bluuebunny/crossref_metadata_2025 huggingface dataset:
A conserved machinery underlies the synthesis of a chitosan layer in theCandidachlamydospore cell wall
Authors: Bemena Leo D. , Min Kyunghun , Konopka James B. , Neiman Aaron M.
Published: January 2021

The polysaccharide chitosan is found in the cell wall of specific cell types in a variety of fungal species where it contributes to stress resistance, or in pathogenic fungi, virulence. Under certain growth conditions, the pathogenic yeastCandida dubliniensisforms a cell type termed a chlamydosospore, which has an additional internal layer in its cell wall as compared to hyphal or yeast cell types. We report that this internal layer of the chlamydospore wall is rich in chitosan. The ascospore wall ofSaccharomyces cerevisiaealso has a distinct chitosan layer. As inS. cerevisiae, formation of the chitosan layer in theC. dubliniensis wall requires the chitin synthaseCHS3and the chitin deacetylaseCDA2. In addition, three lipid droplet-localized proteins Rrt8, Srt1, and Mum3, identified inS. cerevisiaeas important for chitosan layer assembly in the ascospore wall, are required for the formation of the chitosan layer of the chlamydospore wall inC. dubliniensis. These results reveal that a conserved machinery is required for the synthesis of a distinct chitosan layer in the walls of these two yeasts and may be generally important for incorporation of chitosan into fungal walls.

Importance

The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies. This work shows that a set of genes required for assembly of a chitosan layer in the cell wall ofS. cerevisiaeis also necessary for chitosan formation in a different cell type in a different yeast,C. dubliniensis. Because chitosan incorporation into the cell wall can be important for virulence, the conservation of this pathway suggests possible new targets for antifungals aimed at disrupting cell wall function.
Generation and characterization of a laforin nanobody inhibitor
Authors: Simmons Zoe R. , Sharma Savita , Wayne Jeremiah , Li Sheng , Kooi Craig W. Vander , Gentry Matthew S.
Published: January 2021

Mutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood epilepsy Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism. We present the generation and characterization of laforin nanobodies. We identify multiple classes of specific laforin-binding nanobodies and determine their binding epitopes using hydrogen deuterium exchange (HDX) mass spectrometry. Further, one family of nanobodies is identified that serves as an inhibitor of laforin catalytic activity. The laforin nanobodies are an important set of tools that open new avenues to define unresolved questions.
Long‐term safety of combination treatment with methotrexate and tumor necrosis factor (TNF)‐α antagonists versus TNF‐α antagonists alone in psoriatic patients
Authors: Hoffmann Jochen H. O. , Knoop Christian , Schäkel Kunt , Enk Alexander H. , Hadaschik Eva N.
Published: January 2021

Methotrexate, a folic acid analog, is the conventional systemic anti‐psoriatic agent most commonly chosen for combination with biologics in the treatment of psoriasis. Real‐world long‐term safety data of this combination versus biologic treatment alone in dermatological practice are sparse. Here, we present results of a comparative retrospective study of laboratory dynamics and adverse events in psoriatic patients receiving a tumor necrosis factor (TNF)‐α antagonist (adalimumab or etanercept) with and without concomitant methotrexate (176 treatment courses, mean duration of 629 days). Co‐treatment with methotrexate significantly (P < 0.05) correlated with a decrease of leukocyte, neutrophil and erythrocyte counts and an increase of glutamate pyruvate transaminase (GPT) (Pearson correlation, n > 148). The relative risk for a Common Terminology Criteria for Adverse Events (CTCAE) grade 1–2 laboratory adverse event was significantly elevated to 1.11 for anemia and 1.16 for a GPT increase if the patients received concomitant methotrexate at the time the laboratory test was performed. Combination treatment was given for equal or more than 30% of the time (MTX≥30%) during 12% of the treatment courses. During these treatment courses, dynamics of leukocyte (−8.1%), neutrophil (−8.1%), erythrocyte (−3.2%) counts and GPT (+16.9%) from baseline to average under treatment were significantly more pronounced. CTCAE grade 3–4 laboratory adverse events occurred in 9.5% and 5.2% of treatment courses with and without MTX≥30%, respectively (p = 0.70), and affected transaminases in 90% of the cases. Methotrexate was discontinued due to CTCAE grade 3–4 laboratory adverse events in 4.25% of the treatment courses with MTX of 30% or more. Elevated baseline γ‐glutamyl transferase levels significantly predicted the occurrence of CTCAE grade 3–4 laboratory adverse events and should trigger investigations for pre‐existing liver disease or alcohol abuse. In conclusion, our comparative data supplement previous short‐term studies and support a tolerable long‐term safety profile of the combination treatment. However, given the additional toxicities and low evidence for benefits, alternative options such as biologic monotherapy or switching to a different biologic should be considered in a dermatological setting.
Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors
Authors: Shafaati Maryam , Jamalidoust Marzieh , Kargar Mohammad , Arefian Ehsan , Kafilzadeh Farshid
Published: January 2021

