bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch is an alternative splicing gene in brown planthopper, Nilaparvata lugens
Authors: Hu Ding‐Bang , Xiao Shuai , Wang Yefu , Hua Hong‐Xia
Published: April 2022

Much research has assumed that Notch codes one protein. Then the protein will be cleaved into two parts and regenerates a heterodimers receptor to construct Notch signal pathways to regulate development in the past three decades. Here, we show that Notch in brown planthopper is a complex alternatively spliced gene has at least three transcriptional start sites, four exon skips, and 21 transcriptional endpoints that uses these to form variants and codes a series of proteins. When used dsRNAs to suppression different regions of the full‐length variant NlNF resulted in a similar phenotype. Insects were molting after treatment, sensation circles on antennas near to root decayed, bristles on wings shortened, thickened or disappeared, accompanied by thickening veins and blades of fore‐wing apex regions thickened. These results suggested that Notch influenced developmental of sensation circles, bristles, veins, and blades in nymph late periods. This study has deepened our understanding of Notch.
Using e‐learning tools in biochemistry teaching for undergraduate medical students in multicultural environment in Ukraine during COVID‐19 crisis
Authors: Volodarets Svitlana , Chernousova Nataliia , Peleshenko Hanna , Maslak Hanna , Savchenko Anastasiia , Netronina Olha
Published: April 2022

Through the special situation like the COVID‐2019 lockdown, interactive techniques play a prime role in the study process. The strategy of lockdown ways of higher education was provided in Ukraine as well as in other countries since March 2020. Our investigation was performed at the Department of Biochemistry and Medical Chemistry of Dnipro State Medical University during the first lockdown of COVID‐19 from March to June 2020. The main aim of the research was the evaluation of the students' attitudes to studying Biochemistry using Google classrooms and Moodle. Four hundred and sixty‐three students studying in English, French, and Ukrainian took part in the survey. Our results reveal that majority of the students found Google classrooms and Moodle as useful e‐learning tools. However, questions dealing with the technical issues of using the Google classrooms on laptops and mobile phones and submitting the replies to the Google classrooms cause difficulties among the students.
The relationship between isolated hypertension with brain volumes in UK Biobank
Authors: Newby Danielle , Winchester Laura , Sproviero William , Fernandes Marco , Ghose Upamanyu , Lyall Donald , Launer Lenore J. , Nevado‐Holgado Alejo J.
Published: April 2022

Background

Hypertension is a well‐established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertensions, such as isolated hypertension on brain health and its comparison to systolic‐diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure (BP) or systolic‐diastolic hypertension using the largest cohort of healthy individuals.

Methods

Using the UK Biobank cohort, we carried out a cross‐sectional study using 29,775 participants (mean age 63 years, 53% female) with BP measurements and brain magnetic resonance imaging (MRI) data. We used linear regression models adjusted for multiple confounders to compare a variety of global, subcortical, and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic‐diastolic hypertension.

Results

The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller gray matter but larger white matter microstructures and macrostructures compared to normotensives. Isolated systolic hypertensives had larger total gray matter and smaller white matter traits when comparing these regions with participants with systolic‐diastolic hypertension.

Conclusions

These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic‐diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.
Recombinant human erythropoietin accelerated the proliferation of non‐small cell lung cancer cell lines and reduced the expression of VEGF, HIF‐1α, and PD‐L1 under a simulated hypoxic environment in vitro
Authors: Zhang Yajing , Feng Yangchun , Sun Xiaojie
Published: April 2022

Background

As erythropoietin (EPO) has been used to treat anemia in cancer patients, negative controversy has continued. Unfortunately, its effects on non‐small‐cell lung carcinoma (NSCLC) cell lines are uncertain and the phenomenon of inducing immune escape of tumor cells remains to be explored. This study aimed to provide an important basis for the application of exogenous EPO in the treatment of tumor‐associated anemia.

Methods

Cells were cultured in 1% O2, 5% CO2, and 94% N2 to simulate a hypoxic environment of the tumor. A549 cell line (lower expression EPOR) and NCI‐H838 cell line (higher expression EPOR) were treated with 2 and 8 U/ml recombinant human EPO (rhEPO). CCK‐8 method was used to determine the logarithmic growth phase of the cells and to detect cell proliferation. The expression levels of VEGF, HIF‐1α, and PD‐L1 were determined by western blot. One‐way ANOVA was used for statistical analysis between groups, with p < 0.05 indicating a significant difference.

Results

Hypoxia itself could decrease the survival rate of NSCLC cells. Under the hypoxic condition, rhEPO induced tumor cells proliferation, especially in the NCI‐H838 cell line, where 2 U/ml rhEPO increased the total number of surviving cells (Hypoxia + rhEPO 2 U/ml vs. Hypoxia, p < 0.05). Western blot analysis showed that hypoxia upregulated the expression of VEGF, HIF‐1α, and PD‐L1 in NSCLC cell lines (Normoxia vs. Hypoxia, p < 0.05), but may not be dependent on the expression levels of EPOR. RhEPO decreased the expression levels of VEGF and HIF‐1α. In the A549 cell line, it depended on the concentration of rhEPO and was particularly obvious in HIF‐1α (Hypoxia vs. Hypoxia + rhEPO 2 U/ml vs. Hypoxia + rhEPO 8 U/ml, p < 0.05). A low concentration of rhEPO may not reduce VEGF expression. In the NCI‐H838 cell line, the effect of rhEPO on VEGF was more obvious, but it may be independent of rhEPO concentrations. The downregulation of PD‐L1 expression by rhEPO was only presented in the A549 cell line and required higher rhEPO concentrations (Hypoxia + rhEPO 8 U/ml vs. Hypoxia&Hypoxia + rhEPO 2 U/ml, p < 0.05).

