bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation
Authors: Bwayi Monicah N , Garcia-Maldonado Efren , Chai Sergio C , Xie Boer , Chodankar Shirish , Huber Andrew D , Wu Jing , Annu Kavya , Wright William C , Lee Hyeong-Min , Seetharaman Jayaraman , Wang Jingheng , Buchman Cameron D , Peng Junmin , Chen Taosheng 
Published: February 2022

Abstract
The 48 human nuclear receptors (NRs) form a superfamily of transcription factors that regulate major physiological and pathological processes. Emerging evidence suggests that NR crosstalk can fundamentally change our understanding of NR biology, but detailed molecular mechanisms of crosstalk are lacking. Here, we report the molecular basis of crosstalk between the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), where they form a novel heterodimer, resulting in their mutual inhibition. PXR and CAR regulate drug metabolism and energy metabolism. Although they have been broadly perceived as functionally redundant, a growing number of reports suggests a mutual inhibitory relation, but their precise mode of coordinated action remains unknown. Using methods including RNA sequencing, small-angle X-ray scattering and crosslinking mass spectrometry we demonstrate that the mutual inhibition altered gene expression globally and is attributed to the novel PXR–CAR heterodimerization via the same interface used by each receptor to heterodimerize with its functional partner, retinoid X receptor (RXR). These findings establish an unexpected functional relation between PXR, CAR and RXR, change the perceived functional relation between PXR and CAR, open new perspectives on elucidating their role and designing approaches to regulate them, and highlight the importance to comprehensively investigate nuclear receptor crosstalk.
Recent progress in the interaction between energetic particles and tearing modes
Authors: Cai Huishan , Li Ding 
Published: February 2022

Abstract
The dynamics of energetic particles and tearing modes and the interactions between them are of great significance for magnetically confined fusion plasmas. In this review, we focus on these issues in the context of tokamak plasmas. The interaction between energetic particles and tearing modes is considered from two perspectives: (i) the influence of energetic particles on tearing modes and (ii) the transport of energetic particles by tearing modes. The influence of energetic particles on tearing modes is described on the basis of a general dispersion relation for tearing modes. The effects of energetic particles are considered separately in the outer region and the island region of a tearing mode. The physics mainly results from the modification of the perturbed parallel current by energetic particles without wave–particle resonance. In addition, the resonance between energetic particles and tearing modes is also reviewed. For the transport of energetic particles, transport of both circulating and trapped energetic particles by tearing mode is reviewed. Our descriptions of physical phenomena here are based on an analytical approach, while the experiments and simulations are used to illustrate and confirm our results. Finally, a number of open issues are discussed.
Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation
Authors: Wang Judy , Martin-Romano Patricia , Cassier Philippe , Johnson Melissa , Haura Eric , Lenox Laurie , Guo Yue , Bandyopadhyay Nibedita , Russell Michael , Shearin Elizabeth , Lauring Josh , Dahan Laetitia 
Published: February 2022

Abstract

Background
Patients with KRAS-mutant cancers have limited treatment options. Here we present a phase I study of JNJ-74699157, an oral, selective, covalent inhibitor of the KRAS G12C isoform, in patients with advanced cancer harboring the KRAS G12C mutation.

Methods
Eligible patients (aged ≥18 years) who had previously received or were ineligible for standard treatment received JNJ-74699157 once daily on a 21-day cycle. Dose escalation was guided by a modified continual reassessment method.

Results
Ten patients (100 mg: 9 and 200 mg: 1) were enrolled. Tumor types included non–small cell lung cancer (n = 5), colorectal cancer (n = 4), and carcinoma of unknown primary site (n = 1). The median age was 65 (range: 36-74) years and median treatment duration was 2.91 (range: 0.5-7.5) months. Dose-limiting toxicities of grades 3–4 increased blood creatinine phosphokinase (CPK) were observed in 100 mg and 200 mg dose levels. The most common adverse event was increased blood CPK (6 patients). No significant clinical benefit was observed; the best response was stable disease in 4 patients (40%).

