bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whewellite-Bearing Fluid Inclusions in Zircons From a Stromatic Migmatite in the Chinese Sulu Ultrahigh-Pressure Metamorphic Belt
Authors: Fei Chenhui , Liu Jingbo 
Published: July 2022

Abstract
Abundant primary fluid and melt inclusions occur in zircons from a stromatic migmatite sample in the Chinese Sulu ultrahigh-pressure (UHP) metamorphic belt, reflecting an immiscible melt-fluid coexistence during the partial melting process. Raman analysis shows that the fluid inclusions include whewellite, highly disordered carbonaceous matter (CM), diamond, calcite, dawsonite, quartz, cristobalite, H2O-bearing silica glass, muscovite, chalcopyrite, molybdenite, pyrite/pyrrhotite, magnetite, hematite, rutile, CO2 and H2O. The inclusions were entrapped during the exhumation of the rock from UHP to granulite-facies metamorphic conditions. The presence of whewellite suggests that the primary fluids during the entrapment of the inclusions contained some kind of dicarboxylic compound. The highly disordered CM still includes aliphatic hydrocarbon species revealed by the C-H stretching bands at ~2886 and ~2941 cm−1, and a subsidiary band at 1250 cm−1 on the low-frequency side of the D band at 1350 cm−1, indicating that it was derived from incomplete carbonization of an organic compound. The identification of whewellite as well as highly disordered CM in the fluid inclusions provides evidence that abiotic synthesis of organic compounds can happen at elevated pressures and temperatures where both melt and fluids are stable, and in which magnetite and sulphides may play a catalyzing role.
Methylation of a MITE insertion in the MdRFNR1-1 promoter is positively associated with its allelic expression in apple in response to drought stress
Authors: Niu Chundong , Jiang Lijuan , Cao Fuguo , Liu Chen , Guo Junxing , Zhang Zitong , Yue Qianyu , Hou Nan , Liu Zeyuan , Li Xuewei , Tahir Muhammad Mobeen , He Jieqiang , Li Zhongxing , Li Chao , Ma Fengwang , Guan Qingmei 
Published: July 2022

Abstract
Miniature inverted-repeat transposable elements (MITEs) are widely distributed in the plant genome and can be methylated. However, whether DNA methylation of MITEs is associated with induced allelic expression and drought tolerance is unclear. Here, we identified the drought-inducible MdRFNR1 (root-type ferredoxin-NADP+ oxidoreductase) gene in apple (Malus domestica). MdRFNR1 plays a positive role in drought tolerance by regulating the redox system, including increasing NADP+ accumulation and catalase and peroxidase activities and decreasing NADPH levels. Sequence analysis identified a MITE insertion (MITE-MdRF1) in the promoter of MdRFNR1-1 but not the MdRFNR1-2 allele. MdRFNR1-1 but not MdRFNR1-2 expression was significantly induced by drought stress, which was positively associated with the MITE-MdRF1 insertion and its DNA methylation. The methylated MITE-MdRF1 is recognized by the transcriptional anti-silencing factors MdSUVH1 and MdSUVH3, which recruit the DNAJ domain-containing proteins MdDNAJ1, MdDNAJ2, and MdDNAJ5, thereby activating MdRFNR1-1 expression under drought stress. Finally, we showed that MdSUVH1 and MdDNAJ1 are positive regulators of drought tolerance. These findings illustrate the molecular roles of methylated MITE-MdRF1 (which is recognized by the MdSUVH–MdDNAJ complex) in induced MdRFNR1-1 expression as well as the drought response of apple and shed light on the molecular mechanisms of natural variation in perennial trees.
Policing and devolution in the UK: The ‘special’ case of Wales
Authors: Jones Robert , Harrison Michael , Jones Trevor 
Published: July 2022

AbstractPolitical devolution in the UK has been responsible for major legislative changes to police governance, policy, and practice. Although policing in Wales remains formally part of the unitary ‘England and Wales’ system, the devolution of other key policy areas have contributed to the emergence of a distinctive Welsh policy context. In this paper, we explore the ways in which the devolution settlement in Wales has, albeit inadvertently, resulted in growing divergence from policing in England. We argue that devolution has transformed the operation of policing in Wales and has added a significant degree of complexity for Welsh police forces. The paper raises several important questions for policing in post-devolution Wales and underlines the need for further empirical research that can explore the extent, causes and implications of divergence between the policing systems of the constituent nations of the United Kingdom.
Anomalous enhancement of dilepton production as a precursor of color superconductivity
Authors: Nishimura Toru , Kitazawa Masakiyo , Kunihiro Teiji 
Published: July 2022