Conclusion

The effect of prolonged high concentrations of rhEPO under hypoxic conditions resulted in accelerated cells proliferation of non‐small‐cell lung cancer and was independent of EPOR expression levels on the cell lines surface. Hypoxia resulted in increased expression of VEGF, HIF‐1α, and PD‐L1 on the NSCLC cell lines. Under normoxic conditions, rhEPO did not affect the expression of VEGF, HIF‐1α, and PD‐L1; but under hypoxic conditions, the application of rhEPO reduced the expression of VEGF, HIF‐1α, and PD‐L1, producing an impact on the biological behavior of tumor cells.
Advancement of deep learning in pneumonia/Covid‐19 classification and localization: A systematic review with qualitative and quantitative analysis
Authors: Shah Aakash , Shah Manan
Published: April 2022

Around 450 million people are affected by pneumonia every year, which results in 2.5 million deaths. Coronavirus disease 2019 (Covid‐19) has also affected 181 million people, which led to 3.92 million casualties. The chances of death in both of these diseases can be significantly reduced if they are diagnosed early. However, the current methods of diagnosing pneumonia (complaints + chest X‐ray) and Covid‐19 (real‐time polymerase chain reaction) require the presence of expert radiologists and time, respectively. With the help of deep learning models, pneumonia and Covid‐19 can be detected instantly from chest X‐rays or computerized tomography (CT) scans. The process of diagnosing pneumonia/Covid‐19 can become faster and more widespread. In this paper, we aimed to elicit, explain, and evaluate qualitatively and quantitatively all advancements in deep learning methods aimed at detecting community‐acquired pneumonia, viral pneumonia, and Covid‐19 from images of chest X‐rays and CT scans. Being a systematic review, the focus of this paper lies in explaining various deep learning model architectures, which have either been modified or created from scratch for the task at hand. For each model, this paper answers the question of why the model is designed the way it is, the challenges that a particular model overcomes, and the tradeoffs that come with modifying a model to the required specifications. A grouped quantitative analysis of all models described in the paper is also provided to quantify the effectiveness of different models with a similar goal. Some tradeoffs cannot be quantified and, hence, they are mentioned explicitly in the qualitative analysis, which is done throughout the paper. By compiling and analyzing a large quantum of research details in one place with all the data sets, model architectures, and results, we aimed to provide a one‐stop solution to beginners and current researchers interested in this field.
“Corona between myth and science” – Innovative experiments and formats for analyzing fake news in corona times in chemistry lessons
Authors: Otte Lars , Beeken Marco
Published: April 2022

Da Schüler:innen oftmals sehr empfänglich für Fehlinformationen sind, sind (außer‐)schulische Formate von Nöten, die es ermöglichen, Fake News zu identifizieren. Aus diesem Grund wurden insgesamt fünf Wissenschaftskommunikationsformate entwickelt, die sich dem Themenkomplex „Fake News in der Corona‐Pandemie“ widmen. Dazu zählen beispielsweise ein Schülerlaborsetting und ein innovatives Buch. Die Formate können dabei als Ergänzung zum Chemieunterricht aufgefasst werden und einen entsprechenden Kompetenzzuwachs der Schüler:innen ermöglichen. In diesem Artikel werden darüber hinaus zwei der insgesamt 13 Experimente aus Schülerlaborsetting und Buch vorgestellt, die auch Einzug in den Chemieunterricht finden können.
Long‐term survival and toxicity in patients with neuroendocrine tumors treated with 177Lu‐octreotate peptide radionuclide therapy
Authors: Kennedy Kim R. , Turner John Harvey , MacDonald William B. G. , Claringbold Phillip G. , Boardman Glenn , Ransom David T.
Published: April 2022

Background

Peptide receptor radionuclide therapy (PRRT) has shown favorable results in neuroendocrine tumors (NETs). Long‐term safety and efficacy data for 177Lu‐octreotate PRRT, particularly in combination with chemotherapy, is lacking.

Methods

The authors conducted a retrospective review of the long‐term toxicity and survival outcomes of 104 patients with advanced NETs treated on 4 phase 2 clinical trials with Lutetium‐177‐octreotate (177Lu‐octreotate) PRRT, mostly in combination with chemotherapy. Median follow‐up was 68 months, which represents the longest follow‐up study of 177Lu‐octreotate PRRT for NETs to date.

