bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of acute type B aortic dissection
Authors: Munshi Bijit , Ritter Jens C. , Doyle Barry J. , Norman Paul E.
Published: September 2020

Background

The best management of acute uncomplicated type B aortic dissection is currently a controversial area. Recent advances in endovascular intervention have begun to establish pre‐emptive thoracic endovascular aortic repair as a potential strategy. A review about the management for type B aortic dissection has been conducted.

Methods

A narrative review consisting of 157 original articles, meta‐analyses and guidelines was conducted. The findings were synthesized and summarized using 70 articles.

Results

There are clear guidelines directing surgical management of acute complicated type B aortic dissection. However, the best management of acute uncomplicated disease is more ambiguous, which is especially concerning in a condition which is associated with significant morbidity and mortality. Medical management alone is generally favoured. Endovascular intervention is now being considered by some surgeons, but it can be technically difficult, while exposing the patient to potential surgical risks.

Conclusions

Clinical and anatomical risk factors have been identified to help vascular surgeons make decisions about treatment in acute uncomplicated type B aortic dissection. New endovascular strategies are being developed to reduce surgical risk and address technical challenges. Registry data should be used to support future best management.
Synthetic media for preservation of corneal tissues deemed for endothelial keratoplasty and endothelial cell culture
Authors: Parekh Mohit , Ruzza Alessandro , Gallon Paola , Ponzin Diego , Ahmad Sajjad , Ferrari Stefano
Published: September 2020

Purpose

To compare the difference between various endothelial graft preparation methods and endothelial cell culture from tissues that are preserved in serum‐based and synthetic medium.

Methods

In a randomized masked study, the tissues (n = 64) were preserved in Cornea Max (serum‐based) and Cornea Syn (synthetic) series for 36 days at their respective preservation conditions. Following organ culture, corneal tissues (n = 48) were used to prepareDescemet stripping automated endothelial keratoplasty (DSAEK), preloaded ultra‐thin (UT) ‐DSAEK, prestripped Descemet membrane endothelial keratoplasty (DMEK), free‐floating DMEK, and preloaded DMEK with endothelium inward and outward grafts. These tissues were preserved for another 4days at room temperature in dextran supplemented media following which they were subjected to trypan blue, alizarin red, live/dead and Zonula Occludens‐1 (ZO‐1) staining. A separate set of tissues (n = 16) from both the series was used for human corneal endothelial cell (HCEnC) culture. At confluence, the proliferation and cell doubling rate was calculated and the cultured cells were subjected to live/dead, ZO‐1, 2A12 and Ki‐67 staining. Mann–Whitney test was performed with p < 0.05 deemed statistically significant.

Results

After preparation and preservation of the tissues for endothelial keratoplasty, alizarin red showed standard endothelial morphology from both the groups. Endothelial cell loss, hexagonality and uncovered areas did not show statistically significant differences (p > 0.05) between both groups. For HCEnC, cell doubling rate was 4.7 days (p > 0.05). All the antibodies were expressed in both the groups. Hexagonality, polymorphism, cell area, viable/dead cells and Ki‐67 positivity were not statistically significant (p > 0.05).

Conclusions

Complete synthetic organ culture series is safe and advantageous for carrying out advanced endothelial keratoplasty graft preparation procedures and for HCEnC culture as it is free from animal or animal‐derived products.
Résilience d'une méta‐organisation : Le cas d'un commun de l'alimentation
Authors: Lapoutte Alexandrine
Published: September 2020

Meta‐organization is a recent concept that draws attention of management academics. It allows to renew the private‐public partnership approach. There is still little research on meta‐organizations as contributing to sustainable development (Berkowitz and Bor, 2018) as well as to their resources, including mechanisms supporting resilience (Berkowitz, 2018). This paper focuses on the absorptive or resilience capacity of a meta‐organization in the field of sustainable food. Food governance on territories has become a major issue over the past few years. The issue is recently taken in charge by collectives bringing together public and private partners, generally civil society, around food perceived as a common. The study is qualitative and based on the case of a local food policy council in France. Refering to resilience theory (Weick, 1993) and adopting a grounded theory methodology, we identify the characteristics of meta‐organizational resilience. We then discuss the relationship between the resilience of a meta‐organization and social transformation and contribute to the knowledge of policy‐shaper meta‐organizations. Finally, in this case we show how the social and solidarity economy (SSE) and the public authorities meet around a food common, making meta‐organization an expression of institutional diversity in the deployment of the commons.
Comparison of the accuracy of implant position for two‐implants supported fixed dental prosthesis using static and dynamic computer‐assisted implant surgery: A randomized controlled clinical trial
Authors: Yimarj Paweena , Subbalekha Keskanya , Dhanesuan Kanit , Siriwatana Kiti , Mattheos Nikos , Pimkhaokham Atiphan
Published: September 2020

Background

Computer‐assisted implant surgery (CAIS) can facilitate accuracy of single implant placement, but little is known with regards to parallelism between multiple implants.

