bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial
Authors: Wang Changjun , Lin Yan , Zhou Yidong , Mao Feng , Zhu Hanjiang , Guan Jinghong , Zhang Xiaohui , Shen Songjie , Huang Xin , Chen Chang , Yao Ru , Zhao Jialin , Sun Qiang 
Published: July 2020

Abstract
Background
HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting.

Methods/design
The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS.

Discussion
To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients.

Trial registration
ClinicalTrials.gov, ID: NCT03910712. Registered on 10 Apr. 2019.
Spontaneous resolution of a traumatic cataract in a patient with an open-globe ocular injury: a case report
Authors: Zhang Yu-ting , Du Li-qun , Liu Mei , Zhu Jing 
Published: July 2020

Abstract
Background
We report a case of spontaneous resolution of a traumatic cataract in a patient with an open-globe ocular injury. This case highlights the importance of conservative management in these types of cases, as excellent visual outcome is possible without invasive surgical intervention.

Case presentation
A 13-year-old boy presented with a corneal laceration in the left eye caused by a neuter pen. He underwent emergency repair of the corneal laceration under general anesthesia, and at 3 days post-op, a dense posterior cortical cataract was observed. Based on the patient’s age and normal visual development, in addition to preserving accommodative potential, the patient received conservative management and follow-up. Interestingly, the cataract spontaneously resolved over the following 9 months and the corrected distance visual acuity in the injured eye was restored from finger counting at 50 cm, to 20/25 + 3.

Conclusions
To optimize treatment in pediatric traumatic cataract, several critical factors such as age, visual development and the preservation of accommodative potential, need to be comprehensively considered. Conservative management with lens preservation is important to consider in young, traumatic cataract patients where invasive surgical intervention may not be required.
The usage of over-the-counter products by private insured patients in Germany – a claims data analysis with focus on complementary medicine
Authors: Goetz Katja , Kalder Matthias , Albert Ute-Susann , Jacke Christian O. 
Published: July 2020

Abstract
Background
An important contribution to well-being of human beings can be observed by the use of self-medication products that is reflected in the constantly growing volume of over-the-counter (OTC) drugs. The aim of the current study was to extend the measurement concept for OTCs by exploring the relevance of the peripheral assortment provided by the widely accepted framework of the Anatomical Therapeutical and Chemical (ATC) classification of the WHO.

Methods
The focus was on the prescriptions and drug-related receipts submitted by privately insured persons to 18 private health insurers (PHIs) in Germany from the year 2016. The age- and gender-specific average claims amount per risks of outpatient drug expenditure were used as weights to scale up the relative distributions of the item amounts. The ATC-classification defines the commodity groups and discriminates between the main and the peripheral assortment. A descriptive analysis assessed the OTC frequencies and sum scores of the product groups within the main and peripheral assortment whereby the study group explored and assessed the relevance of each category independently according to the OTCs and integrative medicines.

Results
The analysis included 22.1 Mio. packages from the main assortment and examined 10.1 Mio. packages from the peripheral assortment. The latter was examined thoroughly and the commodity groups “Pharmaceutical food products”, “Medicinal products for special therapy options” and particular “Hygiene and body care products” meet the defined requirements for OTCs relevant for integrative medicines. A high proportion of OTC products from the peripheral assortment was associated with the categories “medicinal products for special therapy options”. Homeopathy and anthroposophy present two special therapy options, which are relevant for the extended OTC measurement.

Conclusions
The analysis of OTC drugs is feasible when the main and the peripheral assortment is available and enable to integrate about 18% of all OTCs, which are neglected by the common ATC-based approach. The presented extended approach may help to identify potential users of OTCs or people in need of OTC use. In case of the highly disputed homeopathy and anthroposophy products, more research among interactions with prescriptions drugs (Rx), nutrition’s and other potentially harmful exposures is recommended.
A social-ecological examination into the research, policy and health service delivery environment related to early marriage and sexual and gender-based violence among youth in Jordan
Authors: Gausman Jewel , Othman Areej , Dababneh Abeer , Dabobe Maysoon , Hamad Iqbal , Daas Insaf , Langer Ana 
Published: July 2020

Abstract
Background
The determinants of sexual- and gender-based violence (SGBV) and early marriage are embedded across different levels of the social ecological system, including at the individual, family, community, and policy levels. In Jordan and the Middle East, SGBV, honor killing, and early marriage are priority public health and human rights issues that often overlap, and affect a significant percentage of youth. Jordan is home to a large number of refugees from across the Middle East, who may be even more vulnerable to these forms of violence than the local youth. The purpose of this analysis is to 1) synthesize the existing literature and 2) present the perspectives of key stakeholders to identify research gaps, programmatic lessons learned, and opportunities for policy change from an ecological perspective at the individual, community, health-system, and policy/legal levels.