Abstract
We compute the modification of the photon self-energy due to dynamical diquark fluctuations developed near the critical temperature of two-flavor superconductivity, which is one of the color superconducting phases, through the Aslamasov–Larkin, Maki–Thompson, and density of states terms, which are responsible for the paraconductivity in metals at vanishing energy and momentum. The analysis is performed through an investigation of the diquark fluctuations within the normal phase determined by the mean-field approximation in the massless two-flavor Nambu–Jona-Lasinio model. It is shown that the rate has a significant enhancement in low-invariant-mass regions over a rather wide range of temperatures in the normal phase. This enhancement is worth exploring in the relativistic heavy-ion collisions, which may thereby reveal the significance of the diquark fluctuations in dense quark matter.
Reliability of Muscle Strength and Muscle Power Assessments Using Isokinetic Dynamometry in Neuromuscular Diseases: A Systematic Review
Authors: van der Woude Danny R , Ruyten Thijs , Bartels Bart 
Published: July 2022

Abstract

Objective
The purpose of this study was to critically appraise and summarize the evidence for reliability of muscle strength and muscle power assessment in patients with neuromuscular diseases (NMDs) using isokinetic dynamometry.

Methods
PubMed, CINAHL, and Embase electronic databases were searched from inception to March 8, 2022. Studies designed to evaluate reliability of muscle strength and power measurements using isokinetic dynamometry were included in this review. First, the methodological quality of the studies was assessed according to the Consensus-Based Standards for the Selection of Health Measurement Instruments guidelines. Next, the quality of measurement properties was determined. Finally, the methodological quality and quality of measurement properties of the studies were combined to obtain a best-evidence synthesis.

Results
A best-evidence synthesis of reliability was performed in 11 studies including postpoliomyelitis syndrome (n = 5), hereditary motor and sensory neuropathy (n = 2), motor neuron diseases (n = 1), myotonic dystrophy (n = 1), and groups of pooled NMDs (n = 2). A best-evidence synthesis on measurement error could not be performed. Quality of evidence on reliability ranged from high in postpoliomyelitis syndrome to very low in hereditary motor and sensory neuropathy, motor neuron diseases, and groups of pooled NMDs. The most frequently used outcome measure was peak torque, which was reliable in all populations (intraclass correlation coefficient &gt;0.7).

Conclusion
The quality of evidence for reliability of isokinetic dynamometry was found to vary substantially among different NMDs. High quality of evidence has been obtained only in patients with postpoliomyelitis syndrome. Further research is needed in the majority of known NMDs to determine reliability and validity of isokinetic dynamometry.

Impact
The ability of isokinetic dynamometers to capture clinically relevant changes in muscle strength and muscle power in NMDs remains unclear. Isokinetic dynamometry results in NMDs should be interpreted with caution.
Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis
Authors: Mouawad Joe E , Sharma Shailza , Renaud Ludivine , Pilewski Joseph M , Nadig Satish N , Feghali-Bostwick Carol 
Published: July 2022

Abstract

Objectives
Lung fibrosis is the leading cause of death in SSc, with no cure currently available. Antifibrotic Endostatin (ES) production does not reach therapeutic levels in SSc patients, suggesting a deficit in its release from Collagen XVIII by the main cleavage enzyme, Cathepsin L (CTSL). Thus, elucidating a potential deficit in CTSL expression and activity unravels an underlying molecular cause for SSc-driven lung fibrosis.

Methods
Fibrosis was induced experimentally using TGF-β in vitro, in primary human lung fibroblasts (pLFs), and ex vivo, in human lung tissues. ES and CTSL expression was quantified using ELISA, RT-qPCR, immunoblotting or immunofluorescence. Recombinant NC1-FLAG peptide was used to assess CTSL cleavage activity. CTSL expression was also compared between SSc vs normal (NL)-derived pLFs and lung tissues.

Results
ES levels were significantly reduced in media conditioned by TGF-β-induced pLFs. TGF-β-stimulated pLFs significantly reduced expression and secretion of CTSL into the extracellular matrix (ECM). CTSL was also sequestered in its inactive form into extracellular vesicles, further reducing its availability in the ECM. Media conditioned by TGF-β-induced pLFs showed reduced cleavage of NC1-Flag and reduced release of the antifibrotic ES fragment. SSc-derived pLFs and lung tissues expressed significantly lower levels of CTSL compared with NL.

