bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Smooth Muscle Cell Subpopulations and Neointimal Formation in Mouse Models of Elastin Insufficiency
Authors: Lin Chien-Jung , Hunkins Bridget M. , Roth Robyn A. , Lin Chieh-Yu , Wagenseil Jessica E. , Mecham Robert P.
Published: September 2021

Objective:

Using a mouse model of Eln (elastin) insufficiency that spontaneously develops neointima in the ascending aorta, we sought to understand the origin and phenotypic heterogeneity of smooth muscle cells (SMCs) contributing to intimal hyperplasia. We were also interested in exploring how vascular cells adapt to the absence of Eln.

Approach and Results:

We used single-cell sequencing together with lineage-specific cell labeling to identify neointimal cell populations in a noninjury, genetic model of neointimal formation. Inactivating Eln production in vascular SMCs results in rapid intimal hyperplasia around breaks in the ascending aorta’s internal elastic lamina. Using lineage-specific
Cre
drivers to both lineage mark and inactivate Eln expression in the secondary heart field and neural crest aortic SMCs, we found that cells with a secondary heart field lineage are significant contributors to neointima formation. We also identified a small population of secondary heart field-derived SMCs underneath and adjacent to the internal elastic lamina. Within the neointima of SMC-Eln knockout mice, 2 unique SMC populations were identified that are transcriptionally different from other SMCs. While these cells had a distinct gene signature, they expressed several genes identified in other studies of neointimal lesions, suggesting that some mechanisms underlying neointima formation in Eln insufficiency are shared with adult vessel injury models.

Conclusions:

These results highlight the unique developmental origin and transcriptional signature of cells contributing to neointima in the ascending aorta. Our findings also show that the absence of Eln, or changes in elastic fiber integrity, influences the SMC biological niche in ways that lead to altered cell phenotypes.
Cardiotoxicity of Cancer Treatments: Focus on Anthracycline Cardiomyopathy
Authors: Nishi Masahiro , Wang Ping-yuan , Hwang Paul M.
Published: September 2021

Significant progress has been made in developing new treatments and refining the use of preexisting ones against cancer. Their successful use and the longer survival of cancer patients have been associated with reports of new cardiotoxicities and the better characterization of the previously known cardiac complications. Immunotherapies with monoclonal antibodies against specific cancer-promoting genes, chimeric antigen receptor T cells, and immune checkpoint inhibitors have been developed to fight cancer cells, but they can also show off-target effects on the heart. Some of these cardiotoxicities are thought to be due to nonspecific immune activation and inflammatory damage. Unlike immunotherapy-associated cardiotoxicities which are relatively new entities, there is extensive literature on anthracycline-induced cardiomyopathy. Here, we provide a brief overview of the cardiotoxicities of immunotherapies for the purpose of distinguishing them from anthracycline cardiomyopathy. This is especially relevant as the expansion of oncological treatments presents greater diagnostic challenges in determining the cause of cardiac dysfunction in cancer survivors with a history of multiple cancer treatments including anthracyclines and immunotherapies administered concurrently or serially over time. We then provide a focused review of the mechanisms proposed to underlie the development of anthracycline cardiomyopathy based on experimental data mostly in mouse models. Insights into its pathogenesis may stimulate the development of new strategies to identify patients who are susceptible to anthracycline cardiomyopathy while permitting low cardiac risk patients to receive optimal treatment for their cancer.

Graphic Abstract:

A graphic abstract is available for this article.
Constitutively Activating GNAS Somatic Mutation in Right Ventricular Outflow Tract Tachycardia
Authors: Ip James E. , Xu Linna , Dai Jie , Steegborn Clemens , Jaffré Fabrice , Evans Todd , Cheung Jim W. , Basson Craig T. , Panaghie Gianina , Krogh-Madsen Trine , Abbott Geoffrey W. , Lerman Bruce B.
Published: September 2021

Background:

The cellular mechanism of focal, idiopathic right ventricular outflow tract (RVOT) tachycardia is thought to be due to cAMP-mediated triggered activity. A potential molecular mechanism has not yet been determined. We identified and characterized a novel missense somatic mutation in the gene (GNAS) encoding the G
s
α (stimulatory G protein alpha-subunit) from a patient with RVOT tachycardia that is proposed to be the etiology of the clinical tachycardia.

Methods:

Percutaneous endomyocardial biopsies were obtained from multiple sites in a patient with nonexertional, repetitive monomorphic RVOT tachycardia. Sequencing of extracted genomic DNA identified a G
s
α W234R variant only at the site of tachycardia origin. Functional studies using in vitro transfection with S49 cyc− murine lymphoma cells and measurement of cyclic AMP levels were performed. A trypsin protection assay assessed GTP binding kinetics and structural modeling predicted the impact of the mutation on protein-protein interactions. Whole-cell patch clamp experiments of transfected CHO cells assessed the downstream effects of the mutation.

