bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of patients’ perceptions about, and their experiences of, root canal treatment
Authors: Chandraweera Lahiru , Goh Kelly , Lai‐Tong Julia , Newby Janni , Abbott Paul
Published: October 2018

Root canal treatment (RCT) is widely perceived to be a painful procedure. There is a lack of data regarding patients’ perceptions of RCT within the Australian population. The aims of this pilot study were to investigate the perception of adult Australian patients within the Perth Metropolitan area and to identify how this changes following treatment. Effects of demographic factors on anxiety and pain experience were also explored. Sixty‐nine patients were surveyed, of which 28 (41%) completed both pre‐ and post‐treatment surveys. Modified Visual Analogue scales and multiple choice questions identified patient concerns, nervousness and anticipated or experienced pain. Cost (55%) and pain (51%) were the greatest pre‐treatment concerns. No expectation of pain was reported by 7% of patients, while 28% reported experiencing no pain during the course of treatment. Results suggest that anticipated pain is greater than pain experienced, and that after the treatment, anxiety for future RCT was significantly reduced.
The Developing Regorafenib Eye drops for neovascular Age‐related Macular degeneration (DREAM) study: an open‐label phase II trial
Authors: Joussen Antonia M. , Wolf Sebastian , Kaiser Peter K. , Boyer David , Schmelter Thomas , Sandbrink Rupert , Zeitz Oliver , Deeg Gesa , Richter Annett , Zimmermann Torsten , Hoechel Joachim , Buetehorn Ulf , Schmitt Walter , Stemper Brigitte , Boettger Michael K.
Published: October 2018

Aims

This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age‐related macular degeneration (nAMD).

Methods

Topical regorafenib was investigated in an open‐label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml–1) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best‐corrected visual acuity (BCVA) from baseline to weeks 4 and 12.

Results

In nAMD patients (N = 51), mean changes in BCVA were +1.2 [90% confidence interval (CI) –0.61, 2.97] and −2.4 (90% CI −4.18, −0.54) letters at weeks 4 and 12, respectively. Ocular treatment‐emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was one serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab).

Conclusions

The programme was terminated after phase IIa ended because efficacy was lower than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).
How the CIOMS guidelines contribute to fair inclusion of pregnant women in research
Authors: van der Graaf Rieke , van der Zande Indira S. E. , van Delden Johannes J. M.
Published: October 2018

As early as 2002, CIOMS stated that pregnant women should be presumed eligible for participation in research. Despite this position and calls of other well‐recognized organizations, the health needs of pregnant women in research remain grossly under‐researched. Although the presumption of eligibility remains unchanged, the revision of the 2002 CIOMS International ethical guidelines for biomedical research involving human subjects involved a substantive rewrite of the guidance on research with pregnant women and related guidelines, such as those on fair inclusion and vulnerability. However, close reading of the guidelines reveals morally relevant different approaches to fair inclusion of pregnant women and other under‐represented groups, such as children and incompetents. Where CIOMS sets out that children and adolescents must be included unless a good scientific reason justifies their exclusion, no such claim of having to justify exclusion appears in the guideline on pregnant women. Instead, CIOMS claims that research relevant to pregnant women’s health needs must be promoted. This paper analyses how and to what extent the guideline on pregnant women differs from other guidance on fair inclusion in the document. Accordingly, the paper evaluates to what extent the current phrasing may contribute to fair inclusion of pregnant women in research. We will conclude that a system change towards a learning health system is essential to break down the status quo of knowledge generation in the field of medication use during pregnancy and argue that the CIOMS guidelines allow for this system change.
The epistemic and ethical onus of ‘One Health’
Authors: Beever Jonathan , Morar Nicolae
Published: October 2018

This paper argues that the practical reach and ethical impact of the One Health paradigm is conditional on satisfactorily distinguishing between interconnected and interdependent factors among human, non‐human, and environmental health. Interconnection does not entail interdependence. Offering examples of interconnections and interdependence in the context of existing One Health literature, we demonstrate that the conversations about One Health do not yet sufficiently differentiate between those concepts. They tend to either ignore such distinctions or embrace bioethically untenable positions. We conclude that careful conceptual differentiation can prevent One Health stakeholders either from over‐reaching or under‐reaching the practical and ethical boundaries of this developing paradigm.
The German debate on male circumcision and Habermas’ model of post‐secularity
Authors: Greve Jens
Published: October 2018

This paper considers Habermas’ model of a post‐secular political order in the light of the debate on male circumcision that arose in Germany after a court ruled that male circumcision was an unjustifiable act of bodily harm. Central to this model is the idea that religious reasons can only become effective in central legal institutions when they are translated into secular reasons. My paper demonstrates that there are two distinguishable readings of this proviso. On the one hand, there is a broad reading according to which it is only necessary to reach a conclusion that is in line with the democratic principle stating that all citizens can be regarded as co‐legislators even if non‐generalizable value orientations might then shape the interpretation of fundamental rights (in the case of circumcision, the right to bodily integrity). On the other hand, a truly secular (narrow) reading would avoid the inclusion of non‐generalizable value orientations. The debate on circumcision demonstrates that these two interpretations lead to different and conflicting modes of justification. The broad reading allows for a justification of male circumcision, whereas the narrow reading makes such a justification unlikely. In addition, the filtering function of the proviso is weakened in a broad reading.
Endothelial NOS: perspective and recent developments
Authors: Garcia Victor , Sessa William C
Published: October 2018

Endothelial NOS (eNOS), and its product NO, are vital components of the control of vasomotor function and cardiovascular homeostasis. In the present review, we will take a deep dive into eNOS enzymology, function and mechanisms regulating endothelial NO. The mechanisms regulating eNOS and NO synthesis discussed here include alterations to transcriptional, post‐translational modifications and protein–protein regulations. Also, we will discuss the phenotypes associated with various eNOS mutants and the consequences of a disrupted eNOS/NO cascade, highlighting the importance of eNOS function and vascular homeostasis.

