bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of air‐impingement jet drying on drying kinetics, color, polyphenol compounds, and antioxidant activities of Boletus aereus slices
Authors: Zheng Qiaoran , Li Xiexin , Liu Tingting , Zhang Yan , Liu Jingyi , Zhang Heng , Li Wenfeng , Gao Xiaoxv
Published: April 2021

The aim of the study is to interpret the effects of air‐impingement jet drying (AIJD) on drying kinetics, color, polyphenols, and antioxidation ability of Boletus aereus slices. Page model was most suitable for expressing and predicting AIJD curves of B. aereus slices. The moisture‐effective diffusion coefficient of AIJD ranged from 7.8876 × 10−10 to 2.1426 × 10−9 m2/s, and AIJD also showed high efficiency due to its low activation energy (45.37 kJ/mol). AIJD is better for B. aereus slices than hot air drying (HAD) in accelerating the drying rate (DR) and shortening drying time, and maintaining color. p‐hydroxybenzoic acid, protocatechuic acid, and rutin were identified in B. aereus slices by ultra high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC‐QqQ‐MS). Total polyphenols, flavanone, phenolic acids, and antioxidant activities were significantly lower in dried B. aereus slices than those in fresh B. aereus slices. In AIJD, drying temperature had the greatest effect on the quality of B. aereus slices, and AIJD at 50 °C is the optimum drying condition for B. aereus slices.

Practical Application

Boletus aereus occurs in many countries all over the world. In this paper, the effect of AIJD on color, polyphenols, and antioxidation ability in B. aereus slices and its drying kinetics were studied. AIJD is an efficient drying method for B. aereus by decreasing its drying time, increasing DR, and protecting the color of B. aereus. These findings have provided important reference basis for people to have a better understanding of AIJD method, which was used to dry B. aereus. This study also provides a new technique for drying B. aereus, which could improve dry efficiency and reduce drying cost.
Efficacy of Citrus maxima fruit segment supplemented paranthas in STZ induced diabetic rats
Authors: Somanathan Karthiga Reshmi , Sukhdeo Shinde Vijay , Madhugiri Lakshminarayan Sudha , Mysuru Nanjarajurs Shashirekha
Published: April 2021

The study was conducted to investigate the efficacy of Citrus maxima (Pomelo) fruit segments fortified paranthas compared to pomelo juice and naringin in streptozotocin‐induced diabetic rats. The animals were divided into nine groups, Groups 1 to 3: negative control; Group 4: diabetic control; Groups 5 through 8: treatments with pomelo juice, naringin, plain paranthas, and pomelo supplemented paranthas; and Group 9 was positive control metformin. The groups were monitored for weight, oral glucose tolerance, insulin tolerance, bioavailability, biochemical parameters, and histopathological studies. Based on the result the group treated with paranthas fortified with pomelo fruit segment (Group 8) showed 19% of overall weight gain, approximately 50% reduction in plasma glucose level and improved serum protein (5.70 g/dl) and serum insulin (8.54 ng/ml) level as compared against diabetic control. The treatments had effectively lowered the level of liver enzyme and lipids (except HDL) in the serum along with the improved renal function. The group treated with pomelo juice and pomelo supplemented paranthas exhibited marked tolerance to the glucose and insulin similar to the positive control. Therefore, the antidiabetic activity was found to be more pronounced in the order of pomelo juice > fortified paranthas > naringin. Since pomelo juice is bitter and astringent in nature, the fruit can be better utilized in the form of fortified paranthas, which exerts antidiabetic effect similar to the positive control metformin. Hence, paranthas supplemented with pomelo fruit segments (bioactives‐rich) aids in the reducing the risk of diabetes and can be recommended to gain nutritional benefits for normal and diabetic populations.
Frequency of Growth Differentiation Factor 5 rs143383 and asporin D‐repeat polymorphisms in patients with hand and knee osteoarthritis in Kurdistan province, Iran
Authors: Moghimi Nasrin , Nasseri Sherko , Ghafouri Farzad , Jalili Ali
Published: April 2021

Aim

Osteoarthritis (OA) is the most common chronic joint disorder, resulting from the breakdown of joint cartilage. It occurs in the knees, hands, and hips, leading to pain, stiffness, inflammation, and swelling.

Methods

In this study, 100 hand and knee OA patients, meeting the American College of Rheumatology criteria were included in the case group, and 100 healthy individuals were allocated to the control group. Blood samples were collected from the participants. After DNA extraction, genotyping was carried out for GDF5 rs143383 C/T polymorphism by allele‐specific polymerase chain reaction (ASPCR) and for D‐repeat alleles of asporin (ASPN) by conventional PCR assay.