Hepatitis C virus (HCV) is a positive‐sense, single‐stranded RNA virus that causes chronic hepatitis and hepatocellular carcinoma. Cellular microRNAs (miRNAs) directly modulate the viral infectivity and indirectly through targeting virus‐related host factors. They play an essential role in the progression of different stages of HCV infection. The roles of miR‐196 family in HCV infection and hepatocellular carcinoma progression remain poorly understood. Using ViTa databases, miR‐196a as a high‐score miRNA targeting the NS5A region of HCV genome was selected. Using dual luciferase assay and an established cell‐cultured HCV (HCVcc) system, the effect of miR‐196a on HCV genome was assessed. In silico analysis demonstrated the significant role of miR‐196a in the downregulation of HCV replication. Using dual luciferase assay, the liver‐specific miR‐196a and NS5A gene binding was confirmed. To assess the experimental role of miR‐196a, an HCVcc system was established in the Huh 7.5 cell lines. The HCV‐RNA 1b derived from an infected patient was transfected into Huh 7.5 cells containing miR‐196a lentiviral vectors (Huh 7.5/miR‐196a), mocks (Huh 7.5/mock vector), and naïve Huh 7.5 cells. The rate of reduction of the HCV genome replication was assessed using relative real‐time PCR assay. These results represent miR‐196a overexpression and its roles in regulating HCV genome replication. However, miR‐196a may inhibit HCV replication and accelerate the early stages of apoptosis. Overexpression of miR‐196a in Huh 7.5 replicon cell is a potential new strategy to prevent hepatitis C infection. The results of this study suggest that miR‐196a directly downregulates HCV replication and may serve as a new antiviral therapy.
Stewardship Codes and the Role of Institutional Investors in Corporate Governance: An International Comparison and Typology
Authors: Klettner Alice
Published: January 2021

Over recent decades, share ownership of listed companies has concentrated into the hands of large institutional investors, challenging the traditional agency theory view of corporate governance as a mechanism to resolve the separation of ownership and control. Alternative theories have emerged to explain the role of institutional investors in corporate governance, each with a slightly different view on the motivations of these powerful shareholders and the nature of their relationship with corporate management. These theories share a common thread – the concept of investor stewardship – yet each theory applies it differently. This paper explores whether institutional investors should act primarily as stewards of their investee companies (agency theory), stewards of beneficiaries’ funds (agency capitalism), stewards of a market/economy (universal ownership) or stewards of society (stakeholder theory), and whether this varies internationally. Through an analysis of national stewardship codes, the paper determines which of these theoretical approaches are most strongly reflected in emerging stewardship policy across the world. It presents a typology of stewardship codes as a framework for understanding cross‐country variation in investor stewardship policy. Stewardship codes influence the shareholder–manager relationship and can encourage integration of wider economic and societal concerns into corporate finance.
A patient‐centered knowledge translation tool for treat‐to‐target strategy in rheumatoid arthritis: Patient and rheumatologist perspectives
Authors: Benham Helen , Chiu Hedva , Tesiram Joanne , Mehdi Ahmed , Landsberg Peter , Grosman Sergei , Harrison Andrew , Nash Peter , Thomas Ranjeny , Langbecker Danette , Van Driel Mieke
Published: January 2021

Aim

Implementation of treat‐to‐target (T2T) for rheumatoid arthritis (RA) presents many challenges and an evidence‐practice gap has emerged. This study assessed clinician and patient barriers to the implementation of an RA‐T2T strategy and developed a knowledge translation (KT) tool for use in “real‐life” clinical settings.

Methods

Surveys of patients and rheumatologists measured agreement with RA‐T2T recommendations and use in daily practice. Patient knowledge and perceptions were assessed as was clinician willingness to alter practice and barriers to RA‐T2T using visual analog scales. An electronic KT‐tool was developed and a two‐phase usability trial undertaken to assess use in clinical interactions.

Results

Ninety‐one percent of patients had no prior knowledge of RA‐T2T but agreed with the recommendations showing mean level agreement scores (8.39‐9.54, SD 2.37‐1.54). Ninety percent were willing to try RA‐T2T, 49% felt their treatment could be improved and 28% wanted more involvement in treatment decisions. Rheumatologists agreed with RA‐T2T recommendations (7.30‐9.27, SD 2.59‐0.91). Barriers to implementation identified by rheumatologists included time, appointment availability and perceived patient reluctance to escalate medications. Usability experiences with the KT‐tool were tracked and clinicians reported it was easy to use (100%), resulted in a discussion of RA‐T2T (73%) and a target being set for 63% of consults. Patients reported they read (92%) and understood (87%) the information in the KT‐tool, and that a target was set in 62% of interactions.

