bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and splicing mediate distinct biological signals
Authors: Dam Søren Helweg , Olsen Lars Rønn , Vitting-Seerup Kristoffer 
Published: October 2023

Abstract
Background
Through alternative splicing, most human genes produce multiple isoforms in a cell-, tissue-, and disease-specific manner. Numerous studies show that alternative splicing is essential for development, diseases, and their treatments. Despite these important examples, the extent and biological relevance of splicing are currently unknown.

Results
To solve this problem, we developed pairedGSEA and used it to profile transcriptional changes in 100 representative RNA-seq datasets. Our systematic analysis demonstrates that changes in splicing, on average, contribute to 48.1% of the biological signal in expression analyses. Gene-set enrichment analysis furthermore indicates that expression and splicing both convey shared and distinct biological signals.

Conclusions
These findings establish alternative splicing as a major regulator of the human condition and suggest that most contemporary RNA-seq studies likely miss out on critical biological insights. We anticipate our results will contribute to the transition from a gene-centric to an isoform-centric research paradigm.
The BAF chromatin remodeling complex licenses planarian stem cells access to ectodermal and mesodermal cell fates
Authors: Wiggans Mallory , Zhu Shu Jun , Molinaro Alyssa M. , Pearson Bret J. 
Published: October 2023

Abstract
Background
The flatworm planarian, Schmidtea mediterranea, has a large population of adult stem cells (ASCs) that replace any cell type during tissue turnover or regeneration. How planarian ASCs (called neoblasts) manage self-renewal with the ability to produce daughter cells of different cell lineages (multipotency) is not well understood. Chromatin remodeling complexes ultimately control access to DNA regions of chromosomes and together with specific transcription factors determine whether a gene is transcribed in a given cell type. Previous work in planarians determined that RNAi of core components of the BAF chromatin remodeling complex, brg1 and smarcc2, caused increased ASCs and failed regeneration, but how these cellular defects arise at the level of gene regulation in neoblasts is unknown.

Results
Here, we perform ATAC and RNA sequencing on purified neoblasts, deficient for the BAF complex subunits brg-1 and smarcc2. The data demonstrate that the BAF complex promotes chromatin accessibility and facilitates transcription at target loci, as in other systems. Interestingly, we find that the BAF complex enables access to genes known to be required for the generation of mesoderm- and ectoderm-derived lineages, including muscle, parenchymal cathepsin, neural, and epithelial lineages. BAF complex knockdowns result in disrupted differentiation into these cell lineages and functional consequences on planarian regeneration and tissue turnover. Notably, we did not detect a role for the BAF complex in neoblasts making endodermal lineages.

Conclusions
Our study provides functional insights into how the BAF complex contributes to cell fate decisions in planarian ASCs in vivo.
Simple analysis of gel images with IOCBIO Gel
Authors: Kütt Jaak , Margus Georg , Kask Lauri , Rätsepso Triinu , Soodla Kärol , Bernasconi Romain , Birkedal Rikke , Järv Priit , Laasmaa Martin , Vendelin Marko 
Published: October 2023

Abstract
Background
Current solutions for the analysis of Western Blot images lack either transparency and reproducibility or can be tedious to use if one has to ensure the reproducibility of the analysis.

Results
Here, we present an open-source gel image analysis program, IOCBIO Gel. It is designed to simplify image analysis and link the analysis results with the metadata describing the measurements. The software runs on all major desktop operating systems. It allows one to use it in either a single-researcher environment with local storage of the data or in a multiple-researcher environment using a central database to facilitate data sharing within the research team and beyond. By recording the original image and all operations performed on it, such as image cropping, subtraction of background, sample lane selection, and integration boundaries, the software ensures the reproducibility of the analysis and simplifies making corrections at any stage of the research. The analysis results are available either through direct access to the database used to store it or through the export of the relevant data.

Conclusions
The software is not only limited to Western Blot image analysis and can be used to analyze images obtained as a part of many other widely used biochemical techniques such as isoelectric focusing. By recording the original data and all the analysis steps, the program improves reproducibility in the analysis and contributes to the implementation of FAIR principles in the related fields.
Multi-system diseases and death trajectory of metabolic dysfunction-associated fatty liver disease: findings from the UK Biobank
Authors: Jia Yu , Li Dongze , You Yi , Yu Jing , Jiang Wenli , Liu Yi , Zeng Rui , Wan Zhi , Lei Yi , Liao Xiaoyang 
Published: October 2023

Abstract
Background
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification.

Methods
After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections.

Results
Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results.

