bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of axitinib regulating the pathological blood–brain barrier functional recovery for glioblastoma therapeutics
Authors: Zhang Fengtian , Wen Lijuan , Wang Kai , Huang Zhihua , Jin Xiangyu , Xiong Ruiwen , He Shiying , Hu Fuqiang
Published: December 2021

Aims

Dysfunction of the blood–brain barrier (BBB) is a prominent pathological feature of glioblastoma (GBM). Vascular endothelial growth factor (VEGF) is confirmed to be abnormally elevated in the pathogenesis of GBM, causing BBB pathological disruption, which further allows the leakage of neurotoxic blood‐derived molecules into the central nervous system (CNS), interfering brain homeostasis and leading to poor patient outcome. Since BBB is an integral and pivotal part of the brain microenvironment, which strongly supports the occurrence and the pathological progression of GBM, here we have selected the VEGFR antagonist axitinib as a BBB functional regulator and hypothesized to regulate pathological BBB restoration for GBM effective treatment.

Methods

The pathological BBB cell model was constructed to investigate the timeliness and dose effect of axitinib regulating pathological BBB restoration. In order to investigate the efficacy and safety of axitinib regulating pathological BBB restoration for anti‐GBM treatment, the orthotropic GBM‐bearing mice model was established for in vivo study, and bioluminescent imaging was used to real‐time and noninvasively monitor tumor growth response in vivo, and survival time was also recorded.

Results

Axitinib under non‐cytotoxic dosage regulated pathological BBB restoration in a time‐dependent mode, and multiple intervention of axitinib could realize a visible restoration of pathological BBB in vitro. Moreover, axitinib treatment restored pathological BBB in orthotropic GBM‐bearing mice. We further confirmed that functional restoration of pathological BBB with axitinib had certain curative effect in prolonging median survival of orthotropic GBM‐bearing mice at non‐cytotoxic dosages in vivo.

Conclusion

The mechanism of axitinib involved in BBB functional regulation in the treatment of GBM is first illuminated in this report; moreover, this is the first report first referring to regulating pathological BBB functional recovery for GBM effective therapeutics. Overall, the view of regulating pathological BBB functional recovery may offer a novel sight for other CNS diseases relating to BBB permeability effective therapeutics.
Primary cutaneous extraskeletal osteosarcoma of the pretibial leg: A case report and summary of the literature
Authors: Jerew Katherine S. , Mehregan Darius R.
Published: December 2021

Primary cutaneous extraskeletal osteosarcoma is a rare tumor, with fewer than 30 known cases worldwide. We report the case of a 60‐year‐old female who presented with a solitary right pretibial nodule of 3 mm. She had no known comorbidities, trauma to the area, or prior malignancy. The biopsy specimen showed abundant mineralized osteoid, in which pleomorphic and spindled cells with anaplastic features were embedded. The osteoid matrix in this case contained overtly malignant cells, with frequent mitotic figures, as well as multinucleated giant cells. Immunohistochemistry and imaging led to the conclusion that this nodule represented a primary cutaneous extraskeletal osteosarcoma. The previously reported cases are variable in location, size, gross appearance, and clinical course. The prognosis of osteosarcoma is typically poor, with aggressive behavior; this, however, may be less severe in these strictly cutaneous tumors, though additional follow‐up would be beneficial to determine long‐term outcomes for the known cases. Ultimately, despite the fact that this is an extremely rare entity, primary cutaneous extraskeletal osteosarcomas should be considered when relevant.
Toward a better understanding of transition from paediatric to adult care in type 1 diabetes: A qualitative study of adolescents
Authors: Ladd Jennifer M. , Reeves‐Latour Jonathan , Dasgupta Kaberi , Bell Lorraine E , Anjachak Nadia , Nakhla Meranda
Published: December 2021

Aims

Type 1 diabetes is associated with significant morbidity, with an increasing risk of acute diabetes‐related complications in adolescence and emerging adulthood. Purposeful transition from paediatric to adult‐oriented care could mitigate this risk but is often lacking. Detailed understanding of the perspectives of adolescents in their final year of paediatric care is essential to inform delivery of transition care programs.

Methods

We conducted semi‐structured interviews with adolescents (aged 17 years) with type 1 diabetes at an academic institution from April 2017 to May 2018. Participants were recruited through convenience sampling. Sixty‐one interviews were transcribed for analysis. Coding followed the principles of thematic analysis.

Results

Thirty‐six percent of participants were male, and participants were from diverse socioeconomic backgrounds. We found three overarching themes in our analysis: first, difficulties navigating changing relationships with parents and healthcare teams; second, the need to increase type 1 diabetes self‐management and differing comfort levels based on age of diagnosis; and third, perceived responsibilities for transition care preparation (for both the paediatric team and adolescents themselves) focused not only on type 1 diabetes‐specific skills but also on healthcare system structures.