Linked Articles

This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc
Metabolism of sulfur compounds in homocystinurias
Authors: Kožich Viktor , Ditrói Tamás , Sokolová Jitka , Křížková Michaela , Krijt Jakub , Ješina Pavel , Nagy Peter
Published: October 2018

Background and Purpose

Homocystinurias are rare genetic defects characterized by altered fluxes of sulfur compounds including homocysteine and cysteine. We explored whether the severely perturbed sulfur amino acid metabolism in patients with homocystinurias affects the metabolism of hydrogen sulfide.

Experimental Approach

We studied 10 treated patients with a block in the conversion of homocysteine to cysteine due to cystathionine β‐synthase deficiency (CBSD) and six treated patients with remethylation defects (RMD) and an enhanced flux of sulfur metabolites via transsulfuration. Control groups for CBSD and RMD patients consisted of 22 patients with phenylketonuria on a low‐protein diet and of 12 healthy controls respectively. Plasma and urine concentrations of selected sulfur compounds were analysed by HPLC and LC–MS/MS.

Key Results

Patients with CBSD exhibited plasma concentrations of monobromobimane‐detected sulfide similar to appropriate controls. Urinary homolanthionine and thiosulfate in CBSD were increased significantly 1.9 and 3 times suggesting higher hydrogen sulfide synthesis by γ‐cystathionase and detoxification respectively. Surprisingly, patients with RMD had significantly lower plasma sulfide levels (53 and 64% of controls) with lower sulfite concentrations, and higher taurine and thiosulfate levels suggesting enhanced cysteine oxidation and hydrogen sulfide catabolism respectively.

Conclusion and Implications

The results from this study suggest that severe inherited defects in sulfur amino acid metabolism may be accompanied by only moderately perturbed hydrogen sulfide metabolism and lends support to the hypothesis that enzymes in the transsulfuration pathway may not be the major contributors to the endogenous hydrogen sulfide pool.

Linked Articles

This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc
The affinity, intrinsic activity and selectivity of a structurally novel EP2 receptor agonist at human prostanoid receptors
Authors: Coleman R A , Woodrooffe A J , Clark K L , Toris C B , Fan S , Wang J W , Woodward D F
Published: October 2018

Background and Purpose

Prostanoid EP2 receptor agonists exhibit several activities including ocular hypotension, tocolysis and anti‐inflammatory activity. This report describes the affinity and selectivity of a structurally novel, non‐prostanoid EP2 receptor agonist, PGN‐9856, and its therapeutic potential.

Experimental Approach

The pharmacology of a series of non‐prostanoid EP2 receptor agonists was determined according to functional and radioligand binding studies, mostly using human recombinant prostanoid receptor transfectants. The selectivity of PGN‐9856, as the preferred compound, was subsequently determined by using a diverse variety of non‐prostanoid target proteins. The therapeutic potential of PGN‐9856 was addressed by determining its activity in relevant primate cell, tissue and disease models.

Key Results

PGN‐9856 was a selective and high affinity (pKi ≥ 8.3) ligand at human recombinant EP2 receptors. In addition to high affinity binding, it was a potent and full EP2 receptor agonist with a high level of selectivity at EP1, EP3, EP4, DP, FP, IP and TP receptors. In cells overexpressing human recombinant EP2 receptors, PGN‐9856 displayed a potency (pEC50≥ 8.5) and a maximal response (increase in cAMP) comparable to that of the endogenous agonist PGE2. PGN‐9856 exhibited no appreciable affinity (up 10 μM) for a range of 53 other receptors, ion channels and enzymes. Finally, PGN‐9856 exhibited tocolytic, anti‐inflammatory and long‐acting ocular hypotensive properties consistent with its potent EP2 receptor agonist properties.

Conclusions and Implications

PGN‐9856 is a potent, selective and efficacious prostanoid EP2 receptor agonist with diverse potential therapeutic applications: tocolytic, anti‐inflammatory and notably anti‐glaucoma.
The Earlier the Better? Pausing for Thought …
Authors: Maughan Barbara , Barker Edward D.
Published: October 2018

Is earlier intervention always superior? Using two complementary forms of meta‐analysis, Gardner and colleagues find no support for the “earlier is better” hypothesis in outcomes of parenting programs for child behavior problems across the 2–11 year age range. This commentary explores possible methodological and substantive reasons for the pattern of their findings. We need additional careful analyses of this kind, assessing age variations in intervention effects across broader age ranges, and in other developmental domains, for strong tests of the “earlier is better” hypothesis. At this stage, however, Gardner et al.'s findings give us some pause for thought.
Spin in articles about minimally invasive transanal total mesorectal excision: an assessment of the current literature
Authors: Patel S. V. , Zhang L. , Elsolh B. , Yu D. , Chadi S. A.
Published: October 2018

Aim

Minimally invasive transanal total mesorectal excision (TaTME) is a new approach for treating rectal cancer. ‘Spin’ can be defined as ‘reporting strategies to highlight that the experimental treatment is beneficial’ despite limitations in study design. The aim of this study was to assess spin within publications about TaTME.

