bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial Disparities in MiT Family Translocation Renal Cell Carcinoma
Authors: Lu Xiaofan , Tawanaie Pour Sedehi Nassim , Su Xiaoping , Yan Fangrong , Alhalabi Omar , Tannir Nizar M , Malouf Gabriel G 
Published: June 2023

Abstract
Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.
The Quebec Dental Anomalies Registry: Identifying genes for rare disorders
Authors: Wredenhagen Madeleine S , Goldstein Andee , Mathieu Hélène , Miranda Valancy , Morali Burcin , Santerre Jacinthe , Maftei Catalina , Delrue Marie-Ange , Schmittbuhl Matthieu , Vu Duy Dat , Moldovan Florina , Campeau Philippe M 
Published: June 2023

Abstract
There are more than 900 genetic syndromes associated with oral manifestations. These syndromes can have serious health implications, and left undiagnosed, can hamper treatment and prognosis later in life. About 6.67% of the population will develop a rare disease during their lifetime, some of which are difficult to diagnose. The establishment of a data and tissue bank of rare diseases with oral manifestations in Quebec will help medical professionals identify the genes involved, will improve knowledge on the rare genetic diseases, and will also lead to improved patient management. It will also allow samples and information sharing with other clinicians and investigators. As an example of a condition requiring additional research, dental ankylosis is a condition in which the tooth's cementum fuses to the surrounding alveolar bone. This can be secondary to traumatic injury but is often idiopathic, and the genes involved in the idiopathic cases, if any, are poorly known. To date, patients with both identified and unidentified genetic etiology for their dental anomalies were recruited through dental and genetics clinics for the study. They underwent sequencing of selected genes or exome sequencing depending on the manifestation. We recruited 37 patients and we identified pathogenic or likely pathogenic variants in WNT10A, EDAR, AMBN, PLOD1, TSPEAR, PRKAR1A, FAM83H, PRKACB, DLX3, DSPP, BMP2, TGDS. Our project led to the establishment of the Quebec Dental Anomalies Registry, which will help researchers, medical and dental practitioners alike understand the genetics of dental anomalies and facilitate research collaborations into improved standards of care for patients with rare dental anomalies and any accompanying genetic diseases.
Structural and functional differences in the brains of patients with MCI with and without depressive symptoms and their relations with Alzheimer's disease: an MRI study
Authors: Chiari-Correia Rodolfo Dias , Tumas Vitor , Santos Antônio Carlos , Salmon Carlos Ernesto G 
Published: June 2023

Abstract

Background
The mild cognitive impairment (MCI) stage among elderly individuals is very complex, and the level of diagnostic accuracy is far from ideal. Some studies have tried to improve the 'MCI due to Alzheimer's disease (AD)' classification by further stratifying these patients into subgroups. Depression-related symptoms may play an important role in helping to better define the MCI stage in elderly individuals.

Objective
In this work, we explored functional and structural differences in the brains of patients with nondepressed MCI (nDMCI) and patients with MCI with depressive symptoms (DMCI), and we examined how these groups relate to AD atrophy patterns and cognitive functioning.

Methods
Sixty-five participants underwent MRI exams and were divided into four groups: cognitively normal, nDMCI, DMCI, and AD. We compared the regional brain volumes, cortical thickness, and white matter microstructure measures using diffusion tensor imaging among groups. Additionally, we evaluated changes in functional connectivity using fMRI data.

Results
In comparison to the nDMCI group, the DMCI patients had more pronounced atrophy in the hippocampus and amygdala. Additionally, DMCI patients had asymmetric damage in the limbic-frontal white matter connection. Furthermore, two medial posterior regions, the isthmus of cingulate gyrus and especially the lingual gyrus, had high importance in the structural and functional differentiation between the two groups.

Conclusion
It is possible to differentiate nDMCI from DMCI patients using MRI techniques, which may contribute to a better characterization of subtypes of the MCI stage.
Shakespeare’s Metaphysical Poem: Allegory, Metaphysics, and Aesthetics in ‘The Phoenix and Turtle’
Authors: Tregear Ted 
Published: June 2023