Purpose

To compare the accuracy of position and parallelism of two implants, using static and dynamic CAIS systems.

Materials and methods

Thirty patients received two implants (60 implants) randomly allocated to two different CAIS systems. Optimal implant position and absolute parallelism was planned based on preoperative cone beam CT (CBCT). Patients received implants with a surgical guide (static CAIS, n = 30) or real‐time navigation (dynamic CAIS, n = 30). Implant three‐dimensional deviation and parallelism was calculated after surgery.

Results

The mean 3D deviation in the static and dynamic CAIS group at implant platform were 1.04 ± 0.67 vs 1.24 ± 0.39 mm, at apex were 1.54 ± 0.79 vs 1.58 ± 0.56 mm and angulation were 4.08° ± 1.69° vs 3.78° ± 1.84°, respectively. The angle deviations between two placed implants (parallelism) in static and dynamic CAIS groups were 4.32° ± 2.44° and 3.55° ± 2.29°, respectively. There were no statistically significant differences in all parameters between groups.

Conclusion

Static and dynamic CAIS provides similar accuracy of the 3D implant position and parallelism between two implants.
Relative influence of environmental factors and fishing on coral reef fish assemblages
Authors: McClure Eva C. , Hoey Andrew S. , Sievers Katie T. , Abesamis Rene A. , Russ Garry R.
Published: September 2020

Understanding whether assemblages of species respond more strongly to bottom‐up (availability of trophic resources or habitats) or top‐down (predation pressure) processes is important for effective management of resources and ecosystems. We determined the relative influence of environmental factors and predation by humans in shaping the density, biomass, and species richness of 4 medium‐bodied (10–40 cm total length [TL]) coral reef fish groups targeted by fishers (mesopredators, planktivores, grazer and detritivores, and scrapers) and the density of 2 groups not targeted by fishers (invertivores, small fish ≤10 cm TL) in the central Philippines. Boosted regression trees were used to model the response of each fish group to 21 predictor variables: 13 habitat variables, 5 island variables, and 3 fishing variables (no‐take marine reserve [NTMR] presence or absence, NTMR size, and NTMR age). Targeted and nontargeted fish groups responded most strongly to habitat variables, then island variables. Fishing (NTMR) variables generally had less influence on fish groups. Of the habitat variables, live hard coral cover, structural complexity or habitat complexity index, and depth had the greatest effects on density, biomass, and species richness of targeted fish groups and on the density of nontargeted fishes. Of the island variables, proximity to the nearest river and island elevation had the most influence on fish groups. The NTMRs affected only fishes targeted by fishers; NTMR size positively correlated with density, biomass, and species richness of targeted fishes, particularly mesopredatory, and grazing and detritivorous fishes. Importantly, NTMRs as small as 15 ha positively affected medium‐bodied fishes. This finding provides reassurance for regions that have invested in small‐scale community‐managed NTMRs. However, management strategies that integrate sound coastal land‐use practices to conserve adjacent reef fish habitat, strategic NTMR placement, and establishment of larger NTMRs will be crucial for maintaining biodiversity and fisheries.
Prospective correlation of the radiological, surgical and pathological findings in patients undergoing cytoreductive surgery for colorectal peritoneal metastases: implications for the preoperative estimation of the peritoneal cancer index
Authors: Bhatt A. , Rousset P. , Benzerdjeb N. , Kammar P. , Mehta S. , Parikh L. , Goswami G. , Shaikh S. , Kepenekian V. , Passot G. , Glehen O.
Published: September 2020

Aim

The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications.

Method

From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres.

Results

All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate‐volume (sPCI 13–20) and high‐volume (sPCI > 20) disease than for low‐volume disease (sPCI 0–12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six.

Conclusion

The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate‐volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated.
Protection gaps and restoration opportunities for primary forests in Europe
Authors: Sabatini Francesco M. , Keeton William S. , Lindner Marcus , Svoboda Miroslav , Verkerk Pieter J. , Bauhus Jürgen , Bruelheide Helge , Burrascano Sabina , Debaive Nicolas , Duarte Inês , Garbarino Matteo , Grigoriadis Nikolaos , Lombardi Fabio , Mikoláš Martin , Meyer Peter , Motta Renzo , Mozgeris Gintautas , Nunes Leónia , Ódor Péter , Panayotov Momchil , Ruete Alejandro , Simovski Bojan , Stillhard Jonas , Svensson Johan , Szwagrzyk Jerzy , Tikkanen Olli‐Pekka , Vandekerkhove Kris , Volosyanchuk Roman , Vrska Tomas , Zlatanov Tzvetan , Kuemmerle Tobias
Published: September 2020

Aims

Primary forests are critical for forest biodiversity and provide key ecosystem services. In Europe, these forests are particularly scarce and it is unclear whether they are sufficiently protected. Here we aim to: (a) understand whether extant primary forests are representative of the range of naturally occurring forest types, (b) identify forest types which host enough primary forest under strict protection to meet conservation targets and (c) highlight areas where restoration is needed and feasible.