Conclusions

Our findings suggest that novel transition programs addressing changing inter‐personal relationships, disease‐specific self‐management (adapted for age of diagnosis), and healthcare system navigation, supported by parents and peers, may be needed to improve transition care for adolescents with type 1 diabetes.
Monetarist arithmetic at COVID‐19 time: A take on how not to misapply the quantity theory of money
Authors: Pinter Julien
Published: December 2021

The COVID‐19 crisis has revived an old heated debate on whether significant increases in the money supply ultimately lead to higher inflation. Some observers have alluded to the quantity theory of money for that purpose, though in our view, this has sometimes been in a misleading way. Against this background, this paper seeks to clarify several aspects of the quantity theory of money, which are useful to apply it fairly in the current world. First, we review the meaning of the velocity term in the quantity equation. We argue that it has no relevance as a behavioural concept: there is no such thing as a 'desired velocity'. Rather, income velocity should be seen as a variable deriving from a system of parameters and variables related to money demand, as the monetarist approach clearly puts it, with no intrinsic relevance. Second, we clarify the practical relevance that the quantity theory approach can bear in the 21st century. Third, we review the channels and assumptions underlying the asserted quantity theory link between money growth and inflation. In light of our analysis, we conclude that the high money growth rates seen since the pandemic outbreak are unlikely to translate into higher inflation rates.
Dietary abundance distributions: Dominance and diversity in vertebrate diets
Authors: Hutchinson Matthew C. , Dobson Andrew P. , Pringle Robert M.
Published: December 2021

Diet composition is among the most important yet least understood dimensions of animal ecology. Inspired by the study of species abundance distributions (SADs), we tested for generalities in the structure of vertebrate diets by characterising them as dietary abundance distributions (DADs). We compiled data on 1167 population‐level diets, representing >500 species from six vertebrate classes, spanning all continents and oceans. DADs near‐universally (92.5%) followed a hollow‐curve shape, with scant support for other plausible rank‐abundance‐distribution shapes. This strong generality is inherently related to, yet incompletely explained by, the SADs of available food taxa. By quantifying dietary generalisation as the half‐saturation point of the cumulative distribution of dietary abundance (sp50, minimum number of foods required to account for 50% of diet), we found that vertebrate populations are surprisingly specialised: in most populations, fewer than three foods accounted for at least half the diet. Variation insp50was strongly associated with consumer type, with carnivores being more specialised than herbivores or omnivores. Other methodological (sampling method and effort, taxonomic resolution), biological (body mass, frugivory) and biogeographic (latitude) factors influencedsp50to varying degrees. Future challenges include identifying the mechanisms underpinning the hollow‐curve DAD, its generality beyond vertebrates, and the biological determinants of dietary generalisation.
Financing and governing ecological restoration projects: The Tasmanian Island Ark
Authors: Richardson Benjamin J. , Davidson Neil J.
Published: December 2021

This article examines the financial and governance dimensions of the Tasmanian Island Ark project, in the Tasmanian Midlands. It focuses on the intervention costs, funding sources and the legal context to financing, including property tenure, negotiated agreements and regulatory requirements. The case study shows that it is not easy to extrapolate financial data from one restoration project to another; however, the types of costs, their relative significance and timing, and legal context can be relevant considerations across diverse projects. The Tasmanian case study helps fill a gap in the literature about the financial side of ecological restoration projects and how planners can prepare for large landscape‐scale interventions. The paper discusses the overarching constraints on environmental restoration practices and then presents the specific costs of restoration activities.
The role of open woodland in mitigating microclimatic extremes in agricultural landscapes
Authors: Baker Thomas P. , Marais Zara E. , Davidson Neil J. , Worledge Dale , Mendham Daniel S.
Published: December 2021

The retention of native woodland remnants in agricultural landscapes provides a range of benefits, many of which are linked to the ameliorative effects of trees on local microclimatic conditions. We monitored the reduction in wind speed and extreme temperatures that occurred in and around two native eucalypt woodland remnants in the Tasmanian Midlands and discuss the role of woodland remnants in providing both agricultural and environmental benefits. Monitoring wind speed, temperature and relative humidity every 30 min for over a year showed that an average wind speed reduction of 50% occurred within the woodland remnants as well as higher minimum temperatures by up to 0.5 C. The structural characteristics of the woodland remnants mediated the effects observed, with a 50% reduction in wind speed occurring when there was the equivalent of 20 large trees blocking the wind. This demonstrates that areas with low numbers of trees per hectare can have significant impacts on microclimatic conditions. The microclimatic changes observed will likely benefit agricultural productivity, farm aesthetics and ecological processes.
Tasmanian Midlands: A case study of increasing sophistication in conservation planning and action over four decades
Authors: Gilfedder Louise , Appleby Matt W. , Lechner Alex M. , Sprod Daniel , Carter Oberon , Burgess Sebastian , Davidson Neil J. , Harris Rowan
Published: December 2021

