bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis
Authors: Haydock Rebecca , Hepburn Trish , Ross Jonathan , Daniels Jane , Brittain Clare , Jackson Louise , Ozolins Mara , Wilson Janet 
Published: December 2022

Abstract

Background

Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour and it is associated with serious sequelae. The most frequently prescribed treatment for BV in the UK is 7-day oral metronidazole but recurrences are common following it. Dequalinium chloride (Fluomizin©) is an anti-infective, antiseptic agent administered as a vaginal tablet. Small studies have shown this to be an effective alternative to antibiotics as a BV treatment. This trial aims to investigate whether dequalinium is as effective as current antibiotic treatments for the treatment of BV 1 month after treatment start.

Methods
DEVA is a multi-centre, randomised, open-label, parallel group, non-inferiority trial of dequalinium chloride versus usual care antibiotics for the treatment of BV. Recruitment will take place in 15 GUM clinics in the UK with Leeds Sexual Health also managing remote recruitment via the trial website. Women will be randomised 1:1 to receive dequalinium or usual care antibiotics. The primary outcome is to determine if the proportion of women reporting resolution of BV symptoms 4 weeks after treatment (without the need for additional treatment) is not worse in women treated with dequalinium chloride compared to usual care antibiotics. Questionnaire follow-up will take place 4 and 12 weeks after starting treatment, and remotely recruited patients will also provide a week 4 BV vaginal smear. The sample size is 904.

Discussion
This trial will provide high-quality evidence on the use of dequalinium chloride as a BV treatment, which could result in patients reducing the number of antibiotics they take.

Trial registration
ISRCTN ISRCTN91800263. Prospectively registered on 20 January 2020.
Establishing a Core Domain Set for early-phase clinical trials of electrical stimulation interventions for tinnitus in adults: protocol for an online Delphi study
Authors: Labree Bas , Hoare Derek J. , Fackrell Kathryn , Hall Deborah A. , Gascoyne Lauren E. , Sereda Magdalena 
Published: December 2022

Abstract
Background
Tinnitus is the awareness of a sound in the ear or head in the absence of an external source. It affects around 10–15% of people and current treatment options are limited. Experimental treatments include various forms of electrical stimulation of the brain. Currently, there is no consensus on the outcomes that should be measured when investigating the efficacy of this type of intervention for tinnitus. This study seeks to address this by establishing a Core Domain Set: a common standard of what specific tinnitus-related complaints are critical and important to assess in all clinical trials of electrical stimulation-based interventions for tinnitus.

Methods
A two-round online survey will be conducted, followed by a stakeholder consensus meeting to identify a Core Domain Set. Participants will belong to one of two stakeholder groups: healthcare users with lived experience of tinnitus, and professionals with relevant clinical, commercial, or research experience.

Discussion
This study will establish a Core Domain Set for the evaluation of electrical stimulation-based interventions for tinnitus via an e-Delphi study. The resulting Core Domain Set will act as a minimum standard for reporting in future clinical trials of electrical stimulation interventions for tinnitus. Standardisation will facilitate comparability of research findings.
Comparative study of extension area based methods for spectrophotometric determination of desmopressin acetate in the presence of its acid-induced degradation products
Authors: Kelani Khadiga M. , Nassar Ahmed M. Wafaa , Omran Gamal A. , Morshedy Samir , Talaat Wael 
Published: December 2022

AbstractDesmopressin acetate (DPA) is a synthetic analogue of vasopressin used in the treatment of diabetes insipidus, bedwetting, hemophilia A, and elevated levels of urea in the blood. Sensitive and selective stability-indicating methods are needed to be developed and validated for its assay pure and pharmaceutical dosage forms in the presence of its degradation products as no method has been reported for its determination in the presence of its degradants. This work describes a comparative study of five simple stability-indicating spectrophotometric techniques for determination of DPA in presence of its acid-degradation products (acid-degradants) without prior separation. The proposed spectrophotometric techniques (First derivative, Derivative ratio, Ratio difference, Mean centering and Dual wavelength) were developed and validated according to ICH guidelines. Acid degradation was carried out with 0.1 N HCl; the acid-degradants were separated on TLC plates and the acidic degradation pathway was established by IR, H-NMR and MS techniques. The TLC method was based on the separation of DPA and its acid-induced degradation products on silica gel plates using methanol: water (80:20, v/v) as a developing system and UV detection at 254 nm. All assay suggested methods were successfully applied for quantitation of DPA in pure and tablet forms. They are specific, sensitive, precise and accurate. They showed good linearity in the concentration range of 1–14 µg/mL with good correlation coefficients, and limit of detection (LOD) of 0.304, 0.274, 0.167, 0.248 and 0.199 and limit of quantitation (LOQ) of 0.920, 0.829, 0.506, 0.751 and 0.604) for each method, respectively. These methods were successfully applied for the simultaneous determination of DPA in its pure and tablet dosage form in the presence of its acid-degradants. The results obtained were statistically comparable with those of reported HPLC assay method; no significant differences were observed with relevance to accuracy and precision. All the methods are sensitive, selective and can be used for the routine analysis of DPA in its pure and dosage forms.
Breast neuroendocrine tumor arising in the axilla of a man: a case report
Authors: Kimura Kosei , Kawabata Shigeru , Oku Hiroyo , Ikari Ayana , Tominaga Tomo , Takai Saki , Sakane Junna , Tanaka Michiaki , Aoki Chinatsu , Ota Monika , Minami Erika , Hirose Yoshinobu , Lee Sang-Woong , Iwamoto Mitsuhiko 
Published: December 2022

