bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of long-term athletic training on muscle morphology and tendon stiffness in preadolescence: association with jump performance
Authors: Pentidis Nikolaos , Mersmann Falk , Bohm Sebastian , Giannakou Erasmia , Aggelousis Nickos , Arampatzis Adamantios
Published: September 2020

Purpose

Evidence on training-induced muscle hypertrophy during preadolescence is limited and inconsistent. Possible associations of muscle strength and tendon stiffness with jumping performance are also not investigated. We investigated the thickness and pennation angle of the gastrocnemius medialis muscle (GM), as indicators for potential muscle hypertrophy in preadolescent athletes. Further, we examined the association of triceps surae muscle–tendon properties with jumping performance.

Methods

Eleven untrained children (9 years) and 21 similar-aged artistic gymnastic athletes participated in the study. Muscle thickness and pennation angle of the GM were measured at rest and muscle strength of the plantar flexors and Achilles tendon stiffness during maximum isometric contractions. Jumping height in squat (SJ) and countermovement jumps (CMJ) was examined using a force plate. We evaluated the influence of normalised muscle strength and tendon stiffness on jumping performance with a linear regression model.

Results

Muscle thickness and pennation angle did not differ significantly between athletes and non-athletes. In athletes, muscle strength was greater by 25% and jumping heights by 36% (SJ) and 43% (CMJ), but Achilles tendon stiffness did not differ between the two groups. The significant predictor for both jump heights was tendon stiffness in athletes and normalised muscle strength for the CMJ height in non-athletes.

Conclusion

Long-term artistic gymnastics training during preadolescence seems to be associated with increased muscle strength and jumping performance but not with training-induced muscle hypertrophy or altered tendon stiffness in the plantar flexors. Athletes benefit more from tendon stiffness and non-athletes more from muscle strength for increased jumping performance.
The diversity of neuronal phenotypes in rodent and human autonomic ganglia
Authors: Ernsberger Uwe , Deller Thomas , Rohrer Hermann
Published: September 2020

Selective sympathetic and parasympathetic pathways that act on target organs represent the terminal actors in the neurobiology of homeostasis and often become compromised during a range of neurodegenerative and traumatic disorders. Here, we delineate several neurotransmitter and neuromodulator phenotypes found in diverse parasympathetic and sympathetic ganglia in humans and rodent species. The comparative approach reveals evolutionarily conserved and non-conserved phenotypic marker constellations. A developmental analysis examining the acquisition of selected neurotransmitter properties has provided a detailed, but still incomplete, understanding of the origins of a set of noradrenergic and cholinergic sympathetic neuron populations, found in the cervical and trunk region. A corresponding analysis examining cholinergic and nitrergic parasympathetic neurons in the head, and a range of pelvic neuron populations, with noradrenergic, cholinergic, nitrergic, and mixed transmitter phenotypes, remains open. Of particular interest are the molecular mechanisms and nuclear processes that are responsible for the correlated expression of the various genes required to achieve the noradrenergic phenotype, the segregation of cholinergic locus gene expression, and the regulation of genes that are necessary to generate a nitrergic phenotype. Unraveling the neuron population-specific expression of adhesion molecules, which are involved in axonal outgrowth, pathway selection, and synaptic organization, will advance the study of target-selective autonomic pathway generation.
Open-label phase II study evaluating safety and efficacy of the non-steroidal farnesoid X receptor agonist PX-104 in non-alcoholic fatty liver disease
Authors: Traussnigg Stefan , Halilbasic Emina , Hofer Harald , Munda Petra , Stojakovic Tatjana , Fauler Günter , Kashofer Karl , Krssak Martin , Wolzt Michael , Trauner Michael
Published: September 2020

Background

The PX-104 is an oral non-steroidal agonist for the farnesoid X receptor (FXR), a key regulator of bile acid (BA), glucose and lipid homeostasis.

Aims and methods

This single center, proof of concept study evaluated the efficacy, safety and tolerability of PX-104 in non-diabetic NAFLD patients. 12 individuals were treated daily with 5 mg of PX-104 orally for 4 weeks. Serum liver enzymes, insulin sensitivity by clamp like index (CLIX) and hepatic fat by proton 1H‑MRS, MRI-PDFF and CAP were assessed. Hepatic energy metabolism and Kupffer cell function were evaluated by phosphorus 31P‑MRS and superparamagnetic iron oxide MRI (SPIO-MRI). Other readouts included serum lipids and markers of BA metabolism/signaling besides fecal microbiome and BA analysis.

