bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon regulatory factor 4 as a therapeutic target in adult T-cell leukemia lymphoma
Authors: Rauch Daniel A. , Olson Sydney L. , Harding John C. , Sundaramoorthi Hemalatha , Kim Youngsoo , Zhou Tianyuan , MacLeod A. Robert , Challen Grant , Ratner Lee 
Published: August 2020

Abstract
Background
Adult T-cell leukemia lymphoma (ATLL) is a chemotherapy-resistant malignancy with a median survival of less than one year that will afflict between one hundred thousand and one million individuals worldwide who are currently infected with human T-cell leukemia virus type 1. Recurrent somatic mutations in host genes have exposed the T-cell receptor pathway through nuclear factor κB to interferon regulatory factor 4 (IRF4) as an essential driver for this malignancy. We sought to determine if IRF4 represents a therapeutic target for ATLL and to identify downstream effectors and biomarkers of IRF4 signaling in vivo.

Results
ATLL cell lines, particularly Tax viral oncoprotein-negative cell lines, that most closely resemble ATLL in humans, were sensitive to dose- and time-dependent inhibition by a next-generation class of IRF4 antisense oligonucleotides (ASOs) that employ constrained ethyl residues that mediate RNase H-dependent RNA degradation. ATLL cell lines were also sensitive to lenalidomide, which repressed IRF4 expression. Both ASOs and lenalidomide inhibited ATLL proliferation in vitro and in vivo. To identify biomarkers of IRF4-mediated CD4 + T-cell expansion in vivo, transcriptomic analysis identified several genes that encode key regulators of ATLL, including interleukin 2 receptor subunits α and β, KIT ligand, cytotoxic T-lymphocyte-associated protein 4, and thymocyte selection-associated high mobility group protein TOX 2.

Conclusions
These data support the pursuit of IRF4 as a therapeutic target in ATLL with the use of either ASOs or lenalidomide.
Selling second best: how infant formula marketing works
Authors: Hastings Gerard , Angus Kathryn , Eadie Douglas , Hunt Kate 
Published: August 2020

Abstract
Background
Despite the clear policy intent to contain it, the marketing of formula milk remains widespread, powerful and successful. This paper examines how it works.

Methods
The study comprised a mix of secondary analysis of business databases and qualitative interviews with marketing practitioners, some of whom had previously worked in formula marketing.

Results
The World Health Assembly Code aims to shield parents from unfair commercial pressures by stopping the inappropriate promotion of infant formula. In reality marketing remains widespread because some countries (e.g. the USA) have not adopted the Code, and elsewhere industry has developed follow-on and specialist milks with which they promote formula by proxy. The World Health Assembly has tried to close these loopholes by extending its Code to these products; but the marketing continues. The campaigns use emotional appeals to reach out to and build relationships with parents and especially mothers. Evocative brands give these approaches a human face. The advent of social media has made it easier to pose as the friend and supporter of parents; it is also providing companies with a rich stream of personal data with which they hone and target their campaigns.
The formula industry is dominated by a small number of extremely powerful multinational corporations with the resources to buy the best global marketing expertise. Like all corporations they are governed by the fiduciary imperative which puts the pursuit of profits ahead of all other concerns. This mix of fiscal power, sophisticated marketing, and single-mindedness is causing great harm to public health.

Conclusions
Formula marketing is widespread and using powerful emotional techniques to sell parents a product that is vastly inferior to breast milk. There is an urgent need to update and strengthen regulation.
Pulmonary epithelial–myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations: a case report
Authors: Yanagawa Naoki , Sato Ayaka , Nishiya Masao , Suzuki Masamichi , Sugimoto Ryo , Osakabe Mitsumasa , Uesugi Noriyuki , Saito Hajime , Sugai Tamotsu 
Published: August 2020

Abstract
Background
Pulmonary epithelial–myoepithelial carcinoma is a rare subtype of lung cancer. Because of its rarity, the molecular information on this carcinoma is insufficient.

