bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Manifestation Associated With Multicentric Reticulohistiocytosis
Authors: Yamamoto Toshiyuki
Published: December 2020

Multicentric reticulohistiocytosis (MRH) is a rare multisystem disorder, primarily affecting the skin and joints. As severe joint damage is a possible symptom, early diagnosis and therapeutic intervention are required. Cutaneous lesions present with characteristic features such as discrete reddish nodules, especially on acral locations. Additionally, the face, scalp, trunk and extremities are also affected. Xanthomatous plaques are also seen on the face. The cutaneous manifestations of MRH are various, which therefore should be differentiated from several diseases. In particular, MRH has been reported to assume clinical appearances resembling Gottron papules, periungual erythema, V-neck erythema, shawl sign, and poikiloderma associated with dermatomyositis. Histopathologic features show proliferation of multinucleated giant cells with abundant eosinophilic granular ground glass–like cytoplasm in the dermis. Multicentric reticulohistiocytosis is occasionally paraneoplastic and is associated with internal malignancies. The appropriate therapies are still challenging, and oral prednisolone, immunosuppressants, and recent biologics are used. In this article, cutaneous lesions, histopathology, and pathogenesis of MRH are mainly discussed from a dermatological perspective. It is important, not only for dermatologists but also for rheumatologists and orthopedists, to be able to distinguish between the various types of skin lesions brought on by MRH. Cutaneous signs are important diagnostic clues and assessment tools for therapeutic efficacy.
Multiplex genotyping method to validate the multiallelic genome editing outcomes using machine learning-assisted long-read sequencing
Authors: Kuno Akihiro , Ikeda Yoshihisa , Ayabe Shinya , Kato Kanako , Sakamoto Kotaro , Suzuki Sayaka , Morimoto Kento , Wakimoto Arata , Mikami Natsuki , Ishida Miyuki , Iki Natsumi , Hamada Yuko , Takemura Megumi , Daitoku Yoko , Tanimoto Yoko , Huong Dinh Tra Thi , Murata Kazuya , Hamada Michito , Muratani Masafumi , Yoshiki Atsushi , Sugiyama Fumihiro , Takahashi Satoru , Mizuno Seiya
Published: December 2020

Genome editing can introduce designed mutations into a target genomic site. Recent research has revealed that it can also induce various unintended events such as structural variations, small indels, and substitutions at, and in some cases, away from the target site. These rearrangements may result in confounding phenotypes in biomedical research samples and cause a concern in clinical or agricultural applications. However, current genotyping methods do not allow a comprehensive analysis of diverse mutations for phasing and mosaic variant detection. Here, we developed a genotyping method with an on-target site analysis software named Determine Allele mutations and Judge Intended genotype by Nanopore sequencer (DAJIN) that can automatically identify and classify both intended and unintended diverse mutations, including point mutations, deletions, inversions, and cis double knock-in at single-nucleotide resolution. Our approach with DAJIN can handle approximately 100 samples under different editing conditions in a single run. With its high versatility, scalability, and convenience, DAJIN-assisted multiplex genotyping may become a new standard for validating genome editing outcomes.
Neuroanatomical Norms in the UK Biobank: The Impact of Allometric Scaling, Sex, and Age.
Authors: WILLIAMS Camille , Peyre Hugo , Toro Roberto , Ramus Franck
Published: December 2020

Few neuroimaging studies are sufficiently large to adequately describe population-wide variations. This study's primary aim was to generate neuroanatomical norms and individual markers that consider age, sex, and brain size, from 629 cerebral measures in the UK Biobank (N = 40 028). The secondary aim was to examine the effects and interactions of sex, age, and brain allometry - the non-linear scaling relationship between a region and brain size (e.g., Total Brain Volume) across cerebral measures.
Allometry was a common property of brain volumes, thicknesses, and surface areas (83%) and was largely stable across age and sex. Sex differences occurred in 67% of cerebral measures (median |std. beta|= 0.13): 37% of regions were larger in males and 30% in females. Brain measures (49%) generally decreased with age, although aging effects varied across regions and sexes. While models with an allometric or linear covariate adjustment for brain size yielded similar significant effects, omitting brain allometry influenced reported sex differences in variance.
This large scale-study advances our understanding of age, sex, and brain allometry's impact on brain structure and provides data for future UK Biobank studies to identify the cerebral regions that covary with specific phenotypes, independently of sex, age, and brain size.
High-Throughput Developability Assays Enable Library-Scale Identification of Producible Protein Scaffold Variants
Authors: Golinski Alexander W. , Mischler Katelynn M. , Laxminarayan Sidharth , Neurock Nicole , Fossing Matthew , Pichman Hannah , Martiniani Stefano , Hackel Benjamin J.
Published: December 2020