Conclusions
Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.
Factors affecting haemoglobin dynamics in African children with acute uncomplicated Plasmodium falciparum malaria treated with single low-dose primaquine or placebo
Authors: Onyamboko Marie A. , Olupot-Olupot Peter , Were Winifred , Namayanja Cate , Onyas Peter , Titin Harriet , Baseke Joy , Muhindo Rita , Kayembe Daddy K. , Ndjowo Pauline O. , Basara Benjamin B. , Okalebo Charles B. , Williams Thomas N. , Uyoga Sophie , Taya Chiraporn , Bamisaiye Adeola , Fanello Caterina , Maitland Kathryn , Day Nicholas P. J. , Taylor Walter R. J. , Mukaka Mavuto 
Published: October 2023

Abstract
Background
Single low-dose primaquine (SLDPQ) effectively blocks the transmission of Plasmodium falciparum malaria, but anxiety remains regarding its haemolytic potential in patients with glucose-6-phopshate dehydrogenase (G6PD) deficiency. We, therefore, examined the independent effects of several factors on haemoglobin (Hb) dynamics in falciparum-infected children with a particular interest in SLDPQ and G6PD status.

Methods
This randomised, double-blind, placebo-controlled, safety trial was conducted in Congolese and Ugandan children aged 6 months–11 years with acute uncomplicated P. falciparum and day (D) 0 Hbs ≥ 6 g/dL who were treated with age-dosed SLDPQ/placebo and weight-dosed artemether lumefantrine (AL) or dihydroartemisinin piperaquine (DHAPP). Genotyping defined G6PD (G6PD c.202T allele), haemoglobin S (HbS), and α-thalassaemia status.
Multivariable linear and logistic regression assessed factor independence for continuous Hb parameters and Hb recovery (D42 Hb > D0 Hb), respectively.

Results
One thousand one hundred thirty-seven children, whose median age was 5 years, were randomised to receive: AL + SLDPQ (n = 286), AL + placebo (286), DHAPP + SLDPQ (283), and DHAPP + placebo (282). By G6PD status, 284 were G6PD deficient (239 hemizygous males, 45 homozygous females), 119 were heterozygous females, 418 and 299 were normal males and females, respectively, and 17 were of unknown status.
The mean D0 Hb was 10.6 (SD 1.6) g/dL and was lower in younger children with longer illnesses, lower mid-upper arm circumferences, splenomegaly, and α-thalassaemia trait, who were either G6PDd or heterozygous females. The initial fractional fall in Hb was greater in younger children with higher D0 Hbs and D0 parasitaemias and longer illnesses but less in sickle cell trait. Older G6PDd children with lower starting Hbs and greater factional falls were more likely to achieve Hb recovery, whilst lower D42 Hb concentrations were associated with younger G6PD normal children with lower fractional falls, sickle cell disease, α-thalassaemia silent carrier and trait, and late treatment failures. Ten blood transfusions were given in the first week (5 SLDPQ, 5 placebo).

Conclusions
In these falciparum-infected African children, posttreatment Hb changes were unaffected by SLDPQ, and G6PDd patients had favourable posttreatment Hb changes and a higher probability of Hb recovery. These reassuring findings support SLDPQ deployment without G6PD screening in Africa.

Trial registration
The trial is registered at ISRCTN 11594437.
Cardiovascular outcomes between COVID-19 and non-COVID-19 pneumonia: a nationwide cohort study
Authors: Lee Min-Taek , Baek Moon Seong , Kim Tae Wan , Jung Sun-Young , Kim Won-Young 
Published: October 2023

Abstract
Background
Previous studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization.

Methods
Nationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020–September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1–December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia.

Results
After weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69–1.03). However, the MACE (HR, 7.30; 95% CI 3.29–16.21), dysrhythmia (HR, 1.88; 95% CI 1.04–3.42), acute myocarditis (HR, 11.33; 95% CI 2.97–43.20), myocardial infarction (HR, 6.78; 95% CI 3.03–15.15), congestive heart failure (HR, 1.95; 95% CI 1.37–2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06–16.83) risks were significantly higher in patients with COVID-19 aged 18–39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53–16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38–2.80), regardless of vaccination status.

Conclusions
Hospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.
Screening for atypical porcine pestivirus in Swedish boar semen used for artificial insemination and a characterisation of the seminal RNA microbiome including the virome
Authors: Stenberg Hedvig , Malmberg Maja , Hayer Juliette 
Published: October 2023

Abstract
Background
This study aimed to characterise the RNA microbiome, including the virome of extended semen from Swedish breeding boars, with particular focus on Atypical porcine pestivirus (APPV). This neurotropic virus, associated with congenital tremor type A-II in piglets, was recently demonstrated to induce the disease through insemination with semen from infected boars.