Results:

In vitro studies of the GNAS mutation (W234R) demonstrated basal levels of cAMP ≈16-fold higher than wild-type cells, consistent with constitutive stimulation of G
s
α. Mutant G
s
α was partially protected from proteolysis after incubation with GTP, indicating diminished GTPase activity and reduced GTP hydrolysis as the mechanism for increased basal intracellular cAMP levels. Transfected mutant CHO cells increased unstimulated mean peak L-type calcium channel current density by ≈50% and in silico modeling demonstrated spontaneous delayed afterdepolarizations and triggered activity.

Conclusions:

We identified a novel somatic mutation in GNAS associated with RVOT tachycardia. The mutation results in constitutive activation of G
s
α, impairs GTP hydrolysis, and elevates basal cAMP levels, leading to enhanced L-type calcium current and triggered activity. These findings confirm that RVOT tachycardia can be caused by somatic mutations in signal transduction proteins that regulate intracellular cAMP and its downstream effectors.
Practice Patterns and Patient Outcomes After Widespread Adoption of Remote Heart Failure Care
Authors: Yuan Neal , Botting Patrick G. , Elad Yaron , Miller Shaun J. , Cheng Susan , Ebinger Joseph E. , Kittleson Michelle M.
Published: September 2021

Background:

An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes.

Methods:

We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes.

Results:

Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (
P
<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18–0.22] video versus in-person, 0.18 [0.17–0.19] telephone versus in-person) or prescribe β-blockers (0.82 [0.68–0.99], 0.35 [0.26–0.47]), mineralocorticoid receptor antagonists (0.69 [0.50–0.96], 0.48 [0.35–0.66]), or loop diuretics (0.67 [0.53–0.85], 0.45 [0.37–0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40–0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14–2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97–1.86]) and hospitalizations (1.36 [0.98–1.89]).

Conclusions:

Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.
Contraction Patterns of the Right Ventricle Associated with Different Degrees of Left Ventricular Systolic Dysfunction
Authors: Surkova Elena , Kovács Attila , Tokodi Márton , Lakatos Bálint Károly , Merkely Béla , Muraru Denisa , Ruocco Alessandro , Parati Gianfranco , Badano Luigi P.
Published: September 2021

Background:

The functional adaptation of the right ventricle (RV) to the different degrees of left ventricular (LV) dysfunction remains to be clarified. We sought to (1) assess the changes in RV contraction pattern associated with the reduction of LV ejection fraction (EF) and (2) analyze whether the assessment of RV longitudinal, radial, and anteroposterior motion components of total RVEF adds prognostic value.

Methods:

Consecutive patients with left-sided heart disease who underwent clinically indicated transthoracic echocardiography were enrolled in a single-center prospective observational study. Adverse outcome was defined as heart failure hospitalization or cardiac death. Cross-sectional analysis using the baseline 3-dimensional echocardiography studies was performed to quantify the relative contribution of the longitudinal, radial, and anteroposterior motion components to total RVEF.

Results:

We studied 292 patients and followed them for 6.7±2.2 years. In patients with mildly and moderately reduced LVEF, the longitudinal and the anteroposterior components of RVEF decreased significantly, while the radial component increased resulting in preserved total RVEF (RVEF: 50% [46%–54%] versus 47% [44%–52%] versus 46% [42%–49%] in patients with no, mild, or moderate LV dysfunction, respectively; data presented as median and interquartile range). In patients with severe LV systolic dysfunction (n=34), a reduction in all 3 RV motion components led to a significant drop in RVEF (30% [25%-39%],
P
<0.001). In patients with normal RVEF (>45%), the anteroposterior component of total RVEF was a significant and independent predictor of outcome (hazard ratio, 0.960 [CI, 0.925–0.997],
P
<0.001).

Conclusions:

In patients with left-sided heart disease, there is a significant remodeling of the RV associated with preservation of the RVEF in patients with mild or moderate LV dysfunction. In patients with normal RVEF, the measurement of the anteroposterior component of RV motion provided independent prognostic value.
Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants
Authors: Gigli Marta , Stolfo Davide , Graw Sharon L. , Merlo Marco , Gregorio Caterina , Nee Chen Suet , Dal Ferro Matteo , PaldinoMD Alessia , De Angelis Giulia , Brun Francesca , Jirikowic Jean , Salcedo Ernesto E. , Turja Sylvia , Fatkin Diane , Johnson Renee , van Tintelen J. Peter , Te Riele Anneline S.J.M. , Wilde Arthur A.M. , Lakdawala Neal K. , Picard Kermshlise , Miani Daniela , Muser Daniele , Maria Severini Giovanni , Calkins Hugh , James Cynthia A. , Murray Brittney , Tichnell Crystal , Parikh Victoria N. , Ashley Euan A. , Reuter Chloe , Song Jiangping , Judge Daniel P. , McKenna William J. , Taylor Matthew R.G. , Sinagra Gianfranco , Mestroni Luisa
Published: September 2021

Background:

Filamin C truncating variants (
FLNCtv
) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of
FLNCtv
remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of
FLNCtv
carriers.