Conclusions
Our findings identify CTSL as a protein protective against lung fibrosis via its activation of antifibrotic ES, and whose expression in SSc pLFs and lung tissues is suppressed. Identifying strategies to boost CTSL endogenous levels in SSc patients could serve as a viable therapeutic strategy.
Real-Time Symptom Capture of Hallucinations in Schizophrenia with fMRI: Absence of Duration-Dependent Activity
Authors: Gill Karanvir , Percival Chantal , Roes Meighen , Arreaza Leo , Chinchani Abhijit , Sanford Nicole , Sena Walter , Mohammadsadeghi Homa , Menon Mahesh , Hughes Matthew , Carruthers Sean , Sumner Philip , Woods Will , Jardri Renaud , Sommer Iris E , Rossell Susan L , Woodward Todd S 
Published: July 2022

Abstract

Background
While advances in the field of functional magnetic resonance imaging (fMRI) provide new opportunities to study brain networks underlying the experience of hallucinations in psychosis, there are methodological challenges unique to symptom-capture studies.

Study Design
We extracted brain networks activated during hallucination-capture for schizophrenia patients when fMRI data collected from two sites was merged (combined N = 27). A multidimensional analysis technique was applied, which would allow separation of brain networks involved in the hallucinatory experience itself from those involved in the motor response of indicating the beginning and end of the perceived hallucinatory experience. To avoid reverse inference when attributing a function (e.g., a hallucination) to anatomical regions, it was required that longer hallucinatory experiences produce extended brain responses relative to shorter.

Study Results
For radio-speech sound files, an auditory perception brain network emerged, and displayed speech-duration-dependent hemodynamic responses (HDRs). However, in the hallucination-capture blocks, no network showed hallucination-duration-dependent HDRs, but a retrieved network that was anatomically classified as motor response emerged.

Conclusions
During symptom capture of hallucinations during fMRI, no HDR showed duration dependence, but a brain network anatomically matching the motor response network was retrieved. Previous reports on brain networks detected by fMRI during hallucination capture are reviewed in this context; namely, that the brain networks interpreted as involved in hallucinations may in fact be involved only in the motor response indicating the onset of the hallucination.
Single-Cell RNA-Seq Identifies Dynamic Cardiac Transition Program from ADCs Induced by Leukemia Inhibitory Factor
Authors: Yao Jiayi , Ma Feiyang , Zhang Li , Zhu Ching , Jumabay Medet , Yao Zehao , Wang Lumin , Cai Xinjiang , Zhang Daoqin , Qiao Xiaojing , Shivkumar Kalyanam , Pellegrini Matteo , Yao Yucheng , Wu Xiuju , Boström Kristina I 
Published: July 2022

Abstract
Adipose-derived cells (ADCs) from white adipose tissue are promising stem cell candidates because of their large regenerative reserves and the potential for cardiac regeneration. However, given the heterogeneity of ADC and its unsolved mechanisms of cardiac acquisition, ADC-cardiac transition efficiency remains low. In this study, we explored the heterogeneity of ADCs and the cellular kinetics of 39,432 single-cell transcriptomes along the leukemia inhibitory factor (LIF)-induced ADC-cardiac transition. We identified distinct ADC subpopulations that reacted differentially to LIF when entering the cardiomyogenic program, further demonstrating that ADC-myogenesis is time-dependent and initiates from transient changes in nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. At later stages, pseudotime analysis of ADCs navigated a trajectory with 2 branches corresponding to activated myofibroblast or cardiomyocyte-like cells. Our findings offer a high-resolution dissection of ADC heterogeneity and cell fate during ADC-cardiac transition, thus providing new insights into potential cardiac stem cells.
P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation
Authors: Cheng Fangyuan , Li Mingyue , Thorne Rick Francis , Liu Guangzhi , Zhang Yuwei , Wu Mian , Liu Lianxin 
Published: July 2022

