bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blueberry stem extract and stem active components prevent blue light-emitting diode light-induced retinal photoreceptor cell damagein vitro
Authors: Ogawa Kenjirou , Urata Karin , Suzuki Yosuke , Sugamoto Kazuhiro , Goto Yo , Nakayama Takayuki , Nishiyama Kazuo , Kunitake Hisato , Yamasaki Masao 
Published: January 2023

ABSTRACTBlue light causes retinal damage that can lead to ocular diseases such as age-related macular degeneration. In this study, we determined the protective effect of blueberry stem extract (BStEx) and active components on blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage in vitro. Photoreceptor cells cultured in the presence of BStEx or components were exposed to blue light to induce cell damage. BStEx, fractions of BStEx containing proanthocyanidins, chlorogenic acid, catechin, and epicatechin prevented the cell damage and/or inhibited the generation of reactive oxygen species (ROS). Furthermore, BStEx reduced apoptosis and cell death, and inhibited the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase leading to cellular apoptosis induced by blue light exposure. These findings suggest that BStEx and components exert a protective effect against blue light-induced photoreceptor cell damage through the inhibition of MAPK phosphorylation and ROS production.
The effect of heterospecific and conspecific competition on inter-individual differences in tungara frog tadpole (Engystomops pustulosus) behavior
Authors: Beyts Cammy , Cella Maddalena , Colegrave Nick , Downie Roger , Martin Julien G A , Walsh Patrick 
Published: January 2023

AbstractRepeated social interactions with conspecifics and/or heterospecifics during early development may drive the differentiation of behavior among individuals. Competition is a major form of social interaction and its impacts can depend on whether interactions occur between conspecifics or heterospecifics and the directionality of a response could be specific to the ecological context that they are measured in. To test this, we reared tungara frog tadpoles (Engystomops pustulosus) either in isolation, with a conspecific tadpole or with an aggressive heterospecific tadpole, the whistling frog tadpole (Leptodactylus fuscus). In each treatment, we measured the body size and distance focal E. pustulosus tadpoles swam in familiar, novel and predator risk contexts six times during development. We used univariate and multivariate hierarchical mixed effect models to investigate the effect of treatment on mean behavior, variance among and within individuals, behavioral repeatability and covariance among individuals in their behavior between contexts. There was a strong effect of competition on behavior, with different population and individual level responses across social treatments. Within a familiar context, the variance in the distance swam within individuals decreased under conspecific competition but heterospecific competition caused more variance in the average distance swam among individuals. Behavioral responses were also context specific as conspecific competition caused an increase in the distance swam within individuals in novel and predator risk contexts. The results highlight that the impact of competition on among and within individual variance in behavior is dependent on both competitor species identity and context.
Liquidhope: methylome and genomic profiling from very limited quantities of plasma-derived DNA
Authors: Trinidad Eva María , Vidal Enrique , Coronado Esther , Esteve-Codina Anna , Castel Victoria , Cañete Adela , Gut Marta , Heath Simon , Font de Mora Jaime 
Published: January 2023

Abstract
Analysis of the methylome of tumor cell-free deoxyribonucleic acid (DNA; cfDNA) has emerged as a powerful non-invasive technique for cancer subtyping and prognosis. However, its application is frequently hampered by the quality and total cfDNA yield. Here, we demonstrate the feasibility of very low-input cfDNA for whole-methylome and copy-number profiling studies using enzymatic conversion of unmethylated cysteines [enzymatic methyl-seq (EM-seq)] to better preserve DNA integrity. We created a model for predicting genomic subtyping and prognosis with high accuracy. We validated our tool by comparing whole-genome CpG sequencing with in situ cohorts generated with bisulfite conversion and array hybridization, demonstrating that, despite the different techniques and sample origins, information on cfDNA methylation is comparable with in situ cohorts. Our findings support use of liquid biopsy followed by EM-seq to assess methylome of cancer patients, enabling validation in external cohorts. This advance is particularly relevant for rare cancers like neuroblastomas where liquid-biopsy volume is restricted by ethical regulations in pediatric patients.
Structure-preserved dimension reduction using joint triplets sampling for multi-batch integration of single-cell transcriptomic data
Authors: Xu Xinyi , Li Xiangjie 
Published: January 2023

