bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of brodalumab in improving itching and skin pain in Japanese patients with psoriasis: The ProLOGUE study
Authors: Honma Masaru , Kanai Yasumasa , Murotani Kenta , Ito Kei , Ohata Chika , Yamazaki Fumikazu , Saeki Hidehisa , Seishima Mariko , Mizutani Yoko , Kitabayashi Hiroki , Imafuku Shinichi 
Published: December 2022

AbstractItching and skin pain are bothersome symptoms of psoriasis, but evidence is limited regarding the treatment effectiveness on these symptoms in daily clinical settings. We assessed the changes in the levels of itching and skin pain after brodalumab treatment in Japanese patients with psoriasis using patient‐reported outcomes (PROs). Patients with psoriasis who have inadequate response to existing treatments were enrolled in the single‐arm, open‐label, multicenter, prospective ProLOGUE study and received brodalumab 210 mg subcutaneously in daily clinical practice. Psoriasis Area and Severity Index (PASI) and PRO assessments were performed at baseline and weeks 12 and 48. Seventy‐three patients (men, 82.2%; median age, 54.0 years) were enrolled. The Itch Numeric Rating Scale (NRS; p < 0.0001 at weeks 12 and 48) and Skin Pain NRS (week 12, p = 0.0004; week 48, p < 0.0001) scores significantly decreased from baseline. The Itch NRS score was significantly higher in patients with a Dermatology Life Quality Index (DLQI) score of ≥2 (vs. 0/1; p < 0.0001 at weeks 12 and 48) and in patients with a Treatment Satisfaction Questionnaire for Medication‐9 (TSQM‐9) global satisfaction domain score of ≤70% (vs. >70%; week 12, p = 0.0120; week 48, p = 0.0348). The Itch NRS score cutoff value for achieving a PASI score of ≤2, DLQI score of 0/1, and TSQM‐9 global satisfaction domain score of >70% was 1 at week 12 and 0 at week 48. Brodalumab treatment was associated with improvement in itching and skin pain in Japanese patients with psoriasis. An Itch NRS score of 0 can be a long‐term treatment goal for psoriasis (Japan Registry of Clinical Trials identifier: jRCTs031180037).
Leadership matters in democratic education: Calibrating the role of Principal in one democratic school
Authors: McCutcheon Fintan , Haynes Joanna 
Published: December 2022

Abstract
Through a series of conversations, Fintan McCutcheon and Joanna Haynes explore McCutcheon's reflections on school leadership in the contexts of the Educate Together movement (in the Republic of Ireland) and, specifically, in his aspiration to build an optimally democratic school in Balbriggan. Much of the academic and professional literature on school leadership depicts the role of school leaders as expressing a strong vision for the school, with charismatic communication and strategic skills, and putting explicit emphasis on high educational standards. On the ground, the school leader is required to maintain executive governance standards, is accountable to a range of hierarchies and audiences and is in a custodian role to traditions of school culture and human resource relationships. Taken together, these academic, professional and contractual obligations can corral the school leader into practice of limited scope, obstructed by protocol, risk-averse and curtailed in creativity and, in relation to developing a democratic school, lacking in the necessary room for innovation. The conversation focuses on the rough ground of incident and messiness, identified through critical moments of school life when the aspirations to be democratic, to lead democratically, to teach democracy and to create a sustaining democratic school culture are lived-out. Through this dialogue, the conversants observe a practice of school leadership grounded in practical reason. The dialogue touches on and threads congruence between the on-the-ground risk-taking, rule-breaking, action orientation, nuanced dialogue, passionate engagement and deep reflection that characterise day-to-day school leadership practice. It concludes with ideas concerning the dynamics of forms of democracy that can prevail.
De novo design of the global transcriptional factor Cra‐regulated promoters enables highly sensitive glycolysis flux biosensor for dynamic metabolic control
Authors: Zhu Yuan , Gao Huaxiao , Zhang Jian , Zhao Jingyu , Qi Qingsheng , Wang Qian 
Published: December 2022