Location

Europe.

Methods

We combined a unique geodatabase of primary forests with maps of forest cover, potential natural vegetation, biogeographic regions and protected areas to quantify the proportion of extant primary forest across Europe's forest types and to identify gaps in protection. Using spatial predictions of primary forest locations to account for underreporting of primary forests, we then highlighted areas where restoration could complement protection.

Results

We found a substantial bias in primary forest distribution across forest types. Of the 54 forest types we assessed, six had no primary forest at all, and in two‐thirds of forest types, less than 1% of forest was primary. Even if generally protected, only ten forest types had more than half of their primary forests strictly protected. Protecting all documented primary forests requires expanding the protected area networks by 1,132 km2 (19,194 km2 when including also predicted primary forests). Encouragingly, large areas of non‐primary forest existed inside protected areas for most types, thus presenting restoration opportunities.

Main conclusion

Europe's primary forests are in a perilous state, as also acknowledged by EU's “Biodiversity Strategy for 2030.” Yet, there are considerable opportunities for ensuring better protection and restoring primary forest structure, composition and functioning, at least partially. We advocate integrated policy reforms that explicitly account for the irreplaceable nature of primary forests and ramp up protection and restoration efforts alike.
Industrial policy: Clarifying options through taxonomy and decision trees
Authors: Weiss John , Seric Adnan
Published: September 2020

Motivation

Industrial policy is on the government agenda in many countries at different stages of development. Despite an extensive academic literature, much of the discussion is too general to guide policy‐makers.

Purpose

The article reviews the taxonomies of industrial policy in the literature, highlights some of their limitations and offers a simple alternative based on constraints to industrial development. It applies this framework in the context of one low‐income country —Ethiopia—and suggests a problem‐tree approach to address the binding constraints to growth in particular sectors.

Methods

Case studies of Ethiopia’s garment, leather goods and cut‐flowers sectors are used as illustrations of the simple taxonomy proposed.

Conclusion

In low‐income countries, the key issues for industrial policy often relate to basic issues, such as the provision of adequate infrastructure and access to land, rather than to the choice of particular forms of incentive.

Policy Implications

By focusing on different markets, the simple taxonomy proposed could clarify government options in deciding how best to overcome critical constraints to competitiveness in a given sector.
Heparan sulfate proteoglycan‐mediated dynamin‐dependent transport of neural stem cell exosomes in an in vitro blood–brain barrier model
Authors: Joshi Bhagyashree S. , Zuhorn Inge S.
Published: September 2020

Drug delivery to the brain is greatly hampered by the presence of the blood–brain barrier (BBB) which tightly regulates the passage of molecules from blood to brain and vice versa. Nanocarriers, in which drugs can be encapsulated, can move across the blood–brain barrier (BBB) via the process of transcytosis, thus showing promise to improve drug delivery to the brain. Here, we demonstrate the use of natural nanovesicles, that is, exosomes, derived from C17.2 neural stem cells (NSCs) to efficiently carry a protein cargo across an in vitro BBB model consisting of human brain microvascular endothelial cells. We show that the exosomes are primarily taken up in brain endothelial cells via endocytosis, while heparan sulfate proteoglycans (HSPGs) act as receptors. Taken together, our data support the view that NSC exosomes may act as biological nanocarriers for efficient passage across the BBB. Nanomedicines that target HSPGs may improve their binding to brain endothelial cells and, possibly, show subsequent transcytosis across the BBB.
Dispersal ability predicts spatial genetic structure in native mammals persisting across an urbanization gradient
Authors: Richardson Jonathan L. , Michaelides Sozos , Combs Matthew , Djan Mihajla , Bisch Lianne , Barrett Kerry , Silveira Georgianna , Butler Justin , Aye Than Thar , Munshi‐South Jason , DiMatteo Michael , Brown Charles , McGreevy Thomas J.
Published: September 2020

