bluuebunny/crossref_metadata_2025 huggingface dataset:
A cross‐sectional study of vitreous and serum high mobility group box‐1 levels in proliferative diabetic retinopathy
Authors: Shen Yinchen , Cao Hui , Chen Feng'e , Suo Yan , Wang Ning , Xu Xun
Published: August 2019

Purpose

We determined vitreous and serum levels of high mobility group box‐1 (HMGB‐1) in patients with proliferative diabetic retinopathy (PDR) and elucidate their relationship with receptor for advanced glycation end products (RAGE), vascular endothelial growth factor (VEGF) and interleukin‐1β (IL‐1β).

Methods

In this cross‐sectional study, patients with PDR who underwent vitrectomy were enrolled, and the control group included non‐diabetic eyes. Vitreous and serum samples were analysed for HMGB‐1, RAGE, VEGF and IL‐1β by ELISA. We investigated the correlation between serum and vitreous levels of each cytokine, and we analysed the influence of intravitreal anti‐VEGF treatment prior to vitrectomy on the cytokine levels in PDR.

Results

Of 78 eyes of 78 patients enrolled consecutively, there were 32 PDR eyes and 46 control eyes. The serum levels were higher in diabetic than in non‐diabetic subjects for HMGB‐1, RAGE, VEGF and IL‐1β (all p < 0.001), respectively. Similarly, the vitreous levels were higher in diabetic than in non‐diabetic subjects for HMGB‐1 (p < 0.001), RAGE (p = 0.001), VEGF (p < 0.001) and IL‐1β (p < 0.001), respectively. We found a positive correlation between serum and vitreous levels of HMGB‐1 in patient with PDR (p = 0.047, R = 0.353). There was a negative correlation between serum and vitreous levels of VEGF in patient with PDR (p = 0.001, R = −0.546). For the subgroup analysis, we detected that the vitreous levels of RAGE were significantly lower in patients who underwent anti‐VEGF injection prior to vitrectomy than those who did not (p < 0.001).

Conclusions

Our findings suggest that HMGB‐1 is involved in PDR disorders, and it may be a novel therapeutic target to inhibit progression of PDR.
Analysis and management of intraoperative and early postoperative complications of bag‐in‐the‐lens intraocular lens implantation in different age groups of paediatric cataract patients: report of the Giessen Paediatric Cataract Study Group
Authors: Lytvynchuk Lyubomyr M. , Thiele Maximilian V. , Lorenz Birgit
Published: August 2019

Purpose

To report the rate and management of intra‐ and early postoperative complications of bag‐in‐the‐lens intraocular lens (IOL) implantation technique for cataract treatment in paediatric patients of different age groups.

Settings

Department of Ophthalmology, Justus‐Liebig‐University Giessen, University Hospital Giessen and Marburg GmbH, Campus Giessen, Giessen, Germany.

Design

Retrospective non‐randomized consecutive case series.

Methods

Ninety eyes of 60 paediatric cataract patients were enrolled to this retrospective non‐randomized observational consecutive case series single‐centre study. All patients underwent cataract surgery with bag‐in‐the‐lens IOL implantation between January 2008 and December 2018, performed by two experienced surgeons. The entire cohort was divided into four age groups: first – 0–<3 months, second – 3–<12 months, third – 12–<36 and fourth – >36 months–17 years of age. The intra‐ and postoperative complications were based on the clinical records. The description of management of complications related specifically to bag‐in‐the‐lens IOL technique was based on the 39 consecutive cases operated since 1 Jan 2016 by one single surgeon that were all video documented. The early postoperative period was defined as 12 months after surgery.

Results

Overall, there were 27 unilateral and 33 bilateral surgical cases of 24 female and 36 male children. The mean age at surgery was 45.25 months (range 1–200 months). The most common intraoperative events were vitreous prolapse and anterior capsule rupture with 28.9% and 13.3%, respectively. Within 12 months of follow‐up, five eyes (5.6%) were re‐operated because of visual axis reo‐pacification (VAR). Intraocular hypertension was diagnosed in seven eyes (7.8%), including two cases that required surgical treatment. In all cases with intra‐ and early postoperative complications related specifically to bag‐in‐the‐lens technique, it was possible to manage them and successfully implant bag‐in‐the‐lens IOL.

Conclusions

Implementation of bag‐in‐the‐lens technique in the treatment of paediatric cataract was associated with a relatively low rate of intra‐ and postoperative complications, including rare cases of VAR. The correct management of complications related specifically to bag‐in‐the‐lens IOL implantation technique shall to be considered during the learning curve.
Disorganization of retinal inner layers as a biomarker in patients with diabetic macular oedema treated with dexamethasone implant
Authors: Zur Dinah , Iglicki Matias , Sala‐Puigdollers Anna , Chhablani Jay , Lupidi Marco , Fraser‐Bell Samantha , Mendes Thais Sousa , Chaikitmongkol Voraporn , Cebeci Zafer , Dollberg Dolev , Busch Catharina , Invernizzi Alessandro , Habot‐Wilner Zohar , Loewenstein Anat ,   the International Retina Group (IRG)
Published: August 2019

Purpose

To investigate disorganization of retinal inner layers (DRIL) as a biomarker in eyes with diabetic macular oedema (DME) treated by intravitreal dexamethasone (DEX) implant.

