bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady-like topology of the dynamical hydrogen bond network in supercooled water
Authors: Martelli Fausto 
Published: June 2022

Abstract
We investigate the link between topology of the hydrogen bond network (HBN) and large-scale density fluctuations in water from ambient conditions to the glassy state. We observe a transition from a temperature-dependent topology at high temperatures, to a steady-like topology below the Widom temperature TW ∼ 220 K signaling the fragile-to-strong crossover and the maximum in structural fluctuations. As a consequence of the steady topology, the network suppresses large-scale density fluctuations much more efficiently than at higher temperatures. Below TW, the contribution of coordination defects of the kind A2D1 (two acceptors and one donor) to the kinetics of the HBN becomes progressively more pronounced, suggesting that A2D1 configurations may represent the main source of dynamical heterogeneities. Below the vitrification temperature, the freezing of rotational and translational degrees of freedom allow for an enhanced suppression of large-scale density fluctuations and the sample reaches the edges of nearly hyperuniformity. The formed network still hosts coordination defects, hence implying that nearly hyperuniformity goes beyond the classical continuous random network paradigm of tetrahedral networks and can emerge in scenarios much more complex than previously assumed. Our results unveil a hitherto undisclosed link between network topology and properties of water essential for better understanding water’s rich and complex nature. Beyond implications for water, our findings pave the way to a better understanding of the physics of supercooled liquids and disordered hyperuniform networks at large.
The role of YAP1 target gene CTGF in the anoikis resistance of rheumatoid arthritis synovial fibroblasts
Authors: Janczi Tomasz , Fehrl Yuliya , Kinne Raimund W , Böhm Beate , Burkhardt Harald 
Published: June 2022

Abstract

Objective
To analyse pro-survival mechanisms elicited in RA synovial fibroblasts (RASFs) upon detachment from their extracellular matrix dependent on the disintegrin metalloproteinase ADAM15 and Yes-associated protein kinase 1 (YAP1).

Methods
Detachment-induced apoptosis was determined by caspase 3/7 assays. Immunofluorescent stainings, cell surface biotinylation and immunoblotting were applied to analyse phosphorylated kinases and subcellular localization of YAP1 and connective tissue growth factor (CTGF). Caspase and transwell transmigration assays served to study CTGF function.

Results
Silencing of ADAM15 or YAP1 in RASFs leads to significantly increased levels of detachment-induced caspase activity. In non-silenced RASFs detachment causes simultaneous ADAM15-enhanced phosphorylation of YAP1 at S127, known for promoting its cytoplasmic localization, and Src-dependent phosphorylation at tyrosine Y357. The majority of nuclear YAP1 leaves the nucleus shortly after cell detachment, but prolonged detachment causes a marked nuclear re-entry of YAP1, resulting in significantly increased synthesis of CTGF. The newly synthesized CTGF, however, is not detectable in the supernatant, but is bound to the outside of the plasma membrane. In vitro studies demonstrated autocrine binding of CTGF to the EGF receptor and β1 integrin, with concomitant triggering of survival kinases, AKT1, ERK1/2, Src and focal adhesion kinase. Functional studies revealed anti-apoptotic effects of CTGF on detached RASFs and an enhancement of their potential for endothelial transmigration using HUVEC-coated transwells.

Conclusion
The elucidation of a new molecular mechanism that protects RASFs in the highly pro-apoptotic environment of inflamed RA joints by promoting anoikis-resistance and transendothelial migration via ADAM15/YAP1-mediated CTGF upregulation uncovers potentially new targets for future therapeutic intervention.
Controversies in rheumatology: maintenance therapy with low-dose glucocorticoids in rheumatoid arthritis
Authors: Buttgereit Frank , Kvien Tore K 
Published: June 2022

Abstract
Since the beginning of the use of glucocorticoids in clinical medicine, the risk–benefit ratio of these still very important drugs has been debated. There is no doubt that they produce many desirable therapeutic effects quickly and reliably. However, their potential to cause adverse effects, especially with prolonged use in high doses, limits their applicability. We discuss the arguments against and in favour of maintenance therapy with low-dose glucocorticoids in patients with RA, and present recent studies, assessments and conclusions on this question.
Clinico–pathological phenotypes of systemic sclerosis–associated myopathy: analysis of a large multicentre cohort
Authors: Matas-García Ana , Guillén-Del-Castillo Alfredo , Kisluk Boris , Selva-O'Callaghan Albert , Espinosa Gerard , Prieto-González Sergio , Moreno Lozano Pedro , Garrabou Glòria , Grau-Junyent Josep María , Simeon-Aznar Carmen Pilar , Milisenda José C 
Published: June 2022

Abstract

Objective
The objective of this study was to analyse the clinico–serological and histological phenotypes of patients with SSc with associated myopathy.

