bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental Investigation of Solids Production Mechanisms in a Hydraulic Screen-Through Fracturing Well in a Loose Reservoir and Its Control
Authors: Dilimulati Saifula , Dong Changyin , Zhan Xinjie , Li Jingwei , Cui Guoliang , Liu Quangang , Bai Haobin 
Published: January 2024

Summary
Successful cases of hydraulic screen-through fracturing (HSTF) in the Bohai oil field highlight the possibility that hydraulic fracturing can be an alternative method for enhancing the productivity of loose reservoirs. However, a portion of the HSTF wells in the Bohai oil field suffer from severe solids production, meaning that proppants and stratum sands are produced in the wellbore during production and cause wellbore plugging and ensuing debilitation of productivity. In this study, fluid flow amid the stratum, fracture, and HSTF well is simulated experimentally, and pressure drop, flow rate of the fracture, and stratum are monitored to investigate mechanisms and influencing factors of solids production from HSTF wells. Perspectives on solids control optimization are put forward for the Bohai oil field. Results indicate that the formation of an erosion cavity on lip-sealing in fracture and a dominant fluid channel near the wellbore in the stratum are two main mechanisms of solids production. The higher the flow rate and fluid viscosity are, the more severe solids production can be. For the Bohai oil field, with 725-psi-strength resin-coated proppant, the minimum proportion of resin-coated proppant in fractures to prevent solids production can be reduced from the previous 65% to 30%. With 1,073-psi-strength resin-coated proppant, it can be further reduced to 20%. Reducing the proportion of resin-coated proppant can help optimize the conductivity of fractures. This study aims to provide preliminary insight on solving the solids production problem of an HSTF well, thus enhancing the applicability of hydraulic stimulation in loose reservoirs.
Structures and activation mechanism of Gabija anti-phage system
Authors: Wang Longfei , Li Jing , Cheng Rui , Wang Zhiming , Yuan Wuliu , Xiao Jun , Zhao Xinyuan , Zhu Bin , Wang Lianrong , Du Xinran 
Published: January 2024

Abstract
Bacteria have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly abundant prokaryotic defense system in bacteria and archaea consisting of two components, GajA and GajB8. We previously demonstrated that GajA functions as a DNA endonuclease and is inhibited by ATP9. However, the mechanism of the anti-viral defense by Gabija is elusive. Here, we utilize cryo-EM to capture the Gabija system in five states, GajA in apo or complex with DNA, GajA inhibited by ATP, and GajAB in apo or with ATP/Mg2+. Our structures show that GajA is a rhombus-shaped tetramer that binds DNA in a bipartite manner. GajA recognizes and bends the substrate DNA to align the DNA cleavage site with the catalytic residues in the Toprim domain. DNA binding requires the opening of the hinged clamps, which are locked in a closed conformation upon ATP-binding, therefore inhibited by ATP. GajB does not bind DNA alone but docks on the GajA tetramer and is activated by the nicked DNA generated by GajA. Thus, GajA is activated by local depletion of cellular ATP, generating nicked DNA that activates GajB and ultimately leads to cell death. Our study unveiled a ~500 kDa supramolecular assembly of GajAB and provided mechanistic insights into the Gabija system.
Latitude impacts continental acidity, biotic crisis and recovery.
Authors: Borruel-Abadia Violeta , Barrenechea José F. , Galán-Abellán Ana Belén , López-Gómez José , Esterle Joan , McCann Tom , Horra Raul De la , Ronchi Ausonio , Gianolla Piero , Luque Javier , Rossi Valentina , Paterson Niall , Smith Roger , Wolvaardt Frederik , Brookfield Michael E , Bourquin Sylvie , Ubide Teresa 
Published: January 2024

Abstract

Volcanism from large igneous provinces leads to increases in the Earth’s surface temperature and acidity, thus triggering mass extinction events. However, the dependence of acidity on latitudinal position has remained underexplored and is key to better understand, and react to, global environmental changes today. Here, we study biotic recovery after the catastrophic end-Permian mass extinction, in Early Triassic continental environments. We quantify strontium-rich hydrated aluminum phosphate-sulfate minerals in 179 samples from tropical to circumpolar paleolatitudes in both hemispheres. We provide evidence that latitude controls acidity and its impact on biotic recovery. Subequatorial latitudes concentrate volcanic aerosols through wind circulation patterns, enhancing the impact of acidity on the environment. In contrast, high latitudes provide refuge against environmental change, hosting accelerated recovery after the end-Permian biotic crisis.
Cyclopropanes to Spirocyclic Amine-Boranes: Merging Metal Free C‒H Bond Activation and C‒C Bond Cleavage
Authors: Charette Andre , Siddiqui Saher 
Published: January 2024

