bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid protein evolution, organellar reductions, and invasive intronic elements in the marine aerobic parasite dinoflagellate Amoebophrya spp
Authors: Farhat Sarah , Le Phuong , Kayal Ehsan , Noel Benjamin , Bigeard Estelle , Corre Erwan , Maumus Florian , Florent Isabelle , Alberti Adriana , Aury Jean-Marc , Barbeyron Tristan , Cai Ruibo , Da Silva Corinne , Istace Benjamin , Labadie Karine , Marie Dominique , Mercier Jonathan , Rukwavu Tsinda , Szymczak Jeremy , Tonon Thierry , Alves-de-Souza Catharina , Rouzé Pierre , Van de Peer Yves , Wincker Patrick , Rombauts Stephane , Porcel Betina M. , Guillou Laure 
Published: January 2021

Abstract
Background
Dinoflagellates are aquatic protists particularly widespread in the oceans worldwide. Some are responsible for toxic blooms while others live in symbiotic relationships, either as mutualistic symbionts in corals or as parasites infecting other protists and animals. Dinoflagellates harbor atypically large genomes (~ 3 to 250 Gb), with gene organization and gene expression patterns very different from closely related apicomplexan parasites. Here we sequenced and analyzed the genomes of two early-diverging and co-occurring parasitic dinoflagellate Amoebophrya strains, to shed light on the emergence of such atypical genomic features, dinoflagellate evolution, and host specialization.

Results
We sequenced, assembled, and annotated high-quality genomes for two Amoebophrya strains (A25 and A120), using a combination of Illumina paired-end short-read and Oxford Nanopore Technology (ONT) MinION long-read sequencing approaches. We found a small number of transposable elements, along with short introns and intergenic regions, and a limited number of gene families, together contribute to the compactness of the Amoebophrya genomes, a feature potentially linked with parasitism. While the majority of Amoebophrya proteins (63.7% of A25 and 59.3% of A120) had no functional assignment, we found many orthologs shared with Dinophyceae. Our analyses revealed a strong tendency for genes encoded by unidirectional clusters and high levels of synteny conservation between the two genomes despite low interspecific protein sequence similarity, suggesting rapid protein evolution. Most strikingly, we identified a large portion of non-canonical introns, including repeated introns, displaying a broad variability of associated splicing motifs never observed among eukaryotes. Those introner elements appear to have the capacity to spread over their respective genomes in a manner similar to transposable elements. Finally, we confirmed the reduction of organelles observed in Amoebophrya spp., i.e., loss of the plastid, potential loss of a mitochondrial genome and functions.

Conclusion
These results expand the range of atypical genome features found in basal dinoflagellates and raise questions regarding speciation and the evolutionary mechanisms at play while parastitism was selected for in this particular unicellular lineage.
IL-17A polymorphism (rs2275913) and levels are associated with preeclampsia pathogenesis in Chinese patients
Authors: Lang Xiao , Liu Wei , Hou Yanyan , Zhao Wenxia , Yang Xingyu , Chen Lan , Yan Qi , Cheng Weiwei 
Published: January 2021

AbstractBackgroundPreeclampsia (PE) is a pregnancy-related condition that affects both the infant and the mother. Although the role of various inflammatory molecules in PE has been demonstrated, the importance of pro-inflammatory molecules such as IL-17A, IL-23 is not well understood. In the present investigation, a potential association of common genetic variants in the IL-17A and IL-23A genes with PE was investigated.Methods115 PE clinically diagnosed patients who registered to the International Peace Maternity and Child Health Hospital were enrolled in this research. One hundred two pregnant women and 147 healthy Chinese women were also included. ELISA was used to measure IL-17A and IL-23 serum levels in all enrolled subjects. Common genetic polymorphisms inIL-17A(rs 2,275,913, rs1974226, and rs1974226),IL-23A(rs11171806), andIL-12B(rs3212227) were genotyped using the PCR-RFLP or TaqMan probe-based method.ResultsElevated serum IL-17A levels were found in PE patients compared to pregnant (P < 0.0001) and healthy women (P < 0.0001). However, IL-23 levels were comparable across various clinical groups. In addition, heterozygous (GA) and minor allele (A) for IL-17A (rs2275913) and IL-23A (rs11171806) were more prevalent in PE patients compared to pregnant women indicating an important role in the predisposition to PE growth. Interestingly, IL-17A (r 2,275,913) mutants were associated with elevated IL-17A levels relative to wild type (GG).ConclusionsIL-17A (rs2275913) variants are associated with higher serum levels of cytokine, and predisposed PE development.
Correlation between ZBRK1/ZNF350 gene polymorphism and breast cancer
Authors: Wu Jun , Eni Alibiati , Roussuri Eliar , Ma Binlin 
Published: January 2021