Case presentation
We report a case of pulmonary epithelial–myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations in a 76-year-old woman. Computed tomography revealed a tumor located in the left lower lung. Thoracoscopic left lower lobectomy was performed. Histopathologically, the tumor consisted of duct-like structures and polygonal and spindle cell features. The duct-like structures were composed of two distinct cell layers. The inner layer consisted of cuboidal cells that were positive for pan-cytokeratin and negative for p63, whereas the outer layer consisted of polygonal and spindle cells that were positive for p63 and weakly positive for pan-cytokeratin. We evaluated mutations in AKT1, BRAF, CTNNB1, HRAS, KRAS and PIK3CA but did not detect any mutations.

Conclusion
Pulmonary epithelial–myoepithelial carcinoma is a rare subtype of lung cancer, with only 56 previous cases reported in the English literature. The genetic alterations in pulmonary epithelial–myoepithelial carcinoma are still unknown. We examined the 6 genes mutation analysis, however no mutation was detected.
Impact of the therapeutic positioning report in the P&R process in Spain: analysis of orphan drugs approved by the European Commission and reimbursed in Spain from 2003 to 2019
Authors: Badia Xavier , Vico Tania , Shepherd John , Gil Alicia , Poveda-Andrés José Luis , Hernández César 
Published: August 2020

Abstract
Background
Pricing and reimbursement decisions for orphan drugs are faced with differences access between European countries depending on each reimbursement policies, evaluation processes and timings. In 2013, the therapeutic positioning report was introduced in the pricing and reimbursement process in Spain. The present study aims to identify orphan drugs authorised in Spain and approved by the European Commission between January 2003 and December 2019, analyse the impact of the therapeutic positioning report in the pricing and reimbursement process of orphan drugs in Spain and to assess additional potential criteria that could influence pricing and reimbursement decisions for orphan drugs.

Results
Ninety-four orphan drugs have been approved by the European Commission between January 2003 and December 2019 and have marketing authorisation in Spain. Out of the 94 orphan drugs, 46 (48.9%) had received pricing and reimbursement approval. Before the inclusion of the therapeutic positioning report in year 2013, the mean time from European Commission approval to pricing and reimbursement approval for orphan drugs in Spain was 25.1 ± 16.5. After 2013, timelines have been reduced by an average of 9 months. The mean regulatory time from European Commission approval to Spanish marketing authorisation has decreased nearly 4 months (from 7.5 ± 10.2 months in years 2003–2013 to 3.8 ± 7.6 months in years 2014–2019). The instauration of the therapeutic positioning report could be associated with a reduction of the mean time from the Spanish marketing authorisation to pricing and reimbursement approval by an average of 5 months (from 17.3 ± 13.1 months in years 2003–2013 to 12.3 ± 5 months in years 2014–2019). In addition, orphan drugs with a positive conclusion in the therapeutic positioning report would be more likely to be reimbursed in Spain (p < 0,0001).

Conclusions
This study shows that the therapeutic positioning report plays a key role in the pricing and reimbursement process in Spain. A positive conclusion of the therapeutic positioning report seems to favourably affect pricing and reimbursement decisions in Spain and, since its introduction, has also contributed to reduce pricing and reimbursement approval timelines in Spain.
Reporting of key methodological and ethical aspects of cluster trials in hemodialysis require improvement: a systematic review
Authors: Al-Jaishi Ahmed A. , Carroll Kelly , Goldstein Cory E. , Dixon Stephanie N. , Garg Amit X. , Nicholls Stuart G. , Grimshaw Jeremy M. , Weijer Charles , Brehaut Jamie , Thabane Lehana , Devereaux P. J. , Taljaard Monica 
Published: August 2020