Proteins require high developability - quantified by expression, solubility, and stability - for robust utility as therapeutics, diagnostics, and in other biotechnological applications. Measuring traditional developability metrics is low-throughput in nature, often slowing the developmental pipeline. We evaluated the ability of three high-throughput developability assays to predict the bacterial recombinant expression of paratope variants of the protein scaffold Gp2. Enabled by a phenotype/genotype linkage, assay performance for 105variants was calculated via deep sequencing of populations sorted by proxied developability. We trained a random forest model that predicts expression from assay performance that is 35% closer to the experimental variance and trains 80% more efficiently than a model predicting from sequence information alone. Utilizing the predicted expression, we performed a sitewise analysis and predicted mutations consistent with enhanced developability. The validated assays offer the ability to identify developable proteins at unprecedented scales, reducing the bottleneck of protein commercialization.
Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
Authors: Cejas RB , Tamaño-Blanco M , Blanco JG
Published: December 2020

Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular traffic of IgG mediated by the human neonatal Fc receptor (FcRn) in fibroblast cell lines with trisomy 21. Intracellular IgG trafficking studies in live cells showed that fibroblasts with trisomy 21 exhibit higher proportion of IgG in lysosomes (~10% increase), decreased IgG content in intracellular vesicles (~9% decrease), and a trend towards decreased IgG recycling (~55% decrease) in comparison to diploid cells. Amyloid-beta precursor protein (APP) overexpression in diploid fibroblasts replicated the increase in IgG sorting to the degradative pathway observed in cells with trisomy 21. The impact ofAPPon the expression ofFCGRT(alpha chain component of FcRn) was investigated byAPPknock down and overexpression of the APP protein.APPknock down increased the expression ofFCGRTmRNA by ~60% in both diploid and trisomic cells. Overexpression of APP in diploid fibroblasts and HepG2 cells resulted in a decrease inFCGRTand FcRn expression. Our results indicate that the intracellular traffic of IgG is altered in cells with trisomy 21. This study lays the foundation for future investigations into the role of FcRn in the context of DS.
EMT changes actin cortex rheology in a cell-cycle dependent manner
Authors: Hosseini K. , Frenzel A. , Fischer-Friedrich E.
Published: December 2020

The actin cortex is a key structure for cellular mechanics and cellular migration. Accordingly, cancer cells were shown to change their actin cytoskeleton and their mechanical properties in correlation with different degrees of malignancy and metastatic potential. Epithelial-Mesenchymal transition (EMT) is a cellular transformation associated with cancer progression and malignancy. To date, a detailed study of the effects of EMT on the frequency-dependent viscoelastic mechanics of the actin cortex is still lacking. In this work, we have used an established AFM-based method of cell confinement to quantify the rheology of the actin cortex of human breast, lung and prostate epithelial cells before and after EMT in a frequency range of 0.02 – 2 Hz. Interestingly, we find for all cell lines opposite EMT-induced changes in interphase and mitosis; while the actin cortex softens upon EMT in interphase, the cortex stiffens in mitosis. Our rheological data can be accounted for by a rheological model with a characteristic time scale of slowest relaxation. In conclusion, our study discloses a consistent rheological trend induced by EMT in human cells of diverse tissue origin reflecting major structural changes of the actin cytoskeleton upon EMT.

Significance statement

The actin cortex is a key structure for cellular mechanics and cellular migration. Correspondingly, migratory cancer cells were shown to change their mechanical properties to a softer phenotype. EMT is a cellular transformation associated with cancer progression and malignancy. To date, a detailed study of the effects of EMT on the mechanics of the actin cortex is still lacking. In this work, we provide such a study for human breast, lung and prostate epithelial cells in dependence of the cell cycle stage. We observe a softening of the actin cortex in interphase but stiffening in mitosis upon EMT. In conclusion, our study discloses a consistent mechanical trend induced by EMT in human cells of diverse tissue origin.
Neural network aided approximation and parameter inference of stochastic models of gene expression
Authors: Jiang Qingchao , Fu Xiaoming , Yan Shifu , Li Runlai , Du Wenli , Cao Zhixing , Qian Feng , Grima Ramon
Published: December 2020

Non-Markov models of stochastic biochemical kinetics often incorporate explicit time delays to effectively model large numbers of intermediate biochemical processes. Analysis and simulation of these models, as well as the inference of their parameters from data, are fraught with difficulties because the dynamics depends on the system’s history. Here we use an artificial neural network to approximate the time-dependent distributions of non-Markov models by the solutions of much simpler time-inhomogeneous Markov models; the approximation does not increase the dimensionality of the model and simultaneously leads to inference of the kinetic parameters. The training of the neural network uses a relatively small set of noisy measurements generated by experimental data or stochastic simulations of the non-Markov model. We show using a variety of models, where the delays stem from transcriptional processes and feedback control, that the Markov models learnt by the neural network accurately reflect the stochastic dynamics across parameter space.
Decreased autophagy of vascular smooth muscle cells was involved in hyperhomocysteinemia‐induced vascular ageing
Authors: Yan Wenjing , Cao Yan , Zhen Panpan , Ji Dengyu , Chai Jiayin , Xue Ke , Dai Hongyan , Wang Wen
Published: December 2020