Method

EMBASE and MEDLINE (2009–2017) were searched for publications assessing TaTME in rectal cancer. All papers published between 2009 and 2017 were eligible for inclusion. Study titles and abstracts were assessed for evidence of spin, as previously defined.

Results

A total of 1202 studies were identified through our search, and 73 were included. The majority were case series (n = 48, 66%). A total of 55 publications (75%) had evidence of spin within at least one domain. The most common type of spin was claiming safety without describing how this was defined or tested (56%). Other strategies included claiming superiority without support (33%) and reporting nonsignificance as equivalence (42%). We did not find that year of publication (P = 0.61), study design (P = 0.60), number of patients (P = 0.85) or declared conflict of interest (P = 0.43) were associated with spin.

Conclusion

We have shown that spin is common within studies assessing TaTME for rectal cancer. Despite a lack of support from study results, in the majority of studies authors concluded that TaTME is safe for use in rectal cancer. Readers of study abstracts describing new techniques need to be cautious about accepting the authors’ conclusions, especially in case series and observational studies.
The Influence of Globally Ungrammatical Local Syntactic Constraints on Real‐Time Sentence Comprehension: Evidence From the Visual World Paradigm and Reading
Authors: Kamide Yuki , Kukona Anuenue
Published: October 2018

We investigated the influence of globally ungrammatical local syntactic constraints on sentence comprehension, as well as the corresponding activation of global and local representations. In Experiment 1, participants viewed visual scenes with objects like a carousel and motorbike while hearing sentences with noun phrase (NP) or verb phrase (VP) modifiers like “The girl who likes the man (from London/very much) will ride the carousel.” In both cases, “girl” and “ride” predicted carousel as the direct object; however, the locally coherent combination “the man from London will ride…” in NP cases alternatively predicted motorbike. During “ride,” local constraints, although ruled out by the global constraints, influenced prediction as strongly as global constraints: While motorbike was fixated less than carousel in VP cases, it was fixated as much as carousel in NP cases. In Experiment 2, these local constraints likewise slowed reading times. We discuss implications for theories of sentence processing.
Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
Authors: Zhou Cancan , Qian Weikun , Ma Jiguang , Cheng Liang , Jiang Zhengdong , Yan Bin , Li Jie , Duan Wanxing , Sun Liankang , Cao Junyu , Wang Fengfei , Wu Erxi , Wu Zheng , Ma Qingyong , Li Xuqi
Published: October 2018

Objectives

Gemcitabine is a standard treatment for advanced pancreatic cancer patients but can cause chemoresistance during treatment. The chemoresistant cells have features of cancer stem cells (CSCs). Resveratrol has been reported to overcome the resistance induced by gemcitabine. However, the mechanism by which resveratrol enhances chemosensitivity remains elusive. Here, we explored the mechanism by which resveratrol enhanced chemosensitivity and the role of sterol regulatory element binding protein 1 (SREBP1) in gemcitabine‐induced stemness.

Materials and methods

The pancreatic cancer cell lines MiaPaCa‐2 and Panc‐1 were treated under different conditions. Methyl thiazolyl tetrazolium and colony formation assays were performed to evaluate effects on proliferation. Flow cytometry was conducted to detect apoptosis. Oil red O staining was performed to examine lipid synthesis. The sphere formation assay was applied to investigate the stemness of cancer cells. Immunohistochemistry was performed on tumour tissue obtained from treated KPC mice.

Results

Resveratrol enhanced the sensitivity of gemcitabine and inhibited lipid synthesis via SREBP1. Knockdown of SREBP1 limited the sphere formation ability and suppressed the expression of CSC markers. Furthermore, suppression of SREBP1 induced by resveratrol reversed the gemcitabine‐induced stemness. These results were validated in a KPC mouse model.

Conclusions

Our data provide evidence that resveratrol reverses the stemness induced by gemcitabine by targeting SREBP1 both in vitro and in vivo. Thus, resveratrol can be an effective chemotherapy sensitizer, and SREBP1 may be a rational therapeutic target.
The Nedd8‐activating enzyme inhibitor MLN4924 (TAK‐924/Pevonedistat) induces apoptosis via c‐Myc‐Noxa axis in head and neck squamous cell carcinoma
Authors: Zhang Wenjuan , Liang Yupei , Li Lihui , Wang Xiaofang , Yan Zi , Dong Changsheng , Zeng Mu‐Sheng , Zhong Qian , Liu Xue‐Kui , Yu Jinha , Sun Shuyang , Liu Xiaojun , Kang Jihui , Zhao Hu , Jeong Lak Shin , Zhang Yanmei , Jia Lijun
Published: October 2018

Objectives

The present study aimed to reveal expression status of the neddylation enzymes in HNSCC and to elucidate the anticancer efficacy and the underlying mechanisms of inhibiting neddylation pathway.