Results

The results showed that the frequency of the D14 allele of ASPN was significantly higher than other alleles in the case group (P = .0001). Also, the frequency of the D14 allele among women was significantly higher than in men (P = .004). Moreover, the frequency of the TT allele in GDF5 rs143383 C/T polymorphism was significantly higher than the CC and CT alleles in the case group, compared with the control group (P = .001). A significant difference was found between the TT allele and other alleles in female and male patients compared with the control group (P = .02).

Conclusions

The D14 allele of the ASPN gene and TT allele of the GDF5 gene (rs143383 + 104T/C) are associated with hand and knee OA in the Kurdish population, indicating that these alleles could be risk factors for OA, at least in our populations.
The Data Analytics Journey: Interactions Among Auditors, Managers, Regulation, and Technology*
Authors: Austin Ashley A. , Carpenter Tina D. , Christ Margaret H. , Nielson Christy S.
Published: April 2021

Data analytics is transforming our global markets and significantly impacting the financial reporting environment. We investigate how auditors, company managers, and regulation interact with data analytics and one another to affect the diffusion (i.e., development and spread) of data analytics throughout the financial reporting environment. We interview company managers and their audit partners, as well as additional stakeholders, including regulators. We interpret findings from our interviews using theory that highlights the importance of dynamic interactions between people and their environments, which include the prevailing rules (e.g., regulatory guidance). Our findings contribute to the accounting literature and practice by revealing three areas of conflict emerging from stakeholders' disparate preferences for data analytics. First, we uncover growing tensions between managers and audit partners regarding audit fees. Second, we find that managers and auditors believe the lack of accounting regulation specific to data analytics causes confusion and frustration. Finally, auditors report that they strategically leverage data analytics to provide clients with business‐related insights. However, regulators voice concerns that this practice might impair auditor independence and reduce audit quality. These areas of conflict suggest a need to revisit key tensions surrounding the audit function in a contemporary context characterized with significant technological shift.
The impact of manic symptoms in first‐episode psychosis: Findings from the UK National EDEN study
Authors: Marwaha Steven , Hett Danielle , Johnson Sonia , Fowler David , Hodgekins Joanne , Freemantle Nick , McCrone Paul , Everard Linda , Jones Peter , Amos Tim , Singh Swaran , Sharma Vimal , Birchwood Max
Published: April 2021

Objective

The extant literature is inconsistent over whether manic symptoms in first‐episode psychosis (FEP) impact on its development and trajectory. This study addressed the following: (1) Does Duration of Untreated Illness (DUI) and Duration of Untreated Psychosis (DUP) differ between FEP patients with and without manic symptoms? (2) Do manic symptoms in FEP have an impact on time to remission over 1 year?

Methods

We used data from the National EDEN study, a longitudinal cohort of patients with FEP accessing early intervention services (EIS) in England, which measured manic, positive and negative psychotic symptoms, depression and functioning at service entry and 1 year. Data from 913 patients with FEP (639 without manic symptoms, 237 with manic symptoms) were analysed using both general linear modelling and survival analysis.

Results

Compared to FEP patients without manic symptoms, those with manic symptoms had a significantly longer DUI, though no difference in DUP. At baseline, people with manic symptoms had higher levels of positive and negative psychotic symptoms, depression and worse functioning. At 12 months, people with manic symptoms had significantly poorer functioning and more positive psychotic symptoms. The presence of manic symptoms delayed time to remission over 1 year. There was a 19% reduced rate of remission for people with manic symptoms compared to those without.

Conclusions

Manic symptoms in FEP are associated with delays to treatment. This poorer trajectory persists over 1 year. They appear to be a vulnerable and under‐recognised group for poor outcome and need more focussed early intervention treatment.
Health warning labels and alcohol selection: a randomised controlled experiment in a naturalistic shopping laboratory
Authors: Clarke Natasha , Blackwell Anna K. M. , De‐loyde Katie , Pechey Emily , Hobson Alice , Pilling Mark , Morris Richard W. , Marteau Theresa M. , Hollands Gareth J.
Published: April 2021

Background and aims

Health warning labels (HWLs) on tobacco products reduce smoking. There is an absence of evidence concerning the impact of alcohol HWLs on selection or purchasing in naturalistic settings. Using a commercial‐standard naturalistic shopping laboratory, this study aimed to estimate the impact on selection of alcoholic drinks of HWLs describing adverse health consequences of excessive alcohol consumption.

Design

A between‐subjects randomised experiment with three groups was conducted: group 1: image‐and‐text HWL; group 2: text‐only HWL; group 3: no HWL.

Setting

A commercial‐standard naturalistic shopping laboratory in the United Kingdom.

Participants

Adults (n = 399, 55% female) over the age of 18 years, who purchased beer or wine weekly to drink at home.

Interventions

Participants were randomised to one of three groups varying in the HWL displayed on the packaging of the alcoholic drinks: (i) image‐and‐text HWL (n = 135); (ii) text‐only HWL (n = 129); (iii) no HWL (n = 135). Participants completed a shopping task, selecting items from a range of alcoholic and non‐alcoholic drinks, and snacks.