Abstract
Spirocyclic motifs often require multi-step syntheses but are of high value to medicinal chemists due to frequent improvements in potency, selectivity, and physicochemical properties over their planar parent drug molecules. Due to the ubiquity of C‒H and C‒C bonds, an extremely challenging, yet incredibly attractive way to achieve molecular diversity and complexity is through the tandem and predictable activation of inert C‒H and C‒C bonds. Tandem activation/cleavage of these bonds in readily accessible cyclopropanes to access complex motifs is challenging and has only been reported using transition metals. The merging of C‒H activation and C‒C bond cleavage strategies for the regioselective transformation of unactivated cyclopropane building blocks into spirocyclic scaffolds in a metal-free manner could be a valuable addition to the organic chemist’s synthetic toolbox. Here, we demonstrate a regioselective C‒H bond activation and subsequent C‒C bond cleavage of unactivated cyclopropane amine-boranes (CABs) to form spirocyclic amine-boranes (SABs) possessing a rare N-spiroatom in an intramolecular manner using 5 mol% of Tf2NH. The one-pot transformation yields SABs that are amenable to downstream modification and provides access to potential pharmacophores that may have applications in drug discovery.
Unraveling the first world pandemic in an ancient cosmopolitan city with archaeological and genetic evidence
Authors: Jiang Rays , Adapa Swamy Rakesh , Hendrix Karen , Upadhyay Aditya , Dutta Subhajeet , Vianello Andrea , O'Corry-Crowe Gregory , Ferrer Taitana , Monroy Jorge , wood Elizabeth , Ferreira Gloria , Decker Michael , Tripathy Sucheta , Tykot Robert 
Published: January 2024

Abstract

The first world pandemic (541–767 CE) was investigated using archaeological, proteomic, genetic, and genomic technologies. Focusing on a mass burial site in Jerash, present-day Jordan, we generated evidence of a pandemic for the first time in this region of cultural and geopolitical significance. The burial site predates the Black Death by approximately 800 years, located in a unique cosmopolitan city at a cultural crossroad. The excavation results suggest an abrupt outbreak because the burials appeared to have occurred within a relatively short time range, encompassing a wide demographic range that included children, adolescents, and adults in comparable numbers. The stable isotope data revealed a diverse range of birth origins among the victims, suggesting the presence of first-generation immigrants in the population. Through whole genome capture and genetic analysis, we identified a Yersinia pestis lineage in multiple individuals of differing birth origins corresponding to the Justinian plague timeframe. This finding establishes the first genetic connection between plague pathogens and the first world pandemic long recorded in historical accounts.
Isolating transdiagnostic effects reveals specific genetic profiles in psychiatric disorders.
Authors: Keser Engin , Liao Wangjingyi , Allegrini Andrea , Rimfeld Kaili , Eley Thalia , Plomin Robert , Malanchini Margherita 
Published: January 2024

Abstract
Evidence indicates a great degree of genetic overlap between psychiatric diagnoses. Accounting for these transdiagnostic effects can sharpen research on disorder-specific genetic architecture. Here we isolate genetic effects that are shared across 11 major psychiatric disorders (p factor) to gain further insight into genetic specificity and comorbidity over and above that contributed by the p factor, unique to each psychiatric disorder. After adjusting for transdiagnostic genetic effects, we identified novel SNP associations and some changes in enrichment patterns. We examined genetic correlations among adjusted psychiatric traits as well as relationships with other biobehavioural traits. The landscape of genetic associations between pairs of psychiatric disorders changed substantially, and their genetic correlations with biobehavioural traits showed greater specificity. Isolating transdiagnostic genetic effects across major psychiatric disorders provides a nuanced understanding of disorder-specific genetic architecture and may help guide diagnostic nomenclature and treatment research.
Extraction of fetal heart beat sounds in abdominal phonocardiograms using deep attention transformer network
Authors: Almadani Murad , Alkhodari Mohanad , Ghosh Samit , Hadjileontiadis Leontios , Khandoker Ahsan 
Published: January 2024