Results

A significant decrease in ALT (p = 0.027; 1‑tailed) and GGT (p = 0.019) was observed, without changes in serum alkaline phosphatase or serum lipids. Insulin sensitivity improved in 92% of patients (p = 0.02). However, hepatic steatosis measured by PDFF-MRI, 1H‑MRS and CAP besides extended serum lipoprotein and BA profiles did not change. NADPH/γATP ratios at 31P‑MRS significantly decreased (p = 0.022) possibly reflecting reduced hepatic inflammatory stress, but SPIO-MRI remained unchanged. Reduced preponderance of Coriobacteriaceae (p = 0.036) correlated with a relative reduction of total fecal BAs. There were no serious adverse events but short intervals of cardiac arrhythmia recorded in 2 patients led to termination of the study.

Conclusion

The non-steroidal FXR agonist PX-104 improved insulin sensitivity and liver enzymes after 4 weeks of treatment in non-diabetic NAFLD patients. Changes in fecal BAs and gut microbiota deserve more extensive investigations.
Non-local Impacts on Eddy-Covariance Air–Lake $$\hbox {CO}_2$$ Fluxes
Authors: Esters Leonie , Rutgersson Anna , Nilsson Erik , Sahlée Erik
Published: September 2020

Inland freshwater bodies form the largest natural source of carbon to the atmosphere. To study this contribution to the atmospheric carbon cycle, eddy-covariance flux measurements at lake sites have become increasingly popular. The eddy-covariance method is derived for solely local processes from the surface (lake). Non-local processes, such as entrainment or advection, would add erroneous contributions to the eddy-covariance flux estimations. Here, we use four years of eddy-covariance measurements of carbon dioxide from Lake Erken, a freshwater lake in mid-Sweden. When the lake is covered with ice, unexpected lake fluxes were still observed. A statistical approach using only surface-layer data reveals that non-local processes produce these erroneous fluxes. The occurrence and strength of non-local processes depend on a combination of wind speed and distance between the instrumented tower and upwind shore (fetch), which we here define as the time over water. The greater the wind speed and the shorter the fetch, the higher the contribution of non-local processes to the eddy-covariance fluxes. A correction approach for the measured scalar fluxes due to the non-local processes is proposed and also applied to open-water time periods. The gas transfer velocity determined from the corrected fluxes is close to commonly used wind-speed based parametrizations.
Welsh Nationalism, Language and Students’ Trust in the UK Police
Authors: Machura Stefan , Almjnoni Salim , Vavrik Boris , Williams Einir
Published: September 2020

Where nationality, coupled to minority language, forms a key factor of identities, and there is a history of conflict, it may be difficult for the police to command trust. In north-west Wales, Welsh is the language of the majority. Against the background of historic experiences of exploitation, oppression, and perceived neglect by English authorities, many locals have a negative view of the UK police. But what characterises those who are most in opposition? A total of 283 students at Bangor University participated in a questionnaire study. Results show that students who prefer to communicate in Welsh rather than English are more likely to distrust the UK police. While there are deep rooted tensions based on national identity, the police may gain trust from different sources compensating the cultural divide. They include mass media reports and experiences with the police. Overall however, the results support the group position theory applied to relations between people identifying with different nations.
Prenatal diagnosis of 22q11.2 copy number abnormalities in fetuses via single nucleotide polymorphism array
Authors: Cai Meiying , Lin Na , Su Linjuan , Wu Xiaoqing , Xie Xiaorui , Li Ying , Lin Yuan , Huang Hailong , Xu Liangpu
Published: September 2020

The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.
Frege’s puzzle and the ex ante Pareto principle
Authors: Mahtani Anna
Published: September 2020

The ex ante Pareto principle has an intuitive pull, and it has been a principle of central importance since Harsanyi’s defence of utilitarianism (to be found in e.g. Harsanyi, Rational behaviour and bargaining equilibrium in games and social situations. CUP, Cambridge, 1977). The principle has been used to criticize and refine a range of positions in welfare economics, including egalitarianism and prioritarianism. But this principle faces a serious problem. I have argued elsewhere (Mahtani, J Philos 114(6):303-323 2017) that the concept of ex ante Pareto superiority is not well defined, because its application in a choice situation concerning a fixed population can depend on how the members of that population are designated. I show in this paper that in almost all cases of policy choice, there will be numerous sets of rival designators for the same fixed population. I explore two ways that we might complete the definition of ex ante Pareto superiority. I call these the ‘supervaluationist’ reading and the ‘subvaluationist’ reading. I reject the subvaluationist reading as uncharitable, and argue that the supervaluationist reading is the most promising interpretation of the ex ante Pareto principle. I end by exploring some of the implications of this principle for prioritarianism and egalitarianism.
From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?
Authors: Vitale Giovanni , Dicitore Alessandra , Barrea Luigi , Sbardella Emilia , Razzore Paola , Campione Severo , Faggiano Antongiulio , Colao Annamaria ,   on behalf of NIKE, Albertelli Manuela , Altieri Barbara , Bottiglieri Filomena , De Cicco Federica , Di Molfetta Sergio , Fanciulli Giuseppe , Feola Tiziana , Ferone Diego , Ferraù Francesco , Gallo Marco , Giannetta Elisa , Grillo Federica , Grossrubatscher Erika , Guadagno Elia , Guarnotta Valentina , Isidori Andrea M. , Lania Andrea , Lenzi Andrea , Calzo Fabio Lo , Malandrino Pasquale , Messina Erika , Modica Roberta , Muscogiuri Giovanna , Pes Luca , Pizza Genoveffa , Pofi Riccardo , Puliani Giulia , Rainone Carmen , Rizza Laura , Rubino Manila , Ruggieri Rosa Maria , Sesti Franz , Venneri Mary Anna , Zatelli Maria Chiara
Published: September 2020