Ageing and hyperhomocysteinemia (HHcy) are important risk factors for cardiovascular diseases (CVDs). HHcy affects the occurrence of vascular diseases in the elderly. So far, the mechanism of HHcy‐induced vascular ageing remains largely unknown. Autophagy level is significantly reduced in the ageing process, and restoring impaired autophagy to a normal state may be one of the possible ways to extend the expected longevity and lifespan in the future. In this study, we established the HHcy rat model by feeding a 2.5% methionine diet. Small animal ultrasound and the tail‐cuff method indicated that the vascular pulse wave velocity (PWV) and pulse pressure (PP) of HHcy rats were increased significantly compared with the control group. Vascular morphology and structure have been changed in HHcy rats, including lumen dilation, increased collagen fibre deposition and increased p53/p21/p16 expression. In vitro, under the stimulation of homocysteine (500 μmol/L, 24 hours), the rat vascular smooth muscle cells (VSMCs) presented senescence, which was characterized by the increased expression of ageing‐related markers, such as p16, p21 and p53 as well as increased senescence‐associated beta‐galactosidase (SA‐β‐gal) activity. Meanwhile, the autophagy level was decreased both in vivo and in vitro, shown as the increased level of autophagy substrate p62 and the reduced level of autophagy marker LC3 II/I in the thoracic aorta of HHcy rats and in Hcy‐treated VSMCs, respectively. The senescence phenotype of VSMCs was reversed by increased autophagy levels induced by rapamycin. Our findings indicate that decreased autophagy of VSMCs is involved in hyperhomocysteinemia‐induced vascular ageing.
Exploring the influence of stakeholder personality on crisis response evaluations and outcomes
Authors: Brown‐Devlin Natalie , Lim Hayoung Sally , Bouchacourt Lindsay , Devlin Michael B.
Published: December 2020

While public relations professionals are beginning to utilize psychographic data for more refined audience targeting methods, this study examines how elemental personality traits impact (1) crisis communication outcomes (lessen levels of attributed crisis responsibility, improve individual's reputation and increase positive word‐of‐mouth) and (2) evaluations of crisis response strategies during a paracrisis. This study utilized an experimental design with 368 collegiate participants. Results suggest that several underlying personality traits predict reputation repair‐outcomes regardless of the communication strategy used. For example, findings suggested that stakeholders who rated higher in gentleness and lower in modesty and social boldness reported higher reputational scores pertaining to the offending individual. Yet, other traits, such as prudence, interacted with strategies that prompt the offending individual's preferred crisis communication outcomes.
Acorn flour properties depending on the production method and laboratory baking test results: A review
Authors: Szabłowska Emilia , Tańska Małgorzata
Published: December 2020

Acorns, the fruit of the oak, have long been an important source of food in different cultures around the world. Despite their long culinary tradition, they have become under‐appreciated. Due to their high starch content, acorns are mainly used for flour production, and acorn flour is considered as a replacement for cereal flour in a wide range of applications in food production. This study reviewed the published literature concerning acorn flour production and composition as well as the possibility of using acorn flour in the most popular flour‐based products such as bread, cake, and cookies. The study also presents the advantages resulting from acorn flour incorporation to the human diet and acorn flour influence on the quality of bread and pastry products. This review found that acorn flour is characterized by a lack of gluten proteins and a high content of fiber and minerals as well as the presence of polyphenols with antioxidant properties. However, negative impact of its larger amount on the dough rheological features and product physical properties has been emphasized in many studies. The researchers recommend the incorporation of acorn flour up to a level of 15% in formulating composite flour for bread production. However, the literature data indicates that acorn flour substitution for pastry production depends on the product type and ranges from 10 to even 60%. It is also highlighted that the application of acorn flour into gluten‐free products is particularly favorable from a nutritional point of view.
Insights on the use of alternative solvents and technologies to recover bio‐based food pigments
Authors: de Souza Mesquita Leonardo M. , Martins Margarida , Pisani Luciana P. , Ventura Sónia P. M. , de Rosso Veridiana V.
Published: December 2020

This review will discuss, under the Circular Economy and Biorefinery concepts, the performance of the alternative solvents in the downstream process to recover natural pigments in a more sustainable way. Conventionally, pigments marketed on an industrial scale are produced through chemical synthesis by using petroleum derivatives as the main raw material. Also, the current production chain of the synthetic dyes is linear, with no solvent recycling and waste generation. Thus, the most promising processes of extraction and purification of natural pigments and strategies on the polishing of the solvents are here reviewed. In this review, the use of alternative solvents, namely, ionic liquids, eutectic solvents, aqueous solutions of surfactants, and edible oils, for recovering natural pigments was reviewed. Works discussing higher extraction yields and selectivity, while maintaining the stability of the target pigments, were reported. Also, a panorama between Sustainability and Circular Economy prospection was discussed for better comprehension of the main advances in the field. Behind the analysis of the works published so far on the theme, the most important lacunas to overcome in the next years on the field were pointed out and discussed. Also, the future trends and new perspectives to achieve the economic viability and sustainability of the processes using alternative solvents will be scrutinized.
Bacterial spores in spices and dried herbs: The risks for processed food
Authors: Mathot Anne Gabrielle , Postollec Florence , Leguerinel Ivan
Published: December 2020