Methods

Multicentre, retrospective study including eyes with DME treated with DEX implant and follow‐up of 12 months after the first injection. OCT scans were evaluated for the presence of DRIL and other structural features. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline and at 2, 4, 6 and 12 months after treatment. Correlation between DRIL at baseline and outcomes after DEX treatment and the change in DRIL were analysed.

Results

A total of 177 eyes (177 patients; naïve, n = 131; refractory, n = 46) were included. Patients without DRIL at baseline gained significantly more vision and enjoyed greater reduction in CST over 12 months (both p = 0.03). DRIL at the boundary between the ganglion cell‐inner plexiform complex and inner nuclear layer improved in 48/64 eyes (75%, p < 0.001), while DRIL between the inner nuclear layer and outer plexiform layer improved in 27/77 eyes (35%, p = 0.004).

Conclusions

This is the first study to show that DEX implant has the potential to ameliorate DRIL. Patients without DRIL at baseline have a favourable outcome. DRIL may serve a robust biomarker in DME treated by DEX implant.
Non‐evidence‐based beliefs increase inequalities in the provision of infant‐ and family‐centred neonatal care
Authors: Mendizabal‐Espinosa Rosa Maria , Warren Inga
Published: August 2019

Aim

To identify barriers that might explain why healthcare staff struggle to implement infant‐ and family‐centred developmental care programmes in two neonatal intensive care units in Mexico.

Methods

Ethnographic fieldwork over the course of 10 months examined interactions among healthcare professionals, parents and babies in two Mexican publicly funded hospitals. Data are drawn from interviews with 29 parents and 34 healthcare professionals and participant observations in the hospitals’ neonatal units.

Results

Healthcare professionals believed they acted in babies’ best interests by excluding parents from the neonatal unit. Professional frustration with working conditions seemed to be increased by the belief that parents were ignorant and unhygienic. Parents were perceived as a source of infection; in contrast, healthcare professionals failed to see themselves as a possible source of cross‐contamination.

Conclusions

Beliefs and biases increase health inequalities when evidenced‐based measures to prevent cross‐infection and potentially life‐saving programmes, such as kangaroo mother care and breastfeeding, are not implemented. It is imperative to develop context‐appropriate education and practice guidelines to implement basic programmes.
Bladder/bowel dysfunction at school age is seen in children with high‐grade vesicoureteral reflux and lower urinary tract dysfunction in infancy
Authors: Sjöström Sofia , Ekdahl Helena , Abrahamsson Kate , Sillén Ulla
Published: August 2019

Aim

In approximately one third of cases, congenital high‐grade vesicoureteral reflux (VUR) diagnosed during infancy is seen together with lower urinary tract dysfunction (LUTD), characterised by a high‐capacity bladder and incomplete emptying. In an earlier study, 20 of these infants were treated with clean intermittent catheterisation during a 3‐year period and with surgical treatment of the VUR before catheterisation was ended. In the present study, bladder function was evaluated in these children at school age.

Methods

Bladder function was evaluated in the 20 children at a mean age of 7.3 years using a validated voiding‐bowel questionnaire with scores (cut‐off score 7) and a urine flow/residual study.

Results

Four children (20%) had a normal voiding function at follow‐up, whereas 11 (55%) had a clear bladder/bowel dysfunction (scores 7‐19) and five (25%) had a mild dysfunction (score 6). Ten (63%) of the children with any dysfunction were recognised as dysfunctional voiding. Recurrent febrile urinary tract infections were correlated with the scores of faecal questions (P = .041), but for total scores P = .058.

Conclusion

The follow‐up of bladder function in children at 7.3 years, diagnosed with high‐grade VUR and LUTD in infancy, revealed bladder/bowel dysfunction of varying severity in the majority of cases.
Endogenous testosterone determines metformin action on prolactin levels in hyperprolactinaemic men: A pilot study
Authors: Krysiak Robert , Szkróbka Witold , Okopień Bogusław
Published: August 2019

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case‐control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55‐3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone‐binding globulin adrenocorticotropic hormone, insulin‐like growth factor‐1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment‐induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.
Aspirin for the prevention and treatment of pre‐eclampsia: A matter of COX‐1 and/or COX‐2 inhibition?
Authors: Mirabito Colafella Katrina M. , Neuman Rugina I. , Visser Willy , Danser A. H. Jan , Versmissen Jorie
Published: August 2019

