bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Ethereum blockchain to store and query pharmacogenomics data via smart contracts
Authors: Gürsoy Gamze , Brannon Charlotte M. , Gerstein Mark 
Published: June 2020

Abstract
Background
As pharmacogenomics data becomes increasingly integral to clinical treatment decisions, appropriate data storage and sharing protocols need to be adopted. One promising option for secure, high-integrity storage and sharing is Ethereum smart contracts. Ethereum is a blockchain platform, and smart contracts are immutable pieces of code running on virtual machines in this platform that can be invoked by a user or another contract (in the blockchain network). The 2019 iDASH (Integrating Data for Analysis, Anonymization, and Sharing) competition for Secure Genome Analysis challenged participants to develop time- and space-efficient Ethereum smart contracts for gene-drug relationship data.

Methods
Here we design a specific smart contract to store and query gene-drug interactions in Ethereum using an index-based, multi-mapping approach. Our contract stores each pharmacogenomics observation, a gene-variant-drug triplet with outcome, in a mapping searchable by a unique identifier, allowing for time and space efficient storage and query. This solution ranked in the top three at the 2019 IDASH competition. We further improve our ”challenge solution” and develop an alternate ”fastQuery” smart contract, which combines together identical gene-variant-drug combinations into a single storage entry, leading to significantly better scalability and query efficiency.

Results
On a private, proof-of-authority network, both our challenge and fastQuery solutions exhibit approximately linear memory and time usage for inserting into and querying small databases (<1,000 entries). For larger databases (1000 to 10,000 entries), fastQuery maintains this scaling. Furthermore, both solutions can query by a single field (”0-AND”) or a combination of fields (”1- or 2-AND”). Specifically, the challenge solution can complete a 2-AND query from a small database (100 entries) in 35ms using 0.1 MB of memory. For the same query, fastQuery has a 2-fold improvement in time and a 10-fold improvement in memory.

Conclusion
We show that pharmacogenomics data can be stored and queried efficiently using Ethereum blockchain. Our solutions could potentially be used to store a range of clinical data and extended to other fields requiring high-integrity data storage and efficient access.
Living or deceased-donor kidney transplant: the role of psycho-socioeconomic factors and outcomes associated with each type of transplant
Authors: Basiri Abbas , Taheri Maryam , Khoshdel Alireza , Golshan Shabnam , Mohseni-rad Hamed , Borumandnia Nasrin , Simforoosh Nasser , Nafar Mohsen , Aliasgari Majid , Nourbala Mohammad Hossein , Pourmand Gholamreza , Farhangi Soudabeh , Khalili Nastaran 
Published: June 2020

Abstract
Background
Kidney transplant improves patients’ survival and quality of life. Worldwide, concern about the equality of access to the renal transplant wait-list is increasing. In Iran, patients have the choice to be placed on either the living or deceased-donor transplant wait-list.

Methods
This was a prospective study performed on 416 kidney transplant recipients (n = 217 (52.2%) from living donors and n = 199 (47.8%) from deceased donors). Subjects were recruited from four referral kidney transplant centers across Tehran, Iran, during 2016–2017. The primary outcome was to identify the psycho-socioeconomic factors influencing the selection of type of donor (living versus deceased). Secondary objective was to compare the outcomes associated with each type of transplant. The impact of psycho-socioeconomic variables on selecting type of donor was evaluated by using multiple logistic regression and the effect of surgical and non-surgical variables on the early post-transplant creatinine trend was assessed by univariate repeated measure ANOVA.

Results
Based on standardized coefficients, the main predictors for selecting living donor were academic educational level (adjusted OR = 3.25, 95% CI: 1.176–9.005, p = 0.023), psychological status based on general health questionnaire (GHQ) (adjusted OR = 2.46, 95% CI: 1.105–5.489, p = 0.028), and lower monthly income (adjusted OR = 2.20, 95% CI: 1.242–3.916, p = 0.007). The waiting time was substantially shorter in patients who received kidneys from living donors (p < 0.001). The early post-transplant creatinine trend was more desirable in recipients of living donors (β = 0.80, 95% CI: 0.16–1.44, p-value = 0.014), patients with an ICU stay of fewer than five days (β = − 0.583, 95% CI: − 0.643- -0.522, p-value = < 0.001), and those with less dialysis duration time (β = 0.016, 95% CI: 0.004–0.028, p-value = 0.012). Post-operative surgical outcomes were not different across the two groups of recipients (p = 0.08), however, medical complications occurred considerably less in the living-donor group (p = 0.04).

