bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of levetiracetam and oxcarbazepine on 4‐year fragility fracture risk among prepubertal and pubertal children with epilepsy
Authors: Whitney Daniel G. , Caird Michelle S. , Hurvitz Edward A. , Rajapakse Chamith S. , Fedak Romanowski Erin M.
Published: July 2021

Objective

The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre‐ and midpuberty.

Methods

Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4–13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1‐year baseline (e.g., pre‐ASM exposure) and 4 years of follow‐up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person‐years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims‐based proxy for fragility fracture, for up to 4 years of follow‐up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture.

Results

The crude IR (95% CI) of NTFx was 21.5 (21.2–21.8) for non‐ASM‐users without epilepsy (n = 271 346), 19.8 (12.3–27.2) for LEV (n = 358), and 34.4 (21.1–47.7) for OXC (n = 203). Compared to non‐ASM‐users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63–1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09–2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02–2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99–2.93), which was marginally statistically insignificant (p = .053).

Significance

Initiating OXC, but not LEV, therapy among 4–13‐year‐olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies.
Investment transparency and the disposition effect
Authors: Danbolt Jo , Eshraghi Arman , Lukas Marcel
Published: July 2021

The disposition effect is lower in a trading environment with salient information on current holdings. Using proprietary data from a European fintech platform for social trading, we analyze variation in trading behavior within and between private and publicly visible portfolios. The disposition effect diminishes by about 35% when trades and holdings become public. We find the level of transparency and the way financial information is illustrated can influence trading decisions. Our results suggests that requiring greater transparency from portfolio managers can reduce trading bias.
Spinal ataxia in a 2‐year‐old colt caused by a compressive primary vertebral osteosarcoma
Authors: Fouché N. , Oesch S. , Unger L. , Berenguer Veiga I. , Küchler L. , Molazem M. , Van der Vekens E.
Published: July 2021

Neoplasia is a rare cause of ataxia in horses. This report describes a 2‐year‐old colt presented with sudden‐onset ataxia in which a cervical vertebral osteosarcoma causing severe compression of the spinal cord was diagnosed. Radiological changes included a large osteolytic lesion in the vertebral body, the vertebral arch, the right cranial articular process and the right transverse process of C4, interrupting the borders of the vertebral foramen and the right transverse foramen. Myelography revealed a marked spinal cord compression. Necropsy confirmed the presence of a well‐demarcated, invasive and firm mass protruding from the fourth cervical vertebral body that led to severe compression of the spinal cord. In spite of its strongly pleomorphic nature, the detection of osteoid confirmed the diagnosis of a central osteosarcoma of the combined type. To the best of our knowledge, a primary single vertebral osteosarcoma causing ataxia in a juvenile horse has not previously been reported, and findings of this case report could help in the diagnostic work‐up of similar cases.
Hoof wall separation disease: A review
Authors: Finno C. J.
Published: July 2021

Hoof wall separation disease (HWSD) is a genetic defect in Connemara ponies characterized by separation and cracking of the dorsal hoof wall. The disease can result in chronic inflammation, severe lameness and laminitis. Affected ponies typically show clinical signs within the first 6 months of life. The disease is inherited as an autosomal recessive trait. The genetic mutation is a frameshift mutation in the gene SERPINB11, (c.504_505insC). Carriers are completely normal, only ponies that are homozygous for the mutation will have clinical signs of the disease. Within the Connemara breed, carrier frequency has been estimated at 14.8% and the mutation has not been identified in other breeds at this time. While there is no definitive cure for HWSD, management through targeted hoof care and the use of special shoes may be beneficial. Additionally, environmental management may lessen the severity of clinical disease in affected ponies. Genetic testing of Connemara ponies is required for all new registrations.
A fully homomorphic encryption based on magic number fragmentation and El‐Gamal encryption: Smart healthcare use case
Authors: Kara Mostefa , Laouid Abdelkader , Yagoub Mohammed Amine , Euler Reinhardt , Medileh Saci , Hammoudeh Mohammad , Eleyan Amna , Bounceur Ahcène
Published: July 2021

Nowadays, cloud computing offers a digital infrastructure for smart city development. Cognitive cities are steadily automating daily urban processes. The ever expanding objective‐driven communities gather and share sensitive data that must be stored securely. Cloud computing offers a suitable platform that allows cognitive smart cities to access and re‐access data to learn from their past to adapt its current behaviour. However, the cloud is an untrusted entity that may expose data when decrypted for processing by systems. In this paper, we treat the issue of encrypted data processing. Often, the data is encrypted prior to transferring it to the cloud, where the cloud must have the data in clear to be able to make calculations which raises security and privacy threats if the cloud is considered untrusted. The scenario of asking users to make the calculations after decrypting the received cloud data and encrypting the obtained results before sending them back to the cloud is not a practical solution in distributed multi‐tenant architectures. Homomorphic encryption allows offers a solution for processing encrypted data. Many existing homomorphic encryption schemes suffer from limitations that hinder their usability. This paper presents an efficient fully homomorphic encryption scheme using twin key encryption and magic number fragmentation. The details of the scheme are presented along with cryptanalytic attacks to assess its effectiveness. The proposed scheme exhibits strong resilience against brute‐force attacks compared to its rivals from the literature. Finally, we illustrate the applicability of the proposed scheme using a cognitive smart city application.
Moving reference point goalposts and implications for fisheries sustainability
Authors: Silvar‐Viladomiu Paula , Minto Cóilín , Halouani Ghassen , Batts Luke , Brophy Deirdre , Lordan Colm , Reid David G.
Published: July 2021