Abstract
Long treated as a poetic curio or a biographical riddle, Shakespeare’s poetic contribution to the 1601 Loves Martyr—usually known as ‘The Phoenix and Turtle’—has recently been reclaimed as an experiment in metaphysical poetry. This essay sets out to ask what that means: for the poem, for metaphysical poetry, and for metaphysics itself. It argues that Shakespeare draws on the language of metaphysics, and its canonical problems, to test the relationship between poetic and philosophical thinking. It follows the poem as it charts the efforts, and failures, of both allegory and metaphysics to apprehend the thought-defying love between phoenix and turtle. It shows how that love engages the dilemma of the particular and the universal, a dilemma native to metaphysics since Aristotle, but felt most acutely in the realm of aesthetic experience. And it suggests that, in sounding out the limits of metaphysical reason, Shakespeare’s poem allows for poetry to think in a way that metaphysics cannot. ‘The Phoenix and Turtle’ ends in mourning: for the death of phoenix and turtle, and for the demise of the metaphysical transcendentals they seemed in hindsight to uphold. That mourning might nonetheless offer poetry its vocation, as the space where reason might remember and reflect on the object of its loss.
A true caudal fin or not? New insights in the evolution of the gadiform caudal fin
Authors: Moritz Timo , Walter Jacqueline , Grunow Bianka , Thieme Philipp 
Published: June 2023

Abstract
The distinctive caudal-fin skeleton of gadiforms has puzzled scientists for a long time, because of its many differences in comparison to other teleosts. Contradicting hypotheses interpreted this structure as (i) a highly derived teleostean caudal fin, (ii) a new formation with parts from the caudal, dorsal and anal fins, a so called pseudocaudal, or (iii) a complete evolutionary novelty, a so called neocaudal. To shed light on to this issue, the caudal-fin ontogeny of Lota lota was studied in detail. It differs from the development in non-gadiform teleostean taxa, e.g. by absence of a distinct and early notochord flexion. However, there are also many similarities with other teleosts, e.g. the caudal fin develops before the dorsal and anal fins. Furthermore, the morphology of adult caudal fins of all major gadiform families were studied and reviewed. Our results, in combination with the latest molecular phylogenies, allowed us to discuss the evolution of the gadiform caudal fin and resolve the origin of this highly debated character complex. Although their caudal-fin skeleton shows several derived apomorphies, the gadiform caudal fin is homologous to the caudal fins of other teleosts, without principal inclusion of dorsal- or anal-fin elements.
TATA-box-binding protein promotes hepatocellular carcinoma metastasis through epithelial-mesenchymal transition
Authors: Cao Jiayi , Yang Suzhen , Luo Tingting , Yang Rui , Zhu Hanlong , Zhao Tianming , Jiang Kang , Xu Bing , Wang Yingchun , Chen Fulin 
Published: June 2023

Background:
HCC characterizes malignant metastasis with high incidence and recurrence. Thus, it is pivotal to discover the mechanisms of HCC metastasis. TATA-box-binding protein (TBP), a general transcriptional factor (TF), couples with activators and chromatin remodelers to sustain the transcriptional activity of target genes. Here, we investigate the key role of TBP in HCC metastasis.

Methods:
TBP expression was measured by PCR, western blot, and immunohistochemistry. RNA-sequencing was performed to identify downstream proteins. Functional assays of TBP and downstream targets were identified in HCC cell lines and xenograft models. Luciferase reporter and chromatin immunoprecipitation assays were used to demonstrate the mechanism mediated by TBP.

Results:
HCC patients showed high expression of TBP, which correlated with poor prognosis. Upregulation of TBP increased HCC metastasis in vivo and in vitro, and muscleblind-like-3 (MBNL3) was the effective factor of TBP, positively related to TBP expression. Mechanically, TBP transactivated and enhanced MBNL3 expression to stimulate exon inclusion of lncRNA-paxillin (PXN)-alternative splicing (AS1) and, thus, activated epithelial-mesenchymal transition for HCC progression through upregulation of PXN.

Conclusions:
Our data revealed that TBP upregulation is an HCC enhancer mechanism that increases PXN expression to drive epithelial-mesenchymal transition.
Race differences in pain and pain-related risk factors among former professional American-style football players
Authors: Edwards Robert R. , Tan Can Ozan , Dairi Inana , Whittington Alicia J. , Thomas Julius Dewayne , Campbell Claudia M. , Ross Edgar , Taylor Herman A. , Weisskopf Marc , Baggish Aaron L. , Zafonte Ross , Grashow Rachel 
Published: June 2023

