bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of alginate matrix engineered to mimic the pancreatic microenvironment on encapsulated islet function
Authors: Enck Kevin , Tamburrini Riccardo , Deborah Chaimov , Gazia Carlo , Jost Alec , Khalil Fatma , Alwan Abdelrahman , Orlando Giuseppe , Opara Emmanuel C.
Published: December 2020

Islet transplantation is emerging as a therapeutic option for type 1 diabetes, albeit, only a small number of patients meeting very stringent criteria are eligible for the treatment because of the side effects of the necessary immunosuppressive therapy and the relatively short time frame of normoglycemia that most patients achieve. The challenge of the immune‐suppressive regimen can be overcome through microencapsulation of the islets in a perm‐selective coating of alginate microbeads with poly‐l‐lysine or poly‐
l‐ornithine. In addition to other issues including the nutrient supply challenge of encapsulated islets a critical requirement for these cells has emerged as the need to engineer the microenvironment of the encapsulation matrix to mimic that of the native pancreatic scaffold that houses islet cells. That microenvironment includes biological and mechanical cues that support the viability and function of the cells. In this study, the alginate hydrogel was modified to mimic the pancreatic microenvironment by incorporation of extracellular matrix (ECM). Mechanical and biological changes in the encapsulating alginate matrix were made through stiffness modulation and incorporation of decellularized ECM, respectively. Islets were then encapsulated in this new biomimetic hydrogel and their insulin production was measured after 7 days in vitro. We found that manipulation of the alginate hydrogel matrix to simulate both physical and biological cues for the encapsulated islets enhances the mechanical strength of the encapsulated islet constructs as well as their function. Our data suggest that these modifications have the potential to improve the success rate of encapsulated islet transplantation.
Informed consent in critically ill adults participating to a randomized trial
Authors: Guinchard Milène , Warpelin‐Decrausaz Loane , Schindler Kaspar , Rüegg Stephan , Oddo Mauro , Novy Jan , Alvarez Vincent , Rossetti Andrea O.
Published: December 2020

Objective

The 2014 update of the Swiss law on research increases patients' protection; it adds specific requirements for emergency situations, implying an active search for patients' wishes regarding research participation; the possibility of consent waivers is not clearly stated. We explored its practical impact in a RCT on critically ill adults.

Methods

We considered prospectively collected consents of a multicenter trial addressing the impact of continuous EEG on survival. We assessed the proportions of consents obtained strictly according to the law, of specific waivers for this study obtained from the IRB (early death; relatives' unavailability despite repeated attempts), and the yield of retrieving statements on willingness to research participation. We compared the proportion of consent refusals with those of recent trials in similar environments, and estimated the potential impact on study results.

Results

Of 402 recruited patients, six had double inclusions, one died before intervention, and 27 (6.7%, alive on long‐term) were excluded following consent refusal or withdrawal, leaving 368 analyzable patients. Specific waivers allowed inclusion of 134 (36.4%) patients, while informed consents were obtained for all others. A statement of willingness to research participation was found in only 14.1%. In recent trials, consent refusal oscillated between 0%–23%, according to different waiver policies.

Conclusions

Consent waivers should be specifically foreseen to prevent losing a potentially relevant proportion of patients reaching endpoints, and ensure results generalizability. The yield of looking for willingness to research participation seems low; this questions its current usefulness and calls for a public awareness campaign.
Microstructural white matter abnormalities in pediatric and adult obsessive‐compulsive disorder: A systematic review and meta‐analysis
Authors: Li Qian , Zhao Youjin , Huang Zixuan , Guo Yi , Long Jingyi , Luo Lekai , You Wanfang , Sweeney John A. , Li Fei , Gong Qiyong
Published: December 2020

Objective

To identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive‐compulsive disorder (OCD) in tract‐based spatial statistics (TBSS) studies.

Methods

We reviewed previous TBSS studies (n = 20) in OCD and performed a meta‐analysis (n = 16) of FA differences.

Results

No between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation.

Conclusions

Absent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto‐striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness.
Trends in solitary plasmacytoma, extramedullary plasmacytoma, and plasma cell myeloma incidence and myeloma mortality by racial‐ethnic group, United States 2003‐2016
Authors: Ellington Taylor D. , Henley S. Jane , Wilson Reda J. , Wu Manxia , Richardson Lisa C.
Published: December 2020