For many environmental indicators, the sustainable status can change because of changes in either the monitored state or the policy goal. Fisheries provide an intensively monitored setting to investigate the relative impacts of such change. Key fisheries sustainability indicators comprise the ratio between fishing pressure or biomass and their respective reference levels. We developed a retrospective database of population status, reference point changes and reported reasons for changes for all data‐rich stocks in the ICES region. We derived methods to distinguish the impacts of either source of change (monitored state or policy goal) on sustainable status. We found that reference points changed frequently (64% of populations had reference point changes) with varying magnitudes. Contrary to expectation, reference point changes were often not compensated by changes in the state thus significantly impacting inferred sustainability status and dependent scientific advice. Across a range of life histories and assessments, changes in reference points dominate retrospective revisions in status over the full time series. Overall, status before and after the change of reference point had no significant directional differences that would suggest reference point change effecting movement towards or away from sustainability. Although multiple factors have contributed to reference point changes, our results show that the reference point definition and the technical basis for estimation were the most important reasons for change. Recognizing that reference points are not constant in time but rather form reference series is paramount to quantifying present and historical sustainability. Properly documenting, justifying and quantifying the impacts of such change is an ongoing challenge.
Using participatory video to share people’s experiences of neotropical urban green and blue spaces with decision‐makers
Authors: Fisher Jessica Claris , Mistry Jayalaxshmi , Pierre Meshach Andre , Yang Huichang , Harris Arianne , Hunte Nadia , Fernandes Damian , Bicknell Jake Emmerson , Davies Zoe Georgina
Published: July 2021

Cities are complex, socio‐ecological ecosystems providing both opportunity and detriment to human health and well‐being. Specifically, urban green (e.g., parks) and blue spaces (e.g., coastline) can restore human psychological well‐being. In the Global South, where rapid urbanisation is posing challenges for biodiversity conservation and the mental well‐being of urban human populations, there has been little research on understanding the social and environmental benefits of urban green and blue spaces, which could inform decision‐makers seeking sustainable land‐use planning interventions. Here, we use participatory video (using film to co‐produce research) to explore the relationships people have with urban green and blue spaces in Georgetown, Guyana, and communicate these findings to decision‐makers. Short films created and discussed by city residents highlighted how specific characteristics of green and blue spaces contributed to restorative quality, a sense of place, and alleviated stress. At the same time, locally specific nuances were also revealed, such as folklore associated with urban wildlife and the importance of monuments framing Guyana's complex history. A composite film was screened to government ministries, park managers, and the Mayor and City Council, who articulated intentions to change the way these spaces were managed (e.g., maintaining specific features, encouraging visitation, raising awareness, and increasing the planned distribution of new spaces). We demonstrate how participatory video can allow participants to reflect on and change their interactions with urban green/blue spaces, while facilitating a unique and engaging dialogue between multiple stakeholders, with important, applied implications for both public health and biodiversity conservation.
Characteristics of esophageal achalasia in geriatric patients over 75 years of age and outcomes after peroral endoscopic myotomy
Authors: Ujiie Naoto , Sato Chiaki , Taniyama Yusuke , Koseki Ken , Takaya Kai , Okamoto Hiroshi , Fukutomi Toshiaki , Unno Michiaki , Kamei Takashi
Published: July 2021

Aim

As the population ages, the proportion aged ≥75 years is expected to increase. Many studies on peroral endoscopic myotomy (POEM) as treatment for esophageal achalasia have already been reported; however, few studies have been designed on patients aged ≥75 years. The purpose of this study is to describe the characteristics of esophageal achalasia in patients >75 years and to evaluate the outcomes of POEM.

Methods

This study included 121 patients who underwent POEM for esophageal achalasia, which was divided into the geriatric (n = 18) group aged ≥75 and the young (n = 103) group ≤74 years. The characteristics of esophageal achalasia and the short‐term outcomes after POEM in the geriatric group compared with the young group were retrospectively investigated.

Results

The median age of the geriatric group was 78 years, and two patients were initially diagnosed with refractory pneumonia, and esophageal achalasia was initially overlooked. The preoperative Eckardt score of the geriatric group was significantly lower than that of the young group (4 vs. 6, P = 0.007), particularly in the regurgitation score. The Eckardt score and integrated relaxation pressure of both groups were significantly improved after POEM (P < 0.001). There were no cases of perioperative complications in the geriatric group.