Abstract
Dimension reduction (DR) plays an important role in single-cell RNA sequencing (scRNA-seq), such as data interpretation, visualization and other downstream analysis. A desired DR method should be applicable to various application scenarios, including identifying cell types, preserving the inherent structure of data and handling with batch effects. However, most of the existing DR methods fail to accommodate these requirements simultaneously, especially removing batch effects. In this paper, we develop a novel structure-preserved dimension reduction (SPDR) method using intra- and inter-batch triplets sampling. The constructed triplets jointly consider each anchor’s mutual nearest neighbors from inter-batch, k-nearest neighbors from intra-batch and randomly selected cells from the whole data, which capture higher order structure information and meanwhile account for batch information of the data. Then we minimize a robust loss function for the chosen triplets to obtain a structure-preserved and batch-corrected low-dimensional representation. Comprehensive evaluations show that SPDR outperforms other competing DR methods, such as INSCT, IVIS, Trimap, Scanorama, scVI and UMAP, in removing batch effects, preserving biological variation, facilitating visualization and improving clustering accuracy. Besides, the two-dimensional (2D) embedding of SPDR presents a clear and authentic expression pattern, and can guide researchers to determine how many cell types should be identified. Furthermore, SPDR is robust to complex data characteristics (such as down-sampling, duplicates and outliers) and varying hyperparameter settings. We believe that SPDR will be a valuable tool for characterizing complex cellular heterogeneity.
slORFfinder: a tool to detect open reading frames resulting from trans-splicing of spliced leader sequences
Authors: Song Bo , Li Hao , Jiang Mengyun , Gao Zhongtian , Wang Suikang , Gao Lei , Chen Yunsheng , Li Wujiao 
Published: January 2023

Abstract
Trans-splicing of a spliced leader (SL) to the 5′ ends of mRNAs is used to produce mature mRNAs in several phyla of great importance to human health and the marine ecosystem. One of the consequences of the addition of SL sequences is the change or disruption of the open reading frames (ORFs) in the recipient transcripts. Given that most SL sequences have one or more of the trinucleotide NUG, including AUG in flatworms, trans-splicing of SL sequences can potentially supply a start codon to create new ORFs, which we refer to as slORFs, in the recipient mRNAs. Due to the lack of a tool to precisely detect them, slORFs were usually neglected in previous studies. In this work, we present the tool slORFfinder, which automatically links the SL sequences to the recipient mRNAs at the trans-splicing sites identified from SL-containing reads of RNA-Seq and predicts slORFs according to the distribution of ribosome-protected footprints (RPFs) on the trans-spliced transcripts. By applying this tool to the analyses of nematodes, ascidians and euglena, whose RPFs are publicly available, we find wide existence of slORFs in these taxa. Furthermore, we find that slORFs are generally translated at higher levels than the annotated ORFs in the genomes, suggesting they might have important functions. Overall, this study provides a tool, slORFfinder (https://github.com/songbo446/slORFfinder), to identify slORFs, which can enhance our understanding of ORFs in taxa with SL machinery.
Learning from small medical data—robust semi-supervised cancer prognosis classifier with Bayesian variational autoencoder
Authors: Hsu Te-Cheng , Lin Che 
Published: January 2023

Abstract

Motivation
Cancer is one of the world’s leading mortality causes, and its prognosis is hard to predict due to complicated biological interactions among heterogeneous data types. Numerous challenges, such as censorship, high dimensionality and small sample size, prevent researchers from using deep learning models for precise prediction.

Results
We propose a robust Semi-supervised Cancer prognosis classifier with bAyesian variational autoeNcoder (SCAN) as a structured machine-learning framework for cancer prognosis prediction. SCAN incorporates semi-supervised learning for predicting 5-year disease-specific survival and overall survival in breast and non-small cell lung cancer (NSCLC) patients, respectively. SCAN achieved significantly better AUROC scores than all existing benchmarks (81.73% for breast cancer; 80.46% for NSCLC), including our previously proposed bimodal neural network classifiers (77.71% for breast cancer; 78.67% for NSCLC). Independent validation results showed that SCAN still achieved better AUROC scores (74.74% for breast; 72.80% for NSCLC) than the bimodal neural network classifiers (64.13% for breast; 67.07% for NSCLC). SCAN is general and can potentially be trained on more patient data. This paves the foundation for personalized medicine for early cancer risk screening.