Plasma cell myeloma (also called multiple myeloma), solitary plasmacytoma, and extramedullary plasmacytoma are primarily diseases of the elderly. Evidence suggests an association between excess body weight and multiple myeloma. Few population‐based studies have examined incidence and mortality of each site in one study. We analyzed incidence and death rates by site (solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma) by gender, age, race/ethnicity, and rural‐urban status among adult males and females (aged 20 years or older) in the United States during 2003‐2016. Trends were characterized as average annual percentage change (AAPC) in rates. During 2003‐2016, overall incidence rates among adults were 0.45 for solitary plasmacytoma, 0.09 for extramedullary plasmacytoma, and 8.47 for multiple myeloma per 100,000 persons. Incidence rates for multiple myeloma increased during 2003‐2016 among non‐Hispanic whites (AAPC = 1.78%) and non‐Hispanic blacks (2.98%) 20‐49 years of age; non‐Hispanic whites (1.17%) and non‐Hispanic blacks (1.24%) 50‐59 years of age; and whites non‐Hispanic (0.91%), and non‐Hispanic blacks (0.96%). During 2003‐2016 overall myeloma (extramedullary plasmacytoma and multiple myeloma) death rates among adults was 4.77 per 100,00 persons. Myeloma death rates decreased during 2003‐2016 among non‐Hispanic white (AAPC = −1.23%) and Hispanic (−1.34%) women; and non‐Hispanic white (−0.74%), non‐Hispanic American Indian/Alaska Native (−3.05%) men. The US population is projected to become older and will have a larger proportion of persons who have had an earlier and longer exposure to excess body weight. The potential impact of these population changes on myeloma incidence and mortality can be monitored with high‐quality cancer surveillance data.
Ethnic and border differences on blood cancer presentation and outcomes: A Texas population‐based study
Authors: Bencomo‐Alvarez Alfonso E. , Gonzalez Mayra A. , Rubio Andres J. , Olivas Idaly M. , Lara Joshua J. , Padilla Osvaldo , Orazi Attilio , Corral Javier , Philipovskiy Alexander , Gaur Sumit , Mulla Zuber D. , Dwivedi Alok K. , Eiring Anna M.
Published: December 2020

Background

The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population‐based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes.

Methods

Data from the Texas Cancer Registry (1995‐2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non‐Hispanic) and geographic location (border vs non‐border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel‐Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types.

Results

Hispanic patients were diagnosed at a younger age than non‐Hispanic patients and presented with increased comorbidities. Whereas non‐Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79‐2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07‐1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04‐1.33; P = .0009) compared with Hispanics living elsewhere in Texas.

Conclusions

Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.
Adverse childhood experiences and early maladaptive schemas in adulthood: A systematic review and meta‐analysis
Authors: Pilkington Pamela D. , Bishop Amy , Younan Rita
Published: December 2020

Background

Schema Therapy is based on the theory that trauma and neglect in childhood lead to early maladaptive schemas and psychopathology in adulthood. The aim of this review was to evaluate support for this theory by synthesizing the literature on childhood adversity and schemas.

Methods

A systematic review and meta‐analysis were completed in compliance with PRISMA. PsycInfo, CINAHL and PubMed were searched to identify eligible studies that reported unadjusted association(s) between adverse childhood events and schema scores when participants were 18 years or older. Meta‐analyses were conducted to estimate the pooled effect size of associations between schemas and experiences of childhood adversity.

Results

A total of 33 studies met inclusion criteria and provided sufficient data for meta‐analyses on childhood experiences relating to toxic frustration of needs (emotional neglect and physical neglect) and trauma and victimization (emotional abuse, physical abuse and sexual abuse). Of the 124 meta‐analyses, 65 indicated that schemas show small to large correlations with emotional neglect (range: r = .16 [Failure] to r = .51 [Emotional Deprivation]); small to moderate correlations with emotional abuse (range: r = .20 [Vulnerability to Harm] to r = .44 [Emotional Deprivation]); and small correlations with physical neglect, physical abuse and sexual abuse (range: r = .16 [Vulnerability to Harm] to .26 [Emotional Deprivation and Social Isolation]).

Conclusions

Of the 33 included studies, only one used a longitudinal design. However, based on the correlational studies available, early maladaptive schemas in adulthood are associated with a history of childhood abuse and neglect.
Geolocation analysis for Search And Rescue systems using LoRaWAN
Authors: Bouras Christos , Gkamas Apostolos , Kokkinos Vasileios , Papachristos Nikolaos
Published: December 2020

