bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic parameters for uniformity of harvest weight in Pacific white shrimp (Litopenaeus vannamei)
Authors: García-Ballesteros Silvia , Villanueva Beatriz , Fernández Jesús , Gutiérrez Juan Pablo , Cervantes Isabel 
Published: March 2021

Abstract
Background
Uniformity of body weight is a trait of great economic importance in the production of white shrimp (Litopenaeus vannamei). A necessary condition to improve this trait through selective breeding is the existence of genetic variability for the environmental variance of body weight. Although several studies have reported such variability in other aquaculture species, to our knowledge, no estimates are available for shrimp. Our aim in this study was to estimate the genetic variance for weight uniformity in a farmed population of shrimp to determine the potential of including this trait in the selection program. We also estimated the genetic correlation of weight uniformity between two environments (selection nucleus and commercial population).

Methods
The database contained phenotypic records for body weight on 51,346 individuals from the selection nucleus and 38,297 individuals from the commercial population. A double hierarchical generalized linear model was used to analyse weight uniformity in the two environments. Fixed effects included sex and year for the nucleus data and sex and year-pond combination for the commercial data. Environmental and additive genetic effects were included as random effects.

Results
The estimated genetic variance for weight uniformity was greater than 0 (0.06 ± 0.01) in both the nucleus and commercial populations and the genetic coefficient of variation for the residual variance was 0.25 ± 0.01. The genetic correlation between weight and weight uniformity was close to zero in both environments. The estimate of the genetic correlation of weight uniformity between the two environments (selection nucleus and commercial population) was 0.64 ± 0.06.

Conclusions
The existence of genetic variance for weight uniformity suggests that genetic improvement of this trait is possible. Selection for weight uniformity should not decrease weight, given the near zero genetic correlation between these two traits. The strong genetic correlation of weight uniformity between the two environments indicates that response to selection for uniformity in the nucleus will be at least partially transmitted to the commercial population if this trait is included in the breeding goal.
Imputation accuracy to whole-genome sequence in Nellore cattle
Authors: Fernandes Júnior Gerardo A. , Carvalheiro Roberto , de Oliveira Henrique N. , Sargolzaei Mehdi , Costilla Roy , Ventura Ricardo V. , Fonseca Larissa F. S. , Neves Haroldo H. R. , Hayes Ben J. , de Albuquerque Lucia G. 
Published: March 2021

Abstract
Background
A cost-effective strategy to explore the complete DNA sequence in animals for genetic evaluation purposes is to sequence key ancestors of a population, followed by imputation mechanisms to infer marker genotypes that were not originally reported in a target population of animals genotyped with single nucleotide polymorphism (SNP) panels. The feasibility of this process relies on the accuracy of the genotype imputation in that population, particularly for potential causal mutations which may be at low frequency and either within genes or regulatory regions. The objective of the present study was to investigate the imputation accuracy to the sequence level in a Nellore beef cattle population, including that for variants in annotation classes which are more likely to be functional.

Methods
Information of 151 key sequenced Nellore sires were used to assess the imputation accuracy from bovine HD BeadChip SNP (~ 777 k) to whole-genome sequence. The choice of the sires aimed at optimizing the imputation accuracy of a genotypic database, comprised of about 10,000 genotyped Nellore animals. Genotype imputation was performed using two computational approaches: FImpute3 and Minimac4 (after using Eagle for phasing). The accuracy of the imputation was evaluated using a fivefold cross-validation scheme and measured by the squared correlation between observed and imputed genotypes, calculated by individual and by SNP. SNPs were classified into a range of annotations, and the accuracy of imputation within each annotation classification was also evaluated.

Results
High average imputation accuracies per animal were achieved using both FImpute3 (0.94) and Minimac4 (0.95). On average, common variants (minor allele frequency (MAF) > 0.03) were more accurately imputed by Minimac4 and low-frequency variants (MAF ≤ 0.03) were more accurately imputed by FImpute3. The inherent Minimac4 Rsq imputation quality statistic appears to be a good indicator of the empirical Minimac4 imputation accuracy. Both software provided high average SNP-wise imputation accuracy for all classes of biological annotations.

