bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5/PKA/CREB Pathway After Intracerebral Hemorrhage
Authors: Yan Jun , Xu Weilin , Lenahan Cameron , Huang Lei , Wen Jing , Li Gaigai , Hu Xin , Zheng Wen , Zhang John H. , Tang Jiping 
Published: November 2021

Background and Purpose:
Neuronal pyroptosis is a type of regulated cell death triggered by proinflammatory signals. CCR5 (C-C chemokine receptor 5)-mediated inflammation is involved in the pathology of various neurological diseases. This study investigated the impact of CCR5 activation on neuronal pyroptosis and the underlying mechanism involving cAMP-dependent PKA (protein kinase A)/CREB (cAMP response element binding)/NLRP1 (nucleotide-binding domain leucine-rich repeat pyrin domain containing 1) pathway after experimental intracerebral hemorrhage (ICH).

Methods:
A total of 194 adult male CD1 mice were used. ICH was induced by autologous whole blood injection. Maraviroc (MVC)—a selective antagonist of CCR5—was administered intranasally 1 hour after ICH. To elucidate the underlying mechanism, a specific CREB inhibitor, 666-15, was administered intracerebroventricularly before MVC administration in ICH mice. In a set of naive mice, rCCL5 (recombinant chemokine ligand 5) and selective PKA activator, 8-Bromo-cAMP, were administered intracerebroventricularly. Short- and long-term neurobehavioral assessments, Western blot, Fluoro-Jade C, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunofluorescence staining were performed.

Results:
The brain expression of CCL5 (chemokine ligand 5), CCR5, PKA-Cα (protein kinase A-Cα), p-CREB (phospho-cAMP response element binding), and NLRP1 was increased, peaking at 24 hours after ICH. CCR5 was expressed on neurons, microglia, and astrocytes. MVC improved the short- and long-term neurobehavioral deficits and decreased neuronal pyroptosis in ipsilateral brain tissues at 24 hours after ICH, which were accompanied by increased PKA-Cα and p-CREB expression, and decreased expression of NLRP1, ASC (apoptosis-associated speck-like protein containing a CARD), C-caspase-1, GSDMD (gasdermin D), and IL (interleukin)-1β/IL-18. Such effects of MVC were abolished by 666-15. At 24 hours after injection in naive mice, rCCL5 induced neurological deficits, decreased PKA-Cα and p-CREB expression in the brain, and upregulated NLRP1, ASC, C-caspase-1, N-GSDMD, and IL-1β/IL-18 expression. Those effects of rCCL5 were reversed by 8-Bromo-cAMP.

Conclusions:
CCR5 activation promoted neuronal pyroptosis and neurological deficits after ICH in mice, partially through the CCR5/PKA/CREB/NLRP1 signaling pathway. CCR5 inhibition with MVC may provide a promising therapeutic approach in managing patients with ICH.
Scale Sensitivity of the Gill Circulation. Part I: Equatorial Case
Authors: Reboredo Beatriz , Bellon Gilles 
Published: November 2021

Abstract
We investigate the steady dynamical response of the atmosphere on the equatorial β plane to a steady, localized, midtropospheric heating source at the equator. Expanding Gill’s seminal work, we vary the latitudinal and longitudinal scales of the diabatic heating pattern while keeping its total amount fixed. We focus on characteristics of the response that would be particularly important if the circulation interacted with the hydrologic and energy cycles: the overturning circulation and the low-level wind. In the limit of very small scale in either the longitudinal or latitudinal direction, the vertical energy transport balances the diabatic heating and this sets the intensity of the overturning circulation. In this limit, a fast low-level westerly jet is located around the center of diabatic heating. With increasing longitudinal or latitudinal scale of the diabatic heating, the intensity of the overturning circulation decreases and the low-level westerly jet decreases in maximum velocity and spatial extent relative to the spatial extent of this heating. The associated low-level eastward mass transport decreases only with increasing longitudinal scale. These results suggest that moisture-convergence feedbacks will favor small-scale equatorial convective disturbances while surface-heat-flux feedbacks would favor small-scale disturbances in mean westerlies and large-scale disturbances in mean easterlies. Part II investigates the case of off-equatorial heating.
Implementation and Evaluation of a Double-Plume Convective Parameterization in NCAR CAM5
Authors: Chu Wenchao , Lin Yanluan , Zhao Ming 
Published: November 2021