Methods:

FLNCtv
carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with
LMNA
and 60 with
DSP
-related arrhythmogenic cardiomyopathies were used for prognostic comparison.

Results:

Eighty-five patients carrying
FLNCtv
were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area – right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of
FLNCtv
carriers did not significantly differ from
LMNA
carriers and
DSP
carriers. In
FLNCtv
carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD.

Conclusions:

Among patients referred to tertiary referral centers,
FLNCtv
arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.
Learning at Variable Attentional Load Requires Cooperation of Working Memory, Meta-learning, and Attention-augmented Reinforcement Learning
Authors: Womelsdorf Thilo , Watson Marcus R. , Tiesinga Paul
Published: September 2021

Flexible learning of changing reward contingencies can be realized with different strategies. A fast learning strategy involves using working memory of recently rewarded objects to guide choices. A slower learning strategy uses prediction errors to gradually update value expectations to improve choices. How the fast and slow strategies work together in scenarios with real-world stimulus complexity is not well known. Here, we aim to disentangle their relative contributions in rhesus monkeys while they learned the relevance of object features at variable attentional load. We found that learning behavior across six monkeys is consistently best predicted with a model combining (i) fast working memory and (ii) slower reinforcement learning from differently weighted positive and negative prediction errors as well as (iii) selective suppression of nonchosen feature values and (iv) a meta-learning mechanism that enhances exploration rates based on a memory trace of recent errors. The optimal model parameter settings suggest that these mechanisms cooperate differently at low and high attentional loads. Whereas working memory was essential for efficient learning at lower attentional loads, enhanced weighting of negative prediction errors and meta-learning were essential for efficient learning at higher attentional loads. Together, these findings pinpoint a canonical set of learning mechanisms and suggest how they may cooperate when subjects flexibly adjust to environments with variable real-world attentional demands.
Bilingualism, Executive Function, and the Brain: Implications for Autism
Authors: Romero Celia , Uddin Lucina Q.
Published: September 2021

Autism spectrum disorder (ASD) is associated with marked heterogeneity with respect to the development of executive function abilities. The bilingual advantage refers to the observation that individuals who speak two languages perform better on executive function tasks than monolinguals under some circumstances. There is not yet consensus, however, as to whether this advantage can be reliably demonstrated, nor is there consensus regarding under which conditions it emerges. Bilingual and monolingual children with ASD have comparable developmental outcomes, particularly in the areas of core ASD symptoms, cognitive function, and language. Still, despite the potential advantages that bilingualism may confer, clinicians commonly advise against providing a bilingual environment for children with ASD. The purpose of the present review is to provide an up-to-date assessment of the limited literature on bilingualism in children with ASD in order to inform evidence-based practice. Studies suggest a potential bilingual advantage in ASD in the areas of nonverbal intelligence quotient, adaptive functioning, and expressive vocabulary. A limited yet growing literature provides preliminary evidence for enhanced executive function ability in some children with ASD. Taken together, current evidence suggests that although a bilingual advantage may not be universally present in typical development, it may manifest under specific circumstances, conferring advantage for populations in which executive function is compromised. Further work is needed to develop consistent, evidence-based guidelines around language recommendations for families of children with ASD and to better understand the cognitive and brain mechanisms giving rise to the bilingual advantage in clinical developmental populations.
Hurrah, I.A. & Wagh, V.V. (2021) Revisiting the taxonomy of Geranium kishtvariense (Geraniaceae) & notes on neotypification. Phytotaxa 516 (2): 169–177.
Authors: HURRAH IMTIYAZ AHMAD , WAGH VIJAY VISHNU
Published: September 2021

N/A
Campanula oreodoxa (Campanulaceae), a new critically endangered species from the Aladagh Mountains, NE Iran
Authors: ARJMANDI ALI ASGHAR , EJTEHADI HAMID , MEMARIANI FARSHID , JOHARCHI MOHAMMAD REZA , MESDAGHI MANSOUR
Published: September 2021

Campanula oreodoxa (Campanulaceae) is described and illustrated as a new sub-alpine species from North Khorassan province, Iran. The new species belongs to C. sect. Oreocodon based on dehiscence of the capsules with three middle pores at the base and absence of appendages between the calyx lobes. It is compared morphologically with the closely related species including C. hystricula and C. lourica. The micromorphological characters of seed coat and pollen grains of the new species are presented and compared with the chasmophytic allies in the area. Notes on distribution, habitat characterization, and the associated flora are provided. The new species is assessed as critically endangered (CR) and the conservation value of the habitats in the area is discussed.
Lectotypification of Bulbophyllum crassipes (Orchidaceae) and notes on its taxonomy and distribution
Authors: ADIT ARJUN , KUMAR PANKAJ , KOUL MONIKA , TANDON RAJESH
Published: September 2021