Production and world consumption of spices are constantly increasing. Although the antimicrobial properties of some spices are well documented, their use in the agri‐food industry is also responsible for microbial contamination and spoilage. Bacterial spores introduced by spices can withstand different preparation processes, particularly thermal treatments, leading to food alterations during storage. This review brings together data from the literature about the prevalence and concentrations of spore‐forming bacteria in all commercially available spices. The sporeformers found in spices belong mainly to the genera Bacillus and Clostridium. Such contaminations are very common and sometimes reach high levels, as in pepper and turmeric. Bacillus licheniformis and Bacillus cereus are the most frequently detected species. Studying the harvesting, processing, and storage procedures for spices provides elements to explain why high prevalence and concentrations are observed. Spices are mostly produced in developing countries on small farms using traditional production methods. Spices become contaminated by bacterial spores in two main ways: by contact with soil during harvesting or drying, as for pepper, or by cross‐contamination during the water‐cooking step, as for turmeric. From these observations, we propose some recommendations. Different methods that can be used to eliminate bacterial spores from spices are presented indicating their efficiency and the limitations of their use.
High prevalence of neurodevelopmental problems in adolescents eligible for bariatric surgery for severe obesity
Authors: Björk Anna , Dahlgren Jovanna , Gronowitz Eva , Henriksson Wessely Fanny , Janson Annika , Engström My , Sjögren Lovisa , Olbers Torsten , Järvholm Kajsa
Published: December 2020

Aim

To assess the prevalence of neurodevelopmental problems in adolescents with severe obesity and their associations with binge eating and depression.

Methods

Data were collected at inclusion in a randomised study of bariatric surgery in 48 adolescents (73% girls; mean age 15.7 ± 1.0 years; mean body mass index 42.6 ± 5.2 kg/m2). Parents completed questionnaires assessing their adolescents’ symptoms of attention‐deficit/hyperactivity disorder and autism spectrum disorder and reported earlier diagnoses. Patients answered self‐report questionnaires on binge eating and depressive symptoms.

Results

The parents of 26/48 adolescents (54%) reported scores above cut‐off for symptoms of the targeted disorders in their adolescents, but only 15% reported a diagnosis, 32% of adolescents reported binge eating, and 20% reported symptoms of clinical depression. No significant associations were found between neurodevelopmental problems and binge eating or depressive symptoms. Only a third of the adolescents reported no problems in either area.

Conclusion

Two thirds of adolescents seeking surgical weight loss presented with substantial mental health problems (reported by themselves or their parents). This illustrates the importance of a multi‐professional approach and the need to screen for and treat mental health disorders in adolescents with obesity.
Saving the most lives—A comparison of European triage guidelines in the context of the COVID‐19 pandemic
Authors: Ehni Hans‐Jörg , Wiesing Urban , Ranisch Robert
Published: December 2020

In March 2020, the rapid increase in severe COVID‐19 cases overwhelmed the healthcare systems in several European countries. The capacities for artificial ventilation in intensive care units were too scarce to care for patients with acute respiratory disorder connected to the disease. Several professional associations published COVID‐19 triage recommendations in an extremely short time: in 21 days between March 6 and March 27. In this article, we compare recommendations from five European countries, which combine medical and ethical reflections on this situation in some detail. Our aim is to provide a detailed overview on the ethical elements of the recommendations, the differences between them and their coherence. In more general terms we want to identify shortcomings in regard to a common European response to the current situation.
Authentic Voices in Supervision
Authors: Yerushalmi Hanoch
Published: December 2020

Analytic thinkers incorporated the significance of authenticity for human development and therapeutic processes into their theories. I suggest that, consequently, supervisors search for the supervisees’ authentic voices, often masked by unconscious rhetorical devices, and for the patients’ authentic voices hidden in the supervisees’ voices. Assuming a poetic stance for listening, which highlights the speakers’ unique use of language, beyond the lexical and the prosaic, enables supervisors to perceive and construct implicit musical patterns and symbols woven into the supervisees’ communications. This stance allows the supervisors to perceive the supervisees’ authentic voices, free from their distracting rhetoric, and to imagine the patients’ voices in the supervisees’ heads. When supervisors differentiate and integrate various perceiving and reflective modes that characterize the poetic stance, they function as identification models for the supervisees in their development as analytic therapists.
Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay
Authors: De Rentiis Anna M. A. , Pink Mario , Verma Nisha , Schmitz‐Spanke Simone
Published: December 2020

Background

People are exposed to mixtures containing allergens and irritants often causing contact dermatitis. Therefore, regulatory authorities require systematic information on the effects of mixtures on the sensitization threshold. In this study a moderate (cinnamal) and a weak (ethylene glycol dimethacrylate) allergen were combined with irritants covering different mechanisms of action (sodium dodecyl sulfate, salicylic acid, and α‐pinene). For a systematic approach, the single substances were initially tested using the KeratinoSens assay. Thereafter, each allergen was combined with noncytotoxic concentrations of the irritants.

Method

The KeratinoSens assay was applied for the single substances according to OECD (Organisation for Economic Co‐operation and Development) Test Guideline 442D. Based on these results, three noncytotoxic concentrations of the irritants were selected and applied simultaneously with 12 concentrations of the allergens to the KeratinoSens cells. Sensitization threshold and cytotoxicity were measured and compared with the individual testing.

Results

The combinations of allergens and irritants differed from the effects of the single substances and lowered the sensitization threshold. The quantitative approach allowed a clear description of the changes which varied by factors between 1.1 and 10.3.