Results

Median progression‐free survival (PFS) was 37 months, and median overall survival (OS) was 71 months. Five‐ and 10‐year OS were 62% and 29%, and 5‐ and 10‐year PFS were 36% and 21%, respectively, demonstrating 177Lu‐octreotate can provide durable responses. PRRT was well tolerated with 1.9% of patients developing chronic renal impairment and 1% of patients developing long‐term thrombocytopenia. Interestingly, there was a relatively high rate of myelodysplasia (MDS)/leukemia (6.7%), possibly attributable to the longer follow‐up (with all except 1 case occurring more than 4 years after PRRT treatment) or to the addition of concurrent chemotherapy.

Conclusions

Lutetium‐177‐Octreotate PRRT remains an efficacious and well tolerated treatment in long‐term follow‐up. For clinicians deciding on the timing of PRRT for individual patients, the 6.7% long‐term risk of MDS/leukemia needs to be balanced against the 21% PFS at 10 years.
Environmental conflicts as key factors influencing participatory environmental communication and sustainable development of a rural society
Authors: Zikargae Mekonnen Hailemariam , Woldearegay Amanuel Gebru , Skjerdal Terje
Published: April 2022

Natural resource protection in Africa, particularly in rural communities, requires effective communication between resource managers and community residents. Environmental conflict, however, impedes the efficacy of communication strategies. Thus, this study investigates evidence of environmental conflicts as impeding factors for participatory environmental communication in a rural community‐based environment and forest program in Northern Ethiopia, run by Organization for Rehabilitation and Development (ORDA) in Amhara, Ethiopia, a non‐governmental organization seeking to address rural poverty. It also addresses how these factors could be mediated by local cultural institutions. In addition, the article outlines how these factors influence interventions to promote livelihood development, environmental security, and sustainable development. Qualitative data was collected through in‐depth interviews, focus group discussions, document analysis, and observation. Convenience and purposive sampling were used to contact seventeen study participants. Participants were community members and professionals. The information was analyzed thematically. The study finds that environmental conflicts that arise from the community‐based socioeconomic, cultural, and ecological factors constitute a daunting obstacle to the sustainability of community projects, threatening the capacity of the community to manage common pool forest resources. At the same time, cultural interventions to reduce the occurrences, escalations, and prevalence of environmental conflicts are key to the success of participatory environmental communication measures and sustainable community‐based natural resource management in rural Africa, and should be included in implementation strategies by nongovernmental organizations such as ORDA.
Assessing phenotypic diversity in silflower (Silphium integrifolium Michx.) to identify traits of interest for domestication selection
Authors: Price John H. , Van Tassel David L. , Picasso Valentin D. , Smith Kevin P.
Published: April 2022

Silflower (Silphium integrifolium Michx.) has been identified as a candidate for domestication as a perennial oilseed crop. In order to successfully domesticate silflower it will be necessary to identify traits that should be targeted for selection. We have conducted the first multilocation trial of replicated silflower genotypes at six sites across four states. By observing architectural, phenological, and yield traits in a diversity panel of silflower breeding material, we were able to estimate the heritability of these traits, as well as patterns of correlation across years and environments. We found that this population expressed heritable variation for many, but not all, traits of interest, and that targeted introgression of diversity may be beneficial for some traits. In addition, we used regression analysis to identify several traits, particularly height, number of stalks per plant, and stalk diameter as important contributors to determining levels of yield and levels of lodging. These results will help to guide future silflower domestication efforts and have already shaped the direction of our breeding program.
The neuroinflammatory marker sTNFR2 relates to worse cognition and tau in women across the Alzheimer's disease spectrum
Authors: Bernier Rachel A. , Banks Sarah J. , Panizzon Matthew S. , Andrews Murray J. , Jacobs Emily G. , Galasko Douglas R. , Shepherd Alyx L. , Akassoglou Katerina , Sundermann Erin E. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2022

Introduction

Despite women showing greater Alzheimer's disease (AD) prevalence, tau burden, and immune/neuroinflammatory response, whether neuroinflammation impacts cognition differently in women versus men and the biological basis of this impact remain unknown. We examined sex differences in how cerebrospinal fluid (CSF) neuroinflammation relates to cognition across the aging–mild cognitive impairment (MCI)–AD continuum and the mediating role of phosphorylated tau (p‐tau) versus other AD biomarkers.

Methods

Participants included 284 individuals from the Alzheimer's Disease Neuroimaging Initiative study. CSF neuroinflammatory markers included interleukin‐6, tumor necrosis factor α, soluble tumor necrosis factor receptor 2 (sTNFR2), and chitinase‐3‐like protein 1. AD biomarkers were CSF p‐tau181 and amyloid beta1‐42 levels and magnetic resonance imaging measures of hippocampal and white matter hyperintensity volumes.

Results

We found a sex‐by‐sTNFR2 interaction on Mini‐Mental State Examination and Clinical Dementia Rating‐Sum of Boxes. Higher levels of sTNFR2 related to poorer cognition in women only. Among biomarkers, only p‐tau181 eliminated the female‐specific relationships between neuroinflammation and cognition.