Low‐power wide‐area network (LPWAN) technologies are aiming to provide power‐efficient solutions to the field of Internet of Things (IoT). Over the last years, we have seen a significant development within the area of IoT applications. For many applications, the problem of localization (i.e., determine the physical location of nodes) is critical. An area study of such use case is also the rescue monitor systems. In this study, we start by describing a solution designed for the long range wide area network (LoRaWAN) to localize position of IoT modules such as wearables used from vulnerable groups. Through performance study of the behavior of a LoRaWAN channel and using trilateration and RSSI information, the localization of an IoT wearable can be acquired within a small range. Routing people in need is one of the use cases the above mechanism could be integrated so as to be able to be tracked by familiar people. After that, we evaluate the usage of mathematical model of multilateration algorithms using time difference of arrival (TDoA) as a solution for positioning over LoRaWAN. The research is carried out using simulations in Python by configuring the constant positions of the Gateways inside an outdoor area. The proposed algorithms can be integrated in application for tracking people at any time and especially routing people from vulnerable groups. Through multilateration and algorithm's prediction, we can have an accuracy of 40–60 m in location positioning, ideal for search and rescue use cases. We finally summarize the above algorithms' estimation and general behavior in a SAR system.
Breeding system of diploid sexuals within theRanunculus auricomuscomplex and its role in a geographical parthenogenesis scenario
Authors: Karbstein Kevin , Rahmsdorf Elisabeth , Tomasello Salvatore , Hodač Ladislav , Hörandl Elvira
Published: December 2020

The larger distribution area of asexuals compared with their sexual relatives in geographical parthenogenesis (GP) scenarios has been widely attributed to the advantages of uniparental reproduction and polyploidy. However, potential disadvantages of sexuals due to their breeding system have received little attention so far. Here, we study the breeding system of five narrowly distributed sexual lineages ofRanunculus notabiliss.l. (R. auricomuscomplex) and its effects on outcrossing, inbreeding, female fitness, and heterozygosity. We performed selfing and intra‐ and interlineage crossings by bagging 481 flowers (59 garden individuals) followed by germination experiments. We compared seed set and germination rates, and related them to genetic distance and genome‐wide heterozygosity (thousands of RADseq loci). Selfings (2.5%) unveiled a significantly lower seed set compared with intra‐ (69.0%) and interlineage crossings (69.5%). Seed set of intra‐ (65%) compared to interpopulation crossings (78%) was significantly lower. In contrast, all treatments showed comparable germination rates (32%–43%). Generalized linear regressions between seed set and genetic distance revealed positive relationships in general and between lineages, and a negative one within lineages. Seed set was the main decisive factor for female fitness. Germination rates were not related to genetic distance at any level, but were positively associated with heterozygosity in interlineage crossings. Experiments confirmed full crossability and predominant outcrossing among sexualR. notabiliss.l. lineages. However, up to 5% (outliers 15%–31%) of seeds were formed by selfing, probably due to semi‐self‐compatibility in a multi‐locus gametophytic SI system. Less seed set in intrapopulation crossings, and higher seed set and germination rates from crossings of genetically more distant and heterozygous lineages (interlineage) indicate negative inbreeding and positive outbreeding effects. In GP scenarios, sexual species with small and/or isolated populations can suffer from decreased female fitness due to their breeding system. This factor, among others, probably limits range expansion of sexuals.
Implementation of QbD strategies in the inoculum expansion of a mAb production process
Authors: Böhl Ole Jacob , Schellenberg Jana , Bahnemann Janina , Hitzmann Bernd , Scheper Thomas , Solle Dörte
Published: December 2020

The quality by design approach was introduced to the biopharmaceutical industry over 15 years ago. This principle is widely implemented in the characterization of monoclonal antibody production processes. Anyway, the early process phase, namely the inoculum expansion, was not yet investigated and characterized for most processes. In order to increase the understanding of early process parameter interactions and their influence on the later production process, a risk assessment followed by a design of experiments approach was conducted. The DoE included the critical parameters methotrexate (MTX) concentration, initial passage viable cell density and passage duration. Multivariate data analysis led to mathematical regression models and the establishment of a designated design space for the studied parameters. It was found that the passage duration as well as the initial viable cell density for each passage during the inoculum expansion have severe effects on the growth rate and viability of the early process phase. Furthermore, the variations during the inoculum expansion directly influenced the production process responses. This carry‐over of factor effects highlights the crucial impact of early process failures and the importance of process analysis and control during the first part of mAb production processes.
Functional food mixtures: Inhibition of lipid peroxidation, HMGCoA reductase, and ACAT2 in hypercholesterolemia‐induced rats
Authors: Mohd Rosmi Noor Syafiqa Aqila , Shafie Nurul Husna , Azlan Azrina , Abdullah Maizaton Atmadini
Published: December 2020