Materials and methods

The expression levels of neddylation enzymes were estimated by Western blotting in human HNSCC specimens and bioinformatics analysis of the cancer genome atlas (TCGA) database. Cell apoptosis was evaluated by Annexin V fluorescein isothiocyanate/propidium iodide (Annexin V‐FITC/PI) stain and fluorescence‐activated cell sorting (FACS). Small interfering RNA (siRNA) and the CRISPR‐Cas9 system were used to elucidate the underlying molecular mechanism of MLN4924‐induced HNSCC apoptosis.

Results

Expression levels of NAE1 and UBC12 were prominently higher in HNSCC tissues than that in normal tissues. Inactivation of the neddylation pathway significantly inhibited malignant phenotypes of HNSCC cells. Mechanistic studies revealed that MLN4924 induced the accumulation of CRL ligase substrate c‐Myc that transcriptionally activated pro‐apoptotic protein Noxa, which triggered apoptosis in HNSCC.

Conclusions

These findings determined the over‐expression levels of neddylation enzymes in HNSCC and revealed novel mechanisms underlying neddylation inhibition induced growth suppression in HNSCC cells, which provided preclinical evidence for further clinical evaluation of neddylation inhibitors (eg, MLN4924) for the treatment of HNSCC.
Golgi protein 73 and its diagnostic value in liver diseases
Authors: Xia Yanyan , Zhang Yuanying , Shen Mengjiao , Xu Hongpan , Li Zhiyang , He Nongyue
Published: October 2018

Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis‐Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non‐viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.
A new perspective for pulmonary thromboembolism radiology: ‘Pulmonary vein sign’
Authors: Ermin Sinem , Çinkooğlu Akın , Susam Seher , Batum Özgür , Yılmaz Ufuk
Published: October 2018

Introduction

Pulmonary thromboembolism (PTE) is a clinical condition that can result in sudden death. Computed tomography pulmonary angiography (CTPA) is the most sensitive imaging technique for the diagnosis of PTE. Filling defects in the pulmonary veins, which can be identified in areas adjacent to PTE, have been named the ‘pulmonary vein sign’ (PVS).

Objectives

The aim of our study is to determine the frequency, sensitivity and specificity of PVS due to the decreased venous drainage in the affected area in PTE patients.

Methods

Patients who were admitted to the emergency department due to the suspicion of PTE and who underwent CTPA were evaluated retrospectively. The study group consisted of the patients who had an arterial filling defect on CTPA and were diagnosed with PTE. The control group consisted of the patients who had no arterial filling defect on CTPA.

Results

This study included 286 patients with a mean age of 62(20‐94) years. The PVS was detected in 51(32.7%) of the patients in the study group and in 15(11.5%) of the patients in the control group. The PVS had a sensitivity of 32.69%, a specificity of 88.46%, a positive predictive value of 77.27% and a negative predictive value of 52.27% for PTE. The PVS was significantly more common in the patients having PTE in the bilateral pulmonary arteries or the main pulmonary arteries.

Conclusion

Despite low sensitivity, the presence of PVS on CTPA is a radiographic marker with high specificity for PTE. To use in practice, there is need for studies with large numbers of patients.
The regulation of interferon type I pathway‐related genes RSAD2 and ETV7 specifically indicates antibody‐mediated rejection after kidney transplantation
Authors: Matz Mareen , Heinrich Frederik , Zhang Qiang , Lorkowski Christine , Seelow Evelyn , Wu Kaiyin , Lachmann Nils , Addo Richard K. , Durek Pawel , Mashreghi Mir‐Farzin , Budde Klemens
Published: October 2018

Context

Antibody‐mediated rejection (ABMR) after kidney transplantation (KTx) remains the crucial obstacle to successful long‐term graft function. The identification of gene signatures involved in ABMR could grant the basis for better prevention and treatment strategies.

Objective

The identification of gene signatures in whole blood cells specific for ABMR after KTx.

Materials and methods

Total RNA from blood cells of 16 kidney‐transplanted patients with ABMR, stable graft function (SGF), and with T‐cell‐mediated rejection (TCMR) was isolated. Gene expression was determined by high‐throughput sequencing followed by validation and analyses of differentially expressed candidates on mRNA level and on protein level in a large patient cohort (n = 185) in patients with SGF, urinary tract infection (UTI), borderline rejection (BL), TCMR, ABMR, and interstitial fibrosis and tubular atrophy.

Results

From the 570 genes detected, 111 discriminated ABMR from SGF and TCMR. A distinct enrichment of interferon (IFN) type I and type II signature gene set was observed. The expression of candidate genes IFIT1, ETV7, and RSAD2 distinguished ABMR patients from patients with SGF and also TCMR, whereas ETV7 and RSAD2 differentiated ABMR also from BL.

