bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural characterization of a new subclass of panicum mosaic virus-like 3′ cap-independent translation enhancer
Authors: Johnson Philip Z , Kasprzak Wojciech K , Shapiro Bruce A , Simon Anne E 
Published: January 2022

Abstract
Canonical eukaryotic mRNA translation requires 5′cap recognition by initiation factor 4E (eIF4E). In contrast, many positive-strand RNA virus genomes lack a 5′cap and promote translation by non-canonical mechanisms. Among plant viruses, PTEs are a major class of cap-independent translation enhancers located in/near the 3′UTR that recruit eIF4E to greatly enhance viral translation. Previous work proposed a single form of PTE characterized by a Y-shaped secondary structure with two terminal stem-loops (SL1 and SL2) atop a supporting stem containing a large, G-rich asymmetric loop that forms an essential pseudoknot (PK) involving C/U residues located between SL1 and SL2. We found that PTEs with less than three consecutive cytidylates available for PK formation have an upstream stem-loop that forms a kissing loop interaction with the apical loop of SL2, important for formation/stabilization of PK. PKs found in both subclasses of PTE assume a specific conformation with a hyperreactive guanylate (G*) in SHAPE structure probing, previously found critical for binding eIF4E. While PTE PKs were proposed to be formed by Watson–Crick base-pairing, alternative chemical probing and 3D modeling indicate that the Watson–Crick faces of G* and an adjacent guanylate have high solvent accessibilities. Thus, PTE PKs are likely composed primarily of non-canonical interactions.
Multiple in vivo roles for the C-terminal domain of the RNA chaperone Hfq
Authors: Kavita Kumari , Zhang Aixia , Tai Chin-Hsien , Majdalani Nadim , Storz Gisela , Gottesman Susan 
Published: January 2022

Abstract
Hfq, a bacterial RNA chaperone, stabilizes small regulatory RNAs (sRNAs) and facilitates sRNA base-pairing with target mRNAs. Hfq has a conserved N-terminal domain and a poorly conserved disordered C-terminal domain (CTD). In a transcriptome-wide examination of the effects of a chromosomal CTD deletion (Hfq1-65), the Escherichia coli mutant was most defective for the accumulation of sRNAs that bind the proximal and distal faces of Hfq (Class II sRNAs), but other sRNAs also were affected. There were only modest effects on the levels of mRNAs, suggesting little disruption of sRNA-dependent regulation. However, cells expressing Hfq lacking the CTD in combination with a weak distal face mutation were defective for the function of the Class II sRNA ChiX and repression of mutS, both dependent upon distal face RNA binding. Loss of the region between amino acids 66–72 was critical for this defect. The CTD region beyond amino acid 72 was not necessary for distal face-dependent regulation, but was needed for functions associated with the Hfq rim, seen most clearly in combination with a rim mutant. Our results suggest that the C-terminus collaborates in various ways with different binding faces of Hfq, leading to distinct outcomes for individual sRNAs.
The level of urinary C4d is associated with disease progression in IgA nephropathy with glomerular crescentic lesions: a cohort study
Authors: Wang Zi , Jiang Yuanyuan , Chen Pei , Wang Jinwei , Zhang Xue , Huang Bo , Zhou Xujie , Shi Sufang , Liu Lijun , Lv Jicheng , Zhang Hong 
Published: January 2022

ABSTRACT

Background
Positive glomerular C4d staining, representative of lectin pathway activation, has been proven to be associated with unfavorable outcomes in immunoglobulin A nephropathy (IgAN). Our previous study suggested that urinary C4d correlated positively with an increase in crescents while the relationship between urinary C4d and disease severity and progression remains unelucidated.

Methods
In this study we enrolled 168 patients diagnosed with IgAN with varying proportions of crescent formation at the time of biopsy. An independent cohort of 107 IgAN patients was enrolled for validation. Kidney biopsy specimens were stained using immunohistochemistry. Urinary C4d levels at renal biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was end-stage kidney disease (ESKD).

Results
Higher urinary C4d/creatinine levels were associated with a lower estimated glomerular filtration rate (eGFR); massive proteinuria; hypertension and severe Oxford M, E, T and C scores. After a median follow-up of 19 months (interquartile range 9–27), 53 (31.5%) participants reached ESKD. High urinary C4d/creatinine levels were independently and significantly associated with a risk of developing ESKD [hazard ratio per standard deviation increment of log-transformed C4d/creatinine 7.623 (95% confidence interval 4.117–14.113)].