Mixtures of selected functional foods (MSFF) were composed of nattokinase (fermented soybean), red yeast rice extract, Ginkgo biloba, oat fiber, garlic, bee pollen, and propolis as anti‐hypercholesterolemic were studied. The goal of this study was to determine the bioactive compounds in these mixtures and their cholesterol‐lowering potential effects (biochemical profiles, lipid peroxidation, liver tissue histopathology, and enzymatic activity analysis; HMGCoA reductase and ACAT2. The LC‐MS/MS analysis showed that bioactive compounds such as Monacolin K, naringin, tocopherol, and glutamate, which have potential as anti‐hypercholesterolemic agents, were present in these functional food mixtures. MSFF supplementation at 50 mg/kg 100 mg/kg and 200 mg/kg showed substantial reductions in serum lipid profiles (TC and LDL) (p < .05). The serum liver profiles of AST (115.33 ± 8.69 U/L) and ALT (61.00 ± 1.00 U/L) were significantly reduced (p < .05) with MSFF supplementation at 200 mg/kg. MDA lipid peroxidation has also decreased significantly (p < .05) in serum (3.69 ± 0.42 μmol/L) and liver (15.04 ± 0.97 μmol/mg) tissues and has been shown to protect against hepatic steatosis. The significant (p < .05) inhibition activity of HMGCoA reductase (163.82 ± 3.50 pg/ml) and ACAT2 (348.35 ± 18.85 pg/ml) was also attributed by the supplementation of MSFF at 200 mg/kg.
Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery
Authors: Workman Alan D. , Soylu Selen , Kamani Dipti , Nourmahnad Anahita , Kyriazidis Natalia , Saade Ryan , Ren Yin , Wirth Lori , Faquin William C. , Onenerk Ayşe M. , Nikiforov Yuri E. , Al‐Qurayshi Zaid , Kandil Emad , Kloos Richard T. , Eldeiry Leslie , Lubitz Carrie , Stathatos Nikolaos , Randolph Gregory W.
Published: December 2020

Background

Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine‐needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases.

Design/Method

Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected.

Results

Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA.

Conclusion

In a tertiary‐care setting, one‐third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients.
A snapshot of COVID‐19 infection in patients with solid tumors
Authors: Fuentes‐Antrás Jesús , Manzano Aránzazu , Marquina Gloria , Paz Mateo , Aguado Carlos , Granja Mónica , Benítez Javier , Ortega Justo , Priego Araceli , González Carlos , Tejerina‐Peces Julia , Flores Paloma , de Sa Alfonso López , Toledano Carmen , Olalla Jennifer , de Luna Alicia , Bartolomé Jorge , Pérez‐Segura Pedro
Published: December 2020

Coronavirus disease 2019 (COVID‐19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID‐19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID‐19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in‐hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C‐reactive protein levels and an abnormal neutrophil count. We present prospective, real‐world evidence that can help articulate cancer care protocols for patients infected with SARS‐CoV‐2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID‐19.
Joint optimization ofNOMA‐enabled backscatter communications for beyond5G IoTnetworks
Authors: Khan Wali Ullah , Imtiaz Nouman , Ullah Inam
Published: December 2020

This article optimizes the link‐level of NOMA‐enable backscatter communication (BackCom) for beyond fifth‐generation (B5G) Internet‐of‐things (IoT) networks. Specifically, we jointly optimize the transmit‐power (TP) of IoT users and the reflection‐coefficient (RC) of the backscatter tag (BackTag), where the target is to increase the sum capacity (SumCap) of NOMA‐enabled BackCom. The problem of TP and RC is formulated as convex optimization, and we exploit KKT conditions to obtain the optimal solutions. The pure NOMA without BackCom and conventional orthogonal multiple access (OMA) schemes are also presented as the benchmark schemes. Our results significantly outperform the pure NOMA and conventional OMA schemes.
Practical application of Westgard Sigma rules with run size in analytical biochemistry processes in clinical settings
Authors: Peng SongQing , Zhang JinFei , Zhou WuQiong , Mao WeiLin , Han Zhong
Published: December 2020

Background

The performance of 18 routine chemical detection methods was evaluated by the sigma (σ) metric, and Westgard Sigma rules with run size were used to establish internal quality control (IQC) standards to reduce patient risks.

Materials and methods

External quality assessment (EQA) and internal quality control data from 18 assays in a biochemical laboratory were collected from January to June 2020. The sigma values of each assay were calculated, based on the bias, total error allowable, and coefficient of variation, appropriate quality control rules were selected. According to the quality goal index, the main causes of poor performance were determined to guide quality improvement.

Results

At IQC material level 1, seven of the 18 assays achieved five sigma (excellent), and five assays (UA, Crea, AMY, TC and Na) showed world‐class performance. At IQC material level 2, 14 of the 18 assays achieved 5 sigma (excellent), and thirteen assays (UA, ALT, CK, Crea, AMY, K, AST, ALP, Na, LDH, Mg, TC and GGT) showed world‐class performance. The quality goal index (QGI) was calculated for items with analysis performance <5 sigma, and the main causes of poor performance were determined to guide quality improvement.