As the rate of urbanization continues to increase globally, a growing body of research is emerging that investigates how urbanization shapes the movement—and consequent gene flow—of species in cities. Of particular interest are native species that persist in cities, either as small relict populations or as larger populations of synanthropic species that thrive alongside humans in new urban environments. In this study, we used genomic sequence data (SNPs) and spatially explicit individual‐based analyses to directly compare the genetic structure and patterns of gene flow in two small mammals with different dispersal abilities that occupy the same urbanized landscape to evaluate how mobility impacts genetic connectivity. We collected 215 white‐footed mice (Peromyscus leucopus) and 380 big brown bats (Eptesicus fuscus) across an urban‐to‐rural gradient within the Providence, Rhode Island (U.S.A.) metropolitan area (population =1,600,000 people). We found that mice and bats exhibit clear differences in their spatial genetic structure that are consistent with their dispersal abilities, with urbanization having a stronger effect on Peromyscus mice. There were sharp breaks in the genetic structure of mice within the Providence urban core, as well as reduced rates of migration and an increase in inbreeding with more urbanization. In contrast, bats showed very weak genetic structuring across the entire study area, suggesting a near‐panmictic gene pool likely due to the ability to disperse by flight. Genetic diversity remained stable for both species across the study region. Mice also exhibited a stronger reduction in gene flow between island and mainland populations than bats. This study represents one of the first to directly compare multiple species within the same urban‐to‐rural landscape gradient, an important gap to fill for urban ecology and evolution. Moreover, here we document the impacts of dispersal capacity on connectivity for native species that have persisted as the urban landscape matrix expands.
Evidence for a dominant‐negative mechanism in HARS1‐mediated peripheral neuropathy
Authors: Meyer‐Schuman Rebecca , Antonellis Anthony
Published: September 2020

The pathogenic mechanism of neuropathy‐associated aminoacyl‐tRNA synthetase (ARS) gene variants is poorly defined. Mullen et al. generate new models of pathogenic, dominant HARS1 mutations and show that they increase eIF2α phosphorylation and decrease protein translation in neurons. These results are consistent with a dominant‐negative mechanism of ARS‐mediated peripheral neuropathy.

Comment on: https://doi.org/10.1111/febs.15449
Disciplined discourses: The logic of appropriateness in discourses on organizational gender equality policies
Authors: Amstutz Nathalie , Nussbaumer Melanie , Vöhringer Hanna
Published: September 2020

Organizational gender equality policies must address critical issues in organizations, as well as challenge hierarchies and the unequal distribution of power and resources. At the same time, they are reliant on acceptance by organizations when developing an official course of action. On the basis of a neo‐institutional perspective, this study investigates how gender equality discourses are disciplined so that they fit organizational expectations by maintaining the rationality myth of the organization. The empirical analysis of four Swiss organizations demonstrates that, although they intend to reduce gender inequalities, their gender equality policies are shaped by a logic of appropriateness that leads to a continuous reproduction of heteronormativity within gender equality policies. This study thus contributes to the understanding of how the logic of appropriateness protects the heteronormative matrix in organizations by disciplining gender equality discourses.
Optimizing the management of patients with haemophilia A and inhibitors in the era of emicizumab: Recommendations from a German expert panel
Authors: Escuriola‐Ettingshausen Carmen , Auerswald Günter , Königs Christoph , Kurnik Karin , Scholz Ute , Klamroth Robert , Oldenburg Johannes
Published: September 2020

Standard treatment of haemophilia A is based on replacing the missing coagulation factor VIII (FVIII) to treat and prevent bleeding episodes. The most challenging complication of FVIII therapy is the development of neutralizing antibodies (inhibitors) that can render treatment ineffective. Eradication of the inhibitor through immune tolerance induction (ITI) remains the most effective strategy for managing these patients. Bypassing agents can be used to help restore haemostasis in inhibitor patients. Several novel agents have recently been developed, such as the FVIII mimetic agent emicizumab, which has been effective in reducing the annualized bleeding rate in haemophilia A patients with inhibitors. When coadministered with repetitive high doses of activated prothrombin complex concentrate (ie >100 U/kg/d for ≥24 hours), emicizumab was associated with thrombotic microangiopathy and thrombosis events. As a consequence the United Kingdom Haemophilia Centres Doctors' Organisation (UKHCDO) issued the first guidance on the treatment of bleeding episodes in patients receiving emicizumab. To build on and extend this work, a panel of German haemophilia specialists met to discuss the UK guidance, review current evidence and provide additional guidance for German healthcare professionals on how to optimize the management of patients with haemophilia A receiving emicizumab. Recommendations are provided on the use of bypassing and other agents to manage breakthrough bleeding, ITI in the emicizumab era, haemostatic support during surgery and issues relating to laboratory monitoring.
Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases
Authors: Baidya Falguni , Bohra Mariya , Datta Aishika , Sarmah Deepaneeta , Shah Birva , Jagtap Priya , Raut Swapnil , Sarkar Ankan , Singh Upasna , Kalia Kiran , Borah Anupom , Wang Xin , Dave Kunjan R. , Yavagal Dileep R. , Bhattacharya Pallab
Published: September 2020