N/A
A new species of Mecomera Audinet-Serville earwig (Dermaptera: Spongiphoridae) from the Brazilian Atlantic Rainforest
Authors: HELEODORO RAPHAEL AQUINO
Published: September 2021

A new earwig species, Mecomera ze sp. nov. (Spongiphoridae: Sparattinae: Sparattini) from the Brazilian Atlantic Rainforest is described based on males and females from Piracicaba, São Paulo, Brazil. Mecomera ze sp. nov. has a pygidium shape similar to that of M. chacoensis (Borelli), and can be differentiated by the flattened projections of M. ze sp. nov., with emarginations between each projection, whilst in M. chacoensis the pygidium has cylindrical projections, with a single emargination between apical projections. Mecomera ze sp. nov. is also similar to M. reichardti in that both have cerci as long as the abdomen. However, M. reichardti has an inconspicuous basal projection and a more acute conspicuous projection at middle, whilst M. ze sp. nov. has a more conspicuous basal projection and less conspicuous middle projection. Comparisons are made with the male genitalia of all species.
Evolution of the Moat Associated with the Secondary Eyewall Formation in a Simulated Tropical Cyclone
Authors: Qin Nannan , Wu Liguang , Liu Qingyuan
Published: September 2021

Previous studies have focused on the formation and maintenance of spiral rainbands in the secondary eyewall formation (SEF) of tropical cyclones (TCs). However, the evolution of the moat, a region with weak precipitation separating spiral rainbands from the inner eyewall, is also essential for the SEF. In this study, a semi-idealized numerical experiment is conducted to understand the SEF by focusing on the evolution of the moat. In the simulated TC, a secondary eyewall forms around 32 h, and then intensifies and replaces the inner eyewall at 46 h. It is found that the occurrence and subsequent evolution of the moat in the simulated TC are closely associated with the inner-eyewall structure. As the eyewall updraft becomes strong and the eyewall anvil is well developed, the upper-level inflow develops below the eyewall anvil in response to the diabatic warming in the eyewall anvil. The warming-induced inflow causes a drying effect and promotes the sublimation cooling below the anvil, inducing strong subsidence between the inner eyewall and the spiral rainband through the resulting negative buoyancy. Moreover, the resulting subsidence is enhanced by the compensated downward motion in the outer edge of the inner eyewall. Further analysis indicates that the rapidly decreasing vertical shear of environmental wind and the rapid filamentation zone outside the inner eyewall also play important role in the axisymmetrization of the rainband and the moat subsidence. Our results demonstrate that an intense inner eyewall with a wide upper-level anvil is favorable for the SEF in an environment with decreasing vertical wind shear.
Clustering of Climate Change Impacts on Ocean Waves in the Northwest Atlantic
Authors: Goharnejad Hamid , Perrie Will , Toulany Bash , Casey Mike , Zhang Minghong
Published: September 2021

The provision of reliable results from numerical wave models implemented over vast ocean areas can be considered as a time-consuming process. In this regard, the estimation of areas with maximum similarity in wave climate spatial areas and the determination of associated representative point locations for these areas can play an important role in climate research and in engineering applications. To deal with this issue, we apply a state-of-the-art clustering method, Geo-SOM, to determine geographical areas with similar wave regimes, in terms of mean wave direction (MWD), mean wave period (T0), and significant wave height (Hs). Although this method has many strengths, a weakness is related to detection and accounting of the most extreme and rare events. To resolve this deficiency, an initial preprocessing method (called PG-Geo-SOM) is applied. To evaluate the performance of this method, extreme wave parameters, including Hs and T0, are calculated. We simulate the present climate, represented as 1979 to 2017, compared to the future climate, 2060–98, following the Intergovernmental Panel on Climate Change (IPCC) future scenario RCP8.5 in the northwestern Atlantic Ocean. In this approach, the wave parameter data are divided into distinct groups, or clusters, motivated by their geographical positions. For each cluster, the centroid spatial point and the time series of data are extracted, for Hs, MWD, and T0. Extreme values are estimated for 5-, 10-, 25-, 50-, and 100-yr return periods, using Gumbel, exponential, and Weibull stochastic models, for both present and future climates. Results show that for parameter T0, the impact of climate change for the study area is a decreasing trend, while for Hs, in coastal and shelf areas up to about 1000 km from the coastline, increasing trends are estimated, and in open-ocean areas, far from the coast, decreasing trends are obtained.
‘Depression is not a familiar word’: A mixed-methods approach to describe the experience of primary care nurses treating depression in rural Guatemala
Authors: Stryker Shanna D , Kishton Rachel , Nichols Beatrice , Hargraves Daniel , Goodnow Keesha , Doarn Charles R , Brown Jennifer L
Published: September 2021

Background:

As the burden of mental health disorders continues to increase worldwide, there is significant need to describe the cultural variations in presentation, diagnosis and treatment of these diseases. An understanding of these variations can lead to the development of more effective programs to manage these conditions. In Guatemala, depression is the second-leading cause of disability and yet mental health treatment resources are scarce, particularly for indigenous individuals.