Conclusions

Westgard sigma rules with run size are an effective tool for evaluating the performance of biochemical assays. These rules can be used to more simply and intuitively select the quality control strategy of related items and reduce the risk to patients.
A human diversity analysis of culture and gender in Asian American men's intimate partner violence perpetration
Authors: Kyler‐Yano Jason Z. , Mankowski Eric S.
Published: December 2020

This integrative literature review aims to fill the gap in our understanding of the cultural and gendered predictors of intimate partner violence (IPV) perpetration by Asian American men. A comprehensive search using PsycINFO returned N = 24 peer‐reviewed journal articles that examine Asian American men's IPV perpetration and patriarchal gender role norms and that met inclusion criteria. Patriarchal gender role norms consistently predicted IPV perpetration. However, the associations between acculturation/enculturation and IPV perpetration were less clear. Greater enculturation (Asian cultural identification) was associated with more patriarchal gender role norms while greater acculturation (mainstream US cultural identification) was associated with more masculine gender role strain. Additionally, violence in the family of origin consistently predicted later IPV perpetration as an adult. Results suggest that integrating multiple dimensions of human diversity (e.g., culture, gender, and power) in intersectional models may best explain Asian American men's IPV perpetration.
Equivalence class formation when responding is separated from sample and comparison stimuli: Working memory, priming, and sorting
Authors: Fields Lanny , Doran Erica , Foxe John J.
Published: December 2020

The experiment determined whether equivalence class formation required overlap of comparison stimuli and responding. Each trial contained a sample first, a single, nonoverlapping comparison second, and a nonoverlapping response‐window (RW) third, during which the participant made one of two responses (2R). All 11 participants formed two 3‐member ABC equivalence classes using these “trace‐stimulus‐pairing two‐response with response window” (TSP‐2R‐RW) trials. After adding a fourth stimulus (D) by CD training, ABCD tests showed immediate expansion to 4‐member ABCD classes. When 4‐member probes (AD, DA, BD, DB, CD, DC) were administered without 3‐member probes, many participants showed decrements in class‐indicative responding that then resurged to mastery with test repetition. Thus, 3‐member probes enhanced class expansion. Class formation occurred for all participants when responding was temporally dissociated from the comparisons. In a matched, contemporaneously published experiment, where responding occurred during comparisons, only 54% of participants formed the classes. Thus, the comparison‐response‐separation nearly doubled class formation. Additionally, a special post‐class‐formation sorting test documented the emergence of two explicit equivalence classes. Finally, we noted a 1:1 correspondence for TSP‐2R‐RW and priming trials. Since priming measures neural substrates of equivalence classes, TSP‐2R‐RW trials should do the same.
COVID‐19 therapy with mesenchymal stromal cells (MSC) and convalescent plasma must consider exosome involvement: Do the exosomes in convalescent plasma antagonize the weak immune antibodies?
Authors: Askenase Philip W.
Published: December 2020

Exosome extracellular vesicles as biologic therapy for COVID‐19 are discussed for two areas. The first involves the growing use of mesenchymal stromal cells (MSCs) for the profound clinical cytokine storm and severe pneumonia in COVID‐19 patients. Instead, it is recommended to treat alternatively with their MSC‐released exosomes. This is because many reports in the literature and our data have shown that the release of exosomes from the in vivo administered MSC is actually responsible for their beneficial effects. Further, the exosomes are superior, simpler and clinically more convenient compared to their parental MSC. Additionally, in the context of COVID‐19, the known tendency of MSC to intravascularly aggregate causing lung dysfunction might synergize with the pneumonia aspects, and the tendency of MSC peripheral vascular micro aggregates might synergize with the vascular clots of the COVID‐19 disease process, causing significant central or peripheral vascular insufficiency. The second exosome therapeutic area for severe COVID‐19 involves use of convalescent plasma for its content of acquired immune antibodies that must consider the role in this therapy of contained nearly trillions of exosomes. Many of these derive from activated immune modulating cells and likely can function to transfer miRNAs that acting epigenetically to also influence the convalescent plasma recipient response to the virus. There is sufficient evidence, like recovery of patients with antibody deficiencies, to postulate that the antibodies actually have little effect and that immune resistance is principally due to T cell mechanisms. Further, COVID‐19 convalescent plasma has remarkably weak beneficial effects if compared to what was expected from many prior studies. This may be due to the dysfunctional immune response to the infection and resulting weak Ab that may be impaired further by antagonistic exosomes in the convalescent plasma. At the least, pre selection of plasma for the best antibodies and relevant exosomes would produce the most optimum therapy for very severely affected COVID‐19 patients.
Adipose‐derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR‐25
Authors: Kuang Yaoyun , Zheng Xuan , Zhang Lin , Ai Xiaoyu , Venkataramani Vivek , Kilic Ertugrul , Hermann Dirk M. , Majid Arshad , Bähr Mathias , Doeppner Thorsten R.
Published: December 2020