Methods
From November 2002 to September 2020, 52 patients with SSc underwent a muscle biopsy for suspected myopathy. We established two subgroups according to the histological findings based on the presence of isolated fibrosis or fibrosis together with significant inflammation. These patterns were designated as fibrosing and inflammatory, respectively. Clinical data, antibody profile, electrophysiologic studies, muscle biopsy findings and data regarding treatment, mortality and survival were compared between the two groups.

Results
Fourteen biopsies had a fibrosing pattern, whereas 26 showed an inflammatory pattern that could be classified (according to the predominant pattern) into DM (n = 7), necrotizing myopathy (n = 4) and non-specific myositis (n = 15). Additionally, 12 muscle biopsies were reported as neurogenic atrophy (n = 2), or normal muscle or minimal changes (n = 10). Compared with the inflammatory group, SSc patients with the fibrosing pattern presented a higher prevalence of ischaemic heart disease (38.5% vs 3.8%, P = 0.011), conduction abnormalities or arrhythmias (61.5% vs 26.9%, P = 0.036), anti-topo I antibodies (42.9% vs 11.5%, P = 0.044), greater median ESR (53.5 mm/h vs 32.5 mm/h, P = 0.013), with poor response to treatment and a higher mortality (42.9% vs 3.8%, P = 0.004) and lower cumulative survival (P = 0.035).

Conclusions
Patients with SSc-associated myopathy require a comprehensive approach that encompasses clinical, serological and histopathological aspects, given their outcome predictive capacity. At least two different phenotypes can be drawn, considering clinico–pathological features. Significant differences are delineated between both a fibrotic and an inflammatory phenotype.
Recoding Amino Acids to a Reduced Alphabet may Increase or Decrease Phylogenetic Accuracy
Authors: Foster Peter G , Schrempf Dominik , Szöllősi Gergely J , Williams Tom A , Cox Cymon J , Embley T Martin 
Published: June 2022

Abstract
Common molecular phylogenetic characteristics such as long branches and compositional heterogeneity can be problematic for phylogenetic reconstruction when using amino acid data. Recoding alignments to reduced alphabets before phylogenetic analysis has often been used both to explore and potentially decrease the effect of such problems. We tested the effectiveness of this strategy on topological accuracy using simulated data on four-taxon trees. We simulated alignments in phylogenetically challenging ways to test the phylogenetic accuracy of analyses using various recoding strategies together with commonly used homogeneous models. We tested three recoding methods based on amino acid exchangeability, and another recoding method based on lowering the compositional heterogeneity among alignment sequences as measured by the Chi-squared statistic. Our simulation results show that on trees with long branches where sequences approach saturation, accuracy was not greatly affected by exchangeability-based recodings, but Chi-squared-based recoding decreased accuracy. We then simulated sequences with different kinds of compositional heterogeneity over the tree. Recoding often increased accuracy on such alignments. Exchangeability-based recoding was rarely worse than not recoding, and often considerably better. Recoding based on lowering the Chi-squared value improved accuracy in some cases but not in others, suggesting that low compositional heterogeneity by itself is not sufficient to increase accuracy in the analysis of these alignments. We also simulated alignments using site-specific amino acid profiles, making sequences that had compositional heterogeneity over alignment sites. Exchangeability-based recoding coupled with site-homogeneous models had poor accuracy for these data sets but Chi-squared-based recoding on these alignments increased accuracy. We then simulated data sets that were compositionally both site- and tree-heterogeneous, like many real data sets. The effect on the accuracy of recoding such doubly problematic data sets varied widely, depending on the type of compositional tree heterogeneity and on the recoding scheme. Interestingly, analysis of unrecoded compositionally heterogeneous alignments with the NDCH or CAT models was generally more accurate than homogeneous analysis, whether recoded or not. Overall, our results suggest that making trees for recoded amino acid data sets can be useful, but they need to be interpreted cautiously as part of a more comprehensive analysis. The use of better-fitting models like NDCH and CAT, which directly account for the patterns in the data, may offer a more promising long-term solution for analyzing empirical data. [Compositional heterogeneity; models of evolution; phylogenetic methods; recoding amino acid data sets.]
Detection of schistosome infection in the invasive snail Melanoides tuberculata (Gastropoda: Thiaridae) by polymerase chain reaction from Plateau State, Nigeria: a novel turning point in disease epidemiology and control?
Authors: Adubi Taiwo Oluwakemi , Otubanjo Olubunmi Adetoro , Atalabi Tolulope Ebenezer 
Published: June 2022

Abstract

Background
Melanoides tuberculata is a freshwater snail that serves as an intermediate host for 11 parasitic flukes. This study was conducted with the aim of identifying and screening the snail intermediate hosts in the study site for schistosomiasis using the molecular technique.