Methods
This study includes 1) a systematic literature review of both published and unpublished literature since 2008 and 2) focus group discussions (FGDs) with key stakeholders representing 18 international and local governmental and non-governmental organizations.

Results
The literature review included 27 documents. Stakeholder discussions highlighted important research and policy gaps. Prevalence estimates of SGBV, honor killing, and early marriage vary across sources; however, all of them indicate that they remain important issues for youth in Jordan. Several sources indicate that early marriage has been increasing in Jordan since the beginning of the war in Syria, especially among Syrian refugees. Refugee youth are particularly vulnerable to SGBV and early marriage given the worsening economic situation in Jordan. The norms, attitudes, and practices that support SGBV in Jordan appear to be reinforced within families and communities. Despite ongoing programs, SGBV services are limited, especially for youth, and there is little awareness of service availability amongst target populations. Laws and policies continue to offer legal justification for SGBV, honor killing, and early marriage.

Discussion
As countries across the Middle East face instability and continue to struggle with the urgent health needs of large refugee and youth populations, this review provides valuable insight relevant to research, programs, and policy in Jordan and across the region.
In vivo creation of plasmid pCRT01 and its use for the construction of carotenoid-producing Paracoccus spp. strains that grow efficiently on industrial wastes
Authors: Maj Anna , Dziewit Lukasz , Drewniak Lukasz , Garstka Maciej , Krucon Tomasz , Piatkowska Katarzyna , Gieczewska Katarzyna , Czarnecki Jakub , Furmanczyk Ewa , Lasek Robert , Baj Jadwiga , Bartosik Dariusz 
Published: July 2020

Abstract
Background
Carotenoids are natural tetraterpene pigments widely utilized in the food, pharmaceutical and cosmetic industries. Currently, chemical synthesis of these compounds outperforms their production in Escherichia coli or yeast due to the limited efficiency of the latter. The use of natural microbial carotenoid producers, such as bacteria of the genus Paracoccus (Alphaproteobacteria), may help to optimize this process. In order to couple the ability to synthesize these pigments with the metabolic versatility of this genus, we explored the possibility of introducing carotenoid synthesis genes into strains capable of efficient growth on simple low-cost media.

Results
We constructed two carotenoid-producing strains of Paracoccus carrying a new plasmid, pCRT01, which contains the carotenoid synthesis gene locus crt from Paracoccus marcusii OS22. The plasmid was created in vivo via illegitimate recombination between crt-carrying vector pABW1 and a natural “paracoccal” plasmid pAMI2. Consequently, the obtained fusion replicon is stably maintained in the bacterial population without the need for antibiotic selection. The introduction of pCRT01 into fast-growing “colorless” strains of Paracoccus aminophilus and Paracoccus kondratievae converted them into efficient producers of a range of both carotenes and xanthophylls. The exact profile of the produced pigments was dependent on the strain genetic background. To reduce the cost of carotenoid production in this system, we tested the growth and pigment synthesis efficiency of the two strains on various simple media, including raw industrial effluent (coal-fired power plant flue gas desulfurization wastewater) supplemented with molasses, an industrial by-product rich in sucrose.

Conclusions
We demonstrated a new approach for the construction of carotenoid-producing bacterial strains which relies on a single plasmid-mediated transfer of a pigment synthesis gene locus between Paracoccus strains. This strategy facilitates screening for producer strains in terms of synthesis efficiency, pigment profile and ability to grow on low-cost industrial waste-based media, which should increase the cost-effectiveness of microbial production of carotenoids.
The influence of transketolase on lipid biosynthesis in the yeast Yarrowia lipolytica
Authors: Dobrowolski Adam , Mirończuk Aleksandra M. 
Published: July 2020

Abstract
Background
During the pentose phosphate pathway (PPP), two important components, NADPH and pentoses, are provided to the cell. Previously it was shown that this metabolic pathway is a source of reducing agent for lipid synthesis from glucose in the yeast Yarrowia lipolytica. Y. lipolytica is an attractive microbial host since it is able to convert untypical feedstocks, such as glycerol, into oils, which subsequently can be transesterified to biodiesel. However, the lipogenesis process is a complex phenomenon, and it still remains unknown which genes from the PPP are involved in lipid synthesis.