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.
Computer modeling of some anti-breast cancer compounds
Authors: Abdulrahman Hadiza Lawal , Uzairu Adamu , Uba Sani
Published: September 2020

The research was aimed at exploring the biological activities of novel series of β-lactam derivatives against MCF-7 breast cancer cell lines via computer modeling such as quantitative structure-activity relationship (QSAR), designing new compounds and analyzing the drug likeliness of designed compounds. The QSAR model was highly robust as it also conforms to the least minimum requirement for QSAR model from the statistical assessments with a correlation coefficient squared (R2) of 0.8706, correlation coefficient adjusted squared (R2adj) of 0.8411, and cross-validation coefficient (Q2) of 0.7844. The external validation ofR2predwas calculated as 0.6083 for model 4. The model parameters (MATS5i and MATS1s) were used in designing new derivative compounds with higher potency against estrogen-positive breast cancer. The pharmacokinetics test on the restructured compounds revealed that all the compounds passed the drug likeness test and they could further proceed to clinical trials. These reveal a breakthrough in medicine, in the research for breast cancer drug with higher effectiveness against the MCF-7 cell line.
Demarcating cognition: the cognitive life sciences
Authors: Keijzer Fred
Published: September 2020

This paper criticizes the role of intuition-based ascriptions of cognition that are closely related to the ascription of mind. This practice hinders the explication of a clear and stable target domain for the cognitive sciences. To move forward, the proposal is to cut the notion of cognition free from such ascriptions and the intuition-based judgments that drive them. Instead, cognition is reinterpreted and developed as a scientific concept that is tied to a material domain of research. In this reading, cognition becomes a changeable theoretical concept that can and must be adapted to the findings within this target domain. Taking humans as the best-established existing example of the relevant material target domain, this central case is extended to include all living systems. To clarify what it is about living systems that warrants their role as cognitive target domain, the new concept of cobolism is introduced as a complement to metabolism. Cobolism refers to the systematic ways in which each living system encompasses structures, processes and external events that maintain the fundamental metabolic processes that constitute the core of each living system. Cobolism is perfectly general, applies to bacterial and human cases alike, and provides a general format to describe wildly different cognitive organizations. It provides a clear target for the cognitive sciences to work on, turning them into what we can call the cognitive life sciences.
“Big brother is watching you”: surveillance via technology undermines employees’ learning and voice behavior during digital transformation
Authors: Kensbock Julia M. , Stöckmann Christoph
Published: September 2020

In the digital age, the ability of organizations to create innovation is more important than ever before. By taking an employee perspective to digital transformation, we examine two important and inter-related cornerstones of organizational innovation—employees’ intrinsically motivated learning (i.e., their learning orientation) and employees’ willingness to speak up and raise constructive suggestions (i.e., their voice behavior). We conducted a survey study with 100 employees working in industries that are currently disrupted by digitization. Supporting the idea of self-determination theory, our findings show that digital transformation triggers employees to engage in an intrinsically motivated process during which they adopt a learning orientation, which consequently motivates them to express voice behavior. However, this beneficial process is counteracted by perceived surveillance via technology. When employees feel that digital transformation is accompanied by increased surveillance, they are less likely to adopt a learning orientation and therefore less likely to engage in voice behavior. Theoretical as well as practical implications are discussed.
Patient reported outcome measures concerning urinary incontinence after robot assisted radical prostatectomy: development and validation of an online prediction model using clinical parameters, lower urinary tract symptoms and surgical experience
Authors: Collette Eelco R. P. , Klaver Sjoerd O. , Lissenberg-Witte Birgit I. , van den Ouden Dies , van Moorselaar Reindert J. A. , Vis André N.
Published: September 2020