Conclusion
Kidney transplant from living donors was associated with shorter transplant wait-list period and better early outcome, however, inequality of access to living donors was observed. Patients with higher socioeconomic status and higher level of education and those suffering from anxiety and sleep disorders were significantly more likely to select living donors.
Access to skilled attendant at birth and the coverage of the third dose of diphtheria-tetanus-pertussis vaccine across 14 West African countries – an equity analysis
Authors: Alhassan Jacob Albin Korem , Wariri Oghenebrume , Onuwabuchi Egwu , Mark Godwin , Kwarshak Yakubu , Dase Eseoghene 
Published: June 2020

Abstract
Background
Universal Health Coverage (UHC) remains a critical public health goal that continues to elude many countries of the global south. As countries strive for its attainment, it is important to track progress in various subregions of the world to understand current levels and mechanisms of progress for shared learning. Our aim was to compare multidimensional equity gaps in access to skilled attendant at birth (SAB) and coverage of the third dose of Diphtheria-Tetanus-Pertussis (DTP3) across 14 West African countries.

Methods
The study was a cross sectional comparative analysis that used publicly available, nationally representative health surveys. We extracted data from Demographic and Health Surveys, and Multiple Indicator Cluster Surveys conducted between 2010 and 2017 in Benin, Burkina Faso, Cote d’ Ivoire, The Gambia, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone and Togo. The World Health Organization’s Health Equity Assessment Toolkit (HEAT Plus) software was used to evaluate current levels of intra-country equity in access to SAB and DTP3 coverage across four equity dimensions (maternal education, location of residence, region within a country and family wealth status).

Results
There was a general trend of higher levels of coverage for DTP3 compared to access to SAB in the subregion. Across the various dimensions of equity, more gaps appear to have been closed in the subregion for DTP3 compared to SAB. The analysis revealed that countries such as Sierra Leone, Liberia and Ghana have made substantial progress towards equitable access for the two outcomes compared to others such as Nigeria, Niger and Guinea.

Conclusion
In the race towards UHC, equity should remain a priority and comparative progress should be consistently tracked to enable the sharing of lessons. The West African subregion requires adequate government financing and continued commitment to move toward UHC and close health equity gaps.
Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis
Authors: Wu Yongyan , Zhang Yuliang , Zheng Xiwang , Dai Fengsheng , Lu Yan , Dai Li , Niu Min , Guo Huina , Li Wenqi , Xue Xuting , Bo Yunfeng , Guo Yujia , Qin Jiangbo , Qin Yixiao , Liu Hongliang , Zhang Yu , Yang Tao , Li Li , Zhang Linshi , Hou Rui , Wen Shuxin , An Changming , Li Huizheng , Xu Wei , Gao Wei 
Published: June 2020

Abstract
Background
Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown.

Methods
RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry.

Results
circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial–mesenchymal transition and finally facilitated the malignant progression of LSCC.

Conclusions
circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.
Decidual CD8+T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
Authors: Liu Lu , Huang Xixi , Xu Chunfang , Chen Chunqin , Zhao Weijie , Li Dajin , Li Liping , Wang Li , Du Meirong 
Published: June 2020

AbstractBackgroundDuring early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8+T (CD8+dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined.MethodsWe investigated the distribution patterns of CD8+T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy using flow cytometry and mRNA-Seq. Gene Set Enrichment Analysis was utilized to determine the transcriptional features of CD8+dT cells. Moreover, we examined activation of T cells when they were cocultured with trophoblasts, in addition to the effect of the fetal–maternal environment on peripheral CD8+T (CD8+pT) cells.ResultsWe found that, compared with CD8+pT cells, CD8+dT cells consisted mainly of effector memory cells (TEM) and terminally differentiated effector memory cells (TEMRA). Both TEMand TEMRAsubsets contained increased numbers of CD27+CD28−cells, which have been shown to possess only partial effector functions. In-depth analysis of the gene-expression profiles of CD8+dT cells revealed significant enrichment in T cell exhaustion-related genes and core tissue residency signature genes that have been found recently to be shared by tissue resident memory cells and tumor−infiltrating lymphocytes (TILs). In accordance with gene expression, protein levels of the exhaustion-related molecules PD-1 and CD39 and the tissue resident molecules CD103 and CXCR3 were increased significantly with almost no perforin secretion in CD8+dT cells compared with CD8+pT cells. However, the levels of granzyme B, IFN-γ, and IL-4 in CD8+dT cells were increased significantly compared with those in CD8+pT cells. Both CD8+dT and CD8+pT cells were not activated after being cocultured with autologous trophoblast cells. Moreover, the production of granzyme B in CD103+CD8+dT cells decreased significantly compared with that in their CD103−counterparts. Coculture with decidual stromal cells and trophoblasts upregulated CD103 expression significantly in CD8+pT cells.ConclusionsOur findings indicate that the selective silencing of effector functions of resident CD8+dT cells may favor maternal–fetal tolerance and that the decidual microenvironment plays an important role in promoting the residency of CD8+T cells and their tolerance–defense balance.
Parent-child sexual and reproductive health communication among very young adolescents in Korogocho informal settlement in Nairobi, Kenya
Authors: Maina Beatrice W , Ushie Boniface Ayanbekongshie , Kabiru Caroline W 
Published: June 2020

Abstract
Background
Parents are an important source of sexual and reproductive health (SRH) information for very young adolescents and are likely to have a significant influence on adolescents’ sexual attitudes, values, and risk-related beliefs. This study explored the nature and content of parent-child communication about SRH issues.