Availability and implementation
The source codes reproducing the main results are available on GitHub: https://gitfront.io/r/user-4316673/36e8714573f3fbfa0b24690af5d1a9d5ca159cf4/scan/.

Supplementary information
Supplementary data are available at Bioinformatics Advances online.
Efficient querying of genomic reference databases with gget
Authors: Luebbert Laura , Pachter Lior 
Published: January 2023

Abstract

Motivation
A recurring challenge in interpreting genomic data is the assessment of results in the context of existing reference databases. With the increasing number of command line and Python users, there is a need for tools implementing automated, easy programmatic access to curated reference information stored in a diverse collection of large, public genomic databases.

Results
gget is a free and open-source command line tool and Python package that enables efficient querying of genomic reference databases, such as Ensembl. gget consists of a collection of separate but interoperable modules, each designed to facilitate one type of database querying required for genomic data analysis in a single line of code.

Availability and implementation
The manual and source code are available at https://github.com/pachterlab/gget.

Supplementary information
Supplementary data are available at Bioinformatics online.
Actin-related protein ACTL7B ablation leads to OAT with multiple morphological abnormalities of the flagellum and male infertility in mice
Authors: Clement Tracy M , Geyer Christopher B , Willis William D , Goulding Eugenia H , Upadhyay Srijana , Eddy Edward M 
Published: January 2023

AbstractThe formation of fertilisation-competent sperm requires spermatid morphogenesis (spermiogenesis), a poorly understood program that involves complex coordinated restructuring and specialised cytoskeletal structures. A major class of cytoskeletal regulators are the actin-related proteins (ARPs), which include conventional actin variants, and related proteins that play essential roles in complexes regulating actin dynamics, intracellular transport, and chromatin remodeling. Multiple testis-specific ARPs are well conserved among mammals, but their functional roles are unknown. One of these is actin-like 7b (Actl7b) that encodes an orphan ARP highly similar to the ubiquitously expressed beta actin (ACTB). Here we report ACTL7B is expressed in human and mouse spermatids through the elongation phase of spermatid development. In mice, ACTL7B specifically localises to the developing acrosome, within the nucleus of early spermatids, and to the flagellum connecting region. Based on this localisation pattern and high level of sequence conservation in mice, humans, and other mammals, we examined the requirement for ACTL7B in spermiogenesis by generating and characterising the reproductive phenotype of male Actl7b KO mice. KO mice were infertile, with severe and variable oligoteratozoospermia (OAT) and multiple morphological abnormalities of the flagellum (MMAF) and sperm head. These defects phenocopy human OAT and MMAF, which are leading causes of idiopathic male infertility. In conclusion, this work identifies ACTL7B as a key regulator of spermiogenesis that is required for male fertility.
BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axis
Authors: Li Yali , Zhao Hui , Li Ning , Yuan Chao , Dong Nana , Wen Jin , Li Zihui , Wang Qun , Wang Lina , Mao Haiting 
Published: January 2023

AbstractRecurrent pregnancy loss (RPL) is a common pathological problem during pregnancy, and its clinical etiology is complex and unclear. Dysfunction of trophoblasts may cause a series of pregnancy complications, including preeclampsia, fetal growth restriction, and RPL. Recently, lncRNAs have been found to be closely related to the occurrence and regulation of pregnancy-related diseases, but few studies have focused on their role in RPL. In this study, we identified a novel lncRNA BBOX1-AS1 that was significantly upregulated in villous tissues and serum of RPL patients. Functionally, BBOX1-AS1 inhibited proliferation, migration, invasion, tube formation and promoted apoptosis of trophoblast cells. Mechanistically, overexpression of BBOX1-AS1 activated the p38 and JNK MAPK signaling pathways by upregulating GADD45A expression. Further studies indicated that BBOX1-AS1 could increase the stability of GADD45A mRNA by binding hnRNPK and ultimately cause abnormal trophoblast function. Collectively, our study highlights that the BBOX1-AS1/hnRNPK/GADD45A axis plays an important role in trophoblast-induced RPL and that BBOX1-AS1 may serve as a potential target for the diagnosis of RPL.
Evaluation Options for Wildlife Management and Strengthening of Causal Inference
Authors: Hone Jim , Drake V Alistair , Krebs Charles J 
Published: January 2023