Since the 1970s, we have known that aspirin can reduce the risk of pre‐eclampsia. However, the underlying mechanisms explaining this risk reduction are poorly understood. Both cyclooxygenase (COX)‐1‐ and COX‐2‐dependent effects might be involved. As a consequence of this knowledge hiatus, the optimal dose and timing of initiation of aspirin therapy are not clear. Here, we review how (COX‐1 versus COX‐2 inhibition) and when (prevention versus treatment) aspirin therapy may interfere with the mechanisms implicated in the pathogenesis of pre‐eclampsia. The available evidence suggests that both COX‐1‐ and COX‐2‐dependent effects play important roles in the early stage of aberrant placental development and in the next phase leading to the clinical syndrome of pre‐eclampsia. Collectively, these data suggest that high‐dose (dual COX inhibition) aspirin may be superior to standard low‐dose (selective COX‐1 inhibition) aspirin for the prevention and also treatment of pre‐eclampsia. Therefore, we conclude that more functional and biochemical tests are needed to unravel the contribution of prostanoids in the mechanisms implicated in the pathogenesis of pre‐eclampsia and the potential of dual COX and/or selective COX‐2 inhibition for the prevention and treatment of pre‐eclampsia. This information is vital if we are to deduce the suitability, optimal timing and dose of aspirin and/or a specific COX‐2 inhibitor (most likely using modified forms that do not cross the placenta) that can then be tested in a randomized, controlled trial instead of the current practice of empirical dosing regimens.
“Oh! Teleworking!” Regimes of engagement and the lived experience of female Spanish teleworkers
Authors: Gálvez Ana , Tirado Francisco , Alcaraz Jose M.
Published: August 2019

This research explores female teleworkers' domestic and work experiences in their day‐to‐day lives. We draw on focus groups and interviews carried out in Spain and use thepragmatic regimes of engagementframework developed by Luc Boltanski and Laurent Thévenot to analyse them. Their model further develops contributions from post‐humanist discourse (specially from G. Deleuze, F. Guattari and A. Badiou) and from the so‐called “empirical ethics”. This allows us to explore important issues about the temporal‐spatial and material worlds that shape the daily lives of these women, their perceived agential capacities, and their moral and ethical considerations regarding telework. Our paper contributes to the existing critically oriented (qualitative, interpretative) body of work that examines teleworkers’ lived experience by providing and illustrating important clues for examining ethical issues on work–life balance and gender roles.
Guideline of guidelines: testosterone therapy for testosterone deficiency
Authors: Salter Carolyn A. , Mulhall John P.
Published: August 2019

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations.

All the organisations were in general agreement concerning the following key points:

Only men meeting the criteria for testosterone deficiency (TD) should be treated.

Consider screening asymptomatic men with certain conditions that increase the risk of TD.

Exogenous TTh causes impairment of spermatogenesis.

There is no evidence that TTh causes prostate cancer.

Men on TTh require careful laboratory monitoring.
Scalp‐to‐cortex distance of left primary motor cortex and its computational head model: Implications for personalized neuromodulation
Authors: Lu Hanna , Lam Linda C. W. , Ning Yuping
Published: August 2019

Background

Non‐invasive brain stimulation (NIBS) is increasingly used as a probe of function and therapeutics in experimental neuroscience and neurorehabilitation. Scalp‐to‐cortex distance (SCD), as a key parameter, has been shown to potentially impact on the electric field. This study aimed to examine the region‐specific SCD and its relationship with cognitive function in the context of age‐related brain atrophy.

Methods

We analyzed the SCD and cortical thickness (CT) of left primary motor cortex (M1) in 164 cognitively normal (CN) adults and 43 dementia patients drawn from the Open Access Series of Imaging Studies (OASIS). The degree of brain atrophy was measured by the volume of ventricular system. Computational head model was developed to simulate the impact of SCD on the electric field.

Results

Increased SCD of left M1 was only found in dementia patients (P < .001). When considering CT, the ratio of SCD to CT (F = 27.41, P < .001) showed better differential value than SCD. The SCD of left M1 was associated with worse global cognition (r = −.207, P = .011) and enlarged third ventricle (r = .241, P < .001). The electric field was consequently reduced with the increased SCD across cognitively normal elderly and dementia groups.

Conclusions

Scalable distance measures, including SCD and CT, are markedly correlated with reduced electric field in dementia patients. The findings suggest that it is important to be aware of region‐specific distance measures when conducting NIBS‐based rehabilitation in individuals with brain atrophy.
Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records
Authors: Lentine Krista L. , Koraishy Farrukh M. , Sarabu Nagaraju , Naik Abhijit S. , Lam Ngan N. , Garg Amit X. , Axelrod David , Zhang Zidong , Hess Gregory P. , Kasiske Bertram L. , Segev Dorry L. , Henderson Macey L. , Massie Allan B. , Holscher Courtenay M. , Schnitzler Mark A.
Published: August 2019

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007‐2016) to examine associations (adjusted hazard ratio, LCLaHRUCL) of post‐donation fills of antidiabetic medications (ADM, insulin or non‐insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.364.596.27). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9‐year incidence, 6.87% vs 1.85%, aHR, 3.555.007.04). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1‐year post‐donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.031.482.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.
Odds of Acute Kidney Injury in Patients Receiving Dipeptidyl Peptidase 4 Inhibitors: A National Cohort Study Within the Department of Veterans Affairs
Authors: Sutton S. Scott , Magagnoli Joseph , Cummings Tammy H. , Hardin James W.
Published: August 2019

