bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and immune determinants of resistance to anti-CD38 monoclonal antibody-based therapy in relapsed refractory multiple myeloma
Authors: Ziccheddu Bachisio , Giannotta Claudia , D’Agostino Mattia , Bertuglia Giuseppe , Saraci Elona , Oliva Stefania , Genuardi Elisa , Papadimitriou Marios , Diamond Benjamin , Corradini Paolo , Coffey David , Landgren Ola , Bolli Niccolò , Bruno Benedetto , Boccadoro Mario , Massaia Massimo , Maura Francesco , Larocca Alessandra 
Published: December 2023

SUMMARYAnti-CD38 antibody therapies have transformed multiple myeloma (MM) treatment. However, a large fraction of patients inevitably relapses. To understand this, we investigated 32 relapsed MM patients treated with daratumumab, lenalidomide, and dexamethasone (Dara-Rd;NCT03848676). Whole genome sequencing (WGS) before and after treatment pinpointed genomic drivers associated with early progression, includingRPL5loss and APOBEC mutagenesis. Flow cytometry on 202 blood samples, collected every three months until progression for 31 patients, revealed distinct immune changes significantly impacting clinical outcomes. Progressing patients exhibited significant depletion of CD38+ NK cells, persistence of T cell exhaustion, and reduced depletion of T-reg cells over time. These findings underscore the influence of immune composition and daratumumab-induced immune changes in promoting MM resistance. Integrating genomics and flow cytometry unveiled associations between adverse genomic features and immune patterns. Overall, this study sheds light on the intricate interplay between genomic complexity and the immune microenvironment driving resistance to Dara-Rd.
Ultra-efficient causal deep learning for Dynamic CSA-AKI Detection Using Minimal Variables
Authors: Zhong Qin , Cheng Yuxiao , Li Zongren , Wang Dongjin , Rao Chongyou , Jiang Yi , Li Lianglong , Wang Ziqian , Liu Pan , Zhao Yawei , Li Pei , Suo Jinli , Dai Qionghai , He Kunlun 
Published: December 2023

ABSTRACTCardiac surgery-associated Acute Kidney Injury (CSA-AKI) is a significant complication that often leads to increased morbidity and mortality. Effective CSA-AKI management relies on timely diagnosis and interventions. However, many cases of CSA-AKI are detected too late. Despite the efforts of novel biomarkers and data-driven predictive models, their limited discriminative and generalization capabilities along with stringent application requirements pose challenges for clinical use. Here we incorporate a causal deep learning approach that combines the universal approximation abilities of neural networks with causal discovery to develop REACT, a reliable and generalizable model to predict a patient’s risk of developing CSA-AKI within the next 48 hours. REACT was developed using 21.5 billion time-stamped medical records from two large hospitals covering 23,933 patients and validated in three independent centers covering 30,963 patients. By analyzing the causal relationships buried in the time dimensions, REACT distilled the complex temporal dynamics among variables into six minimal causal inputs and achieved an average AUROC of 0.93 (ranging from 0.89 to 0.96 among different CSA-AKI stages), surpassing state-of-the-art models that depend on more complex variables. This approach accurately predicted 97% of CSA-AKI events within 48 hours for all prediction windows, maintaining a ratio of 2 false alerts for every true alert, improving practical feasibility. Compared to guideline-recommended pathways, REACT detected CSA-AKI on average 16.35 hours earlier in external tests. In addition, we have established a publicly accessible website and performed prospective validation on 754 patients across two centers, achieving high accuracy. Our study holds substantial promise in enhancing early detection and preserving critical intervention windows for clinicians.
Validation of remote collection and quantification of blood Neurofilament light in neurological diseases
Authors: Coleman Annabelle , Touzé Alexiane , Farag Mena , Pengo Marta , Murphy Michael J , Hassan Yara , Thackeray Olivia , Fayer Kate , Field Sophie , Nakajima Mitsuko , Broom Elizabeth L , Huxford Brook , Donkor Natalie , Camboe Ellen , Dey Kamalesh C , Zirra Alexandra , Ahmed Aisha , Costa Ana Rita Gameiro , Sorrell Harriet , Zampedri Luca , Lombardi Vittoria , Wade Charles , Mangion Sean , Fneich Batoul , Heslegrave Amanda , Zetterberg Henrik , Noyce Alastair , Malaspina Andrea , Chataway Jeremy , Tabrizi Sarah J , Byrne Lauren M 
Published: December 2023