Methods
Thirty-two parents and 30 adolescent boys and girls aged between 11 and 13 years participated in narrative interviews in a resource-poor urban setting in Nairobi, Kenya. Interviews were audio-recorded, transcribed, translated into English, and uploaded on Atlas.ti software for coding and analysis.

Results
Findings from the study show gender differences in parent-child communication. More girls than boys reported that they had talked with their parents about romantic relationships. Four approaches—no communication, fear-based communication, supportive communication, and involving an external person were used by parents in SRH communication. Parents hostile attitudes towards romantic relationships during adolescence discouraged adolescents from disclosing their relationship status. While communication did occur, it was mainly reactive, one-sided, and authoritarian, often initiated by parents.

Conclusions
Parents need to be empowered with adequate and factual SRH information and effective communication strategies to enhance communication with very young adolescents. There is a need for further research to identify the most effective parent-child communication approaches to improve SRH outcomes among adolescents.
From Devo to Evo: patterning, fusion and evolution of the zebrafish terminal vertebra
Authors: Cumplido Nicolás , Allende Miguel L. , Arratia Gloria 
Published: June 2020

Abstract
Background
With more than 30,000 species, teleosts comprise about half of today’s living vertebrates, enriched with a wide set of adaptations to all aquatic systems. Their evolution was marked by modifications of their tail, that involved major rearrangements of the metameric organization of the axial skeleton. The most posterior or ural caudal skeleton, primitively included more than 10 vertebrae and, through a series of fusions and losses, became reduced to a single vertebra in modern ostariophysans, one of the largest clades of teleosts. The ontogeny of the ostariophysan Danio rerio recapitulates this process by forming two or three separate vertebrae that become a single vertebra in adults. We characterize the developmental sequence of this change by describing the processes of patterning, fusion and differential growth on each of the constitutive elements that sculpt the adult terminal vertebra.

Results
The ontogenetic changes of the terminal vertebra were characterized, highlighting their shared and derived characters in comparison with other teleosts. In zebrafish, there is: i) a loss of the preural centrum 1, ii) the formation of an hourglass-shaped autocentrum only in the anterior but not the posterior border of the compound centrum, iii) the formation of a vestigial posterior centrum that does not form an autocentrum and becomes incorporated beneath the compound centrum during development, and iv) the elongated dorso-posterior process of the compound centrum or pleurostyle appears as an independent element posterior to the compound centrum, before fusing to the ural neural arches and the anterior portion of the compound centrum.

Conclusions
The unique features of the formation of the terminal vertebra in Danio rerio reflect the remarkable changes that occurred during the evolution of teleosts, with potential shared derived characteristics for some of the major lineages of modern teleosts. A new ontogenetic model is proposed to illustrate the development of the terminal vertebra, and the phylogenetic implications for the evolution of caudal skeleton consolidation in ostariophysans are discussed.
Immediate effects of a lumbar spine manipulation on pain sensitivity and postural control in individuals with nonspecific low back pain: a randomized controlled trial
Authors: Fagundes Loss Jefferson , de Souza da Silva Luciano , Ferreira Miranda Iã , Groisman Sandro , Santiago Wagner Neto Edgar , Souza Catiane , Tarragô Candotti Cláudia 
Published: June 2020

Abstract
Background
According to the American Physical Therapy Association, there is strong evidence to show that vertebral mobilization and manipulation procedures can be used to improve spinal and hip mobility and reduce pain and incapacity in low back pain patients that fit the clinical prediction rule. Objectives: To evaluate the immediate effects of high-velocity low-amplitude (HVLA) manipulation on pain and postural control parameters in individuals with nonspecific low back pain.

Methods
This study used a participant-blinded and assessor-blinded randomized controlled clinical trial involving a single session, in which 24 participants were randomly distributed into control (simulated manipulation) and intervention (HVLA lumbar manipulation) groups. The primary (pain: subjective pain intensity and pressure pain threshold) and secondary outcomes (postural control: ellipse area, center of pressure [COP] excursion, COP RMS velocity, and differences between the COP and center of projected gravity) were evaluated before and after the session using a numerical pain scale, algometer, and a force platform. For all outcomes, multiple mixed 2 (group) × 2 (time) ANOVAs were performed.