The prediction of post-prostatectomy incontinence (PPI) after robot-assisted radical prostatectomy (RARP) depends on multiple clinical, anatomical and surgical factors. There are only few risk formulas, tables or nomograms predicting PPI that may assist clinicians and their patients in adequate risk counseling on postoperative side-effects. Prospective data collection of 1814 patients who underwent RARP between 2009 and 2017 was done. Pre-operative parameters were age, body mass index (BMI), prostate volume, the American Society of Anesthesiologists (ASA) score, severity of Lower Urinary Tract Symptoms (LUTS), type of planned nerve-sparing surgery and surgical experience. The continence status was reported using Patient Reported Outcome Measurements (PROMs) using the validated pad-use questionnaire EPIC26. Continence was defined as either the use of zero pads or one safety pad. Multivariable logistic regression analysis was performed to identify predictors of PPI within one year after RARP. An online prediction tool was developed and validated. The median follow-up was 36 months (range 12–108). The response rate was high at 85.2%. A total of 85% (1537/1814) of patients was continent on follow-up. One-year continence rate was 80.1% (95% CI 78.3–81.9%) (1453/1814) and increased to 87.4% (95% CI 85.4–89.4%) after 5 years. On multivariable analysis, severity of LUTS (OR = 0.56 p = 0.004), higher age (OR = 0.73 p = 0.049), extend of nerve-sparing surgery (OR = 0.60 p = 0.001) and surgeon experience (OR = 1.48 p = 0.025) were significant independent predictors for PPI. The online prediction model performed well in predicting continence status with poor discrimination and good calibration. An intuitive online tool was developed to predict PPI after RARP that may assist clinicians and their patients in counseling of treatment.
Derivation and validation of the clinical prediction model for COVID-19
Authors: Foieni Fabrizio , Sala Girolamo , Mognarelli Jason Giuseppe , Suigo Giulia , Zampini Davide , Pistoia Matteo , Ciola Mariella , Ciampani Tommaso , Ultori Carolina , Ghiringhelli Paolo
Published: September 2020

The epidemic phase of Coronavirus disease 2019 (COVID-19) made the Worldwide health system struggle against a severe interstitial pneumonia requiring high-intensity care settings for respiratory failure. A rationalisation of resources and a specific treatment path were necessary. The study suggests a predictive model drawing on clinical data gathered by 119 consecutive patients with laboratory-confirmed COVID-19 admitted in Busto Arsizio hospital. We derived a score that identifies the risk of clinical evolution and in-hospital mortality clustering patients into four groups. The study outcomes have been compared across the derivation and validation samples. The prediction rule is based on eight simple patient characteristics that were independently associated with study outcomes. It is able to stratify COVID-19 patients into four severity classes, with in-hospital mortality rates of 0% in group 1, 6–12.5% in group 2, 7–20% in group 3 and 60–86% in group 4 across the derivation and validation sample. The prediction model derived in this study identifies COVID-19 patients with low risk of in-hospital mortality and ICU admission. The prediction model that the study presents identifies COVID-19 patients with low risk of in-hospital mortality and admission to ICU. Moreover, it establishes an intermediate portion of patients that should be treated accurately in order to avoid an unfavourable clinical evolution. A further validation of the model is important before its implementation as a decision-making tool to guide the initial management of patients.
The emerging roles of exosomal circRNAs in diseases
Authors: Guo X. , Tan W. , Wang C.
Published: September 2020

Exosomes, the nanoscale phospholipid bilayer vesicles, enriched in selected proteins, nucleic acids and lipids, which they participated in a variety of biological processes in the body, including physiology and pathology. CircRNAs (circular RNAs) are a class of single-stranded closed molecules with tissue development specific expression patterns that have crucial regulatory functions in various diseases. Non-coding RNAs (such as microRNAs and long non‑coding RNAs) in exosomes have also been shown to play an important regulatory role in humans. However, little research has focused on exosomal circRNAs. Recently, CircRNAs have been identified to be enriched and stably expressed in exosomes. In this review, we summarize the biogenesis and biological functions of exosomes and circRNA, and further revealed the potential role of exosome-derived circRNA in different diseases. Besides, we propose its use as a diagnostic marker and therapeutic punctuation for diseases, especially in cancer.
Pre-procedural image-guided versus non-image-guided ventricular tachycardia ablation—a review
Authors: Hendriks A. A. , Kis Z. , Glisic M. , Bramer W. M. , Szili-Torok T.
Published: September 2020

Background

Magnetic resonance imaging and computed tomography in patients with ventricular tachycardia (VT) after myocardial infarction (MI) helps to delineate scar from healthy tissue. Image-guided VT ablation has not yet been studied on a large scale.

Objective

The aim of the meta-analysis was to compare the long-term outcome of image-guided VT ablation with a conventional approach for VT after MI.

Methods

Eight electronic bibliographic databases were searched to identify all relevant studies from 2012 until 2018. The search for scientific literature was performed for studies that described the outcome of VT ablation in patients with an ischaemic substrate. The outcome of image-guided ablation was compared with the outcome of conventional ablations.