AbstractPromising blood-based biomarkers of neuropathology have emerged with potential for therapeutic development and disease monitoring. However, these tools will require specialist tertiary services for integration into clinical management. Remote sampling for biomarker assessment could ease the burden of in-person clinical visits for such tests and allow for frequent sampling. Here we evaluated a capillary finger-prick collection for remote quantification of blood neurofilament light (NfL), a common blood-based biomarker evident in various neurological disorders, and other exploratory markers of neuronal injury and neuroinflammation (GFAP, tau).Matched samples from venepuncture and finger-prick were collected and processed into plasma and/or serum to directly compare NfL levels across four different neurological conditions (HD, MS, ALS, PD). Two delayed processing conditions were compared, three- and seven-day delay, simulating ambient shipment.Capillary NfL and GFAP concentrations were equivalent to those in venous blood serum and plasma. Only NfL remained stable after seven-day processing delay. Capillary NfL replicated disease group differences displayed in venous blood.This data supports our finger-prick method for remote collection and quantification of NfL. With the widespread applications for NfL across the spectrum of neurological disorders, this has the potential to transform disease monitoring, prognosis, and therapeutic development within clinical practice and research.Graphical abstract: Figure 1
SLC25A48 is a human mitochondrial choline transporter
Authors: Patil Suraj , Borisov Oleg , Scherer Nora , Wirth Christophe , Schlosser Pascal , Wuttke Matthias , Eckardt Kai-Uwe , Hunte Carola , Neubauer Björn , Köttgen Anna , Köttgen Michael 
Published: December 2023

AbstractCholine has important physiological functions as a precursor for essential cell components and signaling molecules including phospholipids and the neurotransmitter acetylcholine. Choline is a water-soluble charged molecule and therefore requires transport proteins to cross biological membranes. Membrane transport of choline is incompletely understood. Here we show that SLC25A48 is a human mitochondrial choline transporter. Loss-of-function mutations inSLC25A48are associated with elevated urine and plasma choline levels resulting from impaired choline transport into mitochondria.
MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer’s disease
Authors: Lukacsovich David , O’Shea Deirdre , Huang Hanchen , Zhang Wei , Young Juan I. , Chen X. Steven , Dietrich Sven-Thorsten , Kunkle Brian , Martin Eden R. , Wang Lily 
Published: December 2023

ABSTRACTAlzheimer’s disease (AD) is a common neurodegenerative disorder with a significant impact on aging populations. DNA methylation (DNAm) alterations have been implicated in both the aging processes and the development of AD. Given that AD affects more women than men, it is also important to explore DNAm changes that occur specifically in each sex. We created MIAMI-AD, a comprehensive knowledge base containing manually curated summary statistics from 97 published tables in 37 studies, all of which included at least 100 participants. MIAMI-AD enables easy browsing, querying, and downloading DNAm associations at multiple levels – at individual CpG, gene, genomic regions, or genome-wide, in one or multiple studies. Moreover, it also offers tools to perform integrative analyses, such as comparing DNAm associations across different phenotypes or tissues, as well as interactive visualizations. Using several use case examples, we demonstrated that MIAMI-AD facilitates our understanding of age-associated CpGs in AD and the sex-specific roles of DNAm in AD. This open-access resource is freely available to the research community, and all the underlying data can be downloaded. MIAMI-AD (https://miami-ad.org/) facilitates integrative explorations to better understand the interplay between DNAm across aging, sex, and AD.
Effect of composting and storage on the microbiome and resistome of cattle manure from a commercial dairy farm in Poland
Authors: Zalewska Magdalena , Błażejewska Aleksandra , Szadziul Mateusz , Ciuchciński Karol , Popowska Magdalena 
Published: December 2023