Conclusion
Based on dose-limiting skeletal muscle toxicities and the lack of efficacy at the 100 mg dose, further enrollment was stopped. The safety profile of JNJ-74699157 was not considered favorable for further clinical development.

ClinicalTrials.gov Identifier
NCT04006301
Immune-Desert Tumor Microenvironment in Thoracic SMARCA4-Deficient Undifferentiated Tumors with Limited Efficacy of Immune Checkpoint Inhibitors
Authors: Gantzer Justine , Davidson Guillaume , Vokshi Bujamin , Weingertner Noëlle , Bougoüin Antoine , Moreira Marco , Lindner Véronique , Lacroix Guillaume , Mascaux Céline , Chenard Marie-Pierre , Bertucci François , Davidson Irwin , Kurtz Jean-Emmanuel , Sautès-Fridman Catherine , Fridman Wolf H , Malouf Gabriel G 
Published: February 2022

Abstract

Background
Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Data linking BAF alterations with tumor microenvironment (TME) and efficacy of immune checkpoint inhibitors (ICI) are contradictory. The TME of SMARCA4-UT and their response to ICI are unknown.

Materials and Methods
Patients diagnosed with SMARCA4-UT in our institution were included. Immunostainings for tertiary lymphoid structures (TLS), immune cell markers, and checkpoints were assessed. Validation was performed using an independent transcriptome dataset including SMARCA4-UT, non–small cell lung cancers (NSCLC) with/without SMARCA4 mutations, and unclassified thoracic sarcomas (UTS). CXCL9 and PD-L1 expressions were assessed in NSCLC and thoracic fibroblast cell lines, with/without SMARCA4 knockdown, treated with/without interferon gamma.

Results
Nine patients were identified. All samples but one showed no TLS, consistent with an immune desert TME phenotype. Four patients received ICI as part of their treatment, but the only one who responded, had a tumor with a TLS and immune-rich TME. Unsupervised clustering of the validation cohort using immune cell scores identified 2 clusters associated with cell ontogeny and immunity (cluster 1 enriched for NSCLC independently of SMARCA4 status (n = 9/10; P = .001); cluster 2 enriched for SMARCA4-UT (n = 11/12; P = .005) and UTS (n = 5/5; P = .0005). SMARCA4 loss-of-function experiments revealed interferon-induced upregulation of CXCL9 and PD-L1 expression in the NSCLC cell line with no effect on the thoracic fibroblast cell line.

Conclusion
SMARCA4-UT mainly have an immune desert TME with limited efficacy to ICI. TME of SMARCA4-driven tumors varies according to the cell of origin questioning the interplay between BAF alterations, cell ontogeny and immunity.
The Palaeoproterozoic Gallujavri Ultramafic Intrusion, Karasjok Greenstone Belt; Petrogenesis of a Trans-Crustal Magma System
Authors: Orvik Alf Andre , Slagstad Trond , Hansen Harald , Nilsson Lars Petter , Sørensen Bjørn Eske 
Published: February 2022