Conclusions

POEM for esophageal achalasia is a safe and effective treatment even in geriatric patients >75 years of age. In geriatric patients with recurrent or intractable pneumonia, it is important to rule out esophageal achalasia. Geriatr Gerontol Int 2021; 21: 788–793.
Identifying resilient industries in Mexico's automotive cluster: Policy lessons from the great recession to surmount the crisis caused by COVID 19
Authors: Mendoza‐Velázquez Alfonso , Rendón‐Rojas Liliana
Published: July 2021

This study investigates regional employment and production resilience to adverse crisis shocks. We extend the concept of resilience beyond the notion of resistance and fast recovery to include the potential of positive spillovers to related industries in neighboring regions. The industrial analysis of the automotive cluster in Mexico relies on a spatial shift‐share approach to characterize the resilience ability of regional industries. The study employs the Sub‐Prime crisis as a benchmark to identify the type of employment and production recovery after an adverse shock of similar magnitude. Four industries within the automotive cluster present various degrees of spatial dependence—those industries with the most significant spillover effects on neighboring regions. The type of resilience shown by these automotive industries in the regions during the Sub Prime Crisis serves as a benchmark to base policy government and corporate decisions after the economic crisis caused by the outbreak of SARS‐CoV‐2.
Legitimate but “not for me”: The role of validation in migrant entrepreneur understanding of COVID‐19 business support policies in Shanghai
Authors: Blalock Emily C. , Lyu Xiaojun
Published: July 2021

COVID‐19 pandemic destroyed lives and the global economy, and in the wake left businesses struggling to re‐open in urban China. The Chinese party‐state implemented fiscal reforms targeted towards small businesses, however little research has evaluated business’ understanding of policies and implementation, particular to the focus on rural migrant entrepreneurs. Therefore, we conducted an ethnographic case study including in‐depth interviews to determine to what extent rural migrant micro‐entrepreneurs understand and adopt COVID‐19 business support policies at two retail markets in Shanghai amid a pandemic. Applying an inductive grounded theory approach, the data demonstrated participants believe policies arelegitimatebutnot for mebecauseI am getihu by myself. We maintain their understanding is a legacy ofhukouand is confirmed through the theory of validation includingrecognitionthrough agreement with significant others including other entrepreneurs and family;corroborationwith life experiences in Shanghai; andresonanceof their migration story as self‐sufficient entrepreneurs surviving with their own capabilities. They have a degree of certainty their understanding is fact because it has been repeatedly validated through life experiences of a migrant lackinghukouin Shanghai. The study encourages consideration for the migrant entrepreneur context and has important practical implications for policymakers.
Talking the same language on patient empowerment: Development and content validation of a taxonomy of self‐management interventions for chronic conditions
Authors: Orrego Carola , Ballester Marta , Heymans Monique , Camus Estela , Groene Oliver , Niño de Guzman Ena , Pardo‐Hernandez Hector , Sunol Rosa ,   COMPAR‐EU Group
Published: July 2021

Context

The literature on self‐management interventions (SMIs) is growing exponentially, but it is characterized by heterogeneous reporting that limits comparability across studies and interventions. Building an SMI taxonomy is the first step towards creating a common language for stakeholders to drive research in this area and promote patient self‐management and empowerment.

Objective

To develop and validate the content of a comprehensive taxonomy of SMIs for long‐term conditions that will help identify key characteristics and facilitate design, reporting and comparisons of SMIs.

Methods

We employed a mixed‐methods approach incorporating a literature review, an iterative consultation process and mapping of key domains, concepts and elements to develop an initial SMI taxonomy that was subsequently reviewed in a two‐round online Delphi survey with a purposive sample of international experts.

Results

The final SMI taxonomy has 132 components classified into four domains: intervention characteristics, expected patient/caregiver self‐management behaviours, outcomes for measuring SMIs and target population characteristics. The two‐round Delphi exercise involving 27 international experts demonstrated overall high agreement with the proposed items, with a mean score (on a scale of 1‐9) per component of 8.0 (range 6.1‐8.8) in round 1 and 8.1 (range 7.0‐8.9) in round 2.

Conclusions

The SMI taxonomy contributes to building a common framework for the patient self‐management field and can help implement and improve patient empowerment and facilitate comparative effectiveness research of SMIs.

Patient or public contribution.