Preclinical and clinical data of dipeptidyl peptidase 4 (DPP‐4) inhibitors have demonstrated discordant data regarding acute kidney injury (AKI). Therefore, we aimed to evaluate the association between DPP‐4 use and AKI. This cohort study utilized data from the Department of Veterans Affairs evaluating patients diagnosed with type 2 (T2) diabetes with a DPP‐4 inhibitor and compared with nondiabetic and diabetic patients. The primary end point is the development of AKI, and statistical analyses were performed to examine the association. DPP‐4 use is associated with a lower odds of AKI compared with diabetics (adjusted odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.32–0.48) and nondiabetics (OR = 0.64; 95% CI = 0.52–0.79). DPP‐4 use in patients with T2 diabetes mellitus is associated with lower odds of AKI within 120 days compared with nondiabetic and diabetic controls when adjusting for study covariates.
Prevalence of dentofacial injuries among combat sports practitioners: A systematic review and meta‐analysis
Authors: Polmann Helena , Melo Gilberto , Conti Réus Jéssica , Domingos Fabio Luiz , de Souza Beatriz Dulcineia Mendes , Padilha Ana Clara , Duque Thais Mageste , Porporatti André Luís , Flores‐Mir Carlos , De Luca Canto Graziela
Published: August 2019

Background/Aim

Combat sports might result in injuries to the face and teeth. However, it is unclear how often they occur and which sports presents the highest rates. The aim of this study was to investigate the prevalence of dentofacial injuries in combat sports participants.

Material and Methods

A systematic review was performed. Six main electronic databases and three grey literature databases were searched. Studies were blindly selected by two reviewers based on pre‐defined eligibility criteria. Studies that evaluated the prevalence of dentofacial injuries (teeth, alveolar bone, jaw, lips, and/or cheekbones) among combat sports participants were considered eligible. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. The softwarerstatisticsversion was used to perform all meta‐analyses. Cumulative evidence of the included articles was evaluated using GRADE criteria (Grading of Recommendations Assessment, Development and Evaluation).

Results

From 1104 articles found on all databases, 27 were finally included. Eighteen studies were judged at low, seven at moderate, and two at high risk of bias. The following sports were investigated: boxing, capoeira, fencing, jiu‐jitsu, judo, karate, kendo, kickboxing, kung fu, muay thai, sumo, taekwondo, wrestling, and wushu. Results from the meta‐analysis suggested a dental pooled prevalence of 25.2% (12.3%‐40.8%,i2 = 100%) and dentofacial pooled prevalence of 30.3 (18.1%‐44.1%,i2 = 100%). Considering the sports' categories individually, jiu‐jitsu had the highest pooled prevalence of dentofacial injuries (52.9% [37.9%‐67.8%,i2 = 92%]), while judo was the sport with the lowest pooled prevalence (25.0% [7.6%‐48.2%,i2 = 98%]). Among Panamerican sports, boxing had the highest prevalence of dental injuries (73.7% [58.7%‐86.3%,i2 = 0%]). For dentofacial injuries, the GRADE criteria were considered low.

Conclusions

Overall pooled prevalence of dentofacial injuries in combat sports was approximately 30%. Raising awareness regarding the frequency of these injuries might encourage the use of protective devices and reduce complications related to these incidents.
Neurobiology of resilience in depression: immune and vascular insights from human and animal studies
Authors: Dudek Katarzyna A. , Dion‐Albert Laurence , Kaufmann Fernanda Neutzling , Tuck Ellen , Lebel Manon , Menard Caroline
Published: August 2019

Major depressive disorder (MDD) is a chronic and recurrent psychiatric condition characterized by depressed mood, social isolation and anhedonia. It will affect 20% of individuals with considerable economic impacts. Unfortunately, 30–50% of depressed individuals are resistant to current antidepressant treatments. MDD is twice as prevalent in women and associated symptoms are different. Depression's main environmental risk factor is chronic stress, and women report higher levels of stress in daily life. However, not every stressed individual becomes depressed, highlighting the need to identify biological determinants of stress vulnerability but also resilience. Based on a reverse translational approach, rodent models of depression were developed to study the mechanisms underlying susceptibility vs resilience. Indeed, a subpopulation of animals can display coping mechanisms and a set of biological alterations leading to stress resilience. The aetiology of MDD is multifactorial and involves several physiological systems. Exacerbation of endocrine and immune responses from both innate and adaptive systems are observed in depressed individuals and mice exhibiting depression‐like behaviours. Increasing attention has been given to neurovascular health since higher prevalence of cardiovascular diseases is found in MDD patients and inflammatory conditions are associated with depression, treatment resistance and relapse. Here, we provide an overview of endocrine, immune and vascular changes associated with stress vulnerability vs. resilience in rodents and when available, in humans. Lack of treatment efficacy suggests that neuron‐centric treatments do not address important causal biological factors and better understanding of stress‐induced adaptations, including sex differences, could contribute to develop novel therapeutic strategies including personalized medicine approaches.
Voluntary tic suppression and the normalization of motor cortical beta power in Gilles de la Tourette syndrome: an EEG study
Authors: Zapparoli Laura , Macerollo Antonella , Joyce Eileen M. , Martino Davide , Kilner James M.
Published: August 2019