Conclusions

Overall, the allergen was the prominent compound in the mixture and its nature appeared to determine the degree of the response.
Resection rate curves by location along the small intestine provide perspectives on characteristics of Crohn’s disease
Authors: Suzuki Hideyuki , Watanabe Kazuhiro , Kohyama Atsushi , Ohnuma Shinobu , Karasawa Hideaki , Kajiwara Taiki , Kobayashi Minoru , Hatsuzawa Yuuri , Kamei Takashi , Unno Michiaki
Published: December 2020

Aim

Crohn's disease (CD) can affect any part of the gastrointestinal tract; however, the frequency of CD lesions differs by location. This work aimed to examine resection rates by location to clarify locational characteristics of the small intestine in surgical CD cases.

Method

This was a single‐centre retrospective case note review of patients who had undergone resection for CD affecting the small intestine between January 2014 and February 2020. Operative details, including length of the small intestine, location and extent of the resection, identified the pattern of disease. By normalizing these data the resection rate along the length of the intestine was calculated to create resection rate curves.

Results

One hundred and twenty six surgical cases were identified. The resection rate curves could be divided into two types: exponential and bimodal. For primary surgery, this depended on whether or not surgery was limited to an ileocolic resection. At subsequent surgery, a previous ileocaecal resection influenced the pattern of disease. The peaks of the bimodal curve were located at the proximal and distal ileum.

Conclusion

CD patients requiring resection of the small intestine can be divided into terminal ileum type (exponential type) and proximal ileum type (bimodal type). In the future this analytical method may help predict the site of any recurrent disease but also provides a new perspective on the disease.
Alpha modulation in younger and older adults during distracted encoding
Authors: Wynn Syanah C. , Nyhus Erika , Jensen Ole
Published: December 2020

To successfully encode information into long‐term memory, we need top‐down control to focus our attention on target stimuli. This attentional focus is achieved by the modulation of sensory neuronal excitability through alpha power. Failure to modulate alpha power and to inhibit distracting information has been reported in older adults during attention and working memory tasks. Given that alpha power during encoding can predict subsequent memory performance, aberrant oscillatory modulations might play a role in age‐related memory deficits. However, it is unknown whether there are age‐related differences in memory performance or alpha modulation when encoding targets with distraction. Here we show that both older and younger adults are able to encode targets paired with distractors and that the level of alpha power modulation during encoding predicted recognition success. Even though older adults showed signs of higher distractibility, this did not harm their episodic memory for target information. Also, we demonstrate that older adults only modulated alpha power during high distraction, both by enhancing target processing and inhibiting distractor processing. These results indicate that both younger and older adults are able to employ the same inhibitory control mechanisms successfully, but that older adults fail to call upon these when distraction is minimal. The findings of this study give us more insight into the mechanisms involved in memory encoding across the lifespan.
Regional inflation persistence in Turkey
Authors: Duran Hasan Engin , Dindaroğlu Burak
Published: December 2020

The purpose of the current study is to investigate the degree of inflation persistence, its geographical variation, sources of cross‐regional variation, and presence of geographical/sectoral aggregation bias in national monetary policy. Our data set covers 26 NUTS‐2 level Turkish regions and monthly CPI inflation over the period 2003–2019. We first estimate the degree of regional inflation persistence by autoregressive regressions, check its robustness against the presence of structural breaks (by Bai–Perron's algorithm) and nonlinearities (by Markovian Regime Switching regressions). Second, we examine the possibility of geographical and sectoral aggregation bias. Third, we investigate the cross‐regional determinants of inflation persistence by panel data analysis, employing hybrid‐effects spatial panel regressions. We analyze the direct and indirect effects of the determinants and test for regional spillover effects. Three main results are obtained. First, estimated persistence degrees are heterogeneous across regions. The geographical pattern is empirically robust against structural breaks and nonlinearities. We find that inflation persistence is distributed in a spatially correlated manner. Second, when sectoral and regional aggregation bias is tested, only sectoral aggregation indicates a considerable level of bias. Third, we find that the presence of large firms in the region and a higher share of agricultural output in GDP leads to lower persistence, while an increased share of industrial output, and increased trade volume leads to higher inflation persistence. Moreover, we find spatial spillovers of price variability evident in regression analysis. From a policy standpoint, it is required that structural policy programs are targeted to maintain flexibility in the regions where persistence is high (i.e., providing market entry/exit, institutional quality, policy credibility, stimulation of SMEs). Moreover, sectors that have high persistence, such as Hotels and Restaurants (persistence degree 0.55) and Health Services (0.39) should be weighted more in CPI calculations.
Reconsidering humanitarian advocacy through pressure points of the European ‘migration crisis’
Authors: Hilhorst Dorothea , Hagan Maria , Quinn Olivia
Published: December 2020