Results
For the subjective pain intensity, only time was significant as a main effect, where pre-intervention presented a greater value then post-intervention (F [1.44] = 4.377; p = 0.042; r = 0.30). For the pressure pain threshold no significant effect was found. For the postural control parameters, as a main effect, only the ellipse area was significantly greater in the control group (F [1.44] = 6.760; p = 0.013; effect size = 0.36).

Conclusions
There was a reduction in subjective pain intensity, evaluated using a numerical scale, in both the intervention and control groups immediately after the intervention, suggesting that the spinal manipulation had a similar effect to the placebo procedure. No effect of HVLA lumbar manipulation was identified for postural control variables in either the intervention or control groups.

Trial registration
The study was registered at ClinicalTrials.gov under the number NCT02312778, registered at 14 September 2014.
Targeted-gene sequencing of an undifferentiated gallbladder carcinoma: a case report
Authors: Xiao Ying , Xiang Canhong , Yang Di , Zhao Benqi , Li Yong , Yin Hongfang 
Published: June 2020

Abstract
Background
Undifferentiated carcinomas of the gallbladder are extremely rare. Most undifferentiated carcinomas are accompanied by adjacent foci of other conventional carcinomas, and a transition zone is shared between them. However, genetic alterations of undifferentiated gallbladder carcinoma and the similarities or differences between the undifferentiated carcinoma and the foci conventional carcinoma are unknown.

Case presentation
Herein, we report a case of undifferentiated gallbladder carcinoma with osteoclast-like giant cells with invasion into the liver, duodenum, and stomach in a 56-year-old man. The tumor was microscopically formed from the tubular adenocarcinoma (< 5% of the entire tumor), the undifferentiated carcinoma, and a transition zone between them. Four somatic mutations (TP53, TERT, ARID2, and CDH1), three amplifications (CCND1, FGF19, and MET), and a tumor mutation burden (TMB) of 3.45 muts/Mb were detected in the undifferentiated component using targeted gene sequencing, whereas 102 somatic mutations (including TP53, TERT, ARID2, and CDH1), one amplification (CCND1), and a higher TMB of 87.07 muts/Mb were detected in the tubular component. This patient died of tumor recurrence 2 months after the surgery.

Conclusions
The undifferentiated gallbladder carcinoma had its unique molecular alterations. The similarities in the genetic alterations of the undifferentiated carcinoma and adenocarcinoma provide evidence of a common origin at the genetic level. The occurrence of an undifferentiated carcinoma may be due to heterogeneity-associated branched evolution from the tubular adenocarcinoma.
Fluid removal associates with better outcomes in critically ill patients receiving continuous renal replacement therapy: a cohort study
Authors: Hall Anna , Crichton Siobhan , Dixon Alison , Skorniakov Ilia , Kellum John A. , Ostermann Marlies 
Published: June 2020

Abstract
Background
Fluid overload is associated with morbidity and mortality in patients receiving renal replacement therapy (RRT). We aimed to explore whether fluid overload at initiation of RRT was independently associated with mortality and whether changes in cumulative fluid balance during RRT were associated with outcome.

Methods
We retrospectively analysed the data of patients who were admitted to the multidisciplinary adult intensive care unit (ICU) in a tertiary care centre in the UK between 2012 and 2015 and received continuous RRT (CRRT) for acute kidney injury for at least 24 h. We collected baseline demographics, body mass index (BMI), comorbidities, severity of illness, laboratory parameters at CRRT initiation, daily cumulative fluid balance (FB), daily prescribed FB target, fluid bolus and diuretic administration and outcomes. The day of the lowest cumulative FB during CRRT was identified as nadir FB.

Results
Eight hundred twenty patients were analysed (median age 65 years; 49% female). At CRRT initiation, the median cumulative FB was + 1772 ml; 89 patients (10.9%) had a cumulative FB > 10% body weight (BW). Hospital survivors had a significantly lower cumulative FB at CRRT initiation compared to patients who died (1495 versus 2184 ml; p < 0.001). In the 7 days after CRRT initiation, hospital survivors had a significant decline in cumulative FB (mean decrease 473 ml per day, p < 0.001) whilst there was no significant change in cumulative FB in non-survivors (mean decrease 112 ml per day, p = 0.188). Higher severity of illness at CRRT initiation, shorter duration of CRRT, the number of days without a prescribed FB target and need for higher doses of noradrenaline were independent risk factors for not reaching a FB nadir during CRRT. Multivariable analysis showed that older age, lower BMI, higher severity of illness, need for higher doses of noradrenaline and smaller reductions in cumulative FB during CRRT were independent risk factors for ICU and hospital mortality. Cumulative FB at CRRT initiation was not independently associated with mortality.

Conclusion
In adult patients receiving CRRT, a decrease in cumulative FB was independently associated with lower mortality. Fluid overload and need for vasopressor support at CRRT initiation were not independently associated with mortality after correction for severity of illness.