Conclusion

The IFN‐inducible genes ETV7 and RSAD2 represent specific biomarkers for ABMR episodes after KTx.
Reversible cerebral vasoconstriction syndrome: a rare arteriopathy of childhood
Authors: Dlamini Nomazulu
Published: October 2018

This commentary is on the case series by Durrleman et al. on pages 725–729 of this issue.
Measuring change in gait performance of children with motor disorders: assessing the Functional Mobility Scale and the Gillette Functional Assessment Questionnaire walking scale
Authors: Ammann‐Reiffer Corinne , Bastiaenen Caroline H G , Van Hedel Hubertus J A
Published: October 2018

Aim

To examine the responsiveness and minimal important change (MIC) of two gait performance measures, the Functional Mobility Scale (FMS) and the Gillette Functional Assessment Questionnaire walking scale (FAQ), in a paediatric inpatient setting.

Method

Sixty‐four children and adolescents with a motor disorder, including cerebral palsy, traumatic brain injury, or stroke (25 females, 39 males; mean age [SD] 12y 6mo [3y 2mo], range 6–18y 6mo), were recruited. Physiotherapists scored the FMS and FAQ at the start and end of active gait rehabilitation. Change scores were compared with changes in gait capacity tests, the walking item of the Functional Independence Measure for Children, and a global rating scale (GRS) on the physiotherapists’ perceived change of the child's functional mobility. The GRS was also used to define the MIC.

Results

Change scores of the FMS and FAQ correlated between 0.35 and 0.49 with those of the capacity tests, 0.54 to 0.76 with the Functional Independence Measure for Children walking item change scores, and 0.57 to 0.76 with the GRS. The MIC values for the FMS and FAQ were 0.5 and 1.5 respectively.

Interpretation

FMS and FAQ can illustrate change in inpatient gait performance of children and adolescents with motor disorders. An improvement of one level in the FMS and two levels in the FAQ is considered as a clinically meaningful change.

What this paper adds

The Functional Mobility Scale (FMS) can detect change in children's inpatient gait performance.

The Gillette Functional Assessment Questionnaire walking scale (FAQ) can also detect change in children's inpatient gait performance.

A one‐level improvement in the FMS is clinically relevant.

A two‐level improvement in the FAQ is clinically relevant.
Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety
Authors: Dada Reyad , Usman Binyam
Published: October 2018

Objectives

Relapsed cHL patients after autologous hematopoietic stem cell transplantation (HSCT) with treatment‐sensitive disease are potential candidates for curative allogeneic HSCT. However, there are some concerns around performing such procedure after checkpoint inhibitors (CPIs).

Methods

We collected published data of patients undergoing allogeneic HSCT after treatment with CPIs (cohort 1). Abstracts of recent conferences (2015‐2017; ASCO, ASH, EBMT, ASBMT) were also included. Results were compared with safety of recent studies (2015‐2018) with allogeneic HSCT without CPIs (cohort 2).

Results

A total of 272 records were screened. After exclusion of duplications, cohorts 1 and 2 included each 6 publications with 122 and 978 patients, respectively. Grade 3‐4 acute GVHD in cohort 1 was found in 28% vs 8% in cohort 2 (P = 0.02). Chronic GVHD was observed in 26% vs 29%, respectively. NRM was 15% which remained relatively stable after 6 months of allogeneic HSCT vs 19% in cohort 2.

Conclusions

This is the largest pooled analysis of its kind published so far. Our results suggest that allogeneic HSCT after CPIs is feasible and not associated with higher mortality. However, careful consideration should be given for prevention, early detection, and effective treatment of GVHD in these cases. Additional prospective studies are needed for further clarification.
Recurrent aphthous stomatitis and gene variability in selected interleukins: a case–control study
Authors: Borilova Linhartova Petra , Janos Julius , Slezakova Simona , Bartova Jirina , Petanova Jitka , Kuklinek Pavel , Fassmann Antonin , Dusek Ladislav , Izakovicova Holla Lydie
Published: October 2018

Genetic factors, especially those related to immune system functioning, have been intensively studied to determine their role in the development of recurrent aphthous stomatitis (RAS). The aim of the present study was to analyze gene variability in interleukin (IL)2, IL4 (and its receptor α, IL4Rα), IL10, and IL13, which were selected based on literature review and/or their functional relevance, in Czech patients with RAS and in healthy controls. In total, 252 subjects (178 controls and 74 patients with RAS) were enrolled in this case–control study, and their detailed anamnestic, clinical, and laboratory data were obtained. Nine polymorphisms in the genes encoding interleukins were determined using PCR techniques. There were no significant differences in allele or genotype frequencies of the IL2, IL4, IL4Rα, IL10, and IL13 polymorphisms rs2069762/rs2069763, rs2243250/rs79071878, rs1801275, rs1800896, and rs1800925, respectively, between controls and patients with RAS. The minority alleles rs1800871 and rs1800872, which encode variants of IL10, were associated with a statistically significantly higher risk of RAS, as confirmed by the results of genotype and haplotype analyses. We suggest that variability in the IL10 gene may play an important role in the development of RAS in the Czech population.
Eating disorders: experiences of and attitudes toward oral health and oral health behavior
Authors: Dynesen Anja W. , Gehrt Charlotte A. , Klinker Sabine E. , Christensen Lisa B.
Published: October 2018