This paper contributes to discussions on humanitarian advocacy. The European migration regime as constituted by the Dublin regulation, the EU‐Turkey deal and border deals with Libya among others, contributes to generating migration pressure points where migrants find themselves stuck and in desperate need of humanitarian assistance. Assistance and protection at these sites, inasmuch as they are available, are provided by a makeshift humanitarian arena of volunteer organizations, activists, national social welfare agencies, human rights organizations, international humanitarian organizations and UN agencies. Drawing on interviews and field research, this article analyses the relations between, and advocacy practices of, various actors within humanitarian arenas in three settings: Calais (France), Lesbos (Greece) and Libya. The article reveals how many humanitarians at these pressure points feel disempowered in the scope of their action beyond the provision of limited services, and abandoned by established agencies, especially the UNHCR. They feel that humanitarian principles are not enough to guide their actions in these cases. Emerging advocacy practices at these sites suggest that web‐based humanitarian advocacy based on actor complementarity may be a way forward, making advocacy more effective and contributing to better motivate aid workers who feel disempowered in these contexts.
Overexpression of sortilin is associated with 5‐FU resistance and poor prognosis in colorectal cancer
Authors: Blondy Sabrina , Talbot Hugo , Saada Sofiane , Christou Niki , Battu Serge , Pannequin Julie , Jauberteau Marie‐Odile , Lalloué Fabrice , Verdier Mireille , Mathonnet Muriel , Perraud Aurélie
Published: December 2020

Colorectal cancer (CRC) is the third most common cancer worldwide. Even if 5‐fluorouracil (5‐FU) is used as the first‐line chemotherapeutic drug, responsiveness is only 20‐30%. Acquired resistance to 5‐FU contributes to both poor patient prognosis and relapse, emphasizing the need to identify biomarkers. Sortilin, a vacuolar protein sorting 10 protein (Vps10p), implicated in protein trafficking, is over expressed in CRC cell lines cultured 72 hours in presence of 5‐FU. This overexpression was also observed in 5‐FU‐resistant cells derived from these cell lines as well as in CRC primary cultures (or patients derived cell lines). A significantly higher expression of sortilin was observed in vivo, in 5‐FU‐treated tumours engrafted in Nude mice, as compared with non‐treated tumour. A study of transcriptional regulation allowed identifying a decrease in ATF3 expression, as an explanation of sortilin overexpression following 5‐FU treatment. In silico analysis revealed SORT1 expression correlation with poor prognosis. Moreover, sortilin expression was found to be positively correlated with CRC tumour grades. Collectively, our findings identify sortilin as a potential biomarker of 5‐FU resistance associated with poor clinical outcomes and aggressiveness in CRC. As a new prognostic factor, sortilin expression could be used to fight against CRC.
Gastrodin prevents homocysteine‐induced human umbilical vein endothelial cells injury via PI3K/Akt/eNOS and Nrf2/ARE pathway
Authors: Chen Jiyu , Huang Yanli , Hu Xiaochuan , Bian Xiaohong , Nian Sihui
Published: December 2020

In this study, we investigated the protective effects of gastrodin (Gas) against homocysteine‐induced human umbilical vein endothelial cell (HUVEC) injury and the role of the phosphoinositide 3‐kinase (PI3K)/threonine kinase 1 (Akt)/endothelial nitric oxide synthase (eNOS) and NF‐E2‐related factor 2 (Nrf2)/antioxidant response element (ARE) pathways. We stimulated cells with homocysteine (1 mmol/L, 24 hours) and tested the effects of gastrodin (200‐800 μg/mL) on cell viability and the production of malondialdehyde (MDA), lactate dehydrogenase (LDH) and reactive oxygen species (ROS). Then, Nrf2 distribution in the cytoplasm and nucleus as well as the expression of enzymes downstream of Nrf2 was determined. Furthermore, we analysed the expression of bax, bcl‐2 and cleaved caspase3, and assessed the involvement of the PI3K/Akt/eNOS pathway by Western blots. Finally, we tested the vasoactive effect of gastrodin in thoracic aortic rings. The results showed that gastrodin decreased MDA, LDH and ROS production and increased cell viability, NO production and relaxation of thoracic aortic rings. Moreover, the protective effects of Gas on NO production and relaxation of thoracic aortic rings were blocked by L‐NAME but enhanced by Cav‐1 knockdown, and MK‐2206 treatment abolished the effect of Gas on the ROS. In addition, treatment with gastrodin increased Nrf2 nuclear translocation, thus enhancing the expression of downstream enzymes. Finally, gastrodin increased the expression of PI3K, p‐Akt, and eNOS and decreased Cav‐1 protein expression. In conclusion, our study suggested that gastrodin may protect HUVECs from homocysteine‐induced injury, and the PI3K/Akt/eNOS and Nrf2/ARE pathways may be responsible for the efficacy of gastrodin.
Temperature‐mediated plasticity in incubation schedules is unlikely to evolve to buffer embryos from climatic challenges in a seasonal songbird
Authors: Cones Alexandra G. , Liebl Andrea L. , Houslay Thomas M. , Russell Andrew F.
Published: December 2020