Results

Of the 2990 citations reviewed for eligibility, 38 articles—enrolling a total of 7748 patients—were included into the meta-analysis. Five articles included patients with image-guided ablation. VT-free survival was 82% [74–90] in the image-guided VT ablation versus 59% [54–64] in the conventional ablation group (p < 0.001) during a mean follow-up of 35 months. Overall survival was 94% [90–98] in the image-guided versus 82% [76–88] in the conventional VT ablation group (p < 0.001).

Conclusions

Image-guided VT ablation in ischaemic VT was associated with a significant benefit in VT-free and overall survival as compared with conventional VT ablation. Visualising myocardial scar facilitates substrate-guided ablation procedures, pre-procedurally and by integrating imaging during the procedure, and may consequently improve long-term outcome.
Comparing nutrient reference concentrations in Nordic countries with focus on lowland rivers
Authors: Skarbøvik Eva , Aroviita Jukka , Fölster Jens , Solheim Anne Lyche , Kyllmar Katarina , Rankinen Katri , Kronvang Brian
Published: September 2020

Reference conditions of water bodies are defined as the natural or minimal anthropogenically disturbed state. We compared the methods for determining total phosphorus and total nitrogen concentrations in rivers in Finland, Norway and Sweden as well as the established reference conditions and evaluated the possibility for transfer and harmonisation of methods. We found that both methods and values differed, especially for lowland rivers with a high proportion of agriculture in the catchment. Since Denmark has not yet set reference conditions for rivers, two of the Nordic methods were tested for Danish conditions. We conclude that some of the established methods are promising but that further development is required. We moreover argue that harmonisation of reference conditions is needed to obtain common benchmarks for assessing the impacts of current and future land use changes on water quality.
Sustained absorption of delamanid from lipid-based formulations as a path to reduced frequency of administration
Authors: Ramirez Gisela , Pham Anna C. , Clulow Andrew J. , Salim Malinda , Hawley Adrian , Boyd Ben J.
Published: September 2020

Delamanid is a poorly water-soluble drug currently being used for the treatment of tuberculosis. The high frequency of dosing leads to poor adherence for patients who live in lower economic and nomadic populations. Non-digestible self-assembling lipids as a formulation approach for poorly water-soluble drugs have previously been shown to extend the window of absorption through gastric retention. We hypothesise that this approach could lead to the reduction of dosing frequency for delamanid and thereby has potential to improve adherence. Formulations of delamanid were prepared in selachyl alcohol and phytantriol as non-digestible self-assembling lipid vehicles, and their behaviour was compared with reconstituted milk powder, as a digestible lipid-based formulation, and an aqueous suspension. The self-assembly of selachyl alcohol and phytantriol in aqueous media in the presence of delamanid was studied using small angle X-ray scattering and produced the inverse hexagonal (H2) and inverse bicontinuous cubic (V2) liquid crystal structures, respectively. The times at which maximum delamanid levels in plasma were observed (Tmax) after oral administration of the phytantriol, selachyl alcohol and reconstituted milk powder formulations of delamanid to rats were 27 ± 3, 20 ± 4 and 6.5 ± 1.0 h, respectively, compared with the aqueous suspension formulation with a Tmax of 3.4 ± 1 h, which confirms the hypothesis of an extended duration of absorption after administration in non-digestible self-assembling lipids. The digestion products of the triglycerides in the milk formulation increased the solubilisation of delamanid in the gastrointestinal tract, leading to an increase in exposure compared with the aqueous suspension formulation but did not significantly extend Tmax. Overall, the non-digestible nanostructured lipid formulations extended the duration of absorption of delamanid well beyond that from milk or suspension formulations.
Exploring perspectives on health professions education scholarship units from sub-Saharan Africa
Authors: Van Schalkwyk Susan , O’Brien Bridget C. , Van der Vleuten Cees , Wilkinson Tim J. , Meyer Ilse , Schmutz Anna M. S.
Published: September 2020

Introduction There has been a marked increase in institutional structures developed to support health professions education scholarship recently. These health professions education scholarship units (HPESUs) engage in a diverse range of activities. Previous work provided insight into factors that influence the functioning of such units, but data from European, Asian, Latin American, and African contexts was absent, potentially leading to a single world-view informing international standards for HPESUs. This aim of this study was to explore perspectives from sub-Saharan Africa (SSA) in response to this omission.

Methods Situated within an interpretivist paradigm, the research team conducted semi-structured interviews with nine HPESU leaders in SSA, exploring how participants experienced and understood the functioning of their units. Despite efforts to have representation from across the region, most participants were from South Africa. The researchers analysed data thematically using the theory of institutional logics as an analytical frame.