Abstract
Background
Accessory breast carcinomas of the axilla of males are rare, and primary breast neuroendocrine tumors (BNETs) are rare as well. We present a case of a BNET arising in the axilla of a man.

Case presentation
A 64-year-old Japanese man presented with a hard 15-mm mass in the axilla and axillary lymph node swelling. Histopathological examination of the incisional biopsy specimen revealed a neuroendocrine carcinoma. Therefore, wide radical excision of the axillary tumor and axillary lymph node dissection were performed. Hematoxylin and eosin staining showed that the solid tumor was mainly located in the subcutaneous adipose tissues and appeared to invade the skin. The tumor phenotypes were positive for CAM 5.2, synaptophysin, estrogen receptor, progesterone receptor, and GATA-binding protein 3; they were negative for human epidermal growth receptor 2. The neuroendocrine component comprised more than 90% of the tumor, and the Ki-67 index was 21%. These results indicated that the tumor was a BNET. This patient underwent adjuvant chemotherapy, endocrine therapy, and radiotherapy.

Conclusions
BNET cases in males are rare. The clinical and histological criteria as well as treatment for these rare cases are discussed.
Robust generation of human-chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases
Authors: Ho Beatrice Xuan , Pang Jeremy Kah Sheng , Chen Ying , Loh Yuin-Han , An Omer , Yang Henry He , Seshachalam Veerabrahma Pratap , Koh Judice L. Y. , Chan Woon-Khiong , Ng Shi Yan , Soh Boon Seng 
Published: December 2022

Abstract
Background
Tissue organoids generated from human pluripotent stem cells are valuable tools for disease modelling and to understand developmental processes. While recent progress in human cardiac organoids revealed the ability of these stem cell-derived organoids to self-organize and intrinsically formed chamber-like structure containing a central cavity, it remained unclear the processes involved that enabled such chamber formation.

Methods
Chambered cardiac organoids (CCOs) differentiated from human embryonic stem cells (H7) were generated by modulation of Wnt/ß-catenin signalling under fully defined conditions, and several growth factors essential for cardiac progenitor expansion. Transcriptomic profiling of day 8, day 14 and day 21 CCOs was performed by quantitative PCR and single-cell RNA sequencing. Endothelin-1 (EDN1) known to induce oxidative stress in cardiomyocytes was used to induce cardiac hypertrophy in CCOs in vitro. Functional characterization of cardiomyocyte contractile machinery was performed by immunofluorescence staining and analysis of brightfield and fluorescent video recordings. Quantitative PCR values between groups were compared using two-tailed Student’s t tests. Cardiac organoid parameters comparison between groups was performed using two-tailed Mann–Whitney U test when sample size is small; otherwise, Welch’s t test was used. Comparison of calcium kinetics parameters derived from the fluorescent data was performed using two-tailed Student’s t tests.

Results
Importantly, we demonstrated that a threshold number of cardiac progenitor was essential to line the circumference of the inner cavity to ensure proper formation of a chamber within the organoid. Single-cell RNA sequencing revealed improved maturation over a time course, as evidenced from increased mRNA expression of cardiomyocyte maturation genes, ion channel genes and a metabolic shift from glycolysis to fatty acid ß-oxidation. Functionally, CCOs recapitulated clinical cardiac hypertrophy by exhibiting thickened chamber walls, reduced fractional shortening, and increased myofibrillar disarray upon treatment with EDN1. Furthermore, electrophysiological assessment of calcium transients displayed tachyarrhythmic phenotype observed as a consequence of rapid depolarization occurring prior to a complete repolarization.

