bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of biomarkers predictive of metastasis development in early-stage colorectal cancer using network-based regularization
Authors: Peixoto Carolina , Lopes Marta B. , Martins Marta , Casimiro Sandra , Sobral Daniel , Grosso Ana Rita , Abreu Catarina , Macedo Daniela , Costa Ana Lúcia , Pais Helena , Alvim Cecília , Mansinho André , Filipe Pedro , Costa Pedro Marques da , Fernandes Afonso , Borralho Paula , Ferreira Cristina , Malaquias João , Quintela António , Kaplan Shannon , Golkaram Mahdi , Salmans Michael , Khan Nafeesa , Vijayaraghavan Raakhee , Zhang Shile , Pawlowski Traci , Godsey Jim , So Alex , Liu Li , Costa Luís , Vinga Susana 
Published: January 2023

AbstractColorectal cancer (CRC) is the third most common cancer and the second most deathly worldwide. It is a very heterogeneous disease that can develop via distinct pathways where metastasis is the primary cause of death. Therefore, it is crucial to understand the molecular mechanisms underlying metastasis. RNA-sequencing is an essential tool used for studying the transcriptional landscape. However, the high-dimensionality of gene expression data makes selecting novel metastatic biomarkers problematic. To distinguish early-stage CRC patients at risk of developing metastasis from those that are not, three types of binary classification approaches were used: (1) classification methods (decision trees, linear and radial kernel support vector machines, logistic regression, and random forest) using differentially expressed genes (DEGs) as input features; (2) regularized logistic regression based on the Elastic Net penalty and the proposed iTwiner—a network-based regularizer accounting for gene correlation information; and (3) classification methods based on the genes pre-selected using regularized logistic regression. Classifiers using the DEGs as features showed similar results, with random forest showing the highest accuracy. Using regularized logistic regression on the full dataset yielded no improvement in the methods’ accuracy. Further classification using the pre-selected genes found by different penalty factors, instead of the DEGs, significantly improved the accuracy of the binary classifiers. Moreover, the use of network-based correlation information (iTwiner) for gene selection produced the best classification results and the identification of more stable and robust gene sets. Some are known to be tumor suppressor genes (OPCML-IT2), to be related to resistance to cancer therapies (RAC1P3), or to be involved in several cancer processes such as genome stability (XRCC6P2), tumor growth and metastasis (MIR602) and regulation of gene transcription (NME2P2). We show that the classification of CRC patients based on pre-selected features by regularized logistic regression is a valuable alternative to using DEGs, significantly increasing the models’ predictive performance. Moreover, the use of correlation-based penalization for biomarker selection stands as a promising strategy for predicting patients’ groups based on RNA-seq data.
A draft Diabrotica virgifera virgifera genome: insights into control and host plant adaption by a major maize pest insect
Authors: Coates Brad S. , Walden Kimberly K. O. , Lata Dimpal , Vellichirammal Neetha Nanoth , Mitchell Robert F. , Andersson Martin N. , McKay Rachel , Lorenzen Marcé D. , Grubbs Nathaniel , Wang Yu-Hui , Han Jinlong , Xuan Jing Li , Willadsen Peter , Wang Huichun , French B. Wade , Bansal Raman , Sedky Sammy , Souza Dariane , Bunn Dakota , Meinke Lance J. , Miller Nicholas J. , Siegfried Blair D. , Sappington Thomas W. , Robertson Hugh M. 
Published: January 2023

AbstractBackgroundAdaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm,Diabrotica virgifera virgifera(Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance ofD. v. virgiferato crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown.ResultsA 2.42 Gb draftD. v. virgiferagenome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotatedD. v. virgiferacytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed betweenD. v. virgiferalarvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were betweenMiscanthuscompared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts.ConclusionsManual annotation ofD. v. virgiferaDvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations ofD. v. virgiferalarvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.
Organ-specific expression of genes associated with the UDP-glucose metabolism in sugarcane (Saccharum spp. hybrids)
Authors: Mason Patrick J. , Hoang Nam V. , Botha Frederik C. , Furtado Agnelo , Marquardt Annelie , Henry Robert J. 
Published: January 2023

Abstract
Background
The importance of uridine 5′-diphosphate glucose (UDP-G) synthesis and degradation on carbon (C) partitioning has been indicated in several studies of plant systems, whereby the kinetic properties and abundance of involved enzymes had a significant effect upon the volume of C moving into the hemicellulose, cellulose and sucrose pools. In this study, the expression of 136 genes belonging to 32 gene families related to UDP-G metabolism was studied in 3 major sugarcane organs (including leaf, internode and root) at 6 different developmental stages in 2 commercial genotypes.