Results Several aspects of the HPESUs aligned with the previously identified logics of academic research, service and teaching; and of a cohesive education continuum. By contrast, leaders described financial sustainability as a more prominent logic than financial accountability.

Discussion The similarities identified in this study may reflect isomorphism—a process which sees institutions within a similar field becoming more alike, particularly as newer institutions seek to acquire legitimacy within that field. An important caveat, however, is that isomorphism tends to occur across similar institutional contexts, which was not the case in this study.
Prospects of Genetics and Epigenetics of Alcohol Use Disorder
Authors: Wedemeyer Friederike , Kaminski Jakob A. , Zillich Lea , Hall Alisha S. M. , Friedel Eva , Witt Stephanie H.
Published: September 2020

Purpose of Review

In this study, we illustrate recent findings regarding the genetics and epigenetics of alcohol use disorder (AUD). We further outline the future direction of genetic and epigenetic research in AUD.

Recent Findings

Recent genome- and epigenome-wide studies allow new insight into genetic and epigenetic variation associated with AUD. The largest EWAS of AUD so far/to date found evidence for altered glucocorticoid receptor regulation. Longitudinal studies provide insight into the dynamics of the disease. Analyses of postmortem brain tissue reveal the impact of chronic alcohol consumption on DNA methylation in the brain.

Genetic and environmental factors—mediated via epigenetic mechanisms—play an important role in AUD. Although knowledge of the biological underpinnings of AUD is still limited, ongoing research will ultimately lead to the development of biomarkers for disease classification, course of disease, and treatment response to support personalized medicine in the future.
Ricci curvature of random and empirical directed hypernetworks
Authors: Leal Wilmer , Eidi Marzieh , Jost Jürgen
Published: September 2020

Relationships in real systems are often not binary, but of a higher order, and therefore cannot be faithfully modelled by graphs, but rather need hypergraphs. In this work, we systematically develop formal tools for analyzing the geometry and the dynamics of hypergraphs. In particular, we show that Ricci curvature concepts, inspired by the corresponding notions of Forman and Ollivier for graphs, are powerful tools for probing the local geometry of hypergraphs. In fact, these two curvature concepts complement each other in the identification of specific connectivity motifs. In order to have a baseline model with which we can compare empirical data, we introduce a random model to generate directed hypergraphs and study properties such as degree of nodes and edge curvature, using numerical simulations. We can then see how our notions of curvature can be used to identify connectivity patterns in the metabolic network of E. coli that clearly deviate from those of our random model. Specifically, by applying hypergraph shuffling to this metabolic network we show that the changes in the wiring of a hypergraph can be detected by Forman Ricci and Ollivier Ricci curvatures.
Semilinear problems with right-hand sides singular at u = 0 which change sign
Authors: Casado-Díaz Juan , Murat François
Published: September 2020

The present paper is devoted to the study of the existence of a solution
u
for a quasilinear second order differential equation with homogeneous Dirichlet conditions, where the right-hand side tends to infinity at

u = 0

. The problem has been considered by several authors since the 70's. Mainly, nonnegative right-hand sides were considered and thus only nonnegative solutions were possible. Here we consider the case where the right-hand side can change sign but is non negative (finite or infinite) at

u = 0

, while no restriction on its growth at

u = 0

is assumed on its positive part. We show that there exists a nonnegative solution in a sense introduced in the paper; moreover, this solution is stable with respect to the right-hand side and is unique if the right-hand side is nonincreasing in
u
. We also show that if the right-hand side goes to infinity at zero faster than

1/ |u|

, then only nonnegative solutions are possible. We finally prove by means of the study of a one-dimensional example that nonnegative solutions and even many solutions which change sign can exist if the growth of the right-hand side is

1/ |u|^{\gamma }

with

0 < \gamma < 1

.
Certainty in Language Increases Consumer Engagement on Social Media
Authors: Pezzuti Todd , Leonhardt James M. , Warren Caleb
Published: September 2020

Brands regularly attempt to stimulate consumer engagement by posting messages on social media platforms (e.g., Facebook), but their messages are often ignored. How can managers write social media messages that engage consumers? The present research sheds light on how the language of brand messages influences consumer engagement. Text analyses of brand messages posted on Facebook and Twitter shows that brand messages that include words that express certainty (e.g., always, everything, forever) are associated with higher levels of consumer engagement (e.g., likes, comments, shares/retweets). The results of two controlled experiments demonstrate that messages expressing certainty increase engagement by influencing how consumers perceive brands. Specifically, expressing certainty makes brands seem more powerful, and perceptions of power exert a positive effect on engagement. In addition, the indirect effect of certainty on consumer engagement is stronger (weaker) among consumers with higher (lower) power distance beliefs. These results assist marketing managers by demonstrating how language influences consumer engagement on social media.
The Future of Penile Prosthetic Surgical Training Is Here: Design of a Hydrogel Model for Inflatable Penile Prosthetic Placement Using Modern Education Theory
Authors: Witthaus Michael W. , Saba Patrick , Melnyk Rachel , Ajay Divya , Ralph David , Van Renterghem Koenraad , Warren Gareth , Munarriz Ricardo , Ghazi Ahmed
Published: September 2020

Background

There is a significant need for a non-biohazardous, educational platform to equip and maintain the surgical skills required by urology trainees and low-volume implanters for inflatable penile prosthetic (IPP) placement.