The conservation significance of the Tasmanian Midlands, an agricultural region that is largely privately owned and has suffered significant land degradation and loss of biodiversity, has been recognised since the 1980s. Four decades of conservation planning and implementation has seen the evolution of biodiversity protection, revegetation, bush rehabilitation and climate‐ready habitat restoration. Relationships and trust have been built enabling the development of capacity in the farming community and conservation sector. This paper presents for the first time the chronology of four decades of landscape conservation planning and implementation in the Tasmanian Midlands. Remnant protection, restoration and revegetation efforts have evolved from the site level to landscape scale, leading to a conservation approach incorporating ecological restoration in its broadest sense. Successive iterations saw key initiatives including Midlands Bushweb, Midlandscapes, the Midlands Conservation Fund and the Tasmanian Island Ark project. Spatial tools and models have grown from simple maps and aerial photos to early GIS products including farm plans (revolutionary in their day) and asset maps, to increasingly complex spatial models of corridors using least‐cost path analysis and fine‐scale multi‐species models of functional connectivity. However, critical to success in these challenging agricultural landscapes has been the relationships of trust and collaboration built between local farmers and conservation planners.
Restoring the Midlands of Tasmania: An introduction
Authors: Davidson Neil J. , Bailey Tanya G. , Burgess Sebastian
Published: December 2021

At the dawn of the Anthropocene, with the imminent threat of climate change delivering 3–4°C rise in temperature by the end of the century and biodiversity loss across the globe, restoration projects need to focus on re‐establishing connectivity in vegetation structure at a landscape scale to facilitate the movement of wildlife. To achieve this requires long‐term commitment, robust partnerships and planning and excellent planting technology underpinned by research. In this Special Issue, consisting of 15 papers, we present a multidisciplinary, multi‐institutional, science‐based approach to environmental restoration, focused on a single geographic region, the Midlands of Tasmania. This introductory paper describes the breadth of the material covered in the series and sets the scene for following papers by describing the Midlands, its geography, climate and history, its extraordinary natural values as a biodiversity hotspot, the degree of degradation that has resulted from 200 years of intensive farming and the objectives of the Midlands restoration project. The Midlands also offers opportunities as a model system for landscape scale restoration given it is a circumscribed region, heterogeneous in land forms and land uses. Furthermore, in land management, there is a high level of cooperation between land owners, government departments, environmental agencies and university researchers. We describe how the contributions from a wide range of disciplines can be focused to meet the challenges of ecological restoration in highly altered agricultural landscapes.
Accounting and accountability for the digital transformation of public services
Authors: Agostino Deborah , Bracci Enrico , Steccolini Ileana
Published: December 2021

This paper introduces the special issue on accounting and accountability for the digital transformation of public services. Papers in special issues offer different perspectives on how digital technologies affect performance management, considering the challenges and opportunities that arise when digital data are collected and translated into a set of measures, the complexity of relying on these digital data to enhance transparency and accountability, and the organizational implications of digital data when used to support public‐sector decision makers in a variety of activities, such as auditing or benchmarking.
Academic women and their children: Parenting during COVID‐19 and the impact on scholarly productivity
Authors: Bender Sara , Brown Kristina S. , Hensley Kasitz Deanna L. , Vega Olga
Published: December 2021

Objective

We explored the experiences of academic mothers traversing the simultaneous demands of parenting and their professional roles throughout the pandemic to better understand the impact of COVID‐19 on engagement in scholarship.

Background

In response to reports of reduced scholarship by women across academic disciplines, the goal of this study was to understand the lived experiences of women scholars who identify as mothers.

Method

Academic women, including faculty and students, completed an online survey with demographic items and open‐ended questions. From the collected data, responses from participants who identified as mothers (n = 51) were analyzed using thematic analysis.

Results

Analysis of the data revealed that participants' roles as parents and scholarly women were inextricably intertwined, each serving as foundational components of their identities, a reality highlighted by the exacerbating stressors associated with COVID‐19. Altered childcare demands, conflicting roles, and relational changes emerged as consequences of the ongoing pandemic, which compromised participants' ability to effectively attend to different aspects of their identity and sometimes resulted in the development of negative emotions.

Conclusion

Participants identified additional responsibilities due to the ongoing pandemic. Feeling pulled between their often‐conflicting personal and professional identities, academic mothers cited a lack of supportive professional structures, which became more evident during COVID‐19, as a barrier to their pursuit of scholarship.