Conclusions
The urinary C4d/creatinine level is a potential useful biomarker that was associated with disease severity and progression in patients with IgAN and crescents.
Hospital clinicians’ psychosocial well-being during the COVID-19 pandemic: longitudinal study
Authors: Wynter Karen , Holton Sara , Trueman Melody , Bruce Suellen , Sweeney Sue , Crowe Shane , Dabscheck Adrian , Eleftheriou Paul , Booth Sarah , Hitch Danielle , Said Catherine M , Haines Kimberley J , Rasmussen Bodil 
Published: January 2022

Abstract

Background
Hospital clinicians report poor psychosocial well-being during the COVID-19 pandemic. Few studies have reported data at more than one time point.

Aims
To compare psychosocial well-being among hospital clinicians at two different time points during the COVID-19 pandemic in 2020.

Methods
Participants included doctors, nurses, midwives and allied health clinicians at a multi-site, public health service in Melbourne, Australia. Data were collected via two cross-sectional, online surveys: May to June (wave 1; n = 638) and October to December 2020 (wave 2; n = 358). The Depression, Anxiety and Stress Scale (DASS-21) assessed psychological well-being in the past week. Investigator-devised questions assessed COVID-19 concerns and perceived work impacts. General linear models were used to assess impact of wave on psychological distress.

Results
There were no significant demographic differences between the two groups. Both positive (e.g. learning experience) and negative (e.g. risk of getting COVID-19) impacts were reported. In both waves, staff were most concerned about health risks to family members. Wave 2 respondents were significantly more likely than wave 1 respondents to indicate concerns about colleagues having COVID-19, increased workloads, leave cancellation and increased conflict at work (all P &lt; 0.001). Adjusting for sex, age, self-rated health and discipline group, depression, anxiety and stress scores were significantly higher for respondents in the second than the first wave (all P &lt; 0.001).

Conclusions
Psychological well-being of hospital clinicians was significantly worse during the second wave of the COVID-19 pandemic than the first. Sustained occupational and psychosocial support is recommended even when immediate COVID-19 concerns and impacts resolve.
Transforming project delivery: integrated project delivery
Authors: Ashcraft Howard 
Published: January 2022

Abstract
The design and construction industry has long suffered low productivity and poor project outcomes. Collaborative approaches to project delivery offer an opportunity to transform outcomes by creating incentives in an environment that incentivizes high performance. This paper examines integrated project delivery (IPD), a collaborative contractual approach that alters a project’s fundamental commercial, organizational, and legal structures to minimize dysfunction and stimulate performance. IPD’s basic structures are introduced, followed by a critical examination of current and new research on IPD augmented by the author’s insights from structuring over 150 IPD projects. An online appendix provides additional information regarding the reasoning behind the IPD structures.
Lymphocyte subset abnormalities in early severe scleroderma favor a Th2 phenotype and are not altered by prior immunosuppressive therapy
Authors: Shah Ankoor , Storek Jan , Woolson Rob , Pinckney Ashley , Keyes-Elstein Lynnette , Wallace Paul K , Sempowski Gregory D , McSweeney Peter , Mayes Maureen D , Crofford Leslie , Csuka M E , Phillips Kristine , Khanna Dinesh , Simms Robert , Ballen Karen , LeClercq Sharon , Clair William St , Nixon Andrew B , Nash Richard , Wener Mark , Brasington Richard , Silver Richard , Griffith Linda M , Furst Daniel E , Goldmuntz Ellen , Sullivan Keith M 
Published: January 2022

AbstractObjectivesThe Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy.MethodsLymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization.ResultsCompared with healthy controls, individuals with SSc showed significant reductions in central memory CD8 T cells, activated total and CD4 T cells, γ/δ T cells, memory B cells, myeloid and plasmacytoid dendritic cells and FOXP3+CD25+ Treg cells and increases in naïve CD4 T cells, effector memory CD4 T cells and effector CD8 T cells. A greater bias towards a IL-4+ Th2/T cytotoxic 2 (Tc2) phenotype based on the Th2:Th1 CD4 ratio and Tc2:Tc1 CD8 T cells was also found. Notably, no difference in any lymphocyte subset was observed between those given or not given prior DMARDs.ConclusionsIn patients with early, severe SSc, significant lymphocyte subset abnormalities were observed. Prior treatment with immunosuppressive therapy did not impact the immunophenotype, suggesting that lymphocyte disturbances in scleroderma appeared to be due to the disease itself.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov), NCT00114530.
Implementation of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Scoring System in a randomized phase IIb study of abatacept in psoriatic arthritis
Authors: Østergaard Mikkel , Bird Paul , Pachai Chahin , Du Shuyan , Wu Chun , Landis Jessica , Fuerst Thomas , Ahmad Harris A , Connolly Sean E , Conaghan Philip G 
Published: January 2022