Methods
DNA was extracted from the snails by the hexadecyl trimethyl ammonium bromide method and the Dra1 primer was used to amplify the Dra1 repeated sequence of Schistosoma haematobium.

Results
The presence of schistosome DNA in M. tuberculata by polymerase chain reaction was confirmed.

Conclusions
Our findings show that M. tuberculata is a potential intermediate host of schistosomes.
High phosphate‐induced progressive proximal tubular injury is associated with the activation of Stat3/Kim‐1 signaling pathway and macrophage recruitment
Authors: Richter Beatrice , Kapanadze Tamar , Weingärtner Nina , Walter Stefanie , Vogt Isabel , Grund Andrea , Schmitz Jessica , Bräsen Jan Hinrich , Limbourg Florian P. , Haffner Dieter , Leifheit‐Nestler Maren 
Published: June 2022

AbstractDietary phosphate intake in the Western population greatly exceeds the recommended dietary allowance and is linked to enhanced cardiovascular and all‐cause mortality. It is unclear whether a chronic high phosphate diet (HPD) causes kidney injury in healthy individuals. Here, we show that feeding a 2% HPD in C57BL/6N mice for one up to six months resulted in hyperphosphatemia, hyperphosphaturia, increased plasma levels of fibroblast growth factor (FGF) 23, and parathyroid hormone (PTH) compared to mice on a 0.8% phosphate diet. Kidney injury was already noted after two months of HPD characterized by loss of proximal tubular (PT) cell polarity, flattened epithelia, disruption of brush border membranes, vacuolization, increased PT cell proliferation, marked interstitial mononuclear infiltration, and progressive accumulation of collagen fibers. HPD increased Stat3 activation and Kim‐1 expression in PT epithelial cells and enhanced renal synthesis of chemokines recruiting monocytes and macrophages as well as macrophage related factors. Enhanced recruitment of F4/80+ macrophages around injured PT lesions was timely associated with increased Kim‐1 synthesis, tubular MCP‐1 expression, and degree of PT injury score. Likewise, tubulointerstitial fibrosis was associated with activation of Stat3/Kim‐1 signaling pathway. The stimulation of human proximal tubular cells with high phosphate activated Stat3 signaling and induced HAVCR1 and CCL2 expression. We conclude that high phosphate results in progressive proximal tubular injury, indicating that high dietary phosphate intake may affect kidney health and therefore represents an underestimated health problem for the general population.
A framework of the institutional policies and practice environments of nurse practitioner primary care models
Authors: Hogan Tory H. , Maurer Nicholas R. , Stevens Lena , Hefner Jennifer L. 
Published: June 2022

Purpose
The purpose of this article was to compare the implementation of distinct models of nurse practitioner (NP) integration into primary care offices.

Design/Methodology
A multiple case study design of three NP primary care practice models allowed for in-depth exploration of the management processes supporting the utilization of NPs. At each site, semistructured qualitative interviews, document review, and site tours/observations were conducted and subject to cross-case analysis guided by the NP Primary Care Organizational Framework (NP-PCOF)—developed for this study based on existing theory.

Results
Our case study sites represent three distinct NP primary care models. In the restricted practice model, NPs care for same-day/walk-in acute patients. NPs in the independent practice model have an independent panel of patients and interact collegially as independent coworkers. NPs in the comanagement model function on a team (a physician and two NPs), have a team office space, collectively care for a shared panel of patients, and can earn financial bonuses contingent upon meeting team quality metrics. Our cross-case analysis confirmed differences in physical space design, the relational structure of a workplace, and the capacity for innovation via NP compensation and performance metrics across different NP primary care models.

Conclusion
Our findings suggest that NP primary care models are supported by complex management systems and the NP-PCOF is a tool to help understand this complexity.

Implications
The NP-PCOF is a framework to understand the management systems that facilitate the utilization of NPs within primary care organizations.
Making do by getting real
Authors: Mitra Mahima , Dopson Sue , Hoff Timothy 
Published: June 2022

Background
Health care professionals face greater uncertainty in their careers as traditional jobs wither and new, organizationally controlled jobs proliferate, reducing economic security and professional autonomy.

Purpose
We apply psychological contract and self-efficacy theory to examine the career agency of early-career physicians. We ask the following: (a) What are the unfulfilled expectations and emotions experienced by young physicians at the training and early career stages? (b) What are the forms of career agency exhibited by young physicians in response to unfulfillment?