Measurement

The primary outcome was the proportion of alcoholic drinks selected. Secondary outcomes included HWL ratings on negative emotional arousal and label acceptability.

Findings

There was no clear evidence of a difference in the HWL groups for the percentage of drinks selected that were alcoholic compared to no HWL (44%): image‐and‐text HWL: 46% (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.82, 1.42); text‐only HWL: 41% (OR = 0.87, 95% CI = 0.67, 1.14). Concordant with there being no difference between groups, there was extreme evidence in favour of the null hypothesis (Bayes factor [BF] < 0.01). Negative emotional arousal was higher (P < 0.001) and acceptability lower (P < 0.001) in the image‐and‐text HWL group, compared to the text‐only HWL group.

Conclusions

In a naturalistic shopping laboratory, there was no evidence that health warning labels describing the adverse health consequences of excessive alcohol consumption changed selection behaviour.
Cemental tear: An overlooked finding associated with rapid periodontal destruction. A case series
Authors: Pedercini A , Weitz DF , Heyse JD , Pedercini C , Kormas I , Koutlas IG , Johnson DK , McClanahan SB
Published: April 2021

Cemental tear is defined as cementum fragment completely or partially detached from the root surface, and it has been associated with localized rapid periodontal breakdown. Although history of trauma and/or attrition may be risk factors, the etiopathology of cemental tear remains unknown. This case series aims to discuss the clinical, radiographic and histopathologic features of cemental tears to aid clinicians in making differential diagnosis. Three teeth from three patients presenting a periradicular lesion underwent an exploratory surgery to determine the cause and provide treatment. Soft and hard tissue biopsies were obtained from each lesion and forwarded for histopathologic evaluation. Two patients received a guided tissue regeneration (GTR) procedure, which allowed the tooth to be retained. One patient received an extraction with simultaneous guided bone regeneration (GBR) due to a hopeless prognosis of the tooth. The results after histopathologic evaluation yielded a final diagnosis of cemental tear for all three patients. Cemental tears may be overlooked, and therefore, they should be included in the differential diagnosis of periapical periodontitis, endodontic‐periodontal lesion and vertical root fracture (VRF).
Periodontal health status of children and adolescents with diabetes mellitus: a systematic review and meta‐analysis
Authors: Zainal Abidin Z , Zainuren ZA , Noor E , Mohd Nor NS , Mohd Saffian S , Abdul Halim R
Published: April 2021

Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycaemia resulted from defects in insulin secretion or action, or both. Various studies have reported on the bidirectional relationship between DM and periodontal disease. A systematic search of the literature was performed in several databases, EBSCO Medline Complete, PubMed, Science Direct and a manual search for articles from 2000 until 2019. Literature that fulfilled the inclusion criteria were identified, and data measuring plaque index (PI), gingival index (GI), clinical attachment loss (CAL) and periodontal probing depth (PPD) were extracted and subjected to Random‐effects meta‐analysis. From 947 titles and abstracts screened, 11 articles were included for meta‐analysis. It was found that PI, GI, CAL and PPD were significantly higher in DM children than in non‐DM children according to the Standardized Mean different (SMD) and 95% confidence intervals (CI) (SMD 0.54, 95% CI 0.20–0.87, P = 0.002; SMD 0.63, 95% CI 0.39–0.87, P < 0.001; SMD 0.79, 95% CI 0.52–1.05, P < 0.001, SMD 0.67, 95% CI 0.23–1.11, P = 0.003, respectively). The meta‐analysis showed significant differences in PI, GI, PD and CAL between the two groups, favouring non‐DM children. Therefore, early detection of DM children with periodontal disease is crucial to prevent periodontal disease.
“Pivoting” by food industry firms to cope with COVID‐19 in developing regions: E‐commerce and “copivoting” delivery intermediaries
Authors: Reardon Thomas , Heiman Amir , Lu Liang , Nuthalapati Chandra S.R. , Vos Rob , Zilberman David
Published: April 2021

Coronavirus disease 2019 and related lockdown policies in 2020 shocked food industry firms’ supply chains in developing regions. Firms “pivoted” to e‐commerce to reach consumers and e‐procurement to reach processors and farmers. “Delivery intermediaries” copivoted with food firms to help them deliver and procure. This was crucial to the ability of the food firms to pivot. The pandemic was a “crucible” that induced this set of fast‐tracking innovations, accelerating the diffusion of e‐commerce and delivery intermediaries, and enabling food industry firms to redesign, at least temporarily, and perhaps for the long term, their supply chains to be more resilient, and to weather the pandemic, supply consumers, and contribute to food security. We present a theoretical model to explain these firm strategies, and then apply the framework to classify firms’ practical strategies. We focus on cases in Asia and Latin America. Enabling policy and infrastructural conditions allowed firms to pivot and copivot fluidly.
Diversity and complexity of mouse allergens in urine, house dust, and allergen extracts assessed with an immuno‐allergomic approach
Authors: Mindaye Samuel T. , Sun Carl , Esfahani Sayyed Amin Zarkesh , Matsui Elizabeth C. , Sheehan Michael J. , Rabin Ronald L. , Slater Jay E.
Published: April 2021

Background

Mouse allergy is an important cause of indoor asthma and allergic rhinoconjunctivitis. The major mouse allergen, Mus m 1, is a complex of homologous pheromone‐binding lipocalins called major urinary proteins (MUPs).