Abstract

Conventional methods for assessing fetal well-being often require skilled clinicians and are susceptible to noise interference. Echocardiography, a primary technique for this purpose, is reliable but entails high costs and necessitates specialized equipment and trained personnel, presenting challenges in low- and middle-income countries. Phonocardiography (PCG) has recently emerged as a cost-effective alternative, but its performance and complexity limit its widespread use. In this study, we introduce Fetal Heart Sounds U-NetR (FHSU-NETR), a lightweight, easily deployable deep learning model tailored for the simultaneous extraction of fetal and maternal heart activity from raw PCG signals. Validated with data from 20 normal subjects, including a case of fetal tachycardia arrhythmia, FHSU-NETR demonstrated exceptional performance, accurately identifying 95\% of the total $35,960$ fetal heartbeats. This significantly outperformed the only method published on the same dataset, regarded as a benchmark method, which detected only 270 beats. The model exhibited a low mean difference in fetal heart rate estimation (-2.55±10.25 bpm) across the entire dataset relative to the ground-truth fetal ECG, successfully detecting the arrhythmia case. Similarly, FHSU-NETR showed a low mean difference in maternal heart rate estimation (-1.15±5.76 bpm) compared to the ground-truth maternal ECG. The model's exceptional ability to identify arrhythmia cases within the dataset underscores its potential for real-world application and generalization. Leveraging the capabilities of deep learning, our proposed model holds promise to alleviate the reliance on medical experts for the interpretation of extensive PCG recordings, thereby enhancing efficiency in clinical settings.
3D-printable composites for magnetic refrigeration based on Ni-Mn-In-Co magnetic shape memory alloys
Authors: Sánchez-Alarcos V. , Khanna D. L. R. , Roca P. La , Recarte V. , Lambri F. D. , Bonifacich F. G. , Lambri O. A. , Royo-Silvestre I. , Urbina A. , Pérez-Landazábal J. I. 
Published: January 2024

Abstract
A high filling load (62% weight) printable magnetic composite has been successfully elaborated from the dispersion of Ni45Mn36.7In13.3Co5 alloy microparticles into a PCL polymer matrix. The composite material has been prepared by solution method, resulting in a very homogeneous particles dispersion into the matrix. The structural transitions in the polymer do not seem to be affected by the addition of the metallic microparticles, which in turn results in a significant increase of the mechanical consistency. The good ductility of the elaborated composite allows its extrusion in flexible printable filaments, from which 3D pieces with complex geometries has been grown. The high measured magnetocaloric response of the composite and the possibility to print high surface/volume ratio geometries make this material a promising candidate for the development of heat exchangers for clean and efficient magnetic refrigeration applications. Furthermore, numerical simulations confirm that, in terms of heat transference, a bulk Ni-Mn-In-Co cubic piece may be even less efficient than a PCL/Ni-Mn-In-Co wire containing the same amount of magnetic active material.
SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway
Authors: Sun Jianxun , Jiang Lingyu , Liu Liu , Yang Fan , Cui Yujia , Xie Jing , Song Dongzhe , Huang Dingming 
Published: January 2024

Abstract
The odontogenic differentiation of Stem cells from apical papilla (SCAP) is regulated by many extracellular matrix proteins, which plays a crucial role in dentin formation and regeneration. Extracellular matrix protein SLIT3, a classical axon guidance molecule, can link bone resorption to formation as clastokine. However, there is little information about SLIT3 in odontogenesis. Therefore, our study is aimed to explore the effects and possible mechanism of SLIT3 on the proliferation and differentiation of SCAP. Through Immunohistochemical staining and re-analysis of single-cell RNA sequencing and microarray datasets, we found that SLIT3 was expressed in the dental papilla and odontoblast layer of the developing molar tooth of mice. Real time polymerase chain reaction (RT-PCR) and Western blot assays also revealed an increased expression of SLIT3 during the odontogenic differentiation of SCAP. Afterwards, SLIT3 siRNA was used to knockdown SLIT3 and recombinant human SLIT3 (rhSLIT3) protein was used to treat SCAP. Cell Counting Kit-8 assays (CCK8) assays showed SLIT3 promoted proliferation of SCAP. Alkaline phosphatase (ALP) staining and Alizarin red staining were decreased/increased accordingly. Odontogenic markers DMP-1 and DSPP were also down-regulated/up-regulated. In addition, p-Akt and p-GSK3β levels were increased in rhSLIT3-treated SCAP and the movement into cell nucleus of β-catenin was promoted. The effect of SLIT3 was canceled after treatment with the inhibitor of Akt/Wnt/β-catenin signaling pathway. Taken together, our data show that SLIT3 could promote the proliferation and odontogenic differentiation of SCAP by activating Akt/Wnt/β-catenin signaling pathway.
Deciphering the Allosteric Regulation of Mycobacterial Inosine-5′-Monophosphate Dehydrogenase
Authors: Pichova Iva , Bulvas Ondrej , Knejzlík Zdeněk , Sýs Jakub , Filimoněnko Anatolij , Čížková Monika , Clarová Kamila , Rejman Dominik , Kouba Tomas 
Published: January 2024