Results
From 124 Artificial Insemination (AI) doses from Swedish breeding boars, APPV was detected in one dose in addition to a sparse seminal RNA virome, characterised by retroviruses, phages, and some fecal-associated contaminants. The detected seminal microbiome was large and characterized by Gram-negative bacteria from the phylum Proteobacteria, mainly consisting of apathogenic or opportunistic bacteria. The proportion of bacteria with a pathogenic potential was low, and no antimicrobial resistance genes (ARGs) were detected in the datasets.

Conclusion
Overall, the results indicate a good health status among Swedish breeding boars. The detection of APPV in semen raises the question of whether routine screening for APPV in breeding boars should be instigated.
Caproate production from Enset fiber in one-pot two-step fermentation using anaerobic fungi (Neocallimastix cameroonii strain G341) and Clostridium kluyveri DSM 555
Authors: Seid Nebyat , Ochsenreither Katrin , Neumann Anke 
Published: October 2023

Abstract
Background
Lignocellulosic biomass plays a crucial role in creating a circular bioeconomy and minimizing environmental impact. Enset biomass is a byproduct of traditional Ethiopian Enset food processing that is thrown away in huge quantities. This study aimed to produce caproate from Enset fiber using Neocallimastix cameroonii strain G341 and Clostridium kluyveri DSM 555 in one-pot two-step fermentation.

Results
The process started by growing N. cameroonii on Enset fiber as a carbon source for 7 days. Subsequently, the fungal culture was inoculated with active C. kluyveri preculture and further incubated. The results showed that N. cameroonii grew on 0.25 g untreated Enset fiber as the sole carbon source and produced 1.16 mmol acetate, 0.51 mmol hydrogen, and 1.34 mmol formate. In addition, lactate, succinate, and ethanol were detected in small amounts, 0.17 mmol, 0.08 mmol, and 0.7 mmol, respectively. After inoculating with C. kluyveri, 0.3 mmol of caproate and 0.48 mmol of butyrate were produced, and hydrogen production also increased to 0.95 mmol compared to sole N. cameroonii fermentation. Moreover, after the culture was supplemented with 2.18 mmol of ethanol during C. kluyveri inoculation, caproate, and hydrogen production was further increased to 1.2 and 1.36 mmol, respectively, and the consumption of acetate also increased.

Conclusion
A novel microbial cell factory was developed to convert untreated lignocellulosic Enset fiber into the medium chain carboxylic acid caproate and H2 by a co-culture of the anaerobic fungi N. cameroonii and C. kluyveri. This opens a new value chain for Enset farmers, as the process requires only locally available raw materials and low-price fermenters. As the caproate production was mainly limited by the available ethanol, the addition of locally produced ethanol-containing fermentation broth (“beer”) would further increase the titer.

Graphical Abstract
Comparison of COVID-19 vaccine policies and their effectiveness in Korea, Japan, and Singapore
Authors: Ma Mengyuan , Shi Leiyu , Liu Meiheng , Yang Junyan , Xie Wanzhen , Sun Gang 
Published: October 2023

Abstract
Background
This study aimed to analyze coronavirus disease 2019 (COVID-19)vaccine policies and effectiveness in Korea, Japan, and Singapore, thereby providing empirical experience for vaccination and response to similar public health emergencies.

Methods
The study systematically summarized the COVID-19 vaccine policies in Korea, Japan, and Singapore through public information from the Our World in Data website and the official websites of the Ministries of Health in these three countries.Total vaccinations, COVID-19 vaccination rates, rates of fully vaccinated, rates of boostervaccinated, and total confifirmed cases were selected for cross-sectional comparison of COVID-19 vaccination in these three countries. Combining the basic characteristics of these three countries, daily cases per million, daily deaths per million, and the effective reproduction rate were calculated to measure the effectiveness of COVID-19 vaccine policies implementation in each of these three countries

Results
The countermeasures against the COVID-19 in Korea, Japan, and Singapore, although seemingly different on the surface, have all taken an aggressive approach. There are large similarities in the timing of the start of COVID-19 vaccination, the type of vaccine, how vaccine appointments are made, and whether vaccination are free, and all had high vaccination rates. A systematic comparison of the anti-epidemic practices in the three East Asian countries revealed that all three countries experienced more than one outbreak spike due to the spread of new mutant strains after the start of mass vaccination with COVID-19 vaccination, but that vaccination played a positive role in reducing the number of deaths and stabilizing the effective reproduction rate.