Patients’ representatives contributed as experts in the Delphi process and as partners of the consortium.
Leg rings impact the diving performance of a foot‐propelled diver
Authors: Gómez‐Laich Agustina , Pantano Carolina , Wilson Rory P. , Svagelj Walter S. , Yoda Ken , Gunner Richard , Quintana Flavio
Published: July 2021

Leg rings are frequently used to mark aquatic birds in order to identify individuals, and study population dynamics and migration patterns, with the proviso being that the rings should not affect the birds. The effects of tags and rings are of particular interest in diving birds because any change in body shape could impact swimming efficiency and costs, as water is almost a thousand times denser than air. We attached tri‐axial accelerometers to both ringed and unringed breeding Imperial Shags Leucocarbo atriceps to assess dive performance based on descent angle, descent rate, power stroke rate, power stroke peak acceleration amplitude and Vectorial Dynamic Body Acceleration (VeDBA) as a proxy for energy expenditure. Ringed birds, especially females, had a higher foot‐stroke amplitude than unringed animals. In addition, the overall efficiency of the ringed individuals, as expressed by the descent rate per unit VeDBA, was compromised (by 3.5% in females and 4.3% in males) compared with unringed birds. We conclude that leg rings change the diving performance of Imperial Shags, although the effect is small and may not affect reproductive success. However, given that birds are typically ringed for life, we urge researchers to be particularly careful about the potential cumulative effect of attaching leg rings to foot‐propelled diving species.
Reads in a haystack: extracting complete mitogenome sequences hidden in baculovirus datasets
Authors: Jukes M.D.
Published: July 2021

Thaumatotibia leucotreta(Lepidoptera, Tortricidae) is one of many economically important insect pests for which no complete mitogenome sequence is available. The complete mitochondrial sequences for this species and other key pests could assist in the development of novel molecular techniques, such as enabling the identification of population‐specific markers which could assist in improved monitoring of populations. The objective of this study was to determine whether NGS datasets generated for entomopathogenic viruses contain reads originating from host mitochondrial DNA. A total of 28 NGS datasets generated for the baculovirus Cryptophlebia leucotreta granulovirus (CrleGV) were analysed in this study. Three datasets contained sufficient reads providing adequate coverage for the assembly of complete mitogenomes. All 13 protein‐coding genes, 22 tRNAs and both rRNAs present in the mitogenomes of other species within the Grapholitini tribe, were identified. Phylogenetic analysis of the mitogenomes at both an intrafamilial and interspecies level grouped the sequences within the Olethreutinae andT. leucotretaclades, respectively. Analysis of single nucleotide variations (SNVs) between eachT. leucotretasequence indicated up to 75 differences across the mitogenome. The methodology used in this study could be expanded to other baculovirus NGS datasets enabling the generation of novel lepidopteran mitogenome sequences.
Enigmatic inflammasomes – Sequel (Part 2)
Authors: Triantafilou Kathy
Published: July 2021

In this issue, we introduce the second part of our review series focusing on lesser‐known enigmatic inflammasomes. This part of the collection introduces one more under‐studied NLR, NLRP7, and not only its role as a regulator of inflammation in response to bacterial infections but also its non‐inflammasome role in early pregnancy. In addition, the enigmatic function of extracellular ASC specks is also introduced, where extracellular ASC specks are presented as ‘danger signals’ to propagate inflammation. The series is concluded with an article that reviews the immunometabolic regulation of all of these lesser‐known NLRs, demonstrating that metabolic regulation of inflammasome activation is central for the whole NLR family. These three reviews, together with the four articles that were published in the first part of the series in December 2020, offer new insights into the complex functions of NLRs, well beyond the well‐known NLRP3. The review series as a whole provides a thought‐provoking platform with some of the latest findings in the NLR field and sparks our imagination into what might be discovered in this space in the future.
The process of transitioning for the transgender individual and the nursing imperative: A narrative review
Authors: Evans Shelley , Crawley Jamie , Kane Debbie , Edmunds Kathryn
Published: July 2021

Aims

The objectives of this study were to bring the experience of the transitioning process for the transgender population to the nursing profession and address the lack of knowledge to promote improved patient outcomes.

Design

This study used a narrative review using the literature matrix method. Because of the dearth of trans specific literature, editorials and monologues were included.

Data source

A broad search was undertaken across all databases including CINAHL, PubMed, PsycINFO, Ovid MEDLINE, ProQuest Nursing & Allied Health and Google Scholar. Literature from June 1994 to May 2020 was appraised. Non‐peer reviewed literature and published texts were procured via Google Alerts.

Review methods

Selection for inclusion was based on credibility and relevance from a variety of social science disciplines. A narrative analysis was used to identify common themes, incongruencies in schools of thought and perspectives that require consideration.

Results

Analysis of the literature revealed the following themes: (a) literature and terminology evolution, (b) transitioning as a process, (c) medicalization of transitioning, (d) generational views on transitioning and (e) needs during transition.

Conclusion

This review highlights key issues about the transitioning process imperative to nursing when meeting the needs of the transgender population.

Impact

This review addresses the lack of trans specific literature and lack of consistency in the literature about the understanding of the transitioning process for the transgender population.

Main findings? Terminology to explain the transitioning process is ever evolving. Future studies about transitioning need to go beyond the medical lens. Generational views differ in the approach to transitioning, and there are needs unique to this population required during the process.