Discussion

Women may be more susceptible than men to the adverse effects of sTNFR2 on cognition with a potential etiological link with tau to these effects.
Transjejunal endoscopic ultrasound‐guided pancreatic drainage for pancreatic jejunostomy stricture using a forward‐viewing echoendoscope in a patient with altered anatomy
Authors: Shimizu Hiroshi , Suzuki Rei , Sato Yuki , Takagi Tadayuki , Abe Naoto , Irie Hiroki , Sugimoto Mitsuru , Yanagita Takumi , Kobashi Ryoichiro , Hashimoto Minami , Kato Tsunetaka , Takasumi Mika , Nakamura Jun , Hikichi Takuto , Ohira Hiromasa
Published: April 2022

Pancreatic jejunostomy stricture (PJS) is one of the major late complications after pancreaticoduodenectomy. Endoscopic ultrasound‐guided pancreatic drainage (EUS‐PD) is considered a salvage treatment for symptomatic PJS after endoscopic retrograde pancreatography failure; however, the technical success rate of the endoscopic treatment of PJS remains unsatisfactory, mainly due to surgically altered anatomy. Herein, we describe a case of PJS successfully treated with transjejunal EUS‐PD using a forward‐viewing echoendoscope. A 62‐year‐old man who suffered from repetitive severe back pain due to PJS was referred to our hospital. Since transgastric EUS‐PD was difficult, we attempted transjejunal EUS‐PD using a forward‐viewing echoendoscope. To facilitate scope insertion, we first straightened the afferent jejunal loop and placed a stiff guidewire. With this scheme, we successfully performed transjejunal EUS‐PD and placed a 5‐Fr plastic stent. In conclusion, this technique is useful for treating patients with PJS when transgastric EUS‐PD is difficult.
Initial and advanced endoscopic findings of monomorphic epitheliotropic intestinal T‐cell lymphoma in the duodenum: A case report
Authors: Fukushima Masanori , Honda Tetsuro , Komatsu Naohiro , Sasaki Ryu , Ozawa Eisuke , Miuma Satoshi , Miyaaki Hisamitsu , Irie Junji , Okano Shinji , Nakao Kazuhiko
Published: April 2022

Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL) is an aggressive malignant digestive system lymphoma. We report the case of a 68‐year‐old Asian woman who was diagnosed with MEITL of the duodenum and small intestine due to intestinal obstruction. MEITL is mainly located in the small intestine, and duodenal lesions are rare. Therefore, the endoscopic appearance of MEITL in the duodenum has been reported in only a few cases. In this case, we observed the initial and advanced endoscopic findings of MEITL in the duodenum. The initial findings were only slight mucosal changes; therefore, careful observation is required to detect early‐stage MEITL.
Use of mitochondrial sequencing to detect gene doping in horses via gene editing and somatic cell nuclear transfer
Authors: Maniego Jillian , Pesko Bogusia , Habershon‐Butcher Jocelyn , Hincks Pamela , Taylor Polly , Tozaki Teruaki , Ohnuma Aoi , Stewart Graham , Proudman Christopher , Ryder Edward
Published: April 2022

Gene editing and subsequent cloning techniques offer great potential not only in genetic disease correction in domestic animals but also in livestock production by enhancement of desirable traits. The existence of the technology, however, leaves it open to potential misuse in performance‐led sports such as horseracing and other equestrian events. Recent advances in equine gene editing, regarding the generation of gene‐edited embryos using CRISPR/Cas9 technology and somatic cell nuclear transfer, have highlighted the need to develop tools to detect potential prohibited use of the technology. One possible method involves the characterisation of the mitochondrial genome (which is not routinely preserved during cloning) and comparing it with the sequence of the registered dam. We present here our approach to whole‐mitochondrial sequencing using tiled long‐range PCR and next‐generation sequencing. To determine whether the background mutation rate in the mitochondrial genome could potentially confound results, we sequenced 10 sets of dam and foal duos. We found variation between duos but none within duos, indicating that this method is feasible for future screening systems. Analysis of WGS data from over 100 Thoroughbred horses revealed wide variation in the mitochondria sequence within the breed, further displaying the utility of this approach.
Causes and consequences of pair‐bond disruption in a sex‐skewed population of a long‐lived monogamous seabird
Authors: Sun Ruijiao , Barbraud Christophe , Weimerskirch Henri , Delord Karine , Patrick Samantha C. , Caswell Hal , Jenouvrier Stephanie
Published: April 2022

Many animals form long‐term monogamous pair bonds, and the disruption of a pair bond (through either divorce or widowhood) can have significant consequences for individual vital rates (survival, breeding, and breeding success probabilities) and life‐history outcomes (lifetime reproductive success [LRS], life expectancy). Here, we investigated the causes and consequences of pair‐bond disruption in wandering albatross (Diomedea exulans). State‐of‐the‐art statistical and mathematical approaches were developed to estimate divorce and widowhood rates and their impacts on vital rates and life‐history outcomes. In this population, females incur a higher mortality rate due to incidental fishery bycatch, so the population is male‐skewed. Therefore, we first posited that males would show higher widowhood rates negatively correlated with fishing effort and females would have higher divorce rates because they have more mating opportunities. Furthermore, we expected that divorce could be an adaptive strategy, whereby individuals improved breeding success by breeding with a new partner of better quality. Finally, we posited that pair‐bond disruptions could reduce survival and breeding probabilities owing to the cost of remating processes, with important consequences for life‐history outcomes. As expected, we showed that males had higher widowhood rates than females and females had higher divorce rates in this male‐skewed population. However, no correlation was found between fishing effort and male widowhood. Secondly, contrary to our expectation, we found that divorce was likely nonadaptive in this population. We propose that divorce in this population is caused by an intruder who outcompetes the original partner in line with the so‐called forced divorce hypothesis. Furthermore, we found a 16.7% and 18.0% reduction in LRS only for divorced and widowed males, respectively, owing to missing breeding seasons after a pair‐bond disruption. Finally, we found that divorced individuals were more likely to divorce again, but whether this is related to specific individual characteristics remains an important area of investigation.
FoRAGE database: A compilation of functional responses for consumers and parasitoids
Authors: Uiterwaal Stella F. , Lagerstrom Ian T. , Lyon Shelby R. , DeLong John P.
Published: April 2022