Abstract

Allosteric regulation of inosine 5′-monophosphate dehydrogenase (IMPDH), an essential enzyme of purine metabolism, contributes to the homeostasis of adenine and guanine nucleotides. However, the precise molecular mechanism of IMPDH regulation in bacteria remains unclear. Using biochemical, and cryo-EM approaches, we reveal the intricate molecular mechanism of the IMPDH allosteric regulation in mycobacteria. The enzyme is inhibited by both GTP and (p)ppGpp which bind to the regulatory CBS domains and, via interactions with basic residues in hinge regions, lock the catalytic core domains in a compressed conformation. This results in occlusion of inosine monophosphate (IMP) substrate binding to the active site and, ultimately, inhibition of the enzyme. The GTP and (p)ppGpp allosteric effectors bind to their dedicated sites but stabilize the compressed octamer by a common mechanism. Inhibition is relieved by the competitive displacement of GTP or (p)ppGpp by ATP allowing IMP-induced enzyme expansion. The structural knowledge and mechanistic understanding presented here open up new possibilities for the development of allosteric inhibitors with antibacterial potential.
Melanoma-inhibitor of apoptosis protein: a key driver of microglia phenotype and glioblastoma immune microenvironment
Authors: Snacel-Fazy Emmanuel , Soubéran Aurélie , Grange Magali , Joseph Kevin , Colin Carole , Morando Philippe , Luche Hervé , Brustlein Sophie , Debarbieux Franck , Siret Carole , de Pavert Serge A. van , Rougon Geneviève , Figarella-Branger Dominique , Ravi Vidhya Madapusi , Tabouret Emeline , Tchoghandjian Aurélie 
Published: January 2024

Abstract
Tumor-associated macrophages/microglia (TAMs) are highly plastic and heterogeneous immune cells that can be immune-supportive or tumor-supportive depending of the microenvironment. TAMs are the most abundant immune cells in glioblastoma (GB), and play a key role in immunosuppression. Therefore, TAMs reprogramming toward immune-supportive cells is a promising strategy to overcome immunosuppression. By leveraging scRNAseq human GB databases, we identified that within the tumor microenvironment, ML-IAP, a member of the Inhibitor of Apoptosis Proteins (IAP) known to regulate inflammation, was exclusively expressed by TAMs. To investigate its role in TAMs-related immunosuppression, we antagonized ML-IAP using the central nervous system permeant SMAC mimetic GDC-0152 (SMg). On explants and cultured immune cells isolated from human GB samples, SMg modified TAMs activity. We showed that inhibiting ML-IAP in microglia promoted their pro-apoptotic and anti-tumoral function via caspase-3 pro-inflammatory cleavage and the inhibition of tumoroïds growth. Then we designed a relevant immunogenic mouse GB model to decipher the spatio-temporal densities, distribution, phenotypes and function of TAMs with or without SMg treatment. We used 3D imaging techniques, a transgenic mouse with fluorescent TAM subsets and mass cytometry. We confirmed that SMg promoted microglia activation, antigen-presenting function and tumor infiltration. In addition, we observed a normalization of blood vessels, a decrease in anti-inflammatory macrophages and an increased level of monocytes and their mo-DC progeny. This remodeling of the TAM landscape is associated with an increase in CD8 T cell density and activation. Altogether, these results demonstrated that ML-IAP inhibition drives the immunosuppressive basal microglia toward an active phenotype with pro-apoptotic and anti-tumoral function and modifies the GB immune landscape. This identifies ML-IAP as a target of choice for a potential mechanism-based therapeutic strategy and SMg as a promising molecule for this application.
Hydroalcoholic extract of Centella asiatica and madecassic acid reverse depressive-like behaviors, inflammation and oxidative stress in adult rats submitted to stress in early life
Authors: Bertollo Amanda Gollo , Mingoti Maiqueli Eduarda Dama , Medeiros Jesiel , Silva Gilnei Bruno da , Capoani Giovana Tamara , Lindemann Heloisa , Cassol Joana Vitória , Manica Daiane , Oliveira Tacio , Garcez Michelle Lima , Bagatini Margarete Dulce , Bohnen Lilian Caroline , Roman Walter Antônio , Ignácio Zuleide Maria 
Published: January 2024

