bluuebunny/crossref_metadata_2025_split huggingface dataset:
circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations
Authors: Sun Zhi-Yan , Yang Chang-Lin , Huang Li-Jie , Mo Zong-Chao , Zhang Ke-Nan , Fan Wen-Hua , Wang Kuan-Yu , Wu Fan , Wang Ji-Guang , Meng Fan-Lin , Zhao Zheng , Jiang Tao 
Published: October 2023

Abstract
circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.
HHCDB: a database of human heterochromatin regions
Authors: Wang Hongli , Su Mu , Xing Jie , Zhou Jie , Wang Jinzhang , Chen Long , Dong Haomin , Xue Wenhui , Liu Yubo , Wu Qiong , Zhang Yan 
Published: October 2023

Abstract
Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.
Financial Toxicity: Unveiling the Burden of Cancer Care on Patients in Rwanda
Authors: Rubagumya Fidel , Wilson Brooke , Manirakiza Achille , Mutabazi Emmanuel , A. Ndoli Diane , Rudakemwa Emmanuel , Chamberlin Mary D , Hopman Wilma M , Booth Christopher M 
Published: October 2023

Abstract

Introduction
Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda.

Methods
This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country’s cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin’s and non-Hodgkin’s lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics.

Results
239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment.

Conclusion
Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.
A targeted approach to vaccine hesitancy
Authors: Leston Meredith , de Lusignan Simon , Hobbs F D Richard 
Published: October 2023

Abstract
This short communication makes the case for targeted vaccine research when attempting to counter hesitancy, especially amongst vulnerable or rarefied patient groups. Far from disincentivizing vaccination, the freedom to research and publicize the limitations of these technologies for certain groups and personalizing dosing, pacing, adjuvants, and time-sensitive alternatives in response is essential for optimizing health outcomes while neutralizing the vaccine research landscape itself. Vaccine evangelism only arouses suspicion when it is not tempered by rigorous research into differential vaccine benefit-risk in this way. That said, the long-standing politicization of vaccination—a topic vulnerable to misinterpretation and media sensationalism—along with the commercial incentives associated with universal adoption makes more comparative and critical research difficult to fund and promote in practice. Likewise, a prescriptive approach to vaccination does little to address the issues of vaccine inequality that contribute to both hesitancy and conspiracy globally and will likely prove financially prohibitive in certain markets. These obstacles are not insurmountable, however, provided that comparative research is centrally subsidized, regulations ensure that vaccine development trials explore differentiated outcomes, especially amongst high-risk or rare groups, and findings are used to prioritize global vaccine allocation to those that stand to benefit most from them.
A Fitting Definition of Epistemic Emotions
Authors: Deigan Michael , Piñeros Glasscock Juan S 
Published: October 2023

AbstractPhilosophers and psychologists sometimes categorize emotions like surprise and curiosity as specifically epistemic. Is there some reasonably unified and interesting class of emotions here? If so, what unifies it? This paper proposes and defends an evaluative account of epistemic emotions: What it is to be an epistemic emotion is to have fittingness conditions that distinctively involve some epistemic evaluation. We argue that this view has significant advantages over alternative proposals and is a promising way to identify a limited and interesting class of emotions.
‘I am afraid you will see the stain on my soul’: Direct gaze neural processing in individuals with PTSD after moral injury recall
Authors: Andrews Krysta , Lloyd Chantelle S , Densmore Maria , Kearney Breanne E , Harricharan Sherain , McKinnon Margaret C , Théberge Jean , Jetly Rakesh , Lanius Ruth A 
Published: October 2023