Conclusions

RA‐T2T uptake in clinical practice may be improved through understanding local clinician and patient barriers and an implementation strategy utilizing a patient‐driven KT‐tool.
Crizotinib for recurring non‐small‐cell lung cancer with EML4‐ALK fusion genes previously treated with alectinib: A phase II trial
Authors: Harada Daijiro , Isozaki Hideko , Kozuki Toshiyuki , Yokoyama Toshihide , Yoshioka Hiroshige , Bessho Akihiro , Hosokawa Shinobu , Takata Ichiro , Takigawa Nagio , Hotta Katsuyuki , Kiura Katsuyuki ,   Okayama Lung Cancer Study Group
Published: January 2021

Background

The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC.

Methods

Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest.

Results

Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred.

Conclusions

Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events.
Impact of Caffeine on Ethanol‐Induced Stimulation and Sensitization: Changes in ERK and DARPP‐32 Phosphorylation in Nucleus Accumbens
Authors: Porru Simona , López‐Cruz Laura , Carratalá‐Ros Carla , Salamone John D. , Acquas Elio , Correa Mercè
Published: January 2021

Background

Caffeine is frequently consumed with ethanol to reduce the impairing effects induced by ethanol, including psychomotor slowing or incoordination. Both drugs modulate dopamine (DA)‐related markers in accumbens (Acb), and Acb DA is involved in voluntary locomotion and locomotor sensitization. The present study determined whether caffeine can affect locomotion induced by acute and repeated ethanol administration in adult male CD‐1 mice.

Methods

Acute administration of caffeine (7.5 to 30.0 mg/kg) was evaluated for its effects on acute ethanol‐induced (1.5 to 3.5 g/kg) changes in open‐field horizontal locomotion, supported rearing, and rearing not supported by the wall. DA receptor‐dependent phosphorylation markers were assessed: extracellular signal‐regulated kinase (pERK), and dopamine‐and cAMP‐regulated phosphoprotein Mr32kDa phosphorylated at threonine 75 site (pDARPP‐32‐Thr75) in Acb core and shell. Acutely administered caffeine was also evaluated in ethanol‐sensitized (1.5 g/kg) mice.

Results

Acute ethanol decreased both types of rearing. Caffeine increased supported rearing but did not block ethanol ‐induced decreases in rearing. Both substances increased horizontal locomotion in a biphasic manner, and caffeine potentiated ethanol‐induced locomotion. Although ethanol administered repeatedly induced sensitization of locomotion and unsupported rearing, acute administration of caffeine to ethanol‐sensitized mice in an ethanol‐free state resulted in blunted stimulant effects compared with those seen in ethanol‐naïve mice. Ethanol increased pERK immunoreactivity in both subregions of the Acb, but coadministration with caffeine blunted this increase. There were no effects on pDARPP‐32(Thr75) immunoreactivity.

Conclusions

The present results demonstrated that, after the first administration, caffeine potentiated the stimulating actions of ethanol, but did not counteract its suppressant or ataxic effects. Moreover, our results show that caffeine has less activating effects in ethanol‐sensitized animals.
CYP2D6*10 polymorphism and the enantioselective O‐desmethylation of S‐(+)‐ and R‐(‐)‐venlafaxine in Japanese psychiatric patients
Authors: Sasaki Taro , Yasui‐Furukori Norio , Komahashi‐Sasaki Hazuki , Shinozaki Masataka , Hayashi Yuki , Kato Kazuko , Inoue Yoshimasa , Tsuchimine Shoko , Watanabe Takashi , Sugawara Norio , Shimoda Kazutaka
Published: January 2021

According to previous studies, R‐(‐)‐venlafaxine (VEN) has higher enantioselectivity than S‐(+)‐VEN, and the plasma concentration of R‐(‐)‐VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects of CYP2D6*10 genotypes on the steady‐state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O‐desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (PCR) was used to determine the CYP2D6*10 genotypes. The plasma concentrations of S‐(+)‐VEN were approximately 1.9‐fold higher than those of R‐(‐)‐VEN. The plasma concentrations of S‐(+)‐VEN and R‐(‐)‐VEN seemed to be higher in individuals with two mutant alleles of CYP2D6*10, although no significant differences were found in the plasma levels of S‐(+)‐VEN and R‐(‐)‐VEN between CYP2D6*10 genotypes. The number of mutant alleles of CYP2D6*10 was a significant factor associated with the R‐(‐)‐ODV/R‐(‐)‐VEN ratio (P = .004) in multiple regression analysis. This suggests that CYP2D6*10 mutations affect the metabolism of R‐(‐)‐VEN and S‐(+)‐VEN. Further studies are needed to examine how these findings affect clinical practice.
Influence of external forces on actin‐dependent T cell protrusions during immune synapse formation
Authors: Zucchetti Andrés Ernesto , Paillon Noémie , Markova Olga , Dogniaux Stéphanie , Hivroz Claire , Husson Julien
Published: January 2021

Background Information

We have previously observed that in response to antigenic activation, T cells produce actin‐rich protrusions that generate forces involved in T cell activation. These forces are influenced by the mechanical properties of antigen‐presenting cells (APCs). However, how external forces, which can be produced by APCs, influence the dynamic of the actin protrusion remains unknown. In this study, we quantitatively characterised the effects of external forces in the dynamic of the protrusion grown by activated T cells.