Neurodegeneration is characterized by gradual onset and limited availability of specific biomarkers. Apart from various aetiologies such as infection, trauma, genetic mutation, the interaction between the immune system and CNS is widely associated with neuronal damage in neurodegenerative diseases. The immune system plays a distinct role in disease progression and cellular homeostasis. It induces cellular and humoral responses, and enables tissue repair, cellular healing and clearance of cellular detritus. Aberrant and chronic activation of the immune system can damage healthy neurons. The pro‐inflammatory mediators secreted by chief innate immune components, the complement system, microglia and inflammasome can augment cytotoxicity. Furthermore, these inflammatory mediators accelerate microglial activation resulting in progressive neuronal loss. Various animal studies have been carried out to unravel the complex pathology and ascertain biomarkers for these harmful diseases, but have had limited success. The present review will provide a thorough understanding of microglial activation, complement system and inflammasome generation, which lead the healthy brain towards neurodegeneration. In addition to this, possible targets of immune components to confer a strategic treatment regime for the alleviation of neuronal damage are also summarized.
Localization and distribution of nitric oxide synthase and other neuronal markers in the podia of Holothuria arguinensis
Authors: Marquet Nathalie , Canário Adelino V. M. , Power Deborah M.
Published: September 2020

The organization of the nervous system of the holothurian podia—the tentacles, papillae, and tube feet—is still poorly understood, which limits the development of functional studies. Knowledge of nitric oxide (NO) signaling in sea cucumbers is nonexistent, although it is known to play an important role in many essential biological functions, including neurotransmission, throughout the animal kingdom. The objective of this study was to characterize the holothurian podia in Holothuria arguinensis. To this end, we used classical histology, nitric oxide synthase (NOS) distribution, using NADPH‐diaphorase histochemistry and NOS immunostaining, and neuronal immunohistochemistry. Our results revealed an abundant distribution of NO in the nervous components of the holothurian podia, suggesting an important role for NO as a neuronal messenger in these structures. Nitrergic fibers were intensely labeled in the longitudinal nerve and the nerve plexus surrounding the stem, but were more weakly labeled in the mesothelium. NOS was also found in scattered cell bodies and abundant fibers in the podia terminal end (i.e., the discs in tentacles and tube feet, and the pointed conical structures in the papillae), with evident neuronal projections to the bud surface, especially in the tentacles. The podia terminal end was the most specialized area and was characterized by a specific nervous arrangement, consisting of a distinct nerve plate, rich in cells and fibers containing potential sensory cells staining positively for neuronal markers, which makes this the most likely candidate to be a chemosensory region and an important candidate for future exploration.
Maackiain dampens osteoclastogenesis via attenuating RANKL‐stimulated NF‐κB signalling pathway and NFATc1 activity
Authors: Liu Yuhao , Zeng Weizai , Ma Chao , Wang Ziyi , Wang Chao , Li Shaobin , He Wei , Zhang Qingwen , Xu Jiake , Zhou Chi
Published: September 2020

Osteolytic diseases are typified by over‐enhanced formation and resorbing function of osteoclasts and have a major impact on human health. Inhibition of osteoclastic differentiation and function is a key strategy for clinical therapy of osteolytic conditions. Maackiain is a natural compound extracted from Sophora flavescens, which has been applied to anti‐allergic and anti‐tumour treatments. The present results showed that Maackiain could restrain receptor activator of nuclear factor‐κB ligand (RANKL)‐stimulated osteoclast formation and hydroxyapatite resorption dose‐dependently, and interrupt the structures of F‐actin belts in the mature osteoclasts. It also repressed the expressions of osteoclast‐specific genes and proteins. Furthermore, Maackiain could inhibit RANKL‐stimulated NF‐κB and calcium signalling pathways, and dampen Nuclear factor of activated T cell cytoplasmic 1 activity, protein expression and translocation into the nucleus. These results revealed that Maackiain may have a potential therapeutic effect on osteoclast‐related disorders.
Empagliflozin reduces the senescence of cardiac stromal cells and improves cardiac function in a murine model of diabetes
Authors: Madonna Rosalinda , Doria Vanessa , Minnucci Ilaria , Pucci Angela , Pierdomenico Donato Sante , De Caterina Raffaele
Published: September 2020

The sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduces heart failure in diabetes, but underlying mechanisms remain elusive. We hypothesized that empagliflozin could counteract the senescence of cardiac stromal cells (CSC), the action of which limits cardiac damage and cardiac fibrosis in diabetic‐like conditions in vitro and in vivo. CSC were isolated from murine heart biopsies (n = 5) through cardiosphere (CSp) formation and incubated for 3 or 48 hours with 5.5 mmol/L normal glucose (NG), high glucose (12‐5 and 30.5 mmol/L, HG) or a hyperosmolar control of mannitol (HM) in the presence or absence of empagliflozin 100 nmol/L. The senescent CSC status was verified by β‐gal staining and expression of the pro‐survival marker Akt (pAkt) and the pro‐inflammatory marker p38 (p‐P38). The cardiac effects of empagliflozin were also studied in vivo by echocardiography and by histology in a murine model of streptozotocin (STZ)‐induced diabetes. Compared to NG, incubations with HG and HM significantly reduced the number of CSps, increased the β‐gal‐positive CSC and P‐p38, while decreasing pAkt, all reversed by empagliflozin (P < .01). Empagliflozin also reversed cardiac dysfunction, cardiac fibrosis and cell senescence in mice with (STZ)‐induced diabetes (P < .01). Empagliflozin counteracts the pro‐senescence effect of HG and of hyperosmolar stress on CSC, and improves cardiac function via decreasing cardiac fibrosis and senescence in diabetic mice, possibly through SGLT2 off‐target effects. These effects may explain empagliflozin unexpected benefits on cardiac function in diabetic patients.
Identification and validation of critical alternative splicing events and splicing factors in gastric cancer progression
Authors: Feng Haoran , Jin Zhijian , Liu Kun , Peng Yi , Jiang Songyao , Wang Changgang , Hu Jiele , Shen Xiaoyun , Qiu Weihua , Cheng Xi , Zhao Ren
Published: September 2020