Abstract
The modern concepts of magmatic plumbing systems have evolved from simple models of melt-dominated crustal magma chambers to magmatic systems that span the continental crust. The geochemistry of these systems is challenging to model numerically because of a complex polybaric and multiphase evolution, which is not well described by mathematic end-member formulas. We propose that a recent modelling tool, the Magma Chamber Simulator (MCS), can reveal part of the petrological complexities of such systems. The MCS numerically models phase equilibria, mineral chemistry and major and trace elements in multicomponent–multiphase systems by finding the extremes of the appropriate state functions. This study presents new petrographical and geochemical data from the Palaeoproterozoic Gallujavri ultramafic intrusion in the Karasjok Greenstone Belt, Arctic Norway. Our data indicate that (1) the intrusion is affected by crustal assimilation, (2) phase equilibria require polybaric crystallisation and (3) spinel compositions are similar to sub-volcanic intrusions of continental flood basalt provinces. We utilise the MCS to simulate the petrogenesis of the intrusion and test the model by comparing it against our reported petrological and geochemical data. Our modelling shows that the parental magma of the intrusion is consistent with coeval Karasjok-type komatiites observed at various places throughout the greenstone belt. First, the komatiitic primary magma intruded Archaean lower crust (c. 700 MPa), where fractionation and assimilation resulted in a hybrid melt. Second, the hybrid melt migrated and accumulated in a mid-crustal magma chamber (c. 400 MPa), where it continued to fractionate and assimilate while remaining open to recharge of mantle-derived komatiitic melts, forming the Gallujavri intrusion. We interpret the Gallujavri intrusion as part of a Palaeoproterozoic trans-crustal magma plumbing system, with many similarities to other Fennoscandian ultramafic-mafic layered intrusions.
Sex in the wild: repeated observations of planktonic ciliate conjugation from field samples
Authors: Romano Filomena , Symiakaki Katerina , Pitta Paraskevi 
Published: February 2022

Abstract
Ciliate conjugation is considered a rare event to encounter in the field and it is mostly reported from cultures. In this work, we describe a synchronized conjugation event of planktonic ciliates that was discovered twice; in September 2019, at two different locations in the Cretan Sea, Eastern Mediterranean, and in October 2020. In 2019, first, at 2 m depth of the coastal station POSEIDON-HCB, in samples fixed with acid Lugol and formaldehyde, we found 340 and 200 mating pairs L−1of different ciliate species, respectively; and second, at the Heraklion port, we found 220 mating pairs L−1 of Strombidinopsis sp. and 1960 mating pairs L−1 of Strombidium sp. At the Heraklion port visited again in 2020, we found 800 mating pairs L−1 of Strombidinopsis sp. and 200 mating pairs L−1 of Strombidium sp. Since detailed descriptions of conjugation in pelagic oligotrich ciliates are missing, our observations indicate that ciliate conjugation could be a frequent and periodic phenomenon, under specific conditions.
Defining imaging sub-phenotypes of psoriatic arthritis: integrative analysis of imaging data and gene expression in a PsA patient cohort
Authors: Eder Lihi , Li Quan , Rahmati Sara , Rahman Proton , Jurisica Igor , Chandran Vinod 
Published: February 2022

Abstract

Objectives
To define imaging sub-phenotypes in patients with PsA; determine their association with whole blood gene expression and identify biological pathways characterizing the sub-phenotypes.

Methods
Fifty-five patients with PsA ready to initiate treatment for active disease were prospectively recruited. We performed musculoskeletal ultrasound assessment of the extent of inflammation in the following domains: synovitis, peritenonitis, tenosynovitis and enthesitis. Peripheral whole blood was profiled with RNAseq, and gene expression data were obtained. First, unsupervised cluster analysis was performed to define imaging sub-phenotypes that reflected the predominant tissue involved. Subsequently, principal component analysis was used to determine the association between imaging-defined sub-phenotypes and peripheral blood gene expression profile. Pathway enrichment analysis was performed to identify underlying mechanisms that characterize individual sub-phenotypes.

Results
Cluster analysis revealed three imaging sub-phenotypes: (i) synovitis predominant [n = 31 (56%)]; (ii) enthesitis predominant [n = 13 (24%)]; (iii) peritenonitis predominant [n = 11 (20%)]. The peritenonitis-predominant sub-phenotype had the most severe clinical joint involvement, whereas the enthesitis-predominant sub-phenotype had the highest tender entheseal count. Unsupervised clustering of gene expression data identified three sub-phenotypes that partially overlapped with the imaging sub-phenotypes suggesting biological and clinical relevance of these sub-phenotypes. We therefore characterized enriched differential pathways, which included: immune system (innate system, B cells and neutrophil degranulation), complement system, platelet activation and coagulation function.