AbstractGlycolytic flux is a fundamental index in microbial cell factories. A glycolytic flux biosensor that can monitor glucose metabolism efficiency is a promising strategy in rewiring metabolic flux to balance growth and biosynthesis. A key design feature of the glycolytic flux biosensors is the interaction between the global transcriptional factor Cra and its regulated promoters. However, overexpression and mutation of Cra has unpredictable effects on global metabolism in Escherichia coli. Therefore, new orthogonal biosensor design strategies should be developed to circumvent metabolic issues. In this report, the promoters in glycolytic flux biosensor were replaced with synthetic promoters of varying strengths or phage‐derived promoters, and the Cra DNA‐binding sites were deployed into promoters at different positions and distances to yield biosensors. The de nova biosensors that depended on Cra could sense Fructose‐1,6‐diphosphate (FBP) with broad dynamic ranges and low basal leakage. Then the negative‐response biosensors were applied to fine‐tune the target ATP synthesis gene, leading to the desired increase in pyruvate production (the highest 9.66 g/L) and cell growth. Moreover, the membrane synthesis gene plsC was also dynamically activated by the positive‐response biosensor, leading to effective accumulation of lycopene in the cell membrane and a 50‐fold increase in lycopene titre (100.3 mg/L) when compared with the control strain, demonstrating the effective and broader usages of our biosensors.
Associations among maternal characteristics, labour interventions, delivery mode and maternal antenatal complications in a NSW large rural town, and comparison to NSW state data
Authors: Noonan Sarah Helen Joy , Larkin Theresa Anne 
Published: December 2022

AbstractObjectiveTo determine associations between maternal characteristics, labour interventions, delivery mode and maternal antenatal complications in a NSW rural hospital, and compare these to state data.MethodsData (maternal characteristics, labour type, delivery mode and maternal antenatal complications) pertaining to women who had delivered a singleton birth at Griffith Base hospital were analysed.DesignRetrospective data analysis of Griffith Base Hospital ‘eMaternity’ databaseSettingSingle large rural town in NSW.ParticipantsWomen who delivered a singleton birth between July 2018 and June 2019 inclusive at Griffith Base Hospital.Main outcome measures1. Comparison of maternal characteristics of age, BMI, gravida, parity and gestation data between labour type (spontaneous, augmented, induced and planned caesarean section) and delivery modes (vaginal, instrumental vaginal and caesarean section). 2. Associations between labour type, augmentation or induction method, delivery mode and maternal antenatal complications. 3. Multiple regression analysis for influence of age, BMI, parity and labour type on emergency caesarean section outcome. 4. Comparison of maternal, labour and delivery data with NSW state data.ResultsAmong 457 women, there were higher rates of obesity and spontaneous labour, lower rates of planned caesarean section and augmented labour, and similar rates of induction of labour and emergency caesarean section, compared with NSW. Emergency caesarean section was significantly associated with older age (β = 0.163), and labour augmentation (β = 0.114) and induction (β = 0.169). Labour augmentation with synthetic oxytocin, and induction with balloon catheter, were associated with the highest rates of emergency caesarean section.ConclusionThis large rural town had fewer labour and delivery medical interventions compared with NSW overall. Augmentation and induction of labour contribute to increasing caesarean section rates: directly via associations with emergency caesarean section, and indirectly because previous caesarean section was the most common reason for elective caesarean section.
Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction
Authors: Yuan Penghui , Sun Taotao , Han Zhengyang , Chen Yinwei 
Published: December 2022