Results

Using a micropipette force probe, we applied controlled compressive or pulling forces on primary T lymphocytes activated by an antibody‐covered microbead, and measured the effects of these forces on the protrusion generated by T lymphocytes. We found that the application of compressive forces slightly decreased the length, the time at which the protrusion stops growing and retracts and the velocity of the protrusion formation, whereas pulling forces strongly increased these parameters. In both cases, the applied forces did not alter the time required for the T cells to start growing the protrusion (delay). Exploring the molecular events controlling the dynamic of the protrusion, we showed that inhibition of the Arp2/3 complex impaired the dynamic of the protrusion by reducing both its maximum length and its growth speed and increasing the delay to start growing. Finally, T cells developed similar protrusions in more physiological conditions, that is, when activated by an APC instead of an activating microbead.

Conclusions

Our results suggest that the formation of the force‐generating protrusion by T cells is set by an intracellular constant time and that its dynamic is sensitive to external forces. They also show that actin assembly mediated by actin‐related protein Arp2/3 complex is involved in the formation and dynamic of the protrusion.

Significance

Actin‐rich protrusions developed by T cells are sensory organelles that serve as actuators of immune surveillance. Our study shows that forces experienced by this organelle modify their dynamic suggesting that they might modify immune responses. Moreover, the quantitative aspects of our analysis should help to get insight into the molecular mechanisms involved in the formation of the protrusion.
Drought and soil nutrients effects on symbiotic nitrogen fixation in seedlings from eight Neotropical legume species
Authors: McCulloch Lindsay A. , Piotto Daniel , Porder Stephen
Published: January 2021

Symbiotic nitrogen fixation is a dominant source of nitrogen to many terrestrial ecosystems and thus may influence their responses to global change. High legume species diversity and abundance are thought to lead to high rates of symbiotic nitrogen fixation in Neotropical forests. However, how changes in water and nutrient availability will affect symbiotic nitrogen fixation has only recently been explored, even as droughts begin to increase in severity and frequency in the Neotropics. To explore these effects, we grew eight species of Neotropical woody legume seedlings in a shadehouse for four months while manipulating soil water, phosphorus, and molybdenum availability. Overall, drought reduced nodule biomass, nitrogenase activity (acetylene reduction g‐1 nodule), and acetylene reduction per seedling by 33%, 27%, and 41%, respectively, but reduced seedling biomass by only 18%. Species varied in the manifestation of drought effects. For example, drought reduced the probability that nodules formed in some species, but in others reduced the nitrogenase activity or acetylene reduction per seedling. In contrast, the effects of phosphorus and molybdenum availability were more species‐specific. However, fertilization did affect (both positively and negatively) one or more symbiotic nitrogen fixation response variables in two of the eight species. Our results indicate drought reduces symbiotic nitrogen fixation in Neotropical legume seedlings, but the mechanism of response may be species‐specific. Therefore, predicting the response of symbiotic nitrogen fixation in the Neotropics to a changing climate, with expected increases in drought frequency and severity, may require grappling with the diversity of responses among nitrogen‐fixing legumes.

Abstract in Portuguese is available with online material
Oh No! They Cut My Funding! Using “Post Hoc” Planned Missing Data Designs to Salvage Longitudinal Research
Authors: Feng Yi , Hancock Gregory R.
Published: January 2021

Having one’s funding cut in the course of conducting a longitudinal study has become an increasingly real challenge faced by developmental researchers. The main purpose of the current work is to propose “post hoc” planned missing (PHPM) data designs as a promising solution in such difficult situations. This study discusses general guidelines that can be followed to search for viable PHPM designs within a given budget restriction. Illustrative examples across different longitudinal research contexts are provided, each showing how PHPM data designs can help salvage longitudinal studies when an unexpected funding cut occurs mid‐study. With the illustrative examples, the article also shows how developmental researchers can conveniently identify viable designs using the R package simPM.
Assessment of mirror movements in children and adolescents with unilateral cerebral palsy: reliability of the Woods and Teuber scale
Authors: Magne Victoria A , Adde Lars , Hoare Brian , Klingels Katrijn , Simon‐Martinez Cristina , Mailleux Lisa , Lydersen Stian , Elvrum Ann‐Kristin G
Published: January 2021

Aim

To investigate the inter‐ and intrarater reliability of the Woods and Teuber scale to detect mirror movements in children and adolescents with unilateral cerebral palsy (CP).

