines of sudden intensity change. Resting state carpet plots produce edges with transit times similar to those of DSC carpet plots. Additionally, resting state carpet plots indicate that edge transit times vary at different time points during the scan.