Abstract
Background
This study is to explore the relationship between the ZBRK1/ZNF350 (Zinc finger and BRCA1-interacting protein with KRAB domain-1; also known as zinc-finger protein 350) gene polymorphism and early-onset breast cancer.

Methods
The ZBRK1/ZNF350 gene exon detection analysis was performed with the direct sequencing and Snapshot methods in 80 cases of breast cancer (aged ≤ 40 years old) and 240 healthy subjects (aged ≤ 40 years old).

Results
Totally 9 sequence variants were detected, including 5 missense mutations and 4 synonymous mutations, located at EXON3, EXON4 and EXON5, respectively. The rs4987241 and rs3764538 variants were published for the first time, while the remaining variants had been reported before. There were significant differences in the frequency distribution of family history between the breast cancer and control groups. Moreover, there were significant differences in the CT genotype frequency at the rs138898320 locus between the breast cancer and healthy control groups. Compared with the carriers of CC wild genotype at rs138898320, the risk of breast cancer was reduced by 88.3% in the CT mutant genotype carriers, with significant difference. In the stratification with no family history, compared with the carriers of CC wild genotype at rs138898320, significant differences were observed for the CT mutant genotype carriers. In the stratification with family history, there was no significant difference in the variation of rs138898320.

Conclusion
The rs138898320 CT mutation genotype of ZBRK1/ZNF350 may reduce the risk of breast cancer, and the protecting effect would be increased in the stratification with no family history.
Trial registration Not applicable.
Idiopathic pulmonary fibrosis patients with severe physiologic impairment: characteristics and outcomes
Authors: Pastre Jean , Barnett Scott , Ksovreli Inga , Taylor Jeannie , Brown A. Whitney , Shlobin Oksana A. , Ahmad Kareem , Khangoora Vikramjit , Aryal Shambhu , King Christopher S. , Nathan Steven D. 
Published: January 2021

Abstract
Research question
There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment.

Patients and methods
IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated.

Results
There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ($${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$

6MWT

O
2

group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the $${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$

6MWT

O
2

group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001).

Conclusion
IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.
Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma
Authors: Zhao Qiangqiang , Sun Xiaoying , Wu Bin , Shang Yinghui , Huang Xueyuan , Dong Hang , Liu Haiting , Chen Wansong , Gui Rong , Li Jian 
Published: January 2021

Abstract
Background
Non-Hodgkin’s lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells.

Results
Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis.

Conclusions
Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.
Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids
Authors: Yakavets Ilya , Francois Aurelie , Lamy Laureline , Piffoux Max , Gazeau Florence , Wilhelm Claire , Zorin Vladimir , Silva Amanda K. A. , Bezdetnaya Lina 
Published: January 2021

Abstract
Background
Despite the highly expected clinical application of nanoparticles (NPs), the translation of NPs from lab to the clinic has been relatively slow. Co-culture 3D spheroids account for the 3D arrangement of tumor cells and stromal components, e.g., cancer-associated fibroblasts (CAFs) and extracellular matrix, recapitulating microenvironment of head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated how the stroma-rich tumor microenvironment affects the uptake, penetration, and photodynamic efficiency of three lipid-based nanoformulations of approved in EU photosensitizer temoporfin (mTHPC): Foslip® (mTHPC in conventional liposomes), drug-in-cyclodextrin-in-liposomes (mTHPC-DCL) and extracellular vesicles (mTHPC-EVs).