Aim

To design and develop an anatomic, hydrogel-based simulation platform for training and evaluate IPP placement using modern education theory.

Methods

The backward design concept was used as a framework in the design and development of an IPP simulation platform. Steps included delineating requirements from a physicians’ perspective, translating requirements into engineering tasks (deliverables), developing a prototype, and pilot validation. Using a combination of 3-dimensional printing and hydrogel casting, a genitourinary tract model was constructed to replicate the appropriate steps of IPP placement guided by expert feedback. Full-immersion IPP simulations were performed through both infrapubic and penoscrotal approaches by 4 expert surgeons under operative conditions. Questionnaires evaluating the simulation’s realism, value as a training tool, and further recommendations were completed.

Outcomes

Using backward design educational pedagogy, a high-fidelity, full-procedural IPP simulation was fabricated and verified as an adequate educational tool for training and assessment.

Results

An expert consensus on the anatomic landmarks, steps and substeps, instruments, and errors to be included in the model was reached using a hierarchical task analysis and was successfully translated into a prototype hydrogel model. Experts performed all appropriate steps of IPP surgery and rated the simulation highly in terms of its realism and value as a training tool. On average, experts agreed that the model could function as a training tool, assessment tool, prerequisite for IPP accreditation, and requirement before live surgery. Experts stated they would have their trainees ideally complete an average of 1.75 models before live surgical training. All experts believed an operative checklist would be an ideal assessment tool.
Characterization of the Renin-Angiotensin System in Aged Cavernosal Tissue and its Role in Penile Fibrosis
Authors: Bragina Maiia E. , Costa-Fraga Fabiana , Sturny Mikaël , Ebadi Babak , Ruoccolo Rafael T. , Santos Robson A.S. , Fraga-Silva Rodrigo A. , Stergiopulos Nikolaos
Published: September 2020

Background

The renin-angiotensin system (RAS) plays an important role in erectile function. The RAS contains 2 major axes: one deleterious, composed of ACE-Ang II-AT1 receptor, and another protective, composed of ACE2-Ang-(1-7)-Mas receptor. While aging is a well-known cause for development of male sexual disorders, little is known about local regulation of the RAS in age-related erectile dysfunction (ED).

Aim

The present study aimed to assess regulation of the RAS in aging-associated ED rat model and evaluate possible options for disease management through pharmacological modulation of the RAS.

Methods

Penile tissues were harvested from 3-, 12-, and 24-month-old Wistar rats. Local expression of major RAS components and ED markers was measured by RT-PCR. Protein expression of RAS components was assessed by western blot. Collagen deposition was measured by Sirius Red and immunohistochemical staining. Evaluation of collagen content was also performed in penile sections of Mas-knockout mice by Sirius Red and Masson’s trichrome stainings. Finally, the effect of Ang-(1-7) pretreatment on TGF-β–induced myofibroblast activation was studied in primary cavernosal and immortalized fibroblasts.

Outcomes

Experimental results highlighted the essential role of the RAS in modulation of cavernosal fibrosis.

Results

The present study demonstrates local expression of angiotensinogen mRNA alongside with major RAS components, which suggests local autonomous functioning of the RAS within penile tissue. Gene expression analysis revealed strong positive correlation between ACE-Ang II-AT1 axis with markers for inflammation and fibrosis. While corpus cavernosum from 24-month-old rats was characterized by increased collagen deposition, protein expression of ACE, AT1, and Mas was shown to be upregulated in the penile tissue of this group. At the same time, penile sections from Mas-knockout mice (FVB/N background) were also shown to have increased collagen deposition. Finally, it was demonstrated that Ang-(1-7) treatment of primary cavernosal and immortalized fibroblasts was able to alleviate TGF-β–induced fibroblast-to-myofibroblast transition.

Clinical Translation

The present study suggests Ang-(1-7) treatment as a possible strategy for pharmacological management of fibrosis-associated ED in aging.

Strengths & Limitations

The link between the RAS and penile fibrosis, indicated by a holistic screening of different ED markers, was confirmed by in vivo and in vitro data. However, results, presented in the manuscript, need to be further reinforced by human data. Important to note, the main goal of the study was to characterize RAS regulation in aging condition rather than state any causal relationships.