Method

A convenience sample of children and adolescents with unilateral CP (n=68; 31 males, 37 females; mean age 12y 2mo, SD 3y 6mo) in Manual Ability Classification levels I to III was recruited from Norway, Australia, and Belgium. Three therapists scored mirror movements according to the Woods and Teuber scale from three video‐recorded tasks at two separate time points. A two‐way, mixed model regression was used to calculate intraclass correlation coefficients (ICCs) reflecting overall inter‐ and intrarater reliability. In addition, ICCs for each hand and task were calculated separately.

Results

The overall interrater reliability ICC was 0.90 and the corresponding intrarater reliability ICC was 0.92. The ICCs for each hand ranged from 0.86 to 0.92 and for each task from 0.63 to 0.89.

Interpretation

The Woods and Teuber scale shows excellent reliability for scoring mirror movements in children and adolescents with unilateral CP. The assessment is easy to administer with no need for specific equipment and scoring can be determined from short video recordings, making it a feasible instrument in research and clinical practice.
The Gulf Cooperation Council states: Crystallization of the regional cooperation and alliances amid dwindling resources
Authors: Tok Evren
Published: January 2021

The Gulf Cooperation Council (GCC) states can be divided into two main camps in terms of hydrocarbon endowment per capita which can partially account for differences in policy directions. Kuwait, Qatar, and the UAE (the rich triplet) have small populations while having large hydrocarbon (oil and natural gas) endowments compared to Bahrain, Oman, and Saudi Arabia. Kuwait, Qatar, and the UAE have been effectively using their excess wealth in the form of investment for domestic economic diversification and overseas investments through their sovereign wealth funds (SWFs). Therefore, the rich triplet perceives the upcoming threat of decarbonization of the world's energy system lighter than the remaining members of the GCC in view of their prosperity. The expected decrease in oil demand and revenue within the next decade will put further strain on the relationship between these states.
Improved survival in multiple Myeloma patients undergoing autologous stem cell transplantation is entirely in the standard cytogenetic risk groups
Authors: Afram Gabriel , Susek Katharina Helene , Uttervall Katarina , Wersäll Johanna Dehlsen , Wagner Arnika Kathleen , Luong Vincent , Lund Johan , Gahrton Gösta , Alici Evren , Nahi Hareth
Published: January 2021

Introduction

Novel drugs and drug combinations have improved outcomes for multiple myeloma patients. However, subgroups of patients still have a poor progression‐free survival (PFS) and overall survival (OS). In an attempt to identify how the novel drugs affect the outcome in standard‐risk and high‐risk patients, respectively, we have investigated 715 multiple myeloma (MM) patients who have undergone high dose treatment followed by autologous stem cell transplantation at our center during 1995 ‐ 2020. Outcomes during three time periods, 1995‐1999 (period I), 2000‐2009 (period II), and 2010‐2020 (period III), were compared separately for standard‐risk and high‐risk patients. Risk stratification was based on chromosome analysis for periods II and III.

Results

The whole cohort of patients showed significantly improved OS with time during the three periods being at a median of 5.8, 7.0, and 10.0 years, respectively. There is also a weak tendency for improved PFS, that is, a median of 2.4, 2.6, and 2.9 years, respectively, during the same periods. However, the separate analysis of standard‐risk and high‐risk patients showed that the overall improvement with time was due to improved standard‐risk patients (median OS 8.4 years for the period I and not reached for period II and III). In contrast, no significant improvement was seen in high‐risk patients. For patients with del17p, PFS was even worse during period III as compared to period II (median 1.6 vs 3.2 years respectively).

Conclusion

Our results show that the dramatic improvement in outcome for MM patients during the last 20 years only applies for standard‐risk patients, while high‐risk MM patients still are doing poorly, indicating that the novel drugs developed during this time are preferentially effective in standard‐risk patients. New treatment modalities like CAR‐T cells, CAR‐NK cells, and/or bispecific antibodies should be tried in clinical studies early in the course of the disease, especially in patients with high‐risk cytogenetics.
Democracy and bureaucracy in newly industrialized countries: A systematic comparison between Latin America and East Asia
Authors: de Avila Gomide Alexandre
Published: January 2021

This article analyzes the political‐institutional determinants of bureaucracy quality among a group of newly industrialized countries in Latin America and East Asia democratized in the Third Wave. Four causal conditions are examined for the occurrence of higher levels of bureaucratic “weberianess” in the selected cases: historical sequence, political parties' institutionalization, electoral competition, and ethnic politics. The study employs the fuzzy‐set qualitative comparative analysis to explore the expectation that each of these conditions' implications depends on other conditions' presence or absence. The findings disconfirm claims about the critical role of party system institutionalization for Weberian bureaucracies in new democracies. Besides, the analysis did not declare a professional public administration's prior existence before democratization as a necessary or sufficient condition for the outcome of interest. Finally, although the electoral competition was declared necessary for the outcome occurrence, it does not imply the same result if combined with ethnic politics.
Littering behaviour: A systematic review
Authors: Chaudhary Abdul Haseeb , Polonsky Michael Jay , McClaren Nicholas
Published: January 2021