AbstractPerformance of global climate models (GCMs) is strongly affected by the cumulus parameterization (CP) used. Similar to the approach in GFDL AM4, a double-plume CP, which unifies the deep and shallow convection in one framework, is implemented and tested in the NCAR Community Atmospheric Model version 5 (CAM5). Based on the University of Washington (UW) shallow convection scheme, an additional plume was added to represent the deep convection. The shallow and deep plumes share the same cloud model, but use different triggers, fractional mixing rates, and closures. The scheme was tested in single-column, short-term hindcast, and AMIP simulations. Compared with the default combination of the Zhang–McFarlane scheme and UW scheme in CAM5, the new scheme tends to produce a top-heavy mass flux profile during the active monsoon period in the single-column simulations. The scheme increases the intensity of tropical precipitation, closer to TRMM observations. The new scheme increased subtropical marine boundary layer clouds and high clouds over the deep tropics, both in better agreement with observations. Sensitivity tests indicate that regime-dependent fractional entrainment rates of the deep plume are desired to improve tropical precipitation distribution and upper troposphere temperature. This study suggests that a double-plume approach is a promising way to combine shallow and deep convections in a unified framework.
Effects of Smooth Divergence-Free Flows on Tracer Gradients and Spectra: Eulerian Prognosis Description
Authors: Resseguier Valentin , Chapron Bertrand , Mémin Etienne 
Published: November 2021

AbstractOcean eddies play an important role in the transport of heat, salt, nutrients, or pollutants. During a finite-time advection, the gradients of these tracers can increase or decrease, depending on a growth rate and the angle between flow gradients and initial tracer gradients. The growth rate is directly related to finite-time Lyapunov exponents. Numerous studies on mixing and/or tracer downscaling methods rely on satellite altimeter-derived ocean velocities. Filtering most oceanic small-scale eddies, the resulting smooth Eulerian velocities are often stationary during the characteristic time of tracer gradient growth. While smooth, these velocity fields are still locally misaligned, and thus uncorrelated, to many coarse-scale tracer observations amendable to downscaling [e.g., sea surface temperature (SST), sea surface salinity (SSS)]. Using finite-time advections, the averaged squared norm of tracer gradients can then only increase, with local growth rate independent of the initial coarse-scale tracer distribution. The key mixing processes are then only governed by locally uniform shears and foldings around stationary convective cells. To predict the tracer deformations and the evolution of their second-order statistics, an efficient proxy is proposed. Applied to a single velocity snapshot, this proxy extends the Okubo–Weiss criterion. For the Lagrangian-advection-based downscaling methods, it further successfully predicts the evolution of tracer spectral energy density after a finite time, and the optimal time to stop the downscaling operation. A practical estimation can then be proposed to define an effective parameterization of the horizontal eddy diffusivity.Significance StatementAn analytical formalism is adopted to derive new exact and approximate relations that express the clustering of tracers transported by upper-ocean flows. This formalism bridges previous Eulerian and Lagrangian approaches. Accordingly, for slow and smooth upper-ocean flows, a rapid prognosis estimate can solely be performed using single-time velocity field observations. Well suited to satellite-altimeter measurements, it will help rapidly identify and monitor mixing regions occurring in the vicinity of ocean eddy boundaries.
Effectiveness of early versus delayed rehabilitation following total shoulder replacement: A systematic review
Authors: Moffatt Maria , Whelan Gareth , Gill Peter , Mazuquin Bruno , Edwards Peter , Peach Chris , Davies Ronnie , Morgan Marie , Littlewood Chris 
Published: November 2021