Functional responses, the relationships between consumer foraging rate and resource (prey) density, provide key insights into consumer–resource interactions while also being a major driver of population dynamics and food web structure. We present a global database of 2598 standardized functional responses and parameters extracted from the published literature. We refit the functional responses with a Type II model using standardized methods and report the fitted parameters along with data on experimental conditions, consumer and resource taxonomy and type, as well as the habitat and dimensionality of the foraging interaction. The consumer and resource species covered here are taxonomically diverse, from protozoans filtering algae to wasps parasitizing moth larvae to wolves hunting moose. The FoRAGE (Functional Responses from Around the Globe in all Ecosystems) database (doi: 10.5063/DB807S) is a living data set that will be updated periodically as new functional responses are published. Data are released under a CC‐By‐NC‐SA license, and credit should be given to this paper when referring to this specific version of the data release.
Contrasting patterns of richness, abundance, and turnover in mountain bumble bees and their floral hosts
Authors: Sponsler Douglas B. , Requier Fabrice , Kallnik Katharina , Classen Alice , Maihoff Fabienne , Sieger Johanna , Steffan‐Dewenter Ingolf
Published: April 2022

Environmental gradients generate and maintain biodiversity on Earth. Mountain slopes are among the most pronounced terrestrial environmental gradients, and the elevational structure of species and their interactions can provide unique insight into the processes that govern community assembly and function in mountain ecosystems. We recorded bumble bee–flower interactions over 3 years along a 1400‐m elevational gradient in the German Alps. Using nonlinear modeling techniques, we analyzed elevational patterns at the levels of abundance, species richness, species β‐diversity, and interaction β‐diversity. Though floral richness exhibited a midelevation peak, bumble bee richness increased with elevation before leveling off at the highest sites, demonstrating the exceptional adaptation of these bees to cold temperatures and short growing seasons. In terms of abundance, though, bumble bees exhibited divergent species‐level responses to elevation, with a clear separation between species preferring low versus high elevations. Overall interaction β‐diversity was mainly caused by strong turnover in the floral community, which exhibited a well‐defined threshold of β‐diversity rate at the tree line ecotone. Interaction β‐diversity increased sharply at the upper extreme of the elevation gradient (1800–2000 m), an interval over which we also saw steep decline in floral richness and abundance. Turnover of bumble bees along the elevation gradient was modest, with the highest rate of β‐diversity occurring over the interval from low‐ to mid‐elevation sites. The contrast between the relative robustness bumble bee communities and sensitivity of plant communities to the elevational gradient in our study suggests that the strongest effects of climate change on mountain bumble bees may be indirect effects mediated by the responses of their floral hosts, though bumble bee species that specialize in high‐elevation habitats may also experience significant direct effects of warming.
Impact of a cardio‐oncology unit on prevention of cardiovascular events in cancer patients
Authors: Cuomo Alessandra , Mercurio Valentina , Varricchi Gilda , Galdiero Maria Rosaria , Rossi Francesca Wanda , Carannante Antonio , Arpino Grazia , Formisano Luigi , Bianco Roberto , Carlomagno Chiara , De Angelis Carmine , Giuliano Mario , Matano Elide , Picardi Marco , Salvatore Domenico , De Vita Ferdinando , Martinelli Erika , Della Corte Carminia Maria , Morgillo Floriana , Orditura Michele , Napolitano Stefania , Troiani Teresa , Tocchetti Carlo G.
Published: April 2022

Aims

As the world population grows older, the co‐existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio‐Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications.

Methods and results

We enrolled 231 consecutive patients referred to our Cardio‐Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48 month‐survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow‐up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P = 0.04).

Conclusions

Patients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments.
Evaluation of antioxidant activity of nano‐ and microencapsulated rosemary (Rosmarinus officinalis L.) leaves extract in cress (Lepidium sativum) and basil (Ocimum basilicum) seed gums for enhancing oxidative stability of sunflower oil
Authors: Jafari Seyede Zeynab , Jafarian Sara , Hojjati Mohammad , Najafian Leila
Published: April 2022