Gilles de la Tourette syndrome (GTS) is a neurological condition characterized by motor and vocal tics. Previous studies suggested that this syndrome is associated with abnormal sensorimotor cortex activity at rest, as well as during the execution of voluntary movements. It has been hypothesized that this abnormality might be interpreted as a form of increased tonic inhibition, probably to suppress tics; however, this hypothesis has not been tested so far. The present study was designed to formally test how voluntary tic suppression in GTS influences the activity of the sensorimotor cortex during the execution of a motor task. We used EEG to record neural activity over the contralateral sensorimotor cortex during a finger movement task in adult GTS patients, in both free ticcing and tic suppression conditions; these data were then compared with those collected during the same task in age‐matched healthy subjects. We focused on the levels of activity in the beta frequency band, which is typically associated with the activation of the motor system, during three different phases: a pre‐movement, a movement, and a post‐movement phase. GTS patients showed decreased levels of beta modulation with respect to the healthy controls, during the execution of the task; however, this abnormal pattern returned to be normal when they were explicitly asked to suppress their tics while moving. This is the first demonstration that voluntary tic suppression in GTS operates through the normalization of the EEG rhythm in the beta frequency range during the execution of a voluntary finger movement.
First record of the Japanese grape leafhopper Arboridia kakogawana (Matsumura, 1932) (Hemiptera: Cicadellidae) from Romania
Authors: Chireceanu C. , Nedelcea D. , Seljak G.
Published: August 2019

A new invasive species, the Japanese grape leafhopper, Arboridia kakogawana (Matsumura). is reported for the first time in Romania. Arboridia kakogawana is a serious pest of grapevine (Vitis vinifera L.) in East Asia (South Korea and China) and in Southern Russia (Krasnodar and Rostov regions) and Ukraine. In 2018, very high numbers of A. kakogawana were caught on yellow sticky traps in a vine plot in Romania in Northern Bucharest. Adults were trapped from early June to the middle of November. The dynamics of the adult population were measured using yellow sticky traps, and in 2018 four peaks were observed in the middle of July, in the first 10 days of August, at the beginning of September and in the first 10 days of October. The first overwintering adults appeared from the beginning of June. Foliar symptoms associated with the trophic activity of the leafhopper were observed on grapevine and Virginia creeper (Parthenocissus quinquefolia (L.)). Yellow sticky traps used in prior studies in the Bucharest area were re‐examined and the Japanese leafhopper was discovered on these, which leads to the conclusion that the species has been present at least since 2016 in this area. This is the first report of A. kakogawana in Romania and in the European Union.
NRF2/ABCB1‐mediated efflux and PARP1‐mediated dampening of DNA damage contribute to doxorubicin resistance in chronic hypoxic HepG2 cells
Authors: Xia Xiangwen , Wang Qi , Ye Tianhe , Liu Yiming , Liu Dehan , Song Songlin , Zheng Chuansheng
Published: August 2019

Transarterial chemoembolization (TACE)‐induced hypoxia can trigger residual liver cancer cells to present a more aggressive phenotype associated with chemoresistance, but the underlying mechanisms are still unknown. In this study, the human liver cancer cell line HepG2 was pre‐cultured in different oxygen environments to examine the possible mechanisms of hypoxia‐induced doxorubicin resistance. Our study showed that HepG2 cells pre‐cultured in a chronic intermittent hypoxic environment exhibited significant resistance to doxorubicin, evidenced by increased intracellular doxorubicin efflux, relatively higher cell proliferation, lower apoptosis, and decreased DNA damage. These changes were accompanied by high levels of NRF2 and ABCB1 under conditions of both chronic and acute hypoxia and PARP1 gene expression only under conditions of chronic hypoxia. SiRNA‐mediated silencing of NRF2 gene expression downregulated the expression of ABCB1 and increased the intracellular doxorubicin accumulation and cell apoptosis both in acute and chronic hypoxic HepG2 cells. Moreover, silencing of PARP1 gene expression increased the doxorubicin‐induced DNA damage and cell apoptosis in chronic hypoxic cells. On the basis of these findings, we concluded that NRF2/ABCB1‐mediated efflux and PARP1‐mediated DNA repair contribute to doxorubicin resistance in chronic hypoxic HepG2 cells.
The N‐terminal peptide of the transglutaminase‐activating metalloprotease inhibitor from Streptomyces mobaraensis accommodates both inhibition and glutamine cross‐linking sites
Authors: Juettner Norbert E. , Schmelz Stefan , Anderl Anita , Colin Felix , Classen Moritz , Pfeifer Felicitas , Scrima Andrea , Fuchsbauer Hans‐Lothar
Published: August 2019