Implications

This study aligned with previous scholarly documentation of historical gendered bias common within academia. The potential long‐term professional impact of these conflated circumstances on academic mothers during the pandemic is discussed, and implications and recommendations for addressing the same via future research are provided.
Nrf2 and oxidative stress in liver ischemia/reperfusion injury
Authors: G. Bardallo Raquel , Panisello‐Roselló Arnau , Sanchez‐Nuno Sergio , Alva Norma , Roselló‐Catafau Joan , Carbonell Teresa
Published: December 2021

In response to stress signal, nuclear factor‐erythroid 2‐related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1‐Nrf2 stability, transcriptional regulation (NF‐ĸB, ATF3, ATF4), and post‐transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia‐reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.
Extracellular secretagogin is internalized into the cells through endocytosis
Authors: Khandelwal Radhika , Sharma Anand Kumar , Biswa Bhim B. , Sharma Yogendra
Published: December 2021

Secretagogin (SCGN) is a calcium‐sensor protein with a regulatory role in glucose metabolism and the secretion of several peptide hormones. Many, but not all, functions of SCGN can be explained by its intracellular manifestation. Despite early data on SCGN secretion, the secretory mechanism, biological fate, physiological implications and trans‐cellular signalling of extracellular SCGN remain unknown. We here report that extracellular SCGN is readily internalized into the C2C12 cells in an energy‐dependent manner. Using endocytosis inhibitors, we demonstrate that SCGN internalizes via clathrin‐mediated endocytosis, following which, SCGN localizes largely in the cytosol. Exogenous SCGN treatment induces a global proteomic reprogramming in C2C12 cells. Gene ontology search suggests that SCGN‐induced proteomic reprogramming favours protein synthesis and cellular growth. We thus validated the cell proliferative action of SCGN using C2C12, HepG2 and NIH‐3T3 cell lines. Based on the data, we propose that circulatory SCGN is internalized into the target cells and modulates the expression of cell growth‐related proteins. The work suggests that extracellular SCGN is a functional protein, which communicates with specific cell types and directly modulates cell proliferation.
Blocking PSD95‐PDZ3's amyloidogenesis through point mutations that inhibit high‐temperature reversible oligomerization (RO)
Authors: Saotome Tomonori , Onchaiya Sawaros , Brindha Subbaian , Mezaki Taichi , Unzai Satoru , Noguchi Keiichi , Martinez Jose C. , Kidokoro Shun‐ichi , Kuroda Yutaka
Published: December 2021

The third PDZ domain of the postsynaptic density protein 95 (PSD95‐PDZ3; 11 kDa, 103 residues) has a propensity to form amyloid fibrils at high temperatures. At neutral pH, PDZ3 is natively folded, but it exhibits a peculiar three‐state thermal unfolding with a reversible oligomerization (RO) equilibrium at high temperatures, which is uncharacteristic in the unfolding of a small globular protein as PDZ3 is. Here, we examined the RO's role in PDZ3's amyloidogenesis at high‐temperature using two variants (F340A and L342A) that suppress the high‐temperature RO and five single‐alanine‐mutated variants, where we mutated surface‐exposed hydrophobic residues to alanine. Circular Dichroism (CD), Analytical Ultracentrifuge (AUC), and other spectroscopic measurements confirmed the retention of the native structure at ambient temperature. Differential Scanning Calorimetry (DSC) was used to assess the presence or absence of the high‐temperature RO, and the amyloidogenicity of the variants was measured by Thioflavin T (ThT) fluorescence and Transmission Electron Microscopy (TEM). By comparing the fraction of RO and the ThT signal, we found that mutations that suppressed the high‐temperature RO strongly inhibited amyloidogenesis. On the other hand, all variants forming RO also formed amyloids under the same conditions as the wild‐type PDZ3.
Bringing the state seal of biliteracy to higher education: A case for expansion
Authors: Monto Cecelia
Published: December 2021

State Seals of Biliteracy (SoBL) are a growing trend and present a promising method of serving an increasingly bilingual population. Currently, state SoBLs have been available almost exclusively at the high school level. An Oregon community college initiated the opportunity for students to study and receive the state SoBL in higher education. The expanded higher education option is important because many students miss the opportunity to receive the SoBL credential in high school. This article introduces background information, describes a model for bringing the state SoBL into higher education, presents preliminary findings, and recommends future work. The model could be replicated by other higher education institutions either wholly or in part to expand opportunities for this important state recognized credential and honor the assets of heritage language speakers. Although this article focuses on the SoBL in Spanish, the model could be tailored to the unique linguistic demographics in other regions.
Dynamic changes in antibiotic resistance genes and gut microbiota afterHelicobacter pylorieradication therapies
Authors: Wang Lingling , Yao Haobin , Tong Teresa , Lau KamShing , Leung Suet Yi , Ho Joshua W. K. , Leung Wai K.
Published: December 2021

Background

Short‐term antibiotics exposure is associated with alterations in microbiota and antibiotic resistance genes (ARGs) in the human gut. While antibiotics are critical in the successful eradication ofHelicobacter pylori, the short‐term and long‐term impacts on the composition and quantity of antibiotics resistance genes afterH. pylorieradication are unclear. This study used whole‐genome shotgun metagenomic of stool samples to characterize the gut microbiota and ARGs, before and afterH. pylorieradication therapy.