Abstract

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates potential neuroprotective but has not yet been evaluated in MD models. Objective: This study aimed to evaluate the effect of C. asiaticaextract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Method: Rats (after the first day of birth) were separated from the mother for three hours a day for ten days. These animals, when adults, were divided into groups and submitted to treatment for 14 days. After the animals were submitted to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, they were then euthanized. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. Results: The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. Conclusion: These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through an anti-inflammatory and antioxidant profile.
Identification of the prognosis value of pyroptosis related genes in the NSCLC
Authors: Huang Yuxia , Fan Yingying , Ye Ning , Feng Junpeng , Jiang Lei , Zhang Wentian 
Published: January 2024

Abstract
Backgrounds:Our study aimed to identify the prognosis value of pyroptosis related genes of cancer associated fibroblasts (CAFs) in the NSCLC.
Methods:We downloaded series matrix file data of GSE117570 from the NCBI GEO public database for single cell analysis. And the GSE30219, GSE37745 were used for verification. Furthermore, we downloaded the raw mRNA expression data of processed Lung adenocarcinoma (LUAD) including normal group (n=59), tumor group (n=541) from the TCGA database (https://portal.gdc.cancer.gov/).We performed gene set enrichment analysis (GSEA) and gene set variant analysis (GSVA) for the pyroptosis-related genes. Then we constructed the risk model using the pyroptosis related genes and identify the difference signature of the CAFs between the high risk group and low risk group. Nomogram and Kaplan–Meier method were used to validate the prognostic value of risk model.
Results:We constructed a risk model using the GGA2, TLR2, PKM , CALM3, RBBP7, CAPNS1, YWHAZ and BIRC3. GSEA results showed that carbon metabolism, galactose metabolism, and p53 signaling pathways were all involved. The results of GSVA showed that the differences between patients were mainly enriched in signaling pathways such as mTORC1 signaling. The T cells CD8, Macrophages M0, Macrophages M1 were significantly higher in the high risk group. The expression levels of 8 model genes were significantly correlated with the expression levels of multiple tumor-related genes. BIRC3 and ATM are significantly positively correlated.
Conclusions:The pyroptosis of the CAFs are related to the prognosis of the NSCLC.
Obtaining an Avoidant Restrictive Food Intake Disorder diagnosis in The UK for Individuals with Intellectual and Developmental Disabilities: A Qualitative Study of Families’ Experiences
Authors: Desalesa Jonah Jirehl , Mejía-Buenaño Suzy 
Published: January 2024

Abstract

Background The prevalence of Avoidant Restrictive Food Intake Disorder (ARFID) is generally low among the eating and feeding disorders population. The complexity of the diagnosis, along with its potential comorbidities (e.g., Intellectual and Developmental Disabilities), had led to difficulties in diagnosing ARFID, with limited support and treatment available. This study therefore asked families with lived experience of the ARFID diagnostic process and their access to support for diagnostic evaluation and understandings of available support. Method Data was collected through a qualitative approach using online semi-structured interviews investigating eight participants’ experiences of their children undergoing the ARFID diagnostic process and their access to support. Responses were subjected to thematic analysis. Results From thematic analysis, three major themes were identified: the ups and downs of diagnosis, pushing for support, and looking into the future. Conclusions Participants’ experiences surrounded the ‘lucky’ encounters with the ARFID diagnosis, where the limited support was emphasised. The findings highlighted the need for an improved ARFID diagnostic process for better awareness and support availability for families living with ARFID. Recommendations from study findings were provided for readers and researchers.