Streptomyces mobaraensis is a key player for the industrial production of the protein cross‐linking enzyme microbial transglutaminase (MTG). Extra‐cellular activation of MTG by the transglutaminase‐activating metalloprotease (TAMP) is regulated by the TAMP inhibitory protein SSTI that belongs to the large Streptomyces subtilisin inhibitor (SSI) family. Despite decades of SSI research, the binding site for metalloproteases such as TAMP remained elusive in most of the SSI proteins. Moreover, SSTI is a MTG substrate, and the preferred glutamine residues for SSTI cross‐linking are not determined. To address both issues, that is, determination of the TAMP and the MTG glutamine binding sites, SSTI was modified by distinct point mutations as well as elongation or truncation of the N‐terminal peptide by six and three residues respectively. Structural integrity of the mutants was verified by the determination of protein melting points and supported by unimpaired subtilisin inhibitory activity. While exchange of single amino acids could not disrupt decisively the SSTI TAMP interaction, the N‐terminally shortened variants clearly indicated the highly conserved Leu40‐Tyr41 as binding motif for TAMP. Moreover, enzymatic biotinylation revealed that an adjacent glutamine pair, upstream from Leu40‐Tyr41 in the SSTI precursor protein, is the preferred binding site of MTG. This extension peptide disturbs the interaction with TAMP. The structure of SSTI was furthermore determined by X‐ray crystallography. While no structural data could be obtained for the N‐terminal peptide due to flexibility, the core structure starting from Tyr41 could be determined and analysed, which superposes well with SSI‐family proteins.

Enzymes

Chymotrypsin, EC3.4.21.1; griselysin (SGMPII, SgmA), EC3.4.24.27; snapalysin (ScNP), EC3.4.24.77; streptogrisin‐A (SGPA), EC3.4.21.80; streptogrisin‐B (SGPB), EC3.4.21.81; subtilisin BPN’, EC3.4.21.62; transglutaminase, EC2.3.2.13; transglutaminase‐activating metalloprotease (TAMP), EC3.4.‐.‐; tri‐/tetrapeptidyl aminopeptidase, EC3.4.11.‐; trypsin, EC3.4.21.4.

Databases

The atomic coordinates and structure factors (PDB 6I0I) have been deposited in the Protein Data Bank (http://www.rcsb.org).
Is social licence “going rogue”?
Authors: Mather Charles , Fanning Lucia
Published: August 2019

In this commentary we trace an important change in the use of social licence for resource‐intensive development projects. Social licence is shifting from an approach used by companies to improve relations with affected communities to a concept now used by environmental justice groups, non‐governmental organisations and local communities to contest unpopular resource‐intensive development projects. The term “going rogue” is a productive metaphor to explore this important change in the role of social licence. We focus on the different logics behind how social licence is being used by progressive groups to protest resource‐intensive development, weak state policies and broader economic processes. We end by exploring what the shifting terrain for social licence means for the politics of resource extraction.
Molar volume of SiOH estimated from swelling strains
Authors: Fett Theo , Schell Karl G. , Wiederhorn Sheldon M.
Published: August 2019

As water diffuses into silica glass, it reacts with the silica network to generate hydroxyl groups that cause a volume swelling of the glass. We discuss this effect quantitatively for cases in which hydroxyl groups were produced either by gamma‐irradiation of hydrogen‐saturated silica glass or by high‐temperature diffusion of water into silica glass. From volume swelling measurements, the partial molar volume of hydroxyl groups for both treatments is determined to be 7.5 cm3/mol. Since two moles of SiOH are generated for each mole of water reacting with the glass, the reaction volume, , is 15.0 cm3/mol.
Iron polyphosphate glasses for waste immobilization
Authors: Brow Richard K. , Kim Cheol W. , Reis Signo T.
Published: August 2019

Iron polyphosphate glasses resist attack by water, can dissolve large concentrations of species that are otherwise insoluble in borosilicate glass melts, and can be processed at relatively low temperatures (1000‐1200°C), and so are viable hosts for vitrifying hazardous and radioactive wastes. The properties of iron polyphosphate glasses depend on the distributions of phosphate anions and the nature of the bonds between those anions and various metal polyhedra, and quantitative information can be obtained about those structures using a variety of spectroscopic, diffraction, and chromatographic techniques. This structural information helps explain compositional trends in properties, including dissolution rates, electrical conductivity, thermal properties and crystallization tendency. Studies of waste forms made with low activity and high level wastes are reviewed and related back to an understanding of the structures and properties of simpler iron polyphosphate glasses.
A cost‐effective approach to factor assay calibration using a truncated live calibration curve
Authors: Guy Susan , Sermon‐Cadd Anne M. , Shepherd Fiona M. , Kitchen Steve , Bowyer Annette E.
Published: August 2019

Introduction

The measurements of clotting factor activities are usually performed using a one‐stage clotting assay (OSA) or chromogenic substrate assay (CSA). Advances in automated coagulation analysers have led to the utilization of stored calibration curves. There are sometimes substantial intervals between test calibration and analysis of samples. Variability in results can be influenced by calibrant and methodology. Several guidelines recommend calibration and patient samples be performed together in parallel; this incurs costs, but reliance on a stored calibration curve may lead to inaccuracy of results over time.

Methods

We evaluated inclusion of a live truncated (3 point) calibration curve using calibrator plasma alongside test samples and compared results calculated against the stored calibration curves and live truncated calibration to assess the impact on precision and accuracy. The feasibility of this was tested on two hospital sites in the UK; OSA and CSA were performed on Sysmex CS5100 using Actin FS, SynthASil, Innovin, Biophen chromogenic VIII and Rossix chromogenic IX.

Results

Results of two batches of IQC were compared for FII, FV, FVII, FX, FIX:C, FXI, FXII and OSA FVIII (FVIII:C1) and CSA FVIII:C (FVIII:CR) and FXI:C. By utilizing a live truncated calibration, precision improved with the most striking examples: FXII %CV 23.1% to 3.1% (site A) FXI 7.3% to 2.4% (site B). The improvement in other clotting factors was more modest.