Where and whom will the research impact? The review has significant implications for change in health delivery, nursing policy and formulating nursing practice and education to improve trans competent care.
Moral Disagreement in Theories of Practical Ethics
Authors: Paulo Norbert
Published: July 2021

What is the point of doing practical ethics? Is it to find fruitful modes of reasoning so that the people can make up their mind about contested issues? Or is it rather to try to solve those problems once and for all? This article argues that the epistemology of moral disagreement provides good reasons in favor of the former view. In a recent paper, Andrei Poama suggests understanding public policy ethics (EPP) as falling into two broad categories – applied and constructive EPP. The main difference is their reaction to the factum of moral disagreement: proponents of applied EPP explain moral disagreement away, while proponents of constructive EPP take it to be a fundamental characteristic of morality. This article takes Poama's distinction to suggest a path to decide which of the two approaches to EPP is ‘the right one’, namely to take into account the debate about peer disagreement in epistemology. The article argues that the most promising theory of epistemic peer disagreement – the ‘Total Evidence View’ – fits constructive EPP quite naturally and that this speaks for constructive against applied approaches to EPP and to practical ethics more generally.
Future orientation helps regulate emotion in the future
Authors: Zheng Lei , Chen Yidi , Gan Yiqun
Published: July 2021

Although the adaptive function of future orientation has been demonstrated, whether an individual's orientation toward the future regulates emotions to cope with future stressors remains unknown. The present study aimed to investigate the emotion regulation function of future orientation in a goal‐related stressful situation. Eighty participants were randomly assigned to an experiment group or a control group. The experiment group was primed by a future‐oriented manipulation, whereas the control group was primed by a neutral condition; then, both groups performed the Trier Social Stress Test (TSST). The results showed that the experiment group exhibited reduced negative mood, increased positive mood, and a lower peak cortisol level after the TSST task. In conclusion, future orientation is considered an effective approach to regulate future emotions in response to stress. Our results render insights to developing strategies in coping with occupational stress.
Atrial fibrillation is associated with increased central blood pressure and arterial stiffness
Authors: Pauklin Priit , Eha Jaan , Tootsi Kaspar , Kolk Rein , Paju Rain , Kals Mart , Kampus Priit
Published: July 2021

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and beta blockers (BBs) are the drugs of choice for rate or rhythm control in these patients. The purpose of this study was to describe differences in arterial stiffness (AS), central blood pressure (cBP), and the role of BBs on cBP in patients with AF compared to healthy individuals. The authors included 76 patients with paroxysmal/persistent AF. Carotid‐femoral pulse wave velocity (PWV) and cBP were measured and compared with data from 75 healthy individuals. Patients with AF had higher PWV (8.0 m/s vs. 7.2 m/s, p < .001), central systolic blood pressure (cSBP) (118 mm Hg vs. 114 mm Hg, p = .033), central pulse pressure (cPP) (39 mm Hg vs. 37 mm Hg, p = .035) and lower pulse pressure amplification (PPA) (1.24 vs. 1.30, p = .015), without differences in peripheral blood pressure (pBP) and heart rate (HR). AF patients had significantly increased PWV (β= 0.500, p = .010, adjusted R² = 0.37) after adjustment for confounding factors. The use of BBs significantly reduced PPA (β = ‐0.059, p = .017, adjusted R² = 0.30). AF patients have higher PWV, cSBP, cPP, and lower PPA, compared to healthy patients. These findings support the role of AS in the development of AF. Use of BBs is related to a potential adverse effect on cBP.
Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells
Authors: Latifi‐Navid Hamid , Soheili Zahra‐Soheila , Samiei Shahram , Sadeghi Mehdi , Taghizadeh Sepideh , Pirmardan Ehsan Ranaei , Ahmadieh Hamid
Published: July 2021

Angiogenesis, inflammation and endothelial cells’ migration and proliferation exert fundamental roles in different diseases. However, more studies are needed to identify key proteins and pathways involved in these processes. Aflibercept has received the approval of the US Food and Drug Administration (FDA) for the treatment of wet AMD and colorectal cancer. Moreover, the effect of Aflibercept on VEGFR2 downstream signalling pathways has not been investigated yet. Here, we integrated text mining data, protein‐protein interaction networks and multi‐experiment microarray data to specify candidate genes that are involved in VEGFA/VEGFR2 signalling pathways. Network analysis of candidate genes determined the importance of the nominated genes via different centrality parameters. Thereupon, several genes—with the highest centrality indexes—were recruited to investigate the impact of Aflibercept on their expression pattern in HUVEC cells. Real‐time PCR was performed, and relative expression of the specific genes revealed that Aflibercept modulated angiogenic process by VEGF/PI3KA/AKT/mTOR axis, invasion by MMP14/MMP9 axis and inflammation‐related angiogenesis by IL‐6‐STAT3 axis. Data showed Aflibercept simultaneously affected these processes and determined the nominated axes that had been affected by the drug. Furthermore, integrating the results of Aflibercept on expression of candidate genes with the current network analysis suggested that resistance against the Aflibercept effect is a plausible process in HUVEC cells.
Recombinant platelet‐derived growth factor‐BB alleviates osteoarthritis in a rat model by decreasing chondrocyte apoptosis in vitro and in vivo
Authors: Zhu Pengfei , Wang Zhengchao , Sun Zhenxing , Liao Bokai , Cai Yu
Published: July 2021