Methods

We analyzed the proteome of MUPs in mouse urine, commercial mouse epithelial extracts, and environmental samples using several approaches. These include as follows: two‐dimensional electrophoresis and immunoblotting; liquid chromatography‐high‐resolution mass spectrometry (LC/HRMS); multiple reaction monitoring (MRM) mass spectrometry; and LC/HRMS analysis of glycans at the N‐66 residue of MUP3.

Results

Albumin is predominant in the extracts, while MUPs are predominant in urine. LC/HRMS of 4 mouse allergen extracts revealed surprising heterogeneity. Of 22 known mouse MUPs, only 6 (MUP3, MUP4, MUP5, MUP13, MUP20, and MUP21) could be identified with MRM using unique peptides. Assessment of MUP content in urine, extracts, and dust samples showed good correlation between MRM and other methods working with different detection principles. All 6 identifiable MUPs were found in electrophoretically separated urine bands, but only MUP3 and MUP20 were above LOQ in unseparated mouse urine, and only MUP3, MUP4, and MUP20 were found in mouse epithelial extracts. Glycan heterogeneity was noted among 4 individual inbred mice: of 13 glycan structures detected, 8 were unique to one mouse, and only 2 glycan modifications were present in all 4 mice.

Conclusions

Using mass spectrometry and MRM, mouse allergen extracts and urine samples are shown to be complex and heterogeneous. The efficacy and safety of commercial mouse allergen extracts will be improved with better controls of allergen content.
Neonatal airway immune profiles and asthma and allergy endpoints in childhood
Authors: Chawes Bo L. , Wolsk Helene M. , Carlsson Christian J. , Rasmussen Morten A. , Følsgaard Nilofar , Stokholm Jakob , Bønnelykke Klaus , Brix Susanne , Schoos Ann‐Marie M. , Bisgaard Hans
Published: April 2021

Background

The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood.

Methods

We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one‐month‐old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition.

Results

A neonatal airway immune profile particularly characterized by enhanced IL‐1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune‐associated markers, including IL‐1β and CXCL8, showed trend of association with development of early asthma endpoints.

Conclusions

Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre‐ and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.
Two subsequent seminal productions: A good strategy to treat very severe oligoasthenoteratozoospermic infertile couples
Authors: Ciotti Patrizia Maria , Calza Nilla , Zuffa Silvia , Notarangelo Leonardo , Nardi Elena , Damiano Giuseppe , Cipriani Linda , Porcu Eleonora
Published: April 2021

Background

Sexual abstinence is considered one of the several factors that influence sperm quality. Recent studies show that a shortening of the abstinence period could be beneficial mostly in oligoasthenoteratozoospermic (OAT) patients.

Objective

Retrospective study to verify the efficacy of a second semen sample after a short abstinence to treat severe OAT infertile patients.

Materials and methods

127 couples treated between May 2014 and May 2018 were divided into two groups. Study Group 1 (75 cycles): severe OAT characteristics: count <0.2 × 106/mL no progressive motility; count ≥0.2 × 106/mL and no total or progressive motility; 0% normal morphology; a second semen sample was requested after abstinence of 2 h. Control Group 0 (52 cycles): normozoospermic or mild OAT; only one sample was requested. Intracytoplasmic sperm injection was utilized in all cases.

Results

All semen parameters were significantly different between Group 0 vs both samples of Group 1 (p < 0.001), excluding volume between Group 0 and 1st sample of Group 1 (p = 0.682). The comparison between 1st and 2nd samples from Group 1 showed significant differences in volume, total and progressive motility and morphology (p < 0.001, p < 0.001, p < 0.020) but not in total sperm count (p = 0.970). Fertilization, pregnancy rate/transfer, implantation and miscarriage rates were 85.9% and 61.1% (p < 0.001), 30.6% and 35.8% (p = 0.700), 17.5% and 24.0 (p = 0.292), 20.0% and 25.0% (p = 0.017) in Group 0 and Group 1 respectively.