Results

Forty‐fourH. pylori‐infected patients were recruited, including 21 treatment naïve patients who received clarithromycin‐based triple therapy (CLA group) and 23 patients who failed previous therapies, in which 10 received levofloxacin‐based quadruple therapy (LEVO group) and 13 received other combinations (OTHER group). Stool samples were collected at baseline (before current treatment), 6 week and 6 month after eradication therapy. At baseline, there was only a slight difference among the three groups on ARGs and gut microbiota. After eradication therapy, there was a transient but significant increase in gut ARGs 6 week post‐therapy, among which the LEVO group had the most significant ARGs alteration compared to other two groups. For treatment naïve patients, those with higherErmFabundance were prone to fail CLA eradication and gain more ARGs after treatment. For gut microbiota, the bacteria richness decreased at 6 week and there was a significant difference in microbiota community among the three groups at 6 week.

Conclusions

Our findings demonstrated the dynamic alterations in gut microbiota and ARGs induced by different eradication therapies, which could influence the choices of antibiotics in eradication therapy.
Activating receptor KIR2DS2 bound to HLA‐C1 reveals the novel recognition features of activating receptor
Authors: Yang Yi , Bai Hua , Wu Yankang , Chen Peng , Zhou Jin , Lei Jun , Ye Xiang , Brown Alex J. , Zhou Xi , Shu Ting , Chen Yongshun , Wei Pengcheng , Yin Lei
Published: December 2021

Killer cell immunoglobulin‐like receptors (KIRs) are important receptors for regulating the killing of virus‐infected or cancer cells of natural killer (NK) cells. KIR2DS2 can recognize peptides derived from hepatitis C virus (HCV) or global flaviviruses (such as dengue and Zika) presented by HLA‐C*0102 to activate NK cells, and has shown promising results when used for cancer immunotherapy. Here, we present the complex structure of KIR2DS2 with HLA‐C*0102 at a resolution of 2·5Å. Our structure reveals that KIR2DS2 can bind with HLA‐C*0102 and HLA‐A*1101 in two different directions. Moreover, Tyr45 (in activating receptor KIR2DS2) and Phe45 (in inhibitory KIRs) distinguish the two different binding models and binding affinity between activating KIRs and inhibitory KIRs. The conserved ‘AT’ motif of the peptide mediates recognition and determines the peptide specificity of recognition. These structural characteristics shed light on how KIRs activate NK cells and can provide a molecular basis for immunotherapy by NK cells.
Direct Mailing Education Campaign Impacts on the Adoption of Grazing Management Practices
Authors: Berthold T. Allen , Olsovsky Taylor , Schramm Michael
Published: December 2021

The Texas Commission on Environmental Quality facilitates the Clean Rivers Program where many of Texas' waters are monitored for various parameters. A common approach to address water quality impairments is to develop and implement Watershed Protection Plans, where a key management measure is to increase the adoption of best management practices through existing government programs that provide technical and financial assistance. A key role for watershed managers during implementation is to raise awareness that technical and financial resources are available to assist producers with adoption. Outreach approaches thus far have included in‐person education programs, attendance at local Soil and Water Conservation District (SWCD) meetings, newsletters, and other efforts that have only had minimal reach. As a result, we initiated a mass mailing campaign where 4,921 landowners within Lavaca County, Texas were reached four times in approximately six months with the same message. Partnering with the local SWCD and United States Department of Agriculture Natural Resources Conservation Service offices, the number of individual best management practices were acquired for the current and previous five federal fiscal years to measure changes. Results suggest directly mailing educational materials to landowners is an effective outreach approach to increase the adoption of best management practices. Model results indicate a significant 300% increase in adoption of practices compared to historic levels.
Study of consumer perception about low‐sodium foods and characteristics related to perception and purchase of low‐sodium spreadable processed cheese
Authors: de Melo Leide Roberta Barboza , Torres Fernanda Rodrigues , Guimarães Jonas Toledo , Soutelino Maria Eduarda Marques , Cruz Adriano Gomez , Cortez Marco Antonio Sloboda
Published: December 2021

This study interviewed 1,511 consumers using an online questionnaire to understand consumer behavior on reduced‐sodium products and the buying interest for processed cheese with low sodium content. Likert scale techniques were applied, which was assessed by analyzing factors (49.38%), Cronbach's alpha (0.694) and KMO (0.703), which conferred reliability to the applied test, and word association and completion task, which were evaluated chi‐square and chi‐square per cell, respectively showing X2 = 799,635 and X2 = 6,428.59 (positive and negative stimuli), and X2 = 652.55 (purchase condition stimulus) for p < .0001. The consumer understands the problem of high sodium consumption, understands the use of products reduced in sodium, and recognizes the need to reduce the sodium content in cheeses, associates the purchase condition with the high cost and potential health benefits. However, the lack of technical knowledge about the product negatively influences the decision.