Results
Collagen expression in co-culture stroma-rich 3D HNSCC spheroids correlates with the amount of CAFs (MeWo cells) in individual spheroid. The assessment of mTHPC loading demonstrated that Foslip®, mTHPC-DCL and mTHPC-EVs encapsulated 0.05 × 10− 15 g, 0.07 × 10− 15 g, and 1.3 × 10− 15 g of mTHPC per nanovesicle, respectively. The mid-penetration depth of mTHPC NPs in spheroids was 47.8 µm (Foslip®), 87.8 µm (mTHPC-DCL), and 49.7 µm (mTHPC-EVs), irrespective of the percentage of stromal components. The cellular uptake of Foslip® and mTHPC-DCL was significantly higher in stroma-rich co-culture spheroids and was increasing upon the addition of serum in the culture medium. Importantly, we observed no significant difference between PDT effect in monoculture and co-culture spheroids treated with lipid-based NPs. Overall, in all types of spheroids mTHPC-EVs demonstrated outstanding total cellular uptake and PDT efficiency comparable to other NPs.

Conclusions
The stromal microenvironment strongly affects the uptake of NPs, while the penetration and PDT efficacy are less sensitive to the presence of stromal components. mTHPC-EVs outperform other lipid nanovesicles due to the extremely high loading capacity. The results of the present study enlarge our understanding of how stroma components affect the delivery of NPs into the tumors.
Synergy of hypoxia relief and heat shock protein inhibition for phototherapy enhancement
Authors: Zhang Gutian , Cheng Wenting , Du Lin , Xu Chuanjun , Li Jinlong 
Published: January 2021

AbstractBackgroundPhototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement.ResultsNear-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT.ConclusionThis study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.
Harm reduction in Europe: a framework for civil society-led monitoring
Authors: Rigoni Rafaela , Tammi Tuukka , van der Gouwe Daan , Schatz Eberhard 
Published: January 2021

Abstract
Background
Civil society organisations (CSOs) play a vital role in developing and implementing effective measures to reduce the harms of drug use. They are also fundamental actors to monitor and evaluate programmes and policies for improvement. While harm reduction services are subject to monitoring, and international and European indicators exist, a framework for civil society-led monitoring does not exist. This paper analyses the challenges and added values of developing such a framework for the European region.

Methods
Since 2018, a technical working group within Correlation-European Harm Reduction Network (C-EHRN) is developing and revising a monitoring framework, collecting—through National Focal Points—the experience of harm reduction service providers and service users in 34 European countries. The first round of data collection, in 2019, focused on hepatitis C, overdose prevention, new drug trends and civil society involvement in drug policies.

Results
Developing CSO-based harm reduction monitoring is a learning by doing process. Assuring reliability and national representativeness of the data was a central challenge. As most CSOs have little or no experience with monitoring and research and work in a local-based context, the monitoring approach and its indicators were adjusted to the local context in the second round, bringing more in-depth information and helping to improve results’ reliability. While this implied shifting from the initial focus on comparing responses at a national level, the change to collecting qualitative data reflecting local realities of service policies and delivery provides the foundations for a critical appraisal of these realities against European policy goals. This allowed to map discrepancies between official policies and their implementation, as well as identify gaps in and complement data collection from national-level agencies.

Conclusions
By focusing on local experiences regarding the delivery of global and European policy targets, C-EHRN monitoring uses the unique strengths of its CSOs network and generates information that complements the reporting by other monitoring agencies. Data reflecting the CSOs perspective is essential for optimising local planning of service provision and development of effective and respectful drug policies at national and European level. If data quality issues, as well as the sustainability of reporting, are adequately addressed, civil society monitoring can provide excellent added value for the monitoring of harm reduction in Europe.
Unprovoked internal jugular vein thrombosis: a case report and literature review
Authors: Payrard Loïc , Iten Léa , Donzé Jacques , John Gregor 
Published: January 2021

Abstract
Background
Managing thrombosis in rare sites is challenging. Existing studies and guidelines provide detailed explanations on how to overcome lower-limb thromboses and pulmonary embolisms, but few studies have examined thrombosis in rare sites. Lack of data makes clinical practice heterogeneous. Recommendations for diagnosing, treating, and following-up internal jugular vein thrombosis are not clearly defined and mostly based on adapted guidelines for lower-limb thrombosis.