Grafted mesenchymal stem cells (MSCs) yield neuroprotection in preclinical stroke models by secreting extracellular vesicles (EVs). The neuroprotective cargo of EVs, however, has not yet been identified. To investigate such cargo and its underlying mechanism, primary neurons were exposed to oxygen‐glucose‐deprivation (OGD) and cocultured with adipose‐derived MSCs (ADMSCs) or ADMSC‐secreted EVs. Under such conditions, both ADMSCs and ADMSC‐secreted EVs significantly reduced neuronal death. Screening for signalling cascades being involved in the interaction between ADMSCs and neurons revealed a decreased autophagic flux as well as a declined p53‐BNIP3 activity in neurons receiving either treatment paradigm. However, the aforementioned effects were reversed when ADMSCs were pretreated with the inhibitor of exosomal secretion GW4869 or when Hrs was knocked down. In light of miR‐25‐3p being the most highly expressed miRNA in ADMSC‐EVs interacting with the p53 pathway, further in vitro work focused on this pathway. Indeed, a miR‐25‐3p oligonucleotide mimic reduced cell death, whereas the anti‐oligonucleotide increased autophagic flux and cell death by modulating p53‐BNIP3 signalling in primary neurons exposed to OGD. Likewise, native ADMSC‐EVs but not EVs obtained from ADMSCs pretreated with the anti‐miR‐25‐3p oligonucleotide (ADMSC‐EVsanti‐miR‐25‐3p) confirmed the aforementioned in vitro observations in C57BL/6 mice exposed to cerebral ischemia. The infarct size was reduced, and neurological recovery was increased in mice treated with native ADMSC‐EVs when compared to ADMSC‐EVsanti‐miR‐25‐3p. ADMSCs induce neuroprotection by improved autophagic flux through secreted EVs containing miR‐25‐3p. Hence, our work uncovers a novel key factor in naturally secreted ADMSC‐EVs for the regulation of autophagy and induction of neuroprotection in a preclinical stroke model.
Functional assays to assess the therapeutic potential of extracellular vesicles
Authors: Nguyen Vivian V.T. , Witwer Kenneth W. , Verhaar Marianne C. , Strunk Dirk , van Balkom Bas W.M.
Published: December 2020

An important aspect in the development of extracellular vesicle (EV) therapeutics is identifying and quantifying the key features defining their identity, purity, sterility, potency and stability to ensure batch‐to‐batch reproducibility of their therapeutic efficacy. Apart from EV‐inherent features, therapeutic efficacy depends on a variety of additional parameters, like dosing, frequency of application, and administration route, some of which can be addressed only in clinical trials. Before initiating clinical trials, EV‐inherent features should be tested in well‐standardized quantitative assays in vitro or in appropriate animal models in vivo. Ideally, such assays would predict if a particular EV preparation has the potential to achieve its intended therapeutic effects, and could be further developed into formal potency assays as published by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. Furthermore, such assays should facilitate the comparison of EV preparations produced in different batches, on different manufacturing platforms or deriving from different cell sources. For now, a wide spectrum of in vitro and in vivo assays has been used to interrogate the therapeutic functions of EVs. However, many cannot accurately predict therapeutic potential. Indeed, several unique challenges make it difficult to set up reliable assays to assess the therapeutic potential of EVs, and to develop such assays into formal potency tests. Here, we discuss challenges and opportunities around in vitro and in vivo testing of EV therapeutic potential, including the need for harmonization, establishment of formal potency assays and novel developments for functional testing.
Interpretative immune targets and contemporary position for vaccine development against SARS‐CoV‐2: A systematic review
Authors: Chauhan Nidhi , Soni Shringika , Gupta Abhinandan , Aslam Mohammad , Jain Utkarsh
Published: December 2020

The year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), which causes COVID‐19 infection. Soon after the first evidence was reported in Wuhan, China, the World Health Organization declared global public health emergency and imminent need to understand the pathogenicity of the virus was required in limited time. Once the genome sequence of the virus was delineated, scientists across the world started working on the development of vaccines. Although, some laboratories have been using previously developed vaccine platforms from severe acute respiratory syndrome coronavirus (SARS) and middle east respiratory syndrome‐related coronavirus and apply them in COVID‐19 vaccines due to genetic similarities between coronaviruses. We have conducted a literature review to assess the background and current status of COVID‐19 vaccines. The worldwide implementation and strategies for COVID‐19 vaccine development are summarized from studies reported in years 2015–2020. While discussing the vaccine candidates, we have also explained interpretative immune responses of SARS‐CoV‐2 infection. There are several vaccine candidates at preclinical and clinical stages; however, only 42 vaccines are under clinical trials. Therefore, more industry collaborations and financial supports to COVID‐19 studies are needed for mass‐scale vaccine development. To develop effective vaccine platforms against SARS‐CoV‐2, the genetic resemblance with other coronaviruses are being evaluated which may further promote fast‐track trials on previously developed SARS‐CoV vaccines.
Rhamnolipid–Metal Ions (CrVI and PbII) Complexes: Spectrophotometric, Conductometric, and Surface Tension Measurement Studies
Authors: Hari Om , Upadhyay Santosh K.
Published: December 2020