Practical applications

Sensory analysis techniques helps to elucidate the behavior of consumers towards a specific niche of products, clearly understand positive and negative points that directly influence the buying attitude, and clarify the limits of consumers' knowledge about products reduced in sodium, specifically evaluating the perception, behavior and purchase an interest in the face of a new product developed. The study takes on great relevance when it diagnoses the lack of information about salt, sodium, cheese technology processed by the consumer and demonstrates important points that interfere with safety and how it affects the purchase decision. It also highlights the need for greater transparency of the dairy industries with the consuming public when it comes to better information about the product, both related to the components and the applied technology. The work also provides information that aggregates both in research with consumers and offers a way of approximation between industry and consumer.
No association between a common type 2 diabetes risk gene variant in the melatonin receptor gene (MTNR1B) and mortality among type 2 diabetes patients
Authors: Xue Pei , Tan Xiao , Wu Jiafei , Tang Xiangdong , Benedict Christian
Published: December 2021

The minor G risk allele in the common melatonin receptor gene (MTNR1B, rs10830963) has been associated with an increased risk of myocardial infarction among patients with type 2 diabetes (T2D). Furthermore, activating the melatonin receptor 1B through melatonin has been shown to promote cell proliferation, which could be hypothesized to increase cancer risk. Cardiovascular disease (CVD) and cancer are common causes of death among patients with T2D. Using data from 14 736  patients with T2D who participated in the UK Biobank investigation, we hypothesized an additive effect of the G risk allele on all‐cause mortality, CVD mortality, and cancer mortality. As shown by Cox regression adjusted for confounders such as age, glucose‐lowering medication, and socioeconomic status, no significant trend between the number of G risk alleles and mortality outcomes was found during the follow‐up period of 11.1 years. Our negative findings do not speak against the role of this gene variant in the development of T2D, as repeatedly shown by previous large‐scale studies. Instead, they may suggest that rs10830963 is less relevant for mortality risk in patients with T2D.
Road to elimination of HCV: Clinical challenges in HCV management
Authors: Hayes C. Nelson , Imamura Michio , Tanaka Junko , Chayama Kazuaki
Published: December 2021

Since its discovery in 1989, the road to a cure for hepatitis C virus (HCV) has been slow, but most patients can now expect to achieve a sustained virological response (SVR). With direct‐acting antiviral (DAA) combination therapies such as glecaprevir/pibrentasvir and velpatasvir/sofosbuvir, 98% of patients successfully eradicate the virus, even if previous treatments failed or if resistance‐associated substitutions (RASs) are present. Adverse events are rare or mild, and patients with compensated cirrhosis and other co‐morbidities are often eligible for treatment. However, a small number of patients fail to eradicate the virus even after retreatment. The cause of failure is mainly due to emergence of NS5A P32 deletion mutants after initial DAA therapy in genotype 1b patients, although the reason is unknown for some patients. Alternative therapies that do not rely on NS5A inhibitors, such as sofosbuvir plus ribavirin, can be attempted in these patients. While scaled‐up treatment efforts present a challenge, another problem is that many carriers are unaware of their infection. Long‐term damage to the liver becomes irreversible, and patients who are not diagnosed in time can develop liver cancer or liver failure even after eliminating the virus. The long‐term costs of treatment of advanced liver disease in undiagnosed patients relative to the immediate costs of DAA therapy should be considered. As no vaccine is yet available, eventual elimination of the virus requires identifying and treating undiagnosed cases and screening of high‐risk populations such as injection drug users and men who have sex with men and female sex workers.
Architecture of torovirus replicative organelles
Authors: Ávila‐Pérez Ginés , Rejas María Teresa , Chichón Francisco Javier , Guerra Milagros , Fernández José Jesús , Rodríguez Dolores
Published: December 2021

Plus‐stranded RNA viruses replicate in the cytosol of infected cells, in membrane‐bound replication complexes. We previously identified double membrane vesicles (DMVs) in the cytoplasm of cells infected with Berne virus (BEV), the prototype member of theTorovirusgenus (NidoviralesOrder). Our previous analysis by transmission electron microscopy suggested that the DMVs form a reticulovesicular network (RVN) analogous those described for the related severe acute respiratory syndrome coronavirus (SARS‐CoV‐1). Here, we used serial sectioning and electron tomography to characterize the architecture of torovirus replication organelles, and to learn about their biogenesis and dynamics during the infection. The formation of a RVN in BEV infected cells was confirmed, where the outer membranes of the DMVs are interconnected with each other and with the ER. Paired or zippered ER membranes connected with the DMVs were also observed, and likely represent early structures that evolve to give rise to DMVs. Also, paired membranes forming small spherule‐like invaginations were observed at late time post‐infection. Although resembling in size, the tomographic analysis show that these structures are clearly different from the true spherules described previously for coronaviruses. Hence, BEV shows important similarities, but also some differences, in the architecture of the replication organelles with other nidoviruses.
Optimizing atrio‐ventricular delay in pacemakers using potentially implantable physiological biomarkers
Authors: Keene Daniel , Miyazawa Alejandra A , Johal Monika , Arnold Ahran D , Ali Nadine , Saqi Khulat A , March Katherine , Burden Leah , Francis Darrel P , Whinnett Zachary I , Shun‐Shin Matthew J
Published: December 2021