AbstractManure from food-producing animals, rich in antibiotic-resistant bacteria and antibiotic resistance genes (ARGs), poses significant environmental and healthcare risks. Despite global efforts, most manure is not adequately processed before use on fields, escalating the spread of antimicrobial resistance. This study examined how different cattle manure treatments, including composting and storage, affect its microbiome and resistome. The changes occurring in the microbiome and resistome of the treated manure samples were compared with those of raw samples by high-throughput qPCR for ARGs tracking and sequencing of the V3-V4 variable region of 16S rRNA gene to indicate bacterial community composition. We identified 203 ARGs and mobile genetic elements (MGEs) in raw manure. Post-treatment reduced these to 76 in composted and 51 in stored samples. Notably, beta-lactam, cross-resistance to macrolides, lincosamides and streptogramin B (MLSB), and vancomycin-resistance genes decreased, while genes linked to MGEs, integrons, and sulfonamide resistance increased after composting. Overall, total resistance gene abundance significantly dropped with both treatments. During composting, the relative abundance of genes was lower midway than at the end. Moreover, higher biodiversity was observed in samples after composting than storage. Our current research shows that both composting and storage effectively reduce ARGs in cattle manure. However, it’s challenging to determine which method is superior, as different groups of resistance genes react differently to each treatment, even though a notable overall reduction in ARGs is observed.
Targeting endothelial FOXO1 protects diabetic β-cells and improves wound healing
Authors: Wu Hao , Cui Kui , Zhu Bo , Lu Yao Wei , Sun Liang , Ma Qianyi , Jian Ashish , Hurtado Daniel Osorio , Gao Xinlei , Li Yanqian , Bhattacharjee Sudarshan , Fu Haojie , Birsner Amy E. , Malovichko Marina V. , Li Manna , Wang Beibei , Singh Bandana , Peng Qianman , Wong Scott , Norton Vikram , Li Kathryn , Eisa-Beygi Shahram , Wang Donghai , Cowan Douglas B. , Bielenberg Diane R. , Srivastava Sanjay , Rockowitz Shira , Xu Jian , D’Amato Robert J. , Chen Kaifu , Dong Min , Biddinger Sudha , Chen Hong 
Published: December 2023

AbstractThe forkhead box O1 (FOXO1) transcription factor plays critical roles in regulating not only metabolic activity but also angiogenesis in the vascular endothelium1–4. Our previous studies show that epsin endocytic adaptors can regulate both angiogenesis and lymphangiogenesis5–7. Endothelial cells (ECs) lining the inside of blood vessels are continuously exposed to circulating insulin and insulin-like growth factors (IGFs). Emerging evidences suggest that ECs can affect β-cell function8–11. Excessive IGF2, especially elevated local IGF2 levels in islets, may represent a risk factor for developing diabetes12–15; however, the underlying molecular mechanisms by which aberrant angiogenesis and endothelium-derived factors regulate pancreatic β-cell function in diabetes remain unclear. Here, we report that the pancreas of diabetic patients as well as the pancreas, skin, and plasma of streptozotocin/high fat diet (STZ/HFD)-induced diabetic mice anddb/dbmice contains excess IGF2, which can lead to β-cell dysfunction and apoptosis. Single-cell transcriptomics combined with mass spectrometry analysis reveal that endothelial-specific knockout of FOXO1 increases circulating soluble and cell-membrane or intracellular expression levels of IGF type 2 receptor (IGF2R) and CCCTC-binding factor (CTCF), while decreasing IGF2 levels in diabetes. Both IGFR215–17and CTCF18–21can reduce IGF2 levels and may ameliorate β-cell decline associated with excess IGF2 in diabetes. Furthermore, depletion of FOXO1, epsins, or knockdown of ULK1 inhibits autophagy formation in ECs, preventing degradation of vascular endothelial growth factor receptor 2 (VEGFR2) to promote angiogenesis and improve wound healing in diabetes. Our findings reveal that endothelial FOXO1 regulates epsin-dependent angiogenesis and affects β-cell function and fate through CTCF and IGF2-IGF2R, providing a potential strategy for ameliorating diabetes and accelerating cutaneous wound healing.
E-cadherin-dependent phosphorylation of EGFR governs a homeostatic feedback loop controlling intercellular junction viscosity and collective migration modes
Authors: Fu Chaoyu , Dilasser Florian , Lin Shao-Zhen , Karnat Marc , Arora Aditya , Rajendiran Harini , Ong Hui Ting , Hoon Brenda Nai Mui , Phow Sound Wai , Hirashima Tsuyoshi , Sheetz Michael , Rupprecht Jean-François , Tlili Sham , Viasnoff Virgile 
Published: December 2023