Osteoarthritis (OA) is a common joint disease that mainly affects the diarthrodial joints. Treatments for OA include non‐pharmacological interventions, topical and oral therapies, intra‐articular therapies and joint surgery. However, all the treatments mentioned above mainly aim to control the symptoms instead of improving or reversing the joint condition. In this research, we observed the effect of recombinant platelet‐derived growth factor (PDGF)‐BB on OA in a monosodium iodoacetate (MIA)–induced rat model and revealed the possible mechanisms. In vitro, the level of inflammation in the chondrocytes was gradually alleviated, and the apoptosis rate was gradually decreased by PDGF‐BB at increasing concentrations. The levels of p‐p38, Bax and caspase‐3 decreased, and the level of p‐Erk increased with increasing PDGF‐BB concentration. In vivo, PDGF‐BB could significantly reverse chondrocyte and matrix loss. Furthermore, high concentrations of PDGF‐BB could alleviate cartilage hyperplasia to remodel the tissue. The level of collagen II was up‐regulated, and the levels of collagen X and apoptosis were down‐regulated by increasing concentrations of PDGF‐BB. In conclusion, recombinant PDGF‐BB alleviated OA by down‐regulating caspase‐3‐dependent apoptosis. The effects of PDGF‐BB on OA mainly include inhibiting chondrocyte loss, reducing cartilage hyperplasia and osteophyte formation, and regulating collagen anabolism.
ADMSC Exo‐MicroRNA‐22 improve neurological function and neuroinflammation in mice with Alzheimer's disease
Authors: Zhai Liping , Shen Heping , Sheng Yongjia , Guan Qiaobing
Published: July 2021

The previous study by our group has found that miRNA‐22 can inhibit pyroptosis by targeting GSDMD and improve the memory and motor ability of mice with Alzheimer's disease (AD) mice by inhibiting inflammatory response. In recent years, stem cells and their exosomes have been reported to have good therapeutic effects on AD; therefore, we hypothesize that miRNA‐22 is likely to play a synergistic therapeutic effect. In this study, adipose‐derived mesenchymal stem cells (ADMSCs) were transfected into miRNA‐22 mimic to obtain miRNA‐22 loaded exosomes (Exo‐miRNA‐22), which was further used for the treatment and nerve repair of AD. In brief, 4‐month‐old APP/PS1 mice were assigned into the control group, Exo and Exo‐miRNA‐22 groups. After exosome transplantation, we observed changes in the motor and memory ability of mice. In addition, ELISA was used to detect the expression of inflammatory factors in cerebrospinal fluid and peripheral blood, Nissl staining was used to assess the survival of mouse nerve cells, immunofluorescence staining was used to determine the activation of microglia, and Western blot was utilized to detect the expression of pyroptosis‐related proteins. As a result, the nerve function and motor ability were significantly higher in mice in the Exo‐miRNA‐22 group than those in the control group and Exo group. Meanwhile, the survival level of nerve cells in mice was higher in the Exo‐miRNA‐22 group, and the expression of inflammatory factors was lower than that of the Exo group, indicating Exo‐miRNA‐22 could significantly suppress neuroinflammation. In vitro culture of PC12 cells, Aβ25‐35‐induced cell damage, detection of PC12 apoptotic level, the release of inflammatory factors and the expression of pyroptosis‐related proteins showed that Exo‐miRNA‐22 could inhibit PC12 apoptosis and significantly decrease the release of inflammatory factors. In this study, we found that miRNA‐22‐loaded ADMSC‐derived exosomes could decrease the release of inflammatory factors by inhibiting pyroptosis, thereby playing a synergetic therapeutic role with exosomes on AD, which is of great significance in AD research.
Identification and characterization of Trpm4 gene involved in regulating Japanese flounder (Paralichthys olivaceus) inflammatory response
Authors: Li Shuo , Feng Yu , Zhang Tongtong , Wang Shan , Sun Jinsheng
Published: July 2021

The transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed Ca2+‐impermeable cation channel involved in modulating inflammatory and immune responses in mammals. However, the role of TRPM4 channel in fish immunity remains unclear. In this report, from a comparative immunological point of view, we identified and characterized a Trpm4 gene from Japanese flounder (Paralichthys olivaceus) and analysed its potential role in regulating the fish inflammatory response. The Japanese flounder Trpm4 gene is expressed in a wide range of tissues and encodes a 1264‐amino acid protein which expresses on the cell surface and shares several conserved domains with its mammalian counterparts. In vitro inflammatory challenge and in vivo bacterial infection experiments revealed that Japanese flounder Trpm4 expression was significantly modulated following different immune challenges, indicating the implication of Trpm4 in the fish immune response. Overexpression of TRPM4 significantly attenuated LPS‐ and poly(I:C)‐induced pro‐inflammatory cytokine expression in Japanese flounder FG‐9307 cells. In contrast, pharmacological inhibition of the endogenous TRPM4 channel activity in Japanese flounder head kidney macrophages resulted in increased pro‐inflammatory cytokine expression following LPS and poly(I:C) stimulations. Taken together, these findings indicate that TRPM4 channels may play a conserved role in regulating inflammatory response(s) in fish.
Subcritical low temperature extraction technology and its application in extracting seed oils
Authors: Wang Wen‐Yue , Yan Yuan‐Yuan , Liu Hua‐Min , Qi Kun , Zhu Xin‐Liang , Wang Xue‐De , Qin Guang‐Yong
Published: July 2021

Seed oils are of increasing interest to research and industry because they are a renewable, relatively inexpensive resource, they have valuable mechanical and chemical properties, and they have considerable nutritional benefits. Besides the traditional oil extraction methods, subcritical low temperature extraction as an innovative, clean, and environmentally friendly technology has attracted considerable attention recently. This new technique has many excellent properties, such as low temperature and pressure, short time, better selectivity, environmental compatibility, process simplicity, and the elimination of residual solvent. This review describes the technique of subcritical low temperature extraction, and then focuses on the recent developments in this technology as it is being used for the extraction of various seed oils.

Practical Applications

Majority seeds are generally discarded worldwide as food‐by‐product, even though they have high nutritional value. This analysis provides new ideas for food industry stakeholders concerned with high value utilization of by‐product produced during food processing. It also assessed the combined effects of different extraction methods on the quality of variety seed oils. To our knowledge, no reviews have been conducted on the application of subcritical low temperature technique in plant seed oil extraction. By providing information and insights, this article should facilitate development of subcritical low temperature extraction as an efficient means to extract and isolate substances from plant matrices that can be used in the production of functional foods, nutraceuticals, and pharmaceuticals.
Family members' perspectives on learning cognitively unimpaired older adults' amyloid‐β PET scan results
Authors: Largent Emily A. , Abera Maramawit , Harkins Kristin , Feldman Sara J. , Uhlmann Wendy R. , Roberts J. Scott , Karlawish Jason ,   The REVEAL‐SCAN Team
Published: July 2021

Background/Objectives

Disclosure of Alzheimer's disease (AD) risk information to cognitively unimpaired older adults may become more common if preclinical AD is shown to be identifiable and amenable to treatment. Little, however, is known about how families will react to this information.

Design and Setting

Semi‐structured telephonic interviews.

Participants

Seventy study partners (mean age = 68 [±11]; 50% female; 70% spouses/significant others; 18% children, siblings; 12% friends) of cognitively unimpaired adults who learned a personalized AD dementia risk estimate and an amyloid‐β PET scan result through their participation in preclinical AD research.

Measurement

Interviewees were asked about their desire for information regarding their family member's AD dementia risk, baseline expectations of risk, understanding of amyloid‐β PET scan results, and the impact of AD dementia risk information on emotions, health behaviors, and future plans, as well as on perceptions of their family member's or friend's memory.

Results

Interviewees generally understood the AD dementia risk information (83%) and considered it valuable (75%). Risk information perceived as favorable elicited feelings of happiness and relief; unfavorable information elicited disappointment, as well as increased awareness of the participants' memory and monitoring for incipient changes in cognition. While noting that AD dementia risk information was not medically actionable at this time due to the lack of disease‐modifying therapies, some interviewees described changes to their family members' and their own health behaviors and future plans.

Conclusion

Guidelines for the disclosure of AD dementia risk estimates and biomarker results to cognitively unimpaired adults should account for the needs and interests of individuals and their family members, who may step into a pre‐caregiver role.
Supermarket competence in emergent markets: Conceptualization, measurement, effects, and policy implications
Authors: Grunert Klaus G. , Zhou Yanfeng , Banovic Marija , Loebnitz Natascha
Published: July 2021

When channels of distribution change, consumer competences have to adapt. We define supermarket competence as the set of skills and knowledge that enables consumers to locate, evaluate, and choose among product offerings in a supermarket to fulfill their shopping goals. We develop a scale that measures three components of supermarket competence: finding and locating products, understanding and using packaging information, and interpreting prices. To test the structure and reliability of the scale, it is applied to three consumer samples in China. Supermarket competence is found to be related to shopping trip satisfaction, perceived shopping risk, and use of brand information. In addition, consumers with different levels of supermarket competence are found to differ in their demographic characteristics and in their shopping behavior. Policy implications for strengthening consumers' supermarket competence are discussed.
Revisiting marital health protection: Intraindividual health dynamics around transition to legal marriage
Authors: Mikucka Małgorzata , Arránz Becker Oliver , Wolf Christof
Published: July 2021

Objective

This study analyzes the dynamics of health associated with the transition to first marriage and remaining in marriage up to 24 years in order to estimate the protective effect of heterosexual marriage (compared to being never married, including the unpartnered, partnered, and cohabiting) on physical, mental, and self‐rated health.