Background

Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat‐by‐beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices.

We assess whether laser Doppler can be used instead of BP to optimize AV delay.

Methods

Fifty eight patients underwent 94 AV delay optimizations with biventricular or His‐bundle pacing using laser Doppler and simultaneous noninvasive beat‐by‐beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40–320 ms), with automatic quality control checking precision of the optimum.

Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality.

Results

55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms).

An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms.

Conclusions

Laser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.
Differences in the approaches of cancer specialists toward adolescent and young adult cancer care
Authors: Matsumoto Kimikazu , Yamamoto Kazuhito , Ozono Seiichiro , Hashimoto Hiroya , Horibe Keizo
Published: December 2021

Background

This study investigated the medical care of adolescent and young adult (AYA) cancer patients and compared approaches toward AYA cancer care by pediatric and adult cancer specialists.

Methods

An Internet survey was conducted among 1,305 specialists (192 pediatric and 1,109 adult) in 2016.

Results

The rate of awareness of the term “AYA” was lower for adult specialists than for pediatric specialists. The departments that are responsible for caring for AYA cancer patients change when they reach 20 years of age. For the treatment of AYA patients, both pediatric and adult specialists preferred a multidisciplinary team as a top priority issue. A special ward or hospital rooms for AYA was required mostly for AYA patients under 24, and the needs for special wards or rooms for AYA was higher in pediatric specialists than in adult specialists. However, for AYA patients over 25, about 60% of adult specialists and 35% of pediatric specialists believed that no special care was required. As for desirable follow‐up protocols for pediatric cancer AYA survivors, half of the specialists considered that they should be conducted mainly by pediatric specialists in cooperation with adult specialists, and 30% to 40% of the specialists considered that transition to the corresponding adult medicine department would be preferable.

Conclusions

There were obvious differences in medical care and support for AYA cancer patients according to their age, particularly under the age of 20 or 24, and according to whether the onset of disease occurred during the AYA period or whether it was secondary to pediatric cancers. For each aspect, appropriate programs would require close cooperation between pediatric and adult specialists.
Enabling successful transition—Evaluation of a transition to adult care program for pediatric liver transplant recipients
Authors: Culnane Evelyn , Loftus Hayley , Peters Rebecca , Haydar Madeleine , Hodgson Alexandra , Herd Lauren , Hardikar Winita
Published: December 2021

Background

This study aimed to evaluate the transition to adult care program instituted for liver transplant recipients (LTRs) at a large tertiary pediatric hospital in Melbourne, Australia. Evaluation included the change in a Global Assessment Measure (GAM) before and after the transition program, satisfaction with the program, and measures of transition success including rejection rates and attendance at appointments post‐transfer. We hypothesized that the introduction of our structured transition program would improve disease understanding, health system understanding, and self‐care. We also hypothesized that those who had undergone the transition program would have lower failure to attend rates and lower rates of rejection than historical controls.

Methods

A LTR transition program was instituted at our service from 2013 to 2015. The program involved initial assessment of competencies with a Global Assessment Measure (GAM), followed by the introduction of a personalized goal setting program addressing issues identified in dedicated transition clinics. Assessment of competencies was compared between the commencement of the program and immediately prior to transfer. Patient satisfaction with the transition process was assessed at an interview 6–12 months after transfer to the adult service. Rejection rates and failure to attend rates were compared between the intervention group and a group of LTRs who did not receive the intervention.

Results

Twenty‐eight LTRs participated in the study; 20 received the transition intervention and 8 served as controls. Within the intervention group, all domains of transition competency and reported anxiety regarding transferring had significantly improved at the conclusion of the intervention and all reported satisfaction with the transition program with most (81%) reporting readiness to transfer. There were no significant differences in rejection rates or failure to attend rates between those who did and did not receive the transition intervention.