AbstractBackgroundErectile dysfunction and atherosclerosis are common cardiovascular complications in diseases. Clinical associations between erectile dysfunction and atherosclerosis have been noticed, but the specific mechanisms are not illustrated adequately.ObjectivesThe aim of the study was to further mine associated pathological mechanisms and genetic alterations of atherosclerosis in diabetes mellitus‐related erectile dysfunction.Materials and methodsSignificant atherosclerosis‐related genes were identified from transcriptome data of diabetes mellitus‐related erectile dysfunction and atherosclerosis‐related gene sets from DisGeNET and GeneCard databases. Functional enrichment and immune infiltration analyses were performed to clarify the biological roles and pathways as well as immune responses of significant atherosclerosis‐related gene sets. A protein–protein interaction network was constructed, and gene clusters were performed. Then, data of diabetic plaques and high‐glucose cavernosum endothelial cells were analyzed for validation. And hub atherosclerosis‐related gene sets were identified. Finally, expressed pattern of hub atherosclerosis‐related gene sets were explored by single‐cell profiling and immune analysis.ResultsIn total, 202 significant atherosclerosis‐related gene sets including 100 upregulated and 102 downregulated genes were identified. These genes were related to endothelial cell migration, inflammatory response, regulation of oxidative stress, and immune response. In immune infiltration, immature dendritic cells and monocytes showed differential expression between the diabetes mellitus‐related erectile dysfunction and control groups, A protein–protein interaction network containing 135 nodes was constructed. A hub atherosclerosis‐related gene set signature consisting of HBEGF, LOX, NQO1, and VLDLR was obtained by multi‐omics validation. In addition, Functional enrichment analysis revealed that hub atherosclerosis‐related gene sets were involved in oxidoreductase activity and extracellular matrix organization.Discussion and conclusionWe explored atherosclerosis‐related genetic changes and signaling pathways in diabetes mellitus‐related erectile dysfunction. HBEGF, LOX, NQO1, and VLDLR were identified as hub atherosclerosis‐related gene sets. These may serve as potential biomarkers for the clinical management of atherosclerosis and preventing further cardiovascular risks in diabetes mellitus‐related erectile dysfunction.
Testosterone therapy in diabetes and pre‐diabetes
Authors: Corona Giovanni , Vena Walter , Pizzocaro Alessandro , Vignozzi Linda , Sforza Alessandra , Maggi Mario 
Published: December 2022

AbstractBackgroundType 2 diabetes mellitus and pre‐diabetes are associated with reduced circulating testosterone levels. However, the role of testosterone replacement therapy in these patients is still conflicting.ObjectivesTo summarize and critically analyze available data on the possible effect of testosterone administration in men with glucose abnormalities.Materials and methodsA comprehensive systematic review was performed. When available, meta‐analytic data were preferred. To better analyze the relationship between testosterone and the pre‐diabetes condition, a systematic analysis was performed and the data obtained with the latter search were used for a meta‐analytic approach. Finally, clinical data derived from a consecutive series of 4682 patients seeking medical care for sexual dysfunction at the University of Florence were also considered.ResultsPatients with impaired fasting glucose were characterized by a 3 nmol/L lower level of total testosterone when compared to controls. Similarly, impaired fasting glucose was associated with a 1.8‐fold increased risk of hypogonadism, when compared to subjects with normal glucose levels. Waist circumference and body mass index resulted as being the best predictors of reduced total testosterone levels. Secondary hypogonadism was two times higher in subjects with impaired fasting glucose when compared to rates observed in the general population. Testosterone replacement therapy was able to improve body composition, insulin resistance, and glucose profile both in impaired fasting glucose and type 2 diabetes mellitus whereas its role on body weight, lipid profile, and sexual function was less evident.Discussion and conclusionWeight loss and physical activities are able to improve both metabolic profile and testosterone levels. The combined approach of testosterone replacement therapy and lifestyle modifications could be suggested in symptomatic hypogonadal men to better motivate patients to perform physical activity which can eventually result in weight loss as well as metabolic profile and sexual function improvement. Whether or not these approaches can prevent the development of type 2 diabetes mellitus from pre‐clinical conditions requires more studies.
Quantitative end‐tidal carbon dioxide at initiation of resuscitation may help guide the ventilation of infants born at less than 30 weeks gestation
Authors: Shah Dharmesh , Tracy Mark , Hinder Murray , Badawi Nadia 
Published: December 2022

AbstractAimEstimation of end‐tidal carbon dioxide (EtCO2) with capnography can guide mask ventilation in infants born at less than 30 weeks of gestation. Chemical‐sensitive colorimetric devices to detect CO2 are widely used at resuscitation. We aimed to quantify EtCO2 in the first breaths following initiation of mask ventilation at birth and correlated need for endotracheal intubation.MethodsInfants <30 weeks gestation receiving mask ventilation were randomised into two groups of mask‐hold technique (one‐person vs. two‐person). Data on EtCO2 in the first 30 breaths, time to achieve 5 mmHg, 10 mmHg and 15 mmHg CO2 using a respiratory function monitor was determined.ResultsTwenty‐five infants with a mean gestation of 27.3 (±3 weeks) and mean birth weight 920.4 (±188.3 g) were analysed. The median EtCO2 was 5.6 mmHg in the first 10 breaths, whereas it was 12.6 mmHg for 11–20 breaths and 18 mmHg for 21–30 breaths. There was no significant difference in maximum median EtCO2 for the first 20 breaths, although EtCO2 was significantly lower in infants who were intubated (32.0 vs. 15.0, p = 0.018).ConclusionEtCO2 monitoring in infants <30 weeks gestation at birth is feasible and reflective of alveolar ventilation. EtCO2 may help guide ventilation of preterm infants at birth.
Effects of social norms and message framing on reducing the stigma of gynecological diseases: A cognitive‐affective‐behavioral model
Authors: Dong Yujie , Chen Meng , Wu Yuheng 
Published: December 2022