There has been interest in the use of plant extract as a natural preservative agent for improving the oxidative stability of vegetable oils. However, plant extracts have low stability against heat and environmental stress. In this study, the antioxidant potential of nano‐ and microencapsulated Rosmarinus officinalis L. extract (RE) obtained using the ultrasonication method was measured. The total phenolic and flavonoid content of the extract was 174.4 ± 25.9 mg gallic acid/g extract and 78.30 ± 3.2 mg rutin/g extract, respectively. Antioxidant activity of 50, 100, 200, and 400 ppm of RE was measured by DPPH free radical scavenging methods, ferric reduction assay, and β‐carotene/linoleic acid assay, and then compared to the 100 ppm of TBHQ as a common synthetic antioxidant. The results showed that the antioxidant activity increased with increasing the concentration of the extract in all evaluating methods. The antioxidant activity of 200 ppm of the free and encapsulated extract in cress (Lepidium sativum) and basil (Ocimum basilicum) seed gums at different ratios (1:0, 1:1, and 0:1) was compared to sunflower oil without antioxidants, and oil‐containing TBHQ which was stored at 60°C for 24 days. The oxidation indexes of oil samples include peroxide value, thiobarbituric acid value, and p‐anisidine value measured at 4‐day intervals. A lower oil oxidation was observed in oil‐containing nanoencapsulated extract followed by microencapsulated extract, free extract, and TBHQ. Since producing nanoencapsulated RE requires a higher time and speed of homogenization and due to no statistically significant difference between the antioxidant properties of nanocapsules and microcapsules in oil, the use of microcapsules of RE in basil seed gum to increase the shelf life of sunflower oil is recommended.
Progranulin deficiency promotes persistent neuroinflammation and causes regional pathology in the hippocampus following traumatic brain injury
Authors: Zheng Xiaojing , Mi Tiantian , Wang Rong , Zhang Zihan , Li Wenyan , Zhao Junli , Yang Peiyan , Xia Haibin , Mao Qinwen
Published: April 2022

Traumatic brain injury (TBI) can be progressive and can lead to the development of a long‐term complication termed chronic traumatic encephalopathy. The mechanisms underlying the progressive changes are still unknown; however, studies have suggested that microglia‐mediated neuroinflammation in response to TBI may play a fundamental role. This study aimed to determine whether progranulin (PGRN), a major modulator of microglial activity, plays a role in the progressive damage following TBI. PGRN‐deficient and wild‐type mice were subjected to controlled cortical impact and were observed neuropathologically after 3 days, 7 days, and 5 months. Compared to sham and wild‐type mice, the PGRN‐deficient mice showed overall stronger microgliosis and astrocytosis. The astrocytosis involved broader areas than the microgliosis and was more prominent in the basal ganglia, hippocampus, and internal capsule in PGRN‐deficient mice. Ongoing neuronal death was uniquely observed in the hippocampal CA3 region of PGRN‐deficient mice at 5 months after TBI, accompanying the regional chronic microgliosis and astrocytosis involving the CA3 commissural pathway. In addition, there was M1 microglial polarization in the pericontusional area with activated TLR4/MyD88/NF‐κB signaling; however, the hippocampus showed only mild M1 polarization 7 days after TBI. Lastly, Morris water maze tests showed PGRN‐deficient mice had poorer spatial learning and memory 5 months after TBI than wild‐type or sham mice. The data indicated the PGRN deficiency caused TBI progression by promoting persistent microgliosis with microglial polarization and astrocytosis, as well as regional pathology in the hippocampus. The study suggests that PGRN should be evaluated as a potential therapy for TBI.
Rent appropriation in global value chains: The past, present, and future of intangible assets
Authors: Buckley Peter J. , Strange Roger , Timmer Marcel P. , de Vries Gaaitzen J.
Published: April 2022

Research Summary

The argument of this article is that global strategy research should devote greater attention to rent appropriation in global value chains (GVCs). We discuss the concept of intangible assets, emphasize their scalability at low marginal cost and highlight strategies for the appropriation of rents from these assets. Returns captured by intangible assets are shown to be much greater than those captured by tangible assets in GVCs of manufactured products. Regions in the world are found to be specializing in different GVC stages, with China rising as a key location for rent generation in upstream and production activities. We conclude that the rents from intangible assets are major drivers of economic development and of corporate success and offer insights into rent appropriation trends in the future.

Managerial Summary

Intangible assets include computerized information (such as databases and software), innovative property (such as patents, trademarks, and copyrights), and economic competencies (such as brand equity and organizational capital). Our analysis shows that the returns to intangible assets in the GVCs of manufactured goods have risen substantially in importance over the past 20 years. A further finding is that within GVCs, the rent share of upstream stages has been increasing at the expense of rents shares of both the production and downstream stages. These findings suggest that the effective deployment, management, and protection of intangible assets is of critical importance to the ability of firms to create and maintain sustainable competitive advantages in global markets. In GVCs, intangibles matter, big time!
Threat vigilance and intrinsic amygdala connectivity
Authors: Kirk Peter A. , Holmes Avram J. , Robinson Oliver J.
Published: April 2022

A well‐documented amygdala‐dorsomedial prefrontal circuit is theorized to promote attention to threat (“threat vigilance”). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g., through threat‐of‐shock and movie‐watching). In the present study, we predicted that—for those scoring high in self‐reported anxiety and a behavioral measure of threat vigilance—this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting‐state fMRI data (N = 639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self‐reported anxiety) and intrinsic amygdala‐periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that amygdala‐prefrontal circuitry may only be engaged in response to anxiogenic stimuli.
An international survey on patterns of practice in NAFLD and expectations for therapies—The POP‐NEXT project
Authors: Ratziu Vlad , Anstee Quentin M. , Wong Vincent Wai‐Sun , Schattenberg Jörn M. , Bugianesi Elisabetta , Augustin Salvador , Gheorghe Liana , Zambon Vittoria , Reau Nancy
Published: April 2022

Background and Aims

Differences between countries in NAFLD patient care pathways and management need to be understood prior to defining supranational guidelines.