Conclusions
We identified three sub-phenotypes based on the predominant tissue involved in patients with active PsA. Distinct biological pathways may underlie these imaging sub-phenotypes seen in PsA, suggesting their biological and clinical importance.
Biologic therapy in refractory neurobehçet’s disease: a multicentre study of 41 patients and literature review
Authors: Herrero-Morant Alba , Martín-Varillas José Luis , Castañeda Santos , Maíz Olga , Sánchez Julio , Ortego Norberto , Raya Enrique , Prior-Español Águeda , Moriano Clara , Melero-González Rafael B , Graña-Gil Jenaro , Urruticoechea-Arana Ana , Ramos-Calvo Ángel , Loredo-Martínez Marta , Salgado-Pérez Eva , Sivera Francisca , Torre Ignacio , Narváez Javier , Andreu José Luis , Martínez-González Olga , Torre Ricardo Gómez-de la , Fernández-Aguado Sabela , Romero-Yuste Susana , González-Mazón Íñigo , Álvarez-Reguera Carmen , Hernández José Luis , González-Gay Miguel Ángel , Blanco Ricardo ,   the Neurobehçet Spanish Collaborative Group, Blanco Ana , Callejas José Luis , Brandy-García Anahy , Olivé Alejandro , Díez Elvira , Seijas-López Álvaro , Delgado-Beltrán Concepción 
Published: February 2022

Abstract

Objectives
To assess efficacy and safety of biologic therapy (BT) in neurobehçet’s disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug.

Methods
Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters.

Results
We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30–60) mg/day at the initial visit to 5 (3.8–10) mg/day after 6 months (P &lt; 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)–15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2–12.8) to 0.3 (0.1–3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment.

Conclusions
BT appears to be effective and relatively safe in refractory NBD.
Arabidopsis GOLD36/MVP1/ERMO3 Is Required for Powdery Mildew Penetration Resistance and Proper Targeting of the PEN3 Transporter
Authors: Underwood William 
Published: February 2022

The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter contributes to penetration resistance against nonadapted powdery mildew fungi and is targeted to papillae deposited at sites of interaction with the fungus. Timely recruitment of PEN3 and other components of penetration resistance to the host–pathogen interface is important for successful defense against this biotrophic pathogen. A forward genetic screen was previously carried out to identify Arabidopsis mutants that mistarget the PEN3 transporter or fail to accumulate PEN3 at sites of attempted powdery mildew penetration. This study focuses on PEN3 mistargeting in the aberrant localization of PEN3 4 (alp4) mutant and identification of the causal gene. In the alp4 mutant, PEN3 accumulates within the endomembrane system in an apparently abnormal endoplasmic reticulum and is not exported into papillae at powdery mildew penetration sites. This targeting defect compromises defenses at the host–pathogen interface, resulting in increased penetration success by a nonadapted powdery mildew. Genetic mapping identified alp4 as an allele of GOLGI DEFECTS 36 (GOLD36), a gene encoding a GDSL-lipase/esterase family protein that is involved in maintaining normal morphology and organization of multiple endomembrane compartments. Genetic complementation confirmed that mutation in GOLD36 is responsible for the PEN3 targeting and powdery mildew penetration resistance defects in alp4. These results reinforce the importance of endomembrane trafficking in resistance to haustorium-forming phytopathogens such as powdery mildew fungi. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Bowel Obstruction After Sacrocolpopexy: A Case Series
Authors: Wadensweiler Paul , Whitcomb Emily L. , Jeney Sarah E. S. , Meller Daniel , Moran Katherine , Guaderrama Noelani M. , Brueseke Taylor 
Published: February 2022

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27:e677–e680)
It is estimated that more than 30 million women in the United States are affected by pelvic floor disorders. Of these, 3 million experience pelvic organ prolapse.
Association of Expanded Prenatal Care Coverage for Immigrant Women With Postpartum Contraception and Short Interpregnancy Interval Births
Authors: Rodriguez Maria I. , Kaufman Menolly , Lindner Stephan , Caughey Aaron B. , DeFede Ana Lopez , McConnell K. John 
Published: February 2022