Gene expression and alternative splicing (AS) interact in complex ways to regulate biological process which is associated with cancer development. Here, by integrated analysis of gene expression and AS events, we aimed to identify the hub AS events and splicing factors relevant in gastric cancer development (GC). RNA‐seq data, clinical data and AS events of 348 GC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in 53 GCs. By bioinformatics methods, we found that gene AS event‐ and gene expression‐mediated GC progression shared the same mechanisms, such as PI3K/AKT pathway, but the involved genes were different. Though expression of 17 hub AS events were confirmed in 53 GC tissues, only 10 AS events in seven genes were identified as critical candidates related to GC progression, notably the AS events (Exon Skip) in CLSTN1 and SEC16A. Expression of these AS events in GC correlated with activation of the PI3K/AKT pathway. Genes with AS events associated with clinical parameters and prognosis were different from the genes whose mRNA levels were related to clinical parameters and prognosis. Besides, we further revealed that QKI and NOVA1 were the crucial splicing factors regulating expression of AS events in GC, but not spliceosome genes. Our integrated analysis revealed hub AS events in GC development, which might be the potential therapeutic targets for GC.
Transdisciplinary Generalism: Naming the epistemology and philosophy of the generalist
Authors: Lynch Johanna M. , Dowrick Christopher , Meredith Pamela , McGregor Sue L. T. , van Driel Mieke
Published: September 2020

Background

Transdisciplinary research and generalist practice both face the task of integrating and discerning the value of knowledge across disciplinary and sectoral knowledge cultures. Transdisciplinarity and generalism also both offer philosophical and practical insights into the epistemology, ontology, axiology, and logic of seeing the ‘whole’. Although generalism is a skill that can be used in many settings from industry to education, the focus of this paper is the literature of the primary care setting (i.e., general practice or family medicine). Generalist philosophy and practice in the family medicine setting highly values whole person care that uses integrative and interpretive wisdom to include both biomedical and biographical forms of knowledge. Generalist researchers are often caught between reductionist (positivist) biomedical measures and social science (post‐positivist) constructivist theories of knowing. Neither of these approaches, even when juxtaposed in mixed‐methods research, approximate the complexity of the generalist clinical encounter. A theoretically robust research methodology is needed that acknowledges the complexity of interpreting these ways of knowing in research and clinical practice.

Methods

A conceptual review of literature to define the alignment between (a) the philosophy and practice of generalism in primary care and (b) both the practical (Zurich) and philosophical or methodological (Nicolescuian) schools of transdisciplinarity.

Results

The alignment between generalism and transdisciplinarity included their broad scope, relational process, complex knowledge management, humble attitude to knowing, and real‐world outcome focus.

Conclusion

The concurrence between these approaches to knowing is offered here as Transdisciplinary Generalism – a coherent epistemology for both primary care researchers and generalist clinicians to understand, enact, and research their own sophisticated craft of managing diverse forms of knowledge.
Rheological modeling and activation energy of Persian grape molasses
Authors: Tavakolipour Hamid , Mokhtarian Mohsen , Kalbasi‐Ashtari Ahmad
Published: September 2020

Study the rheological behavior, modeling and activation energy (Ea) of Persian grape molasses (PGM) at different conditions. The shear rate and shear stress of PGM were measured at 25, 45, and 65°C and Brix concentrations (BC) of 35, 50, and 76%. Next different statistical parameters and Sigma plot software were used to test the obtained data on six different rheological models. Then the Ea and consistency coefficient of PGM were calculated at different BC using exponential and power equations. PGM exhibited a shear‐thickening behavior (n > 1) at BC's of 35–76% between 25 and 65°C. It showed the best fitness (R2 = 1.00) with power law (Ostwald–de‐Waele) model. The exponential relationship for computing Ea had higher R2 (0.937) than those in power law relationship (0.876). When the BC in PGM increased from 35 to 50% and then from 50 to 76% both at 25°C, the Ea raised ~10 and >100%. Exponential relationships were more trustable to calculate the effects of BC on consistency coefficient and Ea of PGM than power law equations. There is a high potential to raise the empirical Ea by increasing the BC of PGM to 76% at low temperature and retard its degradation process significantly.