Abstract
Direct eye contact is essential to understanding others’ thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing processes and experience shame which precludes one’s capacity for direct eye contact. We investigated blood oxygenation level-dependent (BOLD) responses associated with direct vs averted gaze using a virtual reality paradigm in individuals with PTSD (n = 28) relative to healthy controls (n = 18) following recall of a MI vs a neutral memory. Associations between BOLD responses and clinical symptomatology were also assessed. After MI recall, individuals with PTSD showed greater activation in the right temporoparietal junction as compared to controls (T = 4.83; pFDR &lt; 0.001; k = 237) during direct gaze. No significant activation occurred during direct gaze after neutral memory recall. Further, a significant positive correlation was found between feelings of distress and right medial superior frontal gyrus activation in individuals with PTSD (T = 5.03; pFDR = 0.049; k = 123). These findings suggest that direct gaze after MI recall prompts compensatory ToM/mentalizing processing. Implications for future interventions aimed at mitigating the effects of PTSD on social functioning are discussed.
Exercise intensity-dependent lactate elevation in skin interstitial fluid and its long-lasting effect
Authors: Dobashi Shohei , Funabashi Daisuke , Sameshima Kazuki , Tsuruoka Noriko , Matsui Takashi 
Published: October 2023

AbstractRegular exercise promotes various anti-ageing adaptations in skin tissue. Although the underlying mechanisms of that might associate to the acute exercise-induced lactate signaling in the skin, it remains uncertain the profile of skin interstitial fluid (ISF) lactate dynamics during and following acute exercise. Here, we investigated whether the skin ISF lactate level increases in association with blood lactate during acute incremental exercise using a single microneedle perfusion system. The rats were acclimated to treadmill running exercise and underwent external jugular vein cannulation. Following comprehensive recovery, a 1 mm single microneedle was implanted into the back skin. Skin ISF lactate progressively increased in tandem with blood lactate during the incremental exercise but did not decrease to baseline levels until 30 minutes following the exercise unlike blood. Moreover, lactate threshold (LT), is a crucial marker of athletic aerobic performance during acute exercise, extrapolated from skin ISF showed significant alignment with blood LT. Our findings reveal that the skin ISF lactate increases associated with blood lactate and the long-lasting elevation state following acute exercise. Moreover, lactate dynamics in skin ISF can predict LT. These findings would be a milestone for elucidating regular exercise-induced physiological adaptations in the skin and evaluating athletic performance.Graphical AbstractLactate levels in rat skin interstitial fluid (ISF) increased in association with blood lactate during acute incremental exercise, but the increase in skin ISF lactate lasted 30 min following acute exercise. Lactate threshold (LT), a crucial marker of aerobic athletic performance, can be predicted from skin fluid dynamics during acute exercise. These findings would be a milestone for elucidating regular exercise-induced physiological adaptations in the skin and evaluating athletic performance.
Low relative air humidity and increased stomatal density independently hamper growth in young Arabidopsis
Authors: Tulva Ingmar , Koolmeister Kaspar , Hõrak Hanna 
Published: October 2023

AbstractStomatal pores in plant leaves mediate CO2uptake for photosynthesis and water loss via transpiration. Altered stomatal density can affect plant photosynthetic capacity, water use efficiency, and growth, potentially providing either benefits or drawbacks depending on the environment. Here we explore, at different air humidity regimes, gas exchange, stomatal anatomy, and growth of Arabidopsis lines designed to combine increased stomatal density (epf1,epf2) with high stomatal sensitivity (ht1-2,cyp707a1/a3). We show that the stomatal density and sensitivity traits combine as expected: higher stomatal density increases stomatal conductance, whereas the effect is smaller in the high stomatal sensitivity mutant backgrounds than in theepf1epf2double mutant. Growth under low air humidity increases plant stomatal ratio with relatively more stomata allocated to the adaxial epidermis. Low relative air humidity and high stomatal density both independently impair plant growth. Higher evaporative demand did not punish increased stomatal density, nor did inherently low stomatal conductance provide any protection against low relative humidity. We propose that the detrimental effects of high stomatal density on plant growth at a young age are related with the cost of producing stomata; future experiments need to test if high stomatal densities might pay off in later life stages.Significance statementThis study delves into the relationship between stomatal density, sensitivity, and environment in Arabidopsis. These findings not only enhance our comprehension of plant responses to humidity but also lay the groundwork for future studies aimed at optimising plant adaptability to varying environmental conditions.
Adipokinetic hormone signaling mediates the enhanced fecundity ofDiaphorina citriinfected by ‘CandidatusLiberibacter asiaticus’
Authors: Li Jiayun , Holford Paul , Beattie George Andrew Charles , Wu Shujie , He Jielan , Tan Shijian , Wang Desen , He Yurong , Cen Yijing , Nian Xiaoge 
Published: October 2023