AbstractThis paper presents an experiment exploring message strategies to reduce the stigma of gynecological diseases and promote women's sexual and reproductive health. Drawing on the cognitive‐affective‐behavioral model of stigma, we propose that social norms and message framing as two message strategies, respectively, address the cognitive and affective components of the stigma of gynecological diseases, which lead to desired changes in the help‐seeking intention as the behavioral component. We conducted a 3 (no norm vs. descriptive norm vs. descriptive plus injunctive norms) by 2 (gain‐framed vs. loss‐framed) between‐subject experiment (N = 202). The results reveal that messages with the combination of descriptive and injunctive norms reduce the greatest cognitive components of stigma. Gain‐framed messages induced fewer affective components than loss‐framed ones. The results suggest that changes in the cognitive and affective components of stigma may sequentially lead to favorable changes in the behavioral component. This study contributes to public understanding of the stigma of gynecological diseases by disentangling the various components and identifying the specific message strategies for stigma reduction.
Exploratory pharmacovigilance with machine learning in big patient data: A focused scoping review
Authors: Kaas‐Hansen Benjamin Skov , Gentile Simona , Caioli Alessandro , Andersen Stig Ejdrup 
Published: December 2022

AbstractBackgroundMachine learning can operationalize the rich and complex data in electronic patient records for exploratory pharmacovigilance endeavours.ObjectiveThe objective of this review is to identify applications of machine learning and big patient data in exploratory pharmacovigilance.MethodsWe searched PubMed and Embase and included original articles with an exploratory pharmacovigilance purpose, focusing on medicinal interventions and reporting the use of machine learning in electronic patient records with ≥1000 patients collected after market entry.FindingsOf 2557 studies screened, seven were included. Those covered six countries and were published between 2015 and 2021. The most prominent machine learning methods were random forests, logistic regressions, and support vector machines. Two studies used artificial neural networks or naive Bayes classifiers. One study used formal concept analysis for association mining, and another used temporal difference learning. Five studies compared several methods against each other. The numbers of patients in most data sets were in the order of thousands; two studies used what can more reasonably be considered big data with >1 000 000 patients records.ConclusionDespite years of great aspirations for combining machine learning and clinical data for exploratory pharmacovigilance, only few studies still seem to deliver somewhat on these expectations.
Acquired Haemophilia A in four north European countries: survey of 181 patients
Authors: Lindahl Rickard , Nummi Vuokko , Lehtinen Anna‐Elina , Szanto Timea , Hiltunen Leena , Olsson Anna , Glenthoej Andreas , Chaireti Roza , Vaide Ines , Funding Eva , Zetterberg Eva 
Published: December 2022

SummaryAcquired haemophilia A (AHA) is a rare bleeding disorder caused by acquired antibodies against coagulation factor VIII. In the Nordic countries, treatment and outcomes have not been studied in recent times. To collect retrospective data on patients diagnosed with AHA in the Nordic countries between 2006 and 2018 and compare demographic data and clinical outcomes with previously published reports, data were collected by six haemophilia centres: three Swedish, one Finnish, one Danish and one Estonian. The study included 181 patients. Median age at diagnosis was 76 (range 5–99) years, with even gender distribution. Type and severity of bleeding was comparable to that in the large European Acquired Haemophilia Registry study (EACH2). Bleedings were primarily treated with activated prothrombin complex concentrate (aPCC) with a high success rate (91%). For immunosuppressive therapy, corticosteroid monotherapy was used most frequently and this may be the cause of the overall lower clinical remission rate compared to the EACH2 study (57% vs. 72%). Survey data on 181 patients collected from four north European countries showed similar demographic and clinical features as in previous studies on AHA. aPCC was used more frequently than in the EACH2 study and the overall remission rate was lower.
Survival rate prediction of nasopharyngeal carcinoma patients based on MRI and gene expression using a deep neural network
Authors: Zhang Qihao , Wu Gang , Yang Qianyu , Dai Ganmian , Li Tiansheng , Chen Pianpian , Li Jiao , Huang Weiyuan 
Published: December 2022