Abstract

Objectives
To investigate if the OMERACT PsA MRI Scoring System (PsAMRIS), including a novel total inflammation score, shows sensitivity to change with an agent (abatacept) known to impact clinical outcomes in PsA.

Methods
We performed a post hoc analysis of a randomized phase IIb study of abatacept in patients with PsA and inadequate DMARD response. Participants received one of three abatacept dosing regimens [ABA3, ABA10 or ABA30/10 mg/kg (30 mg/kg switched to 10 mg/kg after two doses)] or placebo until day 169, then ABA10 through day 365. MRIs at baseline and days 85, 169 and 365 were centrally evaluated by two readers blinded to chronological order and treatment arm. Synovitis, osteitis, tenosynovitis, periarticular inflammation, bone erosions, joint space narrowing and bone proliferation were assessed using the PsAMRIS. A novel total inflammation score was tested.

Results
MRIs for 123 patients were included. On day 169, ABA10 and ABA30/10 significantly reduced MRI synovitis and tenosynovitis, respectively, vs placebo [differences −0.966 (P = 0.039) and −1.652 (P = 0.014), respectively]. Synovitis in the placebo group increased non-significantly from baseline to day 169, total inflammation and tenosynovitis decreased non-significantly and all measures improved significantly after a switch to ABA10 [−1.019, −0.940, −2.275 (P &lt; 0.05), respectively, day 365 vs day 169]. Structural outcomes changed minimally across groups.

Conclusion
Adults with PsA receiving ABA10 and ABA30/10 demonstrated significant resolution of inflammatory components of disease, confirmed by MRI, with synovitis and tenosynovitis improvements consistent with previously reported clinical responses for these doses. Results indicate that a reduction in OMERACT PsAMRIS inflammation scores may provide proof of tissue-level efficacy in PsA clinical trials.

Registration
ClinicalTrials.gov (https://clinicaltrials.gov), NCT00534313.
Gastroparesis in systemic sclerosis: a detailed analysis using whole-gut scintigraphy
Authors: Adler Brittany , Hummers Laura K , Pasricha P Jay , McMahan Zsuzsanna H 
Published: January 2022

Abstract

Objectives
Gastroparesis is a common complication of SSc. We sought to determine the degree of overlap between gastroparesis and dysmotility in other areas of the gut, correlate our findings with gastrointestinal (GI) symptoms, and examine associations between gastroparesis and SSc features.

Methods
Whole-gut scintigraphy was performed on SSc patients who were enrolled in the Johns Hopkins Scleroderma Cohort, for whom detailed longitudinal clinical and serologic data are collected. A subset of patients completed the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) to quantify their GI symptoms. We examined associations between the presence and severity of gastroparesis, GI symptoms, and SSc clinical features.

Results
Ninety-seven SSc patients with and without GI symptoms underwent whole-gut scintigraphy and completed the gastric emptying study. Of the 97, 34 (35%) met criteria for gastroparesis. Of the measures assessed, delayed liquid emptying captured more patients with delayed gastric transit than delayed solid emptying (74% vs 55%), and percentage liquid emptying correlated best with GIT Reflux (ρ = −0.33, P = 0.01) and Distension (ρ = −0.30, P = 0.03) scores. Of 33 patients with gastroparesis, 30 (91%) had abnormal transit in other areas of the GI tract. Higher anti-centromere protein B (CENP-B) titres correlated with slower gastric emptying (ρ = −0.26, P = 0.03), but no specific clinical features of SSc were associated with gastroparesis.