Abstract
Exploiting the pluripotent properties of embryonic stem cells (ESCs) holds great promise for regenerative medicine. Nevertheless, directing ESC differentiation into specialized cell lineages requires intricate control governed by both intrinsic and extrinsic factors along with the actions of specific signaling networks. Here, we reveal the involvement of the p21-activated kinase 4 (Pak4), a serine/threonine kinase, in sustaining murine ESC (mESC) pluripotency. Pak4 is highly expressed in R1 ESC cells compared with embryonic fibroblast cells and its expression is progressively decreased during differentiation. Manipulations using knockdown and overexpression demonstrated a positive relationship between Pak4 expression and the clonogenic potential of mESCs. Moreover, ectopic Pak4 expression increases reprogramming efficiency of Oct4-Klf4-Sox2-Myc-induced pluripotent stem cells (iPSCs) whereas Pak4-knockdown iPSCs were largely incapable of generating teratomas containing mesodermal, ectodermal and endodermal tissues, indicative of a failure in differentiation. We further establish that Pak4 expression in mESCs is transcriptionally driven by the core pluripotency factor Nanog which recognizes specific binding motifs in the Pak4 proximal promoter region. In turn, the increased levels of Pak4 in mESCs fundamentally act as an upstream activator of the Akt pathway. Pak4 directly binds to and phosphorylates Akt at Ser473 with the resulting Akt activation shown to attenuate downstream GSK3β signaling. Thus, our findings indicate that the Nanog-Pak4-Akt signaling axis is essential for maintaining mESC self-renewal potential with further importance shown during somatic cell reprogramming where Pak4 appears indispensable for multi-lineage specification.
An Interferon-γ/FLT3 Axis Positively Regulates Hematopoietic Progenitor Cell Expansion from Human Pluripotent Stem Cells
Authors: Kitajima Kenji , Shingai Minako , Ando Hikaru , Hamasaki Mako , Hara Takahiko 
Published: July 2022

Abstract
Since it became possible to differentiate human pluripotent stem cells (hPSCs) into hematopoietic cells in vitro, great efforts have been made to obtain highly potent hematopoietic stem/progenitor cells (HSPCs) from hPSCs. Immunophenotypical HSPCs can be obtained from hPSCs, but their repopulating potential in vivo is low. Here, we developed a novel hematopoietic differentiation method for human-induced pluripotent stem cells (hiPSCs) to determine why the existing hPSC differentiation systems are inadequate. hiPSC-derived CD45+CD34+ cells in our system were mostly CD38− immunophenotypical HSPCs. The vast majority of human CD45+CD34+ cells in umbilical cord blood, fetal liver, and bone marrow are CD38+ hematopoietic progenitor cells (HPCs); therefore, the poor production of CD38+ HPCs was indicative of a systematic problem. hiPSC-derived CD45+CD34+ cells did not express FLT3, a receptor tyrosine kinase. Exogenous FLT3 activity significantly enhanced the production of CD38+ HPCs from hiPSCs. Thus, poor production of CD38+ HPCs was due to a lack of FLT3 expression. Interferon-γ upregulated expression of FLT3 and increased the number of CD38+ HPCs among hiPSC-derived CD45+CD34+ cells. These results suggest that the poor production of CD38+ HPCs with hPSC differentiation systems is due to a lack of FLT3 expression, and that the addition of interferon-γ can solve this problem.
Phylogenomics Supports the Monophyly of Aphelids and Fungi and Identifies New Molecular Synapomorphies
Authors: Galindo Luis Javier , Torruella Guifré , López-García Purificación , Ciobanu Maria , Gutiérrez-Preciado Ana , Karpov Sergey A , Moreira David 
Published: July 2022

Abstract
The supergroup Holomycota, composed of Fungi and several related lineages of unicellular organisms (Nucleariida, Rozellida, Microsporidia, and Aphelida), represents one of the major branches in the phylogeny of eukaryotes. Nevertheless, except for the well-established position of Nucleariida as the first holomycotan branch to diverge, the relationships among the other lineages have so far remained unresolved largely owing to the lack of molecular data for some groups. This was notably the case aphelids, a poorly known group of endobiotic phagotrophic protists that feed on algae with cellulose walls. The first molecular phylogenies including aphelids supported their sister relationship with Rozellida and Microsporidia which, collectively, formed a new group called Opisthosporidia (the “Opisthosporidia hypothesis”). However, recent phylogenomic analyses including massive sequence data from two aphelid genera, Paraphelidium and Amoeboaphelidium, suggested that the aphelids are sister to fungi (the “Aphelida $+$ Fungi hypothesis”). Should this position be confirmed, aphelids would be key to understanding the early evolution of Holomycota and the origin of Fungi. Here, we carry out phylogenomic analyses with an expanded taxonomic sampling for aphelids after sequencing the transcriptomes of two species of the genus Aphelidium (Aphelidium insulamus and Aphelidium tribonematis) in order to test these competing hypotheses. Our new phylogenomic analyses including species from the three known aphelid genera strongly rejected the Opisthosporidia hypothesis. Furthermore, comparative genomic analyses further supported the Aphelida $+$ Fungi hypothesis via the identification of 19 orthologous genes exclusively shared by these two lineages. Seven of them originated from ancient horizontal gene transfer events predating the aphelid–fungal split and the remaining 12 likely evolved de novo, constituting additional molecular synapomorphies for this clade. Ancestral trait reconstruction based on our well-resolved phylogeny of Holomycota suggests that the progenitor of both fungi and rozellids, was aphelid-like, having an amoeboflagellate state and likely preying endobiotically on cellulose-containing, cell-walled organisms. Two lineages, which we propose to call Phytophagea and Opisthophagea, evolved from this ancestor. Phytophagea, grouping aphelids and classical fungi, mainly specialized in endobiotic predation of algal cells. Fungi emerged from this lineage after losing phagotrophy in favor of osmotrophy. Opisthophagea, grouping rozellids and Microsporidia, became parasites, mostly of chitin-containing hosts. This lineage entered a progressive reductive process that resulted in a unique lifestyle, especially in the highly derived Microsporidia. [Aphelida, fungi, Holomycota, horizontal gene transfer, phylogenomics, synapomorphy.]
Characterization of Legal Claims Involving Patients with Pyoderma Gangrenosum
Authors: Pfeifer Hailey J. , Orfaly Victoria E. , Rick Jonathan W. , Damitio Christopher , Ortega Loayza Alex G. 
Published: July 2022