Conclusions
Our findings shed novel insights into the role of progenitors in CCO formation and pave the way for the robust generation of cardiac organoids, as a platform for future applications in disease modelling and drug screening in vitro.
Guidance of empirical antimicrobial therapy by surveillance cultures in high-risk neutropenic patients: a retrospective cohort study
Authors: de la Court Jara R. , Heijmans Jarom , Huynh Jennifer , Sieswerda Elske , de Jonge Nick A. , van Dijk Karin , Sigaloff Kim C. E. , Schade Rogier P. 
Published: December 2022

Abstract
Background
In neutropenic patients, bloodstream infections (BSI) significantly contribute to morbidity and mortality. Appropriate empirical antibiotic therapy (EAT) of BSI is essential, at the same time overconsumption of very broad-spectrum antibiotics should be avoided. We investigated: (1) whether surveillance cultures can predict BSI with third-generation cephalosporin –resistant Enterobacterales and Pseudomonas aeruginosa (3GC-R), (2) the effect of inappropriate empirical antimicrobial therapy (IEAT) on clinical outcome and (3) the potential reduction of carbapenem use when using surveillance cultures to guide therapy.

Methods
Retrospective study of adult patients with haematological malignancies with febrile episodes during chemotherapy-induced high-risk neutropenia in whom surveillance cultures were collected weekly. IEAT was defined as the absence of in vitro susceptibility of blood-isolates to the administered EAT. Clinical outcome (ICU admission and death) was evaluated within 30 days.

Results
A total of 673 febrile episodes occurred among 372 high-risk neutropenic patients. BSI was present in 20.1% (135/673), of which 25.9% (35/135) were due to Enterobacterales and P. aeruginosa. Of these, 17/35 were 3GC-R and 70.6% (12/17) were preceded by 3GC-R colonization. Negative predictive value of surveillance cultures for 3GC-R BSI was 99.1%. IEAT due to (3GC-R) BSI was not significantly associated with clinical outcome. Using surveillance cultures to guide EAT could potentially reduce carbapenem use by 82.8%, when compared to standard EAT with carbapenem.

Conclusions
This retrospective analysis shows that in patients with high-risk neutropenia, surveillance cultures can potentially reduce the use of carbapenems with infrequent IEAT for 3GC-R BSI and no negative impact on clinical outcome.
Estimation of Failure Mode of Mortar-Filled Sleeve Rebar Splices
Authors: Kim Hyong-Kee , Lee Moon-Sung 
Published: December 2022

AbstractIn order to establish a more rational structural design method for mortar-filled sleeve rebar splices, it is necessary to analyze and evaluate structural factors affecting the structural performance of these rebar splices. It is very desirable to be able to quantitatively estimate the failure mode of the splices at the design stage. A method for estimating the failure mode of mortar-filled sleeve rebar splices presented from the existing research is not clear because the boundary of failure mode is not expressed in formulas. There are also limitations using the methods because the research is based on limited number of test variables, insufficient number of test specimens, and the fact that only steel pipe sleeves were used. Therefore, to establish a more general and comprehensive failure mode estimation method, it needs to be presented in a more quantitative and explicit fashion and evaluated using more diverse variables. In this study, as part of an effort to generate basic data for the establishment of a more rational and quantitative structural design method for mortar-filled sleeve rebar splices, the failure mode estimation method is presented based on the existing bond strength equations of sleeve rebar splices. In addition, to examine the suitability of this failure mode estimation method, the failure modes of 303 sleeve rebar splices were evaluated. The evaluation results indicated that the failure mode estimation method for mortar-filled sleeve rebar splices proposed by this study would yield a failure mode estimation with a sufficiently practical accuracy.
Psychotic features, particularly mood incongruence, as a hallmark of severity of bipolar I disorder
Authors: Elowe Julien , Vallat Julie , Castelao Enrique , Strippoli Marie-Pierre F. , Gholam Mehdi , Ranjbar Setareh , Glaus Jennifer , Merikangas Kathleen , Lavigne Benjamin , Marquet Pierre , Preisig Martin , Vandeleur Caroline L. 
Published: December 2022

Abstract
Background
The occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment.

Methods
A sample of 162 treated patients with BD I (60.5% female, mean age = 41.4 (s.d: 10.2) years) was recruited within a large family study of mood disorders. Clinical, course and treatment characteristics relied on information elicited through direct diagnostic interviews, family history reports and medical records.

Results
(1) A total of 96 patients (59.3%) had experienced psychotic features over their lifetime. Among them, 44.8% revealed MI features at least once in their lives. (2) Patients with psychotic features were much less likely to be professionally active, revealed alcohol abuse more frequently and used health care, particularly inpatient treatment, more frequently than those without psychotic features. Within patients with psychotic symptoms, those with MI features showed more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts and comorbid cannabis dependence.

Conclusion
Our data provide additional support for both the distinction between BD-I with and without psychotic features as well as the distinction between MI and MC psychotic features. The more severe course of patients with psychotic features, and particularly those with MI psychotic features, highlights the need for thorough psychopathological evaluations to assess the presence of these symptoms to install appropriate treatment.
Reliability and validity of the Chinese version of the COVID-19 Phobia Scale
Authors: Xie Yuntian , Arpaci Ibrahim , Xiao Yahui , Meng Fanfei , Xie Ruotong 
Published: December 2022

Abstract
Background
The COVID-19 pandemic has become a source of fear worldwide and has negative mental health effects on the general population. In 2022, the epidemic continues to be characterized by many points, widespread and frequent in China, and the situation is serious and complex. To provide an effective and scientific tool, the study validated the Chinese version of the COVID-19 Phobia Scale (C19P-SC).