Practical Applications

Persian grape molasses (PGM) has high content of glucose and fructose, mineral, organic acid and bioactive compounds. The PGM with good nutritional components can be substituted instead of sugar in different food, and its rheological parameters will enhance the organoleptic (texture, color and flavor) properties of resulting products, considerably. On the other hand, rheological values of PGM will help us to solve numerous engineering calculations involved with this product when is produced in an industrial scale. Additionally, identifying rheological properties will help us to select and control processing equipment (such as mixing, dispersing, refining, spinning, concentration, and packaging), predict energy requirements, and evaluate sensory assessment of this product properly. Additionally, calculation of empirical activation energy could assist us to evaluate the degradation process of PGM and possibly predict its storage time at different brix concentrations and storage temperatures.
Changes in access to educational and healthcare services for individuals with intellectual and developmental disabilities during COVID‐19 restrictions
Authors: Jeste S. , Hyde C. , Distefano C. , Halladay A. , Ray S. , Porath M. , Wilson R. B. , Thurm A.
Published: September 2020

Background

COVID‐19 restrictions have significantly limited access to in‐person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals.

Methods

This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation.

Results

Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy‐four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele‐education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele‐education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home.

Conclusions

COVID‐19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.
Three‐dimensional neuron–astrocyte construction on matrigel enhances establishment of functional voltage‐gated sodium channels
Authors: Karahuseyinoglu Sercin , Sekerdag Emine , Aria Mohammad Mohammadi , Cetin Tas Yagmur , Nizamoglu Sedat , Solaroglu Ihsan , Gürsoy‐Özdemir Yasemin
Published: September 2020

This study aimed to investigate and compare cell growth manners and functional differences of primary cortical neurons cultured on either poly‐d‐lysine (PDL) and or Matrigel, to delineate the role of extracellular matrix on providing resemblance to in vivo cellular interactions in nervous tissue. Primary cortical neurons, obtained from embryonic day 15 mice pups, seeded either on PDL‐ or Matrigel‐coated culture ware were investigated by DIC/bright field and fluorescence/confocal microscopy for their morphology, 2D and 3D structure, and distribution patterns. Patch clamp, western blot, and RT‐PCR studies were performed to investigate neuronal firing thresholds and sodium channel subtypes Nav1.2 and Nav1.6 expression. Cortical neurons cultured on PDL coating possessed a 2D structure composed of a few numbers of branched and tortuous neurites that contacted with each other in one to one manner, however, neurons on Matrigel coating showed a more complicated dimensional network that depicted tight, linear axonal bundles forming a 3D interacted neuron–astrocyte construction. This difference in growth patterns also showed a significant alteration in neuronal firing threshold which was recorded between 80 < Iinj > 120 pA on PDL and 2 < Iinj > 160 pA on Matrigel. Neurons grown up on Matrigel showed increased levels of sodium channel protein expression of Nav1.2 and Nav1.6 compared to neurons on PDL. These results have demonstrated that a 3D interacted neuron–astrocyte construction on Matrigel enhances the development of Nav1.2 and Nav1.6 in vitro and decreases neuronal firing threshold by 40 times compared to conventional PDL, resembling in vivo neuronal networks and hence would be a better in vitro model of adult neurons.

image
Ultrastructural analysis of different skeletal cell types in mucopolysaccharidosis dogs at the onset of postnatal growth
Authors: Jiang Zhirui , Lau Yian Khai , Wu Meilun , Casal Margret L. , Smith Lachlan J.
Published: September 2020

The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Abnormal development of the vertebrae and long bones is a hallmark of skeletal disease in several MPS subtypes; however, the underlying cellular mechanisms remain poorly understood. The objective of this study was to conduct an ultrastructural examination of how lysosomal storage differentially affects major skeletal cell types in MPS I and VII using naturally occurring canine disease models. We showed that both bone and cartilage cells from MPS I and VII dog vertebrae exhibit significantly elevated storage from early in postnatal life, with storage generally greater in MPS VII than MPS I. Storage was most striking for vertebral osteocytes, occupying more than forty percent of cell area. Secondary to storage, dilation of the rough endoplasmic reticulum (ER), a marker of ER stress, was observed most markedly in MPS I epiphyseal chondrocytes. Significantly elevated immunostaining of light chain 3B (LC3B) in MPS VII epiphyseal chondrocytes suggested impaired autophagy, while significantly elevated apoptotic cell death in both MPS I and VII chondrocytes was also evident. The results of this study provide insights into how lysosomal storage differentially effects major skeletal cell types in MPS I and VII, and suggests a potential relationship between storage, ER stress, autophagy, and cell death in the pathogenesis of MPS skeletal defects.
Inhibition of microRNA‐149 protects against recurrent miscarriage through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway
Authors: Wang Peng , Chen Xu , Chang Ying , Wang Yanping , Xu Xinran , Guo Yuling , Cui Hongyan
Published: September 2020

Aim

Recently, microRNA‐149 (miR‐149) has been indicated to act as an oncogene or a tumor suppressor in various malignant tumors, while its inner mechanisms in recurrent miscarriage (RM) are still in infancy. Therein, this study intends to decode the mechanism of miR‐149 in RM.