Conclusion

To the best of our knowledge, this is the first study that demonstrates that the use of a live truncated calibration curve will improve precision and accuracy.
Differential interferon‐gamma production potential among naïve CD4+ T cells exists prior to antigen encounter
Authors: Sood Aditi , Lebel Marie‐Ève , Fournier Marilaine , Rogers Dakota , Mandl Judith N , Melichar Heather J
Published: August 2019

Individual CD4+ T cells can become one of a number of helper (Th) lineages with distinct effector functions. However, whether biases in Th potential exist prior to antigen encounter is unknown. Studies have identified cell‐intrinsic functional heterogeneity among naïve T cells that can be parsed based on the strength of T‐cell receptor (TCR) interactions with self‐peptide. Here, using CD5 levels as a surrogate for the strength of these basal TCR signals, we sought to identify pre‐existing effector biases in the CD4+ T‐cell lineage. We show that ex vivo‐activated CD5lo CD4+ T cells produce greater amounts of the Th1 cytokine interferon‐gamma (IFNγ) than their CD5hi counterparts. In addition, a greater percentage of CD5lo effector CD4+ T cells produce IFNγ in both polyclonal and monoclonal CD4+ T‐cell populations after antigen challenge in vivo. These results suggest that differential IFNγ production potential exists among CD4+ T cells prior to activation and independent of TCR affinity for foreign antigen.
Gd2Zr3(MoO4)9 microwave dielectric ceramics with trigonal structure for LTCC application
Authors: Yang Hongcheng , Zhang Shuren , Yang Hongyu , Yuan Ying , Li Enzhu
Published: August 2019

Gd2Zr3(MoO4)9 is a double trigonal molybdate crystallized in the space group . The optimal microwave dielectric properties were achieved via solid‐state reaction at 725°C for Gd2Zr3(MoO4)9 ceramics: εr = 11.17, Q × f = 57 460 GHz, τf = −31.91 ppm/°C. The three‐dimensional framework type structure is formed by mixed MoO4 tetrahedron and ZrO6/GdO9 polyhedron. The analysis based on complex chemical bond theory shows that the Mo–O bonds account for majority contribution to controlling microwave dielectric properties. The MoO4 tetrahedron and ZrO6 octahedron stabilize the crystal structure by strong binding ability. As it was shown by Raman spectroscopy, the Raman‐active vibrations primarily originate from MoO4 tetrahedron, similarly to molybdate analogies.
Synthesis of high‐purity high‐entropy metal diboride powders by boro/carbothermal reduction
Authors: Liu Da , Liu Honghua , Ning Shanshan , Ye Beilin , Chu Yanhui
Published: August 2019

Synthesis of high‐purity high‐entropy metal diboride powders is critical to implementing their extensive applications. However, the related studies are rarely reported. Herein we first theoretically studied the synthesis possibility of high‐purity high‐entropy diboride powders, namely (Hf0.25Ta0.25Nb0.25Ti0.25)B2 (HTNTB), via boro/carbothermal reduction by analyzing the thermodynamics of the possible chemical reactions and then successfully synthesized the high‐purity and superfine HTNTB powders via boro/carbothermal reduction for the first time. The as‐prepared powders exhibited low‐oxygen impurity content of 0.49 wt% and small average particle size of 260 nm. Meanwhile, they possessed good single‐crystal hexagonal structure of metal diborides and high‐compositional uniformity from nanoscale to microscale. This work will open up a new research field on the synthesis of high‐purity high‐entropy metal diboride powders.
Electrochemical and structural influence on BaZr0.8Y0.2O3‐δ from manganese, cobalt, and iron oxide additives
Authors: Han Donglin , Otani Yuki , Goto Kazuhiro , Uemura Shigeaki , Majima Masatoshi , Uda Tetsuya
Published: August 2019

Proton conductive BaZr0.8Y0.2O3−δ (BZY20) is a promising electrolyte candidate with perspective application in electrochemical devices, including fuel cells, electrolyzer cells. Mn, Fe, and Co are commonly incorporated into BZY20, to improve the sinterability (CoO), or due to possible inter‐diffusion by calcining with cathode materials (eg, La1−xSrxMnO3−δ, La1−xSrxCo1−yFeyO3−δ) for cell preparation. This work was performed to investigate the influence of Mn, Fe, and Co on the structural and electrochemical properties of BZY20. As reported in literature, the sinterability of BZY20 was improved by adding CoO. XANES analysis shows that Mn, Fe, and Co are possibly incorporated into the perovskite crystal structure of BZY20, and are partially reduced when the samples were exposed to hydrogen at 600°C for 24 hours. However, through electrochemical analysis, we found that all these three elements decrease both the proton conductivity and transport numbers of proton conduction of BZY20. Therefore, the BZY20 electrolyte should be carefully handled to avoid the incorporation of these transition metal elements, to fabricate the cells with high performance.
Diagnostic accuracy of an algorithm for detecting atrial fibrillation in a wrist‐type pulse wave monitor
Authors: Kabutoya Tomoyuki , Takahashi Shinichi , Watanabe Tomonori , Imai Yasushi , Uemoto Kazuhiro , Yasui Nobuhiko , Kario Kazuomi
Published: August 2019