Methods
This study selected 1138 Chinese individuals (age ranged 13 to 80).

Results
Cronbach’s alpha coefficient for the C19P-SC was 0.93 (the coefficients of the four dimensions ranged from 0.75 to 0.85). The results of the confirmatory factor analysis supported the four-factor structure of the C19P-SC. Meanwhile, there was a positive and significant correlation between coronaphobia and state anxiety (r = 0.48, p < 0.001). The metric invariance hypothesis and the scalar invariance hypothesis were valid in the different subgroups. Significant multivariate effects of gender, education level, and identity differences on coronaphobia were found.

Conclusions
The Chinese version of the COVID-19 Phobia Scale has good psychometric properties and is suitable for measuring COVID-19 phobia in Chinese individuals.
Psychometric properties and factor structure of the Early Development Instrument in a sample of Jordanian children
Authors: Ababneh Emad G. , Duku Eric K. , Reid-Westoby Caroline , Gaskin Ashley , Janus Magdalena 
Published: December 2022

Abstract
Background
Investing in children’s early years can have a lasting positive effect, such as better academic outcomes throughout their school careers. In Jordan, investments have been made in early childhood development and early childhood care and education to improve children’s school readiness. School readiness comprises a range of abilities needed to succeed in school, including physical, emotional, social, and cognitive skills. To measure the impact of these investments on children’s school readiness, Jordan has been implementing the Early Development Instrument (EDI), a population-level, teacher-completed checklist of children’s school readiness, assessing children’s development in five main areas, referred to as domains.

Methods
The goal of the current study was to examine the psychometric properties of the Arabic version of the EDI, using data collected in 2018 on a sample of 5965 children in Jordan. The EDI was translated from the original English version to Arabic and adapted for use in Jordan. We conducted a categorical confirmatory factor analysis (CFA) for each of the five domains of the EDI and examined the reliability of the domains and subdomains using Cronbach’s alpha reliability coefficient.

Results
With few exceptions, the study results are in line with those of the analysis of the psychometric properties found with the original, Canadian English version of the EDI in a population of Canadian children. Results of CFAs demonstrated, for the most part, good model fits. Internal consistency indices of the domains ranged from 0.74 for physical health and well-being to 0.96 for social competence. For the subdomains, they ranged from 0.42 to 0.94.

Conclusions
Our results provide empirical support for the adaptation of the EDI for population monitoring of school readiness in Jordan. Validation of the Arabic adaptation opens up the possibility of assessing school readiness of young children in Jordan in comparison to the many other countries that have successfully adapted and applied the EDI.
Cost-effectiveness analysis of molecular testing for cytologically indeterminate thyroid nodules
Authors: Dharampal Navjit , Smith Kristine , Harvey Adrian , Paschke Ralf , Rudmik Luke , Chandarana Shamir 
Published: December 2022

Background Thyroid nodules affect up to 65% of the population. Although fine needle aspirate (FNA) cytology is the gold standard for diagnosis, 15–30% of results are indeterminate. Molecular testing may aid in the diagnosis of nodules and potentially reduce unnecessary surgery. However, these tests are associated with significant costs. The objective of this study was to evaluate the cost-effectiveness of Afirma, a commercially available molecular test, in cytologically indeterminate thyroid nodules. Methods The base case was a solitary thyroid nodule with no additional high-risk features and an indeterminate FNA. Decision tree analysis was performed from the single payer perspective with a 1-year time horizon. Costing data were collected through micro-costing methodology. A probabilistic sensitivity analysis was performed. The primary outcome was the incremental cost effectiveness ratio (ICER) of cost per thyroid surgery avoided. Results Over 1 year, mean cost estimates were $8176.28 with 0.58 effectiveness for the molecular testing strategy and $6016.83 with 0.07 effectiveness for current standard management. The ICER was $4234.22 per surgery avoided. At a willingness-to-pay (WTP) threshold of $5000 per surgery avoided, molecular testing is cost-effective with 63% certainty. Conclusion This cost-effectiveness analysis suggests utilizing Afirma for indeterminate solitary thyroid nodules is a cost-effective strategy for avoiding unnecessary thyroid surgery. With a $5000 WTP threshold, molecular testing has a 63% chance of being the more cost-effective strategy. The cost effectiveness varies based on the cost of the molecular test and the value of Afirma for patients with indeterminate thyroid nodules depends on the WTP threshold to avoid unnecessary thyroid surgery. Graphical Abstract