Phenotypic plasticity is hypothesized to facilitate adaptive responses to challenging conditions, such as those resulting from climate change. However, tests of the key predictions of this ‘rescue hypothesis’, that variation in plasticity exists and can evolve to buffer unfavourable conditions, remain rare. Here, we investigate among‐female variation in temperature‐mediated plasticity of incubation schedules and consequences for egg temperatures using the chestnut‐crowned babbler (Pomatostomus ruficeps) from temperate regions of inland south‐eastern Australia. Given recent phenological advances in this seasonal breeder and thermal requirements of developing embryos (>~25°C, optimally ~38°C), support for evolutionary rescue—perhaps paradoxically—requires that plasticity serves to buffer embryos more from sub‐optimally low temperatures. We found significant variation in the duration of incubation bouts (mean ± SD = 27 ± 22 min) and foraging bouts (mean ± SD = 17 ± 11 min) in this maternal‐only incubator. However, variation in each arose because of variation in the extent to which mothers increased on‐ and off‐bout durations when temperatures (0–36°C) were more favourable rather than unfavourable as required under rescue. In addition, there was a strong positive intercept‐slope correlation in on‐bout durations, indicating that those with stronger plastic responses incubated more at average temperatures (~19°C). Combined, these effects reduced the functional significance of plastic responses: an individual's plasticity was neither associated with daily contributions to incubation (i.e. attentiveness) nor average egg temperatures. Our results highlight that despite significant among‐individual variation in environmental‐sensitivity, plasticity in parental care traits need not evolve to facilitate buffering against unfavourable conditions.
Chief to Chief: Reflections on Cultivating the Next Generation of Geriatrics Program Leaders
Authors: Medina‐Walpole Annette M. , Sachs Greg A. , Hazzard William R.
Published: December 2020

What does it take to successfully lead a Division of Geriatrics? Is it the same skill set today as it was two or three decades ago? Is it the same for each chief, given the wide spectrum of geriatrics programs across our nation? Early leaders in our field showcased and role‐modeled the career and job satisfaction that accompanies leadership of traditional geriatrics academic programs. This has been well articulated in past issues of the Journal of the American Geriatrics Society in articles by Dr William Hazzard and Dr Greg Sachs. How can we develop the next generation of geriatrics program leaders and ensure their success? Developed as a conversation between three generations of geriatrics division chiefs, this reflective article offers a shared perspective on what is required for success in advancing as a leader in our field and wholeheartedly enjoying the best job in the world.
Polypharmacy and pattern of medication use in community‐dwelling older adults: A systematic review
Authors: Hsu Hui‐Fen , Chen Kuei‐Min , Belcastro Frank , Chen Yih‐Fung
Published: December 2020

Aim

To synthesise current study findings on the diseases and the corresponding medications that are potentially associated with polypharmacy in community‐dwelling older adults.

Background

Polypharmacy is receiving increased attention as a potential problem for the older population. Although several scientific investigations have studied polypharmacy, most of them were carried out in long‐term care facilities or mixed settings rather than in community settings solely.

Methods

This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). Relevant studies published in the English language in peer‐reviewed journals were identified from searches of seven electronic databases for the period of January 2000 through December 2019. Inclusion criteria were: (1) Participants were older adults aged 65 years and older; (2) Polypharmacy was defined by medication count; (3) Medication classes associated with polypharmacy were revealed; (4) Studies were conducted in outpatient care or community settings. The Joanna Briggs Institute critical appraisal checklists for cross‐sectional studies and for cohort studies were used to assess the methodological quality.

Results

Ten studies were considered having appropriate and acceptable quality to be reviewed, comprising nine cross‐sectional studies and one cohort study. Polypharmacy was most defined as concurrently using five or more medications. Polypharmacy prevalence ranged between 7%–45%. Older age, comorbidity, poor self‐perceived health status, limitations in physical activity, history of falls, depression, and pain were positively associated with polypharmacy. The most prevalent medication taken by older adults with polypharmacy was cardiovascular drugs.

Conclusions

The prevalence of polypharmacy in older adults varying widely may be due to geographical locations, clinical practice guidelines, and polypharmacy definition used.

Relevance to Clinical Practice

Validated measurements to investigate medications associated with polypharmacy are required. How polypharmacy develops over time needs to be investigated in longitudinal studies in order to formulate strategies for reducing polypharmacy.
Stage‐related implications of community‐acquired pressure injuries for the acute medical inpatients
Authors: Sanson Gianfranco , Barbin Ilaria , De Matteis Daniela , Marzinotto Ilaria , Zanetti Michela
Published: December 2020

Aims

To analyse the prevalence of any‐stage pressure injuries at hospital admission and their impact on short‐, mid‐ and late‐term mortality. Patient characteristics associated with pressure injuries and the impact on hospital costs were also investigated.

Background

In medical patients acutely admitted to hospital, no study analysed the presence of pre‐existing pressure injuries and the related short‐ and long‐term mortality according to the overall stages of severity thereof.

Design

Retrospective cohort study following the STROBE guideline.

Methods

In a population of 7217 acute medical inpatients, the presence and staging of pressure injuries were assessed at hospital admission. The impact of pressure injury on 30‐, 180‐ and 365‐day mortality was analysed by multivariate Cox regression models.