Littering is a widespread problem that has negative consequences for the wellbeing of society and has been discussed in a wide range of subject areas. However, the lack of a unified understanding of the literature on littering presents an opportunity for a synthesis of the literature. This systematic review integrated the findings from 70 journal articles spanning 48 years. The articles were analysed for use of theories, models, methods, locations of study, variables and study findings. The researchers also undertook a content analysis of the literature to understand the evolution of approaches across time. The findings show that situational and psychological factors have often been studied using the ‘Focus Theory of Normative Conduct’ and the ‘Integrative Behaviour Model’. However, the findings have been inconsistent, with varying results for some of the situational, psychological and administrative factors. The content analysis identified that the literature from 1971 to 2006 was mostly confined to developed countries (80%) with the majority of studies examining situational and psychological factors. The gaps in the literature provided a basis for proposing five future research directions including the development of social marketing interventions by improving the theoretical groundings of previous works. As littering is consumer behaviour, it is also important to investigate the role of businesses as an integral part of the consumer exchange process to assist in improving the situation. The detailed future research directions and the conclusions of the review are presented.
Protecting children: Testing a stop‐and‐take‐a‐break advergame intervention strategy
Authors: Cho Eunji , Riddle Karyn
Published: January 2021

Research suggests information‐based advertising literacy efforts do not consistently reduce the persuasive effects of advergames on young children. Therefore, the present study builds upon prior research, suggesting a distraction might reduce children's engagement with advergames, lowering their effectiveness through more affective routes. In an experiment conducted on 134 children ages 8–11 in South Korea, we randomly assigned participants to play an advergame either with or without a “stop‐and‐take‐a‐break” intervention. Results suggest the stop‐and‐take‐a‐break intervention strategy works by decreasing player presence, which is subsequently correlated with decreases in mood, game liking and positive attitudes towards the advertised brand. Theoretical and practical implications of the findings are discussed.
Analysis of 3702 patients with acne vulgaris and concomitant comorbidities in Turkey: a multi‐centered, prospective, controlled study
Authors: Ünal Emine , Karadağ Ayşe Serap , Şikar Aktürk Aysun , Dizen Namdar Nazlı , Kelekçi Kıymet Handan , Aksoy Berna , Özlü Emin , Baykal Leyla , Karaman Göksun , Sarıcaoğlu Hayriye , Zindancı İlkin , Balta İlknur , Turan Çağrı , Can Kuru Burçe
Published: January 2021

Background

Acne vulgaris is a chronic inflammatory skin disease that affects the pilosebaceous unit. Although it is considered to be a skin‐limited disease, different clinical studies have recently been published in which the disease is accompanied by systemic symptoms. In this study, systemic comorbidities accompanying acne vulgaris and the relationship between existing comorbidities and disease severity are investigated.

Methods

This prospective multicenter study was conducted by the Turkish Society of Dermatology Acne Study Group. Twelve dermatology clinics and 14 clinicians throughout Turkey participated in the study. A structured physician‐administered questionnaire was used to collect patient demographics, clinical findings, and lifestyle data. Physicians recorded each participant’s medical history, including current and past comorbidities, duration of any comorbidity, smoking, and drinking. Body mass index (BMI) was calculated.

Results

There were 3022 patients in the adolescent acne group and 897 in the control group. The incidence of nonmigraine headache in adolescents with acne was significantly higher than in the nonacne group (P = 0.019). There were 680 patients in the postadolescent acne group and 545 in the control group. In the postadolescent group, incidence of metabolic disease was lower than the control group (P = 0.003). In the postadolescent group, premenstrual syndrome (P < 0.001) and PCOS (P = 0.007) were more common than the control group.

Conclusions

In this study, we observed that acne vulgaris does not cause systemic comorbidities. There is also a need for new studies involving a large number of patients to illuminate systemic diseases accompanying acne vulgaris.
Chemical, thermal and structural properties of alkaline‐cooked (nixtamalised) chickpea (Cicer arietinum) flours
Authors: Mariscal‐Moreno Rosa María , Figueroa‐Cárdenas Juan de Dios , Santiago‐Ramos David , Aguilar Arteaga Karina , Flores Casamayor Verónica , Rincón‐Aguirre Alexandra
Published: January 2021