Conclusions
Our results indicate that imputation to whole-genome sequence is feasible in Nellore beef cattle since high imputation accuracies per individual are expected. SNP-wise imputation accuracy is software-dependent, especially for rare variants. The accuracy of imputation appears to be relatively independent of annotation classification.
Correlation between uniocular deviation and duction changes following different decompression surgeries in thyroid eye disease
Authors: Guo Jie , Li Xiaofeng , Ma Ruiqi , Qian Jiang 
Published: March 2021

Abstract
Background
Postoperative ocular imbalance is an important problem for orbital decompression surgery in thyroid eye disease (TED). The aim of this study was to evaluate the changes in unilateral ocular deviation and duction following orbital decompression and discuss the biomechanics of ocular imbalance.

Methods
Fifty-four TED patients who underwent unilateral orbital decompression were included. Fifteen patients underwent 1-wall (deep lateral wall) decompression, 18 patients underwent 2-wall (deep lateral and medial wall) decompression and 21 patients underwent 3-wall (deep lateral, medial and inferior wall) decompression. Objective and subjective deviation of the operated eyes were evaluated using the prism test and synoptophore, respectively. Ocular ductions were measured using Hirschberg’s method. The diameters of the extraocular rectus were measured by computed tomography.

Results
Ocular deviation and duction showed no significant difference after 1-wall decompression (p = 0.25–0.89). Esotropia increased after 2-wall decompression (p = 0.001–0.02), and hypotropia increased after 3-wall decompression (p = 0.02). Adduction increased but abduction decreased following 2-wall and 3-wall decompression (p < 0.05). Infraduction increased following 3-wall decompression (p < 0.001). Additionally, the increase in esotropia was significantly correlated with the increase in adduction and with the decrease in abduction (r = 0.37–0.63, p < 0.05). There were significant correlations between the diameter of the medial rectus and the increase in esotropia, the increase in adduction and the decrease in abduction postoperatively (r = 0.35–0.48, p < 0.05).

Conclusions
The changes in ocular deviation and duction were different after 1-wall, 2-wall and 3-wall orbital decompression. The increased contractile force of the rectus may be an important reason for strabismus changes after orbital decompression surgery.
Novel ERCC2 variant in trichothiodystrophy infant: the first case report in China
Authors: Chen Jian-Dong , Liao Wei-Dong , Wen Ling-Ying , Zhong Rong-Hua 
Published: March 2021

AbstractBackgroundTrichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder most commonly caused by variants inERCC2.Case presentationHere, we describe the first Chinese patient with a novel variant inERCC2. A male infant, who was born to a healthy non-consanguineous couple, exhibited brittle hair, hair loss ichthyosis, eczema, retinal pigmentation and hypospadias. He carried a novel heterozygousERCC2variant. The maternal variant (c.2191-18_2213del) is a previous described genomic deletion that affects the splicing of intron 22. The paternal variant (c.1666-1G > A), that occurs in the splice site of intron 17 and likely altersERCC2gene function through aberrant splicing, has not been reported previously.ConclusionsOur case reported a novel pathogenic variant inERCC2, which expanded the known genetic variants associated with TTD.
Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
Authors: Cancino-Marentes Martha E. , Hernández-Flores Georgina , Ortiz-Lazareno Pablo Cesar , Villaseñor-García María Martha , Orozco-Alonso Eduardo , Sierra-Díaz Erick , Solís-Martínez Raúl Antonio , Cruz-Gálvez Claudia Carolina , Bravo-Cuellar Alejandro 
Published: March 2021

Abstract
Background
Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) comprises the first line of treatment. However, the response is poor due to chemoresistance and toxicity. On the other hand, Pentoxifylline (PTX) is an unspecific inhibitor of phosphodiesterases; experimental, and clinically it has been described as sensitizing tumor cells to chemotherapy, increasing apoptosis and decreasing senescence. We study whether the PTX sensitizes prostate cancer cells to DTX for greater effectiveness.

Methods
PC3 human prostate cancer cells were treated in vitro at different doses and times with PTX, DTX, or their combination. Viability was determined by the WST-1 assay by spectrophotometry, cell cycle progression, apoptosis, generic caspase activation and senescence by flow cytometry, DNA fragmentation and caspases-3, -8, and -9 activity by ELISA.