Discussion and conclusion

The results show that a short abstinence in severe OAT patients allows us to obtain spermatozoa with better motility. The request for a second semen sample in couples with extreme semen parameters is a valid and simple strategy that helps to achieve the same probability of pregnancy compared to a Control Group. Furthermore, it allows us to utilize fresh spermatozoa avoiding the need to resort to cryopreserved reserves or testicular surgery.
“What did you do this weekend?” Relationships between weekend activities, recovery experiences, and changes in work‐related well‐being
Authors: Ginoux Clément , Isoard‐Gautheur Sandrine , Sarrazin Philippe
Published: April 2021

Recovery refers to the process of replenishing resources that occurs when employees distance themselves from their work, leading to improvements in work‐related well‐being indicators (WRWB), such as burnout and vigor. Research has shown that weekend activities are related to changes in WRWB and that recovery experiences could mediate these relationships. This study aimed to examine the indirect relationships of recovery activities on changes in burnout and vigor, through weekend recovery experiences. It extends past research by considering a greater number recovery activities and experiences and by controlling for job demands. Two hundred and forty‐nine employees from various occupations completed two online surveys before and after the weekend, assessing their WRWB, weekend recovery activities and experiences, and job demands. Structural equation modeling revealed that after controlling for job demands, changes in burnout and vigor were positively predicted by a latent variable—the weekend recovery experience—subjacent to perceptions of detachment, relaxation, mastery, control, and relatedness. In addition, four out of six weekend activities predicted negative (work‐related activities) or positive (social, physical, and creative activities) recovery experiences. Additional analyses showed that the recovery experience was a full mediator of the relationships between weekend activities and vigor change. These results confirm the importance of weekend activities and recovery experience for improving WRWB. They contribute to expanding current knowledge on recovery from work, highlighting the importance of considering creative activities and relatedness in future studies.
Semiparametric analysis of clustered interval‐censored survival data using soft Bayesian additive regression trees (SBART)
Authors: Basak Piyali , Linero Antonio , Sinha Debajyoti , Lipsitz Stuart
Published: April 2021

Popular parametric and semiparametric hazards regression models for clustered survival data are inappropriate and inadequate when the unknown effects of different covariates and clustering are complex. This calls for a flexible modeling framework to yield efficient survival prediction. Moreover, for some survival studies involving time to occurrence of some asymptomatic events, survival times are typically interval censored between consecutive clinical inspections. In this article, we propose a robust semiparametric model for clustered interval‐censored survival data under a paradigm of Bayesian ensemble learning, called soft Bayesian additive regression trees or SBART (Linero and Yang, 2018), which combines multiple sparse (soft) decision trees to attain excellent predictive accuracy. We develop a novel semiparametric hazards regression model by modeling the hazard function as a product of a parametric baseline hazard function and a nonparametric component that uses SBART to incorporate clustering, unknown functional forms of the main effects, and interaction effects of various covariates. In addition to being applicable for left‐censored, right‐censored, and interval‐censored survival data, our methodology is implemented using a data augmentation scheme which allows for existing Bayesian backfitting algorithms to be used. We illustrate the practical implementation and advantages of our method via simulation studies and an analysis of a prostate cancer surgery study where dependence on the experience and skill level of the physicians leads to clustering of survival times. We conclude by discussing our method's applicability in studies involving high‐dimensional data with complex underlying associations.
Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation
Authors: Zhu Xiaoyun , Ye Shengtao , Yu Dongke , Zhang Yanqiu , Li Jie , Zhang Meihui , Leng Yingrong , Yang Ting , Luo Jianguang , Chen Xinlin , Zhang Hao , Kong Lingyi
Published: April 2021

Background and Purpose

Liver fibrosis is one of the leading causes of morbidity and mortality worldwide but lacks any acceptable therapy. The transcription factor glioma‐associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti‐fibrotic activities and potential mechanisms of the phytochemical, physalin B.

Experimental Approach

Two mouse models (CCl4 challenge and bile duct ligation) were used to assess antifibrotic effects of physalin B in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX‐2 also served as in vitro liver fibrosis models. Liver fibrogenic genes, GLI1 and GLI1 downstream genes were examined using Western blot and quantitative real‐time PCR (qRT‐PCR). GLI1 acetylation and LAP2α–HDAC1 interaction were analysed by co‐immunoprecipitation.

Key Results

In vivo, physalin B administration attenuated hepatic histopathological injury and collagen accumulation and decreased expression of fibrogenic genes. Physalin B dose‐dependently suppressed fibrotic marker expression in LX‐2 cells and mouse pHSCs. Mechanistic studies showed that physalin B inhibited GLI activity by non‐canonical Hedgehog signalling. Physalin B blocked formation of lamina‐associated polypeptide 2α (LAP2α)/histone deacetylase 1 (HDAC1) complexes, thus inhibiting HDAC1‐mediated GLI1 deacetylation. Physalin B up‐regulated acetylation of GLI1, down‐regulated expression of GLI1 and subsequently inhibited HSC activation.