AbstractActomyosin tension has been shown to be a ubiquitous driver of tissue morphogenesis1, 2. The Rho pathway, a prominent regulatory network influencing cortical tension, plays a central role in both tissue reorganisation and cell migration3–6. While viscous dissipation in the actin network is commonly regarded as a constant passive parameter in cell migration in both 2D and 3D contexts, there is limited knowledge concerning the regulation of dissipative forces arising from viscous drag between cells during collective rearrangement. Here, we found that the phosphorylation of Epithelial Growth Factor Receptor (EGFR) downstream ofde novoE-cadherin adhesion7, 8orchestrates a feedback loop, thereby governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. Combining molecular cell biology, micropatterning, andin silicosimulation, our work suggests the existence of a regulatory loop by which cells can tune junctional actin viscosity, with implications for the phenomenology of morphogenetic movements.
Psychiatric Genome-wide Association Study Enrichment Shows Promise for Future Psychopharmaceutical Discoveries
Authors: Hatoum Alexander S. , Gorelik Aaron , Blaydon Lauren , Chi Tingying , Baranger David A.A. , Miller Alex P. , Johnson Emma C. , Agrawal Arpana , Bogdan Ryan 
Published: December 2023

AbstractInnovation in psychiatric therapeutics has stagnated on a handful of known mechanisms. Psychiatric genome-wide association studies (GWASs) have begun to identify hundreds of genome-wide significant (GWS) loci and characterize complex polygenic architectures. These data have rapidly advanced our understanding of disease etiology but their ability to inform clinical treatment in psychiatry remains largely unexplored. Here, we show that large psychiatric GWASs (schizophrenia, bipolar disorder, major depressive disorder, and substance use disorders) are enriched (OR: 2.776-27.629) for drug targets of current therapeutics used to treat these disorders (e.g., SNRI’s for MDD; antipsychotics for schizophrenia and MDD). The effect sizes of individual loci and the number of variants identified in a study, but not functional annotations of SNPs, drove enrichment. Psychiatric GWAS results may assist in drug repurposing and novel treatment identification.
Replication stress response in fission yeast differentially depends on maintaining proper levels of Srs2 helicase and Rrp1, Rrp2 DNA translocases
Authors: Baranowska Gabriela , Misiorna Dorota , Białek Wojciech , Kramarz Karol , Dziadkowiec Dorota 
Published: December 2023

AbstractHomologous recombination is a key process that governs the stability of eukaryotic genomes during DNA replication and repair. Multiple auxiliary factors regulate the choice of homologous recombination pathway in response to different types of replication stress. UsingSchizosaccharomyces pombewe have previously suggested the role of DNA translocases Rrp1 and Rrp2, together with Srs2 helicase, in the common synthesis dependent strand annealing sub-pathway of homologous recombination. Here we show that all three proteins are important for completion of replication after hydroxyurea exposure and provide data comparing the effect of overproduction of Srs2 with Rrp1 and Rrp2. Upregulation of Srs2 protein levels leads to enhanced replication stress, chromosome instability and viability loss, as previously reported for Rrp1 and Rrp2. Interestingly, our data suggests that dysregulation of Srs2, Rrp1 and Rrp2 protein levels differentially affects checkpoint response. Overproduction of Srs2 activates simultaneously DNA damage and replication stress response checkpoints, while cells overproducing Rrp1 mainly launch DNA damage checkpoint. Upregulation of Rrp2 primarily leads to replication stress response checkpoint activation. Overall, we propose that Srs2, Rrp1 and Rrp2 have important and independent functions for maintenance of distinct difficult to replicate regions of the genome.
Synthesis, crystal structure and hydrogenation properties of Mg
x
Li3 − x
B48 − y
(x = 1.11, y = 0.40)
Authors: Pavlyuk Nazar , Milashius Viktoria , Kordan Vasyl , Pavlyuk Volodymyr 
Published: December 2023