Results
To address this problem we overexpressed five genes from this metabolic pathway: transaldolase (TAL1, YALI0F15587g), transketolase (TKL1, YALI0E06479g), ribulose-phosphate 3-epimerase (RPE1, YALI0C11880g) and two dehydrogenases, NADP+-dependent glucose-6-phosphate dehydrogenase (ZWF1, YALI0E22649g) and NADP+-dependent 6-phosphogluconate dehydrogenase (GND1, YALI0B15598g), simultaneously with diacylglycerol acyltransferase (DGA1, YALI0E32769g) and verified each resulting strain’s ability to synthesize fatty acid growing on both glycerol and glucose as a carbon source. Our results showed that co-expression of DGA1 and TKL1 results in higher SCO synthesis, increasing lipid content by 40% over the control strain (DGA1 overexpression).

Conclusions
Simultaneous overexpression of DGA1 and TKL1 genes results in a higher lipid titer independently from the fermentation conditions, such as carbon source, pH and YE supplementation.
COVID-19 in Yemen: a crisis within crises
Authors: Mousavi Seyyed Meysam , Anjomshoa Mina 
Published: July 2020

AbstractYemen is suffering deadly airstrikes and heavy bombardment since March 2015 which has created one of the most severe humanitarian crises worldwide. In this miserable situation, several communicable diseases have massively re-emerged including cholera, diarrhea, dengue, and measles, as a result of weapons used during the years of war according to geospatial patterns of the infected cases. According to the world health organization (WHO), only 51% of health care facilities across the country are fully functional, mainly due to the war. The fragile health system has extremely limited capacity to adopt and implement effective preparedness and response measures to the COVID-19 outbreak. The first and most imperative step to combat COVID-19 in Yemen is ending the devastating war without delay and terminating the land, sea and air blockade imposed by the coalition. International humanitarian organizations should also dedicate a high level joint action to implement a series of well-coordinated measures emphasizing both whole-of-government and whole-of-society approach to protect Yemenis’ right in life and health.
Higher sensitivity of female cells to ethanol: methylation of DNA lowers Cyp2e1, generating more ROS
Authors: Penaloza Carlos G. , Cruz Mayra , Germain Gabrielle , Jabeen Sidra , Javdan Mohammad , Lockshin Richard A. , Zakeri Zahra 
Published: July 2020

Abstract
Background
Cells taken from mouse embryos before sex differentiation respond to insults according to their chromosomal sex, a difference traceable to differential methylation. We evaluated the mechanism for this difference in the controlled situation of their response to ethanol.

Methods
We evaluated the expression of mRNA for alcohol dehydrogenase (ADH), aldehyde dehyrogenases (ALDH), and a cytochrome P450 isoenzyme (Cyp2e1) in male and female mice, comparing the expressions to toxicity under several experimental conditions evaluating redox and other states.

Results
Females are more sensitive to ethanol. Disulfiram, which inhibits alcohol dehydrogenase (ADH), increases cell death in males, eliminating the sex dimorphism. The expressions ADH Class 1 to 4 and ALDH Class 1 and 2 do not differ by sex. However, females express approximately 8X more message for Cyp2e1, an enzyme in the non-canonical pathway. Female cells produce approximately 15% more ROS (reactive oxygen species) than male cells, but male cells contain approximately double the concentration of GSH, a ROS scavenger. Scavenging ROS with N-acetyl cysteine reduces cell death and eliminates sex dimorphism. Finally, since many of the differences in gene expression derive from methylation of DNA, we exposed cells to the methyltransferase inhibitor 5-aza- 2-deoxycytidine; blocking methylation eliminates both the difference in expression of Cyp2e1 and cell death.