AbstractTo achieve a better treatment regimen and follow‐up assessment design for intensity‐modulated radiotherapy (IMRT)‐treated nasopharyngeal carcinoma (NPC) patients, an accurate progression‐free survival (PFS) time prediction algorithm is needed. We propose developing a PFS prediction model of NPC patients after IMRT treatment using a deep learning method and comparing that with the traditional texture analysis method. One hundred and fifty‐one NPC patients were included in this retrospective study. T1‐weighted, proton density and dynamic contrast‐enhanced magnetic resonance (MR) images were acquired. The expression level of five genes (HIF‐1α, EGFR, PTEN, Ki‐67, and VEGF) and infection of Epstein–Barr (EB) virus were tested. A residual network was trained to predict PFS from MR images. The output as well as patient characteristics were combined using a linear regression model to provide a final PFS prediction. The prediction accuracy was compared with that of the traditional texture analysis method. A regression model combining the deep learning output with HIF‐1α expression and Epstein–Barr infection provides the best PFS prediction accuracy (Spearman correlation R2 = 0.53; Harrell's C‐index = 0.82; receiver operative curve [ROC] analysis area under the curve [AUC] = 0.88; log‐rank test hazard ratio [HR] = 8.45), higher than a regression model combining texture analysis with HIF‐1α expression (Spearman correlation R2 = 0.14; Harrell's C‐index =0.68; ROC analysis AUC = 0.76; log‐rank test HR = 2.85). The deep learning method does not require a manually drawn tumor region of interest. MR image processing using deep learning combined with patient characteristics can provide accurate PFS prediction for nasopharyngeal carcinoma patients and does not rely on specific kernels or tumor regions of interest, which is needed for the texture analysis method.
Genetic diversity in global populations of the critically endangered addax (Addax nasomaculatus) and its implications for conservation
Authors: Dicks Kara L. , Ball Alex D. , Banfield Lisa , Barrios Violeta , Boufaroua Mohamed , Chetoui Abdelkader , Chuven Justin , Craig Mark , Faqeer Mohammed Yousef Al , Garba Hamissou Halilou Mallam , Guedara Hela , Harouna Abdoulaye , Ivy Jamie , Najjar Chawki , Petretto Marie , Pusey Ricardo , Rabeil Thomas , Riordan Philip , Senn Helen V. , Taghouti Ezzedine , Wacher Tim , Woodfine Tim , Gilbert Tania 
Published: December 2022

AbstractThreatened species are frequently patchily distributed across small wild populations, ex situ populations managed with varying levels of intensity and reintroduced populations. Best practice advocates for integrated management across in situ and ex situ populations. Wild addax (Addax nasomaculatus) now number fewer than 100 individuals, yet 1000 of addax remain in ex situ populations, which can provide addax for reintroductions, as has been the case in Tunisia since the mid‐1980s. However, integrated management requires genetic data to ascertain the relationships between wild and ex situ populations that have incomplete knowledge of founder origins, management histories, and pedigrees. We undertook a global assessment of genetic diversity across wild, ex situ and reintroduced populations in Tunisia to assist conservation planning for this Critically Endangered species. We show that the remnant wild populations retain more mitochondrial haplotypes that are more diverse than the entirety of the ex situ populations across Europe, North America and the United Arab Emirates, and the reintroduced Tunisian population. Additionally, 1704 SNPs revealed that whilst population structure within the ex situ population is minimal, each population carries unique diversity. Finally, we show that careful selection of founders and subsequent genetic management is vital to ensure genetic diversity is provided to, and minimize drift and inbreeding within reintroductions. Our results highlight a vital need to conserve the last remaining wild addax population, and we provide a genetic foundation for determining integrated conservation strategies to prevent extinction and optimize future reintroductions.