Aims:

The primary research aim was to describe primary care nurses’ explanatory models of depression in their clinical work in indigenous communities in Guatemala. A secondary research aim was to describe training and resources which would support and empower these nurses, in order to lessen risk for burnout.

Methods:

A cross-sectional mixed methods survey was designed to elicit nurses’ perspectives on the presentation, cause and treatment of depression in the communities they serve, as well as their clinical and emotional comfort in working with depressed individuals. Two subsequent focus groups gathered qualitative commentary which informed training and resource recommendations. Theoretical thematic analysis was used to generate codes and themes from focus group transcripts and survey responses.

Results:

Guatemalan primary care nurses described symptoms of depression in their cultural context, identified socioeconomic factors which contribute to depression in their communities, and detailed treatment preferences. Limited referral options and concern for privacy made connecting patients to mental health care difficult. Nurses emphasized the need for community education on depression and for supplemental mental health resources which would increase their capacity to identify and treat depression.

Conclusions:

Primary care nurses in Guatemala identify and treat depression despite limited resources. Further investigations should focus on creating training modalities which include front-line nurses, given their critical role in the health system.
Projecting Backward and Forward on Processes of Organizational Change and Innovation
Authors: Van de Ven Andrew H.
Published: September 2021

This essay discusses how views of organizational change and innovation have traditionally focused on planned episodic change that focuses on rational, strategic, top-down and consensus-directed interventions following teleological or regulatory process models. Future scholarship seems to be focusing more on unplanned continuous organizational changes that emphasize experiential, emergent, bottom-up, pluralistic social movements following dialectical and evolutionary models of change. While planned-episodic and unplanned-continuous change may appear to be opposing views of organizational change, they are entangled in one-another, and provide a rich agenda of future scholarship on processes of organizational change and innovation.
Gaining and Training a Digital Colleague: Employee Responses to Robotization
Authors: Ågnes Julie S.
Published: September 2021

This study shows how introducing new technology can be like welcoming a digital colleague. Designed to mimic the actions of employees, robotic process automation is a technology that involves developing software robots to perform standardized tasks. Although beneficial for the firm, robotization may come at a cost for the employees, since the technology puts positions at risk by automating manual procedures. In this study, I used a case study approach to examine how employees responded to robotization in three organizations. The findings revealed that the employee responses were overwhelmingly constructive and positive. In addition to responding with a big-picture perspective and finding opportunities, the employees humanized software robots as new digital colleagues, with whom they developed relationships. The results discussed in this study contribute to understanding technology-driven change by empirically illustrating employees’ multidimensional—affective, behavioral, and cognitive—responses to robotization, and the supportive context securing implementation.
A Liberal Peace?: The Growth of Liberal Norms and the Decline of Interstate Violence
Authors: Gill-Tiney Patrick
Published: September 2021

How have understandings of fundamental norms of international society changed over time? How does this relate to the decline of interstate violence since 1945? Previous explanations have focused on regime type, domestic institutions, economic interdependence, relative power, and nuclear weapons, I argue that a crucial and underexplored part of the puzzle is the change in understanding of sovereignty over the same period. In this article, I propose a novel means of examining change in these norms between 1970 and 2014 by analyzing the content of UN Security Council resolutions. This analysis is then utilized in quantitative analysis of the level of violence dispute participants resorted to in all Militarized Interstate Disputes in the period. I find that as liberal understandings of fundamental norms have increased, that the average level of violence used has decreased. This points to a crucial missing component in the existing literature: that institutions can only constrain when political actors share the right norms.
Nobody Should Die Alone. Loneliness and a Dignified Death During the COVID-19 Pandemic
Authors: Hernández-Fernández Carlos , Meneses-Falcón Carmen
Published: September 2021

During the direst months of the COVID-19 pandemic, thousands of people died alone. This study analyzes these deaths, which occurred without the presence of loved ones, and seeks to a) examine the significance for relatives, as well as professionals, of dying alone, b) determine if these solitary deaths can be considered dignified, or good deaths, and c) evaluate if the treatment of the cadavers and the funeral rites transpired with the desired dignity and sensitivity. The study was carried out in the autonomous community of Madrid using a qualitative, phenomenological, and interpretative approach through in-depth interviews of 49 informants, professionals and relatives. Interviews were conducted between July and November of 2020, followed by an interpretive, categorical, qualitative analysis. Among the key findings are that during the most critical months, deaths lacked the desired dignity, even though the involved professionals did their best to accompany and dignify the deaths.
A Multimethod Examination of Medical Students’ Experiences With Bereavement and Complicated Grief
Authors: Ferguson Kortni A. , Reitschuler-Cross Eva B. , Stahl Sarah T.
Published: September 2021