Conclusions
This study comparatively analyzed the COVID-19 vaccine policies and their effects in South Korea, Japan, and Singapore, and found that there is a common set of logical combinations behind the seemingly different strategies of these three countries. Therefore, in the process of combating COVID-19, countries can learn from the successful experience of combating the epidemic and continue to strengthen the implementation of vaccination programs, as well as adjusting public perceptions to reduce the level of vaccine hesitancy, enhance the motivation for vaccination, and improve the coverage of COVID-19 vaccine based on different cultural factors, which remains the direction for future development.
Evaluating a complex health promotion program to reduce hepatitis C among Aboriginal and Torres Strait Islander peoples in New South Wales, Australia: the Deadly Liver Mob
Authors: Treloar Carla , Beadman Kim , Beadman Mitch , Smith Kerri-Anne , Christian Jade , Jackson Aunty Clair , Tyson Beverley , Anderson Clayton , Smyth Larissa , Walker Melinda , Heslop Jennifer , Gahan Gary , Tawil Victor , Sheaves Felicity , Maher Louise , Page Julie , Tilley Donna , Ryan Ann , Grant Kim , Donovan Basil , Stevens Annabelle , Slattery Trevor , Pearce Kate , John-Leader Franklin , Walden Andrew , Lenton Jo , Crowley Margaret , Cama Elena 
Published: October 2023

AbstractThe Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians, and was introduced in response to the disproportionate number of Aboriginal and Torres Strait Islander Australians who are impacted by blood borne viruses (BBVs) and sexually transmitted infections (STIs). The goal of the program is to increase access to BBV and STI education, screening, treatment, and vaccination in recognition and response to the systemic barriers that Aboriginal and Torres Strait Islander peoples face in accessing health care. This commentary introduces a series of papers that report on various aspects of the evaluation of the Deadly Liver Mob (DLM) program. In this paper, we explain what DLM is and how we constructed an evaluation framework for this complex health promotion intervention.
Genetic screening for anticancer genes highlights FBLN5 as a synthetic lethal partner of MYC
Authors: Masood Motasim , Ding Qize , Cawte Adam D. , Rueda David S. , Grimm Stefan W. , Yagüe Ernesto , El-Bahrawy Mona 
Published: October 2023

Abstract
Background
When ectopically overexpressed, anticancer genes, such as TRAIL, PAR4 and ORCTL3, specifically destroy tumour cells without harming untransformed cells. Anticancer genes can not only serve as powerful tumour specific therapy tools but studying their mode of action can reveal mechanisms underlying the neoplastic transformation, sustenance and spread.

Methods
Anticancer gene discovery is normally accidental. Here we describe a systematic, gain of function, forward genetic screen in mammalian cells to isolate novel anticancer genes of human origin. Continuing with over 30,000 transcripts from our previous study, 377 cell death inducing genes were subjected to screening. FBLN5 was chosen, as a proof of principle, for mechanistic gene expression profiling, comparison pathways analyses and functional studies.

Results
Sixteen novel anticancer genes were isolated; these included non-coding RNAs, protein-coding genes and novel transcripts, such as ZNF436-AS1, SMLR1, TMEFF2, LINC01529, HYAL2, NEIL2, FBLN5, YPEL4 and PHKA2-processed transcript. FBLN5 selectively caused inhibition of MYC in COS-7 (transformed) cells but not in CV-1 (normal) cells. MYC was identified as synthetic lethality partner of FBLN5 where MYC transformed CV-1 cells experienced cell death upon FBLN5 transfection, whereas FBLN5 lost cell death induction in MCF-7 cells upon MYC knockdown.

Conclusions
Sixteen novel anticancer genes are present in human genome including FBLN5. MYC is a synthetic lethality partner of FBLN5.
Elesclomol, a copper-transporting therapeutic agent targeting mitochondria: from discovery to its novel applications
Authors: Tarin Mojtaba , Babaie Maryam , Eshghi Hossein , Matin Maryam M. , Saljooghi Amir Sh. 
Published: October 2023

AbstractCopper (Cu) is an essential element that is involved in a variety of biochemical processes. Both deficiency and accumulation of Cu are associated with various diseases; and a high amount of accumulated Cu in cells can be fatal. The production of reactive oxygen species (ROS), oxidative stress, and cuproptosis are among the proposed mechanisms of copper toxicity at high concentrations. Elesclomol (ELC) is a mitochondrion-targeting agent discovered for the treatment of solid tumors. In this review, we summarize the synthesis of this drug, its mechanisms of action, and the current status of its applications in the treatment of various diseases such as cancer, tuberculosis, SARS-CoV-2 infection, and other copper-associated disorders. We also provide some detailed information about future directions to improve its clinical performance.