Conclusions
Gastric emptying of liquids when given alongside solids may be more sensitive and provide a more clinically relevant measure of gastroparesis in SSc than solid gastric emptying or liquid gastric emptying alone. SSc patients with gastroparesis frequently have dysmotility in other areas of the GI tract, underscoring the need for whole-gut scintigraphy to evaluate the entire gut.
LINC00173 Interacts With DNMT1 to Regulate LINC00173 Expression via Promoter Methylation in Hydroquinone-Induced Malignantly Transformed TK6 Cells and Benzene-Exposed Workers
Authors: Zhang Haiqiao , Pan Zhijie , Ling Xiaoxuan , Tan Qiang , Yuan Qian , Qin Jiheng , Zhong Bohuan , Li Huifang , Chen Jialong , Zhang He , Chen Xiaowen , Shi Zhizhen , Liu Linhua 
Published: January 2022

AbstractLong-term exposure to benzene or its metabolite, hydroquinone (HQ), can causally contribute to acute myeloid leukemia. Long-noncoding RNAs are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed LINC00173 (long intergenic nonprotein coding RNA 173) regulates the pathogenesis of acute myeloid leukemia is not fully understood. Here, we found that the expression of LINC00173 decreased while the expression of DNA methyltransferase 1 (DNMT1) increased, and the methylation of LINC00173 promoter was negatively correlated with LINC00173 expression in GEPIA, CCLE databases, benzene-exposed workers, B-cell non-Hodgkin’s lymphoma, K562, U937, or HQ-induced malignantly transformed TK6 (HQ-MT cells). Furthermore, in 5-aza-2’-deoxycytidine (DNA methyltransferase inhibitor) or trichostatin A (histone deacetylation inhibitor)-treated HQ-MT cells, the expression of LINC00173 was restored by reduced DNA promoter methylation levels. HQ-MT cells with DNMT1 knockout by CRISPR/Cas9 restored the expression of LINC00173 and inhibited the DNA methylation of its promoter as well as enrichment of DNMT1 to promoter. Overexpression of LINC00173 inhibited the expression of DNMT1, cell proliferation, tumor growth, enhanced chemosensitivity to cisplatin, and apoptosis in HQ-MT cells. LINC00173 interacts with DNMT1 to regulate the methylation of LINC00173 promoter. Overall, this study provides evidence that interaction between DNMT1 and LINC00173 regulates the expression of LINC00173 by regulating its promoter methylation level, thus regulating the function of HQ-MT cells in vitro and in vivo, providing a new therapeutic target for benzene-induced tumor.
Profiling Secreted miRNA Biomarkers of Chemical-Induced Neurodegeneration in Human iPSC-Derived Neurons
Authors: You Dahea , Cohen Jennifer D , Pustovalova Olga , Lewis Lauren , Shen Lei 
Published: January 2022

AbstractElucidation of predictive fluidic biochemical markers to detect and monitor chemical-induced neurodegeneration has been a major challenge due to a lack of understanding of molecular mechanisms driving altered neuronal morphology and function, as well as poor sensitivity in methods to quantify low-level biomarkers in bodily fluids. Here, we evaluated 5 neurotoxicants (acetaminophen [negative control], bisindolylmaleimide-1, colchicine, doxorubicin, paclitaxel, and rotenone) in human-induced pluripotent stem cell-derived neurons to profile secreted microRNAs (miRNAs) at early and late stages of decline in neuronal cell morphology and viability. Based on evaluation of these morphological (neurite outgrowth parameters) and viability (adenosine triphosphate) changes, 2 concentrations of each chemical were selected for analysis in a human 754 miRNA panel: a low concentration with no/minimal effect on cell viability but a significant decrease in neurite outgrowth, and a high concentration with a significant decrease in both endpoints. A total of 39 miRNAs demonstrated significant changes (fold-change ≥ 1.5 or ≤ 0.67, p value &lt; .01) with at least 1 exposure. Further analyses of targets modulated by these miRNAs revealed 38 key messenger RNA targets with roles in neurological dysfunctions, and identified transforming growth factor-beta (TGF-β) signaling as a commonly enriched pathway. Of the 39 miRNAs, 5 miRNAs, 3 downregulated (miR-20a, miR-30b, and miR-30d) and 3 upregulated (miR-1243 and miR-1305), correlated well with morphological changes induced by multiple neurotoxicants and were notable based on their relationship to various neurodegenerative conditions and/or key pathways, such as TGF-β signaling. These datasets reveal miRNA candidates that warrant further evaluation as potential safety biomarkers of chemical-induced neurodegeneration.
Comparison of Effects of Propofol and Sevoflurane on the Cerebral Vasculature Assessed by Digital Subtraction Angiographic Parameters in Patients Treated for Ruptured Cerebral Aneurysm: A Preliminary Study
Authors: Joys Steve , Panda Nidhi B. , Ahuja Chirag K. , Luthra Ankur , Tripathi Manjul , Mahajan Shalvi , Kaloria Narender , Jain Chirag , Singh Nidhi , Regmi Sabina , Jangra Kiran , Chauhan Rajeev , Soni Shiv L. , Bhagat Hemant 
Published: January 2022