Results
We found that PTX in PC3 human prostate cancer cells induces significant apoptosis per se and increases that generated by DTX, while at the same time it reduces the senescence caused by the chemotherapy and increases caspases-3,-8, and -9 activity in PTX + DTX-treated cells. Both treatments blocked the PC3 cell in the G1 phase.

Conclusions
Our results show that PTX sensitizes prostate tumor cells to apoptosis induced by DTX. Taken together, the results support the concept of chemotherapy with rational molecular bases.
The impact of early phase price agreements on prices of orphan drugs
Authors: Nuijten Mark , Van Wilder Philippe 
Published: March 2021

Abstract
Background
Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors.

Methods
We used a Pricing Model, which determines the minimum (break-even) price of an innovative drug from an investor’s perspective. This model is based on economic valuation theory, which uses the expected free cash flows and the required cost of capital. We selected two orphan drugs with a positive clinical assessment and an ICER higsher than the Dutch maximum threshold of €80,000 per QALY gained to use as examples in the model: Spinraza for spinal muscular atrophy and Orkambi for cystic fibrosis.
RESULTS: The results show that early pricing agreements before phase III trials can substantially lower the drug price resulting from a lower cost of capital. The minimum price for orphan drugs can be reduced by 27.4%, when cost of capital decreases from 12 to 9%. An additional adjustment of other critical parameters due to early pricing agreements (lower probabilities of phase III failure and lower research and development (R&D) costs) can further reduce the minimal price by 62.8%.

Conclusion
This study shows that earlier timing of price negotiations resulting in an agreement on drug price can substantially lower the minimal price of orphan drugs for the investor.
An epithelial-mesenchymal transition-related 5-gene signature predicting the prognosis of hepatocellular carcinoma patients
Authors: Zhu Gongmin , Xia Hongwei , Tang Qiulin , Bi Feng 
Published: March 2021

Abstract
Background
Tumor metastasis is one of the leading reasons of the dismal prognosis of hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is closely associated with tumor metastasis including HCC. The purpose of this study is to construct and validate an EMT-related gene signature for predicting the prognosis of HCC patients.

Methods
Gene expression data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to found the EMT-related gene sets which were obviously distinct between normal samples and paired HCC samples. Cox regression analysis was used to develop an EMT-related prognostic signature, and the performance of the signature was evaluated by Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. A nomogram incorporating the independent predictors was established. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the hub genes in HCC cell lines, and the role of PDCD6 in the metastasis of HCC was determined by functional experiments.

Results
An EMT-related 5-gene signature (PDCD6, TCOF1, TRIM28, EZH2 and FAM83D) was constructed using univariate and multivariate Cox regression analysis. Based on the signature, the HCC patients were classified into high- and low-risk groups, and patients in high-risk group had a poor prognosis. Time-dependent ROC and Cox regression analyses suggested that the signature could predict HCC prognosis exactly and independently. The predictive capacity of the signature was also validated in two external cohorts. GSEA results showed that many cancer-related signaling pathways such as PI3K/Akt/mTOR pathway and TGF-β/SMAD pathway were enriched in high-risk group. The result of qRT-PCR revealed that PDCD6, TCOF1 and FAM83D were highly expressed in HCC cancer cells. Among them, PDCD6 were found to promote cell migration and invasion.

Conclusion
The EMT-related 5-gene signature can serve as a promising prognostic biomarker for HCC patients and may provide a novel mechanism of HCC metastasis.
Performance of a sensitive haemozoin‐based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon
Authors: de Melo Gisely Cardoso , Netto Rebeca Linhares Abreu , Mwangi Victor Irungu , Salazar Yanka Evellyn Alves Rodrigues , de Souza Sampaio Vanderson , Monteiro Wuelton Marcelo , de Almeida e Val Fernando Fonseca , Rocheleau Anne , Thota Priyaleela , Lacerda Marcus Vinícius Guimarães 
Published: March 2021

Abstract
Background
Vivax malaria diagnosis remains a challenge in malaria elimination, with current point of care rapid diagnostic tests (RDT) missing many clinically significant infections because of usually lower peripheral parasitaemia. Haemozoin-detecting assays have been suggested as an alternative to immunoassay platforms but to date have not reached successful field deployment. Haemozoin is a paramagnetic crystal by-product of haemoglobin digestion by malaria parasites and is present in the food vacuole of malaria parasite-infected erythrocytes. This study aimed to compare the diagnostic capability of a new haemozoin-detecting platform, the Gazelle™ device with optical microscopy, RDT and PCR in a vivax malaria-endemic region.