Conclusion

Present study characterizes RAS regulation in aging-associated ED and indicates its important role in cavernosal fibrosis.
Patient characteristics and admitting vital signs associated with coronavirus disease 2019 (COVID-19)–related mortality among patients admitted with noncritical illness
Authors: Sands Kenneth E. , Wenzel Richard P. , McLean Laura E. , Korwek Kimberly M. , Roach Jonathon D. , Miller Karla M. , Poland Russell E. , Burgess L. Hayley , Jackson Edmund S. , Perlin Jonathan B.
Published: September 2020

Objective:

To determine risk factors for mortality among COVID-19 patients admitted to a system of community hospitals in the United States.

Design:

Retrospective analysis of patient data collected from the routine care of COVID-19 patients.

Setting:

System of >180 acute-care facilities in the United States.

Participants:

All admitted patients with positive identification of COVID-19 and a documented discharge as of May 12, 2020.

Methods:

Determination of demographic characteristics, vital signs at admission, patient comorbidities and recorded discharge disposition in this population to construct a logistic regression estimating the odds of mortality, particular for those patients characterized as not being critically ill at admission.

Results:

In total, 6,180 COVID-19+ patients were identified as of May 12, 2020. Most COVID-19+ patients (4,808, 77.8%) were admitted directly to a medical-surgical unit with no documented critical care or mechanical ventilation within 8 hours of admission. After adjusting for demographic characteristics, comorbidities, and vital signs at admission in this subgroup, the largest driver of the odds of mortality was patient age (OR, 1.07; 95% CI, 1.06–1.08; P < .001). Decreased oxygen saturation at admission was associated with increased odds of mortality (OR, 1.09; 95% CI, 1.06–1.12; P < .001) as was diabetes (OR, 1.57; 95% CI, 1.21–2.03; P < .001).

Conclusions:

The identification of factors observable at admission that are associated with mortality in COVID-19 patients who are initially admitted to non-critical care units may help care providers, hospital epidemiologists, and hospital safety experts better plan for the care of these patients.
A new era of social policy integration? Looking at the case of health, social care and housing
Authors: MCCALL VIKKI , HOYLE LOUISE , GUNASINGHE SAMINDA , O’CONNOR SIOBHAN
Published: September 2020

Service integration is a global trend aiming to create partnerships, cost-effectiveness and joined-up working across public and third sector services to support an ageing population. However, social policy research suggests that the policy making process behind integration and implementation is complex, contradictory and full of tension. This paper explores social policy integration at the ground-level of services in the health and housing sector within a new integrated model for housing for older people. The paper applies a critical Lipskian approach to show that housing can promote integration for both users and wider stakeholders. Front-line workers were central to service integration, often working to integration principles despite policy changes and uncertainty. Challenges of social policy integration include the gaps between policy and practice and the developing nature of interaction at the ground-level – most notably, the role of technology. Technology and digital health platforms could enhance service user and practitioner interactions at the ground-level. The paper calls for renewed focus on policy processes in relation to service integration and consideration of new forms of service user, practitioner and policy maker interaction.
Real-world data for health technology assessment for reimbursement decisions in Asia: current landscape and a way forward
Authors: Lou Jing , KC Sarin , Toh Kai Yee , Dabak Saudamini , Adler Amanda , Ahn Jeonghoon , Bayani Diana Beatriz S. , Chan Kelvin , Choiphel Dechen , Chua Brandon , Genuino Anne Julienne , Guerrero Anna Melissa , Kearney Brendon , Lin Lydia Wenxin , Liu Yuehua , Nakamura Ryota , Pearce Fiona , Prinja Shankar , Pwu Raoh-Fang , Shafie Asrul Akmal , Sui Binyan , Suwantika Auliya , Teerawattananon Yot , Tunis Sean , Wu Hui-Min , Zalcberg John , Zhao Kun , Isaranuwatchai Wanrudee , Wee Hwee-Lin
Published: September 2020

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.
Understanding Aging, Frailty, and Resilience in Ontario First Nations
Authors: Slater Morgan , Jacklin Kristen , Sutherland Roseanne , Jones Carmen , Blind Melissa , Warry Wayne , Valvasori Meghan , Walker Jennifer
Published: September 2020

Following Canadian estimates of frailty, academic researchers and the Chiefs of Ontario came together to create the first Ontario-wide profile of aging in First Nations people in Ontario. Using self-reported data from First Nations adults who participated in the Ontario First Nations Regional Health Survey Phase 2, we found that First Nations people in Ontario experience higher rates of frailty than the general Canadian population and early onset frailty appears to affect First Nations communities. This is important to consider as communities plan for health care needs of an aging population and is particularly relevant in the face of Covid-19, as we know severity is exacerbated by underlying health conditions.