AbstractBackgroundThe hemodialysis setting is suitable for trials that use cluster randomization, where intact groups of individuals are randomized. However, cluster randomized trials (CRTs) are complicated in their design, analysis, and reporting and can pose ethical challenges. We reviewed CRTs in the hemodialysis setting with respect to reporting of key methodological and ethical issues.MethodsWe conducted a systematic review of CRTs in the hemodialysis setting, published in English, between 2000 and 2019, and indexed in MEDLINE or Embase. Two reviewers extracted data, and study results were summarized using descriptive statistics.ResultsWe identified 26 completed CRTs and five study protocols of CRTs. These studies randomized hemodialysis centers (n = 17, 55%), hemodialysis shifts (n = 12, 39%), healthcare providers (n = 1, 3%), and nephrology units (n = 1, 3%). Trials included a median of 28 clusters with a median cluster size of 20 patients. Justification for using a clustered design was provided by 15 trials (48%). Methods that accounted for clustering were used during sample size calculation in 14 (45%), during analyses in 22 (71%), and during both sample size calculation and analyses in 13 trials (42%). Among all CRTs, 26 (84%) reported receiving research ethics committee approval; patient consent was reported in 22 trials: 10 (32%) reported the method of consent for trial participation and 12 (39%) reported no details about how consent was obtained or its purpose. Four trials (13%) reported receiving waivers of consent, and the remaining 5 (16%) provided no or unclear information about the consent process.ConclusionThere is an opportunity to improve the conduct and reporting of essential methodological and ethical issues in future CRTs in hemodialysis.Review RegistrationWe conducted this systematic review using a pre-specified protocol that was not registered.
Social determinants and behavioural factors influencing toothbrushing frequency among primary school children in rural Australian community of Lithgow, New South Wales
Authors: Arora Amit , Nargundkar Subrat , Fahey Paul , Joshua Hema , John James Rufus 
Published: August 2020

Abstract
Objective
This study aims to determine the social determinants and behavioural factors influencing frequency of toothbrushing among primary school children residing in the rural community of Lithgow in New South Wales, Australia. All six primary schools of Lithgow were approached to participate in a cross-sectional survey prior to implementation of water fluoridation. A validated oral health survey questionnaire was completed by 703 parents of the children. Multivariable logistic regression analysis was employed to determine significant predictors associated with frequency of toothbrushing.

Results
Parents with a positive attitude towards water fluoridation had 74% higher odds (OR = 1.74, 95% CI 1.17–2.60) of their children brushing twice or more daily. Children living in a single parent household had 34% reduced odds (OR = 0.66, 95% CI 0.43–0.99) of brushing twice daily. Poor maternal oral health was significantly associated with suboptimal dental hygiene practices in children, where mothers who had any tooth extracted had 7% reduced odds of their children brushing their teeth twice or more daily (OR = 0.93, 95% CI 0.90–0.97). Subsequently, children with increased consumption of chocolates per day were less likely to brush twice or more daily. Finally, children with dental insurance had two times higher odds (OR = 2.04, 95% CI 1.40–2.96) of brushing twice daily.
Blood glucose response to a calamansi drink in healthy adults: a non-randomised study
Authors: Siner Angela , Sevanesan Mauna Sree , Ambomai Tati , Abd. Wahab Zakiah , Lasem Liwan 
Published: August 2020

Abstract
Objective
Glycaemic Index (GI) ranks the body’s response to carbohydrate content in food such that high GI food increases postprandial blood glucose levels. One of the popular drinks at food and beverage outlets is a drink made from calamansi, a citrus that is believed not to induce an increase in blood glucose levels. In this non-randomised single-blind (participants) study, capillary blood from 10 healthy males were sampled following consumption of either glucose or the calamansi drink. The blood glucose measurements were then used to calculate the GI for the drink.

Results
The GI of the calamansi drink tested was calculated as 37, a value within the range of low GI foods.
Trial registration Clinical Trials identifier NCT04462016; Retrospectively registered on July 1, 2020.
Effects of eradication of Helicobacter pylori on oral malodor and the oral environment: a single-center observational study
Authors: Suzuki Nao , Beppu Richiko , Yoneda Masahiro , Takeshita Toru , Asakawa Mikari , Yamashita Yoshihisa , Hanioka Takashi , Hirofuji Takao , Shinohara Tetsuo 
Published: August 2020

Abstract
Objective
Although a relationship between Helicobacter pylori and oral malodor has been suggested, it remains to be confirmed. One reason for this is that many studies assess oral malodor subjectively. Another reason for the uncertainty is that the reduction in oral malodor may be due to the effect of antibiotics on the oral microbiota. In this study, changes in oral malodor along with the eradication treatment of H. pylori were investigated by organoleptic test and gas chromatography. In addition, the salivary bacterial composition and clinical parameters were analyzed.