Objective To investigate the effectiveness of early versus delayed rehabilitation following total shoulder replacement. Design Intervention systematic review with narrative synthesis. Literature search MEDLINE, EMBASE, CINAHL, Scopus and the Cochrane Library were searched from inception to the 29th of July 2021. Study selection criteria Randomised controlled trials comparing early versus delayed rehabilitation following primary anatomic, primary reverse, or revision total shoulder replacement. Data synthesis A revised Cochrane risk of bias assessment tool for randomised controlled trials was used, as well as the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the quality of evidence. A narrative synthesis was undertaken. Results Three eligible randomised controlled trials ( n = 230) were included. There was very low-quality evidence of no statistically significant difference ( P > 0.05) in pain, shoulder function, health-related quality of life or lesser tuberosity osteotomy healing at 12 months between early or delayed rehabilitation. There was conflicting and very low-quality evidence of a difference between the effect of early and delayed rehabilitation on shoulder range of movement. There was limited, very low-quality evidence of statistically significantly improved pain and function ( P < 0.05) in the early post-operative period with early rehabilitation following anatomic total shoulder replacement. Conclusions No differences were seen in patient-reported or clinician-reported outcomes at 12 months post-surgery between early and delayed rehabilitation following total shoulder replacement. There is very low-quality evidence that early rehabilitation may improve shoulder pain and function in the early post-operative phase following anatomic total shoulder replacement.
Novel poly(arylene ether nitrile) containing pendant aliphtatic ring in the chain: Synthesis and properties
Authors: Luo Shajie , Ren Fajian , Dai Jiangang , Chen Yan , Yang Zhongzhu 
Published: November 2021

Two kinds of novel poly(arylene ether nitrile)s (CPDP-DCBN and CHDP-DCBN) containing pendant aliphtatic ring were synthesized by 4,4′-cyclopentane-1,1′-diyldiphenol (CPDP) or 4,4′-cyclohexane-1,1′-diyldiphenol (CHDP) and 2,6-dichlorobenzonitrile (DCBN) in this work. The inherent viscosities of poly(arylene ether nitrile)s (PENs) were in the range of 0.701–0.806 dL g−1. The polymers showed high glass transition temperatures ( T g) of 185.4–196.4°C and weight-loss temperatures ( T5%) of 447.8–454.3°C. The obtained CPDP-DCBN and CHDP-DCBN could be hot pressed into the films, which showed the tensile strengths of 82.6 MPa and 86.8 MPa, respectively. And the storage modulus of CPDP-DCBN and CHDP-DCBN were about 1.0 GPa and 1.5 GPa at 150°C, respectively. Additionally, the PENs could be dissolved in many solutions at room temperature, such as NMP and concentrated H2SO4, indicating that they had good solubility; they can be processed by the solution method. Meanwhile, the optical transmittance of CPDP-DCBN was 78.1% at 450 nm; it has potential to be applied to the heat-resistant optical film.
The Impact of Parenting Styles on Subsequent Parenting Styles in Sons
Authors: Lawall Alexandra R. , Tram Jane M. , Kumar Nandita 
Published: November 2021

Research indicates that there is continuity in both maladaptive ( Chen & Kaplan, 2004 ) and positive parenting from one generation to the next. Within the topic of parenting, intergenerational transmission of specific parenting styles, specifically, the intergenerational transmission of authoritarian, permissive, and authoritative parenting styles has received limited attention in the research. In addition, few researchers have examined the impact of parenting styles applied to specific family members. As such, this study examined whether certain types of parenting styles may be passed down from parent to son. Through an online questionnaire, ( N = 28) men indicated, retrospectively, how they were parented and how they raise (or would raise) their children. The results of this study indicate a positive correlation between sons being parented in an authoritarian or permissive manner and subsequent engagement in the same parenting style.
Endothelial eNAMPT drives EndMT and preclinical PH: rescue by an eNAMPT‐neutralizing mAb
Authors: Ahmed Mohamed , Zaghloul Nahla , Zimmerman Prisca , Casanova Nancy G. , Sun Xiaoguang , Song Jin H. , Hernon Vivian Reyes , Sammani Saad , Rischard Franz , Rafikova Olga , Rafikov Ruslan , Makino Ayako , Kempf Carrie L. , Camp Sara M. , Wang Jian , Desai Ankit A. , Lussier Yves , Yuan Jason X.‐J. , Garcia Joe G.N. 
Published: November 2021