The formation of rhamnolipid complexes with metal ions of chromium (VI) and lead (II) has been studied spectrophotometrically, conductometrically, and by surface tension measurement. The values of the critical micelle concentration (CMC) of rhamnolipid, obtained by spectroscopic, conductometric, and surface tension measurements, were 5.2 × 105, 5.0 × 105, and 5.3 × 105 mol.dm−3, respectively, which are in close agreement. An increase in CMC on increasing metal ion content in the rhamnolipid solution and a shift in λmax in the spectra of rhamnolipid indicated the formation of a complex between rhamnolipid and both the metal ions, namely, chromium (VI) and lead (II). The values of stability constants for the {rhamnolipid–chromium (VI)} and {rhamnolipid–lead (II)} complexes have been determined by spectroscopic data and were as 0.58 × 104 and 0.50 × 104 at 308 K, respectively.

The thermodynamic parameters for micellization, namely, free energy change (∆Gmic), entropy change (∆Smic), and heat enthalpy change (∆Hmic), have been determined by conductivity measurements. An increase in the negative value of ∆Gmic and a decrease in the value of ∆Smicon increasing metal ion content in the surfactant solution indicated lower micellization of rhamnolipid in the presence of metal ions. The electrostatic attractions and entrapment of chromium (VI) in the micelles of the biosurfactants were found to be responsible for {rhamnolipid–lead (II)} and {rhamnolipid–chromium (VI)} complexes, respectively.
Bagging and non‐bagging treatment on the dissipation and residue of four mixed application pesticides on banana fruit
Authors: Wang Ye , Song Qingmei , Wang Fei , Tang Shouying , Pan Tingtiao , Zhang Yuping , Hu Deyu
Published: December 2020

BACKGROUND

Bananas are vulnerable to disease and insect pests after producing fruit. In order to increase the yield and produce high‐quality fruit, the insecticides and fungicides are mixed and applied 2–3 times on banana, then the fruit is bagged. Buprofezin, imidacloprid, difenoconazole, and pyraclostrobin are widely used on banana. However, there is a lack of research on the effect of fruit bagging on pesticide dissipation and residues on bananas.

RESULTS

A versatile liquid chromatography–tandem mass spectrometry method with modified QuEChERS sample preparation has been developed for the determination of buprofezin, imidacloprid, difenoconazole, and pyraclostrobin in bananas. The recovery of four pesticides was satisfactory (74.96–98.63%) with reasonable relative standard deviation (≤ 8.78%). In Hainan and Guangzhou, the half‐lives of the four pesticides were 4.68–13.9 and 5.63–20.4 days in non‐bagged and bagged bananas, respectively. The significance analysis of the half‐lives in the two sites showed that the dissipation rates of the three pesticides (imidacloprid, difenoconazole, pyraclostrobin) on whole bananas were significantly decreased by the effect of bagging (P < 0.05). However, there was no significant difference in the degradation of half‐life of buprofezin under bagging and without bagging (P > 0.05).

CONCLUSION

The high vapor pressure and the non‐systemic property cause buprofezin to evaporate and dissipate the fastest among the four studied pesticides. The ultimate residues of four pesticides in bananas are lower than the maximum residue limits in China after three times of mixed applications under bagging or non‐bagging. The results provide scientific data for evaluating the safety of four pesticides in banana bagging. © 2020 Society of Chemical Industry
Laryngeal Pathologies Associated with the Genre of Singing and Professional Singing Status in a Treatment‐Seeking Population
Authors: Rotsides Janine , Chen Sophia , Winchester Arianna , Amin Milan R. , Johnson Aaron M.
Published: December 2020

Objectives/Hypothesis

Singers have high vocal demands and are at increased risk of developing voice disorders. Different singing genres place different technical demands on the voice. However, differences in laryngeal pathology based on genre have not been well‐researched. The purpose of this study was to determine the prevalence of laryngeal pathology in different genres of professional and amateur singers who present with a voice complaint.

Study Design

Retrospective review.

Methods

Retrospective review of patients seen at a tertiary laryngology practice. Self‐identified singers who reported their primary singing genre and categorized their singing as a full‐time job, part‐time job, or amateur involvement were included. Type and prevalence of pathology were calculated based on genre and professional status.