Conclusion and Implications

Physalin B exerted potent antifibrotic effects in vitro and in vivo by disrupting LAP2α/HDAC1 complexes, increasing GLI1 acetylation and inactivating GLI1. This indicates that the phytochemical physalin B may be a potential therapeutic candidate for the treatment of liver fibrosis.
Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso‐occlusion and nephropathy in mouse models of sickle cell disease
Authors: Tchernychev Boris , Li Huihui , Lee Sung‐Kyun , Gao Xin , Ramanarasimhaiah Raghunath , Liu Guang , Hall Katherine C. , Bernier Sylvie G. , Jones Juli E. , Feil Susanne , Feil Robert , Buys Emmanuel S. , Graul Regina M. , Frenette Paul S. , Masferrer Jaime L.
Published: April 2021

Background and Purpose

Reduced bioavailability of NO, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso‐occlusion and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyses synthesis of cGMP in response to NO. cGMP‐amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate TNFα‐induced inflammation in wild‐type C57BL/6 mice and in ‘humanised’ mouse models of SCD.

Experimental Approach

Effects of the sGC stimulator olinciguat on intravascular inflammation and renal injury were studied in acute (C57BL6 and Berkeley mice) and chronic (Townes mice) mouse models of TNFα‐induced and systemic inflammation associated with SCD.

Key Results

Acute treatment with olinciguat attenuated increases in plasma biomarkers of endothelial cell activation and leukocyte‐endothelial cell interactions in TNFα‐challenged mice. Co‐treatment with hydroxyurea, an FDA‐approved SCD therapeutic agent, further augmented the anti‐inflammatory effect of olinciguat. In the Berkeley mouse model of TNFα‐induced vaso‐occlusive crisis, a single dose of olinciguat attenuated leukocyte‐endothelial cell interactions, improved blood flow and prolonged survival time compared to vehicle‐treated mice. In Townes SCD mice, plasma biomarkers of inflammation and endothelial cell activation were lower in olinciguat‐ than in vehicle‐treated mice. In addition, kidney mass, water consumption, 24‐h urine excretion, plasma levels of cystatin C and urinary excretion of N‐acetyl‐β‐d‐glucosaminidase and neutrophil gelatinase‐associated lipocalin were lower in Townes mice treated with olinciguat than in vehicle‐treated mice.

Conclusion and Implications

Our results suggest that the sGC stimulator olinciguat attenuates inflammation, vaso‐occlusion and kidney injury in mouse models of SCD and systemic inflammation.
Design, synthesis and biological evaluation of N‐substituted indole‐thiazolidinedione analogues as potential pancreatic lipase inhibitors
Authors: George Ginson , Auti Prashant S. , Paul Atish T.
Published: April 2021

Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole‐TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole‐3‐carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50‐6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p < .05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20 ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole‐thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.
Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice
Authors: Nocturne Gaetane , Ly Bineta , Paoletti Audrey , Pascaud Juliette , Seror Raphaele , Nicco Carole , Mackay Fabienne , Vincent F B , Lazure Thierry , Ferlicot Sophie , Stimmer Lev , Pascal Quentin , Roulland Sandrine , Krzysiek Roman , Hacein-Bey Salima , Batteux Frederic , Mariette Xavier
Published: April 2021

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies.
The prognostic value of lymph node metastasis and the eighth edition of AJCC for patients with anaplastic thyroid cancer
Authors: Zhang Hanpu , Zhao Yan‐Ci , Wu Qi , Wang Lijun , Sun Shengrong
Published: April 2021

Objective

The eighth edition of the American Joint Committee on Cancer (AJCC‐v8) for anaplastic thyroid cancer (ATC) made a revision in staging for patients with lymph node metastasis (LNM) based on the seventh edition of AJCC (AJCC‐v7). Our study aimed to evaluate the predictive ability of AJCC‐v8 for survival in patients with ATC by exploring the association between lymph node stage and prognosis of ATC patients.

Methods

Retrospective study of ATC in Surveillance, Epidemiology and End Results (SEER) database. The association between LNM and survival of ATC was estimated by the Kaplan‐Meier method and Cox regression model. The predictive performances of the AJCC‐v8 and AJCC‐v7 were estimated through C‐index, Akaike information criterion (AIC) and Bayesian information criterion (BIC).

Results

A total of 313 patients with ATC were included in our analysis. Notably, LNM was identified as an independent risk factor for ATC mortality (adjusted HR, 1.47, 95% CI, 1.10–1.96; p = .009), while the risk of mortality in N1a group was comparable to that in N1b group according to univariate (HR, 1.30, 95% CI, 0.92–1.82; p = .133) and multivariate (adjusted HR 0.87, 95% CI, 0.60–1.27; p = .467) cox analyses. Applying the AJCC‐v8, the survival of migration population staged T1‐3aN1M0 was significantly worse than that of T1‐3aN0M0 patients (IVA stage), while was not different from that of T3b‐T4bN0/N1M0 patients (IVB stage). With a higher C‐index (0.60 vs. 0.59), lower AIC (2728 vs. 2732) and BIC (2732 vs. 2735), AJCC‐v8 was demonstrably a more favourable prediction model than AJCC‐v7.