(Abstracted from JAMA Network Open 2021;4:e2118912)
In the United States, many immigrant women with low incomes are reliant on Medicaid for obstetric care. However, prenatal and postpartum care is not covered for a large segment of this group who have been in the United States for <5 years.
Placental Growth Factor in Assessment of Women With Suspected Pre-eclampsia to Reduce Maternal Morbidity: A Stepped Wedge Cluster Randomized Control Trial (PARROT Ireland)
Authors: Hayes-Ryan D. , Khashan A. S. , Hemming K. , Easter C. , Devane D. , Murphy D. J. , Hunter A. , Cotter A. , McAuliffe F. M. , Morrison J. J. , Breathnach F. M. , Dempsey E. , Kenny L. C. , O'Donoghue K. 
Published: February 2022

(Abstracted from BMJ 2021;374:n1857)
Placental growth factor (PlGF) has been suggested as a diagnostic biomarker of preeclampsia or placental dysfunction. PIGF typically circulates in maternal plasma and increases as placenta develops.
Early Delivery or Expectant Management for Late Preterm Preeclampsia: A Meta-Analysis of Randomized Controlled Trials
Authors: Chatzakis Christos , Liberis Anastasios , Zavlanos Apostolos , Petousis Stamatis , Tsakmaki Evangelia , Dinas Konstantinos , Sotiriadis Alexandros 
Published: February 2022

(Abstracted from Acta Obstet Gynecol Scand 2021;100:1392–1400)
Worldwide, preeclampsia affects approximately 4.5% of pregnancies. Weighing the maternal benefit of immediate delivery with the risk of severe neonatal complications is important to determine the appropriate time to deliver in cases of preeclampsia.
Personalized Surgical Transfusion Risk Prediction Using Machine Learning to Guide Preoperative Type and Screen Orders
Authors: Lou Sunny S. , Liu Hanyang , Lu Chenyang , Wildes Troy S. , Hall Bruce L. , Kannampallil Thomas 
Published: February 2022

Background
Accurate estimation of surgical transfusion risk is essential for efficient allocation of blood bank resources and for other aspects of anesthetic planning. This study hypothesized that a machine learning model incorporating both surgery- and patient-specific variables would outperform the traditional approach that uses only procedure-specific information, allowing for more efficient allocation of preoperative type and screen orders.

Methods
The American College of Surgeons National Surgical Quality Improvement Program Participant Use File was used to train four machine learning models to predict the likelihood of red cell transfusion using surgery-specific and patient-specific variables. A baseline model using only procedure-specific information was created for comparison. The models were trained on surgical encounters that occurred at 722 hospitals in 2016 through 2018. The models were internally validated on surgical cases that occurred at 719 hospitals in 2019. Generalizability of the best-performing model was assessed by external validation on surgical cases occurring at a single institution in 2020.

Results
Transfusion prevalence was 2.4% (73,313 of 3,049,617), 2.2% (23,205 of 1,076,441), and 6.7% (1,104 of 16,053) across the training, internal validation, and external validation cohorts, respectively. The gradient boosting machine outperformed the baseline model and was the best- performing model. At a fixed 96% sensitivity, this model had a positive predictive value of 0.06 and 0.21 and recommended type and screens for 36% and 30% of the patients in internal and external validation, respectively. By comparison, the baseline model at the same sensitivity had a positive predictive value of 0.04 and 0.144 and recommended type and screens for 57% and 45% of the patients in internal and external validation, respectively. The most important predictor variables were overall procedure-specific transfusion rate and preoperative hematocrit.

Conclusions
A personalized transfusion risk prediction model was created using both surgery- and patient-specific variables to guide preoperative type and screen orders and showed better performance compared to the traditional procedure-centric approach.

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