AbstractWildlife management aims to halt and then reverse the decline of threatened species, to sustainably harvest populations, and to control undesirable impacts of some species. We describe a unifying framework of three feasible options for evaluation of wildlife management, including conservation, and discuss their relative strengths of statistical and causal inference. The first option is trends in abundance, which can provide strong evidence a change has occurred (statistical inference) but does not identify the causes. The second option assesses population outcomes relative to management efforts, which provides strong evidence of cause and effect (causal inference) but not the trend. The third option combines the first and second options and therefore provides both statistical and causal inferences in an adaptive framework. We propose that wildlife management needs to explicitly use causal criteria and inference to complement adaptive management. We recommend incorporating these options into management plans.
Making Desistance Recognizable: How Ex-Offenders Can Signal Their Desistance From Crime to Employers by Strategic Design
Authors: Reich Suzanne E 
Published: January 2023

Abstract
One of the primary concerns employers hold about hiring an ex-offender is the potential reoffending risk they pose. However, criminological literature shows that an ex-offender may be able to mitigate employers’ concerns by signalling their desistance from crime. Less understood is how ex-offenders can signal their desistance to (a) make desistance recognizable and (2) communicate desistance signals that employers value. This article draws on the results from the second phase of an Explanatory Sequential Mixed Methods study with a sample of Australian employers who participated in semi-structured interviews (n = 43). The findings show desistance signals can be communicated to employers via strategic design. These findings along with the theoretical and policy implications are then discussed.
A Disproportionate Risk of Being Executed: Why Pakistani Migrants Are Vulnerable to Capital Punishment in Saudi Arabia
Authors: Hoyle Carolyn , Hutton Jocelyn , Harry Lucy 
Published: January 2023

AbstractMany labour migrants in the Arab Gulf countries are from South Asia. Necessary to local economies, they enjoy few rights and protections from host states, particularly when accused of serious crimes. Our original empirical data suggests a disproportionate number of Pakistanis sentenced to death and executed in Saudi Arabia and we explore explanations within a wider discussion of the place and experiences of South Asian migrants in the Gulf. Our data suggest that drug laws and penal policies leave migrant workers particularly susceptible to capital punishment, with the administration of migrant employment recruitment processes exposing Pakistanis to coercion into drug trafficking such that some could be regarded not as criminally liable but as victims of human trafficking.
Association of metformin use and survival in patients with cutaneous melanoma and diabetes
Authors: Krakowski Isabelle , Häbel Henrike , Nielsen Kari , Ingvar Christian , Andersson Therese M L , Girnita Ada , Smedby Karin E , Eriksson Hanna 
Published: January 2023

Abstract

Background
Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive.

Objectives
To investigate the association between metformin use and survival among patients with CM and diabetes.

Methods
All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses.

Results
Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4–6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57–0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS: the HR for prediagnostic use was 0.90 (95% CI 0.86–0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97–0.98) for 0–6 months to 0.59 (0.49–0.70) for 24–30 months of use. No association was found for metformin use and MSS.

Conclusions
Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose–response pattern. However, further research regarding the underlying mechanisms is warranted.
Insights into atopic dermatitis pathogenesis lead to newly approved systemic therapies
Authors: Trier Anna M , Kim Brian S 
Published: January 2023

AbstractAtopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition.
Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial
Authors: Thaçi Diamant , Vender Ron , de Rie Menno A , Conrad Curdin , Pariser David M , Strober Bruce , Vanvoorden Veerle , Wang Maggie , Madden Cynthia , de Cuyper Dirk , Kimball Alexa B 
Published: January 2023

Abstract

Background
BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings.

Objectives
To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis.

Methods
The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes.

Results
Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24–104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low.

Conclusions
Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.