The ternary magnesium/lithium boride, Mg
x
Li3 − x
B48 − y
(x = 1.11, y = 0.40, idealized formula MgLi2B48), crystallizes as its own structure type in P43212, which is closely related to the structural family comprising α-AlB12, Be0.7Al1.1B22 and tetragonal β-boron. The asymmetric unit of title structure contains two statistical mixtures Mg/Li in Wyckoff sites 8b with relative occupancies Mg:Li = 0.495 (9):0.505 (9) and 4a with Mg:Li = 0.097 (8):0.903 (8). The boron atoms occupy 23 8b sites and two 4a sites. One of the latter sites has a partial occupancy factor of 0.61 (2). Both unique Mg/Li atoms adopt a twelvefold coordination environment in the form of truncated tetrahedra (Laves polyhedra). These polyhedra are connected by triangular faces to four [B12] icosahedra. The boron atoms exhibit four kinds of polyhedra, namely pentagonal pyramid (coordination number CN = 6), distorted tetragonal pyramid (CN = 5), bicapped hexagon (CN = 8) and gyrobifastigium (CN = 8). At the gas hydrogenation of MgLi2B48 alloy, formation of the eutectic composite hydride LiBH4+Mg(BH4)2 and amorphous boron is observed. In the temperature range 543–623 K, the hydride eutectics decompose, forming MgH2, LiH, MgB4, B and H2.
A priori tests of turbulence models for compressible flows
Authors: Sciacovelli Luca , Cannici Aron , Passiatore Donatella , Cinnella Paola 
Published: December 2023

Purpose
The purpose of the paper is to analyse the performances of closures and compressibility corrections classically used in turbulence models when applied to highly-compressible turbulent boundary layers (TBLs) over flat plates.

Design/methodology/approach
A direct numerical simulation (DNS) database of TBLs, covering a wide range of thermodynamic conditions, is presented and exploited to perform a priori analyses of classical and recent closures for turbulent models. The results are systematically compared to the “exact” terms computed from DNS.

Findings
The few compressibility corrections available in the literature are not found to capture DNS data much better than the uncorrected original models, especially at the highest Mach numbers. Turbulent mass and heat fluxes are shown not to follow the classical gradient diffusion model, which was shown instead to provide acceptable results for modelling the vibrational turbulent heat flux.

Originality/value
The main originality of the present paper resides in the DNS database on which the a priori tests are conducted. The database contains some high-enthalpy simulations at large Mach numbers, allowing to test the performances of the turbulence models in the presence of both chemical dissociation and vibrational relaxation processes.
The effect of perceptions of justice in returns on satisfaction and attitudes toward the retailer
Authors: Jones Angela L. , Miller Jason W. , Whipple Judith M. , Griffis Stanley E. , Voorhees Clay M. 
Published: December 2023

PurposeIn the competitive retailing environment, retailers who provide service experiences that stand out from the competition can gain a competitive advantage. Increasingly, an important aspect of the service experience involves product returns, in particular, the fairness of returns policies and procedures. Previous research studies support that interpersonal justice and informational justice relate positively to consumer attitudes and behaviors. In this paper, the authors examine the relative effects of interpersonal justice and informational justice on return satisfaction, positive word-of-mouth (PWOM) and trust. Additionally, the authors examine the moderating effects of returns process convenience and returns policy restrictiveness as indicators of procedural justice.Design/methodology/approachA scenario-based experiment methodology was used to test the relationships of interest.FindingsResults support that the effects of interpersonal justice on the outcome variables are stronger than the effects of informational justice. There is also support for a moderating effect of returns process convenience on the relationships between interpersonal justice and each outcome variable, as well as partial support for the moderating effect of returns policy restrictiveness on the relationship between interpersonal justice and PWOM.Originality/valueThe research extends previous work on the effects of justice on customer outcomes. Results support the importance of retailers treating customers with fairness during the returns experience and further support the benefits of providing a convenient returns experience.