Results

Of the 302 self‐identified singers, 54% (n = 164) had laryngeal pathology. Among those with pathology, the most common finding was fibrotic lesion (38.4%, 63/164). Genres in which a majority of singers had pathology were other (69.2%, 9/13), choral (64.7%, 11/17), pop (63.2%, 12/19), musical theater (61.4%, 43/70), country (100%, 4/4), and Latin (100%, 2/2). The highest prevalence of pathology was seen in part‐time professional singers (62.2%, 41/66) and full‐time professionals (60.8%, 62/102), compared to amateurs (45.1%, 60/133).

Conclusions

Laryngeal pathology is prevalent in singers presenting with a voice complaint. Regardless of genre or professional status, fibrotic lesions were the most common pathological finding. This study provides preliminary data on the prevalence of different laryngeal pathologies found in singers by genre and degree of professional involvement.

Level of Evidence

4 Laryngoscope, 131:2076–2080, 2021
Effects of prolonged sedimentation from permafrost degradation on macroinvertebrate drift in Arctic streams
Authors: Levenstein Brianna , Lento Jennifer , Culp Joseph
Published: December 2020

Retrogressive thaw slumps are areas of unstable degraded permafrost that often drain into nearby watersheds, leading to increased sediment loads and changes in water quality. Thaw slumps are prevalent across the Arctic, including western Canada, Alaska, and Russia, and high‐altitude areas of western China. Over the past several decades, increased temperatures and precipitation in the Arctic have led to increases in the size and frequency of thaw slumps. Our study explored the effects of prolonged sedimentation from thaw slumps in the Peel Plateau, NWT, Canada on benthic macroinvertebrate drift, an important biological function of stream ecosystems. Though sedimentation is known to initiate a catastrophic drift response, studies have generally not considered the drift response to ongoing, long‐term perturbation. Drift densities and sediment loads were measured using drift nets and sediment traps at paired sites upstream and downstream of thaw slumps. We compared drift densities and sediment loads between sites and examined how drift differed over a fine‐sediment gradient. The amount of suspended and settling fine sediments increased significantly at downstream sites. Drift densities decreased at downstream sites; however, when drift was corrected for benthic abundance at each site, there was an increase in proportional drift density associated with increased fine sediments. These results indicate that prolonged impacts from thaw slumps result in lower macroinvertebrate abundance and higher proportional drift relative to undisturbed sites. Ultimately, increased sediment loads from thaw slumps represent a chronic stressor that will continue to prevent recovery of macroinvertebrate communities at impacted sites until these features stabilize.
From “touch” to a “multisensory” experience: The impact of technology interface and product type on consumer responses
Authors: Mishra Anubhav , Shukla Anuja , Rana Nripendra P. , Dwivedi Yogesh K.
Published: December 2020

Online retailers are increasingly using augmented reality (AR) and virtual reality (VR) technologies to solve mental and physical intangibility issues in a product evaluation. Moreover, the technologies are easily available and accessible to consumers via their smartphones. The authors conducted three experiments to examine consumer responses to technology interfaces (AR/VR and mobile apps) for hedonic and utilitarian products. The results show that AR is easier to use (vs. app), and users find AR more responsive when buying a hedonic (vs. utilitarian) product. Touch interface users are likely to have a more satisfying experience and greater recommendation intentions, as compared with AR, for buying utilitarian products. In contrast, a multisensory environment (AR) results in a better user experience for purchasing a hedonic product. Moreover, multisensory technologies lead to higher visual appeal, emotional appeal, and purchase intentions. The research contributes to the literature on computer‐mediated interactions in a multisensory environment and proposes actionable recommendations to online marketers.
Silicone‐Ionic Liquid Elastomer Composite with Keratin as Reinforcing Agent Utilized as Pressure Sensor
Authors: Liu Xue , Yu Liyun , Zhu Zicai , Nie Yi , Skov Anne Ladegaard
Published: December 2020

Development of a flexible pressure sensor is crucial for the future improvement of the wearable electronic devices designed to detect dynamic human motion. In this study, a novel pressure sensor with remarkably improved force sensing characteristics is obtained through combined usage of polydimethylsiloxane (PDMS) and ionic liquid (IL). Keratin is dispersed homogeneously in the PDMS matrix to serve as a reinforcing filler. High conductivity IL is employed as sensitivity‐enhancing constituent in the elastomer, and the effect of the amount of IL on elastomers’ pressure‐sensing performance is investigated. The elastomer with 70 parts per hundred rubber (phr) IL shows excellent pressure‐sensing performance. This novel pressure sensor demonstrates high linear sensitivity (0.037 kPa−1) in the large pressure region of 0–10 kPa. Response and recovery times are 8 and 11 ms, respectively, which are much shorter than previously reported. Moreover, the pressure sensor could distinguish different pressures via stable sensing signals in the pressure range of 0 to 50 kPa. The excellent performance of the novel pressure sensor has application potential in various fields, such as health monitoring and soft robotics.