Few studies have examined grief in medical students. This study used a multimethod approach to describe how bereavement and CG may impact medical students’ educational experience and their perspectives on grief support and training. One hundred three medical students completed an online survey with quantitative and qualitative methods. Seventy-three (71%) students reported experiencing bereavement, of which 12 (18%) screened positive for CG. Medical students who screened positive for CG reported significantly more emotional and behavioral challenges ( M = 3.58 [ SD = 2.64]) compared to medical students without CG ( M = 0.93 [ SD = 1.58], p < .001). Qualitative analyses revealed that bereaved and nonbereaved students wanted more grief education and bereavement support from medical institutions. Therefore, it is crucial for medical institutions, to acknowledge that grief and bereavement may impact students’ performance due to multifactorial causes.
Early Intervention Orientation and Mobility: A Delphi Study of the Content of the Birth to 6 Orientation and Mobility Skills Inventory (B6OMSI)
Authors: Baguhn Sarahelizabeth
Published: September 2021

Introduction: The objective of this research was to identify the appropriate content for an orientation and mobility (O&M) assessment for young children. It is necessary to have a reliable and valid assessment tool to evaluate whether young children are making adequate gains in response to early intervention efforts in O&M. Very little literature exists on the O&M needs of children aged birth to 6 years because of the roots in adult rehabilitation of the field of O&M. Methods: A group of expert-level professionals in the field of early intervention O&M engaged in a consensus process to establish face validity and content validity of the assessment items, which was accomplished using a Delphi study to identify relevant topics for assessment as a first step in developing a research-based assessment tool. Cutoffs for agreement were established prior to analysis, with 90% consensus for face and content validity of a high-stakes assessment that allows the score on the assessment to serve as a snapshot of a child’s progress. Results: All skills and concepts on the assessment were validated, and seven new items were added. Discussion: The resultant assessment tool is comprehensive in measuring the areas of O&M for young children that specialists found useful for determining the need for services and monitoring progress, does not contain extraneous test questions, and can stand alone as a snapshot of student progress. One item was added to the background information portion of the assessment tool because of its usefulness to some practitioners despite a consensus level below 90%. Future research should seek to establish construct validity and reliability measures. Implications for practitioners: Orientation and mobility specialists can begin using the updated item tool with improved content validity available from the New Mexico School for the Blind website.
COVID-19 and anosmia: The story so far
Authors: Meng Xiangming , Pan Yuandan
Published: September 2021

Objectives

The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant characteristics of COVID-19 with a high prevalence. However, many aspects of COVID-19-induced anosmia are still far from being fully understood. The purpose of this review is to summarize recent developments in COVID-19-induced anosmia to increase awareness of the condition.

Methods

A literature search was carried out using the PubMed, Embase, Web of Science, and Scopus. We reviewed the latest literature on COVID-19-induced anosmia, including mechanisms of pathogenesis, olfactory testing, anosmia as predictive tool, pathological examinations, imaging findings, affected factors, co-existing diseases, treatments, prognosis, hypothesis theories, and future directions.

Results

The possible pathogenesis of COVID-19-induced anosmia may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The D614G spike variant may also play a role in the increased number of anosmia patients. Anosmia may also be an essential indicator of COVID-19 spread and an early indicator of the effectiveness of political decisions. The occurrence and development of COVID-19-induced anosmia may be influenced by smoking behaviors and underlying diseases such as type 2 diabetes, gastroesophageal disorders, and rhinitis. Most patients with COVID-19-induced anosmia can fully or partially recover their olfactory function for varying durations. COVID-19-induced anosmia can be treated with various approaches such as glucocorticoids and olfactory training.

Conclusion

Anosmia is one of the main features of COVID-19 and the underlying disease of the patient may also influence its occurrence and development. The possible pathogenesis of COVID-19-induced anosmia is very complicated, which may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system.
A Case of Nasal Rhinosporidiosis in the United States
Authors: Irwin Thomas , Pippin Gregory , Brown James , Luer William
Published: September 2021

Rhinosporidiosis, an infectious granulomatous disease, is seldom encountered in the United States. We present a case of rhinosporidiosis in a 26-year-old man, who presented with an unusual mass in his nasal cavity. Suspicion for rhinosporidiosis was high due to the patient’s travel and activity history. After imaging and proper diagnosis, surgery was performed to excise the lesion. As international travel resumes during the COVID-19 pandemic, the potential for encountering this rare organism is heightened.
Imaging effective oxygen diffusivity in the human brain with multiparametric magnetic resonance imaging
Authors: Kufer Jan , Preibisch Christine , Epp Samira , Göttler Jens , Schmitzer Lena , Zimmer Claus , Hyder Fahmeed , Kaczmarz Stephan
Published: September 2021