ABSTRACT

OBJECTIVE
To review the litigation literature related to patients with pyoderma gangrenosum (PG) to characterize the legal issues they face.

DATA SOURCES
Data sources include law databases Casetext and Lexis Nexis.

STUDY SELECTION
All disability and medical liability claims directly involving patients with PG were included.

DATA EXTRACTION
Data extraction came directly from Casetext and Lexis Nexis. All cases extracted came from September 1965 to December 2020. This resulted in 32 cases, 18 of which were excluded because they did not mention the plaintiff having a diagnosis of PG (n = 14).

DATA SYNTHESIS
The review found a total of six medical liability cases in which adverse health outcomes were reported, including prolonged suffering (2/6 cases), unnecessary treatments or procedures (2/6), exacerbation of disease (1/6 cases), and permanent scarring (1/6 cases). Despite this, two plaintiffs won their case and only one of them received any monetary award. Similarly, of the eight disability claims in the review, four were ruled in the favor of the plaintiffs and only two resulted in immediate awarding of benefits. Half of medical liability cases occurred in correctional facilities after the denial of appropriate care.

CONCLUSIONS
The findings demonstrate a need for access to specialty care in incarcerated populations. Cases that occurred in a hospital setting also stress the importance of initiatives such as telemedicine to efficiently increase access to care in a cost-effective manner. Further, PG has been recognized as a severe impairment in disability claims despite patients being denied because they were deemed able to perform other work.
ALDH2 mutation results in excessive basal nitric oxide production and a delayed response to nitroglycerin
Authors: Zhu Hongming , Hu Jingjing , Dong Zhen , Liu Yang , Sun Xiaolei , Sun Aijun 
Published: July 2022

Abstract

Background and purpose:
Nitroglycerin tolerance is a common phenomenon in patients with coronary artery disease (CAD). Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that metabolizes nitroglycerin to its active form nitric oxide (NO). Previous studies showed altered nitroglycerin in subjects with ALDH2 mutation, but the functional impact on endothelial cells is not fully understood.

Methods:
In the first step of in vitro experiments, we examined functional properties of induced pluripotent stem cell-derived CD144+ endothelial cells (iPSC-ECs) that expressed wildtype (WT) vs ALDH2+/− variant. In the second step of human studies, diameter of the left anterior descending (LAD) coronary artery was determined using angiography in 151 adult volunteers (111 with WT ALDH2, 32 with ALDH2+/− and 8 with ALDH2−/− genotype) prior to as well as after intracoronary injection of 200-μg nitroglycerin.

Results:
Briefly, the ALDH2+/− iPSC-ECs demonstrated impaired low-density lipoprotein (LDL) uptake, proliferation, migration, tube formation, oxidative stress resistance, and viability. In comparison to the WT control, the ALDH2+/− iPSC-ECs had elevated NO production under baseline conditions, but exhibited a delayed NO release after nitroglycerin treatment. Exposure to 10-μg/mL nitroglycerin for 2 h increased NO production in WT iPSC-ECs but 4-h exposure was required to stimulate NO production in the ALDH2+/− iPSC-ECs. In comparison to the WT control, the subjects carrying the ALDH2+/− variants had seemingly larger LAD coronary artery diameter (3.5 and 3.8 mm vs 3.4 mm in the WT control), but attenuated vasodilatory response to nitroglycerin (ALDH2MUT group vs the WT control, 7.1 ± 0.6% vs 10.1 ± 0.8%, P = 0.024).

Conclusion:
These findings indicated elevated NO production by endothelia cells under basal conditions but attenuated response to nitroglycerin upon ALDH2 mutation.