Conclusions

This study demonstrated that LNM was independently associated with poor prognosis of ATC, and AJCC‐v8 with the modified staging of patients with LNM showed better survival predictive performance in ATC patients than AJCC‐v7.
Appropriating the Concept of the Right to the City: Politics, Politicians, and Collective Actors in Mexico City☆
Authors: Zamorano Claudia
Published: April 2021

This article takes into consideration the importance of the concept of right to the city in Mexico City politics and raises three main questions: How have center‐left governments adapted the concept according to their own interests, in a neoliberalizing context marked by mandatory repositioning of planning and capital? How has the right to the city been taken up and modified by diverse social organizations aimed at influencing the production of urban space? To what extent has the concept, despite manipulations and misunderstandings, proved to be politically useful in bridging differences between government agencies and social movements? I focus on the social life of the concept. I suggest that its widespread dissemination has not meant its trivialization. On the contrary, the concept has taken on greater sociological complexity. It was not turned into a fixed concept, rather it became both a field of contention and a tool enabling political encounters.
Corporate governance in the Middle East and North Africa: A systematic review of current trends and opportunities for future research
Authors: Farah Bassam , Elias Rida , Aguilera Ruth , Abi Saad Elie
Published: April 2021

Research Question/Issue

We systematically review the corporate governance (CG) literature on the Middle East and North Africa (MENA), organize it into six main themes and their subthemes, and propose several opportunities for future research.

Research Findings/Insights

We highlight CG's unique characteristics in the MENA region as well as differences and similarities across MENA countries. We shed light on how organizations are governed in this region especially that their ownership structures are centered on families and the state, and that Islam plays a major role in their governance. Our review establishes a solid foundation for future research directed at CG practices in the MENA region and encourages policymakers and practitioners to improve CG in the region.

Theoretical/Academic Implications

To the best of our knowledge, this is the first systematic literature review covering CG in the MENA region. In an effort to encourage the continuing evolution of this research stream and augment its contributions to the broader CG literature, we develop an extensive research agenda focusing on several key topics that deserve further attention such as ownership and countries' political regimes, family business and royal families, Sharia law, and executive compensation, among others.

Practitioner/Policy Implications

This review invites policymakers and investors to consider implementing better policies aimed at improving CG practices, specifically by fomenting transparency, developing financial markets, providing stronger protections for minority shareholders, and enhancing compliance with existing and new regulations.
Incidence, risk factors, treatment, and consequences of antibody‐mediated kidney transplant rejection: A systematic review
Authors: Hart Allyson , Singh Devender , Brown Sarah Jane , Wang Jeffrey H. , Kasiske Bertram L.
Published: April 2021

Background

Antibody‐mediated rejection (AMR) is a leading cause of kidney allograft failure, but its incidence, risk factors, and outcomes are not well understood.

Methods

We searched Ovid MEDLINE, Cochrane, EMBASE, and Scopus from January 2000 to January 2020 to identify published cohorts of ≥500 incident adult or 75 pediatric kidney transplant recipients followed for ≥1 year post‐transplant.

Results

At least two reviewers screened 5061 articles and abstracts; 28 met inclusion criteria. Incidence of acute AMR was 1.1%‐21.5%; most studies reported 3%‐12% incidence, usually within the first year post‐transplant. Few studies reported chronic AMR incidence, from 7.5%‐20.1% up to 10 years. Almost all patients with acute or chronic AMR received corticosteroids and intravenous immunoglobulin; most received plasmapheresis, and approximately half with rituximab. Most studies examining death‐censored graft failure identified AMR as an independent risk factor. Few reported refractory AMR rates or outcomes, and none examined costs. Most studies were single‐center and varied greatly in design.

Conclusions

Cohort studies of kidney transplant recipients demonstrate that AMR is common and associated with increased risk of death‐censored graft failure, but studies vary widely regarding populations, definitions, and reported incidence. Gaps remain in our understanding of refractory AMR, its costs, and resulting quality of life.
Peacebuilding conditionalities: An alternative to migration conditionalities for European Union development policy
Authors: Rodríguez Aurrecoechea Ángel
Published: April 2021

Motivation

The European Union (EU) has securitized its development policy with migration conditionalities, resulting in the subordination of development objectives to the externalization of migration control. This has called into question the legitimacy and effectiveness of EU development policy while failing to provide a solution that prevents future refugee crises. How can these trends be reversed?

Purpose

This article examines the feasibility and implications of peacebuilding conditionalities as an alternative to migration conditionalities with the aim of addressing the root causes of refugee crises, ensuring the effectiveness of EU development policy, and preserving its legitimacy.

Methods and approach

The article outlines a theoretical framework to categorize development policy conditionalities and better understand their strengths and weaknesses. This is followed by an analysis of the EU’s financial, legal, and electoral framework in order to evaluate peacebuilding conditionalities as an alternative policy option.