Case presentation
A 52-year-old Caucasian woman came to the Emergency Department with chest, neck, and left arm pain. Computed tomography imagery showed a left internal jugular vein thrombosis. An extensive workup revealed a heterozygous factor V Leiden gene. Therapy was initiated with intravenous unfractionated heparin, then switched to oral acenocoumarol, which resolved the symptoms. Based on this case presentation and a literature review, we summarize the causes, treatment options, and prognosis of unprovoked internal jugular vein thrombosis.

Conclusions
Managing internal jugular vein thrombosis lacks scientific data from large randomized clinical trials, partly because such thromboses are rare. Our literature review suggested that clinical treatments for internal jugular vein thrombosis often followed recommendations for treating lower-limb thrombosis. Future specific studies are required to guide clinicians on the modalities of diagnosis, screening for thrombophilia or oncologic disease, treatment duration, and follow-up.
Fatal pulmonary arterial thrombosis in a COVID-19 patient, with asymptomatic history, occurred after swab negativization
Authors: Del Nonno Franca , Colombo Daniele , Nardacci Roberta , Falasca Laura 
Published: January 2021

Abstract
Background
A considerable number of SARS-CoV-2 infected individuals could be asymptomatic and don’t need medical treatment. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral pneumonia and respiratory distress. In cases with severe presentation of SARS-CoV-2 infection, the induction of hypercoagulability is one of the pathophysiological mechanism that can contribute to death.

Case presentation
Here, we reported autoptic evidences of thrombotic pulmonary arterial fatal lesions in an asymptomatic COVID-19 patient, after swab negativization. Whole body complete post-mortem examination was performed, showing the presence of a large thrombus occluding the main pulmonary artery that was the cause of death. Histopathological analysis showed heterogeneous pattern of pathological changes in the lung tissue with numerous vascular thrombi, inflammatory cardiomyopathy and other histopathological modifications in kidneys, spleen and liver.

Conclusions
This study provides evidences that also asymptomatic patients may be at risk to develop thrombotic complications. An appropriate diagnostic screening for thrombotic complications and the early treatment recommendations of antithrombotic drugs could represent an important topic even in asymptomatic individuals.
Approaches to motivate physicians and nurses in low- and middle-income countries: a systematic literature review
Authors: Gupta Jaya , Patwa Mariya C. , Khuu Angel , Creanga Andreea A. 
Published: January 2021

AbstractPoor health worker motivation, and the resultant shortages and geographic imbalances of providers, impedes the provision of quality care in low- and middle-income countries (LMICs). This systematic review summarizes the evidence on interventions used to motivate health workers in LMICs. A standardized keyword search strategy was employed across five databases from September 2007 -September 2017. Studies had to meet the following criteria: original study; doctors and/or nurses as target population for intervention(s); work motivation as study outcome; study design with clearly defined comparison group; categorized as either a supervision, compensation, systems support, or lifelong learning intervention; and conducted in a LMIC setting. Two independent reviewers screened 3845 titles and abstracts and, subsequently, reviewed 269 full articles. Seven studies were retained from China (n = 1), Ghana (n = 2), Iran (n = 1), Mozambique (n = 1), and Zambia (n = 2). Study data and risk of bias were extracted using a standardized form. Though work motivation was the primary study outcome, four studies did not provide an outcome definition and five studies did not describe use of a theoretical framework in the ascertainment. Four studies used a randomized trial—group design, one used a non-randomized trial—group design, one used a cross-sectional design, and one used a pretest–posttest design. All three studies that found a significant positive effect on motivational outcomes had a supervision component. Of the three studies that found no effects on motivation, two were primarily compensation interventions and the third was a systems support intervention. One study found a significant negative effect of a compensation intervention on health worker motivation. In conducting this systematic review, we found there is limited evidence on successful interventions to motivate health workers in LMICs. True effects on select categories of health workers may have been obscured given that studies included health workers with a wide range of social and professional characteristics. Robust studies that use validated and culturally appropriate tools to assess worker motivation are greatly needed in the Sustainable Development Goals era.