Pharmacologic interventions to halt/reverse the vascular remodeling and right ventricular dysfunction in pulmonary arterial hypertension (PAH) remains an unmet need. We previously demonstrated extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a DAMP (damage‐associated molecular pattern protein) contributing to PAH pathobiology via TLR4 ligation. We examined the role of endothelial cell (EC)‐specific eNAMPT in experimental PH and an eNAMPT‐neutralizing mAb as a therapeutic strategy to reverse established PH. Hemodynamic/echocardiographic measurements and tissue analyses were performed in Sprague Dawley rats exposed to 10% hypoxia/Sugen (three weeks) followed by return to normoxia and weekly intraperitoneal delivery of the eNAMPT mAb (1 mg/kg). WT C57BL/6J mice and conditional EC‐cNAMPTec−/− mice were exposed to 10% hypoxia (three weeks). Biochemical and RNA sequencing studies were performed on rat PH lung tissues and human PAH PBMCs. Hypoxia/Sugen‐exposed rats exhibited multiple indices of severe PH (right ventricular systolic pressure, Fulton index), including severe vascular remodeling, compared to control rats. PH severity indices and plasma levels of eNAMPT, IL‐6, and TNF‐α were all significantly attenuated by eNAMPT mAb neutralization. Compared to hypoxia‐exposed WT mice, cNAMPTec−/− KO mice exhibited significantly reduced PH severity and evidence of EC to mesenchymal transition (EndMT). Finally, biochemical and RNAseq analyses revealed eNAMPT mAb‐mediated rectification of dysregulated inflammatory signaling pathways (TLR/NF‐κB, MAP kinase, Akt/mTOR) and EndMT in rat PH lung tissues and human PAH PBMCs. These studies underscore EC‐derived eNAMPT as a key contributor to PAH pathobiology and support the eNAMPT/TLR4 inflammatory pathway as a highly druggable therapeutic target to reduce PH severity and reverse PAH.
Hemostatic and thrombotic disorders in the pediatric patient
Authors: O’Brien Sarah H. , Zia Ayesha 
Published: November 2021

AbstractThis review focuses on significant advances in the field of pediatric hemostasis and thrombosis, with a focus on published studies within the past decade. The evaluation and management of patients with excessive bleeding remain cornerstones of consultative hematology. We will describe the development of validated bleeding assessment tools relevant to pediatric practice, laboratory advances in the evaluation of von Willebrand disease, and a shift in clinical practice regarding the interpretation of normal coagulation studies in patients with significant bleeding phenotypes. There have also been critical advances in the management of hemostatic disorders. This review highlights new treatment paradigms in hemophilia and the rise of multidisciplinary medical homes for women living with bleeding disorders. Given the continued increase in the incidence of thrombosis, particularly in the hospital setting, a full call to arms against pediatric venous thromboembolism is now essential. We will describe recently completed clinical trials of direct oral anticoagulants in children and adolescents and ongoing work to elucidate the appropriate duration of therapy for children with provoked thrombosis. Recent work regarding the prevention of pediatric venous thromboembolism is highlighted, including studies of thromboprophylaxis and the development of risk prediction models for hospital-acquired thrombosis. Finally, we review advances in our understanding of thrombotic sequelae and the need for continued refinement of our evaluation tools. Despite the significant advances in pediatric hemostasis and thrombosis over the past decade, many unanswered questions remain for the next generation of investigators.
HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia
Authors: Zaimoku Yoshitaka , Patel Bhavisha A. , Adams Sharon D. , Shalhoub Ruba , Groarke Emma M. , Lee Audrey Ai Chin , Kajigaya Sachiko , Feng Xingmin , Rios Olga Julia , Eager Holly , Alemu Lemlem , Quinones Raffo Diego , Wu Colin O. , Flegel Willy A. , Young Neal S. 
Published: November 2021