Findings

Peacebuilding conditionalities limit the ability of donor countries to influence migration behaviour while promoting capacity development by ensuring stability in migrants’ countries of origin. Replacing migration conditionalities with peacebuilding conditionalities is a feasible policy option in the current EU framework that can help prevent future refugee crises while encouraging synergy between Member States in development co‐operation—a promising policy area for European integration.

Policy implications

Peacebuilding conditionalities for development co‐operation would constitute a legitimate, effective, and integrating alternative to migration conditionalities at a time of crisis for the European project. With the prospect of a ceasefire in Libya, this would be especially suitable for a post‐conflict scenario.
Brain stimulation effects on serum BDNF, VEGF, and TNFα in treatment‐resistant psychiatric disorders
Authors: Valiuliene Giedre , Valiulis Vladas , Dapsys Kastytis , Vitkeviciene Aida , Gerulskis Giedrius , Navakauskiene Ruta , Germanavicius Arunas
Published: April 2021

Resistance to pharmacological treatment poses a notable challenge for psychiatry. Such cases are usually treated with brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Empirical evidence links treatment resistance to insufficient brain plasticity and chronic inflammation. Therefore, this study encompasses analysis of neurotrophic and inflammatory factors in psychiatric patients undergoing rTMS and ECT in order to refine the selection of patients and predict clinical outcomes. This study enrolled 25 drug‐resistant depressive patients undergoing rTMS and 31 drug‐resistant schizophrenia patients undergoing ECT. Clinical efficacy of brain stimulation therapies was gauged using MADRS and HAM‐D scales in the depression group and PANSS scale in the schizophrenia group. Blood‐derived BDNF, VEGF, and TNFα were analysed during the treatment course. For reference, 19 healthy control subjects were also enrolled. After statistical analysis, no significant differences were detected in BDNF, VEGF, and TNFα concentrations among healthy, depressive, and schizophrenic subject groups before the treatment. However, depressive patient treatment with rTMS has increased BDNF concentration, while schizophrenic patient treatment with ECT has lowered the concentration of TNFα. Our findings suggest that a lower initial TNFα concentration could be a marker for treatment success in depressed patients undergoing rTMS, whereas in schizophrenic patient group treated with ECT, a higher concentration of VEGF correlates to milder symptoms post‐treatment, especially in the negative scale.
Frontal circuit specialisations for decision making
Authors: Hunt Laurence T.
Published: April 2021

There is widespread consensus that distributed circuits across prefrontal and anterior cingulate cortex (PFC/ACC) are critical for reward‐based decision making. The circuit specialisations of these areas in primates were likely shaped by their foraging niche, in which decision making is typically sequential, attention‐guided and temporally extended. Here, I argue that in humans and other primates, PFC/ACC circuits are functionally specialised in two ways. First, microcircuits found across PFC/ACC are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. These properties provide the basis of a computational account of time‐varying neural activity within PFC/ACC as a decision is being made. Second, the macrocircuit connections (to other brain areas) differ between distinct PFC/ACC cytoarchitectonic subregions. This variation in macrocircuit connections explains why PFC/ACC subregions make unique contributions to reward‐based decision tasks and how these contributions are shaped by attention. They predict dissociable neural representations to emerge in orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex during sequential attention‐guided choice, as recently confirmed in neurophysiological recordings.
Cycling of reduced phosphorus compounds in soil and potential impacts of climate change
Authors: Kehler Anchen , Haygarth Philip , Tamburini Federica , Blackwell Martin
Published: April 2021

Soil phosphorus (P) remains an ever‐increasing topic of importance, notably for its key role as a nutrient for driving food production but with parallel concerns over damaging water quality, all against a backdrop of uncertainty of long‐term rock phosphate supplies. Soil is a key interface that holds P and regulates its onward flow to plants or leakage to waters. Often overlooked are a ubiquitous group of P compounds that exist in alternative oxidation states to that of phosphate (+5). Redox cycling, and the behaviour that chemically reduced P compounds exhibit in soils, introduces alternative routes of cycling P that may become more important as the soil system itself alters, especially due to the external pressures of climate change, bringing about critical dynamics in rainfall and runoff and also wetting and drying. All of these factors are known to affect soil redox potential and consequently the oxidation state of soil P. This review considers the chemically reduced species in the P cycle, exploring their sources and sinks, while considering their importance within the primary global biogeochemical cycling of P and how this may be impacted by climate change in the temperate climate of the northern hemisphere.

Highlights

This paper addresses how climate change will affect soil phosphorus cycling.

This review is novel as it considers the reduced phosphorus forms when discussing P transfer in soils.

Climate change is likely to increase prevalence of reduced P and free phosphate in northern hemisphere temperate soils.

Phosphorus cycling relies partly on redox P processes. Their importance will increase as climate alters soils.