Conclusion

A longitudinal holistic transition program has the potential to positively impact the competencies and readiness of LTRs to successful transition and transfer to adult care.
Carcinogenic effects of prolonged daily low‐emission phototherapy in psoriasis
Authors: Franken Sylvie Mireille , Spiekstra Sander Wiebrand , Waaijman Taco , Lissenberg‐Witte Birgit , Rustemeyer Thomas
Published: December 2021

Background

Low‐dose UV treatment has been shown to be effective in mild psoriasis. However, the prolonged use of this treatment modality may raise concerns about its safety. These concerns are mainly focused on potential carcinogenic risks and overuse of this treatment modality.

Objectives

This study was set out to evaluate possible carcinogenic risks of prolonged low‐dose phototherapy.

Methods

Three groups of psoriasis patients were evaluated: patients with local treatment only (n = 15); low‐dose UV treatment at home for at least 18 months (n = 39); and patients with conventional NB‐UVB (n = 8). Patients underwent visual inspection for signs of photoageing, and p53, CPDs and γH2AX were measured in skin biopsies. Patients undergoing low‐dose phototherapy answered a survey about their recent patterns of use in a survey.

Results

In the skin biopsies, low‐dose UV treatment caused a lower amount of CPDs (p = .016) and p53 (p = .015) than NB‐UVB. γH2AX did not show a significant difference. Self‐report in patients undergoing low‐dose phototherapy showed only one case of overuse (2.7%). Visual skin inspection showed no difference in signs of photoageing in the three groups.

Conclusion

Prolonged treatment with low‐dose UV for 18 months appears at least as safe as a course of conventional NB‐UVB.
Complaints and tournament population ethics
Authors: Podgorski Abelard
Published: December 2021

In this paper, I develop an approach to population ethics which explains what we are permitted to do in virtue of the possible complaints against our action. This task is made difficult by a serious problem that arises when we attempt to generalize the view from two‐option to many‐option cases. The solution makes two significant moves – first, accepting that complaints are essentially pairwise comparative, and second, reimagining decision‐making as a tournament between options competing two at a time. The right view about when one option defeats another with respect to complaints, paired with the right view about how to pick the winners of the tournament given the relations of defeat, leads to a uniquely attractive view in the person‐affecting tradition.
Innovation and creativity in creative industries
Authors: Wohl Hannah
Published: December 2021

Creativity is the intentional combination of symbols, ideas, or objects in a way that is unexpected for a given audience. While creativity is a process, innovation is the outcome of this process. Moving from the macro‐level to the micro‐level, I survey the literature on innovation and creativity in creative industries, spanning cultural, economic, and organizational sociology as well as management studies. As a broader market force, uncertainty over innovativeness results in powerful status orders with each creative industry. Within these markets, creative producers work to situate their products as innovative within certain categories and breadths of categories. Creative producers' social network configurations and their face‐to‐face interactions within these networks shape both the process of creative collaboration and the resulting innovations. Producers' moment‐to‐moment valuations, modes of cognition, and interactions with material properties of creative products also influence the creative process. I argue that future research should give more attention to how decisions in the creative process evolve over time and are relationally shaped.
Characteristics and outcomes among vaccinated lung transplant patients with breakthrough COVID‐19
Authors: Bollineni Srinivas , Mahan Luke D. , Duncan Patrick , Mohanka Manish R. , Lawrence Adrian , Joerns John , Timofte Irina , Torres Fernando , La Hoz Ricardo M. , Kershaw Corey D. , Terada Lance S. , Kaza Vaidehi , Banga Amit
Published: December 2021

Background

Despite multiple studies evaluating the immunological responsiveness to vaccines, the clinical effectiveness of the two‐dose mRNA vaccine schedule among lung transplant (LT) patients has not been evaluated.

Methods

We included LT patients who tested positive for SARS‐CoV‐2 on a nasopharyngeal swab between March 1, 2020, and August 25, 2021 (n = 70). The study group was divided based on their vaccination status.

Results

During the study period, 14 fully vaccinated LT patients with one of the mRNA vaccines tested positive for COVID‐19 (median age 54, range 30–62 years, M:F 9:5). The vaccinated cohort was younger with bilateral LT, have suppurative conditions as the transplant indication, and present with milder symptoms. However, pulmonary parenchymal involvement was seen among all 12 patients where computed tomography (CT) of chest was available. The laboratory profile indicated a more subdued inflammatory response among the vaccinated group.

A lower proportion of vaccinated patients developed respiratory failure, needed ICU admission or ventilator support, although none of the differences achieved statistical significance. None of the vaccinated patients succumbed to COVID‐19 during the study period, while the 4‐week mortality among unvaccinated patients was nearly 15% (8/56).

Conclusions

In this cohort of vaccinated LT patients who developed breakthrough COVID‐19, the clinical course, risk of complications, and outcomes trended better than unvaccinated patients. However, universal involvement of the allograft demonstrates the continued vulnerability of these patients to significant sequelae from COVID‐19. Future studies may evaluate the incremental protection of vaccination after the completion of the third dose of mRNA vaccines among LT patients.