The present study examined how the alkaline cooking process affects the chemical, thermal and structural properties of the chickpea, evaluating different lime concentrations. Cooking was carried out at 94 °C, with two times of water for 15 min with five different lime concentrations. Regarding chemical composition, a decrease in protein and fat was observed: from 23.64% to a range of 18.26–19.93% for protein and from 8.20% to a range of 6.05–7.74% for fat. However, an increase was observed for ash and mineral content. The same pattern was observed for potassium. Raw chickpea did not present endotherm retrogradation, but a higher endotherm retrogradation was presented in chickpea cooked without lime, denoting that nixtamalisation decreased retrogradation. Additionally, V‐amylose relative crystallinity increased with concentration of lime. Protein digestibility increases by β‐sheet dismissing structure. Finally, it was observed that steeping time plays a key role in the nixtamalisation process.
What is the most anticipated change induced by treatment using gender‐affirming hormones in individuals with gender incongruence?
Authors: Masumori Naoya , Baba Tsuyoshi , Abe Teruo , Niwa Koji
Published: January 2021

Objectives

To identify the most eagerly anticipated change resulting from hormone therapy using gender‐affirming hormones for patients with gender incongruence undergoing a clinical trial.

Methods

Patients diagnosed with gender identity disorders based on the International Classification of Diseases 10th revision classification at three institutions in Japan for whom hormone therapy using gender‐affirming hormones was initiated were analyzed. They were asked what the most anticipated change was due to gender‐affirming hormone that they had thought of between giving informed consent and the first administration of the drug.

Results

The responders were 336 transgender men who were administered androgens and 48 transgender women who received estrogens. The median age at commencement of hormone therapy was 24 years for transgender men and 28 years for transgender women. For transgender men, the most frequent answer was cessation of menses (52.7%) followed by a deepened voice (32.4%). For transgender women, breast development (35.4%) was the most anticipated change, followed by gynoid fat deposition (29.2%).

Conclusions

Cessation of menses in transgender men and breast development/gynoid fat deposition in transgender women might represent primary end‐points in clinical trials evaluating the efficacy of hormonal treatment in these patients.
Bisphenol A at a human exposed level can promote epithelial‐mesenchymal transition in papillary thyroid carcinoma harbouring BRAFV600E mutation
Authors: Li Liuli , Li Hao , Zhang Jun , Gao Xin , Jin Hao , Liu Renqi , Zhang Zhen , Zhang Xuan , Wang Xichang , Qu Peng , Zhao Yuejiao , Lu Xiaobo
Published: January 2021

Bisphenol A (BPA), a ubiquitous endocrine‐disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone‐dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAFV600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAFV600E mutation on epithelial‐mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAFV600E mutation and the level of EMT‐related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT‐related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAFV600E mutation. Moreover, ERK‐Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10‐7 M) synergized with the BRAFV600E mutation promoted EMT via the activation of ERK‐Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAFV600E mutation.
BIBLIOMETRIC TECHNIQUES AND THEIR USE IN BUSINESS AND ECONOMICS RESEARCH
Authors: Rousseau Sandra , Rousseau Ronald
Published: January 2021

Bibliometric indicators and bibliometric techniques have been used in the domains of business and economics (BE) in the context of network studies and the evaluation of universities, journals and researchers, among other purposes. Using a strengths, weaknesses, opportunities and threats analysis as a general framework, we present an overview of the strengths, weaknesses, opportunities and threats related to the use of mainstream bibliometrics in BE. Several weaknesses in the use of bibliometric indicators for research evaluation in BE, and, in general, are discussed. Misuse of bibliometric indicators may lead to goal displacement and gender bias. Yet, being aware of possible problems leads to opportunities for further developments and applications of bibliometrics in the field of BE. We propose that traditional research evaluation should evolve into evaluative inquiry, a method where bibliometric indicators play a role, but in which all aspects of life and work of a scientific professional can be taken into account and assessment is relabelled in positive terms such as organizational and individual development, care and support.
A case of ovarian stimulation for fertility preservation in a patient with Philadelphia chromosome‐positive acute lymphoblastic leukemia after treatment with dasatinib
Authors: Ogawa Tatsuyuki , Ogi Maki , Hirata Shuji
Published: January 2021

Tyrosine kinase inhibitors (TKIs) are effective for treating Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL). However, the use of TKIs may decrease the number of collected oocytes during fertility preservation procedures. We report the case of a 19‐year‐old patient with Ph+ALL for whom 21 oocytes were frozen after controlled ovarian stimulation was initiated 2 days after the completion of 28 days of remission induction therapy with dasatinib. After collecting the oocytes, consolidation therapy was initiated immediately, and a hematopoietic stem cell transplant from her younger brother was scheduled. It is believed that a 2‐day withdrawal period is sufficient for fertility preservation or that the effect of dasatinib on the number of oocytes obtained is minimal.
Criminal Justice Contact, Residential Independence, and Returns to the Parental Home
Authors: Warner Cody , Remster Brianna
Published: January 2021

Objective

The authors investigate whether criminal justice contact is associated with residential transitions—both home‐leaving and home‐returning—among contemporary young adults.

Background

More young adults live with their parents today than live independently. Despite the prevalence of criminal justice contact among young Americans, and research suggesting that such contact can reshape the life course, it is unknown whether the criminal justice system is associated with patterns of home‐leaving and home‐returning.