Results
Analysis of the genes associated with UDP-G metabolism in leaves indicated low expression of sucrose synthase, but relatively high expression of invertase genes, specifically cell-wall invertase 4 and neutral acid invertase 1–1 and 3 genes. Further, organs that are primarily responsible for sucrose synthesis or bioaccumulation, i.e., in source organs (mature leaves) and storage sink organs (mature internodes), had very low expression of sucrose, cellulose and hemicellulose synthesis genes, specifically sucrose synthase 1 and 2, UDP-G dehydrogenase 5 and several cellulose synthase subunit genes. Gene expression was mostly very low in both leaf and mature internode samples; however, leaves did have a comparatively heightened invertase and sucrose phosphate synthase expression. Major differences were observed in the transcription of several genes between immature sink organs (roots and immature internodes). Gene transcription favoured utilisation of UDP-G toward insoluble and respiratory pools in roots. Whereas, there was comparatively higher expression of sucrose synthetic genes, sucrose phosphate synthase 1 and 4, and comparatively lower expression of many genes associated with C flow to insoluble and respiratory pools including myo-Inositol oxygenase, UDP-G dehydrogenase 4, vacuolar invertase 1, and several cell-wall invertases in immature internodes.

Conclusion
This study represents the first effort to quantify the expression of gene families associated with UDP-G metabolism in sugarcane. Transcriptional analysis displayed the likelihood that C partitioning in sugarcane is closely related to the transcription of genes associated with the UDP-G metabolism. The data presented may provide an accurate genetic reference for future efforts in altering UDP-G metabolism and in turn C partitioning in sugarcane.
The multifaceted roles of Arbuscular Mycorrhizal Fungi in peanut responses to salt, drought, and cold stress
Authors: Liu Yuexu , Lu Jinhao , Cui Li , Tang Zhaohui , Ci Dunwei , Zou Xiaoxia , Zhang Xiaojun , Yu Xiaona , Wang Yuefu , Si Tong 
Published: January 2023

Abstract
Background
Arbuscular Mycorrhizal Fungi (AMF) are beneficial microorganisms in soil-plant interactions; however, the underlying mechanisms regarding their roles in legumes environmental stress remain elusive. Present trials were undertaken to study the effect of AMF on the ameliorating of salt, drought, and cold stress in peanut (Arachis hypogaea L.) plants. A new product of AMF combined with Rhizophagus irregularis SA, Rhizophagus clarus BEG142, Glomus lamellosum ON393, and Funneliformis mosseae BEG95 (1: 1: 1: 1, w/w/w/w) was inoculated with peanut and the physiological and metabolomic responses of the AMF-inoculated and non-inoculated peanut plants to salt, drought, and cold stress were comprehensively characterized, respectively.

Results
AMF-inoculated plants exhibited higher plant growth, leaf relative water content (RWC), net photosynthetic rate, maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm), activities of antioxidant enzymes, and K+: Na+ ratio while lower leaf relative electrolyte conductivity (REC), concentration of malondialdehyde (MDA), and the accumulation of reactive oxygen species (ROS) under stressful conditions. Moreover, the structures of chloroplast thylakoids and mitochondria in AMF-inoculated plants were less damaged by these stresses. Non-targeted metabolomics indicated that AMF altered numerous pathways associated with organic acids and amino acid metabolisms in peanut roots under both normal-growth and stressful conditions, which were further improved by the osmolytes accumulation data.

Conclusion
This study provides a promising AMF product and demonstrates that this AMF combination could enhance peanut salt, drought, and cold stress tolerance through improving plant growth, protecting photosystem, enhancing antioxidant system, and regulating osmotic adjustment.
Recruitment and retention into longitudinal health research from an adolescent perspective: a qualitative study
Authors: Jong Stephanie T. , Stevenson Rebecca , Winpenny Eleanor M. , Corder Kirsten , van Sluijs Esther M. F. 
Published: January 2023

Abstract
Background
High quality longitudinal studies investigating changes in health behaviours over the transition into early adulthood are critical. However, recruiting and retaining adolescents is challenging. This study explored adolescents’ perspectives of signing up to and continuing involvement in a hypothetical longitudinal health research study.

Methods
Forty-eight individuals (15-20y) participated in nine in-person focus groups about recruitment and retention in research. Participants were (a) school students in the last year of compulsory school (Year 11, 15-16y), (b) school/college students in Sixth Form (Year 13, 17-18y), (c) Further Education students studying after secondary education, but not higher education (16-18y) and (d) young adults not in education, employment, or training (18-20y) across England. Thematic analysis resulted in seven themes.

Results
Driving factors for sign-up included social connection e.g., joining with peer groups, personalised feedback, and incentives, primarily financial. Key barriers were lack of interest, the perception of commitment, and timing of recruitment. Young people preferred recruitment processes via social media with messages tailored to their motivations, monthly data collection of maximally 20–30 min, and hybrid data collection with some in-person contact with a consistent, non-judgemental researcher. The provision of autonomy, choice, and financial incentives were perceived to promote retention.