Cerebrovascular diseases can impair blood circulation and oxygen extraction from the blood. The effective oxygen diffusivity (EOD) of the capillary bed is a potential biomarker of microvascular function that has gained increasing interest, both for clinical diagnosis and for elucidating oxygen transport mechanisms. Models of capillary oxygen transport link EOD to measurable oxygen extraction fraction (OEF) and cerebral blood flow (CBF). In this work, we confirm that two well established mathematical models of oxygen transport yield nearly equivalent EOD maps. Furthermore, we propose an easy-to-implement and clinically applicable multiparametric magnetic resonance imaging (MRI) protocol for quantitative EOD mapping. Our approach is based on imaging OEF and CBF with multiparametric quantitative blood oxygenation level dependent (mq-BOLD) MRI and pseudo-continuous arterial spin labeling (pCASL), respectively. We evaluated the imaging protocol by comparing MRI-EOD maps of 12 young healthy volunteers to PET data from a published study in different individuals. Our results show comparably good correlation between MRI- and PET-derived cortical EOD, OEF and CBF. Importantly, absolute values of MRI and PET showed high accordance for all three parameters. In conclusion, our data indicates feasibility of the proposed MRI protocol for EOD mapping, rendering the method promising for future clinical evaluation of patients with cerebrovascular diseases.
The cholinergic system modulates negative BOLD responses in the prefrontal cortex once electrical perforant pathway stimulation triggers neuronal afterdischarges in the hippocampus
Authors: Arboit Alberto , Krautwald Karla , Angenstein Frank
Published: September 2021

Repeated high-frequency pulse-burst stimulations of the rat perforant pathway elicited positive BOLD responses in the right hippocampus, septum and prefrontal cortex. However, when the first stimulation period also triggered neuronal afterdischarges in the hippocampus, then a delayed negative BOLD response in the prefrontal cortex was generated. While neuronal activity and cerebral blood volume (CBV) increased in the hippocampus during the period of hippocampal neuronal afterdischarges (h-nAD), CBV decreased in the prefrontal cortex, although neuronal activity did not decrease. Only after termination of h-nAD did CBV in the prefrontal cortex increase again. Thus, h-nAD triggered neuronal activity in the prefrontal cortex that counteracted the usual neuronal activity-related functional hyperemia. This process was significantly enhanced by pilocarpine, a mACh receptor agonist, and completely blocked when pilocarpine was co-administered with scopolamine, a mACh receptor antagonist. Scopolamine did not prevent the formation of the negative BOLD response, thus mACh receptors modulate the strength of the negative BOLD response.
Cavernous haemangioma of the duodenum with acute massive bleeding in the ascending portion: a case report
Authors: Duanmu Jinzhong , Liang Yahang , Huang Zhixiang , Tan Yongming , Li Taiyuan , Lei Xiong
Published: September 2021

Duodenal cavernous haemangiomas are rare, benign disorders, and massive gastrointestinal (GI) bleeding is a rare clinical condition. The present case report describes a 50-year-old male patient who presented with severe, ongoing haematochezia. A peripheral blood smear at the time of admission showed significant anaemia, and haemoglobin level was 52 g/l (normal range, 120–175 g/l). Albumin level was also low at 28 g/l (normal range, 40–55 g/l). Standard computed tomography (CT) showed mural thickening and relative lumen stenosis in the ascending (fourth) portion of the duodenum. Contrast-enhanced CT using hypotonic solution revealed the lesions to be hypervascular haemangiomas. Laparotomy and segmental duodenum resection were performed, and the first jejunal limb was anastomosed using a side-to-end technique. Histopathological examination confirmed the diagnosis of cavernous haemangioma. The patient showed marked improvement during follow-up. The present case findings emphasize that duodenal haemangioma is possible without a history of chronic anaemia, and should remain a consideration in differential diagnosis for patients presenting with massive GI bleeding. CT is useful for preoperative diagnosis of massive bleeding, and surgery with segmental resection is usually curative.
Safety of renal biopsy bleeding prophylaxis with desmopressin
Authors: Sosa Barrios R. Haridian , Burguera Vion Víctor , Álvarez Nadal Marta , Cintra Cabrera Melissa , Elías Triviño Sandra , Villa Hurtado Daniel , Ortego Sofía , Fernández Lucas Milagros , Rivera-Gorrin Maite
Published: September 2021

Background

Percutaneous renal biopsy (PRB) is invasive, and bleeding-related complications are a concern. Desmopressin (DDAVP) is a selective type 2 vasopressin receptor-agonist also used for haemostasis.