Approach and Results

We conducted an anonymous survey in France, Germany, Hong Kong, Italy, Romania, Spain, the United Kingdom, and the United States among physicians providing specialist care for patients with NAFLD. Modalities of patient referral, patterns of practice (diagnosis, staging, monitoring, and indications for liver biopsy), therapeutic management, and expectations for future NASH pharmacotherapies were assessed, with 664 physicians completing the survey. Referral to surveyed physicians (SPs) mostly came from primary care. Prior to referral, NAFLD was rarely diagnosed, and noninvasive tests were not performed. Screening for comorbidities by SPs was incomplete and cardiovascular risk not calculated. Elastometry in combination with a serum biomarker was the most common first‐line method for fibrosis staging. Liver biopsy, when performed, was often delayed by at least 1 year after diagnosis. It was, however, recommended even if noninvasive methods indicated advanced fibrosis. Frequent, biannual monitoring was conducted, including HCC surveillance in Stage 3 fibrosis. SPs rarely implemented and followed dietary and lifestyle changes themselves, and local availability of such programs was highly heterogenous. SPs favored pharmacotherapy based on mechanism of action adapted to the stage of the disease, including for early stages such as steatohepatitis with mild fibrosis.

Conclusions

This international survey revealed major deficiencies and delays in referral pathways, suboptimal screening for comorbidities or managing of lifestyle modifications by SPs, and limited local availability for nonpharmacological interventions. Monitoring practices are not aligned with current guidelines.
Magnetically driven chemically reactive Casson nanofluid flow over curved surface with thermal radiation
Authors: Maity Suprakash , Kundu Prabir K.
Published: April 2022

During this exploration, Casson nanofluid is taken over a sheet that is curved and stretching in nature and its flow equations are analyzed. Radiation and slip provisions are also taken into consideration. A magnetic field of uniform rate is provided. Convective heat and mass transference extract dominant conclusions from the system. The Brownian migration together with thermophoresis is also included in the flow structure. Moreover, the chemical reaction of higher‐order within the nanoingredients also generates interest. Guiding equations furnished by the selected model are resettled to ordinary differential equations of nonlinear type by significant similarity transformation. We have worked on MAPLE‐19 software to work out this with a suitable accuracy rate. Upshots are shown with diagrams and tables. Corresponding physical consignment such as Nusselt number has been analyzed. Determination of skin friction and moreover Sherwood's number is also in the area of interest. Magnificent advancement in heat sifting is dealt with by magnetic and Brownian motion specification. The graphs prescribed the upshots of thermophoresis and slip parameters. Outcomes convey that temperature together with concentration are reduced for stretching parameters but velocity lines are enhanced. Heat transport goes up for magnetic and Brownian motion framework but elevated outcomes are spotted for radiative flow in contrast to nonradiative flow. Mass transfer is reduced for chemical reaction components but the rate of augmentation is elevated for higher‐order chemically reactive flow. Mass Biot number and temperature Biot number both increase the concentration and temperature transport, respectively.
Gender differences in risk factors for the 2 year development of sarcopenia in community‐dwelling older adults
Authors: Choe Hun Jee , Cho Be Long , Park Yong Soon , Roh Eun , Kim Hyeon Ju , Lee Sam‐Gyu , Kim Bong Jo , Kim Miji , Won Chang Won , Park Kyong Soo , Jang Hak Chul
Published: April 2022

Background

Sarcopenia is an age‐related chronic condition that can lead to mobility disabilities. This study aimed to evaluate the risk factors for incident sarcopenia in older Korean adults.

Methods

The Korean Frailty and Aging Cohort Study (KFACS) is a multicentre prospective study with a baseline examination in 2016–2017. A prospective follow‐up study was conducted in 2018–2019. Changes in muscle‐related variables were evaluated for subjects aged 70–84 years lacking sarcopenia at baseline. Sarcopenia was diagnosed according to the 2019 updated Asian Working Group for Sarcopenia consensus.