AbstractDiaphorina citriserves as the primary vector for ‘CandidatusLiberibacter asiaticus’ (CLas), the bacterium associated with the severe Asian form of huanglongbing.CLas-positiveD. citriare more fecund than theirCLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response toCLas infection inD. citri.Knockdown ofDcAKHandDcAKHRnot only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity andCLas titer in ovaries. Combinedin vivoandin vitroexperiments showed that miR-34 suppressesDcAKHRexpression by binding to its 3’ untranslated region, whilst overexpression of miR-34 resulted in a decline ofDcAKHRexpression andCLas titer in ovaries and caused defects that mimickedDcAKHRknockdown phenotypes. Additionally, knockdown ofDcAKHandDcAKHRsignificantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor,methoprene-tolerant(DcMet), and the transcription factor,Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genesvitellogenin 1-like(DcVg-1-like),vitellogenin A1-like(DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result,CLas hijacks AKH/AKHR-miR-34-JH signaling to improveD. citrilipid metabolism and fecundity, while simultaneously increasing the replication ofCLas, suggesting a mutualistic interaction betweenCLas andD. citriovaries.
A fuzzy sequencer for rapid DNA fragment counting and genotyping
Authors: Zhou Wenxiong , Kang Li , Qiao Shuo , Duan Haifeng , Yin Chenghong , Liu Chao , Liao Zhizhao , Tang Mingchuan , Zhang Ruiying , Li Lei , Shi Lei , Du Meijie , Wang Yipeng , Yue Wentao , Xiao Yan , Di Lin , Zhang Xiannian , Pang Yuhong , Li Mingkun , Ren Lili , Wang Jianbin , Chen Zitian , Huang Yanyi 
Published: October 2023

AbstractHigh-throughput sequencing technologies generate a vast number of DNA sequence reads simultaneously, which are subsequently analyzed using the information contained within these fragmented reads. The assessment of sequencing technology relies on information efficiency, which measures the amount of information entropy produced per sequencing reaction cycle. In this study, we propose a fuzzy sequencing strategy that exhibits information efficiency more than twice of currently prevailing cyclic reversible terminator sequencing methods. To validate our approach, we developed a fully functional and high-throughput fuzzy sequencer. This sequencer implements a highly efficient fluorogenic sequencing-by-synthesis chemistry and underwent testing across various application scenarios, including copy-number variation detection, noninvasive prenatal testing, transcriptome profiling, mutation genotyping, and metagenomic profling. Our findings unequivocally demonstrate that the fuzzy sequencing strategy outperforms existing methods in terms of information efficiency and delivers accurate resequencing results with faster turnaround times.One Sentence SummaryA fuzzy sequencer can exceed current limit of information efficiency of DNA sequencers for resequencing applications.
Rapid and Inducible Mislocalization of Endogenous TDP43 in a Novel Human Model of Amyotrophic Lateral Sclerosis
Authors: Ganssauge Johanna , Hawkins Sophie , Namboori Seema , Leung Szi-Kay , Mill Jonathan , Bhinge Akshay 
Published: October 2023

AbstractTransactive response DNA binding protein 43 kDa (TDP43) proteinopathy, characterized by the mislocalization and aggregation of TDP43, is a hallmark of several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). In this study, we describe the development of a new model of TDP43 proteinopathy using human induced pluripotent stem cell (iPSC)-derived neurons. Utilizing a genome engineering approach, we induced the mislocalization of endogenous TDP43 from the nucleus to the cytoplasm without mutating the TDP43 gene or using chemical stressors. Our model successfully recapitulates key early and late pathological features of TDP43 proteinopathy, including neuronal loss, reduced neurite complexity, and cytoplasmic accumulation and aggregation of TDP43. Concurrently, the loss of nuclear TDP43 leads to splicing defects, while its cytoplasmic gain adversely affects microRNA expression. Strikingly, our observations suggest that TDP43 is capable of sustaining its own mislocalization, thereby perpetuating and further aggravating the proteinopathy. This innovative model provides a valuable tool for the in-depth investigation of the consequences of TDP43 proteinopathy. It offers a clinically relevant platform that will accelerate identification of potential therapeutic targets for the treatment of TDP43-associated neurodegenerative diseases including sporadic ALS.
Systematic identification of cargo-carrying genetic elements reveals new dimensions of eukaryotic diversity
Authors: Gluck-Thaler Emile , Vogan Aaron A. 
Published: October 2023