Aim

To evaluate the side effects of intravenous (IV) weight-adjusted desmopressin preceding PRB.

Methods

This was a retrospective study of renal biopsies performed by nephrologists from 2013 to 2017 in patients who received single-dose DDAVP pre-PRB.

Results

Of 482 PRBs, 65 (13.5%) received DDAVP (0.3 µg/kg); 55.4% of the PRBs were native kidneys. Desmopressin indications were altered platelet function analyser (PFA)-100 results (75.3% of the patients), urea >24.9 mmol/L (15.5%), antiplatelet drugs (6.1%) and thrombocytopaenia (3%). Of the 65 patients, 30.7% had minor asymptomatic complications, and 3 patients had major complications. Pre-PRB haemoglobin (Hb) <100 g/L was a risk factor for Hb decrease >10 g/L, and altered collagen-epinephrine (Col-Epi) time was a significant risk factor for overall complications. Mean sodium decrease was 0.6 ± 3 mmol/L. Hyponatraemia without neurological symptoms was diagnosed in two patients; no cardiovascular events occurred.

Conclusion

Hyponatraemia after single-dose DDAVP is rare. A single IV dose of desmopressin adjusted to the patient’s weight is safe as pre-PRB bleeding prophylaxis.
Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall
Authors: Ortega Miguel A , Fraile-Martínez Oscar , García-Montero Cielo , Ruiz-Grande Fernando , Barrena Silve , Montoya Hector , Pekarek Leonel , Zoullas Sofia , Alvarez-Mon Miguel A , Sainz Felipe , Asúnsolo Angel , Acero Julio , Álvarez-Mon Melchor , Buján Julia , García-Honduvilla Natalio , Guijarro Luis G
Published: September 2021

Objectives

Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue.

Methods

We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls.

Results

Our results demonstrate a significant increase in IRS-4 expression in VV tissue.

Conclusions

IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.
A novel GHR-ALK fusion gene in a patient with metastatic lung adenocarcinoma and its response to crizotinib: a case report
Authors: Pan Xue , Zhong Anyuan , Xing Yufei , Li Xi , Du Haiwei , Shi Minhua
Published: September 2021

Anaplastic lymphoma kinase ( ALK) rearrangement occurs in approximately 5% of non-small cell lung cancers (NSCLCS), and EML4-ALK is the most commonly observed ALK fusion variant in NSCLC. However, growth hormone receptor ( GHR) as the fusion partner for ALK and the clinical response to ALK tyrosine kinase inhibitors in patients with metastatic lung adenocarcinoma (LUAD) who carry the GHR-ALK variant have not been documented. This case describes a 63-year-old woman diagnosed with metastatic LUAD. Immunohistochemistry revealed positive ALK expression, and the patient was treated with crizotinib. After 3 weeks of treatment, the patient had a partial response. Because of treatment-related adverse events, the dose of crizotinib was reduced. After 3.7 months, computed tomography uncovered disease progression. Next-generation sequencing identified a novel GHR-ALK fusion in the plasma of the patient. The patient was treated again with crizotinib, but the disease progressed again 2 months later. Then, the patient received chemotherapy. She succumbed to her disease 11 months after the initial diagnosis. Our work provides evidence supporting the use of crizotinib in patients with metastatic LUAD harboring GHR-ALK.
Association of dyslipidemia with chronic non-malignant pain in elderly patients with femoral neck fractures treated by primary total hip arthroplasty: a retrospective study
Authors: Wang Chen , Xu Bo , Wang Pengfei , Yu Weiguang , Zeng Xianshang , Xiong Nana , Yin Pingping , Liu Qilong , Lin Huanyi
Published: September 2021

Objective

The association of chronic non-malignant pain (CNP) with dyslipidemia is unclear. This retrospective study was performed to evaluate the association between CNP and dyslipidemia in elderly patients with femoral neck fractures (FNFs) treated by primary unilateral total hip arthroplasty (THA).

Methods

We retrospectively identified 521 consecutive patients with FNFs (AO/OTA type 31B) who underwent primary unilateral THA from 2009 to 2021. The study population was divided into patients with and without CNP. Serum lipids were measured for each patient. The association between CNP and dyslipidemia was assessed using a multivariate binary logistic regression model.

Results

In total, 436 patients (220 with CNP, 216 without CNP) were eligible for analysis. In the quantile regression, the adverse effect of CNP was significantly attenuated by resilience in patients with a high high-density lipoprotein (HDL) concentration and low low-density lipoprotein (LDL) concentration. The multivariate binary logistic regression model showed that the HDL and LDL concentrations were the only variables significantly associated with the development of CNP.

Conclusion

Both a low HDL and high LDL concentration may result in the occurrence of CNP in elderly patients with FNFs treated by primary unilateral THA.