It is well known that early signs of eating disorders (EDs), such as dental erosion and enlarged salivary glands, may be recognized in the dental clinic. Dentists acknowledge that approaching a patient to discuss the suspicion of an ED is difficult. However, little is known about how persons with EDs experience and manage dental visits. Therefore, this study aimed to uncover knowledge, experience, and attitude of oral health and oral health behavior among persons with EDs. The study design was cross‐sectional and 260 persons with EDs completed an electronic questionnaire. The participants were generally concerned about their teeth. Some participants had anxiety around having severely and irreversibly damaged teeth, and many were overly occupied with oral hygiene procedures. One‐third of participants had good experiences regarding communication with a dentist, and about half of the participants wanted the dentist to address their EDs in the clinic. However, participants with less‐positive experiences stated that there is a need for dentists with specialized knowledge about EDs and communication skills that emphasize an open, empathic, recognition approach from the dentist toward patients with EDs. In addition, it may be advantageous to integrate dental advice and treatment as part of the treatment of EDs in line with psychological and medical therapy.
Dental malocclusion stimulates neuromuscular circuits associated with temporomandibular disorders
Authors: Liu Xin , Zhang Chunkui , Liu Qian , Zhou Kaixiang , Yin Nannan , Zhang Hongyun , Shi Minghong , Liu Xiaodong , Wang Meiqing
Published: October 2018

Unilateral anterior crossbite (UAC) has been demonstrated to cause masseter hyperactivity via the periodontal trigeminal mesencephalic nucleus (Vme)–trigeminal motor nucleus circuit. Here, we studied activation of motor neurons of the facial nucleus (VII), hypoglossal nucleus (XII), nucleus ambiguus (Amb), and spinal nucleus of the accessory nerve (SNA) in rats with UAC via their similar connections with Vme. An anterograde tracer, biotinylated dextran amine (BDA), was injected into the Vme to identify the central axon terminals around the motor neurons of VII, XII, Amb, and SNA. The expression of vesicular glutamate transporter 1 (VGLUT1) in neurons of VII, XII, Amb, and SNA, and the expression of acetylcholinesterase (AChE) were measured in the stapedius, lingualis, palatopharyngeal, and sternocleidomastoid muscles. In BDA‐treated rats, many BDA‐labeled cell bodies in the Vme and terminals in VII, XII, Amb, and SNA were identified. Compared with control rats, rats with UAC showed higher expression of VGLUT1 in these nuclei, and statistically significantly higher expression of AChE in the stapedius, lingualis, and sternocleidomastoid muscles, but not in the palatopharyngeal muscle. These findings suggest that UAC activates orofacial, head, and cervical multimotor behaviors via connections between the Vme and the corresponding motor nuclei.
Guideline‐based and bioinformatic reassessment of lesion‐associated gene and variant pathogenicity in focal human epilepsies
Authors: Niestroj Lisa‐Marie , Du Juanjiangmeng , Nothnagel Michael , May Patrick , Palotie Aarno , Daly Mark J. , Nürnberg Peter , Blümcke Ingmar , Lal Dennis
Published: October 2018

Objective

Increasing availability of surgically resected brain tissue from patients with focal epilepsy and focal cortical dysplasia or low‐grade glioneuronal tumors has fostered large‐scale genetic examination. However, assessment of pathogenicity of germ line and somatic variants remains difficult. Here, we present a state‐of‐the‐art evaluation of reported genes and variants associated with epileptic brain lesions.

Methods

We critically reevaluated the pathogenicity for all neuropathology‐associated variants reported to date in the PubMed and ClinVar databases, including 101 neuropathology‐associated missense variants encompassing 11 disease‐related genes. We assessed gene variant tolerance and classified all identified missense variants according to guidelines from the American College of Medical Genetics and Genomics (ACMG). We further extended the bioinformatic variant prediction by introducing a novel gene‐specific deleteriousness ranking for prediction scores.

Results

Application of ACMG guidelines and in silico gene variant tolerance analysis classified only seven of 11 genes to be likely disease‐associated according to the reported disease mechanism, whereas 61 (60.4%) of 101 variants of those genes were classified as of uncertain significance, 37 (36.6%) as being likely pathogenic, and 3 (3%) as being pathogenic.

Significance

We concluded that the majority of neuropathology‐associated variants reported to date do not have enough evidence to be classified as pathogenic. Interpretation of lesion‐associated variants remains challenging, and application of current ACMG guidelines is recommended for interpretation and prediction.
A plant‐specific model approach to assess effects of repowering measures on existing biogas plants: The case of Baden‐Wuerttemberg
Authors: Güsewell Joshua , Härdtlein Marlies , Eltrop Ludger
Published: October 2018