Results

Among the 1636 participants (54.4% women, age 75.9 ± 3.7) who did not have sarcopenia at baseline, 101 men (13.5%) and 104 women (11.7%) developed sarcopenia by the follow‐up. Those who developed sarcopenia were older (men, 77.9 ± 3.9 vs. 75.7 ± 3.5, P < 0.001; women, 77.5 ± 4.0 vs. 75.5 ± 3.6, P < 0.001) with a lower body mass index at baseline (men, 23.9 ± 2.4 vs. 24.5 ± 2.9 kg/m2, P = 0.025; women, 23.7 ± 2.8 vs. 25.2 ± 2.9 kg/m2, P < 0.001) compared with older adults who remained nonsarcopenic; levels of glycated haemoglobin (men, 6.2 ± 1.0% vs. 5.9 ± 0.8%, P = 0.029) and the homeostasis model assessment of insulin resistance (men, 2.0 ± 1.3 vs. 1.7 ± 1.2, P = 0.022) were higher in men who progressed to sarcopenia but not in women. Development of sarcopenia was associated with older age and the frequency of resistance training (≥2 per week) after adjusting for potential risk factors in men [age, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.10–1.25; frequent resistance training, OR 0.50, 95% CI 0.30–0.82]. In women, advanced age, poor nutritional status, and physical inactivity contributed to the development of sarcopenia (age, OR 1.14, 95% CI 1.08–1.21; mini nutritional assessment short form, OR 0.79, 95% CI 0.70–0.90; moderate to high physical activity, OR 0.57, 95% CI 0.34–0.95).

Conclusions

In this 2 year KFACS follow‐up, modifiable risk factors for incident sarcopenia differed between genders. Resistance training (≥2 per week) helped to prevent sarcopenia in these community‐dwelling older men. In older women, adequate nutritional support and being physically active might play a role in preventing progression to sarcopenia.
Echinacoside alleviates sevoflurane‐induced cognitive dysfunction by activating FOXO1‐mediated autophagy
Authors: Yang Huifang , Zhao Li , Li Qin
Published: April 2022

The current study aimed to examine the effects of echinacoside on cognitive impairment in mice after exposure to sevoflurane. To examine the role of FOXO1, si‐FOXO1 and si‐con were injected into the hippocampus through the left lateral cerebral ventricles. Sevoflurane‐induced mice had serious cognitive dysfunction. However, pretreatment with echinacoside alleviated the cognitive dysfunction, as measured by a shortened escape latency time, and increased platform crossing times, the percentage of distance in the target quadrant and Y‐maze spontaneous alternations. In addition, we found that echinacoside elevated FOXO1 expression in the hippocampus; increased the expression of autophagy‐related proteins including Beclin 1, ATG5, ATG7, and LC3; and reduced P62 expression. Silencing of FOXO1 aggravated the cognitive deficits and reduced expression of the autophagy‐related markers, whereas the effects of si‐FOXO1 on memory were abrogated by echinacoside. Echinacoside attenuated the cognitive impairment in sevoflurane‐induced mice through FOXO1‐mediated autophagy.
Considerations for extracellular vesicle and lipoprotein interactions in cell culture assays
Authors: Busatto Sara , Yang Yubo , Iannotta Dalila , Davidovich Irina , Talmon Yeshayahu , Wolfram Joy
Published: April 2022

With an exponential increase in extracellular vesicle (EV) studies in the past decade, focus has been placed on standardization of experimental design to ensure inter‐study comparisons and validity of conclusions. In the case of in vitro assays, the composition of cell culture media is important to consider for EV studies. In particular, levels of lipoproteins, which are critical components of the interstitial fluid, should be taken into consideration. Results from this study reveal that lipoprotein levels in cell culture medium impact the effects that EVs have on recipient cells. Additionally, evidence of EV binding and fusion to lipoprotein‐like structures in plasma is provided. However, it is unclear whether the impact of lipoproteins in cell culture is due to direct interactions with EVs, indirect effects, or a combination of both mechanisms. Taken together, cell culture studies performed in the absence of physiological levels of lipoproteins are unlikely to reflect interactions that occur between EVs and recipient cells in an in vivo environment.
Detection rate of endoscopic ultrasound and computed tomography in diagnosing pancreatic neuroendocrine neoplasms including small lesions: A multicenter study
Authors: Kurita Yusuke , Hara Kazuo , Kobayashi Noritoshi , Kuwahara Takamichi , Mizuno Nobumasa , Okuno Nozomi , Haba Shin , Yagi Shin , Hasegawa Sho , Sato Takamitsu , Hosono Kunihiro , Endo Itaru , Shimizu Yasuhiro , Niwa Yasumasa , Utsunomiya Daisuke , Inaba Yoshitaka , Nakajima Atsushi , Kubota Kensuke , Ichikawa Yasushi
Published: April 2022

Background/Purpose

The detection ability and role of different imaging modalities to detect pancreatic neuroendocrine neoplasms (PNENs) including small lesions is unclear. This study aimed to compare the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to detect PNENs.

Methods

Data of patients who underwent EUS and contrast‐enhanced CT and were diagnosed with PNENs were analyzed. The detection rates of pancreatic lesions with EUS and CT based on tumor size and influencing factors were investigated.

Results

For 256 PNEN lesions, the detection rate of EUS was better than that of CT (94.5% vs 86.3%; P < .001). EUS was significantly superior to CT for PNENs ≤5 mm (58.3% vs 16.7%; P = .006) and 5‐10 mm (97.7% vs 79.5%; P = .008). There was no significant difference in the detection rate between EUS and CT for PNENs >10 mm (98.4% vs 96.4%; P = .375). Size (≤5 mm) and insulinoma were independent factors associated with poor EUS and CT detection rates.

Conclusions

Endoscopic ultrasound exhibited better detection ability than CT, with an excellent detection rate for PNENs >5 mm, except for insulinomas. CT could detect PNENs >10 mm, which are amenable to treatment.