Conclusions
Adolescent recruitment and retention strategies need to align with contemporary interests and motivations. Studies should involve adolescents early to develop a planned, systematic approach to participant sign-up and follow-up. Effective and ineffective recruitment and retention strategies should be reported as part of study findings. Future research should trial how perceived barriers to study engagement can be overcome.
Understanding illness experiences of patients with primary sclerosing cholangitis: a qualitative analysis within the SOMA.LIV study
Authors: Loesken Caroline , Maehder Kerstin , Buck Laura , Hartl Johannes , Löwe Bernd , Schramm Christoph , Toussaint Anne 
Published: January 2023

Abstract
Background
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with a largely unpredictable course. Due to limited treatment options, individuals may for many years suffer from distressing symptoms and the emotional burden of an uncertain future. The need to shift from cure to care of PSC has spurred an interest into patients’ health-related quality of life. Qualitative research in this context remains scarce. Hence, this study aimed to enrich the clinical understanding about the lived experience of PSC through a qualitative approach.

Methods
A total of 20 patients with PSC were recruited at a specialist centre for autoimmune liver disease in Germany and engaged in semi-structured telephone-based interviews between March and June 2022. Verbatim transcripts were interpreted using inductive thematic analysis.

Results
An overarching concept of ‘a wave-like experience’ was formulated to illustrate the dual and shifting nature of living with PSC. Reflecting upon this central idea, three major themes were generated to address important aspects of participants’ illness experiences: ‘Invisible presence’ focused on perceptions of suffering from a seemingly hidden illness that periodically reveals itself through specific trigger events. ‘Embracing the threat’ captured the psycho-emotional response shift to this chronic disease from a predominantly negative to a coping-oriented pattern with regular setbacks. ‘Between control and constraints’ uncovered restrictions that PSC enforces onto patients’ lives and their desire for controllability.

Conclusions
The present study provides an in-depth look at the fluctuating tensions arising from a life with PSC. Insights on perceived invisibility, disease-related triggers of emotional distress and the complexity behind self-management highlight opportunities for enhanced clinical support of this patient group.
Comparison of adverse pregnancy and birth outcomes using archival medical records before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo: a facility-based, retrospective cohort study
Authors: Arena Patrick J. , Dzogang Camille , Gadoth Adva , Nkamba Dalau Mukadi , Hoff Nicole A. , Kampilu David , Beia Michael , Wong Hui-Lee , Anderson Steven A. , Kaba Didine , Rimoin Anne W. 
Published: January 2023

Abstract
Background
Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC).

Methods
We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions.

Results
In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p < 0.0001). Furthermore, the level of diagnostic certainty declined slightly across all outcomes investigated from the pre-COVID-19 to the intra-COVID-19 period. Nonetheless, diagnostic certainty was especially low for certain outcomes (i.e., stillbirth and NBSI) regardless of period; still, other outcomes, such as preterm birth and LBW, had moderate to high levels of diagnostic certainty. Results were mostly consistent when the analysis was focused on the facilities designated for COVID-19 care.

Conclusion
This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa.
Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers
Authors: Li Fei , Cai He , Tian Li , Bai Haiyan , Shi Juanzi 
Published: January 2023

Abstract
Background
Late follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles.

Methods
The single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models.

Results
LBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response.

Conclusions
In fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.
De novo variations of ANK1 gene caused hereditary spherocytosis in two Chinese children by affecting pre-mRNA splicing
Authors: Wang Yang , Huang Lan , Zhu Yao , An Xizhou , Li Jiacheng , Zhen Jiangwei , Yu Jie 
Published: January 2023

Abstract
Background and aims
Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic disorders. Here, two unrelated families with the probands displaying typical manifestations of HS were enrolled. Our study aimed to characterize the effect of two novel variants in HS patients on gene splicing to help minimize the rate of misdiagnosis of HS and enhance clinicians’ understanding of the disease.

Participants and methods
A retrospective review was conducted. Peripheral blood samples were collected from all the family members, and genomic DNA was extracted for genetic diagnostics. First, high-throughput sequencing technology was used for the preliminary screening of candidate causative variants. Thereafter, the variants were verified via Sanger sequencing. Furthermore, a pathogenicity analysis of the detected variants was performed including in silico prediction and in vitro experiments. We constructed matched wild-type and mutant-type minigene plasmid of ANK1 based on HEK293T cells to address the effects of variants on mRNA splicing.

Results
The c.1305 + 2 T > A (family1) and c.1305 + 2del (family2) variants were detected in the ANK1 gene. These two de novo mutations described by us which have not been reported prior to this study. Moreover, the validation results of splicing reporter systems revealed that the intronic mutations resulted in abnormal pre-mRNA splicing. Specifically, the minigene plasmid expressing the c.1305 + 2 T > A variant transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 229 and r.1305_1306ins1305 + 1_1305 + 552. The minigene plasmid expressing c.1305 + 2del transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 228 and r.1305_1306ins1305 + 1_1305 + 551.

Conclusion
The two de novo variants identified in the ANK1 gene were the genetic etiology of the probands with HS in our study. Our findings further enrich the HS genotype database and provide a basis for genetic counselling and molecular diagnosis.