Methods

miR‐149 and RUNX2 expression in the chorionic tissues of normal pregnant women and RM patients were first examined, and the correlation between miR‐149 and RUNX2 was analyzed. Subsequently, miR‐149 was upregulated in HTR‐8 cells or downregulated in BEWO cells, and then the changes in biological functions of trophoblasts in RM were detected. Furthermore, the expression of PTEN/Akt signaling pathway‐related factors in trophoblasts was detected by western blot analysis.

Results

miR‐149 expression was increased while RUNX2 expression was suppressed in RM patients, and miR‐149 was negatively correlated with RUNX2. Overexpressed miR‐149 induced cell apoptosis and inhibited cell activity, while reduced miR‐149 in trophoblasts contributed to opposite experimental results. Moreover, miR‐149 promoted the expression of PTEN and inhibited Akt phosphorylation by targeting RUNX2, thereby inhibiting trophoblast activity and promoting their apoptosis.

Conclusion

Our study demonstrates that miR‐149 knockdown halted the RM development through upregulating RUNX2 and activation of the PTEN/Akt signaling pathway.
Statistical profiling of oral cancer and the prediction of outcome
Authors: Wang Weilan , Adeoye John , Thomson Peter , Choi Siu‐Wai
Published: September 2020

Background

The global burden of oral squamous cell carcinoma (OSCC) remains formidable. Identifying factors predictive of aggressive tumour behaviour, disease progression and reduced survival time may assist in early identification of “high‐risk” patients and appropriately target combination cancer therapies.

Methods

A retrospective review of 467 OSCC patients treated over a 19‐year period facilitated detailed clinico‐pathological database analysis and determination of clinical outcome categories based upon time to progressive disease (loco‐regional tumour recurrence and/or distant metastasis), overall death and OSCC‐related death (death directly attributable to OSCC). Odds ratio (OR) and hazard ratio (HR) statistical measures were used to investigate relationships between patient demographics and clinico‐pathological tumour features with clinical outcome.

Results

Older age at presentation (P = .002) and a history of previous non–head and neck cancer (P = .010) increased the risk of overall death. OR for progressive disease development (P = .008) and OSCC‐related death (P = .019) was most significant for buccal tumours. HR confirmed advanced‐stage disease increased the risk of progressive disease (P < .001), overall death (P < .001) and OSCC‐related death (P < .001). Positive resection margins were associated with a higher risk of OSCC‐related death (P = .023). Significantly lower risks of progressive disease development (P = .002) and OSCC‐related death (P = .012) were seen in patients undergoing neck dissection, whilst combination chemoradiotherapy reduced HR for overall death (P < .001) and OSCC‐related death (P = .011).

Conclusion

Statistical profiling of OSCC clinico‐pathological data identifies significant influences on clinical outcome. This study adds evidence to the hypothesis that buccal SCC displays aggressive tumour behaviour and poor clinical outcome.
The effect of a progressive taxation scheme on the endogenous formation of jurisdictions
Authors: Oddou Remy
Published: September 2020

This paper analyzes the effect of a progressive taxation scheme on the segregative properties of the endogenous formation of jurisdictions. Households living in the same place form a jurisdiction which aims to produce a local public good and implement a redistribution policy by granting every household a demogrant of an amount determined by the jurisdiction. In every jurisdiction, production of local public services and the demogrant are financed with a local tax based upon the households wealth. Local wealth tax rates and the level of the demogrant are exogenously determined in every jurisdiction. Households are free to leave their jurisdiction for another jurisdiction that would provide them with their highest utility. We found that the existence of a demogrant seems to mitigate the segregative properties of endogenous jurisdiction formation, because the condition identified by Gravel and Thoron to ensure segregation of any stable jurisdiction structure remains necessary, but is no longer sufficient.
Criminal mobility, fugitives, and extradition rules
Authors: Crinó Rosario , Immordino Giovanni , Piccolo Salvatore
Published: September 2020

Two countries set their enforcement noncooperatively to deter native and foreign individuals from committing a crime in their territory. Crime is mobile, ex ante (migration) and ex post (fleeing), and criminals hiding abroad after committing a crime in a country must be extradited. When extradition is not too costly, countries overinvest in enforcement: insourcing foreign criminals is more costly than paying the extradition cost. When extradition is sufficiently costly, instead, significant enforcement may induce criminals to flee the country whose law they infringed on. The fear of paying the extradition cost enables the countries to coordinate on the efficient outcome.