Abstract
Immune aplastic anemia (AA) features somatic loss of HLA class I allele expression on bone marrow cells, consistent with a mechanism of escape from T-cell–mediated destruction of hematopoietic stem and progenitor cells. The clinical significance of HLA abnormalities has not been well characterized. We examined the somatic loss of HLA class I alleles and correlated HLA loss and mutation-associated HLA genotypes with clinical presentation and outcomes after immunosuppressive therapy in 544 AA patients. HLA class I allele loss was detected in 92 (22%) of the 412 patients tested, in whom there were 393 somatic HLA gene mutations and 40 instances of loss of heterozygosity. Most frequently affected was HLA-B*14:02, followed by HLA-A*02:01, HLA-B*40:02, HLA-B*08:01, and HLA-B*07:02. HLA-B*14:02, HLA-B*40:02, and HLA-B*07:02 were also overrepresented in AA. High-risk clonal evolution was correlated with HLA loss, HLA-B*14:02 genotype, and older age, which yielded a valid prediction model. In 2 patients, we traced monosomy 7 clonal evolution from preexisting clones harboring somatic mutations in HLA-A*02:01 and HLA-B*40:02. Loss of HLA-B*40:02 correlated with higher blood counts. HLA-B*07:02 and HLA-B*40:01 genotypes and their loss correlated with late-onset of AA. Our results suggest the presence of specific immune mechanisms of molecular pathogenesis with clinical implications. HLA genotyping and screening for HLA loss may be of value in the management of immune AA. This study was registered at clinicaltrials.gov as NCT00001964, NCT00061360, NCT00195624, NCT00260689, NCT00944749, NCT01193283, and NCT01623167.
Mid-pass whole genome sequencing enables biomedical genetic studies of diverse populations
Authors: Emde Anne-Katrin , Phipps-Green Amanda , Cadzow Murray , Gallagher C. Scott , Major Tanya J. , Merriman Marilyn E. , Topless Ruth K. , Takei Riku , Dalbeth Nicola , Murphy Rinki , Stamp Lisa K. , de Zoysa Janak , Wilcox Philip L. , Fox Keolu , Wasik Kaja A. , Merriman Tony R. , Castel Stephane E. 
Published: November 2021

AbstractBackgroundHistorically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at “mid-pass” 1-7x coverage.ResultsHere, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with highc recall (98%) and precision (97.5%).ConclusionCompared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications.
COVID-19-related acute kidney injury; incidence, risk factors and outcomes in a large UK cohort
Authors: Jewell Paul D. , Bramham Kate , Galloway James , Post Frank , Norton Sam , Teo James , Fisher Richard , Saha Rohit , Hutchings Sam , Hopkins Phil , Smith Priscilla , Joslin Jennifer , Jayawardene Satish , Mackie Sarah , Mudhaffer Ali , Holloway Amelia , Kibble Henry , Akter Mosammat , Zuckerman Benjamin , Palmer Kieran , Murphy Ciara , Iatropoulou Domniki , Sharpe Claire C. , Lioudaki Eirini 
Published: November 2021

AbstractBackgroundAcute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre.MethodsWe analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020.ResultsOf the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24–4,18;p <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27–2.53;p <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19–2.13) for stage 1;p < 0.005, 2.71(95%CI 1.82–4.05);p < 0.001for stage 2 and 2.99 (95%CI 2.17–4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months.ConclusionsThis large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3–6 months.