Methodology
We conducted a study on 48 U.K. early-career primary care physicians, known as general practitioners. The sample comprised both trainees as well as newly qualified physicians. Data were collected through in-depth interviews and focus group discussions.

Results
Physicians interpreted their early-career experiences based on predominantly ideological expectations around what it means to be a successful professional. However, the realities of practice resulted in highly emotional experiences of violation that were associated with a “reactive” agency and job behaviors that were more transactional and less relational.

Conclusion
This study identifies the expectations of early career professionals, which helps understand how and why psychological contract violations occur. It also expands the conceptualization of career agency from a positively framed aspect of professional behavior to one that includes haphazard and self-serving elements.

Practice Implications
Our study highlights several implications of the shifts in physician career agency for primary care practice. It discusses the potential effects of the purposeful self-interest among doctors on professional identity and power, as well as patient care.
The buffering effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants working in aged care facilities
Authors: Pariona-Cabrera Patricia , Meacham Hannah , Tham Tse Leng , Cavanagh Jillian , Halvorsen Beni , Holland Peter , Bartram Timothy 
Published: June 2022

Purpose
The purpose of this study was to examine the effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants (PCAs) working in aged care using the job demands–resources theory.

Methodology
Data were collected from 254 nurses and PCAs of the Australian Nursing Midwifery Federation located in Victoria, Australia. The study takes a quantitative approach and tests the hypotheses through regression analyses.

Findings
The results indicate that experiencing physical violence increases levels of stress, depression, and anxiety. This, in turn, increases nurses’ and PCAs’ intention to leave. However, increased psychological capital can assist nurses and PCAs in dealing with physical violence.

Research Implications
The study acknowledges that physical violence is a factor in nurses’ intention to leave. The significant finding is that psychological capital plays a protective role in ameliorating the negative impact of physical violence on individual well-being and intentions to leave. We note, however, that this is a cross-section study, and more longitudinal research needs to be undertaken.

Practical Implications
There are clear implications for managers to create a supportive organization that cultivates hope, self-efficacy, and resilience, thereby increasing psychological capital. Leadership development programs could build a supportive foundation for nurses to seek support and build resilience. Job construction should be focused on protecting nurses from risk by utilizing manageable workloads to limit stress, depression, and anxiety.

Originality
Our study extends research on retention of these skilled and important health care workers in a demanding environment that has largely been absent from the literature. Specifically, physical violence is often considered part of nursing work, but its impact on mental health, well-being, and intention to leave are underexplored in this sector, as well as the effectiveness of specific measures that bolster the negative impact of physical violence on nurses.
Knowledge of COVID-19 among Brazilian health care professionals and associated factors
Authors: Bernardes João Marcos , Magalhães Daniela Mendes dos Santos , Alonso Melissa Spröesser , Gómez-Salgado Juan , Ruiz-Frutos Carlos , Romero Adolfo , Días Adriano 
Published: June 2022

Abstract
Health care professional's knowledge is essential to contain epidemics. This research aimed to evaluate the knowledge of Brazilian health care professionals regarding COVID-19 to analyze whether there is a difference in knowledge between professionals in Primary Health Care and those in other levels of care or not; and to identify factors associated with knowledge. This is a cross-sectional study, including 716 participants who answered an online questionnaire between April and May 2020. Descriptive statistics, difference tests between groups, and logistic regression models were used to analyze the data. The average knowledge score was 12.42 points (out of a possible total of 15). There was no significant difference between professionals in Primary Health Care and those in other levels of care. Knowledge was associated with age, profession, perception regarding media's information quality, and hours exposed to information on COVID-19. Participants showed adequate knowledge, despite some specific gaps. Continuing education actions should prioritize younger nonmedical professionals.
Dolutegravir plus rilpivirine: benefits beyond viral suppression
Authors: Troya Jesús , Dueñas Carlos , Irazola Idoia , de los Santos Ignacio , de la Fuente Sara , Gil Desiré , Hernández Cristina , Galindo María José , Gómez Julia , Delgado Elisabeth , Moreno-García Estela , Pousada Guillermo , Aldámiz Teresa , Iribarren Jose Antonio , Guerra José Manuel , Morán Miguel Ángel , Galera Carlos , De La Fuente Javier , Peláez Ana , Cervero Miguel , Garcinuño María , Montero Marta , Ceballos Francisco , Buzón Luis 
Published: June 2022

Abstract
Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.
A multicentric retrospective cohort study.
Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.
The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR –40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = –23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.
In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.