Background

Past research produced inconclusive results on marital health protection. This study advances the debate by overcoming theoretical and methodological shortcomings of previous research. The authors use new statistical methods, which go beyond controlling for self‐selection into marriage on health levels and also account for selection on health trajectories.

Method

The authors used German Socio‐Economic Panel (SOEP) data (1992–2018, stratified random sample; N = 27,205 observations for physical and mental health, N = 110,440 observations for self‐rated health). This study relied on fixed effects models with individual slopes, which controlled for individual premarital health trends, as well as fixed effects models with group slopes (FEGS), which modeled self‐selection into marriage on premarital health trajectories.

Results

Compared to health trajectories of the never married, self‐rated health and physical health declined temporarily upon the transition into marriage, but improved in the long run; however, the cumulative protective effect was statistically significant only among men and only for self‐rated health. Mental health improved around the transition into first marriage, but the effect was short‐lived. Men with more sustainable premarital health had a higher chance of marrying.

Conclusion

This study does not support the strong theoretical claims of marital protection and suggests that marriage exerts a mix of protective and adverse effects on health.
Serum concentrations of canine pancreatic lipase immunoreactivity and C‐reactive protein for monitoring disease progression in dogs with acute pancreatitis
Authors: Keany Kirstin M. , Fosgate Geoffrey T. , Perry Sean M. , Stroup Shannon T. , Steiner Joerg M.
Published: July 2021

Background

Reliable biomarkers for monitoring disease progression and management in dogs with acute pancreatitis have not been described.

Objective

To determine if serum concentrations of canine pancreatic lipase immunoreactivity (cPLI) and C‐reactive protein (CRP) can be used as biomarkers for disease progression in hospitalized dogs with acute pancreatitis.

Animals

Thirteen hospitalized dogs with acute pancreatitis diagnosed based on clinical signs, serum cPLI concentrations, and imaging findings were enrolled.

Methods

Serum cPLI and CRP concentrations were determined before and then daily during hospital management and 1 week after hospital discharge. Modified canine activity index (MCAI) and canine acute pancreatitis clinical severity index (CAPCSI) scores were calculated daily for each patient while hospitalized.

Results

The MCAI scores (P = .03) but not CAPCSI scores (P = .31) were significantly different between dogs that survived to discharge (n = 11) and those that did not (n = 2). Serum cPLI concentration was positively correlated with MCAI (rho = 0.42;P = .01). Serum CRP concentration also was positively correlated with the MCAI (rho = 0.42,P = .01).

Conclusions

Serum cPLI and possibly CRP could be used as objective biomarkers for clinical changes in hospitalized dogs with acute pancreatitis. Additional studies involving larger numbers of dogs would be warranted to evaluate the broader impact of these findings.
Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib
Authors: Rapposelli Ilario Giovanni , Tada Toshifumi , Shimose Shigeo , Burgio Valentina , Kumada Takashi , Iwamoto Hideki , Hiraoka Atsushi , Niizeki Takashi , Atsukawa Masanori , Koga Hironori , Hirooka Masashi , Torimura Takuji , Iavarone Massimo , Tortora Raffaella , Campani Claudia , Lonardi Sara , Tamburini Emiliano , Piscaglia Fabio , Masi Gianluca , Cabibbo Giuseppe , Giuseppe Foschi Francesco , Silletta Marianna , Tsuji Kunihiko , Ishikawa Toru , Takaguchi Koichi , Kariyama Kazuya , Itobayashi Ei , Tajiri Kazuto , Shimada Noritomo , Shibata Hiroshi , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Fukunishi Shinya , Ohama Hideko , Kawata Kazuhito , Tani Joji , Nakamura Shinichiro , Nouso Kazuhiro , Tsutsui Akemi , Nagano Takuya , Tanaka Takaaki , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Joko Kouji , Koizumi Yohei , Hiasa Yoichi , Rimini Margherita , Ratti Francesca , Aldrighetti Luca , Cascinu Stefano , Casadei‐Gardini Andrea
Published: July 2021

Background and Aim

Lenvatinib is a standard of care option in first‐line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome.

Methods

We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first‐line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression‐free survival (PFS).

Results

The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46–0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25–2.32, P = .0007) by multivariate analysis. Appearance of hand‐foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56–0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04–1.77, P = .0277).

Conclusions

Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients’ quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.