Abstract
The burden of pain is unequal across demographic groups, with broad and persisting race differences in pain-related outcomes in the United States. Members of racial and ethnic minorities frequently report more pervasive and severe pain compared with those in the majority, with at least some disparity attributable to differences in socioeconomic status. Whether race disparities in pain-related health outcomes exist among former professional football players is unknown. We examined the association of race with pain outcomes among 3995 former professional American-style football players who self-identified as either Black or White. Black players reported more intense pain and higher levels of pain interference relative to White players, even after controlling for age, football history, comorbidities, and psychosocial factors. Race moderated associations between several biopsychosocial factors and pain; higher body mass index was associated with more pain among White but not among Black players. Fatigue and psychosocial factors were more strongly related to pain among Black players relative to White players. Collectively, the substantial social and economic advantages of working as a professional athlete did not seem to erase race-related disparities in pain. We highlight an increased burden of pain among elite Black professional football players and identify race-specific patterns of association between pain and biopsychosocial pain risk factors. These findings illuminate potential future targets of interventions that may serve to reduce persistent disparities in the experience and impact of pain.
TidyTron: Reducing lab waste using validated wash-and-reuse protocols for common plasticware in Opentrons OT-2 lab robots
Authors: Bryant John A. , Longmire Cameron , Sridhar Sriya , Janousek Samuel , Kellinger Mason , Wright R. Clay 
Published: June 2023

AbstractEvery year biotechnology labs generate a combined total of ∼5.5 million tons of plastic waste. As the global bioeconomy expands, biofoundries will inevitably increase plastic consumption in-step with synthetic biology scaling. Decontamination and reuse of single-use plastics could increase sustainability and reduce recurring costs of biological research. However, throughput and variable cleaning quality make manual decontamination impractical in most instances. Automating single-use plastic cleaning with liquid handling robots makes decontamination more practical by offering higher throughput and consistent cleaning quality. However, open-source, validated protocols using low-cost lab robotics for effective decontamination of plasticware—facilitating safe reuse—have not yet been developed. Here we introduce and validate TidyTron: a library of protocols for cleaning micropipette tips and microtiter plates that are contaminated with DNA,E. coli, andS. cerevisiae. We tested a variety of cleaning solutions, contact times, and agitation methods with the aim of minimizing time and cost, while maximizing cleaning stringency and sustainability. We tested and validated these cleaning procedures by comparing fresh versus cleaned tips and plates for contamination with cells, DNA, or cleaning solutions. We assessed contamination by measuring colony forming units by plating, PCR efficiency and DNA concentration by qPCR, and event counts and debris by flow cytometry. Open source cleaning protocols are available athttps://github.com/PlantSynBioLab/TidyTronand hosted on a graphical user interface athttps://jbryantvt.github.io/TidyTron/.
New T2T assembly ofCryptosporidium parvumIOWA annotated with reference genome gene identifiers
Authors: de Paula Baptista Rodrigo , Xiao Rui , Li Yiran , Glenn Travis C. , Kissinger Jessica C. 
Published: June 2023

ABSTRACTCryptosporidium parvumis a significant pathogen causing gastrointestinal infections in humans and animals, that is spread through the ingestion of contaminated food and water. Despite its global impact on public health, generating aC. parvumgenome sequence has always been challenging due to a lack ofin vitrocultivation systems and challenging sub-telomeric gene families. A gapless telomere to telomere genome assembly has been created forCryptosporidium parvumIOWA obtained from Bunch Grass Farms, named here as CpBGF. There are 8 chromosomes that total 9,259,183 bp. The new hybrid assembly which was generated with Illumina and Oxford Nanopore resolves complex sub-telomeric regions of chromosomes 1, 7 and 8. To facilitate ease of use and consistency with the literature, whenever possible, chromosomes have been oriented and genes in this annotation have been given the same gene IDs used in the current reference genome sequence generated in 2004. The annotation of this assembly utilized considerable RNA expression evidence, thus, untranslated regions, long noncoding RNAs and antisense RNAs are annotated. The CpBGF genome assembly serves as a valuable resource for understanding the biology, pathogenesis, and transmission ofC. parvum, and it facilitates the development of diagnostics, drugs, and vaccines against cryptosporidiosis.
Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis
Authors: Ackermann Tobias , Shokry Engy , Deshmukh Ruhi , Anand Jayanthi , Galbraith Laura C.A. , Mitchell Louise , Rodriguez-Blanco Giovanny , Villar Victor H. , Sterken Britt Amber , Nixon Colin , Zanivan Sara , Blyth Karen , Sumpton David , Tardito Saverio 
Published: June 2023

AbstractThe limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour.
A constitutive model for the remodelling erythrocyte membrane skeleton during the active invasion by the malaria merozoite
Authors: Msosa Chimwemwe , Abdalrahman Tamer , Franz Thomas 
Published: June 2023