Results
The organoleptic test score, hydrogen sulfide and dimethyl sulfide concentrations, and all clinical parameters except for tongue-coating score were significantly decreased at 1 week compared with baseline. Although antibiotic treatment also altered the overall composition of the salivary bacterial population, it had recovered at 7 weeks. On the date that H. pylori was determined to have been eradicated from all of the subjects (7 weeks after treatment), only the organoleptic test score was significantly lower compared with baseline. The hydrogen sulfide and dimethyl sulfide concentrations were non-significantly lower than those at baseline.
Genomic resources and toolkits for developmental study of whip spiders (Amblypygi) provide insights into arachnid genome evolution and antenniform leg patterning
Authors: Gainett Guilherme , Sharma Prashant P. 
Published: August 2020

AbstractBackgroundThe resurgence of interest in the comparative developmental study of chelicerates has led to important insights, such as the discovery of a genome duplication shared by spiders and scorpions, inferred to have occurred in the most recent common ancestor of Arachnopulmonata (a clade comprising the five arachnid orders that bear book lungs). Nonetheless, several arachnid groups remain understudied in the context of development and genomics, such as the order Amblypygi (whip spiders). The phylogenetic position of Amblypygi in Arachnopulmonata posits them as an interesting group to test the incidence of the proposed genome duplication in the common ancestor of Arachnopulmonata, as well as the degree of retention of duplicates over 450 Myr. Moreover, whip spiders have their first pair of walking legs elongated and modified into sensory appendages (a convergence with the antennae of mandibulates), but the genetic patterning of these antenniform legs has never been investigated.ResultsWe established genomic resources and protocols for cultivation of embryos and gene expression assays by in situ hybridization to study the development of the whip spiderPhrynus marginemaculatus. Using embryonic transcriptomes from three species of Amblypygi, we show that the ancestral whip spider exhibited duplications of all ten Hox genes. We deploy these resources to show that paralogs of the leg gap genesdachshundandhomothoraxretain arachnopulmonate-specific expression patterns inP. marginemaculatus. We characterize the expression of leg gap genesDistal-less,dachshund-1/2andhomothorax-1/2in the embryonic antenniform leg and other appendages, and provide evidence that allometry, and by extension the antenniform leg fate, is specified early in embryogenesis.ConclusionThis study is the first step in establishingP. marginemaculatusas a chelicerate model for modern evolutionary developmental study, and provides the first resources sampling whip spiders for comparative genomics. Our results suggest that Amblypygi share a genome duplication with spiders and scorpions, and set up a framework to study the genetic specification of antenniform legs. Future efforts to study whip spider development must emphasize the development of tools for functional experiments inP. marginemaculatus.
Life-threatening disseminated enterovirus infection during combined rituximab and ibrutinib maintenance treatment for mantle cell lymphoma: a case report
Authors: Higer Maximilian , Cana Denis , Podlech Juergen , Schadmand-Fischer Simin , Schwarting Andreas , Teschner Daniel , Theobald Matthias , Wölfel Thomas , Hess Georg 
Published: August 2020

Abstract
Background
Rituximab is a well-established component of treatment regimens for B-cell non-Hodgkin lymphoma. Rituximab binds the CD20 antigen on the surface of B lymphocytes, causing an enhanced clearance of malignant and benign B cells. Thus, rituximab leads to depletion of normal B lymphocytes as well, which can cause substantial immunodeficiency. Ibrutinib inhibits the Bruton tyrosine kinase and thereby B-cell activity. It is used for the treatment of different B-lymphocyte malignancies, such as mantle cell lymphoma. Recently, the combination of both drugs has been tested in various clinical scenarios.

Case presentation
We present a case of disseminated enterovirus infection resulting from combined rituximab and ibrutinib maintenance treatment in a 57-year-old Caucasian patient. with mantle cell lymphoma. Initially presenting with myositis symptoms, further diagnostic investigation revealed myocarditis, enteritis, myeloencephalitis, and hepatitis. These organ manifestations led to potentially life-threatening complications such as rhabdomyolysis, delirium, and heart rhythm disturbances. After treatment with high-dose intravenous immunoglobulins, virus clearance was achieved and organ functions could be restored.