Up to the latest versions of the German renewable energy act (EEG), there had been a constant growth of new biogas plants (BGPs). After reaching a stagnation in the last years, today the focus has shifted to improving the existing BGPs. Assuming that most plants have not reached the technical end of life, the question arises on how an operation can be realized beyond the initial EEG support period of 20 years. In addition, new legal and economic conditions require the implementation of adjustments, that is, “repowering measures.” Based on a method review, a plant‐specific model approach is presented to assess repowering measures for a wide range of BGPs differing in capacity, substrate mixture and agricultural structures. The techno‐economic model includes different performance indicators like levelized cost of electricity (LCOE) and temporal aspects like technical progress. Using a data set for BGPs in the state of Baden‐Wuerttemberg (Germany), results are illustrated for the different model modules and three repowering scenarios of an extended operation period of ten years. The scenarios regard different options to meet the requirements of the current EEG, namely the flexibilization and restrictions on energy crops, in comparison with a reference case. While in repowering scenarios, the number of plants decreases between 54% and 69% and the overall power capacity changes between −48% and 13% until 2035. The results further show a reduction potential in the specific area demand and GHG emission up to 12% and 24%, respectively. Technical progress, additional revenues and capacity premiums are shown to be an important factor for efficient substrate utilization, low LCOE and thereby the enabling of an extended operation period. The scenario results indicate that the agricultural areas for energy crop cultivation and the amount of manure used in BGPs will be reduced considerably, inducing new chances and challenges in the future.
Potential harms associated with routine collection of patient sociodemographic information: A rapid review
Authors: Petkovic Jennifer , Duench Stephanie L. , Welch Vivian , Rader Tamara , Jennings Alison , Forster Alan J. , Tugwell Peter
Published: October 2018

Background

Health systems are recommended to capture routine patient sociodemographic data as a key step in providing equitable person‐centred care. However, collection of this information has the potential to cause harm, especially for vulnerable or potentially disadvantaged patients.

Objective

To identify harms perceived or experienced by patients, their families, or health‐care providers from collection of sociodemographic information during routine health‐care visits and to identify best practices for when, by whom and how to collect this information.

Search Strategy

We searchedOVID MEDLINE, PubMed “related articles” viaNLMand healthevidence.org to the end of January 2018 and assessed reference lists and related citations of included studies.

Inclusion Criteria

We included studies reporting on harms of collecting patient sociodemographic information in health‐care settings.

Data Extraction and Synthesis

Data on study characteristics and types of harms were extracted and summarized narratively.

Main Results

Eighteen studies were included; 13 provided patient perceptions or experiences with the collection of these data and seven studies reported on provider perceptions. Five reported on patient recommendations for collecting sociodemographic information. Patients and providers reported similar potential harms which were grouped into the following themes: altered behaviour which may affect care‐seeking, data misuse or privacy concerns, discomfort, discrimination, offence or negative reactions, and quality of care. Patients suggested that sociodemographic information be collected face to face by a physician.

Discussion and Conclusions

Overall, patients support the collection of sociodemographic information. However, harms are possible, especially for some population subgroups. Harms may be mitigated by providing a rationale for the collection of this information.
Cholesterol crystals in periapical lesions of root filled teeth
Authors: Plengwitthaya C. , Dhanuthai K. , Chantarangsu S. , Ratisoontorn C.
Published: October 2018

Aim

To determine the prevalence of cholesterol crystals in periapical biopsies and to evaluate the correlation between cholesterol crystals in periapical biopsies and age, gender, location of the periapical lesion, pathologic diagnosis and lesion size.

Methodology

The biopsy report database (Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand) during 2005–2014 was reviewed. The prevalence of cholesterol crystals in the periapical lesions of root filled teeth was determined. Pathological diagnosis, patients’ age, gender and the location (maxilla or mandible) of the periapical lesion were obtained from treatment records. The area of the lesion from the periapical radiograph before surgery was calculated using ImageJ software. Univariate and multivariate logistic regression analyses were used to determine the association between independent variables and the presence of cholesterol crystals.

Results

The overall prevalence of cholesterol crystals was 20.31%. The periapical biopsies >100 mm2 in size on periapical films had a significantly greater prevalence of cholesterol crystals than those <100 mm2 (P = 0.005). The biopsies diagnosed as radicular cysts had a significantly greater prevalence of cholesterol crystals than the biopsies with other diagnoses (P < 0.001). A pathological diagnosis of radicular cyst was the variable with the strongest association with the presence of cholesterol crystals (P < 0.001; adjusted OR, 12.39).

Conclusions

Presence of cholesterol crystals was associated with periapical lesion diagnosed as a radicular cyst and lesion >100 mm2 in area. Age, gender and location of the lesion did not influence the presence of cholesterol crystals.
Financing knowledge, risk attitude and P2P borrowing in China
Authors: Han Lu , Xiao Jing Jian , Su Zhi
Published: October 2018

The advance of Internet technology has provided a convenient market platform for matching lending and borrowing parties, but many consumers still hesitate to use online borrowing. To better understand consumer behaviour in online borrowing, we use nationally representative survey data in China to explore factors affecting consumer use of one type of online borrowing, person to person (P2P) borrowing. Through empirical analyses, we find that financing knowledge and risk attitude are two key factors associated with P2P borrowing. Results show that financing knowledge is directly associated with P2P borrowing, while risk attitude through an instrument variable is associated with P2P borrowing also. Given these results, an effective way to expand the consumer Internet borrowing market in China is to enhance consumer financial literacy education.
The family meal as an ideal: Children’s perceptions of foodwork and commensality in everyday life and feasts
Authors: Persson Osowski Christine , Mattsson Sydner Ylva
Published: October 2018