Method

Data are drawn from the National Longitudinal Survey of Youth 1997, a sample of 8,984 young adults born between 1980 and 1984. Event history analyses are used to examine the timing of home‐leaving (n = 810,274 person‐months), and among those who leave, the timing of home‐returning (n = 630,394 person‐months). Criminal justice contact is measured via self‐reported arrests and spells of incarceration.

Results

Across both the short term and long term, there is a robust association between criminal justice contact and residential transitions out of and back into the parental home. The risk of experiencing home‐leaving or home‐returning is considerably higher in the month an individual is arrested or completes a spell of incarceration, compared to individuals with no contact. Additionally, especially for arrest, the risk of each residential transition remains elevated in the months and years that follow contact.

Conclusion

Findings highlight how the criminal justice system may complicate the transition to adulthood by contributing to unstable residential trajectories.
Effect of immunized egg proteins on the performance and neonatal diarrhoea incidence in newborn calves
Authors: van Kuijk Sandra , Kinkead Ruth , Scoley Gillian , Morrison Steven , Han Yanming
Published: January 2021

The aim of this study was to assess the effects of feeding immunized egg proteins (IEP) on the health and performance of newborn dairy calves. Sixty‐four Holstein calves, both male and female, were divided over two treatments. Calves either received IEP or a placebo (PCB) in their colostrum and calf milk replacer (CMR) for the first 14 days of their life. Until day 49, CMR was offered at 15% of birth weight (BW), at 10% on days 49–57 and at 5% on days 57–63. In addition, calves received starter concentrate, chopped straw and water from 3 days old until 70 days old at the end of study. Individual CMR and concentrate intake were measured daily whilst BW was recorded weekly. Visual faecal scoring and health observations were conducted daily. Faecal samples were collected weekly up to 4 weeks and during the first 4 days of scouring to screen for presence ofCryptosporidium parvum, rotavirus, coronavirus,E. coliandSalmonella. Results indicated that feeding IEP increased BW (p < .05) at 42 and 56 days old, and BW also tended (p = .06) to be higher after weaning at 63–70 days old compared to the PCB group. When analysed using a repeated measures model, compared to feeding PCB, feeding IEP increased total concentrate consumption (p = .001) by 3.6kg/calf. Over the entire study, daily water intake was higher (p = .002) for the IEP group when compared with the PCB group. In the IEP group, 12 calves were scored as scouring whereas there were 14 calves in the PCB group. There were no significant differences between treatments in faecal pathogen load of neither healthy nor scouring calves. In conclusion, supplementing IEP during the first 14 days of calf life improved the performance of newborn calves. Further work is warranted to understand the mode of action of IEP in calves.
Stable isotope analysis suggests low trophic niche partitioning among co‐occurring land snail species in a floodplain forest
Authors: Němec T. , Líznarová E. , Birkhofer K. , Horsák M.
Published: January 2021

Land snails are abundant invertebrates in many terrestrial ecosystems, playing an essential role in food webs and nutrient cycling. Although snails are commonly considered general grazers with a strong tendency to omnivory, their foraging strategy is well documented only for a few species. Virtually no data exist on trophic niche partitioning within snail assemblages. To fill this gap, we analyzed naturally occurring stable isotope (δ13C, δ15N), an approach widely applied in ecological research, but only rarely in terrestrial snail studies. We collected ten individuals of the dominant co‐occurring land snails (i.e.,Aegopinella nitidula,Fruticicola fruticum,Oxyloma elegans,Succinea putris,Trochulus villosulusandZonitoides nitidus) in a floodplain forest floor, along with their potential food sources and other invertebrates. All species, except forA. nitidula, showed high intraspecific variation in isotope signatures, indicating their opportunistic feeding behavior. Such a high intraspecific variation combined with the active movement range of all the species allows switching between food sources based on their accessibility. We observed that the trophic niches of the studied species highly overlapped, except forZ. nitidus. This suggests that trophic niche compartmentalization among co‐occurring species does not seem to be the mechanism to avoid competition for food. Virtually unlimited resources for snail food are assumed to explain the coexistence of many species in high‐density populations. Our results add to this concept of assembly rules in snail species by the finding of highly variable and overlapping trophic niches among the majority of the studied species.
A Keynesian model of aggregate demand in the long‐run
Authors: McDonald Ian M.
Published: January 2021

This paper develops the Keynesian theory of aggregate demand in the long‐run in which persistently low levels of aggregate demand can generate persistently low levels of activity with the associated persistently high rates of unemployment. Wages are determined by firm‐worker bargaining/sharing. Investment is influenced by monopoly power, aggregate demand and the interest rate. Decreasing rates of deflation of money wages and prices even at high rates of unemployment are prevented by workers being assumed to be loss averse with respect to reductions in their wages below a reference real wage.