AbstractMalaria merozoites phosphorylate erythrocyte membrane proteins to breach the membrane during invasion. This study aimed to develop a constitutive model for erythrocyte membrane phosphorylation that reduces the membrane’s elastic modulus and resistance to merozoite invasion. The hyperelastic Mooney Rivlin constitutive model was adapted by adding an exponential term to represent the mechanical effect of erythrocyte membrane phosphorylation. The modified algorithm was verified with the unmodified Mooney Rivlin model for the intact erythrocyte membrane and used to predict erythrocyte membrane stress for equi-biaxial membrane strain up to 1.1 for different severity of phosphorylation damage. The stability of the damage model was assessed using the Drucker criterion for equi-biaxial strain up to 2.0. Strain and stress predicted with the developed damage model and the Mooney Rivlin model agreed for the intact erythrocyte membrane. The membrane stress at a strain of 1.1 decreased by 42% for minor and 95% for severe erythrocyte membrane damage. The stability strain threshold of the damage model was 1.98 for minor and 1.19 for severe membrane damage. The developed model can represent different degrees of erythrocyte membrane damage through phosphorylation by a malaria merozoite. The model will enablein silicoinvestigations of the invasiveness of malaria merozoites.
Synthetic gene circuits combining CRISPR interference and CRISPR activation inE. coli: importance of equal guide RNA binding affinities to avoid context-dependent effects
Authors: Barbier Içvara , Kusumawardhani Hadiastri , Chauhan Lakshya , Harlapur Pradyumna Vinod , Jolly Mohit Kumar , Schaerli Yolanda 
Published: June 2023

AbstractGene expression control based on CRISPR has emerged as a powerful approach for constructing synthetic gene circuits. While the use of CRISPR interference (CRISPRi) is already well-established in prokaryotic circuits, CRISPR activation (CRISPRa) is less mature and combination of the two in the same circuits is only just emerging. Here, we report that combining CRISPRi with SoxS-based CRISPRa inEscherichia colican lead to context-dependent effects due to different affinities in the formation of CRISPRa and CRISPRi complexes, resulting in loss of predictable behaviour. We show that this effect can be avoided by using the same scaffold guide RNA structure for both complexes.
Alternative splicing is coupled to gene expression in a subset of variably expressed genes
Authors: Karlebach Guy , Steinhaus Robin , Danis Daniel , Devoucoux Maeva , Anczuków Olga , Sheynkman Gloria , Seelow Dominik , Robinson Peter N 
Published: June 2023

ABSTRACTNumerous factors regulate alternative splicing of human genes at a co-transcriptional level. However, how alternative splicing depends on the regulation of gene expression is poorly understood. We leveraged data from the Genotype-Tissue Expression (GTEx) project to show a significant association of gene expression and splicing for 6874 (4.9%) of 141,043 exons in 1106 (13.3%) of 8314 genes with substantially variable expression in ten GTEx tissues. About half of these exons demonstrate higher inclusion with higher gene expression, and half demonstrate higher exclusion, with the observed direction of coupling being highly consistent across different tissues and in external datasets. The exons differ with respect to sequence characteristics, enriched sequence motifs, RNA polymerase II binding, and inferred transcription rate of downstream introns. The exons were enriched for hundreds of isoform-specific Gene Ontology annotations, suggesting that the coupling of expression and alternative splicing described here may provide an important gene regulatory mechanism that might be used in a variety of biological contexts. In particular, higher inclusion exons could play an important role during cell division.
Predicting the placement of biomolecular structures on AFM substrates based on electrostatic interactions
Authors: Amyot Romain , Kodera Noriyuki , Flechsig Holger 
Published: June 2023

AbstractAtomic force microscopy (AFM) and high-speed AFM allow direct observation of biomolecular structures and their functional dynamics. Based on scanning the molecular surface of a sample deposited on a supporting substrate by a probing tip, topographic images of its dynamic shape are obtained. Critical to successful AFM observations is a balance between immobilization of the sample while avoiding too strong perturbations of its functional conformational dynamics. Since the sample placement on the supporting substrate cannot be directly controlled in experiments, the relative orientation isa prioriunknown, and, due to limitations in the spatial resolution of images, difficult to infer froma posteriorianalysis. We present a method to predict the macromolecular placement of samples based on electrostatic interactions with the AFM substrate and demonstrate applications to HS-AFM observations of the Cas9 endonuclease, an aptamer-protein complex, and the ClpB molecular chaperone. The model also allows predictions of imaging stability under tip-scanning. We implemented the developed method within the freely available BioAFMviewer software package. Therefore, predictions based on available structural data can be made even prior to an actual experiment.