Methods
A comparative, double-blind study evaluating symptomatic malaria patients seeking medical care was conducted at an infectious diseases reference hospital in the western Brazilian Amazon. Optical microscopy, PCR, RDT, and Gazelle™ were used to analyse blood samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa values were calculated.

Results
Out of 300 patients, 24 test results were excluded from the final analysis due to protocol violation (6) and inconclusive and/or irretrievable results (18). Gazelle™ sensitivity was 96.1 % (91.3–98.3) and 72.1 % (65.0–78.3) when compared to optical microscopy and PCR, respectively whereas it was 83.9 % and 62.8 % for RDTs. The platform presented specificity of 100 % (97.4–100), and 99.0 % (94.8–99.9) when compared to optical microscopy, and PCR, respectively, which was the same for RDTs. Its correct classification rate was 98.2 % when compared to optical microscopy and 82.3 % for PCR; the test’s accuracy when compared to optical microscopy was 98.1 % (96.4–99.7), when compared to RDT was 95.2 % (93.0–97.5), and when compared to PCR was 85.6 % (82.1–89.1). Kappa (95 % CI) values for Gazelle™ were 96.4 (93.2–99.5), 88.2 (82.6–93.8) and 65.3 (57.0–73.6) for optical microscopy, RDT and PCR, respectively.

Conclusions
The Gazelle™ device was shown to have faster, easier, good sensitivity, specificity, and accuracy when compared to microscopy and was superior to RDT, demonstrating to be an alternative for vivax malaria screening particularly in areas where malaria is concomitant with other febrile infections (including dengue fever, zika, chikungunya, Chagas, yellow fever, babesiosis).
“My first 48 hours out”: drug users’ perspectives on challenges and strategies upon release from prison
Authors: Jamin Daniela , Vanderplasschen Wouter , Sys Orphée , Jauffret-Roustide Marie , Michel Laurent , Trouiller Philippe , Neisa Andreia , Homen Mariana , Mendes Vânia , Stöver Heino 
Published: March 2021

Abstract
Background
Prisoners report much higher prevalence rates of drug use and more harmful consumption patterns than the general population. People who use drugs have above-average experiences with the criminal justice system in general, and the prison system and subsequent release situations in particular. Release from prison is associated with increased mortality rates among drug users due to the risk of overdose. The EU-funded project ‘My first 48 hours out’ aimed to address the gaps in continuity of care for long-term drug users in prison and upon release, with a special focus on drug user’s perspectives on needs and challenges upon release.

Methods
A multi-country (Belgium, France, Germany and Portugal) qualitative study was set up to explore drug users’ perceptions of drug use and risk behaviour upon prison release, experiences of incarceration and release, and strategies to avoid risks when being released. In total, 104 prisoners and recently released persons with a history of drug use participated in semi-structured interviews and focus groups discussions on these topics.

Results
Respondents pointed out that there are numerous challenges for people who use drugs when released from prison. Lack of stable housing and employment support were frequently mentioned, as well as complex administrative procedures regarding access to services, health insurance and welfare benefits. Besides structural challenges, individual issues may challenge social reintegration like ‘old habits’, mental health problems and disrupted social networks. As a result, (ex-)prisoners adopt individual strategies to cope with the risks and challenges at release.

Conclusion
Measures to prepare prisoners for release often do not focus on the individual and specific challenges of persons who use drugs. Psychosocial and medical support need to be improved and adjusted to drug users’ needs inside and outside prison. To improve the quality and continuity of care around release, the perspectives and coping strategies of people who use drugs should be used to better address their needs and barriers to treatment.
A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
Authors: Liu Renjie , Wang Guifu , Zhang Chi , Bai Dousheng 
Published: March 2021

Abstract
Background
Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated.

Methods
To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model.

Results
Compared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram.

Conclusion
Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.
Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries
Authors: Rowley Seth , Garcia-Gonzalez Pat , Radich Jerald P. , Novakowski Ann Kim , Usherenko Irina , Babigumira Joseph B. 
Published: March 2021

Abstract
Purpose
To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs).

Methods
We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid’s GeneXpert® IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives.

Results
The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges.

Conclusion
Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.