Conclusions
This case emphasizes the risk of combined therapy with rituximab/ibrutinib for severe immune-related side effects with the necessity of continuous patient monitoring. High-dose intravenous therapy should be considered as treatment for severe enterovirus infection. In severe enterovirus infections, we recommend subtyping for the development of efficient preventive and therapeutic strategies.
Efficacy assessment of mesenchymal stem cell transplantation for burn wounds in animals: a systematic review
Authors: Yi Hanxiao , Wang Yang , Yang Zhen , Xie Zhiqin 
Published: August 2020

Abstract
Background
Clinically, severe burns remain one of the most challenging issues, but an ideal treatment is yet absent. Our purpose is to compare the efficacy of stem cell therapy in a preclinical model of burn wound healing.

Methods
Research reports on mesenchymal stem cells (MSCs) for burn wound healing were retrieved from 5 databases: PubMed, Embase, MEDLINE, Web of Science, and the Cochrane Library. The primary outcomes reported in this article include the un-healing rate of the wound area, the closure rate, and the wound area. Secondary outcomes included CD-31, vascular density, interleukin (IL)-10, thickness of eschar tissue, vascular endothelial growth factor (VEGF), and white blood cell count. Finally, a subgroup analysis was conducted to explore heterogeneity that potentially impacted the primary outcomes. A fixed-effects model with a 95% confidence interval (CI) was performed when no significant heterogeneity existed. Otherwise, a random-effects model was used. All data analysis was conducted by using Engauge Digitizer 10.8 and R software.

Results
Twenty eligible articles were finally included in the analysis. Stem cell therapy greatly improved the closure rate (2.00, 95% CI 0.52 to 3.48, p = 0.008) and compromised the wound area (− 2.36; 95% CI − 4.90 to 0.18; p = 0.069) rather than the un-healing rate of the wound area (− 11.10, 95% CI − 32.97 to 10.78, p = 0.320). Though p was 0.069, there was a trend toward shrinkage of the burn wound area after stem cell therapy. Vascular density (4.69; 95% CI 0.06 to 9.31; p = 0.047) and thickness of eschar tissue (6.56, 95% CI 1.15 to 11.98, p = 0.017) were also discovered to be significantly improved in the burn site of stem cell-treated animals. Moreover, we observed that animals in the stem cell group had an increased white blood cell count (0.84, 95% CI 0.01 to 1.66, p = 0.047) 5 days post treatment. Other indicators, such as VEGF (p = 0.381), CD-31 (p = 0.335) and IL-10 (p = 0.567), were not significantly impacted.

Conclusions
Despite limited data from preclinical trials, this meta-analysis suggests that stem cell therapy is curative in decreasing the burn wound area and provides some insights into future clinical studies of stem cell therapy for burns.
Jaws of a large belemnite and an ammonite from the Aalenian (Middle Jurassic) of Switzerland
Authors: Klug Christian , Etter Walter , Hoffmann René , Fuchs Dirk , De Baets Kenneth 
Published: August 2020

AbstractAlthough belemnite rostra can be quite abundant in Jurassic and Cretaceous strata, the record of belemnite jaws was limited to a few specimens from Germany and Russia. Here, we describe and figure three cephalopod jaws from the Middle Jurassic Opalinus Clay of northern Switzerland. Although flattened, the carbonaceous fossils display enough morphological information to rule out an ammonoid, nautiloid or octobrachian origin of the two larger jaws. Their similarities to belemnite jaws from Germany and Russia conforms with our interpretation of these specimens as belemnite jaws. Based on their rather large size, we tentatively assign these two jaws to the megateuthididAcrocoelites conoideus. The third jaw is a rather small upper jaw of an ammonoid. SinceLeioceras opalinumis by far the most common ammonite in this unit in northern Switzerland, we tentatively suggest that the upper jaw belongs to this species.