AbstractCargo-carrying mobile elements (CCEs) are genetic entities that transpose diverse protein coding sequences. Although common in bacteria, we know little about the biology of eukaryotic CCEs because no appropriate tools exist for their annotation. For example,Starshipsare fungal CCEs whose functions are largely unknown because they require time-intensive manual curation. To address this knowledge gap, we developed starfish, a computational workflow for high-throughput eukaryotic CCE annotation. We applied starfish to 2, 899 genomes of 1, 649 fungal species and found that starfish recovers knownStarshipswith >95% precision and accuracy while expanding the number of annotated elements ten-fold. ExtantStarshipdiversity is partitioned into 11 families that differ in their enrichment patterns across fungal classes.Starshipcargo changes rapidly such that elements from the same family differ substantially in their functional repertoires, which are predicted to contribute to diverse biological processes such as metabolism. Many elements have convergently evolved to insert into 5S rDNA and AT-rich sequence while others integrate into random locations, revealing both specialist and generalist strategies for persistence. Our work establishes a framework for advancing mobile element biology and provides the means to investigate an emerging dimension of eukaryotic genetic diversity, that of genomes within genomes.
Aberrant Local Synchrony in Distinct Mouse Models of Epileptic Encephalopathy
Authors: Ressler Andrew K. , Dugger Sarah A. , Colombo Sophie , Petri Sabrina , Krizay Daniel , Frankel Wayne N. , Goldstein David B. , Boland Michael J. 
Published: October 2023

AbstractIdentifying and quantifying synchronous activity of primary neuronal networks using multielectrode arrays (MEAs) can potentially provide a medium-throughput platform to screen potential therapeutics for genetic epileptic encephalopathies (EEs). However, successfully identifying screenable synchrony phenotypesin vitroposes significant experimental and analytical challenges. Primary neuronal cultures quickly become highly synchronous and certain measures of synchrony tend to peak and plateau, while other network activity features remain dynamic. High levels of synchrony may confound the ability to identify reproducible phenotypesin vitrofor a subset of EEs. Reducing, or delaying the onset of, high levels of synchronyin vitromay increase the dynamic range of global synchrony measures to identify disease-relevant phenotypesin vitro,but such measures have not been established. We hypothesized that an emphasis on local (nearby) connectivity could elucidate reproducible disease-relevant synchrony phenotypes in cortical cultures not identified by current approaches. We show clear evidence of enriched local synchrony in 48-well MEAs that varies in amplitude during development of neuronal networks. Then, we show new topological-based measures are capable of identifying novel phenotypes of aberrant synchrony in distinct mouse models of EEs. Such topological synchrony measures may provide screenable phenotypes for certain brain diseases and may be further enhanced by experimental innovation reducing global levels of synchrony in primary neuronal networks.SignificanceIn vitrosynchrony phenotypes may provide disease-relevant features that can be used for screening potential therapeutic candidates for epileptic encephalopathies. Here, we incorporate inter-electrode distance to generate tools capable of identifying novel synchrony phenotypes in distinct neurodevelopmental disorders. We additionally report robust topological and globalin vitrosynchrony phenotypes, alongsidein vivosynchrony phenotypes inStxbp1+/-mice. While singular features of disease in anin vitromodel are unlikely to effectively test therapeutic candidates, compounds that reverse a larger subset of distinct features may translate to human patients, suggesting such a model may be ideally suited for therapeutic development using MEAs. Across multiple disease models, the topological tools developed here are complimentary to and expand upon those within meaRtools (Gelfman 2018), which is a suite of computational tools to identify network phenotypes using MEAs.