The present article concerns meals from the point of view of children, focusing on structural and sociocultural aspects of meals in a Western context in general, and Sweden in particular. The aim was to study children's perceptions of meals with regard to what, where and with whom meals are eaten and how meals are made. The method used was an internet‐based, ethnological questionnaire, which is a qualitative method in which participants share their experiences and values regarding a certain topic of interest in writing. A hundred and twelve Swedish children were included. The children almost exclusively chose to write about family meals. These meals were described as well‐structured and organized, and were often portrayed in an idealized way, with family members sharing proper meals at home, spending an enjoyable time together with a nice atmosphere and good conversation. The children made a distinction between everyday meals and festive meals, where the main differences were that festive meals were more prone to include extended family and friends besides the nuclear family, and were described in a more exceptional way with regard to what is served and mealtime conditions. The article concludes that the family meal functioned as a way to construct the family and as a site where children acquire norms and values about meals and family identity, but they did so in an active way, by breaking rules and by challenging norms, thereby also contributing to change. The changing nature of the family meal was also seen in an extended proper meal and the commensal aspects surrounding mealtime, as commensality included both commensal eating and commensal foodwork.
Forensic psychiatric patients’ perceptions of situations associated with mechanical restraint: A qualitative interview study
Authors: Tingleff Ellen B. , Hounsgaard Lise , Bradley Stephen K. , Gildberg Frederik A.
Published: October 2018

To reduce the use and duration of mechanical restraint in forensic settings and ensure evidence‐based patient care, we need more knowledge about patients’ subjective experiences and perceptions. The aim was to investigate forensic psychiatric patients’ perceptions of situations associated with the use of mechanical restraint and what they perceive as factors impacting the use and duration of mechanical restraint. Twenty participants were interviewed. Four themes were identified through a thematic analysis: ‘overt protest reactions’, ‘silent protest reactions’, ‘illness‐related behaviour’, and ‘genuinely calm’, which together characterize patients’ perceptions of their ways of acting and reacting during mechanical restraint episodes. These themes are linked together in two patterns in the process of mechanical restraint: ‘pattern of protest’ and ‘pattern of illness’. Further research is needed to illuminate the associations between patients’ perceptions of being subjected to mechanical restraint and ways of acting and reacting through the process of mechanical restraint.
Oestrogen receptor alpha, growth hormone receptor, and developmental defect of enamel
Authors: Arid Juliana , Oliveira Daniela B. , Evangelista Silvane S. , Vasconcelos Katia R. F. , Dutra André L. T. , de Oliveira Sara S. , de Queiroz Alexandra M. , Nelson‐Filho Paulo , Vieira Alexandre R. , Küchler Erika C.
Published: October 2018

Background

Oestrogen (ES) and growth hormone (GH) are hormones that may have a role in caries aetiology and developmental defects of enamel (DDE) since their receptors (ERs and GHR) are expressed during amelogenesis.

Aim

To evaluate whether genetic polymorphisms in the genes that codify the ERα (ESR1) and GHR are associated with caries experience and DDE in children.

Design

Two hundred and sixteen children of both genders, aged 9‐12 years, were examined and classified according to caries and DDE phenotype. Genomic DNA was extracted from buccal cells in saliva. Genetic polymorphisms in ERS1 (rs1884051 and rs12154178) and GHR (rs297305, rs2940913, rs2910875, and rs1509460) were genotyped using TaqMan chemistry. Data were analysed by PLINK, while the chi‐square test was used to compare allele and genotype distributions (alpha of 5%).

Results

A total of 131 children (60.7%) had caries experience, and 43 (19.9%) presented DDE. Genotype and allele distributions were not associated with caries experience (P > 0.05). Genotype and allele distributions between DDE, affected and unaffected, were associated with the polymorphism rs12154178 in ESR1 (P = 0.01 and P = 0.001, respectively) and with the polymorphism rs1509460 in GHR (P = 0.05 and P = 0.02, respectively).

Conclusions

Genetic polymorphisms in ERS1 (rs12154178) and GHR (rs1509460) are associated with DDE.
Divergent subgenome evolution after allopolyploidization in African clawed frogs (Xenopus)
Authors: Furman Benjamin L. S. , Dang Utkarsh J. , Evans Ben J. , Golding G. Brian
Published: October 2018

Whole genome duplication (WGD), the doubling of the nuclear DNA of a species, contributes to biological innovation by creating genetic redundancy. One mode of WGD is allopolyploidization, wherein each genome from two ancestral species becomes a ‘subgenome’ of a polyploid descendant species. The evolutionary trajectory of a duplicated gene that arises from WGD is influenced both by natural selection that may favour redundant, new or partitioned functions, and by gene silencing (pseudogenization). Here, we explored how these two phenomena varied over time and within allopolyploid genomes in several allotetraploid clawed frog species (Xenopus). Our analysis demonstrates that, across these polyploid genomes, purifying selection was greatly relaxed compared to a diploid outgroup, was asymmetric between each subgenome, and that coding regions are shorter in the subgenome with more relaxed purifying selection. As well, we found that the rate of gene loss was higher in the subgenome under weaker purifying selection and that this rate has remained relatively consistent over time after WGD. Our findings provide perspective from recently evolved vertebrates on the evolutionary forces that likely shape allopolyploid genomes on other branches of the tree of life.