Conclusion
We conclude that the sex-differential cell death caused by ethanol derives from sex dimorphic methylation of Cyp2e1 gene, resulting in generation of more ROS.
Rapid and visual detection of milk vetch dwarf virus using recombinase polymerase amplification combined with lateral flow strips
Authors: Cao Yuhao , Yan Dankan , Wu Xinyang , Chen Ziqiang , Lai Yuchao , Lv Lanqing , Yan Fei , Chen Jianping , Zheng Hongying , Song Xuemei 
Published: July 2020

Abstract
Background
Milk vetch dwarf virus (MDV) is an important ssDNA virus which causes yellowing, stunting and leaf rolling symptoms on legumes. In China, the virus causes great economic losses and has recently been found to infect tobacco. The expansion of its host range and its ability to spread rapidly has given rise to the urgent need for a sensitive, specific and rapid diagnostic assay that can assist in effective disease control.

Methods
Assays based on the polymerase chain reaction combined with lateral flow strip detection (PCR-LFS) and recombinase polymerase amplification combined with LFS (RPA-LFS) were developed targeting the coat protein (CP) gene of MDV.

Results
The PCR and RPA assays could detect respectively 103 copies or 101 copies of MDV by agarose gel electrophoresis. The PCR-LFS and RPA-LFS assays developed could both detect as few as 101 copies per reaction at 37 °C. Both methods could detect MDV in crude leaf extracts.

Conclusions
The RPA-LFS assay developed is a rapid, sensitive and specific method for detecting MDV, which is convenient and has great potential for use in the field.
Research trends and scientific analysis of publications on burnout and compassion fatigue among healthcare providers
Authors: Sweileh Waleed M. 
Published: July 2020

AbstractBackgroundBurnout and compassion fatigue are closely related concepts. Burnout is thought to develop from occupational stress while compassion fatigue results from being in a caregiver role leading to inability to get engaged in a caring relation. The objective of the current study was to investigate research trends, themes, citations, and key players of publications on burnout and compassion fatigue among healthcare providers.MethodsA validated search query was developed and implemented in the Scopus database. The study period was all times up to 2019.ResultsResearch query found 4416 publications. Publications started in 1978. Steep growth in the number of publications was observed in the last decade. There were seven research themes in the retrieved publications; six for burnout and one for compassion fatigue. Approximately 36% of the retrieved publications were about nurses; 36% were about physicians, 10% were about medical residents and the remaining did not include a specific profession. The retrieved publications received an average of 22.2 citations per article. Four of the top 10 active journals were in the field of nursing and two in the field of general medicine, one in public health, one in neurology, one in psychology, and one was multidisciplinary. The USA ranked first with 1292 (29.3%) articles followed by Spain (n = 248; 5.6%) and the UK (n = 247; 5.6%). Mayo Clinic was the most active institution (n = 93; 2.1%) followed by Harvard University (n = 46; 1.0%) and University of Washington, Seattle (n = 45; 1.0%). A total of 16,108 authors participated in publishing the retrieved documents, an average of 3.6 authors per article.Shanafelt, T.D.was the most active author (n = 78; 1.8%) followed byDyrbye, L.N.(n = 43; 1.0%), andWest, C.P.(n = 37; 0.8%). A total of 472 (10.7%) articles declared funding.ConclusionThe current study was carried out to draw attention to the wellbeing of healthcare providers. Retrieved literature was dominated by high-income countries. Lack of information from low- and middle-income countries will hinder planning for interventional strategies and will negatively affect the health system and the patients. Health researchers in low- and middle-income countries need to focus on burn out and compassion fatigue.
HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis
Authors: Karlebach Guy , Hansen Peter , Veiga Diogo FT , Steinhaus Robin , Danis Daniel , Li Sheng , Anczukow Olga , Robinson Peter N 
Published: July 2020

AbstractWe present Hierarchical Bayesian Analysis of Differential Expression and ALternative Splicing (HBA-DEALS), which simultaneously characterizes differential expression and splicing in cohorts. HBA-DEALS attains state of the art or better performance for both expression and splicing and allows genes to be characterized as having differential gene expression, differential alternative splicing, both, or neither. HBA-DEALS analysis of GTEx data demonstrated sets of genes that show predominant DGE or DAST across multiple tissue types. These sets have pervasive differences with respect to gene structure, function, membership in protein complexes, and promoter architecture.
Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation
Authors: Ouidir Marion , Mendola Pauline , Buck Louis Germaine M. , Kannan Kurunthachalam , Zhang Cuilin , Tekola-Ayele Fasil 
Published: July 2020

Abstract
Background
Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies.

Results
Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p’-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10−21 to 2.11 × 10−7). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs).

Conclusions
DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.