We evaluated the diagnostic value of atrial fibrillation (AF) measured by a wrist‐type pulse wave monitor in this case‐control study. Six serial pulse wave values (three in the left and three in the right wrist) were measured using a wrist‐type monitor in 29 AF patients and 30 subjects with sinus rhythm. We defined “monitor AF in irregular pulse peak (IPP) 15/20/25” as follows: (a) IPP: |interval of pulse peak − the average of the interval of the pulse peak| ≥ the average of the interval of the pulse peak × 15/20/25%; (b) irregular heartbeat (IHB): beats of IPP ≥ total pulse × 20%; and (c) monitor AF: ≥4 IHBs of the six pulse wave measurements. In IPP 15, the sensitivity and specificity were 0.97 and 1.00, respectively. Pulse wave analysis by a wrist‐type monitor was shown to have high sensitivity and specificity for the diagnosis of AF.
Experimental evidence for the role of sexual selection in the evolution of cuticular hydrocarbons in the dung beetle, Onthophagus taurus
Authors: Berson Jacob D. , Garcia‐Gonzalez Francisco , Simmons Leigh W.
Published: August 2019

A role for sexual selection in the evolution of insect cuticular hydrocarbons (CHCs) is suggested by observations of selection acting on male CHCs during female mate choice. However, evidence that CHCs evolve in response to sexual selection is generally lacking, and there is a need to extend our understanding beyond well‐studied taxa. Experimental evolution offers a powerful approach to investigate the effect of sexual selection on the evolution of insect CHCs. We conducted such an experiment using the dung beetle, Onthophagus taurus. After six, 12 and 21 generations of experimental evolution, we measured the CHCs of beetles from three populations subject to sexual selection and three populations within which sexual selection had been removed via enforced monogamy. We found that the male CHC profile responded to the experimental removal of sexual selection. Conversely, the CHC profile of females responded to the presence of sexual selection but not to its removal. These results show that sexual selection can be an important mechanism affecting the evolution of insect CHCs and that male and female CHCs can evolve independently.
Context is key: A comment on Herczeg et al. 2019
Authors: Haave‐Audet Elène , Guillette Lauren M. , Mathot Kimberley J.
Published: August 2019

In the last several years, there has been a surge in the number of studies addressing the causes and consequences of among‐individual variation in cognitive ability and behavioural plasticity. Here, we use a recent publication by Herczeg et al. (2019: 32(3), 218–226) to highlight three shortcomings common to this newly emerging field. In their study, Herczeg et al. attempted to link variation in cognitive ability and behavioural plasticity by testing whether selection lines of guppies (Poecilia reticulata) that differ in relative brain size also differ in behavioural plasticity, as might be expected if the costs to plasticity are predominantly derived from the cost of developing large brains. First, residual brain size may not be a suitable proxy for ‘cognitive ability’. Recent work has shown that intraspecific variation in cognitive ability can be better understood by considering variation in the specific brain areas responsible for the relevant behaviours as opposed to whole‐brain mass. Second, the measure of behavioural plasticity, habituation, is unlikely to fulfil the assumptions that plasticity is both adaptive and costly. Finally, we point out several misconceptions regarding animal personality that continue to contribute to the choice of traits that are not well aligned with study objectives. Elucidating the mechanisms underlying among‐individual variation in cognition and behavioural plasticity within populations requires integration between behavioural ecology and comparative cognition, and the study system developed by Herczeg et al. has the potential to provide important mechanistic insights. We hope that by articulating and critically appraising the underlying assumptions that are common in these traditionally separate disciplines, a strong foundation can emerge to allow for more fruitful integration of these fields.
Consistent within‐individual plasticity is sufficient to explain temperature responses in red deer reproductive traits
Authors: Froy Hannah , Martin Julien , Stopher Katie V. , Morris Alison , Morris Sean , Clutton‐Brock Tim H. , Pemberton Josephine M. , Kruuk Loeske E. B.
Published: August 2019

Warming global temperatures are affecting a range of aspects of wild populations, but the exact mechanisms driving associations between temperature and phenotypic traits may be difficult to identify. Here, we use a 36‐year data set on a wild population of red deer to investigate the causes of associations between temperature and two important components of female reproduction: timing of breeding and offspring size. By separating within‐ versus between‐individual associations with temperature for each trait, we show that within‐individual phenotypic plasticity (changes within a female's lifetime) was entirely sufficient to generate the observed population‐level association with temperature at key times of year. However, despite apparently adequate statistical power, we found no evidence of any variation between females in their responses (i.e. no “IxE” interactions). Our results suggest that female deer show plasticity in reproductive traits in response to temperatures in the year leading up to calving and that this response is consistent across individuals, implying no potential for either selection or heritability of plasticity. We estimate that the plastic response to rising temperatures explained 24% of the observed advance in mean calving date over the study period. We highlight the need for comparable analyses of other systems to determine the contribution of within‐individual plasticity to population‐level responses to climate change.