Results

The prevalence of community‐acquired pressure injuries was 14.9% (stage‐1: 8.1%; stage‐2: 3.5%; stage‐3: 1.6%; stage‐4: 1.1%; unstageable: 0.5%). Hemiplegia/paraplegia, anaemia, poor functional status, high nutritional risk, clinical instability and systemic inflammatory response, but not hydration status, were found to be associated with the occurrence of stage‐2‐and‐above pressure injuries. An increasing difference was found in Diagnosis‐Related Groups (DRG) weight according to pressure injury stages. A distinct and progressively increasing risk‐of‐death for any‐stage pressure injury was shown after 365‐days. A significantly increased mortality risk for all considered time intervals was found for unstageable and stage‐4 pressure injuries.

Conclusions

In acute medical inpatients, the presence of community‐acquired pressure injuries is part of a multidimensional clinical complexity. The presence and staging of pressure injuries have an independent dramatic impact on of early‐to‐late mortality and hospital costs.

Relevance to clinical practice

This study documented as community‐acquired pressure injuries are highly prevalent and represents an independent predictor of outcomes in strict dependence of the progression of thereof stage. The presence of community‐acquired pressure injuries should be interpreted as a critical marker of frailty and increased vulnerability.
THE DECLINE IN THE U.S. LABOR FORCE PARTICIPATION RATE: A LITERATURE REVIEW
Authors: Perez‐Arce Francisco , Prados María J.
Published: December 2020

After peaking around the year 2000, the Labor Force Participation Rate (LFPR) of Americans declined substantially. The weakening in LFPR was faster after the financial crisis of 2007, the Great Recession. Since 2015, the LFPR has remained at its lowest in four decades.

This paper constitutes a comprehensive review of the literature investigating the causes of the LFPR's recent decline. We determine what is known and identify the remaining gaps.

The literature reviewed signals multiple causes behind this decline. Trend factors, such as long‐running demographic patterns, explain an important part of the decline. The research on the extent to which the Great Recession caused the decline establishes that most of the drop cannot be attributed to cyclical factors. Part of the decline in LFPR can be attributed to factors such as technological innovations and trade, which affect the participation rates of specific subpopulations, as well as to changes in social programs, like Social Security Disability Insurance. Some subpopulation trends are clear, but their ultimate causes are not fully understood, as is the case for the LFPRs of women and youth. We list these factors and point to important areas for future research.
Examination of the Peleg and Normand equation during relaxation of wheat: The effect of holding time
Authors: Łysiak Grzegorz , Al Aridhee Jawad Kadhim , Kulig Ryszard , Różyło Renata , Wójcik Monika
Published: December 2020

In this study, we analyzed the effect of the duration of relaxation experiments on the parameters of the model proposed by Peleg and Normand. The relaxation experiments were conducted for individual intact wheat kernels in compression. Single kernels were initially loaded with a force of 20 N, then maintained at a constant deformation over time of 300 s. For the following time intervals 0–10, 0–20, 0–30, 0–40, 0–50, 0–60, 0–120, 0–180, 0–240, and 0–300 s coefficients k1, k2 and Y(t) were determined according to the Normand and Peleg equation. The effect of time was compared at variable wheat moisture ranging from 8 to 20%. For longer holding times, the relaxed force was higher and the decay parameter, Y(t), decreased. The coefficient k1 increased proportionally with increase in the time of relaxation from ~3.3 to 23.3 s. The values of coefficient k2 declined for longer experiments, and the decline was relatively quick for up to 60 s and then asymptotically diminished. The effect of time on the decay parameter Y(t) and coefficients k1 and k2 depended on the moisture of kernels. The accuracy of the models was significantly different for the studied holding times. The highest standard error of the estimate was evidenced for 10 s experiments, and its minimum was noted at times close to 120–180 s.
Continuous rate infusion of midazolam as emergent treatment for seizures in dogs
Authors: Bray Kathryn Y. , Mariani Christopher L. , Early Peter J. , Muñana Karen R. , Olby Natasha J.
Published: December 2020

Background

Midazolam delivered by continuous rate infusion (CRI) might be effective in dogs with cluster seizures (CS) or status epilepticus (SE).

Objective

To describe the use and safety of midazolam CRI in dogs with CS or SE.

Animals

One‐hundred six client‐owned dogs presenting to a veterinary teaching hospital with CS or SE.

Methods

Retrospective review of medical records for dogs with CS or SE treated with a midazolam CRI.

Results

Seventy‐nine dogs presented with CS and 27 dogs had SE. Seizure control was achieved in 82/106 dogs (77.4%) receiving a midazolam CRI. The median dose associated with seizure control was 0.3 mg/kg/h (range, 0.1‐2.5 mg/kg/h). The median duration of CRI was 25 hours (range, 2‐96 hours). Seizures were controlled in 34/40 dogs (85%) with idiopathic epilepsy, 32/43 dogs (74%) with structural epilepsy, 12/16 dogs (75%) with unknown epilepsy, and 4/7 dogs (57%) with reactive seizures (P= .20). Seizure control was achieved in 81% of dogs with CS and 67% in dogs with SE (P= .18). Dogs with idiopathic/unknown epilepsy were more likely to survive than those with structural epilepsy (87% vs 63%,P= .009). Adverse effects were reported in 24 dogs (22.6%) and were mild in all cases.

Conclusions and Clinical Importance

Midazolam CRI is apparently safe and might be an effective treatment in dogs with CS or SE.