Background:
Studies have evaluated the effects of volatile and intravenous anesthetic agents on the cerebral vasculature with inconsistent results. We used digital subtraction angiography to compare the effects of propofol and sevoflurane on the luminal diameter of cerebral vessels and on cerebral transit time in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods:
This prospective preliminary study included adult patients with good-grade aSAH scheduled for endovascular coil embolization; patients were randomized to receive propofol or sevoflurane anesthesia during endovascular coiling. The primary outcome was the luminal diameter of 7 cerebral vessel segments measured on the diseased and nondiseased sides of the brain at 3 time points: awake, postinduction of anesthesia, and postcoiling. Cerebral transit time was also measured as a surrogate for cerebral blood flow.

Results:
Eighteen patients were included in the analysis (9 per group). Baseline and intraoperative parameters were similar between the groups. Propofol increased the diameter of 1 vessel segment at postinduction and postcoiling on the diseased side and in 1 segment at postcoiling on the nondiseased side of the brain (P<0.05). Sevoflurane increased vessel diameter in 3 segments at postinduction and in 2 segments at postcoiling on the diseased side, and in 4 segments at postcoiling on the nondiseased side (P<0.05). Cerebral transit time did not change compared with baseline awake state in either group and was not different between the groups.

Conclusions:
Sevoflurane has cerebral vasodilating properties compared with propofol in patients with good-grade aSAH. However, sevoflurane affects cerebral transit time comparably to propofol.
Irreversible Electroporation Ablation for Atrial Fibrillation: Status and Challenges
Authors: Xie Fei , Chen Yonggang , Chen Xinhua , Zhao Zhihong 
Published: January 2022

Abstract
Pulsed electric field (PEF) is a novel energy source by which high-voltage electric pulses are used to create irreversible electroporation. PEF is non-thermal and highly tissue-dependent in which specific targeting of the atrial myocardium is achieved and sparing of adjacent tissues is feasible, theoretically increasing the safety of the procedure, which could potentially break the trade-off between effective lesions and collateral damage and substantially improve risk-benefit ratios in atrial fibrillation (AF) ablation. Although recently published trials have shown a clear effect of AF ablation, large-scale clinical trials are lacking. Current clinical evidence has demonstrated significant efficacy in achieving durable pulmonary vein isolation without ablation-related adverse events. However, their putative benefits regarding efficacy, efficiency, and safety remain to be proven in randomized controlled trials.
With Fearful Eyes: Exploring Relatives' Experiences With Out-of-Hospital Cardiac Arrest
Authors: Larsen Malene Kaas , Mikkelsen Randi , Budin Susanne Holst , Lamberg Dorte Nees , Thrysoe Lars , Borregaard Britt 
Published: January 2022

Background
Out-of-hospital cardiac arrest (OHCA) imposes significant consequences for a family, but little is known about relatives' experiences.

Objective
Our aim was to explore relatives' experiences with the OHCA and the following months after.

Method
A qualitative approach using phenomenological-hermeneutic methodology was applied. Data consisted of semistructured interviews with 12 relatives of OHCA survivors. We analyzed data based on Paul Ricoeur's theory of interpretation.

Results
Relatives experienced OHCA as an abrupt and stressful event filled with imposing concerns for the cardiac arrest survivor. Relatives were fellow sufferers confronted with the possibility of bereavement, watching from the sideline with fearful eyes. After the OHCA, relatives experienced a troubled time with anxiety and edginess, monitoring the survivor for signs of a new cardiac arrest and trying to adapt to a new normality. Relatives' previous identities and positions within their families were disrupted.

Conclusion
Relatives were challenged with the OHCA and the trajectory after it, experiencing a high level of distress and anxiety. Relatives took on an immense responsibility, always watching the survivor for potential symptoms of a new cardiac arrest. The cardiac arrest and the survivor's possible cognitive impairments gave rise to assuming a new authority as a relative. We advocate for a new family approach to relatives, acknowledging relatives' stress and central role in supporting cardiac arrest survivors.